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3 Improving prevention and management of coronary artery disease 303 IMPROVING PREVENTION AND MANAGEMENT OF CORONARY ARTERY DISEASE 1795 EUROASPIRE III: Risk factor and therapeutic management in people at high risk of developing cardiovascular disease from 12 European countries K. Kotseva 1, C. Jennings 1,G.DeBacker 2, D. De Bacquer 2, P. Amouyel 3,D.Gaita 4,U.Keil 5,A.Pajak 6, Z. Reiner 7, D. Wood 1 on behalf of EUROASPIRE Study Group. 1 National Heart and Lung Institute, Imperial College London, London, United Kingdom; 2 University of Ghent, Ghent, Belgium; 3 Institut Pasteur de Lille, Lille, France; 4 Institute of Cardiovascular Disease, Timisoara, Romania; 5 Institute of Epidemiology and Social Medicine, Munster, Germany; 6 Institute of Clinical Epidemiology and Population Studies, Krakow, Poland; 7 University Hospital Rebro, Zagreb, Croatia Objectives: EUROASPIRE III surveyed people in general practice at high risk of developing cardiovascular disease. The aim was to determine whether the 2003 Joint European Societies guidelines on cardiovascular disease prevention for high risk individuals are being followed in clinical practice. Methods: This survey was undertaken in selected geographical areas and general practices in 12 European countries: Belgium, Bulgaria, Croatia, Finland, Germany, Italy, Latvia, Poland, Romania, Slovenia, Spain and the UK. Consecutive patients, men and women <80 years of age, without a history of coronary or other atherosclerotic disease, but treated with antihypertensive and/or lipid lowering and/or anti-diabetes treatments, were identified retrospectively. Data collection was based on a review of patient s medical notes and a prospective interview and examination at least six months after the start of drug treatment. Results: 4366 high risk individuals (57.7% females) were interviewed (participation rate 76.7%). Overall 70.8% had a blood pressure 140/90 mm Hg ( 130/80 in people with diabetes mellitus), 78.9% had a total cholesterol 4.5 mmol/l and 30.2% reported a history of diabetes. Only 26.3% of patients using antihypertensive medication achieved the blood pressure goal, 30.6% of patients on lipidlowering medication achieved the total cholesterol goal and 52.9% of patients with self-reported diabetes had a HbA1c < 6.5%. The use of cardioprotective medication was: aspirin or other anti-platelets 22.0%; beta-blockers 31.2%; ACE inhibitors/arb 55.7%; calcium channel blockers 24.0%; and statins 39.9%. Conclusions: The EUROASPIRE III survey shows that risk factor management in patients being treated as high cardiovascular risk is a major cause for concern. Blood pressure, lipid and glucose control are completely inadequate with a large majority of patients not achieving the targets defined in the prevention guidelines. Primary prevention needs a systematic, comprehensive, multidisciplinary approach, which addresses lifestyle, risk factor and therapeutic management, and a health care system which invests in prevention. (33.6%) was obese (BMI>30 kg/m 2 ) and 65.0% had a metabolic syndrome (IDF definition). Conclusion: Persistent dyslipidemia is highly prevalent in statin-treated patients in Europe and Canada with high proportions of patients not at LDL-C goals and/or with low HDL-C and elevated triglycerides. A more intensive and comprehensive lipid management in this high-risk population, in line with current guidelines, would decrease the prevalence of lipid abnormalities and might contribute to further decrease the CV risk of these patients Trends in acute coronary syndrome management and early mortality: Myocardial Ischaemia National Audit Project (MINAP) 2004 to 2007 C.P. Gale 1, B.A. Cattle 1, A.D. Simms 1, P.D. Baxter 1,T.Munyombe 1, T.H. West 1, D.C. Greenwood 1, K.A.A. Fox 2,R.M.West 1. 1 University of Leeds, Leeds, United Kingdom; 2 The University of Edinburgh, Edinburgh, United Kingdom Purpose: Evidence from international registries suggests ACS mortality has declined and this is associated with increased use of evidence-based therapies. Not all countries demonstrate similar concordance with recommendations for care. In light of contemporary ACS guidelines, we characterised changes in ACS management and early mortality across England and Wales from 01/01/04 to 31/12/07. Methods: Using MINAP, we studied 340,983 ACS events from 228 hospitals. Data were smoothed using splines and in-patient and 30-day mortality rates adjusted for the proportion of admissions corresponding to in-patient and 30-day death respectively. Seasonal trends were investigated by time series structural decomposition. Results: Rates of NSTEACS were consistently greater than those of STEMI. Acute aspirin therapy increased for AMIs, but was lower for NSTEACS than for STEMIs. Chronic aspirin use for NSTEACS was greater than that for STEMI. Rates of recording of evidence-based secondary preventative medication at discharge reduced. There was an increase in the rate of recording of clopidogrel use. The total rates of revascularisation for STEMI increased (Figure 1). There was a reduction in the rate of thrombolysis and increase in the rate of primary PCI. Rates of in-patient and 30-day mortality for STEMI and NSTEACS declined in parallel. Early morality rates were higher for NSTEACS than for STEMI High prevalence of dyslipidemia in 18,574 patients treated with statins in Europe and Canada: Results of the dyslipidemia international study A.K. Gitt 1, J.P.P. Kastelein 2 on behalf of DYSIS Study Group. 1 Institut fuer Herzinfarktforschung Ludwigshafen, Ludwigshafen am Rhein, Germany; 2 Academic Medical Center, Amsterdam, Netherlands Background: Although statins are the cornerstone of cardiovascular (CV) prevention, patients treated with statins remain at substantial risk of CV events. Persistent lipid abnormalities are likely to contribute to this residual CV risk. The objective of the study was to assess the prevalence of dyslipidemia in patients receiving statin therapy. Methods: This cross-sectional study was conducted by 2,929 primary care physicians, cardiologists, endocrinologists and internists in 12 countries (Europe, Canada). Patients were consecutive outpatients 45 years-old, on statin therapy for 3 months with available lipid values. A clinical examination and the recording of the latest lipid values on statin were performed in all patients. Results: 18,574 patients (mean age 65.8±9.8 years old; 58.4% male) have been enrolled since April, Of these patients, 74.6% had hypertension, 39.7% diabetes, 28.9% a family history of premature CV disease and 15.0% were current smokers. CHD was present in 36.8% of patients, cerebrovascular disease in 9.5% and peripheral arterial disease in 10.5%. One third of the study population Table 1 Patients with CHD or Diabetes Patients with or SCORE risk 5% SCORE risk <5% N=14,929 (80.4%) N=3,645 (19.6%) LDL-C not at goal [ 2.5/2.0 mmol/l (high risk); 3.0 mmol/l (low risk)] 47.1%/70.9% 55.7% TC not at goal [ 4.5/4.0 mmol/l (high risk); 5 (low risk)] 51.5%/70.6% 62.9% Low HDL-C [<1.0 mmol/l (male); <1.2 mmol/l (female)] 28.2% 18.7% Elevated TG [>1.7 mmol/l] 39.2% 34.4% LDL-C not at goal and low HDL-C and/or high TG 24.6%/35.5% 23.9% No residual lipid abnormalities 26.4%/13.5% 25.9% CHD = coronary heart disease; LDL-C = low-density lipoprotein cholesterol; TC = total cholesterol; HDL-C = high-density lipoprotein cholesterol; TG = triglycerides. Figure 1. Pharmacological and invasive revascularisation rates for STEMI 2004 to 2007 adjusted for STEMI admission rate (with time series decomposition graphs for thrombolysis (above right) and primary PCI (below right)); first row: raw data, second row: effect of season, third row: decomposed trend, fourth row: extracted noice. Conclusions: These data demonstrate significant changes in ACS performance and improvement in early mortality for STEMI and NSTEACS. Although early mortality rates have improved, NSTEACS have higher early mortality rates, and lower rates of acute aspirin use than those with STEMI. Despite a reduction in thrombolysis rates, total STEMI revascularisation rates improved and were associated with increased primary PCI rates Persistence with beta-blockers in coronary heart disease patients in UK primary care E. Setakis 1,C.Morley 2,S.Cockle 3, T.P. Van Staa 1, G. Kassianos 4. 1 GPRD Division, MHRA, London, United Kingdom; 2 Bradford Royal Infirmary, Bradford, United Kingdom; 3 Servier Laboratories Limited, Slough, United Kingdom; 4 Birch Hall Medical Centre, Bracknell, United Kingdom Purpose: To investigate persistence with beta-blocker therapy in CHD patients treated in UK primary care. Methods: Retrospective cohort study (UK General Practice Research Database (GPRD)). Patients were included if they had a 1st ever diagnosis of CHD (angina, heart failure, previous MI) after 1st April 2004 and a 1st ever prescription for a beta-blocker on or after that CHD diagnosis. Patients with a history of hypertrophic (obstructive) cardiomyopathy were excluded. Kaplan-Meier life tables analysis was used to estimate the persistence with treatment. Treatment was considered continuous if a new prescription was given within 3 months of the expected end of the current prescription. Patients were followed from index date until the earliest of date of death, transfer out of practice or last collection date.

4 304 Improving prevention and management of coronary artery disease / Diabetes prevention, treatment and control Results: 12,493 patients (68.0% male; mean age 58.0 years (s.d years)) were included. Overall, 27% of patients had discontinued treatment by 1 year, rising to 39% by 2 years and 50% by 3 years after initiation of beta-blockers. Persistence was greater for males than females (discontinued at 1 year: 25% versus 31%; 2 years 37% versus 44%; 3 years: 47% versus 57%) and for patients with a history of MI, compared to those with angina or heart failure (discontinued at 1 year: 21%, 32% and 29%; 2 years: 32%, 44% and 45%; 3 years: 43%, 55% and 56%, respectively). Continuation with beta-blockers Conclusions: Around a quarter of patients have discontinued beta-blocker therapy within 1 year of initiation, rising to half of patients at 3 years. Persistence is greater in those with a history of MI compared to those with heart failure or angina. Adverse events are commonly associated with beta-blockers and this may contribute to the lack of persistence with treatment Identification of patients with impaired outcome on ACE-inhibitor therapy J. Brugts 1, E. Boersma 1,A.Isaacs 2, W. Remme 3, M. Bertrand 4, K. Fox 5,R.Ferrari 6, M. De Maat 2, A. Danser 2, M.L. Simoons 1 on behalf of EUROPA-trial investigators. 1 Erasmus MC - Thoraxcenter, Rotterdam, Netherlands; 2 Erasmus MC, Rotterdam, Netherlands; 3 STICARES, Rhoon, Netherlands; 4 Hopital Cardiologique CHRU de Lille, Lille, France; 5 Royal Brompton Hospital, London, United Kingdom; 6 Azienda Ospedaliera Di Ferrara (Arcispedale S. Anna), Ferrara, Italy Background: The efficacy of ACE-inhibitors in stable CAD may be increased by targeting therapy to those patients who are most likely to benefit. However, these patients cannot be identified based on clinical characteristics. Genetic profiling could be a new approach to identify patients who do, or do not respond to therapy. Objective: To investigate whether genetic polymorphisms in the reninangiotensin-system (RAAS) and bradykinin pathways modify the treatment benefit of the ACE-inhibitor perindopril. Methods: In 8907 stable coronary artery disease patients from the randomized placebo-controlled EUROPA-trial, we analyzed 52 haploytpe-tagging SNP s in 12 genes within the pharmacodynamic pathways of ACE-inhibitors. The primary outcome was the reduction in cardiovascular mortality, non-fatal MI and resuscitated cardiac arrest during four years of follow-up. Cox regression was performed with correction for multiple testing by permutation analysis. Our genetic findings were verified in the PROGRESS trial. In addition, the genetic variation was related to plasma measurements of RAAS hormones. Findings: Three polymorphisms in the angiotensin-ii receptor type I and bradykinin receptor type I genes significantly modified the treatment benefit of perindopril. We identified a pharmacogenetic profile, which defined a group of patients (73.5%), who experienced a more pronounced treatment effect (HR 0.68; 95% CI ) and a group of patients (26.5%), who did not benefit from treatment with perindopril (HR 1.26; 95% CI ) with significant interaction (P for interaction = ). Pharmacogenet. profile of ACE-i therapy Interpretation This unique pharmacogenetic analysis identified genetic determinants of treatment benefit of ACE-inhibitor therapy by perindopril Impact of non steroidal anti-inflammatory drugs (NSAIDs) on CV outcomes in atherothrombotic patients: insights from the European REACH registry O. Barthelemy 1,J.P.Collet 1,G.Cayla 1, T. Chastre 1,U.Zeymer 2, P.G. Steg 3,D.L.Bhatt 4, G. Montalescot 1 on behalf of the REACH Registry investigators. 1 Pitie-Salpetriere Hospital (AP-HP), Paris, France; 2 Klinikum der Stadt Herzzentrum Ludwigshafen, Ludwigshafen am Rhein, Germany; 3 Bichat-Claude Bernard Hospital (AP-HP), Paris, France; 4 Cleveland Clinic, Cleveland, United States of America Aim: We analysed whether the use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with an increased risk of cardiovascular (CV) events in stable atherothrombotic patients. Methods: We analysed 21,253 patients of the European REACH Registry performed in 18 European countries between 2003 and ,406 (86.6%) patients had established atherothrombotic disease and 2,847 (13.4%) were selected on the basis of multiple risk factors but had no prior history of vascular disease. The use of aspirin (ASA) and/or NSAIDs was determined at enrolment and ischemic events were recorded over two years of follow-up. MACCE was defined as the composite of death, MI or stroke. The composite of MACCE and re-hospitalization (MACCE/H) was also evaluated. Results: The mean age was 67.1±9.7 years, and 68.5% were male. Four groups were defined: 1) no ASA no NSAIDs, 2) ASA only, 3) NSAIDs only, 4) NSAIDs + ASA with 6,814 patients (32.1%), 13,043 (61.4%), 544 (2.6%) and 852 (4.0%) patients in these groups, respectively. In patients not taking ASA, the prescription of NSAIDs was associated with non-significant trends for an excess of MACCE, death, stroke or bleeding (see figure). In patients on chronic aspirin treatment, the use of NSAIDs was associated with a significant excess of MACCE and stroke; the trends for more death, MI or bleeding were not significant (see figure). The composite of MACCE/H was significantly higher in NSAIDs users, without (26.3% vs 18.5%) or with (27.8% vs 20.6%) concomitant ASA, p< for both. Figure 1 Conclusions: With or without concomitant ASA use, the use of NSAIDs appears to be associated with a modest increase of ischemic risk. This excess of risk is particularly clear in patients taking ASA which identifies the subset of patients with a prior history of vascular event. DIABETES PREVENTION, TREATMENT AND CONTROL 1821 Risk of death differs according to type of oral glucose-lowering therapy in patients with diabetes and a previous myocardial infarction: a nationwide study T.K. Schramm 1,G.H.Gislason 1, M.L. Norgaard 2, J.N. Rasmussen 3, F. Folke 2, M.L. Hansen 2, C.H. Jorgensen 2, A. Vaag 3, L. Kober 1, C. Torp-Pedersen 2. 1 Rigshospitalet (The Heart Centre), Copenhagen, Denmark; 2 Gentofte University Hospital (Dept. of Cardiology), Hellerup, Denmark; 3 Steno Diabetes Center, Gentofte, Denmark Purpose: The potential risk of individual oral glucose-lowering agents is largely unknown. We conducted a nationwide analysis of risk of death associated to different oral glucose-lowering drugs used as monotherapy in diabetes patients with a previous myocardial infarction (MI). Methods: All residents in Denmark 20 years of age with a previous MI who initiated monotheraphy with oral glucose-lowering therapy during 1997 to 2006 were included. The population was followed by individual-level-linkage of nationwide registers up till 9 years. The use of oral glucose-lowering drugs was identified by prescription claims. The risk of death associated with use of individual oral glucose-lowering drugs with metformin as the reference, was estimated by multivariable, time-dependent Cox proportional-hazard analyses, adjusted for age, gender, comorbidity, socioeconomic status and concomitant cardiovascular medication. By entering drug use as time-dependent variables, risk assessment of single drug use only was ensured. Results: A total of 8,220 subjects were included. The distribution of drugs was: metformin 2,758 (33.6%), glimeperide 3,651 (44.4%), gliclazide 487 (5.9%), glibenclamide 1,132 (13.8%), glipizide 642 (7.8%), tolbutamide 485 (5.9%), repaglinide 178 (2.2%) and acarbose 34 (0.4%), respectively. During the study period 1,377 (16.4%) died. An increased risk of death was associated to treatment with glimeperide, glibenclamide, glipizide, and tolbutamide when compared with

5 Diabetes prevention, treatment and control 305 metformin, whereas no significant difference was found for gliclazide, repaglinide and acarbose deaths from any cause during approximately person-years of follow-up. HbA1c was 1.0% lower among those randomized to intensive glucose control over an average of 5 years. Intensive therapy resulted in a 16% reduction in non-fatal MI (RR 0.84, 95% CI ) and a 15% reduction in CHD (RR 0.85, 95% CI ). No significant effect on stroke was observed (RR 0.90, 95% CI ) or all-cause mortality (RR 1.02, 95% CI ). In absolute terms 2 non-fatal MIs or 3 CHD events were avoided for every 200 patients treated for 5 years Conclusion: We provide robust evidence that a reduction in HbA1c of 1% over 5 years significantly reduced coronary events without an excess risk of death. Total Death Conclusion: Individual oral glucose-lowering drugs carry a difference in the risk of death. Gliclazide and repaglinide, being as safe as metformin, whereas other commonly used sulfonylureas were associated with higher risk of death Do angiotensin-converting enzyme inhibitors and angiotensin receptor blockers prevent the incidence of diabetes? A meta-analysis of more than 100,000 patients M. Al-Mallah, S. Siddiqui, M. Sinno, A. Abu Samra. Henry Ford Health System, Detroit, United States of America Background: The prevalence of diabetes mellitus (DM) increased exponentially over the past years, with 100 million people expected to develop diabetes in the coming 15 years. The impact of medical therapy on the incidence of new onset DM is not clear. We performed a systematic review and meta analysis to study the impact of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) on the incidence of new onset DM. Methods: MEDLINE, EMBASE, BIOSIS, Cochrane databases from inception till February 2009 for randomized controlled trials (RCT) that reported new incident DM with ACEI or ARB therapy. A total of 18 RCT are included in this meta analysis. A random-effect model was used and between-studies heterogeneity was estimated with I2. Results: There were patients randomized to ACEI or ARB and patients randomized to other therapies. ACEI/ARB use was associated with a decrease in new onset DM (RR 0.78, 95% CI , p=0.003 for ACEI and RR 0.8, 95% CI , p< for ARB) (figure 1). Treating 100 patients with ACEI or 50 patients with ARB prevents one case of new onset DM. Forest Plot Conclusions: The cumulative evidence suggests that the use of ACEI/ARB prevents the incidence of diabetes mellitus. This may be of special clinical benefit in patients with pre-diabetes or metabolic syndrome Does more intensive control of glucose reduce cardiovascular events in type 2 diabetes? K.K. Ray, S.R.K. Sheshasai, S. Wijesuriya, R. Sivakumaran, S. Nethercott, D. Preiss, S. Erqou, N. Sattar. University of Cambridge, Cambridge, United Kingdom Background: It remains unclear whether intensive control of glucose reduces cardiovascular events among individuals with type 2 diabetes mellitus. Methods: We conducted a meta-analysis of randomized controlled outcome trials to assess the impact of intensive v.s. standard glucose control on death and cardiovascular outcomes. Rates of non-fatal myocardial infarctions (MI), fatal and non-fatal coronary heart disease (CHD), strokes and all-cause mortality were calculated from relevant publications. We conducted a random effects meta-analysis of the rate ratio in intensive vs standard therapy groups. Results: 5 trials involving participants fulfilling the eligibility criteria were included. There were 1497 non-fatal MIs, 2318 CHD events, 1127 strokes and 1824 Does tighter glycemic control improve macrovascular outcomes in people with type II diabetes mellitus? A meta-analysis of patients in randomised controlled trials K.Y. Ooi 1, B. Billah 2,H.Krum 2. 1 The Alfred Hospital, Melbourne, Australia; 2 Monash University, Melbourne, Australia Background: There remains considerable uncertainty regarding the relationship between long-term glycemic control in people with type II diabetes mellitus (DM) and the risk of developing macrovascular disease. Methods: We therefore performed a meta-analysis of randomised controlled trials (RCTs) that compared tighter glycemic control in people with type II DM versus those receiving standard DM therapy. RCTs were identified by systematic search of manuscripts, abstracts and databases. Only studies with populations of greater than 500 subjects were included. Major endpoints that could be meta-analysed included all-cause mortality, cardiovascular mortality and the incidence of acute myocardial infarction (AMI), stroke and peripheral vascular disease (PVD). Results: Data was able to be extracted from 5 RCTs contributing patients. This is summarised in the table. Outcome # of Patients Risk Ratio (95% CI) p-value for significance All cause mortality ( ) Cardiovascular mortality ( ) AMI ( ) Stroke ( ) PVD ( ) Conclusions: This meta-analysis suggests no significant survival benefit or reduction in major cardiovascular events with tighter glycemic control in people with type II DM, with the exception of a decrease in the risk of AMI. Therefore, a focus on other modifiable cardiovascular risk factors may be of more importance in reducing the risk of type II DM associated macrovascular disease Diabetes is the strongest independent predictor of mortality in acute cerebrovascular disease R. Margato 1, H. Ribeiro 1,S.Carvalho 1, C. Ferreira 1, J. Gabriel 2, A. Velon 2, P. Guimaraes 2, P. Mateus 1, P. Fontes 1, I. Moreira 1. 1 Centro Hospitalar de Trás os Montes e Alto Douro, Cardiology Department, Vila Real, Portugal; 2 Centro Hospitalar de Trás os Montes e Alto Douro, Neurology Department, Vila Real, Portugal Purpose: Cerebrovascular disease is the leading cause of dead in Portugal. There are few studies that report the underlying prevalence of preventable cardiovascular (CV) risk factors and there respective impact on prognosis. Methods: We did a retrospective study of patients (pts) consecutively admitted to a Cerebrovascular Disease Unit with the diagnosis of stroke or transient ischemic attack (TIA) over a period of 5 years. Demographic data, CV risk factors, clinical parameters and in- hospital mortality were analyzed. In statistical analysis, X2 and Student s t test were used; logistic regression was performed for multivariate analysis. Results: 3508 pts were studied, with a mean age of 73±11.51 years and 52.3% male; 55.2% of pts had hypertension, 19% diabetes, 14% dyslipidemia, 5% obesity and 2.5% smoking. On admission 8.4% of pts presented with TIA, 15.8% with hemorrhagic stroke and 75.8% with ischemic stroke. Mean hospital stay was 7.1±6.7 days and in-hospital mortality was 15.4%. Multivariate analysis that adjusted for age, sex, cardiovascular risk factors and type of stroke identified hypertension (OR= 1.49; IC95% ; p=0. 02), diabetes (OR=2.5; IC95% ; p=0.01) and hemorrhagic stroke (OR= 1.9; IC95% ; p= 0,032) as independent predictors of in-hospital mortality. Conclusions: In this large cohort of patients admitted for acute cerebrovascular accident, hypertension was the most prevalent cardiovascular risk factor and diabetes the strongest independent predictor of in-hospital mortality.

6 306 Diabetes prevention, treatment and control / Predictors of outcome in cardiac resynchronisation therapy 1826 Effect of multifactorial comprehensive cardiac rehabilitation on risk factor control and mortality in type 2 diabetes - three years results of the randomized DANSUK study A.M.B. Soja 1, A.D.O. Zwisler 1,S.Rasmussen 2,T.M.Melchior 3, E. Hommel 4, J. Fischer Hansen 5, M. Madsen 2 on behalf of The DANREHAB Study Group. 1 The Heart Centre, Rigshospitalet, Department of cardiology, Copenhagen University Hospital, Copenhagen, Denmark; 2 National Institute of Public Health, Copenhagen, Denmark; 3 Department of cardiology, Roskilde, Denmark; 4 Steno Diabetes Centre, Gentofte, Denmark; 5 Bispebjerg University Hospital, Department of cardiology, Copenhagen, Denmark Bagground and aims: The Steno 2 study has shown beneficial effect of multifactorial intervention in patients with type 2 diabetes (T2DM) and microalbuminuria although results from the ACCORD study have given rise to some dispute according to the antihyperglycemic treatment. In a randomized clinical trial on comprehensive cardiac rehabilitation (CR) we found improvement in lifestyle and risk factors after 12 months of intervention compared to usual care (UC) among patients with T2DM. We now report if these effects are translated into clinical endpoints after 3 years. Materials and methods: We used a centrally randomized clinical trial comparing CR with UC. Of 1614 eligible patients, 770 (47%) were randomized in ways of 390 patients receiving UC and 380 patients CR. A total of 151 patients (20%) had known T2DM at randomization and 75 patients were allocated to CR and 76 patients to UC. Patients randomized to CR received 12 weeks of individually tailored, multi-disciplinary programme and clinical control after 3, 6 and 12 months. A composite blinded administrative register-based primary outcome measure included total mortality, myocardial infarction or first acute re-admissions due to heart disease. For secondary outcomes we used acute re-admissions and acute length of stay. We used Cox-regression for analysing time-to-event and Poisson regression for analysing length of stay and number of re-admissions. The follow-up time was 3 years after randomization. Results: Significantly differences in traditionally cardiovascular risk factors were obtained at the end of study period (p<0.05). More patients in the CR group received cardio protective agents compared to UC (p<0.05). There was no significant difference in the composite outcome (CR vs. UC; Hazard ratio: %CI: ) or when looking separately at the components in the primary outcome. Amongst the CR and UC patients, 57% and 62% were acute re-admitted at least once (p=0.80). There were 238 and 355 acute re-admissions for CR patients and UC patients (p=0.17) with a mean length of stay of 5.8 days and 7.7 days, respectively (p<0.05). Conclusion: Although the DANSUK trial find significantly greater reduction in blood pressure and improvement in glycemic control in patients with T2DM receiving CR compared to UC, these effects do not yet translate into the primary clinical endpoint at 3 years follow-up. A marginally significant reduction in acute length of stay in patients receiving CR was obtained. Shortness of intervention or follow-up period or a small sample size could explain some of the results that failed to appear. vs 75 years). The use of CRT-D declined with advancing age (48 vs 43 vs 29%; p<0.05 for <65 vs 75 years and for vs 75 years). At the 6-months evaluation, the prevalence of responders to CRT was similar in the three groups (58 vs 60 vs 62%, p>0.5). At the 12-months evaluation, LVEF (34±11%, 34±11%, 37±12%) and NYHA Class (2.0±0.7, 2.1±0.7, 2.2±0.7) significantly and similarly improved at all ages (p<0.05 vs baseline for all groups). During the follow-up (length: 19±13 months), all-cause mortality was higher only when comparing the 75 vs the <65 years patients (Kaplan-Meier analysis, p=0.005). In all groups, mortality was significantly associated with the non responder condition. Conclusions: CRT significantly improves left ventricular performance and functional capacity also in selected elderly patients. Mortality seems to be determined by the non responder condition. Specifically designed controlled clinical trials will have to verify and, eventually, generalize the results we have obtained Differences in dyssynchrony and response to cardiac resynchronization therapy between native LBBB and pacing-induced LBBB T. Arita, K. Ando, Y. Soga, M. Goya, H. Yokoi, M. Iwabuchi, M. Nobuyoshi. Kokura Memorial Hospital, Kitakyushu, Japan Background: Cardiac resynchronization therapy (CRT) improves global cardiac function through exerting more coordinated contraction/relaxation among segments. Although most of patients with heart failure and LBBB well respond to CRT, there still remains unclear whether effects of CRT are comparable between patients with native LBBB (Group: nl) and pacing-induced LBBB (Group: pl). Methods: Twentry-four patients in group nl and 12 patients in group pl underwent CRT due to conventional indications. At pre and 3-6 month post CRT, echocardiography was performed by which left ventricular volumes, functions and dyssynchrony parameters were obtained. In this study, global discoordination (spatial nonuniformity) index (GDI=ISR/(GSR+ISR), where ISR (internal strain rate)= ( S (n) - S (n) )dt)/2, GSR=global strain rate) was calculated in addition to conventional dyssynchrony (temporal nonuniformity) parameters. Results: LVESV were significantly different between two groups (p<0.01, 38.0±19.8ml (nl) vs 15.5±19.2ml (pl)), however, EF, MR area were not significantly different (9.7±8.2% vs 4.9±6.3%, 0.10±0.20 vs 0.065±0.13, respectively). Tissue Doppler derived longitudinal dyssynchrony parameters showed no difference (42.4±13.9ms vs 36.5±12.0ms), however, SPMWD showed significant difference (p<0.01, 268.9±84.6ms vs 155.2±94.7ms). More circumferential discoordination were observed throughout the cardiac cycle. However, no significant difference was observed as regards longitudinal discoordination. PREDICTORS OF OUTCOME IN CARDIAC RESYNCHRONISATION THERAPY 1899 Cardiac resynchronisation therapy is effective in elderly patients. The results of the InSync registry S. Fumagalli 1, M. Gasparini 2, M. Lunati 3,M.Santini 4, M. Landolina 5, A. Achilli 6, F. Tronconi 7, S. Valsecchi 7, N. Marchionni 1, L. Padeletti 8. 1 ICU, Geriatric Cardiology and Medicine Unit, AOU Careggi and University, Florence, Italy; 2 Istituto Clinico Humanitas, Rozzano, Italy; 3 Niguarda Hospital, Milano, Italy; 4 Ospedale San Filippo Neri, Rome, Italy; 5 Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; 6 Belcolle Hospital, Viterbo, Italy; 7 Medtronic Italia, Milan, Italy; 8 Internal Medicine and Cardiology Unit, AOU Careggi and University, Florence, Italy Purpose: The aging process of population arises some important issues about the usefulness in elderly subjects of medical interventions essential in younger patients. Aim of this study was to assess the influence of age on the effectiveness of cardiac resynchronisation therapy, alone (CRT) or in combination with an ICD (CRT-D). Chronic heart failure (CHF) is, in fact, one of the most important syndromes in elderly patients, associated with an increased incidence of disability and hospital admissions, and with a worsened health-related quality of life and a greater mortality. Methods: We evaluated the 1787 consecutive patients admitted for CRT or CRT- D in the eight Italian Centers taking part in the InSync Registry between 1999 and Accordingly to the endpoint of the present study, patients were divided into three age-groups (<65 years, n=571, age: 57±7; years, n=740, age: 70±3; 75 years, n=476, age: 78±3). Results will be presented following this stratification criterion. Results: Male gender (p<0.001) and the prevalence of coronary artery disease (p<0.001) increased with age. COPD, diabetes and renal insufficiency reached the highest prevalence in the years group. Left ventricular ejection fraction (LVEF) did not differ by age (26±8 vs 26±7 vs 27±8%, p>0.5), while NYHA Class worsened in elderly patients (2.9±0.6 vs 3.0±0.6 vs 3.0±0.6; p=0.017 <65 Global discoordination index Conclusion: In comparison to heart failure with pacing-induced LBBB, those with native LBBB have more dyssynchrony/discoordination especially in circumferential direction which might result in more reverse remodeling after CRT Outcome of chronic heart failure patients after device implantation is highly dependent on concomitant medical treatment regimen C. Adlbrecht, M. Huelsmann, M. Gwechenberger, C. Khazen, F. Wiesbauer, M. Ehlenitzky, S. Neuhold, T. Binder, I.M. Lang, R. Pacher. Medical University of Vienna, Vienna, Austria Background: Device implantation in chronic heart failure (CHF) for cardiac resynchronization therapy (CRT) with or without implantable cardioverter/defibrillator (ICD) is an established treatment option for symptomatic patients under medical baseline therapy. However, in the real world, medical therapy is not always up-titrated to the desirable dosages. This provides the opportunity to evaluate the impact of optimizing medical therapy in patients who had received a device therapy with proven effectiveness. Aim: This observational cohort study assessed the real life - effect of CRT compared to CRT/ICD therapy and the impact of concomitant pharmacotherapy on outcome. Results: Mean follow-up for the 205 CHF patients (95 CRT and 110 CRT/ICD) was 16.8±12.4months. In the total study cohort 83 (41%) reached the combined primary endpoint of all-cause death or cardiac hospitalization (CRT group: 25 (26%), CRT/ICD group: 58 (52.7%), p<0.001). Cox regression analysis revealed non-optimized medical therapy at follow-up (HR=2.080 [ ], p=0.013) and CRT/ICD versus CRT (HR=2.504 [ ], p 0.001) as significant predictors of the primary endpoint.

7 Predictors of outcome in cardiac resynchronisation therapy / ICD therapy: patient and device monitoring 307 Conclusion: Our data stress the importance of professional monitoring and titration of pharmacotherapy not only in medically treated CHF patients but also in patients under device therapy by a heart failure unit or a specialized cardiologist Effect of heart failure history on CRT patient survival D. Gras 1,C.Muto 2, T. Maounis 3, A. Schuchert 4, M.-G. Bongiorni 5, R. Frank 6, T. Vesterlund 7, E. Boulogne 8, L. Padeletti 9 on behalf of the MASCOT Investigators. 1 NCN, Nantes, France; 2 Ospedale Loreto Mare, Naples, Italy; 3 Onassis Cardiac Surgery Center, Athens, Greece; 4 Friedrich-Ebert-Krankenhaus, Neumuenster, Germany; 5 Ospedale Cisanello, Pisa, Italy; 6 Hopital Pitié-Salpetrière, Paris, France; 7 Aalborg Hospital, Aalborg, Denmark; 8 St. Jude Medical, Zaventem, Belgium; 9 Ospedale Careggi, Florence, Italy Purpose: Patients candidate for Cardiac Resynchronization Therapy (CRT) often have a long history of Heart Failure (HF) having required numerous hospitalizations for their heart disease. We investigated whether the time since the first diagnosis of HF and the number of hospitalizations for HF in the 6 months preceding the implantation of the CRT device, had any effect on patient survival. Methods: The MASCOT study enrolled patients candidate for CRT and followed them for 2 years. Information on the patients heart failure history was collected at baseline. Post-hoc survival analyses were performed on the 393 randomized patients to investigate the effect of time since HF diagnosis (above vs. below median) and the number of HF hospitalizations in the 6 months preceding the CRT device implant (none vs. 1 vs. 2 or more) on the 2 year patient survival. Results: The median duration since the diagnosis of heart failure was 31.2 months. 43% of patients had no HF hospitalization, 32% had 1 hospitalization only, and 25% of patients had at least 2 hospitalizations in the 6 months preceding CRT device implant. Both a longer history of Heart Failure (p=0.04) and an increasing number of hospitalizations for Heart Failure in the 6 months preceding CRT implantation (p< Figure 1) were significantly associated with decreased survival over a 2-year follow-up period. Reverse remodeling, defined as at least a 10% decrease in LVESV, was less in the older group (26% vs 46%; p=0.03). Moreover, there was no difference between two groups neither in the time to first occurrence of Atrial Fibrillation (AF) nor in the time of occurrence of permanent AF. Parameters <70 (n=202) 70 (n=207) P-value Age (years) 60±7 75±4 NYHA Class III/IV (%) 87/13 86/ Ischemic Cardiomyopathy Diabetes (%) QRS width (ms) 165±31 162± CRT-P/CRT-D (%) 42/58 46/ ACE/ARB (%) Beta Blocker (%) Diuretics (%) Amiodarone (%) Spironolactone (%) Quality of life 45±21 45± LVEF (%) 24±6 26± Conclusions: Pts >70 yrs benefited as well as pts <70 yrs from CRT, in terms of symptoms, cardiac function, mortality and HF hospitalization. Reverse remodeling was observed more frequently in pts <70 years Heart disease and QRS duration predict hyperresponse to cardiac resynchronization therapy L. Koutbi, F. Franceschi, J. Mancini, E. Bastard, G. Habib, J.C. Deharo. AP-HM - Hopital de la Timone, Marseille, France Purpose: After cardiac resynchronization therapy (CRT), some patients experience a remission of heart failure symptoms. They have been qualified as hyperresponders (HR) to CRT. Little is known about this population. The aim of this study was to determine the incidence and predictive factors of hyperresponse to CRT. Methods: We performed a single-center study of patients successfully implanted with CRT devices at our institution from 2004 to At implantation, all patients had a III NYHA functional status and a left ventricular ejection fraction (LVEF) 35%. Clinical and echographic data were prospectively collected before implantation and at 6 months. Patients were considered as HR when LVEF was above 45% and NYHA functional class was II at 6 months. Results: Out of 175 consecutive patients who succesfully received a CRT device, 18 (10.3%) were HR at 6 months. In HR, non-ischemic cardiomyopathy (NICM) was more frequent than in non-hr (72.2% vs 41.4%; p=0.013), baseline LVEF was less depressed (28.8±5% vs 24.7±5%; p=0.003), baseline QRS duration was higher (180±25 ms vs 164±30 ms; p=0.03), and QRS narrowing after CRT was more important (-51±28 ms vs -32±29 ms; p=0.013). No difference was found in age, sex and medical therapy. Conclusion: Hyperresponse to CRT occurred in 10.3% of our patients at 6 months. HR were more likely to occur in case of NICM, less depressed LVEF, wider baseline QRS and a higher shortening of the QRS after CRT. Figure 1 Conclusions: HF patients who are typically candidate for CRT, could potentially benefit from earlier consideration for device implantation, in terms of further improvement in survival and hospitalization. These preliminary findings should, however, be confirmed by a controlled study Old age does not influence cardiac resyncronization therapy effects A. Vicentini 1,S.DeFeo 1,C.Muto 2, T. Maounis 3, A. Schuchert 4, C. Gazzola 5, E. Boulogne 6, L. Pedeletti 7. 1 Casa di Cura Dott. Pederzoli, Peschiera del garda, Italy; 2 Ospedale Loreto Mare, Naples, Italy; 3 Onassis Cardiac Surgery Center, Athens, Greece; 4 Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany; 5 St. Jude Medical, Milan, Italy; 6 St. Jude Medical, Zaventem, Belgium; 7 Ospedale Careggi, Firenze, Italy Purpose: Cardiac resynchronization therapy (CRT) has been demonstrated to improve symptoms, cardiac function and survival in pts with systolic heart failure and electrical dyssynchrony. Whether age negatively affects the response to CRT is unclear. Methods: The MASCOT study enrolled 409 pts candidate for CRT, with no exclusion criteria on upper age limit. We performed post-hoc analyses on pts either > or <70 yrs old at the time of device implantation. Results: Pts >70 yrs has more often an ischemic cardiomyopathy, were less on b-blockers and spironolactone, had a slightly better cardiac function than pts < 70 yrs (Table 1). After 12 months of CRT, pts > 70 yrs derived significant improvements in NYHA Class, Quality of Life, LVEF, with similar degree to pts < 70 yrs. Mortality (12% vs. 9%) and HF hospitalizations (15% of pts vs. 16% of pts) were no different. IMPLANTABLE-CARDIOVERTER DEFIBRILLATOR THERAPY: PATIENT AND DEVICE MONITORING 1909 Event notifications by remote monitoring systems performing automatic daily checks: load, characteristics and clinical utility N. Varma 1,A.Epstein 2,A.Irimpen 3,L.Gibson 4,C.Love 5. 1 Cleveland Clinic, Cleveland, United States of America; 2 University of Alabama Medical Center, Birmingham, United States of America; 3 Tulane University Medical Center, New Orleans, United States of America; 4 BIOTRONIK, Inc., Lake Oswego, United States of America; 5 Davis Heart & Lung Research Institute, Columbus, United States of America Purpose: Remote Monitoring technology (RMT) may facilitate data access but this has not been tested. RMT systems that automatically (w/o patient or physician interaction) perform daily surveillance may best detect important events but there is concern that this mode risks data overload, potentially increasing office visits (OVs). The TRUST multicenter trial tested this hypothesis. Methods: 1,312 patients implanted with ICDs with RMT were randomized 2:1 to remote monitoring (RM) or conventional (C) groups. In RM, follow up OVs occurred at 3 and 15 months. In between, RMT updated device status daily and triggered event notifications (EN) for conditions listed in Table. Evaluation of EN by RMT and ENs prompting OVs were tracked. C patients were evaluated with OVs every 3 months. Results: RM was a typical ICD population (63±13 yrs; 72% male; NYHA class II 56%; LVEF 29±11%; CAD 65%; amiodarone 14%; 1 prevention indication 72%; and DDD 58%). During a possible 372,011 transmission days, 5715 ENs were received (1.5%). 409 of 843 (48.5%) RM patients generated 1 EN (median 6 EN/patient). Most ENs were due to arrhythmias. Median time from onset to evaluation of VT/VF

8 308 Implantable-cardioverter defibrillator therapy: patient and device monitoring events in RM patient was < 2days,vs.> 30 days in C. EN evaluation resulted in management decision made remotely in 89%. Of 11% resulting in OV, 51% required significant reprogramming or anti-arrhythmic medication change (compared to 29% of OV in C). Event Notification Type Total ENs # Pts Mean per pt ± SD Median per pt VT and/or VF detection (32.8%) 8.01± Duration of mode switching or Atrial burden > 10% (2.5 h) (8.3%) 30.8± SVT detection (10.0%) 8.87± Shock impedance <25 or > (0.5%) 12.2± Ventricular lead impedance <250 or > (0.5%) 7.6± VT/VF and 30 J shock ineffective (2.2%) 1.24± Atrial lead impedance <250 or > (0.4%) 6± VT/VF detection programmed to OFF 1 1 (0.1%) N/A N/A Conclusions: Event notifications generated by RMT systems with automatic daily surveillance occur infrequently, without overburdening clinic resources, and provide rapid detection and notification of important events Early detection of heart failure decompensation by Optivol fluid status monitoring R. Bover Freire 1, I. Fernandez Lozano 2, J. Fernandez De La Concha 3, X. Beiras Torrado 4, V. Monivas Palomero 2, J.J. Garcia Guerrero 3, E. Garcia Campo 4, J. Perez-Villacastin 1. 1 Cardiology Department, Hospital Clinico San Carlos, Madrid, Spain; 2 Cardiology Department, Hospital Puerta de Hierro, Madrid, Spain; 3 Cardiology Department, Hospital Infanta Cristina, Badajoz, Spain; 4 Cardiology Department, Hospital Xeral de Vigo, Vigo, Spain Introduction: Up to 90% of heart failure decompensations present progressive pulmonary congestion. Intrathoracic impedance monitoring (Optivol feature, Medtronic) may alert of progressive heart failure patient deterioration. The diagnostic accuracy of Optivol monitoring is not well established. Methods: We performed a multicentre prospective observational trial in four hospitals in Spain. All patients had a Medtronic ICD or ICD/CRT device with Optivol capability. Heart failure decompensations (defined by worsening of heart failure signs and symptoms) and Optivol alerts were recorded during the study. Results: 100 patients were included in the study protocol. 89% were male, and the mean age was 65.0±11.55 years. 60.8% had an ICD and 39.2% an ICD/CRT device. Etiologies were more frequently ischemic (64.6%) or idiopathic (26.4%) myocardiopathy. 60.7% had a heart failure diagnosis, 21.6% were in NYHA functional class II, and 56.9% in NYHA III. Mean ejection fraction was 31.0±13.3%, and the mean BNP value at study entry was pg/ml. 74.2% were on beta blockers, 95% on ACEIs or ARBs. During the follow-up were performed 140 device interrogations. There were 20 events of new-onset or decompensated heart failure (13 with preceding Optivol alert) and 40 Optivol sound alerts (27 without posterior clinical changes) during a mean follow-up of 52 months. The Optivol alert detected clinical heart failure deterioration with 65% sensitivity, 77.5% specificity, 32.5% positive predictive value, and with a negative predictive value of 93%. Multivariate analysis showed BNP values (p=0.001), patient age (p=0.049) and left ventricular ejection fraction (p=0.059) at baseline as predictors of heart failure decompensation preceded by Optivol alert (true positive events). There was no difference in Optivol diagnostic capability stratified by type of device (ICD vs. ICD/CRT) or patient medication (beta blockers and/or ACEIs/ARBs). Conclusions: A device-based algorithm that alerts patients in case of decreasing intrathoracic impedance may facilitate the detection of heart failure decompensation. In our prospective study, despite an acceptable sensitivity, the positive predictive value was too low. Adequate patient selection before implanting a device with Optivol capability could be crucial for improving diagnostic accuracy Implantable cardioverter defibrillator recipients: comparison of primary and secondary indicated patients during long-term follow-up C.J.W. Borleffs, G.H. Van Welsenes, L. Van Erven, R.J. Van Bommel, E.T. Van Der Velde, F.R. Rosendaal, E.E. Van Der Wall, J.J. Bax, M.J. Schalij. Leiden University Medical Center, Leiden, Netherlands Background: Large trials have shown the beneficial effect of an implantable cardioverter defibrillator (ICD) for secondary, as well as primary prevention of sudden death. The aim of this study was to assess the long-term follow-up of ICD recipients and to compare patients with a primary to those with a secondary indication. Methods: A total of 1870 consecutive patients (1519 male, age 63±12 years) were evaluated at ICD implantation. Seven-hundred-eighty-seven patients (42%) received an ICD for secondary prevention: after a ventricular arrhythmia lasting longer than 30 seconds or with hemodynamic consequences. The remaining 1083 had a primary indication. During follow-up, all events triggering appropriate device therapy and death were noted. Results: During a mean follow-up of 39±31 months, a total of 323 (17%) patients died. Appropriate device therapy was noted in 590 (32%) patients, consisting of 2.3±5.3 shocks and 24.8±148.0 ATP. Cumulative event rate (Figure) for death after six years was 28% for primary prevention and 26% for secondary prevention (p=0.2). Calculated cumulative rate of appropriate therapy at six years was 34% for primary prevention and 52% for secondary prevention (p<0.001). Conclusions: In a large cohort of ICD-recipients, comparison of the long-term follow-up in patients with a primary or a secondary indication shows major differences in the occurrence of ventricular arrhythmias, causing ICD therapy. Survival is not significantly different between the two groups Hypertrophic Cardiomyopathy: Single-center experience with ICD implantation & follow-up L. Valtuille, N. Galizio, J.L. Gonzalez, M. Ramirez, A. Fernandez, J.H. Casabe, E. Guevara, F. Landeta, M. Diez, L. Favaloro. Favaloro Foundation - University Hospital, Buenos Aires, Argentina Introduction: Implantable cardioverter defibrillator (ICD) implantation in survivors of sudden cardiac death (SCD) and/or sustained VT in hypertrophic cardiomyopathy (HCM) is widely accepted. However, experts recommendations regarding primary prevention (PP) patients (pts) is not uniform. Prospective registries could offer additional information in clinical decision-making. Objectives: To describe a group of pts with HCM undergoing ICD implantation at our institution, to analyze implantation characteristics and to describe the outcomes of this population. Methods: Between 1994 and 2009, from a prospectively followed HCM group of 349 pts, 45 (12.8%) received an ICD. Pts were divided according to primary (PP) or secondary prevention (SP) of SCD. A high defibrillator threshold (DFT) was defined as >20 J for VF reversion. Follow-up analysis was performed with the Kaplan Meier method. Baseline characteristics: age 35.5 yr (range 4-81 yr), 27 males (60%), NYHA II-IV 29.6%, mean LVEF 54.1% (9 pts LVEF<50%). Results: Thirty-six pts underwent ICD implantation for PP and nine for SP. Among PP pts, 10 (27.8%) presented one major risk factor for SCD and 24 (66.7%) two or more major risk factors. The remaining 2 pts (5.6%) presented either LVEF <30% or NYHA III with left ventricular tract obstruction. ICD implantation: most devices were unicameral (66.7%). Nine out of 41 pts (22%) had a high DFT. Follow-up was longer in SP pts than in PP pts (87.6 vs 22.5 months, p 0.01). Appropriate shocks: Six pts (13.3%) had shocks due to VT/VF. Mean time to shock was 20.9 months (range 15 days to 68.2 months). The SP group had a higher proportion of pts receiving shocks (n=3, 33.3%) compared to the PP group (n=3, 8.3%) However, there were no differences in survival free of shocks between these two groups (log rank=0.56). Inappropriate shocks: In the PP group, 9 pts (25%) received shocks (7 SVT, 2 noise). In the SP group, two pts (22.2%) received shocks (AF and noise). Four pts (8.8%) underwent heart transplantation. Death occurred in 3 pts (8.3%), all of them in the SP group. Mean time to death was 59.3 months (range months). Cause of death was either sudden or presumed to be sudden. Conclusions: In our study population, most pts presented two or more risk factors for SCD. Rate of ICD implantation was 12.8%. One-fifth of pts presented high DFTs. A higher proportion of pts in the SP group received shocks due to VT/VF; however, event free survival was not different between SP and PP groups. PP pts presented more than three times the incidence of inappropriate shocks compared to the incidence of shocks due to VT Longevity of ICD pulse generators: 10-year multicenter experience L.M. Kallinen, R. Hauser on behalf of Multicenter Registry Investigators. Minneapolis Heart Institute Foundation, Minneapolis, United States of America Purpose: Despite their widespread use the clinical performance of ICD pulse generators (IPG) is poorly characterized. The aim of this prospective multicenter study was to assess IPG battery longevity, and causes of other IPG failures and replacements. Methods: Data for IPGs that were removed from service at 9 centers were entered into the Multicenter Registry. Information included manufacturer, model, dates of implant and failure, signs of battery depletion or failure, and cause of failure. Results: From 1998 to 2008, 2,320 IPGs were removed from service for normal battery depletion, electronic or housing defects, and for manufacturers advisories (Table). Overall, there was no difference in longevity between manufacturers (p=0.053). However, Medtronic single and dual chamber IPGs exhibited longer battery life than Boston-Scientific or St. Jude Medical IPGs (p>0001). ICD- CRT IPGs exhibited shorter battery longevity for all manufacturers compared to single or dual chamber IPGs (p>0.0001). The incidence of electronic and housing defects was significantly different between manufacturers (p>0.01).

9 Implantable-cardioverter defibrillator therapy: patient and device monitoring / Antibradycardia pacing: from stimulation to function 309 Reason for removal from service and average implant times for IPG type and manufacturer All ICD Pulse Boston Medtronic St. Jude Generators Scientific Medical No. ICD Pulse Generators 2,320 1,022 1, No. Removed for Battery Depletion 2,161 (93%) 973 (95%) 912 (91%) 276 (93%) No. Removed for Electronic, Housing, or Other Failure 91 (4%) 33 (3%) 42 (4%) 16 (5%) No Removed for Advisory 68 (3%) 16 (2%) 47 (5%) 5 (2%) Average Implant Times (months ± SD) All Pulse Generators 51±20 52±17 51±23 49±18 ICD Pulse Generators Removed for Normal Battery Depletion Single Chamber PG 60±17 59±15 67±18 53±18 n=1,021 n=502 n=314 n=205 Dual Chamber PG 54±15 52±12 57±17 46±14 n=658 n=321 n=279 n=58 ICD-CRT PG 41±12 38±10 42±12 42±10 n=235 n=58 n=169 n=8 Conclusion: Short ICD-CRT battery longevity, electronic and housing defects, and manufacturers advisories have had a negative impact on ICD pulse generator performance Lead dislodgement and lead related cardiac perforation in ICD patients G.M. Nair, J.S. Healey, L. Long, J. Dean, S. Divakaramenon, S.C. Ribas, C.A. Morillo, S.J. Connolly. McMaster University, Hamilton, Canada Introduction: Lead related issues following ICD implantation in published literature range from 1% to as high as 8% and necessitate repeat surgical procedures. Methods: A retrospective analysis of ICD implants between April, 2005 and October, 2008 at our institution was performed. Results: A total of 1339 patients received ICDs with active fixation RV leads. 125 (9.3%) lead related issues were identified of which 47 (3.5%) were attributed to lead dislodgements and 7 (0.5%) to lead related cardiac perforation. A statistically significant difference in lead dislodgement rates between the three major vendors was not noted. ICD leads from vendor 1 (see table) was associated with a higher rate of cardiac perforation compared to leads from the other vendors- 5cases (0.88%; p <0.001). This was close to the lower end of published lead perforation rates for leads of similar design. There were no deaths related to repeat procedures. 3 (0.22%) patients needed more than 1 procedure for lead repositioning. 2 (0.15%) patients developed device infection following intervention for lead dislodgement. ICD Manufacturer Total No of Devices - Right Ventricular Right Ventricular From April 2005 Active Fixation Active Fixation to October 2008 Lead Dislodgement Lead Perforation (N) N (%) N (%) Vendor (5.07) 5 (0.88) Vendor (2.86) 1 (0.24) Vendor (1.72) 1 (0.29) P value for Test of Two P value for Test of Two Proportions - Dislodgement Proportions - Perforation Vendor 1 vs (NS) <0.001 Vendor 1 vs (NS) <0.001 Vendor 2 vs (NS) 0.9 (NS) Conclusions: Lead dislodgement and lead related cardiac perforation are responsible for repeat interventions in ICD patients. ANTIBRADYCARDIA PACING: FROM STIMULATION TO FUNCTION 1920 The relationship between left ventricular dyssynchrony and left atrial function in right ventricular pacing D. Leong, A. Mitchell, H. Lim, H. Dimitri, B. John, M. Stiles, M. Alasady, D. Lau, P. Sanders, G. Young. University of Adelaide, Adelaide, Australia Purpose: Right ventricular (RV) pacing may be associated with deleterious effects on cardiac function and left ventricular (LV) synchrony. The effect of RV pacing and LV dyssynchrony on left atrial (LA) structure and function are unknown, however. We hypothesised that LA function is impaired by 1) RV pacing and 2) LV dyssynchrony. Methods: Fifty subjects (mean age 73±13 years) and left ventricular ejection fraction (60±9%) were studied: 40 with permanent RV pacing over a 28±8-month period, and 10 free of cardiac disease, hypertension, and diabetes mellitus (controls). During transthoracic echocardiography, M-mode images were acquired in the parasternal short axis view at the level of papillary muscles, and grey-scale and tissue velocity images were acquired in 3 apical views. LV synchrony was measured by 1) standard deviation of values for time-to-peak systolic tissue velocity on a 12-segment model (tissue Doppler DI), 2) standard deviation of values for time-to-peak systolic longitudinal 2D strain on an 18-segment model (2D DI), and 3) septal-posterior wall motion delay (SPWMD). LA strain was measured using speckle tracking: a region of interest was marked on the left atrium in apical 4- and 2-chamber views and longitudinal strain values were averaged. Septal A was measured as the peak tissue velocity at the septal mitral annulus in late diastole on tissue velocity imaging. LA volume wasmeasured using biplane method of discs. Results: RV pacing was associated with greater LV dyssynchrony than controls; tissue Doppler DI 41.7±3.4 v. 17.3±5ms (p =0.003), 2D DI 69.6±3.4 v. 37.5±5.2ms (p<0.001). Longitudinal LA strain and septal A were significantly greater among controls than paced subjects (24.8±9.3 v. 15.3±6.2%, p = and 8.5±1.2 v. 6.6±1.9cm/s, p = 0.01 respectively). There was a significant linear association between longitudinal LA strain and both tissue Doppler DI (r = 0.34, p = 0.03) and 2D DI (r =0.39,p =0.01). There was a trend towards a linear relationship between LA strain and SPWMD (r =0.37, p = 0.07). There was a significant linear association between septal A and tissue Doppler DI (r =0.42, p =0.002), 2D DI (r =0.3,p =0.04), and SPWMD (r =0.37, p =0.03). LA volume indexed to body surface area increased in a linear fashion with the duration paced (r =0.45, p =0.005). Conclusions: There is a consistent association between different indices of LV dyssynchrony and LA contractile function in patients undergoing permanent RV pacing. The LV dyssynchrony induced by RV pacing may impair LA function,resulting in adverse LA remodelling. LA volume increases with the duration paced Long term results of patients with AV-block randomized to biventricular pacing versus DDD(R)-pacing A.E. Albertsen, P.T. Mortensen, H. Egeblad, J.C. Nielsen. Aarhus University Hospital, Aarhus, Denmark Introduction: Experimental studies and clinical trials indicate that single site right ventricular pacing causes left ventricular (LV) dyssynchrony and dysfunction increasing the risk of congestive heart failure. We investigate if biventricular (BIV) pacing can preserve LV ejection fraction (LVEF) as compared with standard dual chamber DDD(R)-pacing in patients with high grade AV-block referred for conventional pacemaker implantation. Methods: Twenty nine consecutive patients with high-grade AV-block were randomized to permanent DDD(R) (n=15) or BIV pacing (n=14). All patients had bipolar active fixation leads implanted in the right atrium and in the right ventricular septum connected to a BIV pacemaker. In the BIV-group, a dedicated LV-lead was implanted in a lateral coronary sinus tributary. Endpoints were: LVEF measured by 3-D echocardiography and 6 minutes walk test, all estimated the day after pacemaker implantation (baseline) and after one and 3 years of follow-up. Mean±SD are reported. Results: Mean age was 75 (range 25-90) years. At three years of follow-up, LVEF decreased in the DDD(R)-group from 60.0±4% at baseline to 53.2±11% (p=0.06) and remained unchanged in the BIV-group 54.5±8% and 56.6±11%, (p=0.50). No difference in LVEF was observed between groups at the end of follw-up (DDD(R)-group 53.2±11% vs. BIV-group 56.6±11%, p=0.44). Walking distance was unchanged in the DDD(R)-group after 36 months of pacing (baseline 480±46m, 36 months 485±70m; p=0.74) but increased significantly in the BIV-group (baseline 469±70m, 36 months 509±66m; p<0.001). Conclusions: In patients with high-grade AV-block, BIV-pacing preserves LVEF and increases walking distance as compared to DDD(R)-pacing. These results indicate that BIV-pacing may prevent pacing induced heart failure in patients with AV-block who need ventricular pacing LV apex and LV septal pacing for long term preservation of mechanical coordination and ventricular contractility F.W. Prinzen 1, R.W. Mills 1,L.M.Mulligan 2, N. Skadsberg 2, R.N. Cornelussen 1, F. Van Wijk 3. 1 Cardiovascular Research Institute, Maastricht, Netherlands; 2 Medtronic, Minneapolis, United States of America; 3 Bakken Research Institute Medtronic, Maastricht, Netherlands Objective: Conventional right ventricular (RV) apex pacing is associated with asynchronous activation and reduced left ventricular (LV) pump function. Previous studies have shown acute hemodynamic benefits over RV apex pacing by LV septal or LV apex pacing. We investigated whether this improvement translates into a long-term benefit and how acute LV function during single site LV pacing compares to biventricular pacing. Methods: After AV-nodal ablation, mongrel dogs were randomized to receive 16 weeks of VDD pacing at the RV apex (RVa, n = 9), RV septum (RVs, n=7), LV apex (LVa, n = 7), or LV septum (LVs, n = 8; trans-ventricular septal approach). LV contractility (dp/dtmax/pinstantaneous) was measured during normal ventricular conduction from atrial pacing (AP) and during ventricular pacing 1-3 hours and 16 weeks after implant. At 16 weeks, contractility was also measured after an acute switch from the implant site (IS) to the non-implanted apex (both for LV septal group) and to RV apex + LV lateral (BiV) pacing. Results: While acute and chronic RVa and RVs apex pacing significantly reduced contractility (Figure a; mean ± SD, *p<0.05 contrasted to 100%), LVs and LVa pacing maintained contractility near AP levels. After 16 weeks of RVa pacing, switching to LVa pacing (but not BiV pacing) increased contractility (Figure

10 310 Antibradycardia pacing: from stimulation to function / Predictors of cardiovascular events: lessons from large databases b). After 16 weeks of LV pacing, switching to RV apex pacing decreased contractility. Collectively, acute LV apex pacing enhanced contractility over acute BiV (p<0.001). synchronisn > 94%. Pts were divided in two groups on the basis of RVSP and RVEF: Group I (RVSP < 40 mmhg and RVEF > 50%) and Group II (RVSP>40 mmhg and RVEF<50%).After 48 months there was statistical significant variation in LVEF,LVDD and MPI in both groups (p<0.001).however the Kaplan Meier curve demonstrated that only in group II there was a significant increase in the overall morbidity and/or hospitalization for HF during time as compared to pts of group I (p<0.05). Conclusion: right systolic pressure and function contribute to identify pts with baseline abnormal LVEF who develop a worse clinical course after permanent RVAp in long term follow-up. Therefore such parameters allow detecting pts in whom avoid RVAp and who need alternative and/or integrated modality of pacing. Figure 1 Conclusions: Chronic LVa and LVs pacing maintain contractility near normal levels, and at a higher level than RVa and RVs pacing. Acutely, LV apex pacing improves contractility compared to BiV pacing Adeno-associated virus-mediated HCN4 gene transfer increases spontaneous ventricular escape beats in canine model of AV block N. Murakoshi 1, R. Kamimura 2,K.Setoyama 2,D.Xu 1, M. Igarashi 1, K. Yoshida 1, K. Tanoue 2, Y. Sekiguchi 1, I. Yamaguchi 1,K.Aonuma 1. 1 University of Tsukuba, Tsukuba, Japan; 2 Kagoshima University, Kagoshima, Japan Purpose: Hyperpolarization-activated, cyclic nucleotide-gated cation (HCN) channels, carrying an inward current termed If, were encoded by four subtypes of HCN genes. HCN4 is the predominant HCN transcript in the adult sinoatrial node, and plays an important role in the generation of cardiac pacemaker potentials. In this study, we investigated whether the HCN4 gene therapy using an adeno-associated virus (AAV) vector was effective and safe for canine model of atrioventricular (AV) block. Methods: Canine model of AV block was generated by catheter ablation to AV node. Electronic pacemaker was implanted, and pacing rate was set at 40 bpm in each group. AAV-HCN4 was injected around the right bundle of the heart (AAV- HCN4 group). As control, AAV-EGFP was transferred likewise (AAV-EGFP group). We checked the percentage of electronically paced beats and sensed beats in both groups once a week for 8 weeks. Four weeks after gene transfer, we investigated the conduction sequence in the right ventricle using CALTO system, and the response of HR to an infusion of isoprotelenol (ISP). Results: In AAV-EGFP group, approximately all of the ventricular rhythm was originated from electronic pacemaker, and spontaneous ventricular escape beats were rare. In AAV-HCN4 group, spontaneous ventricular escape beats accounted for 23% of all ventricular beats at 2 weeks, 14% at 4 weeks, and 16% at 8 weeks. No arrhythmias such as sustained ventricular tachycardia were observed in both groups. The HR increased by 171% in response to an infusion of ISP in AAV- HCN4 group, whereas HR increased by 146% in AAV-EGFP group. The CALTO system showed that the initiation of the conduction sequence was around the injected points in all animals of the AAV-HCN4 group. GFP-positive cells were focally detected in the right ventricular septum of AAV-EGFP group. Conclusions: AAV-mediated HCN4 gene transfer has a therapeutic potential as a partial alternative to electronic pacemakers. However, it appears that the therapeutic strategy cannot sufficiently compensate for the decreased HR, further development of approach will be needed for the clinical application Assessment of right ventricular function can predict the long term clinical evolution of patients with permanent conventional dual-chamber pace-maker E.Moro,C.Marcon,E.Marras,G.Allocca,N.Sitta,P.Delise. Conegliano General Hospital, Conegliano, Italy Introduction: the negative haemodynamics effects of permanent dual-chamber right ventricular apical pacing (RVAp) on cardiac performance are well known, however which patients (pts) are at risk of heart failure (HF) and/or worse clinical outcome is still not exactly established. Aim: identify which parameters of cardiac function predict negative long term clinical evolution in pts with permanent RVAp and reduced left ventricular ejection fraction (LVEF) but who have not indication to cardiac resynchronization therapy (CRT). Population: we studied 38 pts (22 M, 16 F, mean age 74 years) with advanced atrio-ventricular block and clinical indication to permanent cardiac pacing. All pts had basal LVEF 50% and absent indication to CRT. Methods: pacemaker interrogation, clinical and Echo/Doppler follow-ups were performed at post-implantation and after 12, 24, 36 and 48 months. The following parameters were collected: LVEF, left ventricular end-diastolic diameter (LVDD), myocardial performance index (MPI), right ventricular systolic pressure (RVSP), right ventricular ejection fraction (RVEF) and HF morbidity/hospitalization. Results: the percentage of ventricular pacing was > 95% and of atrio-ventricular 1925 Left ventricular electromechanical dyssynchrony after long-term ventricular pacing in patients with acquired atrioventricular block R. Costa, M.I.P. Leao, R.F. Mori, G. Giannini, K.R. Silva, R.T. Silva, C.E.B. Lima, S.P.L. Costa, I.M. Penteado. Associação para Estudo e Desenvolvimento da Eletroterapia Cardíaca, Sao Paulo, Brazil Background: Right ventricular pacing (RVP) may lead patients with impaired left ventricular (LV) function to dyssynchrony and heart failure. The effects of RVP in patients with normal LV function remain unclear. Purpose: To evaluate the effects of long-term RVP on ventricular synchrony in patients with normal LV function. Methods: Electromechanical delay was accessed by Tissue Doppler in 36 consecutive patients with acquired AV block and normal LV function at first implant. LV dyssynchrony was measured by the time interval between the shortest and longest electromechanical delays in the five LV segments. It was established by a delay greater than 65ms. LV ejection fraction was estimated by Simpson. Patients were divided in two groups according to the LV dyssynchrony occurrence and assessed under clinical, demographic and echocardiographic aspects. Student s t- test, Qui-square test and Person s coefficient were performed. Results: After 8.4±6.4 years of RVP 25 patients (69.9%) were in NYHA FC I. LV dyssynchrony was detected in 14 (38.9%) pts. Electromechanical delay was 125.8±40.5 ms and 34.2±17.2 ms in patients with and without dyssynchrony, respectively. No significant difference was observed between both groups of patients (Table). The correlation between the studied variables and LV dyssynchrony was not significant. Variables LV Dyssynchrony absent LV Dyssynchrony present N 22 (61.1%) 14 (38.9%) Male 59.1% 50.0% Age at PM implantation (y.o.) 68.0± ±12.1 Time under pacing (years) 8.2± ±7.1 NYHA FC I 59.1% 67.7% LVEF 0.54± ±0.09 Conclusion: Although LV dyssynchrony were frequent after long-term RV pacing, no correlation was found with clinical or cardiac functional performance. PREDICTORS OF CARDIOVASCULAR EVENTS: LESSONS FROM LARGE DATABASES 1950 The eight independent predictors of elevated resting heart rate among 8922 patients with stable coronary artery disease L. Lorgis 1, M. Zeller 2, P. Jourdain 3, J. Beaune 4, J.P. Cambou 5, B. Vaisse 6, B. Chamontin 5,Y.Cottin 1 on behalf of LHYCORNE. 1 Centre Hospitalier Universitaire de Dijon, Dijon, France; 2 LPPCE,IFR 100, University of Burgundy, Dijon, France; 3 Centre Hospitalier Rene Dubos, Pontoise, France; 4 Centre Hospitalier Universitaire, Lyon, France; 5 Centre Hospitalier Universitaire, Toulouse, France; 6 Centre Hospitalier Universitaire, Marseille, France Background: Heart rate (HR) is a key determinant of both myocardial ischemia and prognosis in patients with coronary disease. Reducing HR is known to relieve ischemia and improve cardiovascular prognosis. However, there is currently no information about HR distribution and predictors of high heart rate in patients with stable coronary artery disease (CAD). Method: The LHYCORNE cohort was a prospective, observational study primary care physicians included consecutive stable CAD patients with treated hypertension. 98% of patients were also followed by cardiologists. Only patients with atrial fibrillation were excluded from the analysis. In these patients, we analysed HR distribution, and factors independently associated with HR above the mean cohort HR. Results: 8922 stable CAD patients in sinus rhythm (76% of males, 66±11 years, BP:141/82 mmhg, 26% diabetes). Mean resting HR was 70±6 bpm and the distribution was: <60 bpm (7%); bpm (38%); bpm (38%); bpm (14%); >90 bpm (2%). Sixty-two percent of patients were on beta-blockers and had a mean 69±8 bpm resting HR versus 73±8 bpm without beta-blockers

11 Predictors of cardiovascular events: lessons from large databases 311 (p<0.001). In multivariate analysis we identified 8 independent predictors of HR over 70 bpm (figure). Conclusion: This large cohort shows that in the real life, over 50% of stable coronary patients have a HR>70 bpm, presenting a particularly high-risk profile. These data underline the need to measure and analyse HR in stable coronary patients taking into account its therapeutic and prognostic role. Methods: The CHADS2 score was calculated in 18,888 patients without AF included in the European REACH registry in 18 European countries between 2003 and ,254 (86%) patients had established cardiovascular disease ( symptomatic patients) and 2,634 (14%) were included on the basis of multiple risk factors with no prior vascular disease ( asymptomatic patients). Ischemic events wererecordedduringa2yearsfollow-upperiod.maccewasdefinedasthe composite of CV Death, MI or Stroke. Results: The mean age of the population was 66.6±9.7 years. 69% of patients were male and 32.5% diabetic. A CHADS2 score of 0, 1, 2, 3, 4, 5 and 6 was found in 1,911 (10.1%), 5,323 (28.2%), 5,478 (29%), 3,623 (19.2%), 1,930 (10.2%), 527 (2.8%), and 96 (0.5%) patients, respectively. CHADS2 score levels were associated with a stepwise increase in rates of death and MACCE (p< for both) (Figure). The correlation between CHADS2 score and events was stronger in symptomatic patients. Among symptomatic patients (without AF) the CHADS2 score was also predictive of the occurrence of non fatal stroke (5.5% for CHADS2 3 vs 1.5% for CHADS2 <3; p< ) Prognostic value of resting heart rate in a general population of patients with stable coronary artery disease: a prospective, single center, cohort study M. Ruiz Ortiz, E. Romo Penas, C. Ogayar Luque, D. Mesa Rubio, M. Delgado Ortega, J.C. Castillo Dominguez, M. Anguita Sanchez, A. Lopez Granados, J.M. Arizon Del Prado, J. Suarez De Lezo. Hospital Universitario Reina Sofia, Cordoba, Spain Purpose: Resting heart rate (RHR) has proven to be an adverse prognostic factor in selected populations of patients with stable coronary artery disease (CAD), referred for coronary angiography or participants in clinical trials. Our aim is to assess the prognostic value of RHR in a general, non-selected, population of patients with stable CAD. Methods: From February 1, 2000 to January 31, 2004, all patients with stable CAD attended at two outpatient cardiology clinics were included in the study and followed for major events (total mortality, acute coronary syndrome ACS, coronary revascularization, stroke and hospitalization for heart failure). The association of RHR ( 70 beats per minute -bpm- versus <70 bpm) with major events and total mortality was assessed. Results: We included 1264 patients, with a mean age of 67±10 years, followed for 26±16 months. Follow-up was complete in 99.45% of cases. RHR was 70 bpm in 645 patients (51%) and <70 bpm in 619 (49%). Probability of events at mean follow-up was 17.99% if RHR 70 bpm and 17.91% if RHR <70 bpm (p=0.32) and total mortality, 2.32% and 2.82%, respectively (p=0.56). Baseline features of both groups are shown in the table. After adjusting for them all, no significant association between RHR and major events was found (Hazard Ratio HR- 1.01, CI , p=0.94). Neither association was found for women (n=338), patients with previous ACS (n=1043) or patients with ejection fraction <0.40 (n=128). In patients aged 75 years (n=275), RHR was a protective factor (HR 0.50, CI , p=0.037). There was not significant association between RHR and total mortality in the entire series or any of the subgroups. Conclusion: RHR was not an adverse prognostic factor in this general, nonselected, low-risk population of patients with stable CAD. Prognostic relevance of RHR in clinical practice can be low in this setting The CHADS2 score predicts adverse cardiovascular outcome in atherothrombotic patients without atrial fibrillation: Insights from the European REACH registry O. Barthelemy 1,F.Beygui 1,J.Silvain 1, A. Bellemain-Appaix 1, U. Zeymer 2, D.L. Bhatt 3, P.G. Steg 4, G. Montalescot 1 on behalf of the REACH Registry investigators. 1 Pitie-Salpetriere Hospital (AP-HP), Paris, France; 2 Klinikum der Stadt Herzzentrum Ludwigshafen, Ludwigshafen am Rhein, Germany; 3 Cleveland Clinic, Cleveland, United States of America; 4 Bichat-Claude Bernard Hospital (AP-HP), Paris, France Aim: The CHADS2 score is a reliable, easy-to-use, and popular bedside score to assess the risk of stroke in patients with atrial fibrillation (AF). The items of the score are all key determinants of prognosis in vascular patients. We hypothesized that the CHADS2 score would adequately assess the risk of death and major events in stable atherothrombotic patients in absence of AF Figure 1 Conclusions: In stable atherothrombotic patients without AF, the CHADS2 score appears to adequately evaluate the 2 years risk of death, stroke or MACCE. This score is simple, does not require computerized calculation and is commonly used by cardiologists in the setting of AF Pharmacogenetic of Acenocoumarol in patients with extreme requirements V. Perez-Andreu 1, V. Roldan-Schilling 1, M.F. Lopez 2, A.I. Anton 1, I. Alberca 3,J.Corral 1,J.Hermida 4, F. Espana 5, V. Vicente 1, R. Gonzalez-Conejero 1. 1 Centro Regional de Hemodonacion. Universidad de Murcia, Murcia, Spain; 2 Hospital Juan Canalejo, A Coruna, Spain; 3 Hospital Universitario, Salamanca, Spain; 4 CIMA. Navarra, Pamplona, Spain; 5 Hospital La Fe, Valencia, Spain It is well known that common polymorphisms (SNPs) in CYP2C9 and in VKORC1 determine coumarin dose requirements and together with environmental factors can explain about 40% of the total variance in such dose. SNPs in new genes could also explain modest percentages in interpersonal variability, and hence be involved in the risk of therapy. Due to patients are treated by traditional trial-anderror dosing, those with extreme dose requirements to achieve a steady coagulation are also those with the higher risk at starting therapy. Aim: To better define these additional candidate genes, we investigated the pharmacogenetic of acenocoumarol in patients who need extreme doses for reaching a therapeutic INR level. Patients and Methods: We reviewed patients with a steady anticoagulation from 5 Spanish hospitals. We make a statistical approach about acenocoumarol dose requirements in our population, establishing the minimum dose requirement as 5 mg/week (corresponding percentile 5) and the maximum dose as 30 mg/week (p95). For each patient, we selected a control subject taking 13,5mg/week (p50), adjusted by sex and age. Patients older than 75 years or taking any medication known to interfere with acenocoumarol were excluded. Finally, 80 patients in p5 group, 196 in p95 and their respective controls (n=80+196) were included. Genotyping included: VKORC1 C1173T, calumenin A29809G, FVII - 323Ins/Del, GGCX R325Q, CYP2C9 and CYP4F2 V433M. Results: Patients in p5 were older than patients in p95 (71 vs 61 years, p<0.001). Multivariate analysis showed that only the alleles VKORC1 1173T and CYP2C9*3 were significantly more frequent in patients in p5 vs their controls (p=0.004 and p=0.001, respectively). In p95 group, VKORC1 1173C, CYP2C9*no-3 and, interestingly, CYP4F2 433M variants were also overrepresented vs their controls (multivariate analysis all p 0.001). Conclusions: Our results confirm that VKORC1 C1173T and CYP2C9 play a significant role in patients taking extreme acenocoumarol dose. Moreover, we provide new information about the pharmacogenetics of acenocoumarol, as the CYP4F2 V433M polymorphism might play a relevant role in the higher dose requirements. Abstract 1951 Table 1 Age (years) Male sex DM SBP (mmhg) DBP (mmhg) SR LVEF Statins Antiplatelets BB ACEI/ARA RHR 70 bpm 67±11 71% 36% 131±15 75±9 93% 0.55± % 88% 57% 52% RHR < 70 bpm 66±10 76% 26% 128±16 73±9 96% 0.58± % 96% 71% 43% p value <0.001 < <0.001 < ACEI/ARA, angiotensin converting enzyme inhibitors/angiotensin receptor antagonists; BB, beta-blockers; DPB, diastolic blood pressure; DM, diabetes mellitus, LVEF, left ventricular ejection fraction, RHR, resting heart rate, SBP, systolic blood pressure, SR, sinus rhythm.

12 312 Predictors of cardiovascular events: lessons from large databases / Update on risk assessment in acute coronary syndromes 1954 D-dimer testing, thrombophilia screening and recurrences in patients with venous thromboembolism: a 6-year follow-up J. Conard 1, E. Ombandza-Moussa 1,M.M.Samama 1, A.G. Turpie 2, M.H. Horellou 1,I.Elalamy 1. 1 AP-HP - Hopital Hotel-Dieu, Paris, France; 2 McMaster University, Hamilton, Canada Purpose: The clinical relevance of D-dimers (D-di) measurement and thrombophilia screening in the follow-up of patients with history of a venous thromboembolism (VTE) event remains uncertain. Methods: We studied retrospectively 149 patients referred for thrombophilia screening following at least one VTE episode. 9 patients were lost to 6 year followup. D-di were measured by ELFA (Vidas BioMérieux) at first assessment. Results: At first assessment, 63 patients (group A) were without oral anticoagulant treatment (OAT) and 77 patients (group B) were still on OAT. Hereditary thrombophilia was present in 48% of group A and 65% of group B (p<0.02). D-di were significantly lower in patients on OAT (194±130 vs 399±242 ng/ml) (p<0.001). The prevalence of VTE recurrences during follow-up was higher in group A (10 patients, 16%, including 7 with a hereditary thrombophilia), than in group B (one patient with homozygous FV Leiden mutation, 1.3%) (p<0.001). In group A, D-di were higher in the 10 patients with recurrence (512±244 ng/ml) as compared with the 53 without (328±202 ng/ml) (p<0.001). Of the 77 patients on OAT, 24 discontinued OAT during follow-up and 8 (33%) had a recurrent VTE episode after an average interval of 11±9 months (extremes 2 to 38 months); D-di levels were significantly higher than in the 16 without recurrence (p<0.05). Among these 24 patients, hereditary thrombophilia was more frequent in those with a recurrent thrombosis: 75% (6/8) than in those without recurrence: 37% (6/16); p<0.05. D-di level at first assessment was predictive of recurrent VTE, independently of OAT intake (36% patients with D-di over 500 μg/l versus 9% patients with D-di below 500 μg/l, RR=3.90, 95% CI: ). Conclusions: Increased D-di level is a marker of hypercoagulation which could facilitate prediction of recurrent thromboembolic episodes. The efficiency of OAT in patients with symptomatic thrombophilia was demonstrated. After discontinuation of OAT, recurrence was more frequent in patients with thrombophilia. This suggests that thrombophilia is a risk factor for recurrence. UPDATE ON RISK ASSESSMENT IN ACUTE CORONARY SYNDROMES 1956 The HEART score for chest pain patients at the emergency room B.E. Backus 1,A.J.Six 2, J.C. Kelder 1,T.P.Mast 3, F. Van Den Akker 3, P.A. Doevendans 3. 1 St Antonius Hospital, Nieuwegein, Netherlands; 2 Zuwe Hofpoort Ziekenhuis, Woerden, Netherlands; 3 University Medical Center Utrecht, Utrecht, Netherlands Purpose: Chest pain is a common reason for presentation at the emergency room. The diagnosis of Acute Coronary Syndrome without ST elevation (Non ST-ACS) causes uncertainty, as absolute criteria for Non ST-ACS are lacking. Arguments are: suspicious patient History, typical ECG changes, higher Age, Risk factors for atherosclerotic diseases and elevated serum levels of Troponin. Each can be scored with zero, one or two points, depending on the severity. The HEART score is the sum of these five. The purpose of the current study is to validate the HEART score. Methods: A total of 2161 cardiology patients presented at the emergency rooms of the four participating hospitals during January-March 2006, of which 910 (42%) patients due to chest pain. Patients with ST elevation myocardial infarction were not evaluated as they went straight to the catheterization laboratory. End points were acute myocardial infarction (AMI), Percutaneous Coronary Intervention (PCI), Coronary Artery Bypass Grafting (CABG) or death, occurring within 6 weeks after presentation. Results: An AMI was diagnosed in 92 (10.45%) patients, 82 (9.32%) underwent PCI and 36 (4.09%) CABG and 13 (1.48%) died. The HEART scores in the patients with and without an end point were 7.2±1.7 and 3.8±1.9 respectively (p<0.0001). The percentage of patients with an endpoint in the various HEART groups is given in figure Evaluation of the TIMI and GRACE scores in developing countries: insights from the ACCESS registry J.C. Nicolau 1, G. Montalescot 2, C. Martinez-Sanchez 3, N. Antepara 4, A. Escobar 5,S.Alam 6, M. Sobhy 7,A.Leizorowicz 8 on behalf of The ACCESS Investigators Group. 1 Heart Institute (InCor) - University of São Paulo Medical School, São Paulo, Brazil; 2 Pitie-Salpetriere Hospital (AP-HP), Paris, France; 3 Instituto Nacional de Cardiologia Ignacio Chaves, Mexico City, Mexico; 4 Hospital Universitário, Caracas, Venezuela; 5 Clinica Medellin, Medellin, Colombia; 6 American University, Beirut, Lebanon; 7 Alexandria University, Alexandria, Egypt; 8 Univ. Claude Bernard, Lyon, France Purpose: Various risk scores have been proposed to risk stratify patients presenting with non-st-elevation acute coronary syndromes (NSTEACS). However, little is known on the performance of these scores specifically in developing countries. Methods: The ACCESS (ACute Coronary Events a multinational Survey of current management Strategies) is a registry from developing countries that included patients hospitalized with suspected acute coronary syndromes. From these, 6320 (mean age 61±11.9 y.o., 67.2% males) had NSTEACS, being 2055 from Africa (Algeria, Egypt, Morocco, South Africa and Tunisia), 2562 from Latin America (Argentina, Brazil, Colombia, Dominican Republic, Ecuador, Guatemala, Mexico and Venezuela) and 1703 from Middle East (Iran, Jordan, Koweit, Lebanon, Saudi Arabia and United Arab Emirates). Two score performances (TIMI and GRACE) were analyzed for the whole population and for each region; ROC curves considering in-hospital death and death or recurrent ischemia were constructed and the area under the curves (AUC) were compared in the different scenarios. For the GRACE score, cardiac arrest at admission was not considered (information not retrieved). Results: 1) The mean ± SD GRACE score for Africa (AF), Latin America (LA) and Middle East (ME) were 119.6±35, 125.9±35.5 and 120.8±35.5 (P<0.001), respectively; for the TIMI score, the numbers were 3.1±1.4, 3.4±1.4 and 3.3±1.4 (P<0.001); 2) The mortality rates for AF, LA and ME were 1.4%, 2.0%, and 0.9% (P=0.014); the rates of death or recurrent ischemia were 12.3%, 9.1%, and 10.6% (P=0.002). 3) The AUC ± SE for the GRACE and TIMI scores taking into account death were, respectively, 0.81±0.02 vs. 0.65±0.03 for the whole population (P<0.001), 0.81±0.04 vs. 0.57±0.06 (P=0.001) for AF, 0.78±0.03 vs. 0.65±0.04 for LA (P=0.009), and 0.83±0.06 vs. 0.78±0.05 for the ME (P=0.570). 3) Taking into account death or recurrent ischemia the AUC were, respectively, 0.60±0.01 vs. 0.61±0.01 for the whole population (P=0.855), 0.60±0.02 vs. 0.64±0.02 for AF (P=0.139), 0.63±0.02 vs. 0.60±0.02 for LA (P=0.253), and 0.58±0.02 vs. 0.58±0.02 (P=0.853) for the ME. Conclusions: 1) There are significant differences among the different developing regions in terms of clinical outcome, the highest risk patients and higher mortality rates being seen in Latin America. 2) The GRACE score performed significantly better than the TIMI score to predict mortality globally, and also for AF and LA. The two scores were less accurate, but fared similarly, when considering death or recurrent ischemia. Figure 1 Conclusions: A HEART score of 0-3 points holds a risk < 0.9% for an endpoint and supports early discharge. With a risk of 12% a HEART score of 4-6 points implies admission for clinical observation. A HEART score 7 points, with a mean risk of 65%, supports early invasive strategies. The HEART score helps to make accurate diagnostic and therapeutic choices and facilitates communications Gastrointestinal bleeding in patients with acute coronary syndromes: incidence, predictors and clinical implications (analysis from the ACUITY Trial) E. Nikolsky 1, R. Mehran 1,A.J.Kirtane 1,A.J.Lansky 1,A.M.Lincoff 2, A. Caixeta 1,M.Fahy 1, J.W. Moses 1, E.M. Ohman 3, G.W. Stone 1. 1 The Columbia University Medical Center and the Cardiovascular Research Foundation, New York, Ny, United States of America; 2 The Cleveland Clinic Cleveland, Ohio, United States of America; 3 Duke University, Durham, Nc, United States of America Objective: Gastrointestinal bleeding (GIB) is one of the sources of hemorrhage in patients (pts) with acute coronary syndromes (ACS) undergoing early invasive management. The data are scarce, however, regarding the implications of GIB in pts with ACS whose contemporary management includes composite antithrombotic and antiplatelet therapy. Our aim was to assess the incidence, predictors and outcomes of GIB in intermediate- to high-risk pts with ACS. Methods: The study represents post hoc analysis of pts with moderateand high risk ACS in the randomized Acute Catheterization and Urgent Intervention Triage strategy (ACUITY) trial who were enrolled in 17 countries between August 2003 and December Pts were randomized to the open-label use of 1 of 3 antithrombin regimens started prior to angiography (heparin+gp IIb/IIIa inhibitors [H+GPI], bivalirudin+gpi, or bivalirudin monotherapy), and based on angiography were triaged to PCI, CABG or medical management. Results: GIB within 30 days of randomization occurred in 178 (1.3%) pts. In the entire study population, older age, baseline anemia and smoking were identified as independent predictors of GIB. In pts triaged to medical management, randomization to bivalirudin monotherapy decreased the likelihood of GIB compared with randomization to H+GPI (OR 0.22 [0.07, 0.67], P=0.007). At 1-year F/U pts with

13 Update on risk assessment in acute coronary syndromes 313 vs. without GIB had remarkably worse clinical outcomes (Table). On multivariable analysis, GIB independently predicted 1-year all-cause mortality (HR 3.95 [2.62, 5.96]), cardiac mortality (HR 3.70 [2.10, 6.52]), and composite ischemia (HR 1.86 [1.34, 2.60]) (all P<0.0001). Clinical outcomes at 1 year follow-up GIB (+) n=178 GIB ( ) n=13641 P value All-cause death 21.9% 3.9% < Cardiac death 13.2% 2.3% < Myocardial infarction 15.8% 7.3% < Unplanned revascularization 12.3% 9.0% 0.12 Composite ischemic outcome* 34.7% 16.3% < Stent thrombosis 5.8% 2.4% *All cause death, myocardial infarction and unplanned revascularization, By Academic Research Consortium definition. Conclusions: GIB is a devastating condition in the scenario of ACS. Future trials are warranted to determine effective measures to prevent GIB in high-risk populations Four times higher hospital mortality due to major bleeding complications in NSTE-ACS in clinical practice: lessons from the Euro Heart Survey ACS registry A.K. Gitt 1, H. Bueno 2,W.Wojakowski 3, M. Tendera 3,H.Katus 4, M. Gierlotka 5, M. Tubaro 6,Y.Hasin 7,F.Schiele 8, J.P. Bassand 8 on behalf of ACS Registry. 1 Institut fuer Herzinfarktforschung Ludwigshafen, Ludwigshafen am Rhein, Germany; 2 Hospital General Universitario Gregorio Maranon, Madrid, Spain; 3 Slaski Uniwersytet Medyczny w Katowicach, Katowice, Poland; 4 Universitaetsklinikum Heidelberg, Heidelberg, Germany; 5 Slaskie Centrum Chorob Serca, Zabrze, Poland; 6 Ospedale San Filippo Neri, Rome, Italy; 7 Poria Medical Centre, Tiberias, Israel; 8 CHU de Besancon - Hopital Jean Minjoz, Besancon, France Background: Data from recent randomised trials of antithrombotic treatment for ACS have highlighted the influence of bleeding complications on outcome. Little is known about the prevalence of major bleeding complications in NSTE-ACS in clinical practice. Methods: Between Oct 2006 to Oct 2008, 21,582 consecutive patients with ACS were enrolled into the ACS-Registry of the Euro Heart Survey Programme to document treatment and hospital outcome. We examined the impact of major bleeding complications (bleeding with drop of haemoglobin >5g/dl or hematocrit > 15%) on hospital outcome of NSTE-ACS. Results: Of 12,850 patients with NSTE-ACS, 270 (2.1%) had major bleeding complications. Patients with major bleedings were older, more often female and did receive treatment with GP IIb/IIIa blockers and heparins more frequently. Hospital mortality was significantly higher in patients with major bleeding even after correction for differences in patient characteristics, kind of NSTE-ACS and treatment (OR 4.22, 95% CI ). Major bleeding (n=270) No major bleed (n=12,580) p-value Age [years] < 0.01 Female Gender 47.0% 36.4% <0.01 Prior MI 32.3% 29.6% ns Prior PCI 18.2% 17.8% ns Prior Bypass 10.4% 6.8% <0.05 Prior Stroke 11.1% 6.4% <0.01 Diabetes mellitus 33.0% 29.9% ns Renal Failure 16.7% 7.9% <0.01 PCI 60.2% 42.6% <0.01 GP IIb/IIIa 22.2% 11.7% <0.01 ASA 93.3% 93.3% ns Clopidogrel 79.3% 80.8% ns LMW-Heparin 54.7% 53.6% ns Unfr. Heparin 65.2% 55.4% <0.05 Hospital Mortality 11.1% 3.1% <0.01 Conclusion: The incidence of major bleeding complication in NSTE-ACS in clinical practice in Europe was 2.1%. Major bleeding complications were associated with 4-fold increased hospital mortality ST2 and IL33 have independent prognostic value in patients with acute coronary syndromes compared with GRACE score and N-terminal pro-b-type natriuretic peptide O.S. Dhillon, S.Q. Khan, H. Narayan, N.G. Kh, M. Noor, Q. Pa, I.B. Squire, J.E. Davies, L.L. Ng. University of Leicester, Leicester, United Kingdom Purpose: ST2, a member of the interleukin-1 receptor family is up-regulated after applying mechanical strain to cardiac myocytes. In study populations with STelevation myocardial infarction (STEMI) ST2 has demonstrated prognostic value but interleukin 33 (IL33), its natural ligand, has not been investigated in ACS. We assessed the prognostic value of ST2 and IL33 in unselected patients with both STEMI and nonstemi for death/heart failure (HF) combined and death, HF or MI separately. Comparison was made with N-terminal pro-b-type natriuretic (NTproBNP) and GRACE Score. Methods: In this prospective single centre study we recruited 1254 ACS patients (902 men, mean age 66.4 SD 12.6 yrs, 672 STEMI) with mean follow up 797 days [range ]. A single blood test was taken 3-5 days after admission for ST2, IL33 and NTproBNP. Results: In a Cox regression model containing baseline characteristics we discovered IL33 was associated with increased risk of late mortality in patients with STEMI only (HR 1.33 p=0.001 along with age, egfr) which remained after adjustment for GRACE score and NTproBNP. Kaplan-Meier analysis revealed that STEMI patients with both IL33 and NTproBNP levels above median had the highest mortality rates (log rank p<0.001). No significant association between IL33 and HF or MI was found in either STEMI or NSTEMI. ST2 levels were predictive of death/hf combined (HR 2.25 p=0.001) as were age, KillipClass>1 and egfr. The association of ST2 with mortality was stronger than for HF (HR 2.39 p<0.001 vs HR 1.87 p=0.028) and particularly evident for early mortality in STEMI. A 1-SD increase in ST2 levels was associated with 9.30-fold rise in the hazard of death at 30 days p<0.001 and is also highly discriminatory C-statistic 0.82 p<0.001 compared with NSTEMI HR 6.07 p=0.009, C-statistic 0.73 p< After addition of NTproBNP and GRACE score to the model ST2 remained associated with death and MI (HR 0.12 p=0.002) but not with HF. C- statistic increased to 0.90 p<0.001 for death at 30 days in STEMI using a model combining GRACE, NTproBNP and ST2. In patients with high GRACE scores or NTproBNP levels further stratification by ST2 identified those at highest risk of death/hf (log rank and respectively both p<0.001). Conclusions: This is the first report identifying IL33 as a novel prognostic marker of mortality in STEMI patients beyond clinical factors, GRACE score and NTproBNP levels. ST2 is an independent predictor of cardiac events in ACS which is particularly evident for early events in the STEMI population. Knowledge of biomarker levels improves risk stratification beyond GRACE scoring alone Performance of the GRACE risk score in acute coronary syndromes: impact of patient-related variables and of variables associated with the acute event P. Carmo, J. Ferreira, C. Aguiar, P. Goncalves, R. Gomes, S. Lima, J. Brito. Hospital de Santa Cruz, Carnaxide, Portugal Purpose: The GRACE risk score, recommended as the preferred multi-factorial tool for predicting outcome on admission in acute coronary syndromes (ACS), incorporates 8 variables, of which 6 are associated with event severity (heart rate, systolic blood pressure, Killip class, ST-segment deviation, elevated cardiac markers, and cardiac arrest), and 2 with the patient (Pt) (age and creatinine).the aim of our study was to evaluate the prognostic performance of the global GRACE risk score and of each of it s 2 subsets of variables variables associated with event severity and patient-related variables for outcomes before and after the first 30 days. Methods: We studied 460 Pts with non-st-elevation ACS (age 63±11 years, 22% female, and 57% with elevated troponin). For each patient we calculated the global GRACE risk score (Global S), the sum of points attributed to variables associated with acute event severity (Event S), and the sum of points attributed to the 2 patient-related variables (Patient S).ROC curve analyses were performed to assess the prognostic accuracy of the Global S, the Event S, and the Patient S, for incidence of death (D) and myocardial infarction (MI) at 30 days after admission and between 30 days and 1 year.the best discriminatory value for each Score was used to calculate the risk of events during follow-up (Hazard Ratio, HR). Results: The incidence of D/MI was 7,6% at 30 days and 15% at 1 year.the prognostic accuracies of the Global S, Event S, and Patient S are shown on the Table.The Global S had a good performance at 30 days (Global S>148, HR=4.53, 95% CI, ) as well as between day 30 and 1 year (Global S>128, HR=5.13, 95% CI, ). The Event S but not the Patient S predicted outcome at day 30. Between day 30 and 1 year, both the Event S and the Patient S were associated with risk of D/MI, but the Patient S showed the best performance. Table 1 Partial Score Incidence of D/MI 0-30 days Incidence of D/MI days Event Score Score >88: 17%; Score 88: 6% Score <47: 10%; Score 47: 5% HR=2.93 ( ) P=0.003 HR=2.53 ( ) P=0.027 Patient Score Score >63: 9%; Score 63.3: 6% Score >63: 12%; Score 63: 2% HR=0.72 ( ) P=0.369 HR=7.05 ( ) P=0.001 Conclusion: In a real-world population of non-st-elevation ACS, the excellent performance of the GRACE risk score at 30 days was essentially due to variables associated with the acute event severity, whereas for outcomes between day 30 and 1 year it was strongly explained by patient-related variables.

14 314 Update on risk assessment in acute coronary syndromes / Long-term problems in patients with coarctation of the aorta 1961 Serial assessment of MPO in patients with ACS provides independent prognostic information M. Weber, H. Nef, H. Moellmann, C. Liebetrau, M. Woelken, C. Hamm. Kerckhoff Klinik GmbH, Bad Nauheim, Germany Background: Decision on the therapeutical strategy in patients presenting with acute coronary syndromes is mainly based on the individual risk. Besides clinical factors biomarkers, namely cardiac troponins have become the cornerstone for risk stratification. However, there is an ongoing search for new biomarkers enabling improved risk stratification. In the present study we investigate the predictive value of serial assessment of myeloperoxidase in consecutive patients with an ACS. Methods and results: From April 2005 until November 2006 all consecutive patients (n=762, 29% females, aged 65 (IQR 55-75) years) admitted to our center because of an ACS with an episode of chest pain within the last 48 hours were included. Admission diagnosis was STEMI in 54% of the patients and NSTE-ACS in 46%. Clinical follow up after 6 months (175±48 days) was available for almost all patients; only 8 patients were lost to follow up. During this period 55 (7.2%) patients died. From baseline (n=699) and day 1 (n=555) EDTA plasma samples BNP, TnI and MPO were measured. MPO levels on admission were highly elevated with a strong relation to the time interval from onset of symptoms until blood drawing. However, no difference between those who survived and those who deceased was observed (858 pg/ml vs. 804 pg/ml; p=0.412). In contrast, MPO plasma levels assessed on day 1 were highly predictive for subsequent death (Log Rank 8.33; p=0.039) and remained a significant prognosticator even after adjusting for clinical factors, egfr, TnI and BNP (HR 3.3, 95%CI ; p=0.015). Conclusion: MPO is highly elevated in patients with an ACS. Assessed on day 1 it provides incremental and independent information beyond that derived from traditional clinical risk factors and established biomarkers. LONG-TERM PROBLEMS IN PATIENTS WITH COARCTATION OF THE AORTA 1999 A novel approach to assess vascular function using aortic wall tissue Doppler imaging. Study of repaired aortic coarctations versus normal subjects M. Serban, M. Iancu, I. Ghiorghiu, I. Craciunescu, C. Ginghina. Institute of Cardiovasc.Diseases C.C.Iliescu/Inst. De Boli CV, Bucharest, Romania Background: Tissue Doppler imaging (TDI) has recently emerged as a new technique for the evaluation of aortic wall velocities and superior to standards measurements of arterial function. Aortic coarctation (CoA) is associated with increased morbidity, even after correction. Impaired vascular function of precoarctational arterial bed may be related to long term prognosis of this patients. Purpose: The aim of the study was to investigate the potential clinical application of TDI for the assessment of aortic elastic properties in patients with repaired CoA. Methods: Study groups were composed of 23 patients with repaired CoA (mean age 28,65±9,98 years) and 20 age and sex-matched healthy subjects. Aortic stiffness was assessed using M-mode evaluation of systolic (ASD) and diastolic (ADD) aortic diameters, parasternal long-axis view, 3 cm above the aortic valve. The following indexes of aortic elasticity were calculated using accepted formulae: aortic strain (Ao Strain), aortic distensibility (Ao Dis), aortic stiffness index (Ao SI). Using TDI, at the same point as in M-mode, systolic maximum wall expansion velocity (SW) and early and late wall contraction (EW, AW) diastolic velocities were determined online. Results: CoA patients had highly statistically significant reduced aortic wall velocities comparing with control subjects for SW (7,54±2,24 vs 11,70±2,30 cm/s, p<0,001) and EW (8,47±2,80 vs. 11,26±2,94 cm/s, p=0,005). SW was positively related to Ao Dis and Strain and negatively related to ADD and Ao SI, with high statistical significance; EW had also a high statistically significant positive correlation with Ao Dis and Strain and a negative one with Ao SI. Correlation coefficients are shown in the table. ADD ASD Ao Dis Ao Strain Ao SI SW -0,402** -0,163 0,554** 0,578** -0,494** EW -0,287-0,124 0,347* 0,426** -0,367* AW - 0,086-0,083 0,031 0,045-0,03 *p<0,05, **p<0,01. Conclusions: Systolic and early diastolic velocities of aortic wall were decreased in patients with repaired aortic coarctation versus normal subjects, in correlation with aortic dilatation and altered M-mode derived aortic stiffness parameters. TDI assessment of aortic wall velocities is a very feasible and useful tool in the evaluation of vascular function Late expansion of an implanted stent in growing patients with coarctation of aorta J. Suarez De Lezo 1,M.Pan 1,M.Romero 1, J. Segura 1,D.J.Pavlovic 1, S. Ojeda 1, A. Gamez 1, I. Tejero 1, M. Lafuente 1, A. Medina 2. 1 Hospital Universitario Reina Sofia, Cordoba, Spain; 2 Hospital Universitario Dr Negrin, Las Palmas, Spain Objectives: Stent repair of severe coarctation of the aorta seems to be an effective and definitive treatment in adult patients. However, the use of stents at early ages has not been recommended due to the absence of growth capacity in the stented segment throughout the child s life, leading to relative stenosis at adulthood. In this study, we assess the feasibility of late stent re-expansion in growing children with stent-treated coarctation of the aorta. Methods: From Novenber 1993 to December 2008, 123 patients with coarctation of the aorta were treated at our institution by stent implantation. From them, we studied 10 patients who were treated under the age of 6 years. All 10 patients had late stent re-expansion at a mean of 11±4 years after the original procedure. Results: The mean age at stent implantation was 2±1.5 years. Reasons for stenting at an early age included life-threatening conditions (n=2), failure of previous treatment (n=4), and extreme hypoplasia (n=10). The implanted stent diameter at the first procedure was 8.8±1.2 mm and the minimal lumen diameter of the aorta changed from 2.3±0.3 mm pre-implant to 9.6±1.2 mm post-procedure. Two patients also underwent coil obliteration of an aneurysm. For the re-expansion procedure a surgical subclavian approach was used in 3 patients and a conventional femoral puncture in the remaining 7. The balloon diameter used for re-expansion was 15±1.3 mm. After balloon dilatation, the minimal lumen diameter of the stented segment rose from 9±2 to13±2 mm and the stent shortened from 37±11 to 32±9 mm. Minor fractures (detachment of 1-2 struts) of the stent occurred after re-expansion in 6 patients; 4 patients required one additional stent to improve the immediate result. The peak gradient across the coarctation changed as follows: baseline 53±17 mmhg, post-stent 5±4 mmhg, follow-up 30±12 mmhg, and post re-expansion 5±5 mmhg. There were no complications associated with balloon dilation of the stent or damage to the aorta. All patients remain symptom-free without hypertension 29±33 months later. Conclusions: Balloon re-expansion of a stent implanted in the aorta in small children is feasible, although a second stent may be required to improve the outcome of the procedure. This final treatment may be delayed for years, until the target stent diameter can be accommodated to the final growth of the aorta in a single additional procedure Aortic growth late after coarctation repair R.J. Franken 1, P. Luijendijk 2, B.J. Bouma 2, M. Groenink 2, A.M. Spijkerboer 2, B.J.M. Mulder 2. 1 Leiden University Medical Center, Leiden, Netherlands; 2 Academic Medical Center, Amsterdam, Netherlands Purpose: Long-term outcome of repaired aortic coarctation (CoA) may be complicated by dilatation of the thoracic aorta. Aim of the study was to demonstrate the presence and progression of aortic dilatation late after coarctation repair. Methods: We analyzed retrospective data of adult post-coarctectomy patients, who had serial Magnetic Resonance Images (MRI) performed at least 3 years apart, on the presence and progression the thoracic aorta dilatation. Determinants for the presence and progression of ascending aorta dilatation were identified. Results: Forty-five patients (mean age 31±9.3 years, male 53%) had a mean MRI follow-up of 5.5±1.3 years. The mean maximum diameter of the aorta at baseline was 30.4 mm ± 5.7 (range mm), at the end of follow-up 32.4±6.1 (range mm). Dilatation ( 35 mm) of the ascending aorta was present in 8% of the patients at baseline and in 15% at the end of follow up. Determinants for a dilated aortic baseline diameter were older age (R = 0,562 P = < 0.001) and a bicuspid aortic valve (R= 0,450, P = 0.002). Although growth was found in all segments of the thoracic aorta, it was most prominent in the ascending aorta with 2 mm/5 yrs (range mm/5yrs). Compared to other surgical modalities, end-to-end anastomosis was associated with increased ascending aorta growth rates (R = 0,321, P = 0.03). Conclusions: Aortic dilatation is a significant problem in coarctation patients late after repair. Older age and a bicuspid aortic valve are predictors for ascending aortic dilatation. Corrective surgery by end-to-end anastomosis is associated with increased growth of the ascending aorta Complications of aortic coarctation repair assessed using cardiovascular magnetic resonance S.S.M. Chen, R.H. Mohiaddin. Royal Brompton Hospital, London, United Kingdom Purpose: Surgical repair for coarctation of the aorta (CoA) has been the main form of treatment and more recently, aortic stenting. We used cardiovascular magnetic resonance (CMR) to assess the long-term success of repair of CoA with respect to structural complications and residual stenosis. Methods: CMR studies between were reviewed. Details of age at,

15 Long-term problems in patients with coarctation of the aorta / Atrial septal defect closure Unresolved issues 315 date and type of repair were obtained from medical notes. Multi-slice HASTE, cine and turbo-spine echo T2 images, and aortic in-plane and through-plane flow studies were analysed for complications (aneurysmal dilatation, false aneurysm, dissection) and residual stenosis. Aneurysmal dilatation was defined as widening at the repair site in comparison to the diameter of the pre- and post-aortic segments. Residual stenosis was defined as constriction at the repair site with flow acceleration on in-plane flow analysis, ±peak recorded velocity on through-plane measurement of >2.5m/s. Results: 281 studies were analysed (167 males, 114 females, aged 31±9 years). Average time between surgery and balloon dilatation, and CMR imaging 18±7 years, and in aortic stenting 4±0.8 years. Types of repair: resection+end-to-end anastomosis (n=94), subclavian flap repair (n=62), aortic stenting (n=43), interposition graft repair (n=31), balloon dilatation (n=24), dacron patch repair (n=19), and bypass graft (n=8). Structural complications were found in patch repair (15/19 aneurysmal dilatation of the patch, 2/19 suture line false aneurysms, 2/19 residual stenosis), and subclavian flap repair (38/62 aneurysmal dilatation of the flap, 2/62 suture line false aneurysms, and 2/62 residual stenosis). Residual stenosis was the main complication in resection+end-to-end anastomosis. (57/94). Balloon dilatation had 17/24 residual stenosis and mild aneurysmal dilatation in 4/24. Aortic stenting had less residual stenosis (6/43), with minimal structural complications (no dissection, but 1/43 displacement of the stent, 1/43 aneurysm). Graft repairs had good long term results: interposition grafts (3/31 suture line false aneurysms, 4/31 residual stenosis at arch-graft anastomosis) and bypass grafts (no residual stenosis, and 2/8 suture line false aneurysm). Conclusion: Patch and flap aneurysms are frequent complications of patch and subclavian flap repairs, and residual stenosis was high in resection+end-to-end anastomosis. Balloon dilatation had frequent residual stenosis. Graft and bypass graft repair are the most favourable surgical repairs with limited complications and residual stenosis. Aortic stenting appears quite successful but long term follow-up is not yet available Comparison between a beta-adrenergic receptor blocker and angiotensin II receptor antagonist for the treatment of hypertension in repaired aortic coarctation E. Moltzer 1, F.U.S. Mattace Raso 2, Y. Karamermer 3,E.Boersma 3, G. Webb 4, M.L. Simoons 3, A.H.J. Danser 5, A.H. Van Den Meiracker 5, J.W. Roos-Hesselink 3. 1 Dept of Cardiology, Thoraxcenter and Division of Pharmacology, Dept of Internal Medicine, Erasmus MC, Rotterdam, Netherlands; 2 Section of Geriatric Medicine, Department of Internal Medicine, Erasmus MC, Rotterdam, Netherlands; 3 Department of Cardiology, Thoraxcenter, Erasmus MC, Rotterdam, Netherlands; 4 Philadelphia Adult Congenital Heart Center, University of Pennsylvania, Philadelphia, United States of America; 5 Division of Pharmacology and Vascular and Metabolic Diseases, Dept of Internal Medicine, Erasmus MC, Rotterdam, Netherlands Purpose: To compare effects on 24-hour blood pressure, large artery stiffness and neurohormonal status of metoprolol (beta-adrenergic receptor blockade) versus candesartan (angiotensin II type 1 receptor blockade) in hypertensive patients after repaired aortic coarctation. Methods: In an open label randomised crossover pilot study, hypertensive adult post-coarctectomy patients were treated with metoprolol 100 mg and candesartan 8 mg. Treatment effects were assessed with 24-hour ambulatory blood pressure monitoring, measurements of large artery stiffness by Pulse Wave Velocity (PWV) and carotid stiffness and neurohormonal plasma levels at baseline and after eight weeks of either treatment. Patients with current use of antihypertensive medication were enrolled after a washout period of three weeks. In case hypertension persisted after four weeks of treatment, medication dose was doubled. Results: Sixteen patients (mean age 36.9±12.3 years, 25.7±14.7 years after repair, 62.5% male) completed the study. Twenty-four hour mean arterial pressure (MAP) at baseline was 97.7±6.2 mmhg. Metoprolol (mean dose 162.5±50.0 mg daily) decreased MAP more than candesartan (mean dose 13.0±4.0 mg daily, resp. 7.0±4.2 and 4.1±3.6 mmhg, p=0.018). Daytime systolic blood pressure (BP) at baseline was 148.6±6.7 mmhg and daytime diastolic BP 82.9±8.2 mmhg. Metoprolol reduced both systolic (10.1±1.7 mmhg, p=0.008) and diastolic (8.8±1.2 mmhg, p=0.032) BP more than candesartan (resp. 4.4±2.0 mmhg and 4.6±1.2 mmhg), Large artery stiffness did not change on either treatment. With metoprolol, plasma B-type natriuretic peptide increased (p<0.05), whereas plasma renin decreased (p=0.008). With candesartan, plasma renin and noradrenaline increased (resp. p=0.002 and p=0.022), whereas aldosteron levels decreased (p=0.031). Conclusion: In hypertensive adult post-coarctectomy patients, metoprolol had more antihypertensive effect than candesartan. An 8-week treatment had no measurable effect on large artery stiffness Do we need to screen all patients with coarctation of the aorta for intracranial aneurysms? S.L. Curtis 1, M. Bradley 2, P. Wilde 1,J.Aw 1, S. Chakrabarti 1, M. Hamilton 1,R.P.Martin 1, M.S. Turner 1, A.G. Stuart 1. 1 Bristol Congenital Heart Centre, Bristol Royal Infirmary, Marlborough Street, Bristol BS2 8HW, Bristol, United Kingdom; 2 Department of Neuroradiology, Frenchay Hospital, Frenchay Park Road, Bristol BS16 1UU, Bristol, United Kingdom Purpose: Intracranial aneurysms ( IAs ) are found in approximately 2.3% of adults with a mean age at detection of 52 years. IAs<7mm are at low risk of rupture. Older studies have suggested that 10-50% of patients with coarctation of the aorta have IAs and that 5% total deaths in the early surgical era were due to haemorrhagic stroke. Screening recommendations for detecting IAs in patients with coarctation of the aorta are variable. We questioned the current prevalence of IAs in coarctation and the necessity for screening. We also sought to investigate the association between hypertension and IAs. Methods: Consecutive patients over 16 years with coarctation of the aorta undergoing MRA of the brain between May 1999 and October 2007 were included. MRA was performed using a Siemens Avanto 1.5 Tesla scanner using a 3D time of flight protocol. Scans were independently double-reported by a neuroradiologist. IAs were described in terms of site and size. Statistics are described as mean±s.d. and median±range. Continuous variables were compared using the student t-test and the Mann-Whitney U test. Categorical variables were compared using Fisher s Exact test. Results: 122 scans were retrieved and 116 were available for double-reporting. Median age of the patients was 28±11 years (range years). IAs were found in 11 patients (9.5%). The mean diameter of the aneurysms was 3.9mm (range mm). The patients with aneurysms (IA) were older than those without (no IA) (IA-median 35 years, range years; no IA-median 27 years, range years; Z=-1.730; p=0.08). Hypertension affected almost half of patients (45%), and was significantly more common in the aneurysm group (IA-82% v no IA - 41%; p=0.024). 29 patients fulfilled criteria for hypertension but were neither diagnosed as such nor receiving treatment. More patients in the IA group had aortic aneurysms but this was not statistically significant (IA-18%, no IA-9%, p=0.32). There was no association between ascending aortopathy, bicuspid aortic valves and IAs. Conclusion: Patients with coarctation of the aorta have a higher prevalence of IAs and they occur at a much earlier age than in population studies. However the aneurysms are small and thus at low risk of rupture. Elective endovascular repair of IAs has a morbidity/mortality rate of 3-5% and therefore the benefits of treating small unruptured aneurysms are finely balanced against conservative management. This study suggests that routine screening of aneurysms may not be necessary. Hypertension is likely to be an important pathophysiological factor and should be treated aggressively. ATRIAL SEPTAL DEFECT CLOSURE UNRESOLVED ISSUES 2005 Closure of the atrial septal defect in the elderly patients M. Pieculewicz, P. Podolec, T. Przewlocki, L. Tomkiewicz-Pajak, M. Hlawaty, P. Wilkolek, W. Tracz. Department of Cardiac and Vasculare Disease Collegium Medicum Jagiellonian Univercity, John Paul II, Krakow, Poland Objective: Closure of the atrial septal defect in the elderly patients is controversial. The aim of the study was to evaluate the outcomes of transcatheter closure of secundum atrial septal defect (ASD) in elderly patients. Methods: From a total of 281 pts with ASD who underwent transcatheter closure 42 pts over 60 years (30 F, 12 M) with a mean age of 65.3±15.7 (60-75) were analyzed. All patients had an isolated secundum ASD with a mean Qp:Qs: 2.69±1.6 ( ). A symptom-limited treadmill exercise tests with respiratory gas exchange analysis and transthoracic color Doppler echocardiographic study as well as Quality of life (QoL) measured using the SF36 questionnaire (SF36q) were repeated in all pts before procedure and after 12 months of follow-up. Results: The ASO device was successfully implanted in all pts (procedure time 37.7±4.5 (13-59) minutes, fluoroscopy time 11.2±9.9 (6-40) minutes). There were no major complications. The defect echo diameter was 17.7±5.8 (12-30) mm. The mean balloon stretched diameter of ASD was 22.4±7.9 (14-34) mm. The diameter of the implanted devices ranged mm. After 12 months of ASD closure, all the pts showed a significant improvement of exercise capacity parameters. 7 QoL parameters (except mental health) improved at 6 months follow up compared to their baseline data. The mean SF36q scale increased signifi- Table 1 Before ASD closure 12 months after ASD closure p value Time of exercise (min) 9.1± ±5.1 <0.001 VO2peak (ml/kg/min) 8.2± ±5.1 <0.001 SF36q scale ± ±22.7 < The right atrial area (cm 2 ) 24,8±1,3 17.2±1,2 < The right ventricular area (cm 2 ) 19,5±1,37 12±1,3 <0.0001

16 316 Atrial septal defect closure Unresolved issues cantly in 22 (88%) pts of mean 46.2±19,1 (5-69). The right ventricular dimension decreased in 20 pts (80%) (Table 1). Conclusions: Closure of ASD in elderly patients caused a significant clinical and hemodynamic improvement after percutaneous treatment, which is maintained to long-term follow-up what justified this procedure in old age Real time three dimensional transoesophageal echocardiography improves anatomical analysis before and during device transcatheter closure of atrial septal defects E. Brochet, P. Aubry, J.M. Juliard, L. Lepage, D. Detaint, D. Messika Zeitoun, A. Vahanian. Bichat-Claude Bernard Hospital (AP-HP), Paris, France Objectives: to compare the value of real time 3D (RT3D) and bi-dimensional (2D) transoesophageal echocardiography (TEE) in the assessment of atrial septal anatomy before and during transcatheter closure of atrial septal defects (TCASD) Methods: 2Dand RT3DTEE were performed in 27 consecutive patients (age 42±15 yrs) undergoing TCASD using a matrix array TEE transducer (X7-2, Philips imaging). Multiplane 2D and 3D en face views of ASDs were used to assess the shape, location, size and number of defects. Maximal ASD diameter (Max D) was measured on line by 2Dand off line by RT3DTEE after adequate choice of section planes within a 3D volume data set (QLab, Philips). 2D and RT3DTEE were compared before and during intervention. Results: RT3D en face views provided excellent visualization of the shape and location of ASD in all patients. In pts with multifenestrated ASD (n=4) RT3D identified a higher number of defects (n=11) than 2D (n=7)(p=0.002) Overall, Max D was significantly higher with RT3D than with 2DTEE (18±6vs16±6 mm p=0.02). This difference was observed in non circular ASD (n=16) but not in circular ASD (n=7). Differences between balloon stretched diameter and Max D were lower with RT3D (7±3 mm) than with 2DTEE (8.5±3mm) (p=0.003). During the procedure RT3D was superior to 2DTEE to monitor adequate crossing of the defect, especially in multiple defects, defect sizing and device s deployment monitoring. Finally, RT3D was superior to 2DTEE in identifying the final shape and position of the device before release. p<0.0001, respectively) and almost returned to previous value (Fib = 253±49 mg/dl; TAT = 2.1±1.2, respectively) at 1 month after TCO-ASD. TAT at 5 days significantly positively correlated with age (r=0.39, p<0.002), Qp to Qs ratio (r=0.27, p<0.03), fluoroscopic time (r=0.51, p<0.0001) and device size (r=0.45, p<0.0001). 50(+) showed significantly higher TAT and Fib than 50( ) at any time point except for pretreatment Fib and no 50(+) complained neurological symptom but 12 of 65 (18.5%) in 50( ) complained neurological symptom at 5 days to 3 weeks after TCO-ASD (ns). In 50( ), H(+) showed significantly higher TAT than H( ) before (5.2±5.6 vs. 2.0±3.7, p<0.02) and at 5 days after TCO-ASD (10.2±6.5 vs. 6.5±3.4, p<0.01). Conclusions: Coagulation activity transiently increased after TCO-ASD and this increase was pronounced in older patients 50 years old. In patients < 50 years old, this increased coagulation activity may be associated with transient neurological symptoms after TCO-ASD One year efficacy of patent foramen ovale closure using the new bioabsorbable septal repair implant B. Van Den Branden, M.C. Post, H.W.M. Plokker, J.M. Ten Berg, M.J. Suttorp. St Antonius Hospital, Nieuwegein, Netherlands Background: A high rate of residual shunting is present at short-term follow up, using the new bioabsorbable device for patent foramen ovale (PFO) closure. We report the efficacy of PFO closure with the bioabsorbable device at one year follow up. Methods: All consecutive patients, undergoing a percutaneous closure of a symptomatic PFO using the bioabsorbable closure device between November 2007 and January 2009, were included. The efficacy was based on residual shunting and graded as minimal, moderate or severe, using contrast transthoracic echocardiography (ctte) with the Valsalva manoeuvre. Results: In total 62 patients were included (55% female, mean age 47.2±11.8 years). The implantation was successful in 97%. In hospital (IH), one day after closure (n=60), a residual shunt was present in 60% of patients (minimal 32%, moderate 20%, large 8%). A residual shunt at one month (n=56) was present in 39% (minimal 27%, moderate 9%, large 4%, p=0.002 compared to IH), at six month (n=37) in 27% (minimal 16%, moderate 11%, p=0.004 compared to IH), and at one year follow up (n=19) in 21% (all minimal, p=0.004 compared to IH). A moderate or large shunt was present in 28%, 13%, 11%, and 0% at 1 day, 1, 6, and 12 months follow up, respectively. A predictor for residual shunt could not be identified. Conclusion: There is a significant decrease in the residual shunt rate during the first year after PFO closure with the new bioabsorbable device. However, there is still residual shunting 1 year after closure in 21% of the examined patients. Therefore, we will perform further echocardiographic follow-up to assess longterm efficacy more accurately. Conclusion: RT3DTEE improves anatomical analysis before and during transcatheter closure of ASD. In addition, RT3D facilitates the monitoring of ASD closure Therefore, RT3DTEE should become the preferred echocardiographic method during percutaneous ASD closure Transient hypercoagulable state and neurological symptom after transcatheter occlusion of atrial septal defect using amplatzer septal occluder K. Suda 1,Y.Kudo 1,S.Itoh 2, Y. Tananari 2,H.Nishino 1,H.Ishii 1, M. Iemura 1, Y. Maeno 1, H. Yasunaga 2,T.Matsuishi 1. 1 Kurume University School of Medicine, Kurume, Japan; 2 St. Mary s Hospital, Kurume, Japan Background: Although transcatheter occlusion of atrial septal defect using Amplatzer septal occluder (TCO-ASD) became popular, there was little information about the change in coagulation profile. Objective: To determine change in coagulation activity and its association with headache after TCO-ASD. Material and Methods: Subjects were 73 patients who underwent TCO-ASD. Prospectively blood samples were obtained before, at 5 days, and 1 month after TCO-ASD and fibrinogen (Fib) and thrombin-antithrombiniii complex (TAT) were measured. Also, we determined if they had neurological symptoms such as headache and nausea [H(+) or H( )] within a month. Then the patients were divided into 2 groups; 50 years old [50(+), n=8] and <50 years old [50( ), n=65] because generally older patients showed higher TAT. Coagulation activity was compared among 3 time points; before, at 5 days, and 1 month after TCO-ASD and the time course of TAT was compared between 50(+) and 50( ). Correlation of the maximum TAT and demographic data were determined and the maximum TAT was compared between (H+) and (H ). Results: Both Fib and TAT increased significantly at 5 days (Fib = 235±55 before vs. 311±66 mg/dl at 5 days, p<0.0001; TAT = 3.2±6.4 before vs. 8.4±8.0, 2009 Cardiac troponin I release after transcatheter closure of the atrial septal defect M. Pieculewicz, P. Podolec, T. Przewlocki, P. Wilkolek, L. Tomkiewicz- Pajak, E. Suchon, M. Hlawaty, M. Olszowska, W. Tracz. Department of Cardiac and Vasculare Disease Collegium Medicum Jagiellonian Univercity, John Paul II, Krakow, Poland Cardiac troponin-i (ctni) is a very specific and sensitive marker of myocardial injury. A significant increase of ctni levels after percutaneous atrial septal defect (ASD) closure has been reported. The aim of the study was to identify ctni rise after percutaneous ASD closure, to determine its prognostic significance and to assess the relationship between supraventricular ectopy (SVE) in early follow-up and procedural increase of cardiac markers. Methods: Consecutive 281 patients (161 F, 120 M) with a mean age of 47.2±17.2 (15-74) with ASD who underwent transcatheter closure, were analyzed. The troponin I (TnI) and CK-MB level was measured at 0, 8, 16 and 24 hours after procedure. Holter monitoring was performed on all pts before procedure, 1 and 6 months of follow-up. Results: The ASO device was successfully implanted in all patients (procedure time 39.1±4.2 (11-52) minutes, fluoroscopy time 11.0±7.0 (4-41) minutes). A significant increase in number of SVE premature beats/24 hours was noted 1 month after procedure: 1020,9±431 ( ) compared to baseline data 54,5±43 (0-560) (p<0,0001), after 6 month SVE decreased to 61,8±51 (4-701). In none of the pts ctni was elevated before the procedure. Periprocedurally, the increase of cardiac markers: TnI over 50% beyond reference level was observed in 57,2% of pts, and two-folded increase of CK-MB levels in 2.2%. There was a significant correlation between SVE premature beats/24 hours 1 month after procedure and periprocedural increase of TnI (p<0,0001 r =95921). In addition, ctni rise was significantly related with the procedure time (p<0,001), fluoroscopy time (p<0,001), and the device size (p<0,001). In multivariable analizes (including 12 clinical, procedural and anatomical factors) number of SVE ectopy 1 month afrer ASD closure, procedural time and device size were independent risk factors for TnI rise. Conclusions: The significant increase of ctni is noted frequently after the transcatheter closure of ASD not connected with myocardial infarction symptoms or other serious clinical complications. The independent risk factors for ctni rise are:

17 Atrial septal defect closure Unresolved issues / Science Hot Line 317 number of the peri-procedural supraventricular ectopy, elongated time of procedure and larger device size Symptomatic tachy- and bradyarhythmias after transcatheter closure of interatrial communications with Amplatzer devices M. Szkutnik, J. Bialkowski. Silesian Center for Heart Diseases, Zabrze, Poland Introduction: Transcatheter closure of interatrial communications (ASD) with Amplatzer occluders (ASO) became standard treatment in many centers. We analyzed the incidence of cardiac arrhythmias after such treatment. Methods: The group of 759 patients (pts) after transcatheter closure of ASD with ASO were retrospectively analyzed. Only pts with a new and symptomatic arrhythmias were included to the study. All pts, who had arrhythmias prior to ASD closure, were excluded. Results: New tachy- and bradyarhtymias after implantation of ASO were observed in 11 pts (1,5%). There were 9 pts (mean age 36,7 y) with atrial tachyarhythmias (AF in 8 and SVT in 1 pt), which appeared between 1 day and 3 months after implantation. Seven pts were treated initially by pharmacotherapy; in 2 of them sinus rhythm returned just after cardioversion. In another 2 cardioversion was performed as initial therapy. In non but one recurrence of tachycardia was observed, however 7 of them had prolonged (till one) year pharmacotherapy. In 2 pts aged 15 and 16 years complete a-v block appeared 4,3 and 1,5 year after ASO implantation respectively. In the first one intermittent II degree a-v block (Mobitz II) was observed before ASD closure. DDDR pacemaker was implanted in both pts. Conclusions: Transcatheter closure of ASD with ASO is associated with the risk of new atrial tachyarythmias (usually early after the procedure and in older patients). The risk of complete heart block is low, but it can appear in late follow-up. Thence close long term follow-up of all patients is obligatory. SCIENCE HOT LINE 2015 Focal adhesion kinase regulates load-induced PGC-1a expression and mitochondrial biogenesis in mice left ventricle T. Tornatore, C. Clemente, C. Judice, S. Rocco, T. Theizen, A.H. Macedo, A.P. Dalla Costa, M. de Oliveira, J. de Lima, K. Franchini. University of Campinas, Department of Internal Medicine, Faculty of Medical Sciences, Campinas, Brazil Aims: Mechanical stress invokes mitochondrial biogenesis and shifts of the substrate metabolism of myocardium. These processes are mostly drive by NRF-1 and Tfam transcription factors, which are coordinately regulated by transcriptional co-activator PGC-1a. The molecular mechanisms involved in the activation of PGC-1a by the mechanical stimuli are not known. Herein, we examined whether signaling mediated by FAK (Focal Adhesion Kinase) plays a role in the activation of PGC-1a and mitochondrial biogenesis induced by pressure overload in mice left ventricle (LV). Methods: Knockdown of FAK in mice LV was obtained by administering sirna targeted to FAK (sirnafak) through the jugular vein. Pressure overload of LV was induced by transverse aortic constriction (TAC). The levels of FAK and ANP transcripts were obtained by quantitative RT-PCR (qrt-pcr). Western blotting was used to detect the protein levels of FAK, phosphofak-tyr397, PGC-1a and NFR-1. Mitochondrial biogenesis was assessed by the mtdna/ndna ratio obtained by qrt-pcr of D-Loop and 18S genes. Myocardial AMP and ATP levels were obtained by a chromatographic method. Results: sirnafak reduced myocardial FAK transcript and protein by 50, 25 and 20% after 1, 7 and 15 days of TAC, respectively. FAK depletion markedly attenuated the hypertrophic growth and the increases of myocardial ANP transcript in TAC mice, in respect to TAC mice treated with sirnagfp. TAC enhanced the myocardial PGC1a and NRF-1 and FAK knockdown attenuated this increase. Pressure overload lasting 7 and 15 days markedly increased the mtdna/ndna ratio in the LV. Depletion of FAK attenuated the rises in the mtdna/ndna ratio induced by aortic banding. The AMP/ATP ratio was show to remain unchanged in the myocardium of 1 day but it was progressively reduced in 7 and 15 day TAC in respect to SO mice Connexin 43 is fundamental for cytoprotective signal transduction on mitochondrial KATP channels U. Hoppe, D. Rottlaender, M. Wolny, M. Guido, J. Endres-Becker, K. Boengler, R. Schulz, G. Heusch. University of Cologne, Cologne, Germany Background: Potassium (K + ) channels of the inner mitochondrial membrane influence cell function and survival. Multiple signaling pathways and pharmacological actions converge on mitochondrial adenosine triphosphate-sensitive K + (mitokatp) channels and protein kinase C (PKC) as pivotal components of cytoprotection against necrotic and apoptotic cell injury. However, the molecular structure of mitokatp channels remains unresolved and no mitochondrial phosphoprotein has yet been identified that may mediate cytoprotection by these kinases. Methods and Results: We show that mitochondrial connexin 43 is essential for drug- and PKC-mediated mitokatp channel activation, which is restricted to a specific mitochondrial subpopulation. By patch-clamping the inner membrane of subsarcolemmal murine cardiac mitochondria, we found that mitokatp channel activity is significantly increased by the epsilon isoform of PKC (PKCε). Baseline mitokatp channel properties are similar in wildtype and connexin 43 deficient (Cx43+/-) mice. However, genetic connexin 43 deficiency or pharmacological connexin inhibition by carbenoxolone significantly reduce drug- and PKCmediated stimulation of mitokatp channels, explaining loss of cytoprotection in Cx43+/- mice in vivo. Connexin 43 and PKCε associate in mitochondrial protein complexes. Furthermore, mitokatp channels of interfibrillar mitochondria, which do not contain any detectable connexin 43, are completely drug- and PKCinsensitive, (i) confirming the fundamental role of connexin 43 for mitokatp channel stimulation and (ii) indicating compartimentation of mitochondria in cell signaling. Conclusion: Our results define a novel molecular function of mitochondrial connexin 43 and provide a link between cytoprotective stimuli and mitokatp channel opening. Thus, mitochondrial connexin 43 is a major target for drug development against cell injury Myocardial ischemia/reperfusion injury is mediated by leukocytic TLR2 and reduced by systemic administration of a novel anti-tlr2 antibody F. Arslan 1, M. Smeets 1, L.A.J. O Neill 2, B. Keogh 3,P.McGuirk 3, L. Timmers 1, I.E. Hoefer1, P.A. Doevendans 1, G. Pasterkamp 1, D. De Kleijn 1. 1 University Medical Center Utrecht, Utrecht, Netherlands; 2 Trinity College Dublin, Dublin, Ireland; 3 Opsona Therapeutics Ltd. Background: Reperfusion therapy for myocardial infarction is hampered by detrimental inflammatory responses partly via Toll-like receptor (TLR) activation. Targeting TLR signaling may optimize reperfusion therapy and enhance cell survival and heart function after myocardial infarction. Here we evaluated the role of TLR2 as a therapeutic target using a novel monoclonal anti-tlr2 antibody. Method and Results: Mice underwent 30 minutes ischemia, followed by reperfusion. Antibody and controls were administered 5 minutes prior to reperfusion. Cardiac function and dimensions were assessed at baseline and 28 days postinfarction, using 9.4T mouse-mri. Saline and IgG isotype treatment resulted in 34.5±3.3% and 31.4±2.7% infarction, respectively. Bone marrow transplantation experiments between wild-type and TLR2null mice revealed that final infarct size is determined by circulating TLR2 expression. A single intravenous bolus injection of anti-tlr2 antibody reduced infarct size to 18.9±2.2% (p=0.001). Compared to saline, anti-tlr2 treated mice exhibited less expansive remodeling (end-diastolic volume: 68.2±2.5 μl versus 76.8±3.5 μl; p=0.046), and preserved systolic performance (ejection fraction: 51.0±2.1% vs. 39.9±2.2%, p=0.009; systolic wall thickening: 3.3±6.0 versus 22.0±4.4%, p=0.038). Anti-TLR2 treatment significantly reduced neutrophil and macrophage infiltration. Furthermore, TNFα, IL1α, GM-CSF and IL-10 were significantly reduced as were phosphorylated-c-jnk and phosphorylated-p38-mapk levels. Conclusions: Circulating TLR2 expression mediates myocardial I/R injury. Antagonizing TLR2 5 minutes prior to reperfusion reduces infarct size and preserves cardiac function and geometry. Anti-TLR2 therapy exerts its action by reducing leukocyte influx, cytokine production and pro-apoptotic signaling. Hence, monoclonal anti-tlr2 antibody is a potential candidate as an adjunctive for reperfusion therapy in patients with myocardial infarction Exosomes are the active cardioprotective component in MSC secretion D. De Kleijn 1,R.C.Lai 2,F.Arslan 1,L.M.May 3,S.K.Sze 4, L. Timmers 1,A.Choo 3,G.Pasterkamp 1, C.N. Lee 5,S.K.Lim 2. 1 UMC Utrecht, Experimental Cardiology, Utrecht, Netherlands; 2 IMB, Singapore, 3 BTI, Singapore, 4 NTU, Singapore, 5 NUH, Singapore, Secretion from Human ESC-derived mesenchymal stem cells (MSCs) has shown to reduce infarct size for 60% in a mouse and porcine model after reperfusion and provides an off-the-shelf MSC-based therapeutic option. The cardioprotective effect was associated with large complexes in the secretion of nm in diameter. It is, however, unknown how MSC secretion exerts its therapeutic effect. Here we demonstrate that these complexes in MSC secretion contain small RNAs and exosome associated proteins CD9, CD81, and Alix. Flotation density analyses revealed that these proteins were located in detergent-sensitive phospholipid vesicles. In addition, we identified exosomes as a homogenous population in MSC-CM with a particle size of rh=45-55 ηm using High Performance Liquid Chromatography. This exosome fraction separated from MSC secretion also reduced infarct size for 60% in a mouse myocardial ischemia/reperfusion injury model. These findings identifies exosomes, for the first time, as the biologically active cardioprotective component in MSC secretion that can be used as a therapeutic compound for the treatment of myocardial infarction. Due to the affordable costs, excellent quality control and consistency and potential vehicle properties that can cross membranes, exosomes have the potential to be used in a broad therapeutic range in cardiovascular disease.

18 318 Science Hot Line / You want prognosis? Do echo 2019 Focal C-reactive protein and all cause mortality B.G. Nordestgaard, J. Zacho, A. Tybjærg-Hansen. Copenhagen University Hospital, Herlev Hospital, Herlev, Denmark Context: Elevated levels of C-reactive protein (CRP) associate with increased risk of all cause mortality. Objective: We tested whether this is a robust and causal association. Design: We studied 10,388 white persons from the general population, the Copenhagen City Heart Study. During 12 years 2754 persons died. We measured baseline high-sensitivity CRP and fibrinogen levels, and genotyped for 4 CRP polymorphisms. Results: Levels of CRP >3 mg/l, compared with levels <1 mg/l, associated with a multifactorially adjusted 2-fold increased risk of all cause mortality. Stratifying CRP into tertiles, quintiles or octiles resulted in step-by-step increased risk of all cause mortality (all trend, p<0.0001). Excluding those who died within 2 years after CRP measurement resulted in similar but slightly attenuated risk increases (all trend, p<0.0001). After adjustment for fibrinogen levels the association between CRP and all cause mortality attenuated further, but persisted. Genotype combinations of the 4 CRP polymorphisms associated with up to a 49% increase in CRP levels, resulting in a theoretically predicted increased risk of up to 16% for all cause mortality. However, these genotype combinations did not associate with increased risk of all cause or cardiovascular mortality. Conclusions: A single CRP measurement robustly associates with increased risk of all cause mortality. However, adjustment for fibrinogen levels largely attenuated this association and genetically elevated CRP levels did not associate with increased mortality. Therefore, elevated CRP levels do not appear to cause early death but more likely is a marker of hidden inflammatory disease possibly leading to death Chronic, low dose epoetin-β treatment following PCI significantly improves left ventricular ejection fraction in ischemic heart failure M. Bergmann 1, F. Knobelsdorff-Brenckhahn 2, R. Wassmuth 2, H. Mehling 2, A. Busjahn 3, J. Schulz-Menger 2,R.Dietz 2. 1 ASKLEPIOS Clinic St. Georg, Hamburg, Germany; 2 Charite Campus Buch, Berlin, Germany; 3 HealthTwist, Berlin, Germany Background: Experimentally, low doses of epoetin-β not affecting hemoglobin levels were shown to be beneficial for left ventricular both concerning cardiomyocyte protection as well as angiogenesis. The latter effect is due to enhanced mobilization of endothelial progenitor cells. However, chronic low dose epoetin treatment has not been tested previously in the clinical setting. Here, we analysed the effects of epoetin-β over 6 months on left ventricular cardiac remodeling following succesful percutaneous coronary intervention (PCI). Study design: We performed an investigator-initiated, randomized, placebocontrolled, double-blind, single-center study in patients with symtomatic ischemic cardiomyopathy following PCI (NCT ). Inclusion criteria were reduced ejection fraction and succesful revascularization by PCI within the last 14 days. Major exclusion criteria were hemoglobin higher than 16mg/dl and contraindications for cardiac MRI. Patients were treated according to current guidelines. Echocardiography, cardiac MRI, exercise capacity and brain natriuretic peptide levels were measured at baseline and after 6 months; data analysis was finalised in a double-blind fashion. Results: At the end of the study, follow up data for 28 patients were complete; data are reported as mean ± SEM. Both between groups as well as in-group differences were statistically analysed. Serum erythropoetin levels were significantly higher but in the normal range at the 6 months final visit in the EPO group. Hemoglobin levels and exercise capacity increased and bnp levels decreased in both groups during the 6 months follow up without significant differences. Five patients had to be re-admitted to the hospital during the 6months study course, all events were judged unrelated to the treatment. Specifically, no target vessel revascularization had to be performed. Epoetin-β treatment significantly improved global ejection fraction as measured by echocardiography (EPO EF 5.2±2.0%, p<0.05; placebo EF 0.3±1.6% p=ns) and cardiac MRI ( EF 3.1±1.6%, p<0.05; placebo -1.9±1,2, p=ns). Summary: To our knowledge, this pilot trial has examined for the first time the effectiveness of low dose epoetin-β treatment in patients with ischemic cardiomyopathy following PCI and normal hemoglobin levels. The treatment proved to be safe. Analysis of ejection fraction by two independent methods, namely echocardiography and cardiac MRI, suggest the treament to be effective regarding global left ventricular ejection fraction. This approach warrants further mechanistic studies as well as larger trials to confirm effectiveness. YOU WANT PROGNOSIS? DO ECHO 2043 Left atrial enlargement and dysfunction - a new marker of long-term poor proognosis in dilated cardiomyopathy E. Michalak 1, Z.T. Bilinska 1, J.M. Michalak 2, J. Grzybowski 1, W. Ruzyllo 1,P.Hoffman 1. 1 Institute of Cardiology, Warsaw, Poland; 2 Central Clinical Hospital of the MSWiA (Ministry of Interior & Administr. of the Republic of Poland), Warsaw, Poland Coexistence of systolic and diastolic dysfunction is frequent in heart failure. Pts with dilated left ventricle and EF<30% had a poor prognosis. Left atrial (LA) enlargement and dysfunction indices could be additional markers of poor long-term prognosis in this disease. M-mode, 2-dimesional, pulse and color Doppler echocardiography were performed in 165 pts with non-coronary dilated cardiomyopathy (mean age 40,6±12,6yrs, 24F). LA diameters and volumes: maximal (LAVmax, LADmax), pre-systolic (LAVpreP, LADpreP, ECG P wave) and minimal (LAVmin, LADmin) and left ventricular diastolic (LVVD) and systolic volumes (LVVS) were assessed using 2D acoustic quantification method with modified Simpson s rule in apical 4-chamber view. The following parameters were evaluated: LA and LV diameter and volume indices, LA total emptying fraction (LAV TE%=[LAVmax-LAVmin]*100/LAVmax), LA active emptying fraction (LAV AE%= [LAVpreP-LAVmin]*100/LAVpreP),LA vcf [LADpreP-LADmin]/[LAD*tA], LVEF%, Emax/Amax, t dece, mitral regurgitant fraction (MR%), mean CWP. 61pts had significant mitral regurgitation fraction MR%>30%. During follow-up 7,1±2,6yrs (13,3-1,4yrs) 68 pts died. Multifactor regression analysis revealed that all parameters except MR%, Emax/Amax, LAV TE% and LV EF% were significant independent predictive factors of survival (p<0,001). Kaplan_Meier estimates of survival showed that pts with LAV TE% >21,6% had better survival than those with LAV TE%<21,6%. Kaplan-Meier estimate of survival Conclusion: LA maximal, presystolic and minimal volumes and diametres, active emptying fraction and LA vcf were additional valuable factors of poor long-term prognosis in dilated cardiomyopahty Prediction of life-threatening ventricular tachyarrhythmias and death in patients with previous myocardial infarction by left ventricular longitudinal strain analysis C.T.A. Ng 1,M.Bertini 1, J.W. Borleffs 1, V. Delgado 1,G.Nucifora 1, G. Boriani 2, D.Y. Leung 3, M.J. Schalij 1,J.J.Bax 1. 1 Leiden University Medical Center, Leiden, Netherlands; 2 Univ. di Bologna - Istituto di Cardiology, Bologna, Italy; 3 The University of New South Wales, Sydney, Australia Purpose: Impaired left ventricular (LV) ejection fraction (EF) is an important clinical criterion for insertion of implantable cardioverter-defibrillators (ICD) in patients with previous myocardial infarctions. However, better risk stratification is needed as most patients with ICD do not experience appropriate therapy. Therefore, the aim of this study was to risk stratify patients with previous myocardial infarction

19 You want prognosis? Do echo 319 and ICD implantation by assessing segmental longitudinal strains in the infarct, peri-infarct and remote LV zones. Methods: Echocardiographic 2-dimensional speckle tracking longitudinal strain analysis using a 17-segment LV model was performed in 148 patients with previous myocardial infarction and ICD implantation for primary prevention. An infarct segment was defined as a longitudinal strain value of -5%. A peri-infarct segment was defined as immediately adjacent to an infarct segment. A remote segment was defined as any segment that is not an infarct or peri-infarct segment. Mean longitudinal strains of the infarct, peri-infarct and remote zones were calculated. All patients were followed up for combined endpoint of occurrence of life-threatening ventricular tachyarrhythmias treated with appropriate ICD therapy and death. Results: The mean age was 65±11 years, 127 men. 74 (50%) patients had cardiac resynchronization therapy (CRT). Mean LVEF was 28±6%. Mean longitudinal strains of the infarct, peri-infarct and remote zones were -0.9±2.5%, -10.5±2.0%, and -14.1±3.4% respectively, p< After a mean follow-up period of 23±19 months, 46 (31%) patients experienced the combined endpoint. Patients with the combined endpoint had no significant differences in LVEF (24±6 vs. 26±7%, p=0.09) but had higher wall motion score index (2.04±0.30 vs.1.90±0.39, p=0.010). Similarly, mean longitudinal strain in the peri-infarct zone was more impaired in patients who experienced the combined endpoint as compared to others (-9.5±1.5 vs ±2.1%, p<0.001), but there were no significant differences in mean longitudinal strains of the infarct and remote zones. Only mean longitudinal strain in the peri-infarct zone (hazard ratio 1.4, 95% confidence interval , p=0.012) and CRT (hazard ratio 0.5, 95% confidence interval , p=0.040) were independent predictors of the combined endpoint during follow-up on multivariate Cox regression analysis. Conclusions: Longitudinal strain of the peri-infarct zone may be a useful risk stratification parameter for patients with previous myocardial infarction who are candidates for ICD implantation for primary prevention Global longitudinal strain is superior to ejection fraction and wall motion scoring for the prediction of mortality T. Stanton, R. Leano, T.H. Marwick. The University of Queensland, Brisbane, Australia Purpose: Global LV systolic function is an important determinant of mortality, usually measured by ejection fraction (EF) which has some technical limitations. Global longitudinal strain (GLS) is an automated technique for measurement of long-axis function. The aim of this study was to compare GLS with EF and wall motion scoring (WMS) for the prediction of mortality. Methods: We followed 546 consecutive individuals (64% male, mean age 60.9±11.9 years) undergoing echocardiography for all-cause mortality over 5.2±1.5 years. EF was calculated using Simpson s biplane. WMS was determined by 2 experienced readers. GLS was calculated using 2D speckle tracking as the mean GLS from 3 standard apical views. Significant univariate predictors of mortality were identified using Cox Models. Nested models of significant baseline variables followed by the separate addition of EF, WMS and GLS were then undertaken. Results: Means were EF 57.6±12.1%, WMS 1.3±0.4 and GLS -16.6±4.3%. There were 91 deaths. Clinical factors associated with outcome (model chisquare=20.2) were age (HR 1.5, 95%CI , p<0.01), diabetes (HR 1.8, 95%CI , p=0.01) and hypertension (HR 1.6, 95%CI , p<0.05). 3 separate models were used to evaluate the additional prognostic information obtained from imaging (Figure). Although addition of EF (HR 1.2, 95%CI , p<0.05) or WMS (HR 1.3, 95%CI , p<0.01) added to the predictive power of clinical variables, the addition of GLS (HR 1.5, 95%CI , p<0.001) caused the greatest increment in model power (chi square=33.7, p<0.001, figure) Speckle tracking echocardigraphy for the prognosis of patients with systolic and diastolic heart failure H. Dokainish, M. Alam, J. Nguyen, N. Lakkis, M. Stampehl. Baylor College of Medicine, Houston, United States of America Background: There are no published data on the utility of speckle strain echocardiography for the prediction of outcome in patients with heart failure (HF). Methods: Patients who fit the Framingham criteria for HF underwent comprehensive echocardiography and were followed prospectively for events. In the 3 apical views, speckle-based automated functional imaging (AFI) was utilized to obtain average global systolic strain (GSS) using General Electric EchoPAC software. Optimum cut-off values for the prediction of outcome were generated from receiver operating characteristic curves, and Kaplan-Meier survival curves were generated using log rank statistics. The primary endpoint was cardiac death or rehospitalization for heart failure requiring intravenous therapy. Results: 177 patients had >/=90 day follow-up. The mean age was 56.5±8.9 years, 60/118 (51%) were female, 103 (87%) hypertensive, 47/118 (40%) diabetic, and 59/118 (50%) had coronary artery disease. The mean left ventricular ejection fraction (LVEF) was 36.4±16.7%, with 52/177 (30%) of patients with LVEF>/=45%. There were 41 primary outcomes (23%) at a mean of 104±46 days follow-up: 4 cardiac deaths and 37 HF rehospitalizations. The optimal cut-off to predict the primary endpoint was AFI GSS<13%, which was a significant predictor of event-free survival (log rank statistic=7.4, p=0.007), while LVEF was not a significant predictor of outcome (Figure, 35% p=0.08). Conclusion: Global longitudinal strain is a superior predictor of outcome compared to either ejection fraction or wall motion scoring and is now the optimal method for assessment of global left ventricular systolic function Prognostic value of peak treadmill exercise echocardiography in patients with normal post-exercise treadmill echocardiography J. Peteiro, A. Bouzas-Mosquera, A. Campos, P. Pazos, P. Pinon, A. Castro-Beiras. University of A Coruna, A Coruna, Spain Background and purpose: American and European practice guidelines state that treadmill exercise echocardiography (EE) relies on post-exercise imaging. Although peak treadmill EE may have higher sensitivity for the detection of coronary artery disease (CAD), its prognostic value remains to be determined. Our aim was to assess the value of peak treadmill EE for predicting outcome in patients with known or suspected CAD and negative post-exercise echocardiography. Methods: We studied 2527 consecutive patients who underwent treadmill EE and had normal results at post-exercise imaging. Wall motion score index and left ventricular ejection fraction were evaluated at rest, peak and post-exercise (45 secs). Ischemia was defined as the development of new or worsening wall motion abnormalities with exercise. The end-points were all-cause mortality and major cardiac events. Figure 1 Conclusions: In a HF population consisting of preserved and depressed LVEF, AFI GSS was a significant predictor of cardiac death or rehospitalization for HF, more so than LVEF. This may connote a more comprehensive LV function assessment by GSS compared to LVEF in this population. Survival (%) according to peak ischemia

20 320 You want prognosis? Do echo / Diastology: jump into the future? Results: Overall, 124 patients (4.9%) developed new or worsening wall motion abnormalities. During a follow-up of 2.9±1.8 years, 104 patients died. The 5-year mortality rate was 3.5% in patients without ischemia vs. 15.3% in those with ischemia (p <0.001). In the multivariate analysis, ischemia at peak exercise was an independent predictor of mortality (hazard ratio [HR] 1.90, 95% confidence interval [CI] , p=0.014) and major cardiac events (HR 2.25, 98% CI , p=0.017). The addition of the peak EE results to clinical and exercise variables provided significant incremental prognostic information for predicting mortality (p=0.025) and major cardiac events (p=0.021). Conclusion: Peak treadmill exercise echocardiography provides significant prognostic information for predicting mortality and major cardiac events in patients with known or suspected CAD and negative post-exercise echocardiography Prognostic implication of stress echocardiography result in hypertensives and normotensives. A study on 10,054 patients L. Cortigiani 1,R.Sicari 2,R.Bigi 3, F. Bovenzi 1, E. Picano 2. 1 Ospedale Civile, Lucca, Italy; 2 Fondazione G Monasterio, Pisa, Italy; 3 Universita di Milano, Milan, Italy Background: The relative prognostic meaning of stress echocardiography (SE) result in hypertensives (H) and normotensives (N) remains to be addressed. Aim. To compare the prognostic implication of SE in a large cohort of H and N with known or suspected coronary artery disease (CAD). Methods: The study group was formed by 10,054 patients (5,355 H and 4,699 N) who underwent exercise (n=536), dobutamine (n=2,007) or dipyridamole (n=7,511) SE for evaluation of known (n=4,075) or suspected (n=5,979) CAD. Patients were followed-up for a median of 24.4 months. Results: Ischemia at SE was assessed in 2,873 patients. During follow-up, 1,391 events (782 deaths, 609 infarctions) occurred. Independent prognostic indicators were ischemia at SE (HR 2.67, CI , p<0.0001), resting wall motion abnormality (RWMA) (HR 1.41, CI , p<0.0001), diabetes (HR 1.55, CI , p<0.0001), age (HR 1.03, CI , p<0.0001), male sex (HR 1.26, CI , p=0.003), left bundle branch block (HR 1.55, CI , p=0.006), and prior angioplasty (HR 1.26, CI , p=0.02) in H, and ischemia at SE (HR 1.41, CI , p<0.0001), peak wall motion score index (HR 2.57, CI , p<0.0001), diabetes (HR 1.84, CI , p<0.0001), age (HR 1.04, CI , p<0.0001), RWMA (HR 1.36, CI , p=0.007), and male sex (HR 1.27, CI , p=0.01) in N. Annual event rate was markedly higher in H than in N with no ischemia and no RWMA (2.6% and 1.6%, p<0.0001): figure. Moreover, event-rate associated to ischemic SE was similar (p=0.97) in H with and without RWMA, but lower (p=0.006) in N without RWMA (Figure). Conclusions: SE result allows effective prognostication in H and N. However, a non ischemic test predicts better survival in N than in H with no RWMA. DIASTOLOGY: JUMP INTO THE FUTURE? 2049 Normal values for diastolic strain rate from combined speckle tracking and Doppler tissue imaging. Preliminary data from the HUNT3-study H.D. Dalen, A. Thorstensen, C.B. Ingul, S.A. Aase, A. Stoylen. Norwegian university of science and technology, Trondheim, Norway Purpose: Strain rate imaging is becoming a widely published method for quantifying both systolic and diastolic left ventricular (LV) function. The aim of the study is to establish normal values for global diastolic strain rate. Methods: 1296 persons aged 20 to 89 which participated in the HUNT 3 study was randomised to echocardiographic examination which included colour tissue Doppler imaging Personell were eligible for inclution if they were without known heart diseases, diabetes or treated hypertension. 31 were excluded after echocardiographic examination. Post-prosessing analysis was performed with a semi-automatic software with segmentation of the myocardium and tracking along ultrasound beam with tissue Doppler and tracking perpendicular to the ultrasound beam with speckle tracking. Segments with poor data quality were discarded manually. An 18 segment LV model was used segments were analysed. Global diastolic strain rate was calculated as the average of accepted segments for E and A respectively. 98,9% had segments accepted for global strain rate measurement. Results: The over all longitudinal diastolic strain rate E and A (s -1 ) was (SD) 1,29 (0,29) and 0,98 (0,23). Participants were divided into 3 age groups: <40, and >60 years. In females longitudinal diastolic strain rate E (s -1 ) was (SD) 1,56 (0,24), 1,36 (0,25) and 1,08 (0,20) respectively and in males 1,41 (0,23), 1,21 (0,22) and 1,03 (0,23). There was a very highly significant decrease of strain rate E with increasing age with p<0,0001 between all adjacent age groups. Mean strain rate E was higher in female groups than in male and the significance of difference between genders was very highly significant with p<0,0001. Longitudinal strain rate A (s -1 ) in females was 0,83 (0,17), 0,98 (0,22) and 1,37 (0,29) respectively. The increase in mean strain rate A with increasing age was very highly significant with p<0,0001 between adjacent age groups, but there was no significant difference between genders. Conclusions: The study presents preliminary normal values for global diastolic strain rate E and A for both genders. Mean strain rate E decreases significantly with increasing age and is significant higher in females than in males. Mean strain rate A increases significantly with increasing age but there is no significant difference between genders. In all age groups there is a significant variability for both diastolic strain rate E and A which has to be taken into account in individual clinical decision making. Abbreviations: LV - Left ventricle SD - Standard deviation 2050 Are E/Ea and E/(Ea x Sa) ratios reliable predictors of left ventricular diastolic pressures in an unselected population? E. Chieffo, M. Previtali, A. Repetto, M. Ferrario, C. Klersy. IRCCS Pol. S.Matteo Università di Pavia, Pavia, Italy Background: E/Ea and E/(Ea x Sa) ratios are considered reliable non-invasive predictors of LV diastolic pressures (LVDP), but recent studies in pts with heart failure have shown a lack of correlation between these parameters and invasively measured LVDP. Aim of this study was to: 1) assess the correlation between E/Ea and E/(Ea x Sa) with LVDP in an unselected population; 2) evaluate the influence of LV systolic function and end-diastolic volumes (EDV) on this relationship; 3) define sensitivity (SE) and specificity (SP) of E/Ea in predicting normal or increased LVDP. Methods: 100 pts (81 men and 19 women, aged 63±11) 43% with EF 50%, 50% with LV dilation (LVEDV >75 ml/m 2 ) in sinus rhythm and no significant valvular regugitation, underwent hemodynamic study with measurement of pre-a LVDP and LVEDP with fluid-filled catheters and complete echo-doppler evaluation in the same day; septal (S), lateral (L) and average (Av) E/Ea and E/(Ea x Sa) were calculated. Results: In the overall population a statistically significant correlation was found between pre-a LVDP and S E/Ea (r =0.29 P=0.004), Av E/Ea (r =0.25 P=0.01), S E/(Ea x Sa) (r =0.31 P=0.002), L E/(Ea x Sa) (r =0.29 P=0.004) and Av E/(Ea x Sa) (r =0.31,P=0.002); the strongest correlation was found for S E/Ea (r=0.48, p=0.0002) and E/(Ea x Sa) (r=0.45, P=0.001) in the subgroup with normal LVEDV. A significant correlation with LVEDP was found only for L E/(Ea x Sa) (r=0.41, P=0.01) in the subgroups with EF 50% and for S E/(Ea x Sa) (p=0.003, r=0.40) in the subgroup with normal LVEDV. Pts with normal ( 15 mmhg) or increased LVEDP showed no significant difference in S (11.6 vs 12.6), L (13.8 vs 14.9) and Av E/Ea (12.4 vs 13.1). Moreover, LVEDP was not significantly different in the 3 subgroups with E/Ea 8, between 8-15 and 15, while a significant difference in pre-a LVDP between the 3 subgroups was found only for S E/Ea (P=0.0005). An E/Ea 8 had a low sensitivity (S 11, L 41 and Av 20%) but high specificity (S 89, L 66, AV 88%) for identifying normal LVEDP; a E/Ea 15 had a low sensitivity (S 47, L 26 and Av 29%) but high specificity (S 68, L 83, AV 74%) for LVEDP >15mmHg. Conclusions: 1) In an unselected population E/Ea and E/(EaxSa) show a statistically significant but weak correlation with pre-a LVDP, while a significant correlation with LVEDP is found only in pts with systolic LV dysfunction or normal LVEDV. 2) The E/Ea cut-off values for normal or increased LVEDP have a good specificity but a low sensitivity for predicting normal and increased LVEDP and are therefore of limited clinical value for predicting LVEDP in the individual pt Long term endurance training does not prevent the age related decline in left and right ventricular diastolic function assessed by Doppler echocardiography A.J. Teske 1,N.H.Prakken 2,B.W.DeBoeck 1, B.K. Velthuis 2, P.A. Doevendans 1,M.J.Cramer 1. 1 University Medical Center Utrecht, Department of Cardiology, Utrecht, Netherlands; 2 University Medical Center Utrecht, Department of Radiology, Utrecht, Netherlands Purpose: 1) to evaluate the effect of long term endurance training on LV and RV diastolic function and 2) whether the normal aging effect on diastolic function is impeded due to endurance training. Methods: A total of 289 healthy individuals were prospectively enrolled for echocardiographic evaluation. Groups were defined based on age and athletic

21 Diastology: jump into the future? 321 activities: 1) young non-athletes (18-40 y, n=62), 2) old non-athletes (>40y, n=53), 3) young regular (9-18 h/sp/wk, n=58), 4) young professional (>18h/sp/wk, n=63) and 5) old athletes (>40 y, >9 h/sp/wk, n=53). LV and RV pulsed wave Doppler indices for diastolic function were obtained in rest. Differences were calculated using ANOVA-Bonferroni. Correlations were evaluated using Pearson. Results: No significant differences were found between the young controls, regular- and professional athletes in LV (MV E/A-ratio 2.08±0.5 vs. 2.12±0.5 vs. 2.30±0.7, E/E 5.24±0.9 vs. 5.36±0.9 vs. 5.01±0.8, respectively, p=ns) and RV (TV E/A-ratio 2.35±0.6 vs. 2.40±0.6 vs. 2.56±0.6, E/E 4.25±0.9 vs. 4.11±1.0 vs. 4.44±1.0, respectively, p=ns) diastolic parameters. These were also comparable between controls and athletes >40y (MV E/A-ratio 1.68±0.4 vs. 1.52±0.4, E/E 6.22±1.5 vs. 5.90±1.1, TV E/A-ratio 2.02±0.6 vs. 2.04±0.5, E/E 4.00±0.7 vs. 4.20±1.2, p=ns). In both the athletes and controls, similar and significant correlations were found between age and diastolic parameters (figure). In all parameters, age was the most important determinant in multivariate analysis while the influence of training was <2% of the observed variance. Methods: 214 consecutive patients (aged 58±11 years, 64% male) with preserved ejection fraction ( 50%) undergoing exercise stress echocardiography were followed over 2.7±1.7 years. Left ventricular (LV) filling pressure was estimated as the ratio of early diastolic transmitral flow (E-velocity) and early diastolic tissue velocity (septal E ), with E/E >15 at exercise considered raised. Ischaemia was identified by inducible regional wall motion abnormalities. Deaths and cardiovascular hospitalisations were recorded, and analysed by the Kaplan Meier and Cox regression methods. Results: 69 patients developed ischaemia with stress and 19 had a raised E/E. There were 63 events (7 deaths, 56 cardiovascular hospitalisations). Event-free survival (see Figure) in patients with raised exercise E/E and no ischaemia was comparable to patients with ischaemia alone (p=0.84). The combination of raised exercise E/E and ischaemia yielded a significantly worse survival curve than patients with normal exercise E/E with or without ischaemia (P<0.05). Independent, significant predictors of outcome by Cox regression analysis were; exercise E/E >15 (HR=2.052; p=0.041), ischaemia (HR=1.814; p=0.021) and peak heart rate (HR=1.014; p=0.014). Conclusion: The amount of endurance training does not alter diastolic properties in either ventricle. The decrease in diastolic function observed in healthy, nonathletic individuals with age is also observed in the aging athletes heart A new global tissue Doppler index: correlation with left ventricular end-diastolic pressure in patients with severe mitral regurgitation C. Mornos, D. Cozma, A. Ionac, L. Petrescu, D. Dragulescu, S. Pescariu, D. Maximov, D. Popa, S.I. Dragulescu. Institute of Cardiovascular Diseases, Timisoara, Romania The ratio between early diastolic transmitral velocity and early mitral annular diastolic velocity (E/Ea) reflects left ventricular (LV) filling pressure in a variety of cardiac diseases. We belive that combining the index of diastolic function (E/Ea) and a parameter that explores LV systolic performance (Sa, peak systolic velocity of mitral annulus) provides a close prediction of left ventricular end-diastolic pressure (LVEDP). Aim: to assess the relationship between a new parameter, E/(Ea Sa), and LVEDP in patients with severe mitral regurgitation. Methods: We screened 67 consecutive patients with severe mitral regurgitation, in sinus rhythm, referred for LV cathetherism. Patients with inadequate echocardiographic image, paced rhythm, mitral prosthesis, severe mitral annular calcification, pericardial disease, acute coronary syndrome or coronary artery by-pass within 72 hours were excluded. The remaining 55 patients formed our study group. Echocardiography was performed simultaneously with LVEDP measurement. E/Ea and E/(Ea Sa) were calculated; the average of the velocities of septal and lateral mitral annulus was used. LVEDP were obtained with micromanometertipped catheters. Results: Simple regression analysis demonstrated a significant linear correlation between E/(Ea Sa) and LVEDP (r=0.81, p<0.001). Significant but weaker correlations were found between LVEDP and E/Ea (r=0.73, p<0.001), Sa (r=-0.59, p=0,004), pulmonary artery systolic pressure (r=0.57, p=0.007), E wave (r=0.45, p=0.009), Ea (r=-0.31, p=0.01), left atrial volume (r= 0.28, p=0.02). We couldn t demonstrate significant relationships between LVEDP and LV ejection fraction. The area under the receiver-operating characteristic curve (ROC) for prediction of LVEDP>15 mmhg was greatest for E/(Ea Sa) (AUC=0.87, p<0.001) followed by E/Ea ratio (AUC=0.81, p<0.001). A statistical comparison of the ROC curves provides that E/(Ea Sa) was more accurate than E/Ea (p=0.02). The optimal E/(Ea Sa) cut-off to predict a LVEDP level >15 mmhg was 1.95 (sensitivity of 85% and specificity of 83%). Conclusions: E/(Ea Sa) correlates strongly with LVEDP and can be a simple and accurate echocardiographic index for the estimation of LVEDP in patients with severe mitral regurgitation, in sinus rhythm Role of exercise E/E and ischaemia in predicting outcome in patients undergoing exercise echocardiography D.J. Holland, S.B. Prasad, T.H. Marwick. The University of Queensland, Brisbane, Australia Background: Raised LV filling pressure after exercise may be accurately measured from exercise E/E. We sought to define the relative contribution of raised exercise E/E and ischaemia to outcomes. Conclusion: An elevated E/E response to exercise holds similar prognostic outcomes as inducible ischaemia, implicating the importance of measuring E/E during stress echocardiography Incremental prognostic value of the novel diastolic indices for prediction of clinical outcome in patients with ST elevation myocardial infarction M. Shanks, A.C.T. Ng, N.R.L. Van Der Veire, L.M. Antoni, S.A. Mollema, M.J. Schalij, E.E. Van Der Wall, J.J. Bax. Leiden University Medical Center, Leiden, Netherlands Purpose: Echocardiographic predictors of outcome after acute ST-elevation myocardial infarction (STEMI) include left ventricular (LV) ejection fraction (EF), endsystolic volume index (ESVI), and mitral insufficiency. Prognostic value of newer diastolic function indices by 2-dimensional speckle tracking (2DST) after STEMI is unknown. Methods: Echocardiograms were performed within 48 hours of admission in 371 consecutive, first STEMI patients (mean age 62.6±11.7 years, 77.6% male). Indices of diastolic function including mean strain rate during isovolumic relaxation (SRIVR), mean early diastolic strain rate (SRE) and mean diastolic strain at peak transmitral E wave (DSE) by 2DST were obtained from the 3 apical views. Mean Em from 4 basal segments by color-coded tissue Doppler imaging was also measured. Indices of diastolic filling including E/SRIVR, E/SRE, E/DSE, and E/Em were calculated. Primary endpoint was a composite of death, hospitalization for heart failure, repeat myocardial infarction and repeat revascularization. Results: Primary endpoint occurred in 84 patients (22.6%) during a mean follow-up of 16.8±11.9 months. Patients with clinical events had lower baseline LVEF (39.7±8.2 vs 45.7±7.7%, p<0.001), ESVI (36.1±16.8 vs 28.4±9.2 ml/m 2, p=0.045), higher troponin (13.0±11.2 vs. 6.5±5.0 μg/l, p=0.002) and more likely to have multivessel disease (68.6 vs 38.7%, p<0.001). Similarly, these patients had higher E/Em (15.6±8.3 vs 12.3±4.9, p=0.003) and E/SRIVR (481.4±458.8 vs 391.2±517.1, p<0.001), and more impaired Em (5.09±1.95 vs 5.96±2.02 cm/s, p=0.001), SRIVR (0.20±0.12 vs 0.31±0.21 s -1,p<0.001) and DSE (7.71±2.88 vs 8.78±2.63%, p=0.030). Mean SRIVR (p<0.001), number of stenosed vessels (p<0.001) and LVEF (p=0.011) were independent predictors of the combined endpoint on Cox regression analysis. When the patient population was dichotomized based on the median SRIVR, patients with SRIVR 0.24 s -1 post-stemi had significantly higher event rates than others (HR 2.74, 95% CI , p<0.001). Conclusion: After acute STEMI, mean SRIVR, LVEF and number of stenosed vessels were independent predictors of the combined endpoint. Evaluation of LV diastolic function by mean SRIVR after STEMI may be useful in identifying high risk patients.

22 322 Diastology: jump into the future? / Coronary artery surgery: miscellaneous POSTER SESSION 3 MODERATED POSTERS 1 CORONARY ARTERY SURGERY: MISCELLANEOUS P2065 DNA enzyme targeting transcription factor c-jun reduces intimal hyperplasia in human saphenous vein explants and inhibits Vein Graft stenosis in rabbits J. Ni, A. Waldman, L. Khachigian. The University of New South Wales, Sydney, Australia Background: Previous studies from our group using DNAzymes (catalytic oligodeoxynucleotides) have demonstrated that the bzip transcription factor c- Jun is required for inducible smooth muscle cell (SMC) proliferation and migration. DNAzymes (Dz13) targeting c-jun inhibit intimal thickening in ligated rat carotid arteries and balloon-injured rabbit carotid arteries. The present study was designed to validate the hypothesis that Dz13 may reduce intimal hyperplasia in human saphenous veins ex vivo, and in an animal model of vein graft transplantation. Methods/Results: By immunohistochemical staining, we found that c-jun is expressed together with PCNA in alpha-sm actin+ cells in failed human coronary artery bypass saphenous vein graft segments. c-jun levels increase after SMC exposure to fluid shear stress (10 dynes/cm 2 ), which was inhibited by DNAzyme Dz13 (34 nucleotides length, with a 3-3 -linked inverted T) and ERK and JNK inhibitors, but not Dz13scr (scrambled arm counterpart of Dz13). We generated an adenovirus vector overexpressing c-jun using the padeasy system. SMCs were transduced/transfected with adeno-c-jun, adeno-c-jun/dz13 or adeno-c- Jun/Dz13scr. Western blotting and RT-PCR verified the induction of c-jun, and the activation of c-jun inducible genes, such as MMP-2. Overexpression of c-jun increased SMC proliferation, whereas Dz13 inhibited adeno-c-jun inducible SMC growth. Using an in vitro scratch assay, SMC transduced with adeno-c-jun underwent accelerated wound repair, which was inhibited by Dz13 but not Dz13scr. Intimal hyperplasia in human saphenous veins ex vivo was attenuated by Dz13, but not Dz13scr. Moreover, Dz13 delivery to the jugular veins of rabbits immediately prior to end-to-side autologous transplantation into carotid arteries inhibited intimal thickening after 4 weeks. On the other hand, overexpression of c-jun by adenovirus in this model lead to accelerated neointimal hyperplasia. Conclusions: These studies indicate that c-jun is expressed in failed human coronary artery bypass saphenous veins and in jugular veins after carotid artery transplant in rabbits. Dz13 inhibits vein graft failure, whereas c-jun overexpression stimulates this process. Targeting c-jun may therefore be useful to reduce the incidence of coronary bypass graft failure. P2066 Appraise a Customized strategy for left main revascularization. The Customize study D. Capodanno 1,M.E.DiSalvo 1, A. Caggegi 1, D. Tomasello 1, G. Cincotta 1,M.Miano 1, S. Tolaro 2, L. Patane 2, A.M. Calafiore 1, C. Tamburino 1 on behalf of CUSTOMIZE. 1 University of Catania, Catania, Italy; 2 Centro Cuore Morgagni, Cardiac Catheterization Laboratory, Pedara, Italy Purpose: Current guidelines strictly recommend coronary artery bypass grafting (CABG) as the first choice of revascularization for patients with left main coronary artery (LMCA) disease. However, the SYNTAX trial has recently suggested the utility of a tailor-made strategy of revascularization for treating patients with LMCA disease by using clinical tool as the Syntax score. We tested the hypothesis that a non-guideline driven approach using percutaneous coronary intervention (PCI) as the first choice and demanding CABG if strictly mandatory may be as safe as the traditional guideline-driven approach. Methods: Between January 2002 and January 2008, PCI have been used as a default strategy for LMCA revascularization in Center 1 (non guidelinedriven group), whereas CABG has been used as a default strategy in Center 2 (guideline-driven group). We compared clinical outcomes of these two populations using extensive adjustment with a non parsimonious model of variables including Syntax score, EuroSCORE and percentage of complete revascularization. Primary endpoint was the long term rate of MACE, defined as the composite of cardiac death, myocardial infarction (MI) and target vessel revascularization (TVR). Results: PCI was performed in 390 patients (60%) of Center 1 and 41 patients of Center 2 (14%), whereas CABG was performed in 257 patients of Center 1 (40%) and 242 patients of Center 2 (86%). Syntax score was 29±12 in the non guideline-driven group and 31 in the guideline-driven group (p = 0.03). At long-term follow up (787±652 days), no differences were observed between non guideline-driven group vs the guideline-drive group with regards to MACE (HR 1.35, 95% CI , p = 0.143). A trend towards lower rates of cardiac death was in favour of non-guideline driven group (HR 0.55, 95% CI , p = 0.057), whereas TVR were more likely to be performed in the non guideline-driven group (HR 2.70, 95% CI , p = 0.003). Conclusions: A tailor-made strategy of PCI as a default option for LMCA revascularization gives similar results when compared with the traditional strategy based on current guidelines. P2067 Assessment of repolarization features after coronary artery bypass grafting A. Ben Halima, M. Ben Halima, A. Ben Youssef, S. Bouraoui, S. Ouerghi, K. Mzoughi, Z. Ibn El Hadj, T. Mestiri, T. Kilani, S. Kachboura. Abderrahmane Mami University Hospital, Ariana, Tunisia Introduction: Imbalances in autonomic nervous system and impaired myocardial repolarization have been shown to increase the risk for arrhythmias in patients with coronary artery disease. Purpose: Study of the effect of on-pump and off-pump coronary artery bypass grafting (CABG) on QT intervals Methods: The study group consisted of 100 consecutive patients (mean age 62±10 years) with coronary artery disease who underwent elective CABG. Fifty two patients underwent on-pump CABG (group 1) and 48 patients underwent offpump CABG (group 2). The 2 groups were comparable regarding clinical and postoperative characteristics. All patients had 12 lead ECG before surgery and 1 day after CABG. We measured QT end intervals (max and min) and QT apex intervals (max and min) corrected according to Bazett Formulae and calculated their dispersion (QT max QT min) Results: In group 1, we noticed a significant increase of QT apex et QT end intervals after surgery compared to baseline. In group 2, there was no significant variation of QT intervals. Results are summerized in the following table Comparison of QT interval before and after CABG Group 1 on-pump Group 2 off-pump Before surgery After surgery p Before surgery After surgery p RR 937± ±128 < ± ±155 NS QT apex min 313±44 342± ±44 334±34 NS QT apex max 344±39 382± ±51 342±36 NS QT apex dispersion 31±20 40±30 NS 13±8 12±8 NS QT end min 402±55 450± ±39 419±41 NS QT end max 438±51 495±57 < ±48 432±45 NS QT end Dispersion 37±20 48±29 NS 13±8 12±9 NS Conclusion: On-pump CABG is associated with a non-uniform recovery of repolarization compared with off-pump CABG. This may be explained by loss of liquids and problems of myocardial protection during on-pump CABG. These results suggest that off-pump CABG may be associated with a lower risk of ventricular arrhythmia P2068 Randomized comparison of Minimally Invasive Direct Coronary Artery Bypass (MIDCAB) surgery versus sirolimus-eluting stenting in isolated proximal LAD-stenosis H. Thiele, P. Neumann-Schniedewind, S. Jacobs, E. Boudriot, T. Walther, F.W. Mohr, G. Schuler, V. Falk. Herzzentrum der Universitaet Leipzig, Leipzig, Germany Background: Bare-metal stenting is inferior to minimally invasive direct coronary artery bypass grafting (MIDCAB) in patients with isolated proximal left anterior descending (LAD) lesions due to a higher reintervention rate with similar results for mortality and reinfarction. Sirolimus-eluting stents (SES) are effective in restenosis reduction. The purpose of this randomized study was to compare PCI using SES with MIDCAB for patients with isolated proximal LAD coronary artery disease. Methods: A total of 130 patients with significant proximal LAD stenosis were randomized to either SES (n=65) or surgery (n=65). The combined clinical endpoint was freedom from major adverse cardiac events (MACE), such as death from cardiac causes, myocardial infarction, and the need for target vessel revascularization (TVR) within 12 months. Clinical symptoms were assessed by the CCS-classification. Results: Follow-up was completed for all patients. MACE occurred in 7.7% of patients after stenting, as compared with 7.7% after surgery (P=0.03 for noninferiority). The individual components of the combined endpoint revealed mixed results. While non-inferiority was revealed for the difference in death and myocardial infarction (1.5% versus 7.7%, non-inferiority P<0.001), non-inferiority was not established for the difference in target vessel revascularization (6.2% versus 0, non-inferiority P=0.21). Clinical symptoms improved significantly in both treatment groups in comparison to baseline and the percentage of patients free from angina after 12 months was 81% versus 74% (p=0.49). Conclusions: In isolated proximal LAD disease, PCI using SES is non-inferior to MIDCAB surgery at 12-month follow-up with respect to MACE at a similar relief in clinical symptoms and less periprocedural complications.

23 Coronary artery surgery: miscellaneous / Creating alternative image 323 P2069 Influence of on-pump versus off-pump cardiac surgery on completeness of revascularization in patients with stable coronary artery disease - MASS III trial N.H. Lopes, E.G. Lima, R.D. Vieira, C.L. Garzillo, L.A.M. Cezar, A. Hueb, L.A.O. Dallan, F.S. Paulitsch, J.A.F. Ramires, W.A. Hueb. Heart Institute of University of Sao Paulo, Sao Paulo, Brazil Background: Coronary Artery Bypass Surgery (CABG) with use of Cardiopulmonary Bypass (CPB) is a routine and safe procedure with low mortality in elective patients. Recent data in performing CABG on Off-pump (OPCAB) suggest reduced morbidity. However, comparisons of selected patients undergoing offpump versus conventional on-pump CABG have yielded inconsistent results and raised concerns about completeness of revascularization in off-pump CABG, as well in its influence on five-year survival. Methods: In a single center randomized trial, patients undergoing myocardial revascularization were randomly assigned OPCAB or On-pump (ONCAB) technique. Both surgical and anesthetic techniques were standardized. Primary composite end-points were freedom from overall death, myocardial infarction further revascularization (surgery or angioplasty) and stroke. Besides, they were stratified considering completeness of revascularization. Results: Of 308 patients randomized to CABG, 153 underwent on-pump and 155 underwent off-pump surgery. Baseline characteristics were similar among patients. In the OPCAB group 71 and 82 patients had received complete and incomplete revascularization respectively. On the other hand, in the ONCAB group 89 had complete and 66 incomplete revascularization. Comparing two techniques we observed a tendency of more complete revascularization in ONCAB group (p=0,053). But, in five-year follow up, the composite event free probability rates were: 82,5% for complete and 77,7% for incomplete revascularization (p=0.219). Conclusion: Although there was a tendency of more complete revascularization in ONCAB group, incomplete revascularization was associated with similar outcomes compared to complete revascularization during five years follow-up regardless the technique of CABG. P2070 C-reactive protein is not predictive of atrial fibrillation following coronary artery bypass surgery A. Kourliouros, O. Valencia, A. Tsiouris, M. Tavakkoli Hosseini, A. Kiotsekoglou, A.J. Camm, M. Jahangiri. St George s Healthcare NHS Trust, London, United Kingdom Purpose: Atrial fibrillation (AF) is the commonest arrhythmia following cardiac surgery. Inflammation has been implicated in the pathogenesis of postoperative AF, however, the predictive value of inflammatory cytokines in its occurrence remains controversial. We set out to examine the association of baseline and postoperative C-reactive protein levels (CRP) with AF following CABG. Methods: 316 consecutive patients undergoing first-time CABG with the use of cardiopulmonary bypass and no history of AF were included. Heart rhythm was assessed with continuous tele-monitoring for 72 hours postoperatively, 6- hourly clinical examinations and daily electrocardiograms thereafter. CRP measurements were performed prior to surgery and on a minimum of two occasions during hospital stay. Results: Baseline CRP was not significantly different between patients who developed postoperative AF (n=80, 25.3%) and those who remained in sinus rhythm (SR) (p=0.61). Multivariate logistic regression analysis with the inclusion of baseline CRP as an independent variable, revealed non-use of statins as the only independent risk factor associated with postoperative AF (p=0.043). Peak incidence of AF was observed on the second postoperative day (39%) followed by postoperative day 3 (31%). Peak CRP levels were observed on day 3, but did not differ significantly between the AF and SR groups (median, 231 vs. 238mg/L, p=0.68). There was a trend for increased CRP levels in the AF group when compared to the SR group on postoperative days 4, 5 and 6, which, however, remained nonsignificant (p=0.14). P2071 Impact of on-pump and off-pump coronary artery bypass surgery in incidence of early postoperative atrial fibrillation E.G. Lima, R.D. Vieira, H.B. Ribeiro, C.L. Garzillo, F.S. Paulitsch, A. Hueb, L.A.O. Dallan, J.A.F. Ramires, N.H. Lopes, W.A. Hueb. Heart Institute of University of Sao Paulo, Sao Paulo, Brazil Background: The incidence of atrial fibrillation (AF) may reach 40% of the patients submitted to coronary artery bypass graft (CABG) surgery. Moreover, there are few prospective and randomized studies comparing the occurrence of AF in the on-pump versus the off-pump CABG. It is unclear, whether the development of inflammatory systemic response, secondary to the extracorporeal circuit, might contribute to the physiopathology of AF. Methods: Between 2002 and 2008, patients with multivessel coronary artery disease, stable angina, and preserved ventricular function, according to surgeon s agreement that revascularization could be attained by either strategies, were randomly assigned to on or off-pump CABG. The primary end-points were cardiovascular death, stroke, and unstable angina requiring additional revascularization along five years of follow-up. Continuous electrocardiograph monitoring, and clinical symptoms during hospitalization were used to the diagnostic of AF. Results: In MASS III study 308 subjects were randomly assigned to intervention: 153 to the on-pump group and 155 to the off-pump group. AF occurred in 29 subjects (15%) in the off-pump group vs. 6 (4%) in the on-pump group (p=0,001). Baseline characteristics were similar among groups, except for patients presented AF were older (p=0.027). The incidence of primary end-points was similar among both groups. Nonetheless, patients presented AF had longer ICU (p<0,001) and hospitalization stay (p<0,001). Conclusion: Off-pump surgery was associated with higher incidence of AF compared with on-pump procedure. AF after CABG contributed to prolonged ICU and hospitalization stay. Even though, there is no difference on mortality and primary end-points at late follow-up. P2072 Low cardiopulmonary bypass perfusion temperature is an independent risk factor for acute kidney injury after coronary artery bypass surgery A. Kourliouros, O. Valencia, S.D. Phillips, P.O. Collinson, J.P. Van Besouw, M. Jahangiri. St George s Healthcare NHS Trust, London, United Kingdom Purpose: Acute kidney injury (AKI) is a common complication after coronary artery bypass surgery (CABG). The role of hypothermia in postoperative renal function remains controversial. We set out to examine the effect of varying cardiopulmonary bypass (CPB) temperatures on early postoperative renal function. Methods: Patients undergoing first time CABG between 2002 and 2006 and without evidence of preoperative renal insufficiency (estimated creatinine clearance 50 ml/min, calculated by Cockcroft-Gault formula) were studied. Medical history and intraoperative variables, including nasopharyngeal and arterial line CPB perfusion temperatures, were collected prospectively. Primary endpoint was the development of early postoperative AKI (defined as creatinine clearance <50 ml/min), which was assessed using multivariate and propensity score analyses. Results: 1072 patients were included. Acute kidney injury occurred in 175 (16%). Univariate analysis demonstrated that lower CPB perfusion temperatures (and not nasopharyngeal ones), were significantly associated with renal dysfunction following CABG. Multivariate regression analysis identified reduced CPB perfusion temperature as an independent risk factor for AKI (OR 0.92, 95% CI 0.86 to 0.98, p=0.012), along with age (OR 1.07, 95% CI 1.04 to 1.10, p<0.001) and depressed preoperative creatinine clearance (OR 0.89, 95% CI 0.87 to 0.91, p<0.001). Propensity score adjustment confirmed that lower CPB perfusion temperatures (<27 C) were associated with postoperative AKI (OR 1.66, 95% CI 1.16 to 2.39, p=0.0056). Conclusions: Lower CPB perfusion temperatures are significantly associated with AKI following CABG. In addition to the known age-related decline in renal function, it appears that hypothermia and/or the rewarming process contribute to renal injury during cardiac surgery. MODERATED POSTERS 2 CREATING ALTERNATIVE IMAGE Conclusions: Baseline CRP levels were not predictive of AF after on-pump CABG. Increased CRP coincided with the occurrence of postoperative AF but its plasma concentrations were not significantly different between the AF and SR groups. P2074 Cardiac MSCT as an alternative to coronary angiography in the pre operative assessment of coronary disease before aortic valve surgery J.-C. Cornily, M. Gilard, V. Jan, P.Y. Pennec, G. Le Gal, J. Boschat. CHU de Brest - Hopital de la Cavale Blanche, Brest, France Purpose: In patients with severe aortic valve disease, conventional coronary angiography (C-CAG) is still recommended before surgery. A preliminary study suggests that, when compared to C-CAG, MSCT-Coronary Angiography (MSCT- CAG) was able to rule out coronary artery disease (CAD) in many of these patients. Our objective was to prospectively assess the safety of ruling out CAD solely on the basis of a normal MSCT-CAG.

24 324 Creating alternative image Methods: We included all consecutive patients scheduled for C-CAG before aortic valve surgery. We first estimated calcium scoring (Agatston score equivalent (ASE)). Patients underwent injected MSCT if ASE was < C-CAG was cancelled when MSCT-CAG quality was sufficient and showed no significant coronary artery stenosis. Patients benefited from C-CAG in case of calcium scoring 1000, bad quality of the MSCT images or evidence of CAD. Our primary endpoint was to assess the occurrence of per- and post-operative myocardial infarction defined by the apparition of a Q wave on the ECG or an abnormal post operative troponin Ic elevation (>20 ng/ml) in these patients who underwent surgery with no prior C-CAG. Results: Between Aug 1st 2005 and Aug 30th 2008, we included 199 patients: 118 men (58%); aged 69±12 years; valvular disease: Aortic stenosis: n = 164, aortic regurgitation: n = 29, annuloaortic ectasia: n = 6. A total of 63 patients went directly through C-CAG because of a 1000 ASE. MSCT-CAG was performed in 136 patients. We performed both C-CAG and MSCT-CAG on 30 patients because of abnormal MSCT (n = 18) or bad quality MSCT (n = 12). Finally,106 patients benefited from surgery without previous C-CAG. A single patient over 106 (0.9%) suffered a per surgery myocardial infarction after a sub-normal MSCT. The post surgery C-CAG confirmed the occlusion of a small diagonal artery that had been detected on MSCT but considered <50% stenosis. This <1% ischemic event after normal MSCT-CAG is close to the published data about valve surgery after normal C-CAG. Conclusion: When ASE<1000, MSCT was performed and allowed us to avoid C-CAG in 106/136 patients (78%) with good clinical outcome. MSCT is safe in this particular indication and might be recommended first instead of C-CAG when ASE<1000. P2075 Predictive Value of Multi-Slice Computed Tomography (MSCT) for ischemia on myocardial perfusion imaging J.E. Van Velzen 1,J.D.Schuijf 1, J.M. Van Werkhoven 1,E.Boersma 2, F.R. De Graaf 1, M.P. Stokkel 1, P. Kaufmann 3, J.W. Jukema 1, E.E. Van Der Wall 1,J.J.Bax 1. 1 Leiden University Medical Center, Leiden, Netherlands; 2 Erasmus MC - Thoraxcenter, Rotterdam, Netherlands; 3 University Hospital Zurich, Zurich, Switzerland Purpose: Previous studies have shown a large discrepancy between the presence of stenosis on MSCT angiography and the presence of ischemia. Therefore, identification of high risk features on MSCT for ischemia may improve guidance of the clinician in their decision for further diagnostic and/or therapeutic options. The purpose of this study was to identify variables on MSCT angiography that may indicate a higher likelihood for ischemia. Methods: Both MSCT and myocardial perfusion imaging (MPI) by means of SPECTwere performed in 616 patients (59% male, age 60±11 years) with known or suspected coronary artery disease (CAD). Based on MSCT angiography, the presence, extent and degree of stenosis ( 50% luminal narrowing or not) were determined. Lesions were classified as non-calcified, mixed and calcified. Ischemia on MPI was defined as a SSS >4. Results: Ischemia was observed in 28% (n=168) of patients. Multivariate analysis showed that extent of disease ( 3 diseased segments) was a significant independent predictor of ischemia (OR 1.6, p =0.03). Also degree of stenosis (presence of >50% stenosis) was a strong independent predictor for ischemia (OR 3.4, p<0.0001). Interestingly, plaque composition was identified as predictive for ischemia as well with the presence of 3 mixed plaques in particular (OR 2.9, p<0.0001). Chi-square analysis showed that MSCT variables had significant incremental value over clinical risk stratification for the prediction of abnormal MPI. Conclusions: More advanced and severe atherosclerosis on MSCT is predictive for ischemia on MPI. MSCT variables (describing extent, degree and composition) have significant incremental value over clinical risk stratification for the prediction of abnormal MPI. P2076 Effect of glucose lowering on carotid intima-media thickness, coronary artery calcification and coronary circulatory function in type 2 diabetes mellitus T.H. Schindler 1,A.D.Facta 2, J. Cadenas 2,J.Sayre 2,J.Goldin 2, H.R. Schelbert 2. 1 University Hospitals of Geneva, Cardiovascular Center, Geneva, Switzerland; 2 Department of Molecular and Medical Pharmacology at UCLA, Los Angeles, United States of America Objective: To determine the effect of plasma glucose lowering on coronary circulatory function, carotid intima-media thickness (IMT) and coronary artery calcification (CAC). Methods: In twenty-two patients with type 2 diabetes, and in 17 healthy controls coronary circulatory function was determined with positron-emission-tomography (PET) measured myocardial blood flow (MBF) at rest, during cold pressor testing (CPT), and during adenosine-stimulated hyperemia, while structural alterations of the carotid IMT were assessed with high resolution vascular ultrasound and CAC with electron beam tomography (EBT). In diabetic patients, measurements were repeated again after a 1 year follow-up of glucose-lowering therapy with glyburide and metformin and also in healthy controls. Results: At baseline, the endothelium-related MBF increase to CPT ( MBF- CPT) and to adenosine-stimulation ( MBF-ADO) were less in diabetic patients than in controls (0.09±0.09 vs. 0.25±0.12 and 1.08±0.31 vs. 1.37±0.41 ml/g/min, p<0.05; respectively), while carotid IMT and CAC were abnormally increased diabetic patients (0.83±0.19 vs. 0.68±0.11 mm 2 and 35.28±68 vs. 4.25±9HU,p<0.05; respectively). Treatment with glyburide and metformin significantly decreased plasma glucose concentrations from 205±72 to 160±44 mg/dl. This decrease in plasma glucose resulted in a significant increase in MBF to CPT and a non-significantly to ADO, respectively (0.09±0.09 vs. 0.19±0.17 and 1.19±0.51 ml/g/min), while a further abnormal mild increase in carotid IMT and CAC was observed (0.86±0.18mm 2 and 59.88±102 HU). The decrease in plasma glucose levels correlated with an improvement in MBF to CPT and to ADO, respectively (r=0.46, p and r=0.36, p 0.056) and, also with a lower progression of carotid IMT and CAC, respectively (r=0.46, p and r=0.48, p 0.036). Further, on multivariate analysis, the improvement in endotheliumdependent coronary artery function was an independent predictor of the slowed progression of CAC (p by ANOVA). Conclusions: The close association between the decrease in plasma glucose concentrations and its beneficial effects on functional and structural abormalities of the arterial wall denotes direct adverse effects of hyperglycemia on diabetesrelated vasculopathy. An improvement of coronary endothelial function in type 2 diabetes mellitus may mediate, at least in part, direct preventive effects on the progression of structural epicardial disease. P2077 Evaluation of arterial healing after stent implantation by optical frequency domain (OFDI) imaging: an in vivo comparison with histology in a pig coronary artery model C. Templin 1,M.Meyer 1, M. Mueller 1, P. Kronen 2, K. Weber 3, D. Paunovic 4,S.Hoerstrup 1,R.Corti 1, T.F. Luescher 1, U. Landmesser 1. 1 University Hospital Zurich, Zurich, Switzerland; 2 Vetsuisse Faculty, Zurich, Switzerland; 3 Harlan Laboratories, Itingen, Switzerland; 4 Terumo Europe, Leuven, Belgium Background: Optical frequency domain imaging (OFDI), a second-generation form of optical coherence tomography (OCT), is capable of acquiring images of histological resolution at a markedly higher speed (pullbacks of up to 40mm/s) and willsubstantially facilitateuse of coronary optical imaging, given that coronary arteries have to be flushed for light imaging for blood removal. We present the first validation study of OFDI for in vivo examination of stent healing. Methods: Twenty stents were implanted in coronary arteries of Landrace Large White Duroc pigs (bare-metal-stents, BMS, and Biolimus A9 drug-eluting stents, DES, Nobori). After 1, 3, 10, 14 and 28 days the animals underwent follow-up angiography with coronary OFDI (Terumo-OFDI). A comparison between OFDI and light microscopic (histology) and electron microscopic images (SEM) is performed. Results: Neointima thickness increased from day 10/14 to day 28 (BMS 0.085±0.07 mm vs ±0.07 mm, p<0.0001; DES 0.038±0.04 mm vs ±0.06 mm, p<0.0001); however, to a lesser extent with DES (p<0.0001). Furthermore, struts with a thrombosis-like pattern (Class V) were visible at the early time points (i.e. day ±15.3%), but disappeared after day 10. Stent Strut classification

25 Creating alternative image 325 strut coverage could be clearly detected and number of uncovered struts was reduced over time (0-3 vs days: 72.75±19.94% vs. 2.28±2.30%, p<0.001). Conclusions: Our results suggest that OFDI provides valuable information and represents a viable method for coronary in vivo imaging of arterial healing after stent implantation. Given its ability to provide microscopic information at high speed, this technology may represent an excellent tool for examination of stent healing, detection of smaller stent-strut associated thrombosis and neointima proliferation patterns. P2078 Optimal acquisition time for myocardial perfusion imaging using an ultrafast cardiac gamma camera with a novel detector technique R. Buechel, B. Herzog, V. Treyer, R. Katz, L. Husmann, I. Burger, A. Pazhenkottil, I. Valenta, O. Gaemperli, P. Kaufmann. University Hospital Zurich, Zurich, Switzerland Purpose: To establish the optimal scan time for a novel ultrafast cardiac gamma camera with cadmium zinc telluride (CZT) solid-state detectors for myocardial perfusion SPECT imaging. Methods: Twenty patients (17 males, age range years, BMI range kg/m 2 ) underwent a one-day 99mTc-tetrofosmin adenosine-stress (325MBq)/rest (913MBq) imaging protocol (15 minutes per scan) on a standard dual-detector SPECT camera (Ventri, GE Healthcare). Each scan was immediately repeated on a ultra fast camera (Discovery NM 530c, GE Healthcare) with 9 (low dose) and 6 minutes (high dose) scan time and reconstructed using list mode to obtain scan durations of 1 minute, 2 minutes etc. up to a maximum of 9 minutes for low and 6 minutes for high dose. Percent uptake from the Discovery NM 530c (20 segment model) for each scan duration was compared for each patient to Ventri data for low and high dose using Pearson coefficient. For the scan duration above which no further correlation improvement was observed, Bland- Altman (BA) limits of agreement were obtained for the uptake in the five main anatomical left ventricular regions (apex, anterior, septal, lateral, and inferior). Results: Maximum correlation of quantitative uptake was achieved after 3 minutes with low dose and at 2 minutes with high dose. BA limits were -13.2% to 14.4% for low dose and -11.6% to 16.4% for high dose at 3 and 2 minutes, respectively, yielding 97.5% clinical agreement with the Ventri images. Correlation of quantitative uptake Conclusions: Discovery NM 530c with new CZT solid-state detectors allows substantial reduction in acquisition time for SPECT myocardial perfusion imaging. Alternatively, this may allow reduction in radiation dose. P2079 Can ventricular dyssynchrony during exercise predict response to resynchronization therapy? A radionuclide angiography study C. Valzania 1,F.Fallani 1,G.Gavaruzzi 2,M.Biffi 1, C. Martignani 1, I. Diemberger 1,M.Bertini 1, G. Domenichini 1,C.Rapezzi 1, G. Boriani 1. 1 Institute of Cardiology, Univ. of Bologna, Bologna, Italy; 2 Department of Nuclear Medicine, Policlinico S.Orsola-Malpighi, Bologna, Italy The aim of the study was to evaluate the possibility to predict the response to cardiac resynchronization therapy (CRT) at mid-term follow up by radionuclide angiography with Fourier phase analysis, performed both at rest and during exercise. Methods: Twenty-one consecutive heart failure patients (76% men, 65±9 yrs) with idiopathic dilated cardiomyopathy, NYHA class III, and left ventricular (LV) dysfunction, were enrolled into the study. All patients underwent equilibrium Tc99 radionuclide angiography with bicycle exercise at 3 times: during spontaneous rhythm, immediately after CRT activation, and after 3 months of CRT. Ejection fraction (EF) and Fourier phase analysis were evaluated in both ventricles. Interventricular dyssynchrony was expressed as the difference between LV and right ventricular (RV) mean phases. Intraventricular dyssynchrony was assessed by the standard deviation of the mean phase in each ventricle. Results: At baseline, immediately after CRT activation, 10/11 (91%) among midterm responders had a decrease in LV dyssynchrony during exercise, compared to only 4/10 (40%) among mid-term non-responders (p=0.03). Overall, a decrease in LV dyssynchony vs. spontaneous rhythm was observed at 3-month follow-up, both at rest (from 52±26 to 34±22 ms, p=0.002), and during exercise (from 52±25 to 42±23 ms, p=0.03). Moreover, LVEF improved at 3 months at rest (32±12 vs. 26±9%, p<0.001), as well as during exercise (32±13 vs. 26±9%, p=0.002), and a correlation was observed between LVEF and LV dyssynchrony (r= at rest and r= during exercise, p<0.05). No significant variations in RV dyssynchrony or RVEF were observed during CRT, either acutely or during follow-up. Interventricular dyssynchrony decreased at 3 months only during exercise (p=0.012 vs. spontaneous rhythm). Conclusions: These data suggest that a decrease in LV dyssynchrony during exercise immediately after CRT activation may be predictive of mid-term response to CRT. Further efforts to optimize CRT programming during follow-up might be focused on patients without an acute decrease in exercise LV dyssynchrony. P2080 Different patterns of myocardial iron overload by T2* Cardiovascular MR as markers of risk for cardiac complication in thalassemia major A. Pepe 1, A. Meloni 1, V. Positano 1,G.Rossi 2, P. Pepe 2, M.C. Galati 3,A.Zuccarelli 4,G.Restaino 5,G.Valeri 6, M. Lombardi 1. 1 MRI Lab, Institute of Clinical Physiology, G Monasterio Foundation, Pisa, Italy; 2 Epidemiology and Biostatistics Unit, Institute of Clinical Physiology, CNR, Pisa, Italy; 3 UOS Talassemie A.O. Pugliese-Ciaccio, Catanzaro, Italy; 4 Centro di microcitemia Ospedale civile, Olbia, Italy; 5 Radiology Department, Università Cattolica del Sacro, Campobasso, Italy; 6 Radiology Department, Ospedali Riuniti, Ancona, Italy Purpose: Cardiac complications mainly related to myocardial iron overload (MIO) remain the main cause of mortality in thalassemia major (TM). Thalassemia cardiomyopathy is treatable and reversible if appropriate chelation therapy is instituted in time. The validated multislice multiecho T2* CMR technique has permitted to quantify segmental and global myocardial iron burden detecting different patterns of iron overload. Aim of our study was to verify the risk of cardiac complications (heart failure, arrhythmias and pulmonary hypertension) related to different patterns of MIO in a large cohort of TM patients. Methods: Within the MIOT (myocardial iron overload) project we consecutively studied 568 TM patients using the multislice multiecho T2* CMR technique to quantify segmental and global MIO. The MIOT project is a previously validated network of six CMR centres and 56 thalassemia centres sharing a common clinical-instrumental database. Three short-axis views (basal, medium, apical) of the left ventricle were acquired using a multislice multiecho T2* sequence. Using a previously validated software the 16 segmental T2* values and the mean global heart T2* value were provided. A conservative cut off of 20 ms was considered the limit of normal for the segmental and global T2* values. Results: We identified 4 groups of patients: group I (23%) with homogeneous MIO (all segments with T2* values < 20 ms), group II (12%) with heterogeneous MIO and global heart T2* < 20 ms (the majority of segments with T2* values < 20 ms); group III (25%) with heterogeneous MIO and global heart T2* > 20 ms (the majority of segments with T2* values > 20 ms); group IV (39%) with no MIO (all segments with T2* values > 20 ms).the percentage of patients with cardiac complications was significantly different in the 4 groups (group I 36% vs group II 14% vs group III 17% vs group IV 3.2%; P=0.001). In particular, the percentage of patients with heart failure was significantly different in the 4 groups (group I 18% vs group II 14% vs group III 5% vs group IV7%; P=0.001). No significant differences were found among groups in the percentage of arrhythmias and pulmonary hypertension. Odds Ratio for cardiac complications was 2.4 ( OR 95%CI; P= ) for patients with homogeneous MIO vs patients with no MIO. Conclusions: Cardiac complications (in particular heart failure) are correlated with MIO distribution increasing from the patients with no MIO to the patients with homogeneous MIO. Homogeneous MIO predicts a significantly higher risk to develop cardiac complications suggesting an intensive chelation therapy in this group of patients. P2081 Aortic dilatation and reduced elasticity after surgical repair of tetralogy of fallot - assessment by magnetic resonance imaging A. Silva Ferreira 1,E.Rizzo 2, M. Ladouceur 2, A. Redheuil 2, M. Bensalah 2,A.Azarine 2, Y. Boudjemline 2, E. Mousseaux 2. 1 Hospital dos Lusiadas, Lisbon, Portugal; 2 European Hospital George Pompidou (AP-HP), Paris, France Purpose: Despite anatomically successful repair of tetralogy of Fallot (TOF), a significant proportion of survivors develop late dilatation of the proximal aorta, possibly as a consequence of intrinsic histological abnormalities. This study sought to assess aortic elasticity in patients with surgically corrected TOF, and its relationships to aortic dimensions, aortic valve competence and left ventricular (LV) function. Methods: Magnetic Resonance Imaging (MRI) was performed on 71 patients with successfully repaired TOF (mean age 28±12 years, 20±9 years after corrective surgery) and 30 healthy controls (mean age 29±8 years). Aortic diameters were measured at five levels: sinuses of Valsalva, sinotubular junction, tubular aorta, aortic arch and descending aorta. Steady-state free precession and velocity-encoded MRI sequences were used to assess LV ejection fraction, aortic regurgitation (AR) fraction, and two indices of aortic elasticity: pulse wave velocity (PWV) and aortic distensibility.

26 326 Creating alternative image / Thrombosis and anti-thrombotic therapy Results : Compared to healthy subjects, repaired TOF patients showed reduced aortic elasticity as indicated by increased PWV (7.4±5.9 m/s vs. 4.4±1.2 m/s, p <0.001) and reduced aortic distensibility (3.9± mmhg -1 vs. 5.6± mmhg -1, p=0.002). Patients with repaired TOF also had higher aortic diameters in all the predefined levels (p<0.001) except the descending aorta (p=ns). Mild or moderate degrees of AR were present in 10 patients (median AR fraction 3% vs. 1% in controls; p<0.001). The mean LV ejection fraction was significantly lower in corrected TOF patients (58%±9 vs. 65%±3, p<0.001). An increased PWV correlated with aortic regurgitation fraction (r=0.21, p=0.037) and also with dilatation of the aortic sinuses, sinotubular junction, tubular aorta and aortic arch (r=0.23 to 0.30, p 0.034). Aortic distensibility correlated with LV ejection fraction (r=0.35, p=0.001) and aortic regurgitation fraction (r=-0.34, p=0.001). Conclusion : Reduced aortic elasticity and dilatation of the proximal aorta are frequently present in patients with corrected TOF. Reduced aortic elasticity correlates with and may contribute to progressive aortic dilatation, aortic regurgitation and LV dysfunction. THROMBOSIS AND ANTI-THROMBOTIC THERAPY P2083 Slow response to clopidogrel predicts low response A. Bellemain, J. Silvain, J.-P. Collet, F. Beygui, O. Barthelemy, R. Choussat, N. Vignolles, D. Brugier, B. Bertin, G. Montalescot. Pitie-Salpetriere Hospital (AP-HP), Paris, France Aim: The fast onset of inhibition of platelet aggregation may be relevant in the setting of acute coronary syndromes and percutaneous coronary intervention, but its relation to the final degree of inhibition is not well established. Low clopidogrel response and high post-treatment platelet reactivity are known to be associated with poor clinical outcome. We performed a post-hoc analysis of the ALBION randomized study to determine if the slow response to clopidogrel loading dose predicts clopidogrel low response and high post-treatment platelet reactivity. Methods: ALBION included 103 NSTEACS low to intermediate risk patients, randomised to receive 300, 600 or 900mg LD of clopidogrel. Early kinetic profile of delta Maximal Platelet Aggregation (deltampa, ADP 20 μmol/l) and MPA were studied (with baseline sample as reference), with 8 time points within the 24 hours postloading. Low response was defined as deltampa < 10% over the first 24 hours, fast response was defined as a deltampa 10% within the first hour after loading (the other patients were slow responders), and high post-treatment platelet reactivity as MPA 56.56% (threshold of the fourth quartile). Inflammatory markers (PAC1 and P-selectin) were also evaluated according to the type of response. Results: 55% of patients were slow responders. Slow response was a reliable marker of low response to clopidogrel, whatever the LD group (figure). Low and slow response were both associated with high post-treatment platelet reactivity. Faster onset of action was more frequent with higher clopidogrel LD. Slow responders had also less decrease in inflammatory markers. Figure 1 Conclusion: Slow response to clopidogrel is a marker of low response at 24 hours and high post-treatment platelet reactivity. The clinical relevance of this finding remains to be shown. P2084 Correlation of inhibition of platelet aggregation after clopidogrel with post discharge bleeding events: assessment by different bleeding classifications V.L. Serebruany 1,S.Rao 2,M.Siva 3, J.L. Donovan 3, A.O. Kannan 3, L.M. Makarov 1,S.Goto 4,D.Atar 5. 1 Johns Hopkins University, Towson, United States of America; 2 Duke Clinical Research Institute, Durham, United States of America; 3 University of Massachusetts, Worcester, United States of America; 4 University of Tokai, Kanagawa, Japan; 5 Akers University, Oslo, Norway Background: Data from ACS trials and registries suggest a link between increased risk of bleeding and cardiovascular mortality. However, the potential association of bleeding risk and the inhibition of platelet aggregation (IPA) is not established. It may play a critical role for the safety of more aggressive platelet inhibition, or/and individual tailoring of antiplatelet strategies. We correlated (IPA) with bleeding events assessed by TIMI-, GUSTO-, and BleedScore scales in a large cohort of patients with coronary artery disease (CAD) and ischemic stroke (IS) treated with chronic low dose aspirin plus clopidogrel. Methods: We conducted secondary post-hoc analyses of 5μM ADP-induced IPA and bleeding complications assessed by TIMI, GUSTO, and BleedScore scales in a dataset consisting of patients with documented CAD (n=246) and previous IS (n=117). Results: Demographic characteristic differ substantially dependent on the underlying vascular disease, however IPA and bleeding risks were similar between CAD and IS. All three bleeding scales adequately captured serious hemorrhagic events, where the TIMI scale was the most exclusive, while BleedScore was the most inclusive. Over half of all patients experienced superficial event(s), most commonly occurring during 2-3 distinct bleeding episodes. There was no correlation between IPA and duration of antiplatelet therapy. IPA above 50% strongly predicts minor (r2 =0.583), but not severe (r2 =0.109) bleeding events. Conclusion: Chronic oral combination antiplatelet regimens are associated with a very high ( %) prevalence of superficial bleeding episodes. We postulate that in trials and registries, these hemorrhages are grossly underestimated. The role of such frequent mild complications for the overall benefit of antiplatelet therapy is entirely unknown, as is their effect on compliance. While IPA is well suited for defining the risk of minor complications, more serious bleeding events cannot be predicted. P2085 The clopidogrel patient information card significantly improves knowledge and adherence to anti-platelet therapy S. Bhattacharyya, H. Madani, S. Myers, R. Rakhit. Royal Free Hospital, London, United Kingdom Background: Stent thrombosis is a serious and sometimes fatal complication of drug eluting stent (DES) implantation. Premature anti-platelet therapy discontinuation is a major predictor of both early and late stent thrombosis. Patient education level is an independent risk factor associated with discontinuation of antiplatelet therapy. The clopidogrel warning card has been suggested as possible mechanism to improve patient education and possible adherence. The card was introduced into clinical practice at our institution in We sought to investigate the effect of the introduction of a clopidogrel card on patient knowledge base. Methods: 100 consecutive patients undergoing percutaneous coronary intervention (PCI) with DES implantation were identified over a 6 month period. Group 1 consisted of 50 patients recruited prior to introduction of the clopidogrel card (March May 2006). Group 2 consisted of 50 patients after the introduction of the clopidogrel card (May 2006-July 2006). Patients in group 1 did not receive a clopidogrel card. Patients in group 2 received a clopidogrel card. 6 months post PCI all patients were seen in clinic. Knowledge in four categories was documented: (1) Indication for clopidogrel (2) Minimum duration of clopidogrel therapy (3) Side effects of clopidogrel and (4) Medical advice sought prior to temporary interruption/early cessation of clopidogrel. Results: The percentage of patients who knew the correct answer for each category are listed below. (1)Indication for clopidogrel: 44% of patients in group 1 versus 76% of patients in group 2 (Odd ratio 4, 95% Confidence Interval (CI) ( ), p=0.002). (2)Minimum Duration of Clopidogrel: 30% of patients in group 1 versus 90% of patients in group 2 (Odd ratio 21, 95% CI (7-63), p<0.0001). (3)Side Effects of Clopidogrel: 24% of patients in group 1 versus 12% of patients in group 2 (Odd ratio 0.4, 95% CI ( ), p=0.19). (4)Medical advice sought prior to discontinuation of clopidogrel: 84% of patients in group 1 versus 98% of patients in group 2 (Odd ratio 5.4, 95% CI ( ), p=0.2). Conclusion: The introduction of the clopidogrel card may have significantly improved patient knowledge of the indication for clopidogrel and the minimum duration of clopidogrel therapy. No difference was noted in knowledge of side effect profile. By improving patient knowledge the clopidogrel card may potentially improve adherence to therapy. This has important implications for minimizing the risk of stent thrombosis associated with anti-platelet withdrawal. P2086 The effect of duration of Clopidogrel treatment on outcome in following coronary stent implantation D. Zahger, H. Gilutz, C. Cafri, R. Ilia, A. Porat. Soroka University Medical Center, Beer Sheva, Israel Background: Dual anti platelet therapy for 9-12 months is superior to 1 month only following coronary stenting. Whether an intermediate treatment period might be sufficient, while reducing the risk and cost of clopidogrel treatment, is unknown. Objectives: To examine the continuous relation between the duration of clopidogrel use during the first year following coronary stenting and outcome. Methods: We studied all patients who underwent coronary stenting at our center between 6/03 8/05 and performed a landmark analysis of patients who were event free (death or non-fatal AMI) 1, 3, 6, 9 and 12 months following stenting.

27 Thrombosis and anti-thrombotic therapy 327 Each cohort was followed for one year; the occurrence of death and of death or non-fatal AMI was compared between clopidogrel users and non-users at the beginning of each time point. The effect of clopidogrel on outcome was assessed in a multivariate model. Results: Demographic and clinical data were available for 1154 patients. 974 were treated with bare-metal stents (BMS). Within this group multivariate analysis at the various time points showed a significant reduction of mortality: 6 months: 4.4% vs. 1.7%, OR: , 9 months: 3.1% vs. 0.9%, OR: and 12 months: 3.2% vs. 1.3%, OR: The composite of mortality or non-fatal AMI was also independently reduced by clopidogrel at all time points: 6 months: 9.5% vs. 6%, OR: , 9 months: 8.5% vs. 2.7%, OR: and 12 months: 7.8% vs. 2%, OR: No statistically significant differences were shown among DES users. Conclusions: In an observational study of 1154 consecutive patients we found that clopidogrel treatment for 12 months after coronary stenting is associated with a lower risk of death or the composite of death or non-fatal AMI in patients treated with BMS. These findings suggest that shorter treatment periods are not sufficient. The apparent lack of benefit in DES recipients was probably due to the very high rate of clopidogrel utilization among these patients. P2087 The variable response of PCI subjects with apparent Clopidogrel resistance to re-loading with 600mg A.S.P. Sharp, R.T. Gerber, C. Godino, A. Latib, M. Ferraro, A. Colombo. San Raffaele Hospital, Milan, Italy Background and methods: It is increasingly recognized that subjects undergoing PCI may exhibit a variable response to clopidogrel pretreatment. When platelet inhibition is measured using the VerifyNow assay, a high platelet P2Y12 reactive units score (PRU>240), reflecting a relatively impaired response to clopidogrel, has been associated with an increased risk of clinical events. However, it is unclear whether a high residual PRU represents a patient who is simply under-treated, or a patient who truly is resistant to the effects of clopidogrel. We ran a prospective study to assess the response of those with a high PRU at the time of their PCI (despite the recommended Clopidogrel and aspirin pre-pci regimens) to re-loading with 600mg clopidogrel and subsequently re-assessed their PRU 24 hours post-procedure so see if platelet activity was now within a more favourable range. Results: Of 106 patients tested, 23 patients had a PRU value 240 at the time of their PCI. Of these, 19 patients had their first exposure to clopidogrel within a month prior to their PCI, whilst the remaining four were taking clopidogrel for more than one year. Mean age, sex and renal function did not differ between the two response groups, but diabetes was more prevalent in subjects with a high PRU (30.4% vs. 14.4%; p=0.08). Overall, of the 23 patients who exhibited a sub-optimal PRU (>240) at the time of their PCI, 14 of these patients achieved a PRU<240 after an additional 600mg loading dose of clopidogrel (mean drop in PRU in these subjects 161 ± SD 57). However, nine subjects continued to show a PRU of>240 despite the extra 600mg on top of their standard treatment and exhibited only a small change in their baseline PRU (mean drop in PRU 32±49). There were no bleeding sequelae in any of the patients given additional clopidogrel. Conclusion: In this cohort of patients, 61% of those subjects with an apparently sub-optimal response to standard clopidogrel loading had a large fall in their PRU after re-loading, suggesting these patients were either under-treated or partially resistant. This could be easily rectified with an additional loading dose. However, 39% of patients with a sub-optimal PRU after traditional loading regimes exhibited little response to an additional 600mg loading dose and may represent truly resistant subjects. These two groups may require different strategies to ensure appropriate inhibition of platelets, with consideration given to the merits of an alternate anti-platelet drug in those with a poor response to clopidogrel re-loading. P2088 The frequency and intra-individual variation of clopidogrel non-responsiveness over time as measured by VerifyNow in patients with stable coronary heart disease A.A. Pettersen, H. Arnesen, I.U. Njerve, M.T. Kase, I. Seljeflot. Dept. of Cardiology, Oslo University Hospital, Ullevål, Oslo, Norway Evaluation of in vitro treatment effect of clopidogrel has lately been given large attention, and different laboratory methods are now available for this purpose. Aims and Methods: We investigated the frequency and stability of clopidogrel non-responsiveness in patients with stable coronary heart disease by use of the VerifyNow P2Y12 method. The method gives results both in platelet reaction units (PRU) and as %-inhibition. Patients on chronic single aspirin treatment (160 mg/d) were randomized to continue on aspirin or change to clopidogrel 75 mg/d. Followup time for laboratory assessements were 1 month and 1 year. All blood samples were drawn in fasting condition 24 hour after the last intake of medication. The cut-off for response was defined as the 95%/5% percentile of all patients tested when being on aspirin (n=227, mean age 62 yrs, 78% male), giving PRU value 170 and %-inhibition 24% to be non-responders. Results: After 1 month on clopidogrel (n=89) the mean PRU-level was 144 (SD 69) and %-inhibition 43 (SD 25). After 1 year blood samples from 70 patients on clopidogrel were available and the mean PRU-level was 154 (SD 79) and %- inhibition 35 (SD 28), significantly different from 1 month (p=0.050 and p=0.013, respectively). The frequency of non-responders defined with PRU and % inhibition was 35% and 28%, respectively at 1 month and 43% and 41% respectively at 1 year. To evaluate the intra-individual variation of non-responsiveness over time we performed an agreement calculation, which shows an agreement of 67% when using the PRU with kappa =0.321 (p=0.001) and 77% with kappa =0.504 (p<0.001) when using the % inhibition, judged to be fair or moderate. In conclusion, the frequency of clopidogrel non-responsiveness evaluated by the VerfyNow P2Y12 method is considerable, in agreement with data obtained with other methods. The intra-individual variation over time, although significant agreement, indicate that precaution has to be taken when judging the individual response. The concequences for clinical outcome is under investigation. P2089 The presence of the CYP p450 C19*2 allele is associated with impaired response to clopidogrel as measured by the verifynow P2Y12 near-patient testing device in patients undergoing coronary angiography A. Worrall 1, A. Armesilla 2,M.Norell 1, S. Khogali 1,M.Cusack 1, A. Smallwood 1, J. Cotton 1. 1 Heart and Lung Centre, Wolverhampton, United Kingdom; 2 University of Wolverhampton, Wolverhampton, United Kingdom Objectives: To investigate the effect of the presence of the cytochrome (CYP) p450 C19*2 loss-of-function allele on the response to clopidogrel, as measured by a near-patient testing device, in a cohort of patients with acute coronary syndrome (ACS). Background: Recent studies have linked the common polymorphism CYP p450 C19*2 to impaired clopidogrel response in certain patients. We sought to relate the presence of the polymorphism to clopidogrel response as measured by a wellvalidated near-patient testing device in a real-world cohort of high-risk patients. Methods: 259 consecutive patients admitted with high-risk acute coronary syndromes were enrolled in the study. All patients were able to take dual anti-platelet therapy and received loading and maintenance doses of both aspirin and clopidogrel according to our local protocol. The study was approved by the local research and ethics committee and informed consent gained from all patients. Angiography was performed and a management plan of angioplasty, CABG or medical therapy was pursued. Clinical follow up was recorded to 1 year. Whole blood was taken for determination of clopidogrel response in P2Y12 reaction units (PRU) using a VerifyNow near patient testing device (Accumetrics). A second sample was stored at -80 C for later genotypic analysis. Results: 193/259 (74.5%, CI 69-80%) patients were found to be homozygous wild-type (*1/*1) and 66/259 (25.5%, CI 21 31%) had at least one copy of the *2 polymorphism (*1/*2 or *2/*2). Significantly higher P2Y12 activity was observed in the *2 group (Mean PRU 222.5, SD ±96.6 vs 283.8, SD ±80.7; P<0.0001). This finding was replicated in the 135 patients retested at 30 days (Mean PRU 189.2, SD ±98.0 vs 256.3, SD ±76.8; P=0.003). In patients undergoing PCI for their ACS, the 12 month MACCE events were numerically higher in the group with the *2 allele, but this did not reach statistical significance 6/80 (7.5%, CI 3 16%) events vs 4/24 (16.7%, CI %) events P=0.17. Conclusions: The results confirm that presence of the cytochrome p450 C19*2 polymorphism is an important determinant of response to clopidogrel in patients with acute coronary syndromes, and that this effect may be measured with a widely available near-patient testing device in a real-world population. This effect is evident both early after loading and at 30 days. Near-patient testing is likely to play an important role in tailoring anti-platelet treatment to reduce adverse events in patients with impaired clopidogrel response. P2090 The relative contribution of the CYP2C19*2 polymorphism in the low responsiveness to clopidogrel in the VASP-02 study B. Aleil 1,F.DePoli 2, M. Zaehringer 1, J.P. Collet 3, G. Montalescot 3, C. Leon 4, J.P. Cazenave 4,M.C.Dickele 2, J.P. Monassier 5, C. Gachet 4. 1 Clinique de l Orangerie, Strasbourg, France; 2 Service de Cardiologie, Centre Hospitalier Général, Haguenau, France; 3 Institut de Cardiologie and INSERM U856, Hôpital Pitié-Salpêtrière (AP-HP), Paris, France; 4 UMR_S 949 INSERM, Université de Strasbourg, Etablissement Français du Sang-Alsace, Strasbourg, France; 5 Service de Cardiologie, Hôpital Emile Muller, Mulhouse, France Purpose: The CYP2C19*2 genetic variant is known to contribute to low responsiveness to clopidogrel treatment, leading to a higher rate of cardiovascular events. Systematic identification of the 2C19*2 carriers to predict the individual patient s response to clopidogrel is a matter of debate. Methods: Data of the VASP-02 study comparing patients responsiveness to 75 and 150 mg/day maintenance dose of clopidogrel were reanalyzed by determining the 2C19*2 carrier status of the patients. Platelet reactivity index (PRI) was determined using the VASP method. A PRI>69% defines low responsiveness to clopidogrel. Results: In the 37 non responder patients, 42.4% were 2C19*2 carriers versus 22.0% in the responder patients (p=0.022). After multivariate analysis, 2C19*2

28 328 Thrombosis and anti-thrombotic therapy polymorphism and high body weight were two independent predictors of high PRI (odds ratio [95% confidence interval] 3.39 [ ] p=0.039 and 3.14 [ ] p=0.021) respectively. Increasing the maintenance dose of clopidogrel from 75 to 150 mg/day in non responder patients resulted in a significant decrease of PRI from 76.4±4.6 to 62.8±10.4% (p<0.01) in 2C19*2 carriers and from 76.1±5.3 to 60.8±13.4% (p<0.01) in non carriers. The mean decrease of PRI after doubling the dose was not significantly different between carriers and non carriers of the genetic variant (-13.6±9.3 and -15.3±11.8% p=0.39, respectively). Conclusions: CYP2C19*2 is an important determinant of the responsiveness to clopidogrel while other independent factors such as body weight also are involved. Hyporesponsiveness in 2C19*2 carriers can be easily overcome by doubling the maintenance dose of clopidogrel. Thus, combined functional pharmacodynamic monitoring and genetic determination of CYP profile should help improve patient s responsiveness to clopidogrel. P2091 The significance of clopidogrel low-responsiveness assessed by a point-of-care assay in acute coronary syndrome patients undergoing coronary stenting K.H. Lee, S.H. Lee, J.W. Lee, J.K. Sung, H.S. Wang, Y.J. Youn, N.S. Lee, J.Y. Kim, J.H. Yoon, K.H. Choe. Wonju Christian Hospital, Wonju, Korea, Republic of Perpose: To prevent atherothrombotic events, clopidogrel and aspirin is currently routinely used in treatment of patients undergoing percutaneous coronary intervention (PCI). Despite clopidogrel therapy, patients undergoing PCI are at risk of recurrent coronary events. Therefore, we sought to prospectively evaluate the death and myocardial infarction (MI) of acute coronary syndrome patients and their responsiveness to clopidogrel. Methods: We enrolled consecutive 610 patients (pts, 160 males, 65.2±10.3 years) who received percutaneous coronary intervention (PCI) with acute coronary syndrome (Unstable angina, non-st elevation MI and ST elevation MI) from Jan to Jun Endpoint was defined by cardiac death and stent thrombosis (ST) by definitions of the Academic Research Consortium (ARC). Aspirin and clopidogrel responsiveness were evaluated by VerifyNow tests (Accumetrics Inc, CA). Clopidogrel low-responsiveness was defined as the less than 20%.inhibition of P2Y12 receptor. Results: Baseline demographic characteristics were similar between normal group (370 pts) and low responsiveness group (240 pts) of clopidogrel. Cardiac death occurred in 7 pts (1.9%) of normal group and 14 pts (5.8%) in low group (p=0.009). Stent thrombosis occurred in 5 pts of normal group (0.7%, 4 definit and 1 probable) and 10 pts of low group (4.2%, 7 definite, 2 probable and 1 possible)(p=0.028). The associations between cardiac death and clopidogrel low-responsiveness were evaluated with multivariable logistic regression models adjusted for age and sex. The adjusted Odds ratio for cardiac death was (p=0.013, 95%CI; ) Conclusions: The low-responsiveness of clopidogrel measured with a point-ofcare assay is an independent predictor of cardiac death and stent thrombosis in acute coronary syndrome patients undergoing PCI. P2092 Adverse events associated with high clopidogrel loading doses after acute coronary syndrome C. Pizzi 1, M. Dorobantu 2, G. Tatu-Chitoiu 2,L.Calmac 2, O. Manfrini 1, M. Udeanu 1,E.Craiu 3, C. Macarie 4, R. Bugiardini 1. 1 University of Bologna, Bologna, Italy; 2 Emergency Hospital of Bucharest/Spitalul Clinic de Urgenta Bucuresti (Floreasca), Bucharest, Romania; 3 Hospital of Constanta, Constanta, Romania; 4 Institute of Cardiovasc.Diseases C.C.Iliescu/Inst. De Boli CV, Bucharest, Romania Background: In clinical practice, the use of standard or higher than standard clopidogrel loading doses is becoming more common even in those patients not receiving percutaneous coronary intervention (PCI). However, there is no clinical evidence to support such a strategy. Objective: We sought to assess whether patients with acute coronary syndromes (ACS) not undergoing PCI would receive additional benefit from 2 clopidogrel loading dose strategies (standard: 300 mg, and high: >300 mg) versus a noloading regimen with a single daily dose of 75 mg. Methods: We performed a retrospective analysis of outcomes in 763 patients with ACS not undergoing PCI who received standard-loading dose (n=361) or high-loading dose (n=105) versus no-loading dose (n=297) clopidogrel, in 14 study hospitals (International Registry for Acute Coronary Syndrome in Transitional Countries, IRACS-TC) between January 2006 and December All patients received a maintenance daily dose of clopidogrel 75 mg and aspirin 175 mg all throughout the study period. The primary efficacy end point was in-hospital cardiovascular death and recurrent ischemia. The key safety end point was major bleeding. Results: The rate of the combined endpoint of in-hospital cardiovascular death and recurrent ischemia was higher in the high-loading dose compared with the no-loading dose group (59.0% vs. 42.9%; p <0.0001). After adjustment for any clinical confounder (age, sex, risk factors, heart rate, systolic blood pressure, prior AMI, Killip class, ST-elevation myocardial infarction, and in-hospital acute medications) the odds ratio for high-loading dose versus no-loading dose was 3.28 (95% CI ; p=0.001). There was no benefit for the use of 300 mg loading dose over no-loading dose clopidogrel (odds ratio for the combined endpoint 1.59; 95% CI ; p=0.11). Bleeding event rates did not significantly differ (p=0.26) among no-loading dose (0.70%), standard-loading (1.1%) or high-loading dose (1.9%) groups. Conclusions: The use of clopidogrel loading doses is not associated with additional clinical benefit in patients with ACS not undergoing PCI. It may harm them if doses are >300 mg. P2093 Anti-thrombotic effects of an anti-von willebrand factor a1 domain aptamer in blood from patients under aspirin and clopidogrel therapy D. Arzamendi Aizpurua, F. Dandachli, G. Ducrocq, J.F. Theoret, W. Mourad, J. Gilbert, J. Gilbert, R. Schaub, Y. Merhi, J.F. Tanguay. Montreal Heart Institute, Montreal, Canada Background: Anti-thrombotic therapy, together with coronary intervention, is the base of treatment of acute coronary syndromes (ACS). Different anti-platelet therapies have shown a reduction in myocardial infarction and mortality, but with the cost of increasing bleeding. Platelets adhere to damaged arteries via binding of GPIb to the A1 domain of von Willebrand Factor (VWF), under high shear. The anti-vwf, ARC1779, is considered to be active on damaged sites under shear, without systemic effects on platelets and bleeding. Aim: To determine the anti-thrombotic effects of ARC1779 in an ex-vivo model with blood from patients on double anti-platelet therapy. Methods: Venous blood from 27 patients under aspirin and clopidogrel and 5 normal volunteers was labeled with 111In-autologous platelets and perfused over injured porcine aortic segments in Badimon chambers at high shear rate. Blood was treated with nm ARC1779, 100 nm Reopro or placebo, 5 min before beginning the perfusion (therapy) or 10 min after (rescue). Platelet adhesion and aggregation, thrombus mass and P-selectin expression were measured by gamma counter, impedance aggregation, SEM and flow cytometry, respectively. Results: Under therapy, we observed a significant reduction in platelet adhesion (106/cm 2 ) for ARC1779 at 75 and 250 nm and for Reopro vs. placebo (4.8, 3.8 and 2.9 vs. 7.2, p <0.05). Lower thrombus mass was confirmed by SEM. Rescue treatments had no effects on adhesion. ARC1779 did not affect P-selectin expression compared to placebo (2.2% vs. 2.5%) neither platelet aggregation in response to TRAP-1 (10.5 vs. 11.8). Conclusion: ARC1779 achieves anti-thrombotic potency comparable to Reopro, without any systemic effects on platelet activation and aggregation. These properties make ARC1779 suitable for clinical development as a new anti-platelet agent. P2094 Prevalence and predictors of bleeding in patients on prolonged dual oral antiplatelet therapy undergoing DES implantation R. Rossini 1, G. Musumeci 1, C. Lettieri 2, N. Lortkipanidze 1, M. Romano 2, T. Nijaradze 1,A.Izzo 2, G. Biondi Zoccai 3, A. Gavazzi 1, D.J. Angiolillo 4. 1 Ospedali Riuniti di Bergamo, Bergamo, Italy; 2 Ospedale Carlo Poma, Mantova, Italy; 3 Division of Cardiology, University of Turin, Torino, Italy; 4 University of Florida-Shands Jacksonville, Jacksonville, United States of America Purpose: Bleeding has emerged as a predictor of early and late mortality after percutaneous coronary interventions. Although dual oral antiplatelet therapy with aspirin and clopidogrel is associated with a higher risk of bleeding, the prevalence and predictors of bleeding events in patients on prolonged (12 months) treatment after drug-eluting stent (DES) implantation has been poorly explored. Methods: All consecutive patients (n=579) undergoing DES implantation and discharged on dual antiplatelet therapy with aspirin and clopidogrel for 12 months at our Institution were included in this study. Patients were followed-up for 12 months and the prevalence and predictors of in-hospital and long-term bleeding events were evaluated. The impact of bleeding events on all cause death, major adverse cardiac events (MACE), definite stent thrombosis, and premature discontinuation of antiplatelet therapy were also assessed. Results: The incidence of in-hospital major and minor/nuisance bleeding was 1.2% and 3.7%, respectively. The incidence of cumulative long-term major and minor/nuisance bleeding was 1.9% and 6.7%, respectively. Multivariable analysis showed that in-hospital bleeding was predicted by previous peptic ulcer disease (odds ratio [OR]=7.55, p=0.040) and long-term bleeding was associated with female gender (OR=2.04, p=0.014), previous peptic ulcer disease (OR=2.21, p=0.037), and previous myocardial infarction (OR=2.10, p=0.012). The incidence of overall mortality and MACE was significantly higher in patients who experienced a major bleeding (11.4% vs 2.2%, p<0.001). Patients who had any bleeding event were more likely to prematurely discontinue antiplatelet therapy (73.7% vs 14.2%, p<0.001) and had a higher risk of definite stent thrombosis (7.1% vs 1.3%; p=0.023). Conclusions: In DES treated patients on long-term dual antiplatelet therapy bleeding events are more common in females and in patients with a prior history of peptic ulcer disease and myocardial infarction. Patients experiencing a bleeding event are more likely to discontinue prematurely antiplatelet therapy and have stent thrombosis.

29 Thrombosis and anti-thrombotic therapy 329 P2095 High-risk patients for GI bleeding on dual antiplatelet therapy in Spain are more like to receive PPI therapy than their American peers A. Lanas 1,L.Guastello 2, R. Casado 1, D. Saini 2, M. Polo-Tomas 1, J. Scheiman 2,A.DelRio 1. 1 Hospital Clinico Universitario Lozano Blesa, Zaragoza, Spain; 2 University of Michigan Medical Center, Ann Arbor, United States of America Background: Proton-pumpinhibitor (PPIs) therapy is now recommended for the prevention of upper GI complications (UGIC) in patients on antiplatelet therapywith > 1 risk factors. Patients undergoing percutaneous coronaryintervention (PCI) require aggressive dual antiplatelet therapy. No study has determined whether PPIs are being used appropriately to reduce GI bleeding risk in such patients and whether there are different prescription habits between countries. Methods: We have performed a parallel retrospective cross-sectional study of medical records at the University in USA and University in Spain. Patients admitted to the hospital for PCI in 2006 and 2007 were included. Data were extracted on: (1) patient demographics; (2)medications used; (3)indication for PPI use; and, (4)risk factors for GI bleeding (age 70; history of peptic ulcer disease; concurrent warfarin,corticosteroids 10 mg daily, or daily NSAIDs). Patients with 1 risk factor were defined as high-risk (HR) for GI bleeding. The proportion of patients discharged on PPI therapy was calculated and stratified by GI bleeding risk. OR were calculated using Chi squared test. Results: 612 patients were included. Patients from Spain were older than those from USA (67.3±9.1 vs. 62.5±11.6; p < 0.001); the proportion of HR patients for GI bleeding was different (Table). However, HR patients from Spain had a higher probability of receiving PPI therapy at hospital discharge (OR: 2.90; 95%CI: ; p = ) than their American peers. Variable USA patients (n=199) Spain patients (n=413) p-value High-risk patients (HR) 40% 51% PPI at admission 30% 31% PPI at discharge 41% 75% HR patients on PPI at admission 48% 58% HR patients on PPI at discharge 58% 80% Low-risk patients on PPI at discharge 30% 71% Conclusions: There are important differences regarding PPI prescription habits among cardiologists from two different centers in the USA and Spain when managing PCI patients on dual antiplatelet therapy. HR patients for GI bleeding from Spain had a significantly higher probability of receiving PPI therapy at hospital discharge than their American peers. P2096 Age-related differences in the antithrombotic therapy in patients with PCI. Results from the ALKK-PCI Registry A.K. Schwarz 1,R.Zahn 1, M. Hochadel 2, S. Kerber 3, K.E. Hauptmann 4, H. Mudra 5,H.Darius 6, J. Senges 2,U.Zeymer 1. 1 Klinikum der Stadt Herzzentrum Ludwigshafen, Ludwigshafen am Rhein, Germany; 2 Institut fuer Herzinfarktforschung Ludwigshafen, Ludwigshafen am Rhein, Germany; 3 Klinik für Kardiologie, Herz- und Gefäß-Klinik GmbH, Bad Neustadt, Germany; 4 Krankenhaus der Barmherzigen Brüder Trier, Trier, Germany; 5 Klinik für Kardiologie, Pneumologie und Intern. Intensivmedizin, Klinikum Neuperlach, Städt. Klinik., München, Germany; 6 Klinik für Innere Medizin - Kardiologie, Vivantes Klinikum Neukölln, Berlin, Germany Purpose: Antithrombotic therapy plays a crucial role in the therapy of patients with CAD. With increasing life expectancy, the number of elderly (>75 years) coronary patients is constantly increasing. This analysis examines possible agerelated differences in the antithrombotic therapy in patients with Acute Coronary Syndrome and elective PCI. Methods: We analyzed data of unselected patients with ST-elevation myocardial infarction (STEMI), Non-ST-elevation myocardial infarction (NSTEMI), unstable Angina (UA) and elective PCI from the ALKK-PCI Registry Results: In 2006, a total of consecutive patients with PCI were enrolled in 42 hospitals. Thereof, 33,7% (n=6762) were and 66,3% (n=20033) were < 75 years. Patients 75 with NSTEMI and STEMI received significantly less often a clopidogrel loading dose of 600 mg (NSTEMI: 40,1% vs. 47,6%, p<0,001; STEMI: 55,6% vs. 60,9%, p<0,01). Furthermore, elderly patients with UA, NSTEMI and STEMI were significantly less often treated with aspirin i.v. (UA: 30,3% vs. 35,3%, p=0,026; NSTEMI: 42,3% vs. 47,6%, p<0,01; STEMI: 64,0% vs. 69,1%, p<0,01). There was no difference found in clopidogrel loading dose and aspirin i.v. in pa- tients with elective PCI. The frequency of the administration of GPIIb/IIIa antagonists is shown in the table below. Conclusion: Elderly patients ( 75) with ACS receive significantly less intensive antithrombotic treatment with aspirin i.v., 600 mg clopidogrel loading dose as well as GPIIb/IIIa antagonists, while there is no difference in elective PCI. P2097 The in vitro effects of E5555, a PAR-1 antagonist, on platelet biomarkers in healthy volunteers and patients with coronary artery disease V.L. Serebruany 1, M. Kogushi 2, D. Dastros-Pitei 3,M.Flather 4, D.L. Bhatt 5. 1 Johns Hopkins University, Towson, United States of America; 2 Eisai, LTD, Tsukuba, Japan; 3 Eisai, London, United Kingdom; 4 Royal Brompton Hospital, London, United Kingdom; 5 Brigham and Women s Hospital, Boston, United States of America Background: E5555 is a potent protease activated receptor (PAR-1) antagonist targeting the G-coupled receptor and modulating thrombin-platelet-endothelial interactions. The drug is currently being tested in Phase II trials in patients with coronary artery disease (CAD) with potential antithrombotic and antiinflammatory benefits. We investigated the in vitro effects of E5555 on platelet function beyond PAR-1 blockade in healthy volunteers and CAD patients treated with aspirin (ASA) with or without clopidogrel. Methods: Conventional aggregation induced by 5 μm ADP, 1 μg/ml collagen, 10 μm TRAP, whole blood aggregation with 1 μg/ml collagen, and expression of 14 intact, and TRAP-stimulated receptors by flow cytometry were utilized to assess platelet activity after preincubation with escalating concentrations of E5555 (20 ng/ml,50 ng/ml, and 100 ng/ml) in healthy volunteers, CAD patients treated with ASA, and CAD patients treated with ASA and clopidogrel combination (n=10, for each group). Results: E5555 inhibited a number of platelet biomarkers. Platelet inhibition was usually moderate, present already at 20 ng/ml, and was not seemingly dose-dependent without TRAP stimulation. E5555 caused 10-15% inhibition of ADP- and collagen-induced platelet aggregation in plasma, but not in whole blood. TRAP-induced aggregation was inhibited almost completely. PECAM-1, GP IIb/IIIa antigen, and activity withpac-1, GPIb, thrombospondin, vitronectin receptor expression, and formation ofplatelet-monocyte aggregates was also significantly reduced by E5555. TRAP stimulation caused dose-dependent effects between 20 and 50 ng/ml E5555 doses. P selectin, LAMP-1, LAMP,and CD40- ligand were not affected by E5555. Conclusion: E5555 in vitro moderately but significantly inhibits platelet activity beyond PAR-1 blockade. Antiplatelet potency of ASA alone, and the combination of ASA and clopidogrel are enhanced by E5555 providing rationale for their synergistic use. Selective blockade ofplatelet receptors suggests unique antiplatelet properties of E5555 as a potential addition to the current antithrombotic regimens. P2098 Thrombin generation curve in patients submitted to angioplasty with a combination of antiplatelet agents, fondaparinux and unfractionated heparin F. Schiele, E. Racadot, N. Meneveau, M.F. Seronde, V. Descotes- Genon, R. Chopard, J. Dutheil, J.P. Bassand. University hospital, Besancon, France Rationale: The thrombin generation curve (TGC) allows a dynamic measure of the thrombin generation, sensitive to platelet and coagulation activity. We compared TGC variables in patients pre treated with combinations of antiplatelet, Fondaparinux and unfractionated heparin (UFH). Methods: TGC was performed in 30 healthy volunteers (group 1) and in 141 patients treated according to their clinical situation: stable patients with aspirin and Clopidogrel (group 2), unstable patients with additional 2.5 mg Fondaparinux (group 3), with additional Tirofiban (group 4) and with 50U/kg of UFH (group 5). TGC was performed in platelet rich plasma by fluorimetry technique. The TGC parameters were: Endogenous Thrombin Potential (ETP= area under the curve), latence (time to initiation of thrombin), maximal concentration of thrombin (Cmax), time to reach this peak (T max) and maximal rising slope (slope). Results: Aspirin and Clopidogrel induced a 32% reduction in ETP (1 vs 2). When Fondaparinux was added, there was no change in ETP despite a decrease in slope and in Cmax (2 vs 3). When Tirofiban was added there was a 22% decrease Age GPIIb/IIIa antagonist p value Elective 75 6,9% n.s. <75 7,7% UA 75 14,9% <0,01 <75 20,8% NSTEMI 75 32,1% <0,00001 <75 43,0% STEMI 75 56,9% <0,0001 <75 64,2% n.s. = not significant. ETP, slope and Tmax in the 5 groups

30 330 Thrombosis and anti-thrombotic therapy in ETP, in Cmax and in slope (3, vs 4). After a bolus of 50U/kg UFH, no thrombin formation could be detected by TGC. There was no effect of Fondaparinux in coagulation times (comparable latence and Tmax between groups 2 and 3), but a significant decrease in Cmax and slope (figure). The modest reduction in ETG (50%) after Fondaparinux, even with double or triple antiplatelet therapy might explain the catheter thrombus formation and the need of additional bolus of UFH during PCI. Conclusions: TCG provide important information of the efficacy of antiplatelet and anticoagulant agents, particularly in patients treated with Fondaparinux and could be helpful for monitoring in the setting of PCI P2099 Elevated residual platelet reactivity to adenosine diphosphate and arachidonic acid in patients after myocardial infarction compared to patients after elective coronary stenting T.F. Althoff 1,M.Fischer 2, F. Knebel 1, E. Langer 3,S.Ziemer 3, G. Baumann 1. 1 Charite - Universitätsmedizin Berlin, Campus Mitte, Klinik für Kardiologie und Angiologie, Berlin, Germany; 2 Vivantes Klinikum im Friedrichshain, Department of Cardiology, Berlin, Germany; 3 Charite - Universitätsmedizin Berlin, Institut für Laboratoriumsmedizin und Pathobiochemie, Berlin, Germany Purpose: Elevated residual platelet reactivity despite treatment with clopidogrel and acetyl salicylic acid (ASA) is associated with ischemic events after coronary stenting. For patients who have undergone coronary stenting for myocardial infarction, standard antiplatelet therapy equals that recommended for patients after elective coronary stenting for a minimum of four weeks. We sought to demonstrate that there is a persistent enhancement of residual platelet reactivity after myocardial infarction requiring a continued intensified antiplatelet regime. Methods: This study prospectively enrolled subjects after coronary stenting for myocardial infarction (STEMI or NSTEMI) and control subjects after elective coronary stenting. Platelet function testing was performed 48 hours and 30 days after coronary stenting. We assessed residual platelet reactivity with lighttransmittance aggregometry (LTA) using adenosine-5 -diphosphate (ADP, 5μM and 2,5μM) and arachidonic acid (AA) as agonists. Moreover we performed multiple electrode aggregometry (MEA), a point-of-care test recently developed, using ADP, ADP + prostaglandin E1 (PG) and AA as agonists. Results: A total of 66 patients were included. Fourty-eight hours after coronary stenting all measures of residual platelet reactivity were significantly elevated in the infarction group (Figure). Residual platelet reactivity to ADP was still consistently elevated at the 30 day follow up - albeit statistically not significant. Contrarily, residual platelet reactivity to AA significantly decreased over time in the infarction group. Early stent thrombosis (within 30 days) was documented in 91 (38%) patients, late stent thrombosis (from 31 to 365 days) in 39 (16%) patients and very late stent thrombosis (later than 365 days) in 107 patients (45%). Late stent thrombosis occurred steadily at a constant rate of % per year up to 5 years after stent implantation. Independent predictors of overall stent thrombosis were acute coronary syndrome at presentation (hazard ratio 2.75, 95% CI ), diabetes (2.08, ) and age (0.96, ). Conclusion: Up to 5 years after DES implantation, we observed a steady increase in the cumulative incidence of late stent thrombosis. P2101 Differential proteomic profiling of coronary stent thrombosis versus atherothrombosis K. Distelmaier, M. Kubicek, B. Redwan, C. Adlbrecht, O. Wagner, I.M. Lang. Medical University of Vienna, Vienna, Austria Purpose: Coronary stent implantation is reducing the risk of major adverse cardiac events. However, the occurrence of stent thrombosis (ST) remains a severe complication that results in abrupt coronary artery closure and acute myocardial infarction (AMI). The underlying molecular and cellular mechanisms of ST are not fully understood. Methods: We compared thrombus aspirated from the site of plaque rupture of 34 patients with ST and 39 patients with AMI due to atherosclerotic occlusion within a native coronary artery (time from first medical contact to balloon inflation 89±12 versus 81±16 minutes) by proteomic profiling. Results: While leukocytes were low at the culprit site in ST (-0.48±2.45 G/L), they accumulated at the site of atherosclerotic plaque rupture (1.71±4.41 G/L, p=0.019). In contrast to native thrombus, stent thrombus was characterized by high levels of von Willebrand factor, and platelet specific proteins e.g., Platelet glycoprotein I beta and Platelet glycoprotein IX and Platelet factor IV. Local complement activation was not detected in ST, with low levels of C-reactive protein, serum amyloid P, cell adhesion molecules, and low levels of other mediators of inflammation. Conclusion: Our results demonstrate different proteomic patterns in stent thrombus compared with native coronary artery thrombus, displaying proteins involved in platelet aggregation rather than inflammation. Platelet reactivity 48 h after stenting Conclusion: In patients undergoing coronary stenting for acute myocardial infarction, residual platelet reactivity remains elevated for at least 48 hours, indicating a need for a continued intensified antiplatelet therapy. P2100 Incidence of late stent thrombosis up to 5 years after implantation of drug-eluting stent in routine practice Y. Onuma 1, P. Wenaweser 2, J. Daemen 1, G. Hellige 2, K. Tsuchida 1, P. Juni 2,R.VanDomburg 1,P.W.Serruys 1, S. Windecker 2. 1 Erasmus MC - Thoraxcenter, Rotterdam, Netherlands; 2 Department of cardiology, university of Bern, Bern, Switzerland Background: Stent thrombosis (ST) has been a safety concern of drug-eluting stents. Late ST was reported to occur at an annual rate of % up to 4 years after drug-eluting stent (DES) implantation. Little is known, however, about occurrence of ST more than 4 year after implantation of DES. Methods: Between April 2002, and December 2005, 8,146 patients underwent percutaneous coronary intervention with sirolimus-eluting stents (SES; n=3,823) or paclitaxel-eluting stents (PES; n=4,323) at two academic hospitals. We investigated the incidence and time course of stent thrombosis up to 5 years. Results: Angiographically documented stent thrombosis occurred in 237 patients of 8,146 patients with an incidence density of 0.78 per 100 person-years and a cumulative incidence at 5 years of 3.5%. Kaplan-meier survival estimate is presented in the figure. P2102 Fibrin clot structure/fibrinolysis and relationship to ischaemic heart disease and metabolic factors in older individuals with type 2 diabetes: the Edinburgh Type2DiabetesStudy R.A. Ajjan 1,K.A.Hess 1,A.M.Carter 1, A. Trehan 1, K.S. Standeven 1, P.J. Grant 1, R.M. Williamson 2, R.M. Reynolds 3,J.F.Price 3, M.W.J. Strachan 2. 1 University of Leeds, Leeds, United Kingdom; 2 Metabolic Unit, Western General Hospital, Edinburgh, United Kingdom; 3 The University of Edinburgh, Edinburgh, United Kingdom Thrombus formation represents the final step in the atherothrombotic process and studies have shown that fibrin clot structure predicts predisposition to cardiovascular events. This study assessed the relationship between clot structure/fibrinolysis and cardiac ischaemia as well as metabolic parameters in older individuals with type 2 diabetes (T2DM). Fibrin clot structure and fibrinolysis were assessed ex vivo in 255 T2DM patients [mean age 68.9 ( ); male=158] using a validated turbidimetric assay. Clot maximum absorbance (MA), a measure of clot density, and time from full clot formation to 50% lysis were recorded. Ischaemic heart disease (IHD) was defined as a history of myocardial infarction or symptoms of angina and/or medical treatment for this condition with or without ECG changes. After controlling for age and sex, MA correlated with a history of IHD (r=0.48, p=0.002), and lysis time correlated with plasma glucose and triglyceride levels (r=0.47, p=0.002 and r=0.42, p=0.007, respectively). Neither MA nor lysis time correlated with HbA1c, total cholesterol or cholesterol subfractions. Individuals with IHD (n=106) had higher MA at 0.338±0.01 as compared with those without an ischaemic history [0.307±0.01 au; p=0.02], whereas lysis time was not affected [781±37 and 755±37 seconds, respectively; p=0.62]. In a logistic regression model including MA, lysis time, age, sex and body mass index (BMI), only MA was an independent predictor of cardiac ischaemia with odds ratio of 1.40 (1.03, 1.92; p=0.03). In conclusion, an increase in clot MA is associated with a higher risk of myocardial

31 Thrombosis and anti-thrombotic therapy 331 ischemia in older individuals with T2DM. The correlation between lysis time and plasma glucose, but not HbA1c, suggests that fluctuation in glucose levels is more important at determining fibrinolysis potential than long term glycaemic control. Further clinical studies are warranted to fully elucidate the role of clot structure in predisposition to cardiac events in this group of individuals. P2103 The novel synthetic cyclic peptide (S,S) PSRCDCR- NH2, inhibits carotid artery thrombosis in rabbits V. Roussa 1, E.M. Stathopoulou 2, K. Egglezopoulos 3, N.D. Papamichael 1,V.Mousis 2, V. Tsikaris 2, C.S. Katsouras 1, K.K. Naka 1,A.D.Tselepis 2, L.K. Michalis 1. 1 University Hospital of Ioannina, Cardiology Department, Ioannina, Greece; 2 University of Ioannina, Department of Chemistry, Ioannina, Greece; 3 Michaelidion Cardiac Center, University of Ioannina, Ioannina, Greece Purpose: Platelet activation and aggregation, which play a key role in the pathogenesis of acute coronary syndromes, are primarily mediated by GPIIb/IIIareceptors binding to their ligands, through the RGD (Arg-Gly-Asp) sequence. GPIIb/IIIa inhibitors used in clinical practice compete to fibrinogen for the binding to the GPIIb/IIIa receptor through RGD-mediated interactions. We have recently synthesized a constraint cyclic peptide, (S,S) PSRCDCR-NH2, that exhibits potent non-rgd antiplatelet activity in vitro, possibly interacting with the ligand rather than the receptor. We studied the peptide s effect on a rabbit experimental thrombosis model. Methods: Three groups (n=5 in each group) were studied, receiving intravenously a. normal saline, 6ml/kg/h (control group), b. (S,S) PSRCDCR-NH2, 6 mg/kg bolus plus 2.4 mg/kg/h, c. eptifibatide, 900 μg/kg bolus plus 10 μg/kg/h. Carotid artery thrombus formation was induced by electrical stimulation, under continuous blood flow monitoring. Ex vivo platelet aggregation to 20 μm ADP and 500 μm AA in platelet rich plasma (PRP) was determined before (baseline) and at 60 min after the initiation of drug administration (instantly prior to electrical stimulation). Ninety minutes after electrical stimulation the carotid thrombus was removed and weighed. Blood loss was calculated by the amount of blood, gathered on a pre-weighed gauze, positioned on a standardized incision, performed on the anterior abdominal wall. Results: In the control group, carotid artery was totally occluded within 23.3±3.2 min after electrical stimulation. By contrast, in the (S,S) PSRCDCR-NH2 and eptifibatide groups, carotid artery blood flow at 90 min after electrical stimulation, was reduced to 45.9±1.5% and 35.3±2.0% respectively (p<0.001 vs control). Thrombus weight was significantly reduced in animals receiving (S,S) PSRCDCR-NH2 or eptifibatide vs control (1.5±0.3mg or 2.1±1.1mg vs 5.7±0.8mg, respectively, p<0.008 vs control). Platelet maximum aggregation to ADP and AA in the control group was not altered compared to baseline 60 min after electrical stimulation, whereas was significantly inhibited in the (S,S) PSRCDCR-NH2 and eptifibatide groups by 42.1±3.1 and 38.3±11.0% to ADP (p<0.005 vs control), and 75.6±12.0 and 40.0±11.1%, to AA (p<0.007 vs control). There was no significant increase of blood loss observed in (S,S) PSRCDCR-NH2 and eptifibatide groups compared to control. Conclusions: (S,S) PSRCDCR-NH2, a non-rgd novel cyclic peptide, reduces experimental thrombus formation in rabbits by inhibiting platelet aggregation, without affecting bleeding assays. P2104 A proinflammatory and prothrombotic environment in young individuals with type 1 diabetes: the effects of glycaemic control K.A. Hess, M. Mathai, T. Koko, K.F. Standeven, P. Holland, A.M. Carter, F. Phoenix, P.J. Grant, R.A. Ajjan. University of Leeds, Leeds, United Kingdom C-reactive protein (CRP) and complement C3 are both predictors of cardiovascular events, and the latter is possibly a better indicator of arteriosclerotic burden. In addition to inflammatory molecules, fibrin clot structure has been linked to cardiovascular disease, as compact clots are associated with premature and more severe atherothrombotic conditions. Although the atherosclerotic process starts at an early age, little is known about CRP and C3 plasma levels in younger individuals with type 1 diabetes (T1DM). Also, studies investigating blood clot structure in this cohort are still lacking. The present work analyses CRP and C3 plasma levels and evaluates fibrin clot structure in children with T1DM and investigates the effects of improving glycaemic control in young adults with this condition. ELISA was used to determine CRP and C3 plasma levels in 30 Type 1 DM children [14 yrs (range 11-17)] and 17 age matched controls, whereas fibrin clot structure was studied using a validated turbidimetric assay. The above parameters were further assessed in 18 young adults [23 yrs (range 18-26)], before and after improving glycaemic control. T1DM children had higher C3 levels (mean±sem) compared with controls (1.13±0.24 versus 0.83±0.24 mg/ml respectively; p<0.001), whereas the difference in CRP levels failed to reach statistical significance (0.85±1.36 versus 0.5±1.21 mg/l respectively; p=0.06). Clot final turbidity (FT), an indicator of clot density, was higher in diabetes children at 0.38±0.01, compared with controls (0.31±0.02;p<0.01). In young adults with T1DM, a reduction of HbA1c from 10.5% to 9.2% (p<0.05) was associated with a decrease in C3 levels from 1.09±0.05 mg/ml to 0.96±0.05 mg/ml (p<0.05) but had no effect on plasma CRP levels. Improving glycaemic control was associated with a reduction in FT from 0.30±0.02 to 0.26±0.02 (p<0.05), demonstrating the formation of less compact clots. Analysing all diabetes individuals together, clot FT correlated positively with C3 plasma levels (r=0.39, p<0.01) but not CRP, suggesting an interaction between C3 and clot structure. This is the first report describing a denser ex vivo clot structure and elevated C3 levels in children with T1DM, further confirming that the vascular inflammatory/thrombotic process starts at a young age in individuals at risk. Moreover, the drop in clot FT and C3 plasma levels after improving glucose control, suggests that early glycaemic intervention is important to prevent long term cardiovascular complications, a concept backed by clinical outcome studies. P2105 Effect of edoxaban (DU-176b) on thrombin generation and platelet activation in shed and venous blood with fondaparinux as active comparator M.M. Samama 1,M.Wolzt 2,K.Ogata 3, J. Mendell 4, S. Kunitada 4. 1 Hotel Dieu University Hospital, Paris, France; 2 Medical University of Vienna, Vienna, Austria; 3 Daiichi Sankyo Co., Ltd., Tokyo, Japan; 4 Daiichi Sankyo Pharma Development, Edison, United States of America Purpose: The shed blood model allows for the study of activated coagulation at a site of standardized tissue injury due to local release of tissue factor which may add insight into pathophysiological states. Edoxaban is an oral, direct factor Xa (FXa) inhibitor in development for stroke prevention in atrial fibrillation patients. The aim of this study was to investigate the effect of 3 doses of edoxaban on markers of coagulation in shed and venous blood compared with placebo and fondaparinux, an active comparator. Methods: Healthy, male subjects (n = 100) were randomized to either single doses of edoxaban (30, 60 and 120 mg PO), placebo or fondaparinux (2.5 mg SC). Primary objective was comparison of various assays for coagulation including prothrombin fragment 1+2 (F1+2), thrombin-anti-thrombin (TAT) and platelet activation [β-thromboglobulin (β-tg)] in venous and shed blood, obtained after percutaneous incision, for edoxaban, placebo and fondaparinux. Secondary objectives included pharmacokinetics, blood volume and safety of edoxaban. Results: There was a rapid and sustained reduction in F1+2, TAT and β-tg following edoxaban mg in both venous and shed blood. Reductions after fondaparinux were significantly less marked. Baseline-corrected F1+2, TAT, and β-tg values remained decreased for edoxaban up to 24 hours for shed blood but were less pronounced in venous blood. The treatments were well tolerated with a few cases of mild bleeding distributed across the 4 active treatment arms. Conclusions: Edoxaban at single doses up to 120 mg causes rapid and sustained inhibition of coagulation up to 24 hours as demonstrated by decreased F1+2, TAT and β-tg in the shed blood model which approximates a procoagulant pathophysiological state. P2106 Concomitant administration of low-dose rivaroxaban - an oral, direct Factor Xa inhibitor - with clopidogrel and acetylsalicylic acid enhances antithrombotic efficacy in rats E. Perzborn, E. Fischer, U. Lange, M. Harwardt. Global Drug Discovery, Cardiology Research, Bayer Schering Pharma, Wuppertal, Germany Purpose: Rivaroxaban an oral, direct Factor Xa inhibitor is currently undergoing phase III studies for the secondary prevention of acute coronary syndromes in patients receiving acetylsalicylic acid (ASA) or ASA and a thienopyridine (ATLAS2 TIMI51). The present study assessed the effects of low doses of rivaroxaban, the thienopyridine clopidogrel, ASA, or their combinations, on arterial thrombosis and haemostasis in a rat arteriovenous (AV)-shunt model. Methods: The effects of intravenous rivaroxaban (0.01, 0.03, and 0.1 mg/kg; study A, B and C, respectively), oral clopidogrel 1 mg/kg, oral ASA 3 mg/kg and their combinations on thrombosis were investigated in a rat AV-shunt model. The shunt was located between the right common carotid artery and the left jugular vein. Bleeding times were measured in a rat tail-transection model. Results: Rivaroxaban dose dependently reduced thrombus formation, with an ED 50 of 0.33 mg/kg. Thrombus formation was not significantly inhibited by low doses of rivaroxaban (0.01 and 0.03 mg/kg) or ASA alone, but was moderately inhibited by clopidogrel (28 35%). Addition of either ASA or low doses rivaroxaban to clopidogrel did not enhance its antithrombotic effects. However, the combinations of either low dose of rivaroxaban (0.01 and 0.03 mg/kg) with ASA resulted in a significant reduction of thrombus formation (24%, p<0.05; and 37%, p<0.001, respectively). Addition of these same two low doses of rivaroxaban to the com-

32 332 Thrombosis and anti-thrombotic therapy bination of clopidogrel and ASA resulted in a slight further increase (43%) in the antithrombotic effect. Combining an effective dose of rivaroxaban (0.1 mg/kg) to either ASA or clopidogrel, or to the combination of ASA and clopidogrel, increased the antithrombotic effect to 39, 52 and 51%, respectively (p<0.001 vs control). The antithrombotic efficacy of the combination of rivaroxaban and ASA was similar to that of the combination of ASA and clopidogrel (37%, p<0.001 vs control). Rivaroxaban or ASA alone did not affect bleeding times, but there was a slight, non-significant increase in bleeding time with clopidogrel alone ( fold vs control). Addition of rivaroxaban (either 0.03 or 0.1 mg/kg) to the combination of clopidogrel and ASA slightly increased bleeding time beyond the increase observed with clopidogrel alone, but this effect did not reach statistical significance (2.8- and 2.5-fold vs control, respectively). Conclusion: These results suggest that low doses of rivaroxaban co-administered with either ASA or the combination of clopidogrel and ASA may have greater antithrombotic effect than the individual treatments. P2107 High Density Lipoprotein (HDL) from healthy subjects, but not from patients with coronary artery disease, exerts anti-thrombotic effects on human endothelial cells E.W. Holy 1,C.Besler 1,G.G.Camici 2, T.F. Luescher 1, U. Landmesser 1, F.C. Tanner 1. 1 University Hospital Zurich, Zurich, Switzerland; 2 Inst. of Physiology, University of Zurich-Irchel, Zurich, Switzerland Background: Arterial thrombus formation is determined by the balance between pro- thrombotic mediators such as tissue factor (TF) and plasminogen activator inhibitor type 1 (PAI-1), and anti-thrombotic factors like tissue factor pathway inhibitor (TFPI) or tissue plasminogen activator (tpa). Native HDL from healthy subjects (HS) has anti-thrombotic properties; however, it remains unknown whether this is the case for HDL from patients with stable coronary disease (CAD) or acute coronary syndrome (ACS). Methods: HDL was isolated by sequential ultracentrifugation from HS and patients with CAD and ACD. The effects of HDL (50 μg/ml) on TF, TFPI, and PAI-1 expression in human endothelial cells were determined by Western blot analysis; tpa release was measured by ELISA. Results: HDL from HS impaired thrombin-induced TF expression (-45±5%, p<0.05, n=16) and activity (-33±8%, p<0.05, n=7); in contrast, HDL from CAD and ACS patients did not (p=ns, n=12 and n=8). Similarly, HDL from HS increased TFPI expression by 2-fold (p<0.01, n=8), while HDL from CAD and ACS patients had no effect (p=ns). HDL from HS enhanced tpa release (+26±3%; p=0.05, n=8); in contrast, HDL from CAD and ACS patients did not (p=ns, n=6). Furthermore, HDL from HS did not affect PAI-1 expression, while HDL from CAD patients enhanced PAI-1 expression by 62% (p<0.05 vs. healthy, n=12) and HDL from ACS patients by 2 fold (p<0.05 vs. control and p<0.05 vs. healthy, n=8). Pretreatment with the inhibitor of NO formation, L-NAME (100 μm), abolished the anti-thrombotic effects of HDL from HS on TF, TFPI, and tpa expression. The exogenous nitric oxide donor, DETANO, mimicked the effects of HDL from HS on TF, TFPI, and tpa. Conclusion: This study demonstrates that HDL from healthy subjects exerts antithrombotic effects on endothelial cells. In contrast, HDL from CAD and ACS patients loses these antithrombotic properties and instead enhances PAI-1 expression, thereby becoming pro-thrombotic. This observation might be highly relevant for HDL-targeted therapies. P2108 Vitamin K epoxide reductase complex subunit 1 (VKORC1) gene polymorphism is associated with atherothrombotic complication after drug-eluting stent implantation J.-W. Suh 1,H.-S.Kim 2,J.-S.Park 2, H.-J. Kang 2, I.-H. Chae 1, D.-J. Choi 1. 1 Seoul National University Bundang Hospital, Seongnam, Korea, Republic of; 2 Seoul National University, Seoul, Korea, Republic of Background: Single nucleotide polymorphisms (SNPs) of vitamin K epoxide reductase complex subunit 1 (VKORC1) was reported to have association with arterial vascular disease. We investigated whether SNP of VKORC is associated with clinical outcomes among patients who underwent drug-eluting stent (DES) implantation. Methods: We prospectively collected genomic DNA in patients who underwent DES deployment from Sep 2003 to Dec 2006 and compared clinical outcomes according to their VKORC1 genotype at the locus (rs ). The primary end-point was composite of atherothrombotic events [cardiac death, myocardial infarction, and non-hemorrhagic stroke]. Results: Mean follow-up duration was 631±251 days. Genotyping was completed in 764 cases (TT genotype (n=640, 83.8%) vs. non-tt (CC or CT) genotype (n=124, 16.2%)). Non-TT group showed more composite events than TT group (7.3% vs. 3.0%, p=0.032). In the Cox regression analysis, non-tt genotype of VKORC gene was a significant predictor of atherothrombotic events (Hazard ratio 2.56, 95% confidence interval ). In the event-free survival analysis, non-tt group also showed significantly poorer cardiovascular events-free survival rate than TT group (p=0.02). Conclusions: VKORC1 genotype is associated with cardiovascular events in patients with DES implantation, suggesting the role of coagulation system. P2109 The impact of the genetic polymorphism G455A on the b-chain fibrinogen gene on thrombotic process in patients with coronary artery disease D. Tousoulis, N. Papageorgiou, C. Antoniades, G. Hatzis, A. Miliou, A. Giolis, A. Antonopoulos, C. Tentolouris, C. Toutouzas, C. Stefanadis. 1st Cardiology Unit Hippokration Hospital Athens, Athens, Greece Purpose: Evidence suggests that fibrinogen plays a critical role in atherosclerosis. A genetic polymorphism on fibrinogen chain B, the G455A, has been associated with fibrinogen levels in healthy individuals, but its effect on thrombotic process in patients with coronary artery disease (CAD) is unclear. In the present study we examined the effect of this polymorphism on prothrombotic profile of patients with CAD. Methods: The study population consisted of 243 individuals, 191 of which with angiographically documented CAD and the rest with angiographically documented absence of any significant coronary stenoses. The G455A polymorphism was detected by polymerase chain reaction (PCR) and appropriate restriction enzymes. Fibrinogen levels were measured by immunonephelometry, while other factors of thrombosis such as plasma levels of d-dimers, factors V and X, plasminogen and thrombin time were measured by standard coagulometry techniques. Results: The genotype distribution was GG: 48.2%, AG: 40.3%, AA: 11.5% and GG: 50.0%, AG: 34.6%, AA: 15.3% for CAD patients and healthy individuals respectively. Among CAD patients AA patients had significantly higher levels of fibrinogen than GA patients. There was no difference among other genotypes (AA: 517.5±144.0, AG: 434.0±132.2, GG: 443.0±121.0 mg/dl p<0.05 for AAvsGA, p=ns for AAvsGG, GAvsGG). Plasma plasminogen levels did not differ across the three genotypes GG (106.3±19.1u/ml) compared to GA (112.5±20.0 u/ml) and AA (115.8±11.5u/ml), p=ns for all. Moreover, there was no significant difference in plasma levels of factor X (AA: 94.1±20.3 vs GA: 91.6±26.1 vs GG: 101.2±23.2%, p=ns for all), factor V (AA: 124.9±28.4 vs AG: 125.7±34.4 vs GG: 122.0±32.2%, p=ns for all), thrombin time (AA: 19.5±3.2 vs GG: 20.8±18.4 vs GA: 19.0±1.7 sec, p=ns) and D-dimers (AA: 551.7±321.5 vs GA: 511.4±526.7 vs GG: 616.3±817.4 mg/l p=ns). Conclusions: Genetic polymorphism G455A on fibrinogen b-chain gene affects fibrinogen levels, but has no effect on other thrombotic markers. These findings indicate that this polymorphism may play important role in the process of atherothrombosis by affecting only fibrinogen levels, but not other thrombotic parameters. P2110 Effects of direct thrombin or factor Xa inhibition on clot thrombogenicity in vitro: Comparison of dabigatran with rivaroxaban and apixaban J. Van Ryn, M. Kink-Eiband, I. Kuritsch, W. Wienen. Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany A thrombus can remain active for hours to days, mostly due to surface-bound activated clotting factors that are protected from inhibition by heparin therapy. In contrast, the new, small molecule inhibitors of either thrombin (dabigatran) or factor Xa (rivaroxaban and apixaban) can inhibit clot-bound thrombin or factor Xa, respectively. However, it is unknown if this direct inhibition results in reduced clot thrombogenicity as measured by the ability of the thrombus to convert fibrinogen into fibrin. This study investigated the ability of dabigatran, a direct inhibitor of thrombin, or rivaroxaban and apixaban, direct inhibitors of factor Xa to reduce the thrombogenicity of a clot, measured as inhibition of FPA generation in human plasma in vitro. Clots were generated in human platelet rich plasma supplemented with Ca 2+, and then extensively washed in buffer to remove all trapped FPA. Clots were then transferred to 0.5 ml plasma containing either dabigatran, rivaroxaban or apixaban and further incubated for 1 hr at 37 C. Clots were then removed and the reaction was stopped using bentonite. Fibrin formation was measured as FPA release using ELISA. In separate experiments, prothrombin fragment 1+2 (F1+2) was measured as an indices of thrombin generation to directly assess effectiveness of factor Xa inhibitors in the clot. In untreated plasma containing a thrombus, there was an average of 30±5 ng/ml of FPA generation (mean ± SE, n=8). In plasma containing increasing concentrations of dabigatran (1nM-10 μm), there was a concentration-dependent inhibition of FPA, with an IC50 of 127 nm, n=4/conc. Apixaban and rivaroxaban had no effect on FPA release when tested at concentrations up to 10 μm. FPA release with both inhibitors was similar to control, untreated plasma containing a clot, resulting in generation of ng/ml FPA. Prothrombin F1+2 generation was not elevated when the thrombus was added to plasma, even in the absence of treatment. Only when clots were placed in a buffer system with factor Va and prothrombin supplementation, could an elevation of prothrombin F1+2 be measured. In this purified system, the factor Xa inhibitors were shown to inhibit prothrombin F1+2. This study demonstrates that a thrombus alone is thrombogenic when added to plasma and can induce fibrin formation and that thrombin in an existing clot plays a key role in thrombus propagation. Dabigatran could inhibit this thrombogenicity by directly binding thrombin in the clot, this occurred at clinically relevant concen-

33 Thrombosis and anti-thrombotic therapy / Controversial issues in the management of acute coronary syndromes 333 trations. The factor Xa inhibitors, rivaroxaban and apixaban had no effect in this experimental setting. P2111 Heparin induced thrombocytopenia after cardiac surgery and the tale of complications A. Neykova, B.T. Tzvetkov, M.K. Kirsch. AP-HP - Hopital Henri Mondor, Creteil, France Heparin-induced thrombocytopenia (HIT) occurs in 1 to 3% of patients after cardiac surgery. HIT induces a prothrombotic state which may adversely affect postoperative outcomes. It may be complicated in 30 75% of cases by a paradoxical thrombotic syndrome (HITT), either arterial or venous. The aim of the present study was to evaluate the rate of thrombosis and other complications hemorrhagia and infections in case of HIT after cardiac surgery and and compare with other patients with thrombocytopenia. In this study we included 29 patients with HIT after cardiac surgery and 70 patients after cardiac surgery with thrombocytopenia without HIT (control group). Those are all 29 patients with HIT in our clinic in the period HITT is present in 7 patients (22.2%), and three of them are with multiple sites of thrombosis. Three patients of the control group present a thrombosis event. All patients are treated with non fractioned heparin and almost all (except 2 patients) of HIT cases are treated by danaparoid as alternative anticoagulation. The data from HIT patients and the control group were compared using t-test and chi-square test for continuous and categorical variables, respectively. The mean time of HIT diagnosis is on day 8 after the surgery. We observed a very low incidence of thrombosis in our HIT group, 22.2%. The p value comparing the rate of thrombosis in the two groups is on the limit of significance, N=97, p=0.04. There are no significant differences between groups comparing the rate of hemorrhagia and infections, N=97, p=1 and p=0.36. The rate of all complications is significantly higher in HIT group χ 2 =12.10, df=1, N=97,p= HIT is a serous disease, witch favored clinically important events in the postoperative setting of cardiac surgery. P2112 Patient s clinical characteristics according to clopidogrel and aspirin response tested in the cath lab during coronary stenting: data from the Verifynow french registry (Verifrenchy) C. Thuaire 1, G. Range 1, M. Kerkeni 2,R.Berthier 3, E. Teiger 4, J.P. Claudel 5, N. Delarche 6, P. Brunel 7, F. Albert 1, J.P. Collet 8. 1 Hopitaux de Chartres, Chartres, France; 2 Clinique Saint-Hilaire, Rouen, France; 3 Hôpital de Corbeil, Corbeil, France; 4 AP-HP - Hopital Henri Mondor, Creteil, France; 5 Infirmerie Prostestante, Lyon, France; 6 Hôpital de Pau, Pau, France; 7 Nouvelles Cliniques Nantaises, Nantes, France; 8 Pitie-Salpetriere Hospital (AP-HP), Paris, France Purpose: An impaired response to anti-platelet treatment is associated with an increased risk of adverse events after PCI. We prospectively evaluated clinical factors influencing clopidogrel and aspirin response in patients included in the Verifynow French Registry (Verifrenchy). Methods: Verifrenchy is a large prospective multicentric registry of 1001 patients undergoing coronary stenting in 20 French centers evaluating the aspirin and clopidogrel response tested with point-of-care method (Verifynow/Accumetric) in the cath lab. Non clopidogrel response was defined as P2Y12 platelet inhibition < 15%. Non aspirin response was defined as ARU 550. Results: In this cohort, 36% were clopidogrel non responder and 8.6% were aspirin non responder Significant Patients characteristics according to Clopidogrel and Aspirin response are listed below. Clinical factors/antiplatelet response Variable Total Clopidogrel Clopidogrel p-value cohort non responder responder n=1001 n=360 n=641 Age (years) 66,5 68,3 65,5 <0,001 BMI, kg/m 2 26,5 27,2 26,2 <0,001 Diabetes, n (%) 181 (18,1) 127 (35,3) 134 (20,9) <0,001 Current smoker, n (%) 181 (18,1) 49 (13,6) 132 (20,6) 0,02 Clopidogrel pretratment > one week, n (%) 534 (53,4) 152 (42,2) 383 (59,8) < 0,001 Clopidogrel loading dose (mg) 441,7 423,5 454,1 0,04 Aspirin non response, n (%) 84 (8,6) 47 (13,6) 37 (5,9) <0,001 Variable Total Aspirin Aspirin p-value cohort non responder responder n=972 n=84 n=888 Male gender, n (%) 807 (83,3) 78 (92,9) 729 (82,1) 0,03 Clearance creatinin (μmol/ml/mn) 81,6 88, Aspirin pre-treatment > one week, n (%) 660 (68) 47 (56) 613 (69,1) 0,02 ACE-inhibitor, n (%) 524 (53,9) 34 (40,5) 490 (55,2) 0,01 Beta-blocker, n (%) 699 (71,9)) 52 (61,9) 647 (72,9) 0,03 Statin, n (%) 783 (80,6) 59 (70,2) 724 (81,5) 0,01 Clopidogrel non response, n (%) 345 (35,5) 47 (56) 298 (33,6) <0,001 Conclusions: Despite the differences in clinical characteristics influencing these antiplatelet responses, there is a significant link between aspirin and clopidogrel non response suggesting an in vivo antiplatelet interaction. CONTROVERSIAL ISSUES IN THE MANAGEMENT OF ACUTE CORONARY SYNDROMES P2113 Metoprolol administration pre-reperfusion reduces infarct size by diminishing myocardial reperfusion injury B. Ibanez 1,G.Cimmino 1, S. Prat-Gonzalez 1, G. Vilahur 2, R. Hutter 1,M.J.Garcia 1,V.Fuster 1,J.Sanz 1,L.Badimon 2, J.J. Badimon 1. 1 Mount Sinai Hospital, New York, United States of America; 2 Hospital de Sant Pau, Barcelona, Spain The administration of metoprolol (MET) prior to coronary reperfusion has been shown to reduce myocardial infarction (MI) size; however the mechanisms of action remain elusive. In addition whether the oral post-reperfusion MET administration, as the current guidelines recommend, exert similar cardioprotective effect is unknown. Recent evidences suggest that myocardial reperfusion injury significantly contributes to the final size of MI The aims of the present work were 1) to study the effect of MET administration on myocardial reperfusion injury and 2) to assess whether early oral post-reperfusion administration results in similar cardioprotective effect than the i.v. pre-reperfusion administration Methods: Yorkshire pigs (n=30) underwent a MI by 90 min LAD coronary occlusion. Animals were randomized to one of the following 3 strategies: prereperfusion MET (7.5mg i.v. 60 pre-reperfusion followed by 50mg/12h oral), postreperfusion MET (placebo i.v. plus 50mg/12h oral), or non-met (placebo i.v. and no further medication). 12 animals (4/group) were sacrificed at 24h for reperfusion injury analysis (neutrophil infiltration, myocardial apoptosis, and degree of salvage kinases activation). The remaining pigs underwent a Magnetic Resonance Imaging (MRI) at 3d for area at risk (AAR, % of LV on T2-weighted images) and infarct size (% of AAR showing delayed enhancement after gadolinium) Results: Despite similar AAR on MRI in the 3 groups, MI size was significantly smaller in the pre-reperfusion MET group (69±4% of AAR) than in the postreperfusion MET (87±6%, p=0.036 vs. the pre-reperfusion) and the non-met (93±4%, p=0.002 vs. the pre-reperfusion and p=0.4 vs. the post-reperfusion). Neutrophil infiltration was significantly (p<0.05) lower in the pre- than in the postand the non-met groups (0.27, 0.56 and 0.54 MPO units). Myocardial apoptosis (cleaved caspase-3 by western blot) was significantly (p<0.05) lower in the pre- than in the post- and the non-met groups (114, 153, and 140 arbitrary units respectively). Salvage kinases activation (phosph-akt by western blot) was significantly (p<0.05) higher in the pre- than in the post- and the non-met groups (118, 91, and 96 arbitrary untis respectively). Conclusions: In a large animal model of MI, the pre-reperfusion i.v. metoprolol administration resulted in significantly smaller MI size than the post-reperfusion oral administration. The smaller MI size was observed along with a significant reduction in myocardial reperfusion injury. Our results suggest that circulating levels of metoprolol at the time of reperfusion are necessary in order to attain cardioprotection. P2114 Lower rate of invasive revascularisation in acute coronary syndrome patients with significant stenosis on coronary angiography when angiography is performed on a diagnostics only hospital A. Hvelplund 1, S. Galatius 2, M. Madsen 3, J.N. Rasmussen 1, S. Rasmussen 1, J.K. Madsen 2, S.Z. Abildstrom 4 on behalf of The DANAMICS group. 1 National Institute of Public Health, Copenhagen, Denmark; 2 Gentofte Hospital, Hellerup, Denmark; 3 University of Copenhagen, Inst. of Public Health, Copenhagen, Denmark; 4 Glostrup University Hospital, Glostrup, Denmark Purpose: We studied the population of all acute coronary syndrome (ACS) patients with a significant stenosis on their coronary angiography (CAG) in order to evaluate differences in invasive revascularisation rate related to type of hospital where CAG was performed. Denmark (population 5.5 million) has a universal health insurance coverage system and uniform national guidelines for the treatment of ACS. In Denmark there are 5 hospitals with tertiary invasive centres performing both percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). An additional 8 hospitals perform diagnostic coronary angiographies and a further 36 hospitals without these facilities receive patients with ACS. Methods: All patients hospitalised with a first ACS from January 2005 to December 2007 were identified in the National Patient Register. We included those patients who were found to have significant stenosis on their CAG, which was recorded in the Danish Heart Registry along with subsequent revascularisation. Information on comorbidity was also recorded. Information on education, personal income and vital status and previous medication was obtained from Statistics Denmark on an individual basis. Cox proportional-hazard models, with revascularisation within 60 days as outcome, was used to estimate the difference in revascularisation related to type of CAG hospital. Results: Of patients with first ACS in the period, were examined with CAG.

34 334 Controversial issues in the management of acute coronary syndromes Of 2207 patients having significant stenosis in one or more vessels from the diagnostics only hospitals there were 78% receiving revascularisation vs. 91% of the patients from the invasive hospitals. Adjusting for known differences between the groups such as gender, age, number of stenotic vessels and the other variables mentioned, there was a hazard ratio (HR) of 0.37 (95% CI , p < ) of receiving revascularisation for the patients examined with CAG in the diagnostics only hospitals in comparison to those examined in the invasive centres. Excluding the acute CAGs (day 0-1) we found 2070 patients having significant stenosis from the diagnostics only hospitals and 78% received revascularisation vs. 84% of the 4661 patients from the invasive hospitals. This gave a HR of 0.55 (95% CI , p < ). Conclusion: Patients hospitalised with a first ACS who have significant stenosis on their CAG are treated with a less aggressive invasive approach if the CAG is performed in a hospital with only diagnostic CAG facilities. The difference persists when excluding the acute CAGs which are more often performed in the invasive centres. P2115 Primary PCI with a new drug eluting stent: mid term results of multicentre NOBORI STEMI study F. Fath-Ordoubadi 1,A.Serra 2,Z.Xu-Ming 3, P. Laanmets 4, N. Jagic 5, J. Monsegu 6, D. Hildick-Smith 7, J. Guarinos 8, S. Hoffmann 9, G.B. Dnazi 10 on behalf of NOBORI STEMI study group. 1 Manchester Royal Infirmary, Manchester, United Kingdom; 2 Hospital del Mar, Barcelona, Spain; 3 Kiang Wu Hospital, Macau, Macau SAR, People s Republic of China; 4 North-Estonia Regional Hospital, Tallinn, Estonia; 5 Clinical Centre Kragujevac, Kragujevac, Serbia; 6 Val de Grace, Paris, France; 7 Sussex Cardiac Centre, Brighton, United Kingdom; 8 Hospital Joan XXIII, Taragona, Taragona, Spain; 9 Vivantes Netzwerk für Gezundheit GmbH, Berlin, Germany; 10 Ospedale Maggiore Policlinico, Milan, Italy Purpose: Use of drug eluting stents (DES) in patients presenting with ST elevation myocardial infarction (STEMI) is still controversial, despite their efficacy in reducing restenosis. Our aim was to study safety of a new DES, in this vulnerable population. Nobori stent employs biodegradable polymer and Biolimus A9 applied only abluminally. Once polymer is degraded and the drug is completely released this stent is expected to behave similarly to BMS. Therefore it is hypothesized that besides its proven efficacy this stent could have very good safety profile. Methods: NOBORI 2 is a multicentre study involving 125 centres across Europe and Asia. Out of the first 1000 consecutive patients treated with Nobori stent in this registry study 234 had STEMI while 524 had stable angina or silent ischemia (SA). Data were entered electronically and source data verification is planned for all patients. Primary endpoint is MACE (composite of death, MI, and TLR), at 6 and 12 months; secondary endpoints include rate of death/mi, stent thrombosis, TVR at 1, 6 and 12 months and yearly up to 5 years. Results: In the STEMI group, compared to the SA group, mean age (63±12 vs 64±10 years), sex (male: 79% vs 82%), proportion of diabetics (25.1 vs 31.1%), smokers (58 vs 51.1%), average number of lesions (1.37±0.64 vs 1.4±0.74), and stents per patients (1.65±1.18 vs 1.72±1.13) were comparable. However, patients with STEMI were less likely to have hypertension (53.9 vs 70%, p<0.001), dyslipidemia (56.4 vs 74.2%, p<0.001) and previous revascularisation (25.1 vs 44.8%, p<0.001). At 1 month follow-up hierarchical MACE rate was low in both groups (1.65 in STEMI vs 1.15% in SA). One patient (0.4%) died in the STEMI group, 3 patients (1.2%) had reinfarction and 1 patient (0.4%) underwent TLR. There were 5 MIs (0.9%) and 4 TLRs (0.8%) in the SA group. By the time of the presentation complete 6 months follow-up will be available, including adjudicated events and stent thrombosis. Conclusion: These preliminary data show a favourable outcome trend for Nobori stent in patients treated for STEMI. Longer term data will be available at the time of presentation. P2116 Procedural characteristics of radial versus femoral arterial access during primary percutaneous coronary intervention in STEMI patients W. Dorniak 1, G.D. Pinna 2, J. Klaudel 1,Z.Lajkowski 1, K. Pawlowski 1, W. Krasowski 1, G. Raczak 3. 1 St Wojciech-Adalbertus Hospital, Gdansk, Poland; 2 Fondazione S. Maugeri Clinica Del Lavoro e della Riabilizatione, Montescano, Italy; 3 Medical University of Gdansk, Gdansk, Poland Background: Primary percutaneous coronary intervention (PCI) in STEMI patients is usually performed via femoral artery. There are data suggesting that the hemorrhagic risk of the procedure can be significantly reduced if the radial artery approach is chosen. Safety and effectiveness of this approach are well documented for elective procedures, but concerns persist on the potential reperfusion delay when it is applied to STEMI pts. Aim: To assess the immediate angiographic results and duration of primary PCI for STEMI, performed via radial vs. femoral arterial access. Methods: 223 consecutive STEMI patients with <12 hour anginal pain, admitted to hospital between and , randomized to either femoral (n=107) or radial artery (n=116)approach. Patients randomized to radial approach were switched to femoral approach if arterial arch patency (Allen s test) proved abnormal. Results: Good immediate angiographic result (TIMI3) was achieved in 94% and 95% of patients in radial and femoral group, respectively ( p=0.99). Total procedural time and time to first balloon inflation [min] following the femoral or radial approach, were [median (interquartile range)] 37 (32-44) and 39 (32-45) (p=0.93), and 22 (19-25) and 22 (20-24) (p=0.92), respectively. Total cannulation time (patient lying on the table to arterial access) [min] was 7.8 ( ) and 8.2 ( ) in the femoral and radial group, respectively (p=0.40). Fluoroscopy time during angiography [min] was 0.9 ( ) and 1.2 ( ) for the femoral and radial approach, respectively (p< ). Total fluoroscopy time [min] was 5.9 ( ) and 6.1 ( ) for the femoral and radial approach, respectively (p= 0.75). The amount of contrast media [ml] used in both groups was very similar: 150 ( ) and 140 ( ); p= Betweengroup switch rate was 3% in initially femoral and 4% in initially radial group. Conclusion: These results show that radial approach is equally effective in terms of reperfusion rates and is not related to reperfusion delay as compared to femoral approach in STEMI patients treated by primary PCI. P2117 Longer distance from home to invasive centre is associated with lower rate of coronary angiographies following acute coronary syndrome A. Hvelplund 1, S. Galatius 2, M. Madsen 3, J.N. Rasmussen 1, S. Rasmussen 1, J.K. Madsen 2,S.Z.Abildstrom 4 on behalf of The DANAMICS group. 1 National Institute of Public Health, Copenhagen, Denmark; 2 Gentofte Hospital, Hellerup, Denmark; 3 University of Copenhagen - Institute of Public Health, Copenhagen, Denmark; 4 Glostrup University Hospital, Glostrup, Denmark Purpose: We studied the unselected population of all acute coronary syndrome (ACS) patients of an entire nation in order to evaluate differences in coronary angiography (CAG) rate. Denmark (population 5.5 million) has a universal health insurance coverage system and uniform national guidelines for the treatment of ACS. There are 5 tertiary invasive centres performing CAG, percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG), 8 hospitals with diagnostic units performing CAG only, and a further 36 hospitals without these facilities receiving patients with ACS. We investigated if there was a difference in the rate of CAG after admission with ACS depending on distance between place of residence and invasive centre. Methods: All patients, hospitalised with a first ACS from January 2005 to December 2007, were included from the National Patient Register. Age, gender and information on co-morbidity were recorded for each patient. Information on distance from each patients place of residence to the nearest invasive centre was obtained from Statistics Denmark along with information on education, family income, previous medicine use and vital status. Patients were grouped in tertiles according to distance to centre. Outcome was CAG within 60 days identified in the Danish Heart Registry. Cox proportional-hazard models were used to estimate the difference in the rate of CAG related to distance when adjusting for explanatory variables. Results: Of patients with first ACS 33% lived less than 21 km from one of the 5 invasive centres, 33% lived between km, and 33% >64 km away. Longer distance to an invasive centre was associated with less invasive examination after the event. The cumulative incidence of CAG was 77% for the third living closest to a centre vs. 68% for those living farthest away. When adjusting for patient characteristics such as gender, age, income, education, admission year, previous revascularisation, co-morbidity and medicine use there was a hazard ratio (HR) of 0.79 (95% CI , p < ) of receiving CAG for the patients living farthest away in comparison to those living closest to the centres. Conclusion: Despite uniform national guidelines, patients hospitalised with a first acute ACS are treated with a less aggressive invasive diagnostic approach the farther away they live from an invasive centre. When planning the management of ACS patients it is imperative that all parts of the healthcare system perform equally well so patients can rely on the same optimal treatment regardless of their place of residence. P2118 In-hospital management and outcome of Acute Coronary Syndromes (ACS) in developing countries: results of the ACCESS registry G. Montalescot 1, M. Sobhy 2,S.Alam 3, C. Martinez-Sanchez 4, A. Escobar 5, N. Antepara 6, J.C. Nicolau 7, P. Blondin 8, A. Leizorowicz 9. 1 Pitie-Salpetriere Hospital (AP-HP), Paris, France; 2 Alexandria University, Alexandria, Egypt; 3 American University, Beirut, Lebanon; 4 National Institute of Cardiology Ignacio Chavez, Mexico city, Mexico; 5 Clinica Medellin, Medellin, Colombia; 6 Hospital Universitario, Caracas, Venezuela; 7 Heart Institute (InCor) - University of Sao Paulo Medical School, Sao Paulo, Brazil; 8 Medical Affairs Department Sanofi Aventis Intercontinental, Paris, France; 9 Universite Claude Bernard, Lyon, France Purpose: Randomized studies and registries in ACS are usually performed in

35 Controversial issues in the management of acute coronary syndromes 335 developed countries which have substantial health care resources. ACCESS is the first large international ACS registry performed in developing countries. Methods and Results: 19 countries (Algeria, Argentina, Brazil, Colombia, Dominican Republic, Ecuador, Egypt, Guatemala, Iran, Jordan, Kuwait, Lebanon, Mexico, Morocco, Saudi Arabia, South Africa, Tunisia, United Arab Emirates, Venezuela) enrolled ACS patients, 6320 with non-st elevation ACS (NSTE-ACS) and 5411 with ST elevation myocardial infarction (STEMI). Mean age was 59.6 years, 75% were males and 74% were non-caucasians. Risk factors were dominated by active smoking (n=4730, 41%) and diabetes (n=4208, 36%) while 57% had hypertension, 42% dyslipidemia and 28% a BMI>30. Prior MI (22%), heart failure (5%), peripheral vascular disease (5%) and stroke (4%) were the most frequently found in medical history. Health insurance coverage was governmental in 51% but 25% patients had no insurance coverage at all. At admission, an ECG was performed in 99.2% but 7.3% had no necrosis biomarker measured neither at admission nor during hospitalization. In STEMI, fibrinolysis was used in 2127 patients (39.3%), predominantly streptokinase (n=1517, 71.7%); 26% of the STEMI patients had primary or rescue PCI within the first 24 hours. In NSTE-ACS, a coronary angiogram was performed during hospitalization in 59% of patients, a PCI in 31% and CABG in 7%. In PCI patients, 94% received at least one stent, 44% being drug-eluting stents. Aspirin (94%), clopidogrel (81%), beta-blockers (78%), statins (91%), ACE-inhibitors (68%) were largely prescribed. In contrast, GPIIbIIIa inhibitors (17%), bivalirudin (0.1%) and fondaparinux (0.1%) were rarely used. The in-hospital mortality rate was 2.6% (3.9% in STEMI, 1.5% in NSTEACS, p<0.0001). After multivariable analysis, the factors most strongly associated with death were age, high heart rate, low blood pressure, high killip class, type of ACS (STEMI), non-use of betablockers or ACE inhibitors, use of amiodarone or insulin. Conclusion: ACS in developing countries seem to occur at a younger age with higher rates of smokers and diabetics than in western countries. Management is somewhat more conservative with low intervention rates, use of less expensive drugs but higher use of DES than expected, with finally low in-hospital mortality. Statins and antiplatelet agents were widely prescribed. Betablockers, thienopyridines and ACE inhibitors were associated with improved survival. P2120 Intramyocardial percutaneous stem cell injection guided by endocardial mapping in patients early after acute myocardial infarction K. Krause, K. Jaquet, C. Schneider, B. Koektuerk, K.-H. Kuck. Asklepios Clinic St. Georg, Hamburg, Germany Background: Intramyocardial cell injection has been demonstated to have superior effects on cell distribution and tissue retention compared to the intracoronary approach in preclinical studies. This first-in-man study aims to implement PICI in patients early after acute myocardial infarction (AMI). Methods: On day 10.5±5 after AMI and PCI (culprit lesion: 18 LCA, 2 RCA) 20 patients (mean 60.4±11.4 years) received bone marrow derived mononuclear cells in the vital low voltage region of the infarction area using left ventricular electromechanical mapping (EMM). We injected 2.0± cells including 1.0± CD45-/CD34+ stem cells in each patient. In a subgroup of 15 patients EMM was performed at 6-month follow-up. Echocardiography, laboratory data and clinical assessment (6-month and 12-month follow-up) were performed in all 20 patients. Results: None of the patients showed periprocedural complications or major adverse events related to the PICI during the 12-month follow-up. Baseline normalized unipolar voltage UV improved from 45.5±14.3% to 59.3±19.2% in the infarction area (p=0.002) and reduction of the low voltage area from 28.7±12% to 20.3±13.5% (p=0.016) in 15 patients with EMM follow-up after 6 months. Endocardial electrogram fragmentation showed no increase in the area of injection. There was no sustained ventricular tachycardia documented in the Holter-ECG s. During the 12-month follow-up in all 20 patients LVEF improved from 40.8±6.8% to 47,0±10,5%. P2119 Distal protection with thrombectomy reduced death and onset of heart failure at chronic state in patients with reperfused anterior myocardial infarction S. Hosokawa, Y. Hiasa, S. Miyazaki, R. Ogura, T. Takahashi, K. Kishi. Tokushima Red Cross hopital, Komatsushima, Japan Background: Studies have found conflicting results regarding the efficacy of distal protection with thrombectomy. Objective: We sought to determine the effect of distal protection on heart failure for patients with acute anterior myocardial infarction undergoing primary percutaneous coronary intervention (PCI). Methods and Results: We performed 2D echocardiographic assessment 2 weeks (predischarge: baseline) and 6 months (chronic stage) after the onset of MI in consecutive 333 patients (114 patients with the distal protection: group DP, 219 without: group non-dp). Intravenous myocardial contrast echocardiography was underwent 2 weeks after PCI. Contrast defect was calculated as contrast defect area/myocardial area. All patients were followed for 4.25±0.7 years, and major adverse cardiac events (MACEs: death, re-hospitalization caused by heart failure) were found in 33 patients (10%). There are no significant differences between two groups in maximum CPK, ejection fraction and WMSI at baseline and 6month after PCI. However contrast defect of group non-dp was larger than that of group DP (15±11 vs 11±9, P=0.0034). Multivariate logistic analysis demonstrated that DP is independent negative predictor of MACEs after STEMI [RR (95%CI ), p=0.02]. Figure 1 Conclusions: These findings suggest that distal protection reduced death and onset of heart failure with reperfused anterior myocardial infarction. Distal protection preserves microvascular integrity; thus, it may represent a useful adjunct to pharmacotherapy EMM: injection points (dark spots) Conclusion: Intramyocardial percutaneous cell injection and left ventricular mapping in patients early after AMI was shown to be a safe procedure and is associated with improved electromechanical parameters and increased LVEF during a 12-month-follow-up. P2121 Proton Pump inhibitors and clopidogrel response on cardiovascular major events in patients after acute myocardial infarction. Data from the FAST-MI registry of the french society of cardiology T. Simon 1, P.H. Quandalle 2, J. Machecourt 3, R. Sader 4, L. Ledain 5, V. Bataille 6, P.H. Brunel 7,P.Djiane 8, J.M. Julliard 9, N. Danchin 10 on behalf of FAST-MI investigators. 1 APHP, Saint Antoine Hospital; UPMC-Paris 06, Paris, France; 2 Department of Cardiology, Roubaix, France; 3 Centre Hospitalier Universitaire de Grenoble, Grenoble, France; 4 Department of Cardiology, Laon, France; 5 Department of Cardiology, La Rochelle, France; 6 INSERM, Toulouse, France; 7 Nouvelles Cliniques Nantaises, Nantes, France; 8 AP-HM - Hopital de la Timone, Marseille, France; 9 Bichat-Claude Bernard Hospital (AP-HP), Paris, France; 10 European Hospital George Pompidou (AP-HP), Paris, France Background: Proton pump inhibitors (PPIs) are frequently administered in patients after AMI. Studies have suggested that co-prescription of PPIs with clopidogrel decreases the effect of clopidogrel on platelet activation due to a potential drug-drug interaction at the CYP 2C19 level. Aim: To assess in-hospital death and clinical major events at one year followup according to the use of PPIs alone or associated with clopidogrel in patients admitted for AMI. Methods: We analyzed data on the prescription of PPIs within 48 hours of admission and in-hospital death in 3059 patients enrolled in the French registry of Acute ST-elevation and non-st-elevation Myocardial Infarction (FAST-MI). Use of PPIs at hospital discharge and 1-year clinical outcomes were also analyzed among hospital survivors receiving clopidogrel. Results: PPIs were prescribed in 1922 (63%) of the patients (omeprazole (n= 1346), other PPIs (n= 576)) of whom 88% received also clopidogrel. Early use of PPIs was not a correlate of in-hospital death in patients with or without clopidogrel (OR =0.91; 95% CI: ). Among hospital-survivors, 2178 patients received clopidogrel of whom 1289 patients (59%) received PPIs at hospital dis-

36 336 Controversial issues in the management of acute coronary syndromes charge. At one year, death occurred in 6.6% and 5.1% of patients with or without PPIs, respectively. After adjustment, prescription of PPIs at discharge was not an independent correlate of events. Similarly, the rate of death, recurrent MI, stroke and hospitalization for bleeding did not differ with regard to the use of PPIs (10.6% vs 8.4% with or without PPIs respectively, p=0.34). No difference was observed between patients on omeprazole and those on other PPIs for the risk of in-hospital or one-year mortality. Conclusion: The use of PPIs in AMI patients had no effect on the clinical response to clopidogrel with regard to in-hospital death or death and major cardiovascular events at one year follow-up. P2122 Effect of thrombolysis with immediate transport to PCI vs. thrombolysis with ischemia-guided strategy on left ventricular function in ST-elevation myocardial infarction N. Mistry 1, E. Bohmer 2,P.Hoffmann 3, R. Bjornerheim 1, S.E. Kjeldsen 1, S. Halvorsen 1. 1 Department of Cardiology, Oslo University Hospital, Ullevål, Oslo, Norway; 2 Department of Medicine, Innlandet Hospital Trust, Lillehammer, Lillehammer, Norway; 3 Department of Radiology, Oslo University Hospital, Ullevål, Oslo, Norway Objectives: Treatment of acute ST-elevation myocardial infarction (STEMI) with prehospital or in-hospital thrombolysis is widely used in rural areas with long transfer delays to invasive centers. In this setting it is unclear which treatment strategy that best preserves left ventricular function. In the NORDISTEMI study (NORwegian Study on DIstrict Treatment of ST-Elevation Myocardial Infarction) we aimed to test the hypothesis that thrombolysis with immediate transport to percutaneous coronary intervention (PCI) results in better preserved left ventricular function compared to a more conservative, ischemia-guided strategy. Methods: 266 patients with STEMI of less than 6 hours duration and more than 90 minutes time delay to PCI were randomized to thrombolysis followed by PCI or thrombolysis followed by concervative strategy. Ejection fraction (EF), end systolic volume (ESV) and end diastolic volume (EDV) in the two treatment strategies were assessed by echocardiography, magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT) when clinically feasible, three months after the myocardial infarction. Results: EF ranged from 55 to 65% with the three different methods, but was literally identical in the two treatment strategies (table). ESV and EDV were also the same in the two treatment stategies. The median EDV (ml) in the conservative and in the early invasive strategy measured with echocardiography, MRI and SPECT was 108 vs. 106 (p=0.76), 157 vs. 162 (p=0.41) and 101 vs. 104 (p=0.34), respectively. Purposes: Pharmacological modulation of Monocytes activities represents an important strategy for the prevention and treatment of atherosclerosis. The study performed to analysis the possible anti-inflammatory mechanism of pioglitazone. Methods: A total of 97 subjects with ACS were entrolled into 12-week, prospective, open-label,double-blind, controlled clinical study. They were randomized to receive either pioglitazone (30mg QD) (n=42) or placebo (n=55) in addition to standard therapy. 21 subjects with non-chd chest pain and 20 healthy subjects also were observed. Clinical characteristics (age, heart rate, lipid profile, fasting glucose, blood pressure, etc.), inflammatory markers (high-sensitivity C- reactive protein,monocyte chemoattractant protein-1, tumour-necrosis factor-α, interleukin-6, soluble CXCL-16, soluble CD40 ligand, MMP-9) in plasm and expressions of CCR2 and TLR-4 on circulating monocytes were measured at baseline and after 12 weeks. Results: Levels of hs-crp, MMP-9, scxcl-16, IL-6,TNF-α, scd40l and MCP- 1 in patients with ACS were significantly higher than those in the two control groups (P<0.01). The frequencies of CCR2 or TLR-4 and both of CCR2 and TLR- 4 on CD14+ monocytes in patients with ACS were significantly higher than that in healthy and non-chd chest pain subjects,and expression of CCR2 is directly correlated with expression of TLR-4 on monocytes (r=0.229, P=0.027). Real-time PCR analysis showed that mrna expression of CCR2 and TLR-4 on monocytes in patients with ACS was higher than that of non-chd chest pain groups (P<0.01). Pioglitazone could decrease circulating leucocyte count, TG and plasm levels of hs-crp than placebo (P<0.05), and decreased levels of scd40l, MMP- 9, scxcl-16 and MCP-1 in plasm (P<0.05). Pioglitazone could lower expression of CCR2 and TLR-4 on monocytes (P<0.01), and only inhibit mrna expression of CCR2 on monocytes (P<0.01). Conclusions: Pioglitazone significantly reduces biomarkers of monocytes activation and levels of acute-phase reactants in ACS patients. Potential underlying mechanisms include direct modification of transcription within the monocytes. P2124 Pharmacologic inhibition of MyD88 ameliorates adverse cardiac remodeling and apoptosis after experimental acute myocardial infarction B. Van Tassell, F.N. Salloum, L. Smithson, A. Varma, N.H. Hoke, I.M. Seropian, C. Gelwix, V. Chau, A. Abbate. Virginia Commonwealth University, Richmond, United States of America Purpose: Myocardial ischemia activates an inflammation, apoptosis, and ventricular remodeling. Myeloid differentiation factor 88 (MyD88) coordinates the inflammatory response from Toll-like receptor and interleukin-1 (IL-1) receptor agonists. We evaluated the effects of pharmacologic MyD88 inhibition on left ventricular remodeling and cardiomyocyte apoptosis after experimental myocardial infarction (MI). Methods: ICR mice (male, n=21) were randomized to daily intraperitoneal injections with a IMG2005 (1 mg/kg, n=10) or saline (n=11) for 14 days following permanent coronary artery ligation. A second experimental group of ICR mice were randomized to pre-treatment with MyD88 small interfering RNA (sirna, 0.45 mg/g, n=3) or IL-1 receptor associated kinase inhibitor (IRAK, 0.1 mg/kg, n=3) for 7 days after the same infarction protocol. Echocardiography was performed at baseline, 7 days, and 14 days after surgery. Animals were then sacrificed for histologic evaluation of infarct size and cardiomyocyte apoptosis. Results: MyD88 inhibition, IRAK inhibition, and MyD88 sirna all reduced LV end-systolic and end-diastolic diameter. MyD88 inhibition also reduced cardiomyocyte apoptosis in the peri-infarct myocardium (0.3±0.1%) versus saline (1.4±0.4%, P<0.05). There was no difference in infarct size with treatment and a trend toward improved survival at 14 days after MI. Table. Ejection Fraction after 3 months Ejection Fraction Conservative strategy Early invasive strategy p-value Echocardiography (n=191) 55 ( ) 55 (49-62) 0.70 MRI (n=178) 57 (53-63) 57 (49-65) 0.87 SPECT (n=241) 65 (55-71) 63 (51-70) 0.41 Conclusion: Ejection fraction and left ventricular volumes assessed with echocardiography, MRI and SPECT three months post-myocardial infarction did not differ between the two treatment strategies. Our data suggest that, in patients with STEMI, an early invasive strategy following thrombolysis does not preserve left ventricular function better than a conservative strategy. P2123 The effects of pioglitazone treatment on inflammatory activity of monocytes in patients with acute coronary syndrome W.P. Zhang, Y. Wu, Y. Liu, Z.Y. Yuan. Department of Cardiology, the First Affiliated Hospital of Medical School, Xi an JIAOTONG University, Xi an, China, People s Republic of Conclusion: Pharmacologic MyD88 inhibition attenuates pathologic ventricular remodeling and cardiomyocyte apoptosis after MI without altering infarct scar formation, and may represent a novel translational approach for the prevention of heart failure after MI. P2125 Follow-up results after interventional treatment of infarct related saphenous vein graft occlusion R. Hoffmann, G. Nitendo, V. Deserno, M. Kelm, U. Adamu. Universitaetsklinikum Aachen, Medizinische Fakultaet der RWTH, Aachen, Germany Acute occlusion of saphenous vein grafts resulting in acute coronary syndromes may be treated by interventional revascularization. There are little data on intermediate and long term results after revascularization of acute saphenous vein graft occlusion. Methods: 50 patients (67±10 years, 47 male) with troponin positive acute coronary syndrome due to acute total or subtotal occlusion (TIMI flow 0=39, TIMI 1=8, TIMI 2=3) of one saphenous vein graft (12.0±5.3 years after surgery, 3.6±0.9 grafts) were treated by percutaneous coronary intervention (39 patients using bare metal stents, 11 patients using drug eluting stents). Clinical follow-up was obtained in all patients. Angiographic 6 month follow-up was performed in 35 patients (70%). Results: Acute revascularization of the infarct related saphenous vein graft (lesion length 17.6±10.3 mm, reference diameter 3.1±0.8 mm) was possible in 94% of patients. After a mean follow-up of 32.5±17.4 months 13 patients (26%) died, 13 patients (26%) had recurrent myocardial infarction and 20 patients (40%) had recurrent coronary revascularization (PCI or CABG). Angiographic follow-up demonstrated reocclusion of the vein graft in 3 cases (9%). 21% of lesions were found to be restenotic. Conclusion: Acute revascularization of an infarct related saphenous vein graft is possible in the majority of cases. Angiography demonstrates a high patency rate at 6 months follow-up. Still, the clinical prognosis of patients with revascularized infarct related saphenous vein graft is quite poor.

37 Controversial issues in the management of acute coronary syndromes 337 P2126 Long-term effects of music therapy on patients with acute myocardial infarction and previous revascularization; 7-year experience P.M. Mitrovic, B. Stefanovic, Z. Vasiljevic, M. Radovanovic, N. Radovanovic, G. Krljanac, D. Rajic, G. Matic, A. Novakovic, M. Ostojic. University Institute for Cardiovasculari Diseases, CCS, School of Medicine, Unversity of Belgrade, Belgrade, Serbia Unrelieved anxiety can produce an increase in sympathetic nervous system activity leading to an increase in cardiac workload. The purpose of this study was to evaluate the effectiveness of music therapy for reduction of new coronary events in patients with acute myocardial infarction (AMI) and previous revascularization. Methods: 740 patients (males 82.4%, mean age 58.9±7.2 yrs) with AMI after previous revascularization have been selected from the patients consecutively submitted from April 1990 to January The patients with early perioperative AMI were excluded from the study. The average time interval from CABS to AMI was 92.6±14 months. The average number of grafts was 3.2 grafts/pts. All patients were randomized and divided in 2 groups: Study group of 370 patients treated with music therapy and Control group of 370 patients with no music therapy. Each patient in study group underwent two sessions of medical therapy (12 minutes) in a day. Both groups were similar in baselines, post-ami characteristics and post-ami medical therapy. Results: Comparing parameters of Study and Control group of patients in 7-year follow-up period, Study group had lower anxiety score (r=-0.22, p=0.15) with statistically significant reduction in systolic blood pressure (p=0.0009), diastolic blood pressure (p=0.0008), heart rate (p=0.0046), heart failure expression (p=0.0014), angina (p=0.0048), reinfarction (p=0.0146), sudden deaths (p=0.0456) and reoperation (p=0.0028). Conclusion: This study provides support for the use of musical therapy in patients with AMI and previous revascularization to reduce blood pressure, heart rate and new coronary events expression. These effects of music therapy are probably because of decreasing in sympathetic nervous system activity. P2127 The effect of pioglitazone on arterial baroreflex sensitivity and sympathetic nerve activity in patients with type 2 diabetes mellitus after myocardial infarction H. Yokoe 1, F. Yuasa 1, T. Sugiura 2,T.Iwasaka 1. 1 kansai medical university, Osaka, Japan; 2 kochi medical university, Kochi, Japan Background: Pioglitazone has been shown to reduce the occurrence of fatal and nonfatal cardiovascular events in type2 diabetes mellitus (DM) after myocardial infarction (MI). However the mechanisms of such favorable effects remain speculative. The aim of this study was to investigate the effect of pioglitazone on the sympathetic and baroreflex function in the type2 DM patient after MI. Methods: Thirty patients with type2 DM after MI were assigned to a pioglitazone group (n=15) or control group (n=15). Baroreflex sensitivity (BRS) and muscle sympathetic nerve activity (MSNA) (microneurography at peroneal nerve) were measured at rest and during baroreceptor stimulation (phenylephirine infusion) and baroreceptor deactivation (nitroglycerin infusion). Insulin resistance and plasma adiponectin were measured. Insulin resistance was evaluated using the homeostasis model assessment insulin resistance (HOMA-IR). These measurement were performed at baseline and after 3 months. Results: Resting MSNA reduced significantly (from 37±7 to 25±8 burst/min; p=0.007) and BRS improved significantly (from 6.7±3.0 to 9.9±3.2 msec/mmhg; p=0.01) after pioglitazone. MSNA response to baroreceptor activation (change of integrated MSNA from -26±13 to-45±11%; p=0.001) and baroreceptor deactivation (change of integrated MSNA from 115±14 to 153±23%; p=0.01) improved significantly after pioglitazone. Adiponectin (6.9±3.3 to 12.2±7.1μg/ml; p=0.01) and HOMA-IR (4.0±2.7 to 2.1±0.9; p=0.006) improved significantly after pioglitazone. The change in resting MSNA was related significantly to the changes in HOMA-IR (r=0.6; p<0.05) and plasma adiponectin (r=0.7; p<0.05) after pioglitazone. However, there were no significant changes in measured variables in the control group. Conclusion: Pioglitazone treatment increased arterial BRS and decreased sympathetic nerve traffic through the improvement of insulin resistance and adiponectin in the patients with type2dm after MI, which indicate that the sympathoinhibitory effects of this agent may contribute to the benefical effects of pioglitazone in type 2 DM after MI. P2128 Implementation of the ESC guidelines on the management of AMI in community hospitals J. Ferrieres 1, J.B. Ruidavets 1, D. Arveiler 2, J. Dallongeville 3, B. Haas 2,M.Montaye 3, A. Bingham 4, V. Bongard 1, P. Ducimetiere 4. 1 Department of Cardiology B and Department of Epidemiology, INSERM U558, Toulouse University Hospital, Toulouse, France; 2 Department of Epidemiology and Public Health, Louis Pasteur University, Medical Faculty, EA 1801, Strasbourg, France; 3 Department of Epidemiology and Public Health, INSERM U744, Pasteur Institute of Lille, Lille, France; 4 IFR69, Paul Brousse Hospital, Villejuif, France Background: Guidelines should help physicians to make decisions in daily practice. However, discrepancies may exist between guidelines and their implementation in daily practice. So, ongoing audits are needed to ensure the appropriate implementation of guidelines. The aim of this study was to analyze management of acute myocardial infarction (AMI) in three population registries. Methods: In three areas of France (North, North-East, Southwest), we registered in 2006 all acute coronary syndromes (ACS) aged years, without any previous history of coronary heart disease, in the 3 former MONICA Registries of Lille, Strasbourg and Toulouse. We obtained precise data before, during and after hospitalization for all consecutive cases of ACS hospitalized in all hospitals covered by the 3 registries. In order to compare with the 2008 ESC guidelines on management of AMI, we restricted our analysis in patients (pts) with a discharge diagnosis of incident AMI. Results: Among 2018 incident ACS hospitalized in 2006, 1212 (60%) were discharged with a diagnosis of incident AMI. Mean age was 57.2±10.3, and 79.2% were men. The delay between symptom onset and first medical contact was <1 h in 25%, <2 h in 45% and <4 h in 59% of pts. The first medical contact was a physician-manned ambulance for 48% of pts. The delay between symptom onset and hospitalization was <1 hin8%,<2 h in 26% and <4 h in 53% of pts. Pre-hospital care included pre-hospital fibrinolysis in 10.6%, aspirin in 35.5% and clopidogrel in 15.1% of pts. Among all AMI, 74% were hospitalized in a percutaneous coronary intervention (PCI)-capable hospital and 53% had a primary angioplasty. During the first 24 h of hospitalization, 60.7% had PCI, 5.0% inhospital fibrinolysis, 89.2% aspirin, 86.2% clopidogrel, 66.0% β-blockers, 60.7% angiotensin-converting enzyme (ACE) inhibitors and 42.2% statins. Among all pts treated with PCI, 95.2% had stents and 28.4% drug-eluting stents. An impaired ejection fraction (<40%) was recorded in 9.8% of pts. Among discharged pts, 93.7% had aspirin, 86.3% clopidogrel, 87.0% β-blockers, 75.6% ACE inhibitors and 90.8% had statins. One month mortality was 6.0%. Conclusion: The management of AMI including emergency medical system, ambulance service, pre-hospital fibrinolysis, hospitalization in PCI-capable hospital, rate of PCI, discharge preventive drugs has greatly improved in France. However, the first medical contact often remains a general practitioner and about half of the pts are admitted at hospital more than 4 hours after symptom onset. Surveys of real-life daily practice are highly needed. P2129 Emergency department bypass reduces the time to reperfusion therapy V. Gomes, J. Trigo, P. Gago, J. Mimoso, R. Faria, N. Marques, W. Santos, V. Brandao. Hospital Central de Faro, Faro, Portugal Purpose: In patients (pts) with ST elevation myocardial infarction (STEMI) the reperfusion therapy (RT) is associated with better survival. The delay to RT remains too long. The pre-hospital emergency system- Green Way AMI (GWAMI)- with pre-hospital ECG, STEMI triage, emergency department (ED) bypass and direct admission to the Cardiology Department- aims to reduce the time to RT in STEMI. We evaluated the reduction of the time to RT in the pts admitted with STEMI through the GWAMI during 5 consecutive years ( ). Methods: We studied 1073 pts admitted with STEMI between 01/01/2004 and 30/11/2008.The pts were allocated in 2 groups according the admission: Group A (GA): Admitted through the GWAMI-390 pts (36%); Group B (GB): Admitted through the ED-683 pts (64%). The pts of the 2 groups were compared in the following parameters: age, sex, cardiovascular (CV) risk factors, CV event history, pre-hospital delay (PHD), in-hospital delay (IHD), RT and time door-toneedle/balloon (TD-N/B). We also consider the rate of pts who underwent RT in the recommended times: below 30 min to TD-N; bellow 90 min to TD-B. Results: The rate of pts admitted through the GWAMI was 11% in 2004, 13% in 2005, 30% in 2006 and 51% in 2007 and 64% in The mean age of the pts studied was 66±14 years, being 799 pts (74,5%) male. 69,9% of the pts were submitted to RT (fibrinolysis: 25,9% and primary angioplasty: 74,1%) with higher rate in GA (85,9% vs 60,8%, p< 0,0005). Significant reductions of the PHD, IHD and TD-NB were seen in GA. The rate of RT within the recommended times was significantly higher in GA (table). Group A Group B p PHD: median (Q25-75) 3h30 (2h17-5h47) 4h02 (2h03-10h03) <0,0005 TD-N: median (Q25-75) 0h14 (0h06-0h31) 1h07 (0h42-2h00) <0,0005 TD-B: median (Q25-75) 0h20 (0h15-0h33) 1h31 (1h03-2h26) <0,0005 TD-N<30 min (%) <0,0005 TD-B<90 min (%) <0,0005 Conclusion: The rate of pts admitted through GWAMI is increasing in this region. The GWAMI has had a very significant impact in the reduction of the pre-hospital delay, in-hospital delay and in the door-to-needle/balloon times, allowing increasing numbers of pts to be treated with early reperfusion therapy according to the recommendations.

38 338 Controversial issues in the management of acute coronary syndromes P2130 The effect of prehospital remote ischemic perconditioning on left ventricular function in STEMI patients treated with primary angioplasty: a randomised study K. Munk, N.H. Andersen, M.R. Schmidt, S.S. Nielsen, C.J. Terkelsen, E. Sloth, H.E. Botker, T.T. Nielsen, S.H. Poulsen. Aarhus University Hospital, Aarhus, Denmark Purpose: We have found that remote ischemic perconditioning (rperc) - i.e. episodes of nonlethal ischemia in a distant organ while the heart suffers lethal ischemia - administrated as an adjunct to primary percutaneous coronary intervention (ppci) - increases myocardial salvage in patients with acute STEMI. In the present study we assessed the effects of rperc on left ventricular function and remodeling. Methods: Among 260 patients with ongoing first STEMI randomized to rperc (5 periods of 5 minutes upper limb ischemia) during transfer to ppci versus ppci alone, early and/or late echocardiographic evaluation of LV function was performed in 227. Echocardiographic outcome measures were global systolic longitudinal strain of left ventricle (GLS, %) by speckle tracking, ejection fraction and LV volumes. Results: The two groups had similar baseline characteristics. For all patients, no difference in echocardiographic indexes of LV function early after ppci and after 1 month follow up was found. In high risk patients with first time LAD STEMI and no procedural and follow up adverse cardiac events (N=91) LV ejection fraction after 30 days was higher in the group of rperc vs. ppci alone (55.1±7.7%; 50.9±10.1%, respectively (p=0.049)). GLS showed borderline improvement in rperc treated patients (-16.4±2.9%) compared with patients treated with ppci alone (-14.9±3.4%) (p=0.055) after 30 days. P2132 Mortality reduction in acute myocardial infarction following organization of a regional network in a population of 1 million inhabitants with low-adherence to European guidelines I.S. Benedek, M. Chitu, I. Kovacs, A. Sarbu, M. Kurtinecz, C. Matei, S.Z. Madaras, G. Kozma, I. Benedek, T. Benedek. University Emergency Hospital Targu-Mures, Targu Mures, Romania Purpose: We followed the evolution of mortality in Acute Coronary Syndromes (ACS) in a period of 4 years during which all the cases recorded in a territory of 1 million inhabitants with low-adherence to european guide-lines were included in Regional Registry of ACS in Romania. Methods: The registry included 13 hospitals, having the closest interventional center at a maximum distance of 200 km. Population groups: gr.1 pts. presented at the territorial hospitals, without PCI facilities, gr. 2- pts. presented directly to the interventional center. Results: The registry included a total number of patients with ACS, out of which Acute Myocardial Infarction and Unstable Angina. The percentage of reperfusion therapy (primary PCI + thrombolysis) in gr.1 was 9.15% in 2004, increasing up to 17.16% in Only 0.3% of these patients were sent for primary PCI in the first year, this percentage increasing to 5.6% in the last year. In gr.2, reperfusion therapy was possible in 99.39% of cases, consisting in primary PCI in 76.96% cases, facilitated PCI in 15.75% cases and thrombolysis in 6.6% cases. Mortality rates in gr.1 showed a continuous decrease, from 20.77% in 2004 to 14.2% in 2008, correlated with the increase of reperfusion therapy (p=0.001). In group 2 global mortality was 6.6% for patients arrived in time for PCI, compared with 17.65% for patients with late arrival (>12 hours) (p<0.001). Conclusions: We succeeded to decrease the mortality rates in AMI in a territory of 1 million inhabitants from 20.77% to 14.2%, representing a 31.6% reduction in mortality for AMI patients presented in territorial hospitals without PCI facilities. This was mainly due to a complex educational and organizational activity which resulted in more than double rates of patients receiving reperfusion therapy and 18 times higher percentage sent to interventional center in 2008 compared with Still, the percentage of reperfusion therapy in the territorial hospitals remain very low in this region of Romania with very low adherence to european guidelines, reflected in high mortality rates. Left ventricular function - 30 days Conclusion: In this echocardiographic study, adjunctive treatment to ppci with prehospital rperc, improved LV function and remodeling after 1 month in high risk patients with first LAD STEMI. P2131 The radial approach reduces bleeding complications in STEMI patients without increasing the time to revascularization D. Arzamendi Aizpurua, J.F. Tanguay, H.Q. Ly, P. Lavoie-L allier, R. Ibrahim, Y. Reyna, R. Gallo, P. Deguise, G. Gosselin, S. Doucet on behalf of Group of Research in Interventional Cardiology from the Montreal Heart Institute. Montreal Heart Institute, Montreal, Canada Background: In the current era of reperfusion therapy, primary percutaneous coronary intervention (PPCI) combined with adjunctive antithrombotic therapy performed in a timely fashion has become the mainstay for ST elevation myocardial infarction (STEMI). Nevertheless, bleeding remains one of the major complications of these therapies and might be associated with an increase in mortality. Aim: To analyze the clinical impact of the radial approach on both the rate of bleeding and the time to revascularization in patients with STEMI undergoing PPCI. Methods: From April 2007 to March 2008, demographic, clinical and procedural data on all patients with STEMI referred for PPCI to the Montreal Heart Institute s cardiac catheterization laboratories were analyzed. Data were compared between each study group of patients undergoing PPCI either from a radial or a femoral approach. Results: Of the 488 patients included in the study, 236 (48.4%) patients underwent PPCI using the radial approach and the femoral approach was used in 252 patients (51.6%). No differences were found in baseline characteristics in terms of age, gender and cardiovascular risk factors. ST segment deviation, TIMI flow preprocedure and hemodynamic values at admission were comparable between both groups. Time from patients arrival to the cath-lab to puncture was of 8.15±4.5 minutes for the radial approach vs. 8.8±5.8 minutes for the femoral approach (p=0.15). Access site major bleeding was significantly higher in the femoral group vs. the radial group, 13.5% vs. 2.9% respectively (p<0.001). Using multivariable analysis, the femoral approach showed to be the main variable associated with an increased risk of bleeding with a HR of 5.86 (CI 95% ). Conclusions: In the setting of PPCI and adjunctive pharmacological therapies for STEMI, the radial approach was associated with a significantly lower incidence of major bleeding compared to the femoral approach, without compromising time to reperfusion. P2133 RADIal vs femoral approach with the usage StarClose for PCI for patients with Acute Myocardial Infarction. The RADIAMI II study, prospective, randomized, single center trial P. Chodor, T. Kurek, A. Kowalczuk, M. Swierad, T. Was, G. Honisz, A. Swiatkowski, W. Streb, Z. Kalarus. Silesian Center for Heart Diseases,Medical University of Silesia, Zabrze, Poland Background: The transradial approach for percutaneous coronary intervention (PCI) is associated with lower number of puncture site and bleeding complications, faster rehabilitation and better quality of life. These advantages were also identified for same available closure devices like StarClose clip. There is limited data of comparing transradial approach vs. transfemoral approach with the useage of closure device for PCI in acute myocardial infarction (MI). Methods: 108 patients with acute MI, symptoms <12hour, age <75 years, I and II Kilip-Kimbale class were randomly assigned to transradial approach (group I; n=49) or transfemoral approach with use of closure device at the end of the procedure (group II; n=59). We compare the timing of the procedure, angiographic results, serious cardiac events (MACE necessity of repeating the revascularization procedure in the infarct-related artery, a necessity of aortocoronary by-pass grafting, new onset of MI, death from any cause and stroke), bleeding complication, puncture site complications, time period of patient partial and full mobilization. Results: 108 patients were included in the study, 63.9% male, aged 59.6±10.04 years. Transfemoral approach was used in 2 (4.08%) patients belonging to group I and there was no need to use transradial approach in patients belonging to group II. Time intervals between patient s admission to hospital and artery puncture, balloon inflation, and total procedure timing in group I and group II were: 51.±22.1min vs. 40.4±16.3min (P=0.005); 67.4±17.1 vs. 58.0±17,4 (P0.015); 87.0±24.9min vs. 80.5±21.4min (P=0.163). TIMI 3 flow was achieved in 49 (100%) of patients in group I and 58 (98.3%) of group II. There were no significant differences in serious cardiac events (group I n=1 (2.1%) vs. group II n=1 (1.7%); P=NS) and bleeding complications (group I n=2 (4.2%) vs. group II n=2 (3.4%); P=NS). The mean period of time to partial and full mobilization in group I was 25.9±16.8 h. and 4.26±1.30 days vs 24.3±11.9 h. and 4.37±1.35 days in group II (both P=NS). Conclusions: The transradial approach compared to transfemoral approach for PCI in acute MI is associated with significantly increased of door to needle and door to balloon time. There were no differences in major cardiac events between both groups. The usage of StarClose clip after PCI allows to reduce the number of bleeding complication in this group as well as enables earlier initiation of rehabilitation comparable to transradial group.

39 Controversial issues in the management of acute coronary syndromes 339 P2134 Early versus late invasive strategy in successful thrombolysis reperfused acute myocardial infarction S. Champagne 1, D. Pongas 1, E. Aptecar 2, P. Dupouy 2, R. Cohen 3, S. Elhadad 3, J.L. Dubois-Rande 1, E. Teiger 1. 1 AP-HP - Hopital Henri Mondor, Creteil, France; 2 clinique les fontaines, Melun, France; 3 Centre Hospitalier General de Lagny-Marne-la-Vallee, Lagny/Marne, France New ESC guidelines recommend to perform angiography 3 to 24 hours after successful fibrinolytic therapy. However few convincing data exist about the optimal timing of PCI following successful reperfusion by thrombolysis. The aim of this study was to assess the prognosis of those patients in regard of the delay of PCI following successful thrombolysis. Methods: 204 consecutive patients were admitted in intensive care unit for definite reperfused acute myocardial infarction from 3 institutions. Two groups were defined according the delay of PCI from thrombolysis: early (<24 hours; n= 132) versus late (>24 hours; n=72). End point of the study was the rate of in hospital MACCE, defined as death, Congestive heart failure (CHF), haemorrhagic stroke and Re infarction (Re MI). Results: Baseline clinical and angiographic characteristics were similar between two groups.there was a non significant trend of 12.5% MACCE in the early group versus 9% in the late group (p= 0.13). Re MI occurred more significantly in the early group (6.7%) than in the delay (1.4%); p< In hospital Death was 1.6% in the early group and 0% in the delay group (p = 0.6). CHF occurred in 10.6% in the early group and in 7.5% in the delay (p= 0.6). No haemorrhagic stroke was noted. See table. Clinical characteristics and outcomes Early PCI (n=132) Delay PCI (n=72) p Age, yr 56.4± ± Previous MI 7% 12% 0.2 Time from PCI, day 0 6.3±9.6 Death 1.6% Re MI 6.7% 1.4% < CHF 10.6% 7.5% 0.6 Haemorrhagic strokes 0 0 MACCE 12.5% 9% 0.1 Data are expressed as seam ± SD or as number (percentage) except as indicated. Conclusion: Early PCI (<24 hours) in successful thrombolysis reperfused acute myocardial infarction seems to be harmful even in the delay recommend by the new ESC guidelines because of increased re infarction. It might be safer to postpone PCI more than 24 hours after the thrombolysis when the pro thrombotic status related to fibrinolysis is over. P2135 Efficacy of statin therapy in patients with acute myocardial infarction is determined by polymorphism of enos gene promoter Y.A. Lutay 1, A.N. Parkhomenko 1, V.E. Dosenko 2, A.A. Moibenko 2. 1 NSC The M.D. Strazhesko Institute of Cardiology, Kiev, Ukraine; 2 Institute of Physiology, Kiev, Ukraine The benefits of statins have been demonstrated in patients with stable coronary artery disease and non ST elevation acute coronary syndromes (ACS). These benefits, however, have not been well documented in patients with ST-segment elevation acute myocardial infarction (STEMI). The aim of this study was to analyze the impact of early statin therapy upon hospital complications in patients with STEMI depending on genotypes of enos gene promoter. 162 patients with recent ST elevation MI were investigated. The enos gene polymorphism has been analyzed by PCR-RFLP analysis. 70 patients were treated with statins (atorvastatin 20 mg or simvastatin 40 mg) in addition to standard treatment since the first hours of ACS and 92 patients did not received statins until discharge. Genotype distributions of enos TT, TC and CC genotypes in promoter region were 0.40 (N =28), 0.46 (N = 32) and 0.14 (N = 10) in statin group and 0.46 (N =42), 0.44 (N = 40) and 0.11 (N = 10) in controls, respectively. Groups were similar regarding baseline characteristics and concomitant treatment. -786TT genotype of enos gene promoter was associated with decreased risk of recurrent ischemic events (myocardial infarction and post-mi angina) and acute heart failure during the period of hospitalization in statin treated patients. While there were no benefits of early statin treatment in patients with TC, CC and both (TC+CC) genotypes. Patients with -786TT genotype of enos gene promoter should be the target for early statin therapy after acute ST elevation MI. P2136 Early statin treatment prior to primary PCI for acute myocardial infarction: a randomized placebo controlled trial S. Post 1,M.C.Post 2, F.D. Eefting 2, M.J. Goumans 3, M.A. Bosschaert 2, P.R. Stella 3,F.H.DeMan 3,B.J.Rensing 2, P.A. Doevendans 3. 1 St Antonius Hospital Nieuwegein and University Medical Centre, Utrecht, Netherlands; 2 St Antonius Hospital, Nieuwegein, Netherlands; 3 University Medical Center Utrecht, Utrecht, Netherlands Purpose: Early statin therapy might reduce reperfusion injury, which develops after primary percutaneous coronary intervention (PCI) following acute myocardial infarction (AMI). The aim of this study was to determine whether early atorvastatin treatment will reduce left ventricle (LV) remodelling, infarct size and improve microvascular perfusion. Methods: Forty-two consecutive patients (82% male, mean age 61.2±9.8) who underwent a primary PCI for a first ST-elevated AMI were randomized for pretreatment with atorvastatin 80 mg (n=20) or placebo (n=22), continued for one week. All patients received atorvastatin 80 mg once daily seven days after primary PCI. The LV function and infarct size were measured by MRI (1.5 T Philips ) within 1 day, after 1 week and at 3 months follow up. The primary endpoint was the end-systolic volume index (ESVI) at 3 months. Secondary endpoints were global LV function measurements, myocardial infarct size, biochemical markers, TIMI flow and ST-T elevation resolution. Results: ESVI three months after AMI was 25.0 ml/m 2 in the atorvastatin arm and 25.0 ml/m 2 in the placebo arm (p=0.84). Overall, the differences in change from baseline to 3 months follow up, in global LV function and myocardial infarct size did not differ between both treatment arms. Furthermore, biochemical markers, TIMI flow and ST-T elevation resolution did not differ between atorvastatin and placebo arm. Conclusion: Pre-treatment with atorvastatin in an acute myocardial infarction does not result in an improved cardiac function, microvascular perfusion or decreased myocardial infarct size. P2137 Germany Reperfusion hemorrhage: a new therapeutic target in ST-elevation myocardial infarction A. Kumar 1,J.D.Green 1, V. Sabhaney 1, S. Poeschko 2,R.Dietz 2, M.G. Friedrich 1. 1 University of Calgary, Calgary, Canada; 2 Charite - Campus Buch, Franz-Volhard-klinik, HELIOS Klinikum, Berlin, Introduction: Reperfusion injury in myocardial infarction leads to microvascular obstruction, which can occur with or without hemorrhage. The incidence and implications of reperfusion hemorrhage are not well investigated. Purpose: We performed an in vivo study in patients with acute reperfused STEMI to assess the relationship of hemorrhage to microvascular obstruction, infarct size and functional parameters using cardiovascular magnetic resonance. Methods: 19 patients (age 56±11years, 3 female) with ST-elevation myocardial infarction were recruited in a tertial referral centre, and a comprehensive CMR study was performed to assess tissue injury on day 6±4 post reperfusion therapy using a protocol to quantify LV functional parameters (cine SSFP CMR), hemorrhage (T2*w-CMR), microvascular obstruction (early post-contrast CMR) and infarct size (late enhancement). Results: From 19 patients with STEMI, 10 had microvascular obstruction with hemorrhage (MO+H+ group), 3 had microvascular obstruction without hemorrhage (group MO+H ), and 6 had myocardial infarction not complicated by microvascular injury (group MO ). These groups were not different for major clinical parameters including TIMI risk score and time to reperfusion. There were no patients with hemorrhage but without MO. In patients with hemorrhagic infarction (MO+H+), hemorrhage was smaller than the amount of MO (7.3±6.4g of hemorrhage vs. 12.2±6.9g of MO), and hemorrhage was located in the subendocardium of the MO zone, occupying a mean of 58.6±31.2% of the MO zone. Hemorrhage occurred in the largest infarcts of this study only, and infarct size in the hemorrhage group was larger than in both other groups (infarct size MO+H+ 61.9±24.6g, MO+H 14.9±8.6g, MO- 12.6±4.4g, p<0.05 for MO+H+ vs. both other groups). Hemorrhagic infarcts had a larger MO zone than infarcts with MO but without hemorrhage (amount MO MO+H+ 12.2±6.9g vs. MO+H 2.2±2.1g, p<0.05). Overall, hemorrhage was observed exclusively in patients who had infarction involving more than 25g of myocardial necrosis and more than 5g of microvascular obstruction. This was also reflected in significantly worse functional parameters (LV ejection fraction and LV end-systolic volume) in the hemorrhage group compared to both other groups MO+H and MO. Conclusion: Reperfusion hemorrhage is associated with larger infarct size, larger amount of microvascular obstruction and worse functional parameters. Hemorrhage should therefore be considered a new therapeutic target in acute STelevation myocardial infarction. P2138 Early vs. late referral for coronary angiography after thrombolysis for STEMI G. Almpanis, P. Davlouros, G. Vagenakis, Z. Kopsida, K. Sheffneux, M. Papathanasiou, G. Hahalis, A. Mazarakis, J. Chiladakis, D. Alexopoulos. University of Patras, Patras, Greece Purpose: To investigate any difference in outcome between patients with STelevation myocardial infarction (STEMI) subjected to coronary angiography (CAG) early (within 24 hours post-thrombolysis) vs. late (> 24 hours), within a health network serving approximately 1.5 million people in western Greece. Methods: Retrospective analysis and telephone follow-up of all thombolysed STEMI patients referred for CAG to our hospital from January 2005 till June Results: OUt of 437 thrombolysed STEMI patients referred for CAG, 127 (29.1%), (Group-A), were refered within 24 hours post-thrombolysis and 310 (70.9%), (Group-B), >24 hours post-thrombolysis (6.91±5.2days). Group-A pa-

40 340 Controversial issues in the management of acute coronary syndromes / Echocardiography in cardiomyopathy tients were younger (57.95±12 vs ±11 years, p=0.006), had less frequently non significant CAD (3.9% vs 10% p=0.036), more frequently one vessel disease (60.6% vs 45%, p=0.006), and were subjected to PCI more frequently (85% vs 69.2%, p <0.001) compared to group-b. The latter were more frequently treated conservatively (7% vs 15.5%, p=0.018). Coronary risk factors were similar between the two groups. Telephonic follow-up regarding MACE (major coronary events: death, myocardial infarction, revascularisation, reinfarction), was conducted at 30.3±11.8 months. Death occured in 7.8% of Group-A patients vs 5.8 group-b patients (p=0.273), reinfarction in 1.5% vs 1.9% (p=0.576), revascularisation with PCI in 4.7% vs 3.8% (p=0.430), revascularisation with coronary bypass-grafting in 5.5% vs 1.9% p=0.051, CAG without intervention in 2.3% vs 2.2% (p=0.594) and the combined MACE occurred in 23.6% vs 18% (p=0.117). Conclusion: Despite the ESC guidelines for early referral for CAG postthrombolysis, this practice was applied infrequently in our area in the past four years. However early vs. late CAG referral groups did not differ in mortality, or major cardiovascular events. P2139 ECHOCARDIOGRAPHY IN CARDIOMYOPATHY Prognostic implications of left ventricular dyssynchrony early after non-st elevation myocardial infarction without congestive heart failure C.T.A. Ng, D.T. Tran, C. Allman, J. Vidaic, D.Y. Leung. The University of New South Wales, Sydney, Australia Purpose: To determine the independent predictors of left ventricular (LV) dyssynchrony after non-st elevation myocardial infarction (NSTEMI), and predictive value of dyssynchrony for long term LV dysfunction. Methods: LV dyssynchrony was performed in 100 NSTEMI patients (age 60.0±11.8 years, 71 men) using 4 dyssynchrony parameters at baseline. Coronary angiography was performed in 97 patients with 70% diameter stenosis defined as significant. Repeat echocardiography was performed at 6 and 12 months. Results: Early LV dyssynchrony was independently predicted by presence of significant proximal left circumflex artery stenosis and global systolic function. LV end-diastolic volume index decreased with time (47.1±14.2 vs 46.4±13.6 vs 43.1±12.8 ml/m 2,p<0.001) and was independently predicted by lower number of diseased vessels and absence of early dyssynchrony. LV end-systolic volume index decreased with time (23.5±12.3 vs 22.1±10.9 vs 20.2±10.2 ml/m 2, p<0.001), and was independently predicted by absence of early dyssynchrony, lower number of diseased vessels and revascularization. LVEF increased with time (52.1±11.0 vs 53.8±10.2 vs 54.8±9.7%, p=0.014), and was independently predicted by absence of early dyssynchrony, lower number of diseased vessels and revascularization. Figure Conclusions: After NSTEMI, proximal left circumflex artery stenosis independently predicted LV dyssynchrony. Early LV dyssynchrony independently predicted persistent lower LVEF and larger LV end-systolic volume index at baseline and follow-up. P2140 Early detection of functional abnormalities in asymptomatic arrhythmogenic right ventricular cardiomyopathy gene carriers using echocardiographic deformation imaging A.J. Teske, M.G. Cox, B.W. De Boeck, P.A. Doevendans, R.N. Hauer, M.J. Cramer. University Medical Center Utrecht, Department of Cardiology, Utrecht, Netherlands Purpose: The first presentation of arrhythmogenic right ventricular cardiomyopathy (ARVC) is often potentially lethal ventricular arrhythmias originating from the right ventricle (RV), typically at a young age. This emphasizes the importance of an early recognition of this disease, for instance in ARVC- family members. The aim of this study is to evaluate the value of tissue deformation imaging to detect subclinical RV functional abnormalities in asymptomatic genotyped carriers of ARVC. Methods: A total of 43 asymptomatic first degree family members of ARVC probands (not fulfilling the diagnosis of ARVC according to the task-force criteria (TF-c)) were prospectively enrolled for echocardiographic examination. In a total of 14 (38.0±13.2 years), a genetic mutation (PKP2) could be identified (others had no mutation or genetic screening). All individuals were age-matched with 4 controls (n=56, 38.2±12.7 years) undergoing the same echocardiographic evaluation (dimensions, global systolic parameters, visual assessment, and deformation imaging of the RV free wall). Echocardiographic evaluation was performed blinded. Deformation analysis was analyzed blinded to group and findings from the conventional echocardiogram. A peak systolic strain >-18% and/or postsystolic shortening (post-systolic index >15%) in any segment was considered abnormal. Results: No significant differences in baseline characteristics were seen between the groups. RV dimensions in the family group were similar to the controls (RVOT 15.4±2.9 vs. 14.4±1.9 mm/m 2, RVIT 18.6±2.6 vs. 19.1±2.6 mm/m 2,p=NS). Global systolic parameters were moderately reduced in the family group (TVI-syst 9.1±1.6 vs. 11.1±1.7 cm/s, TAPSE 20.0±3.2 vs. 23.9±2.8 mm, p<0.001). On visual assessment (according to the TF-c), a major criterion was scored in 4 (20%) and 3 (5%), and a minor in 4 (20%) and 13 (23%) of family members and controls, respectively. Mean TDI and 2D-strain deformation (-rate) values were reduced in the ARVC family members in the basal and mid RV segment. A peak systolic strain of >-18% was seen in 6 family members (43%) and post systolic strain in 10 (71%). Either abnormality was observed in 11 (79%), almost exclusively in the basal segment, and in non of the controls. 2D-strain showed abnormal segments in 8 (57%) of family members and 5 (9%) controls. Conclusion: Echocardiographic deformation imaging detects functional abnormalities in the basal RV segment in almost 80% of asymptomatic ARVC gene carriers. Furthermore, false positive findings in visual assessment (28%) could be prevented since all showed normal deformation values and patterns. P2141 Identification and characterization of super-responders to cardiac resynchronization therapy: an echocardiographic study A. Zaroui 1, P. Reant 1, E. Donal 2, A. Deplagne 1, A. Mignot 1, P. Bordachar 1, A. Solnon 2, C. Leclercq 2, R. Roudaut 1, S. Lafitte 1. 1 Hopital Cardiologique Haut-Leveque, Bordeaux, France; 2 CHU de Rennes - Hopital de Pontchaillou, Rennes, France Background: In some patients, cardiac resynchronization therapy (CRT) has been recently shown to induce a spectacular effect on left ventricular (LV) function and inverted remodelling with nearby normalization of LV contraction. Objectives: To analyze and characterize super-responders (CRTSR) by echocardiography before CRT using conventional and dedicated tools for contractility assessment such as strain techniques. Methods: 186 patients have been investigated in 2 French specialized centers before and 6 months after implantation of a CRT device accordingly to ESC guidelines. Echocardiographies including measurements of LV dimensions, function and contraction by 2-dimensional strain, right ventricular function and pressure assessment, mitral valve analysis were performed at baseline and at 6 months by an independent core-center lab. CRTSR were defined as a reduction of endsystolic volume of at least 15% and an ejection fraction (EF)>50% and were compared to conventional responder patients (CRTCR, patients with a reduction of end-systolic volume of at least 15% but an EF<50%). Results: 18/186 patients (9.7%) were identified as CRTSR, only 2/18 patients had ischemic cardiomyopathy (p<0.01). No difference was observed regarding NYHA status, EKG duration or EF between CRTSR and CRTCR at baseline. CRTSR presented with significant lower end-diastolic and end-systolic diameters (64±8mm vs 70±8mm (p<0.01) and 54±7mm vs 59±9mm (p<0.01), respectively), and end-diastolic and end-systolic volumes (149±46ml vs 182±68ml (p<0.02) and 117±42ml vs 137±59ml (p<0.01)), lower left atrial volume (50.4±28 vs 77±41.5, p<0.001), and higher LV dp/dtmax (796±312mmHg s -1 vs 688±256 mmhg s -1 (p<0.05)). Regarding strain analysis, CRTSR had significantly higher longitudinal values than CRTCR (-12.8±3% vs -9±2.6%, p<0.001) whereas no difference was observed for other components (p ns). ROC curves identified global longitudinal strain as the best parameter for predicting CRTSR with cut-off values of -12% (Se=71%, Spe=85%, AUC=0.87, p<0.0001). The multiparametric logistic regression identified global longitudinal strain >-12% and left atrial volume <50mL as independent predictors of CRTSR (OR: 14.1; CI at 95%:3.8; 25.3; p<0.004 and OR: 1.3, CI at 95%:1.1; 2.8; p<0.01, respectively). Conclusion: In a large multicenter study, CRT super-responders (EF>50%) were observed in 9.7% of the population and were associated with less-depressed LV function as determined by strain analysis. Global longitudinal strain appears to be the best predictor of CRTSR. P2142 Use of tissue Doppler velocity as an index of global myocardial function in atrial fibrillation with preserved left ventricular ejection fraction H.J. Yoon, H. Kim, C.D. Han, H.S. Park, H.T. Kim, Y.K. Cho, C.W. Nam, S.H. Hur, Y.N. Kim, K.B. Kim. Keimyung University DongSan Hospital, Daegu, Korea, Republic of Background: Although atrial fibrillation (AF) has been reported to be a risk factor

41 Echocardiography in cardiomyopathy 341 in cardiovascular adverse event, the relationship of AF to the prognosis of AF with preserved ejection fraction is still uncertain. We evaluated the relationship between tissue Doppler-derived index including conventional echocardiographic parameters and clinical outcomes of AF by retrospectively cross-sectional study. Methods: One hundred forty eight patients with permanent AF who had preserved ejection fraction were included in this study. Clinical data were obtained and echocardiographic study was performed. Development of clinical events was defined as the composite of cardiovascular death, readmission of heart failure and ischemic stroke. Results: During the mean follow-up time of 2.2 years, there were 35 clinical events (2 deaths, 22 heart failures, and 11 ischemic strokes). In univariate analyses, age, ejection fraction, systolic mitral annular velocity (Sm), early diastolic annular velocity (Em) and left atrial dimension were correlated to clinical events. Multivariate regression analyses identified three significant parameters: patients with events demonstrated significantly lower Sm, Em and larger left atrial dimension as compared to those without events. Furthermore, patients with both Sm > 5 cm/s and Em > 7cm/s were significantly free of clinical endpoint (odds ratio=2.63, 95% CI , p=0.001). Kaplan-Meier Survival Curve Conclusions: In AF with preserved ejection fraction, tissue Doppler indexes, reflected by Sm and Em, were found to be the most powerful predictor of cardiovascular events. P2143 Strain ST-T change on the electrocardiogram reflects subendocardial dysfunction: Demonstration using 2D speckle tracking echocardiography M. Takeuchi 1, T. Nishikage 1,H.Nakai 1,V.Mor-Avi 2, R.M. Lang 2, Y. Otsuji 1. 1 University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan; 2 The University of Chicago Medical Center, Chicago, United States of America Purpose: Strain ST-T change on the surface ECG might reflect subsendocardial dysfunction. 2D speckle tracking echocardiography has the potential for the assessment of left ventricular (LV) strain and twist profile. We hypothesized that strain ST-T change is associated with (1) the preferential reduction of longitudinal strain and (2) the reduction of both clockwise twist at early systole and untwisting during early diastole and (3) the paradoxical augmentation of peak twist due to subendocardial dysfunction. Methods: 3 levels of LV short axis views and 3 LV apical views were acquired in 46 hypertensive patients with LV hypertrophy diagnosed by 2D echocardiography and 23 age-matched control subjects. Using 2D strain software, longitudinal, radial and circumferential strain was measured. Time domain LV twist curve was generated from the basal and the apical short-axis views, from which clockwise twist at early systole, end-systolic twist and untwisting values at early diastole was determined. Patients were divided into two groups according to the presence (n=18) or absence (n=28) of strain ST-T change on the 12-lead ECG. Results: No significant differences of LV ejection fraction were noted among the three groups. Longitudinal strain was significantly reduced in patients with strain ST-T change (-13.4±3.2) compared to those without strain ST-T change (-17.4±3.4, p<0.001) or control subjects (-19.9±2.0, p<0.001). Radial and circumferential strain was also significantly lower in patients with strain ST-T change compared to control subjects. Although LV twist at end-systole was similar between patients with strain ST-T change and those without ST-T change (16.2±6.7 degree vs. 15.1±4.1 degree), clockwise LV twist at early systole (0.03±0.91 degree vs ±1.01 degree, p<0.0167) and LV untwisting (10% of diastole: 3.0±11.0% vs. 14.7±17.8%, p<0.0167, 20% of diastole: 26.1±31.1% vs. 47.5±25.6%, p<0.0167) was significantly depressed in strain ST-T change group compared to no ST-T change group. Conclusions: The reduction of longitudinal strain, early systolic clockwise twist and LV untwisting variables in patients with strain ST-T change reflect subendocardial dysfunction, which can be assessed by 2D speckle tracking echocardiography. P2144 Attenuated coronary flow reserve is associated with subtle changes in left ventricular diastolic function among healthy individuals P. Kamvrogiannis 1, E. Alexandridis 1, G. Karayannis 1, G. Giamouzis 2, H. Parissis 1, A. Chamaidi 1, G. Sitafidis 1, J. Skoularigis 1,J.Butler 2, F. Triposkiadis 1. 1 Department of Cardiology, Larissa University Hospital, Larissa, Greece; 2 Emory University Hospital, Atlanta, United States of America Background: Coronary flow reserve (CFR) may be reduced in healthy individuals in the presence of major cardiovascular risk factors. The purpose of this study was to examine whether depressed CFR is associated with sub-clinical LV diastolic dysfunction in this population. Methods: A total of 101 consecutive asymptomatic individuals (age 52.5±13.2 years; 68% male; election fraction 62±6%) with normal resting ECG and at least one major risk factor formed the study population. Transthoracic two-dimensional and Doppler echocardiography was performed on all individuals. To evaluate left ventricular (LV) diastolic function the following parameters were determined: mitral E/A ratio, deceleration time, E/E average ratio of septal and lateral annular velocities, isovolumic relaxation time (IVRT), and left atrial volume index (assessed with the biplane area-length method). Phasic coronary flow velocities were obtained in the left anterior descending coronary artery at rest and during hyperemia (0.15 mg/kg/min adenosine triphosphate infusion IV). CFR was estimated from the ratio of hyperemic/baseline diastolic velocity. Based on CFR values, patients were divided into three groups: normal CFR (group A, CFR 2.5, n=60), borderline CFR (group B, 2.5>CFR 2.00, n=26), and abnormal CFR (group C, CFR<2.00, n=15). Diastolic function indices were compared in the three groups with one-way analysis of variance. Results: See Table. Parameter Group A Group B Group C E/A 1.13± ± ±0.53 Deceleration time, msec 205±46 205±38 195±56 Isovolumic relaxation time, msec 85±11 88±15 94±12* E/E average 8.4± ± ±3.1 Left atrial volume index, cm 3 /m ± ± ±7.0 *p<0.05 vs. A; p<0.01 vs. A; p<0.05 vs. B/ Conclusions: CFR is often impaired in healthy individuals in the presence of major cardiovascular risk factors and is associated with sub-clinical LV diastolic dysfunction, characterized by prolongation of IVRT and increased left atrial size. These findings suggest that more aggressive risk factor treatment in this group may delay onset of clinical HF. P2145 Echocardiographic assessment of left ventricular diastolic pressures validated using an implantable pressure sensor T.C. Poerner, B. Goebel, E. Luthardt, C. Schmidt-Winter, S. Otto, J. Gummert, H.R. Figulla. Universitaetsklinikum Jena, Jena, Germany Background: Noninvasive assessment of left ventricular (LV) diastolic pressures in patients with heart failure is essential for clinical decision making and adjustment of therapy. Aim of the study was to evaluate the accuracy of echocardiographic estimation of LV mean diastolic (LVMDP) and end-diastolic (LVEDP) pressures against intraventricular pressure measurements from an implantable manometer. Methods: Permanent LV pressure sensors (Transoma LVP-1000) were implanted in 5 patients with poor LV function, who underwent cardiac surgery. All devices were verified again 6 months later using Millar catheters and showed no measurement errors. In this time interval patients were followed-up several times, performing a total of 21 simultaneous echocardiographic examinations and pressure readings from the Transoma device. Results: Results are summarized in Table 1. Early mitral velocity E enabled a slightly better estimation of LVMDP compared to the indices E/E and E/A. Values of E >85 cm/s predicted LVMDP >12 mmhg with a sensitivity of 83% and specificity of 87%, respectively. On the other hand, the ratio E/A was the best predictor of elevated LVEDP (E/A >1: 71% sensitivity and 83% specificity for LVEDP >15 mmhg). Table 1 Parameter Echocardiographic Echocardiographic assessment of LVMDP assessment of LVEDP Linear Prediction of Linear Prediction of Correlation LVMDP > 12 mmhg Correlation LVEDP > 15 mmhg E r=0.60; p=0.003 AUC=0.927; p=0.002 r=0.48; p=0.016 AUC=0.821; p=0.026 E/A r=0.56; p=0.005 AUC=0.901; p=0.003 r=0,45; p=0.025 AUC=0.839; p=0.019 E/Eprop r=0.169; p=n.s. AUC=0.604; p=n.s. r=0.26; p=n.s. AUC=0.714; p=n.s. PVr-A r=0.64; p=0.012 AUC=0.667; p=n.s. r=0.58; p=0.024 AUC=0.565; p=n.s. E/E r=0.23; p=n.s. AUC=0.875; p=0.005 r=0.36; p=n.s. AUC=0.786; p=0.048 AUC: area under ROC-Curve, E: early mitral inflow velocity (cm/s), A: late mitral inflow velocity (cm/s), E : early diastolic mitral annulus velocity (cm/s), PVr-A: difference in duration between pulmonary venous regurgitation and mitral A wave (ms), Eprop: propagation velocity of early mitral inflow (cm/s).

42 342 Echocardiography in cardiomyopathy Conclusions: In patients with systolic heart failure conventional Doppler parameters of mitral inflow proved to be robust enough for a quick and noninvasive assessment of elevated filling pressures. P2146 Echocardiographic predictors of global systolic strain in patients with heart failure H. Dokainish, J. Nguyen, M. Alam, N. Lakkis, M. Stampehl. Baylor College of Medicine, Houston, United States of America Background: There are few data on the echocardiographic correlates of left ventricular speckle-based global systolic strain (GSS) in patients with heart failure (HF), and whether GSS can be depressed in patients with preserved LVEF. Methods: Patients with HF underwent comprehensive echocardiography. In the 3 apical views, speckle-based automated functional imaging (AFI) was utilized to obtain GSS using General Electric EchoPAC software. Univariate and multivariate predictors were determined using linear regression analysis. Results: 177 patients were studied, with mean age of 56.5±8.9 years; 60/118 (51%) were female, 103 (87%) were hypertensive, 47/118 (40%) were diabetic, and 59/118 (50%) had known coronary artery disease. The mean left ventricular ejection fraction (LVEF) was 36.4±16.7%. Fifty-two (30%) of patients had LVEF 45%, of whom 27/52 (52%) had GSS<16% (previously published lower limit of normal). In the entire population, the best echocardiographic correlates of GSS were LVEF (R=0.66), followed by mitral annular systolic velocity (Sa, R=0.63), mitral annular late diastolic velocity (Aa, R=0.51), LV mass (R=0.45), LV end-diastolic dimension (R-0.45), mitral annular early diastolic velocity (Ea, R=0.44), E/Ea (R=0.33, p<0.001), and left atrial volume (R=0.28, Figure). In a multivariate model, independent predictors of GSS (R=0.76 for combined model) were LVEF (p<0.001), Aa (p<0.001), Ea (P=0.002), and LV mass (0.005). Figure 1. Correlation of GSS with LVEF Conclusions: In patients with HF, global systolic strain (GSS) is depressed in a significant proportion who have preserved LVEF. Among all patients, independent predictors of GSS were systolic, diastolic and morphologic variables. These data suggest that GSS may provide information on myocardial systolic performance beyond that provided by LVEF. P2147 Semi-automated left ventricular function assessment by real-time three-dimensional echocardiography is ready for prime time O.I.I. Soliman 1,B.M.VanDalen 1,M.L.Geleijnse 1, W.B. Vletter 1, A.M. Al-Amin 2, F.J. Ten Cate 1. 1 Erasmus MC - Thoraxcenter, Rotterdam, Netherlands; 2 Al-Azhar University, Cairo, Egypt Objectives: To investigate the inter-observer agreements of real-time threedimensional echocardiography (RT3DE) assessment of the left ventricular (LV) function in real-world practice. Background: RT3DE provides accurate LV function with a good variability between two expert observers. However, the variability between several observers with varying degrees of experience, a real-world practice, is yet to be determined. Methods: Twenty patients (mean age 50±15 years, 13 men) in sinus rhythm with a wide range of LV function (from normal to severe heart failure) underwent RT3DE full-volume acquisition of LV. Ten blinded observers performed off-line 3DE LV function analysis with varying degrees of experience in RT3DE. Eight observers analysed all datasets twice after limited early experience (< 20 cases of acquisition and analysis) and after advanced learning (>50 cases of acquisition and analysis). Two experts with several hundred cases of acquisition and analysis analysed all datasets twice within 12 weeks. Semi-automated border detection with bi-plane projections was performed using semi-automated software with a minimal manual interference according to a standard protocol. Inter- and intra-observer variability among non-experts was calculated as coefficient of variation and as percentage of absolute difference from average measurement. Linear regression was used to test interclass correlation between non-experts and experts. Results: The volume rate of 3DE datasets ranged from 30 to 37 Hz (mean 35 Hz). Mean global LV end-diastolic volume, LV end-systolic volume, and the LV ejection fraction were 169 ml, 103 ml, and 40%, respectively. Experts interand intra-observer variability was 5%, 3% for LV end-diastolic volume, 6%, 4% for LV end-systolic volume, and 7%, 5% for the LV ejection fraction, respectively. Experts interclass correlation was 0.98, 0.97, 0.96 for LV end-diastolic volume, LV end-systolic volume, and the LV ejection fraction, respectively. Coefficient of variation among non-experts was 5±6% vs. 3±1% for global LV end-diastolic volume, 8±7% vs. 5±2% for LV end-systolic volume, and 11±13% vs. 5±3% for the LV ejection fraction during early and late experience, respectively. Linear correlations (R2 = 0.89, 0.88 and 0.87 vs. 0.95, 0.94 and 0.93) between experts and non-experts improved during advanced experience for global LV end-diastolic volume, end-systolic volume and ejection fraction, respectively. Conclusions: RT3DE provides, fast, simple, reproducible assessment of LV function after a short learning curve. P2148 Strain rate imaging demonstrates impaired regional right ventricular deformation in adult unoperated patients with Marfan syndrome A. Kiotsekoglou 1, G.R. Sutherland 1, J.C. Moggridge 1, V. Kapetanakis 1, B.H. Bijnens 2, M.J. Mullen 3, N. Bunce 1, D.K. Nassiri 1,A.J.Camm 1, A.H. Child 1. 1 St. George s University of London, London, United Kingdom; 2 Catholic University Leuven, Leuven, Belgium; 3 Royal Brompton Hospital, London, United Kingdom Introduction: Marfan syndrome (MFS) is an autosomal dominantly inherited connective tissue disorder caused by mutations in the fibrillin-1gene that encodes for the protein fibrillin-1. Fibrillin-1 has been identified as a regulator of transforming growth factor-β (TGF-β) bioactivity in the extracellular matrix. TGF- β dysregulation has been linked to reduced left ventricular (LV) stroke volume in the MFS mouse model. LV dysfunction has also been demonstrated in humans but little attention has been paid to the right ventricle (RV). We aimed to assess RV function in adult unoperated patients with MFS. Methods: Forty-three patients with MFS (mean age 30±12 years, 25 men and 18 women) and 49 normal controls without significant differences in age, sex and body surface area from the patient group were examined. No patient had more than mild valvular disease. All subjects underwent an echocardiographic examination at rest. Dp/Dt was measured for all patients. 2D colour Doppler data was recorded using a 4-chamber apical view to evaluate longitudinal systolic strain/strain rate (εsys/srsys) in the RV free lateral wall. Diastolic strain rate was also assessed in the same region. Measurements were averaged over 3 consecutive cardiac cycles. Results: Values are presented as mean ± SD. Dp/Dt values were significantly lower in patients with MFS compared to normal controls (746.79± mmhg vs ± mmhg, p < 0.001). Both longitudinal εsys and SRsys were significantly reduced in the basal, mid- and apical segments of RV free lateral wall in patients with MFS when compared to normal controls (p < 0.001). Diastolic strain rate values were also significantly lower in the MFS group (p < 0.001). In a multiple regression analysis including age, sex, heart rate and pulmonary systolic pressure, MFS was negatively associated with reduced RV free lateral wall regional deformation (p < 0.001). Conclusion: These findings suggest reduced regional RV systolic and diastolic deformation in patients with MFS. This could be attributed to fibrillin-1 deficiency in the cardiac extracellular matrix. Treatment may need to be tailored to prevent further deterioration by supporting RV function. P2149 Global strain, functional capacity and outcome in patients with dilated cardiomyopathy G. Karatasakis, A. Dimopoulos, E. Leontiadis, E. Andreanides, G. Athanasopoulos, S. Polymeros, D.V. Cokkinos. Onassis Cardiac Surgery Center, Athens, Greece Introduction: Global strain (GS) and strain rate (GSR) of the left (LV) and right (RV) ventricle offer new possibilities for the evaluation of ventricular function. The relation of these new indices to functional capacity and patients outcome has not been elucidated. Methods: We studied 34 pts (age years) with previously diagnosed dilated cardiomyopathy (DCM) with LVEF< 40%. They all underwent complete echocardiographic and TDI study for the evaluation LV ejection fraction by the Simpson s rule, longitudinal GS and GSR of the LV and RV and circumferential strain (CS) of the LV. They also underwent cardiopulmonary exercise test for the evaluation of O2 consumption (VO2). Study end- points (EP) were defined as: 1. cardiac death, 2. heart transplantation (TX) and 3. ventricular assist device (LVAD) implantation. Pts were followed up for 28±8 months. Results: During follow up 6 pts had LVAD implantation 2 orthotopic cardiac TX and 2 pts died. Two of the LVAD pts had subsequent cardiac Tx. Pts that reached EP during follow up had lower VO2 (12.±3.6 vs 22±4.6 ml/kg/min p=0.0001), LVEF (23±11 vs 35±10%, p=0.0001), GS of the LV (-4.2±3.8 vs -11.7±5.1%, p=0.0001), GSR of the LV (-019±0.29 vs -0.65±0.26 1/s, p=0.0001), GS of the RV (-16.4±7 vs -26.2±9%, p=0.0001), GSR of the RV (-1.1±0.6 vs -1.5±0.3 1/s, p=0.001) and CS (-4.8±2.2 vs 8.3±3.7%, p=0.001). Overall VO2 was related to GSLV (r=0,64, p=0.0001), GSRLV (r=0.52, p=0.001), GSRV (r=0.52, p=0.002), GSRRV (r=0.047, p=0.000), and CS (r=0.56, p=0.003). and Str (r=0.58, p=0.001). By stepwise logistic regression, among univariate predictors of endpoints, Str was the only independent predictor of pts outcome (p=0.021)

43 Echocardiography in cardiomyopathy 343 Conclusion: In pts with DCM and compromised ventricular function, global longitudinal and circumferential strain are lower in pts that are going to die or need TX and LVAD implantation during F/U. Functional capacity expressed by VO2 is related to longitudinal and circumferential global strain of both ventricles. GSLV (p=0.047) and GSRV (p=0.035) were the only independent predictors of outcome while EF had no prognostic value. Aims: Accurate quantification of left ventricular (LV) volumes and ejection fraction (EF) is of critical importance. MRI is considered as the reference and then we sought to compare standard two-dimensional echocardiography (2DE), threedimensional echocardiography (3DE) and left ventricular angiography for LV volumes and EF assessment, relative to cardiac magnetic resonance imaging (MRI) in heart failure patients. Methods: We studied 24 patients (17 men, age 58±15 years) with history of heart failure who underwent echocardiographic assessment of LV volumes and function as well as cardiac catheterisation. All patients underwent 2DE followed by 3DE (Full volume real-time 3DE images were acquired from apical views with the ie33 ultrasound system (Philips Medical system), and analyzed using a QLAB workstation with a semi-automated endocardial border detection software), LV angiography and MRI in a 48-hour delay. No patient was excluded from the study due to poor image quality. Results/Discussion: The heart failure etiology was: 41,7% (n=10) ischemic cardiomyopathy, 50% (n=12) dilated idiopathic cardiomyopathy and 8,3% (n=2) of patients suffered from heart failure with preserved EF. The mean LV end-diastolic volume (LVEDV) evaluated by MRI was 208±108mL (121±64 ml/m 2 ), mean EF 31±13% and mean LV end-systolic volume (LVESV) was 149±97 ml. LVEDV was underestimated by 3DE (mean LVEDV 153±49 ml) and left ventricular angiography (mean LVEDV 157±52mL). 3DE data sets highly correlated with MRI, especially concerning EF (r: 0.86, 0.88, and 0.96 for LVEDV, LVESV, and EF, respectively) with small biases (-55 ml, -44 ml, 1,1%) and acceptable limits of agreement. 2DE measurements correlated less well with MRI (r: 0.70, 0.82, 0.84), which correlated well with LV volume evaluation on angiography. The 3DE-derived LV volumes are underestimated in most of our patients with severe LV dysfunction, and 3DE data sets do not correlate as well as expected. We didn t exclude patients with poor echocardiographic windows, sometimes with LV not totally accommodated within the pyramidal volume of acquisition. We then determined that with a LVEDV below 240 ml, 3D was more accurate for volumes and EF evaluation. We can therefore apply our results in the everyday life of heart failure, with real patients. Conclusion: Compared with MRI, 3DE is a good method to evaluate LVEF, but it appears to underestimate significantly LV volumes (especially when LVEDV 240mL) with the problem of foreshortened apical views in heart failure patients: as LVEDV increase, 3D accuracy simultaneously decrease. P2150 Myocardial tissue Doppler echocardiography and atorvastatin in heart failure M. Correale, M. Ceglia, N.D. Brunetti, A. Libertazzi, R. Ieva, M. Di Biase. University of Foggia, Foggia, Italy Background: Observational studies, prospective studies and posthoc analyses of randomised clinical trials have suggested that statins could be beneficial in patients with chronic heart failure. Statins have pleiotropic effects beyond reducing the low-density lipoprotein-cholesterol concentration. Recent studies have explored the prognostic role of TDI-derived parameters in major cardiac diseases, such as heart failure. In these conditions, myocardial mitral annular (S ) systolic and early diastolic (E ) velocities have been shown to predict mortality or cardiovascular events. In particular, those with reduced S or E values of <3cm/s have a very poor prognosis. In heart failure noninvasive assessment of LV diastolic pressure by transmitral to mitral annular early diastolic velocity ratio (E/E ) is a strong prognosticator, especially when E/E is > or =15. This study sought to determine whether treatment with atorvastatin affects left ventricular dysfunction in patients with chronic heart failure, using newly developed ultrasonic tissue Doppler imaging. Methods and Results: A total of 236 patients (aged 68,24±12,87 years; 152 were male) with chronic heart failure were randomized to either administration of atorvastatin (118 patients: aged 67,36±11,58; male 79%; LVEF: 37,59±11,70%) or no atorvastatin therapy (118 patients: aged 63,65±16,56; male 80%; LVEF: 41,30±13,07%) for 12 months. Conventional echocardiography Doppler was used to assess left ventricular (LV) ejection fraction, peak velocities of transmitral early and late diastolic LV filling, the ratio of transmitral early to late LV filling velocity, and E-deceleration time. TDI measurements recorded at the mitral annulus included systolic velocity (S ), early (E ) and late (A ) diastolic velocities, and the ratio of early to late diastolic velocity (E /A ). The transmitral to mitral annular early diastolic velocity ratio (E/E ) was calculated. Results: During the follow-up period (12±2 months), patients in the atorvastatin group showed lower E/E ratio (13,62±8,33 vs 20,95±7,91, P < 0,05), and higher early (E ) diastolic TDI velocity of the mitral annulus at septal annulus (P < 0,05), compared with the no atorvastatin group. Conclusions: One year of atorvastatin treatment improved LV function in patients with chronic heart failure. Tissue Doppler Imaging has the potential to become a sensitive tool for detecting the effects of early medical intervention on myocardial dysfunction in this patient population. P2151 Assessment of left ventricular function in heart failure: limits of real-time three-dimensional echocardiography in real life P.Moceri,D.Bertora,P.Gibelin.CHU de Nice - Hopital Pasteur, Nice, France P2152 Correlation of Doppler echocardiographic parameters and N-terminal B-type Natriuretic Peptide (NT-BNP) levels in elderly patients with systolic heart failure A. Bernheim 1,S.Y.Min 1, M. Wachter 1, D. Jenny 2, M. Neuhaus 2, P. Mussio 3,L.Joerg 4,M.Pfisterer 1, H.P. Brunner-La Rocca 1, P. Buser 1 on behalf of TIME-CHF investigators. 1 University Hospital Basel, Basel, Switzerland; 2 Kantonsspital Baden, Baden, Switzerland; 3 Spital Bülach, Bülach, Switzerland; 4 Kantonsspital St. Gallen, St. Gallen, Switzerland Purpose: Doppler echocardiography and brain-type natriuretic peptide (BNP) have been proposed for the non-invasive estimation of intracardiac filling pressures and the assessment of cardiac performance. Little is known about the correlation between Doppler echocardiography and BNP in patients shortly after stabilization for decompensated systolic heart failure (SHF). Methods: NT-BNP levels and echocardiographic parameters were assessed at baseline in 391 patients (mean age, 76±8 years) with SHF (left ventricular ejection fraction [LVEF] 45%). Estimation of LV filling pressures was derived from the ratios of the early transmitral inflow velocity (E) to the mitral annular velocity of the septal (E/e septal) or the lateral (E/e lateral) annulus. Systolic right ventricular to atrial pressure gradients (RVPG) were measured as an estimate of systolic pulmonary artery pressures. Tricuspid annular motion (TAM) served as a marker of RV function. Results: Median values of NT-BNP and Doppler echocardiographic data are presented in Table 1. NT-BNP showed a significant, but weak association with E/e septal (r=0.17, p=0.009). For E/e lateral (r=0.11, p=0.1) and LVEF (r=-0.07, p=0.21), no correlation with NT-BNP was observed. NT-BNP and E/e septal exhibited a similar correlation with RVPG (NT-BNP: r=0.29, p<0.0001; E/e septal: r=0.28, p<0.0001) and an inverse relation to TAM (NT-BNP: r=-0.19, p=0.0002; E/e septal: r=-0.16, p=0.01). Table 1 NT-BNP (median, interquartile range), pg/ml 4406 ( ) LVEF, % 30±8 E/e septal 20±11 E/e lateral 16±12 TAM, mm 15±5 RVPG, mmhg 34±11 Abbreviations as indicated in text. Conclusions: E/e septal showed a significant relation to NT-BNP. Moreover, both parameters were linked to increased pulmonary artery pressures and decreased RV function. However, the correlation between Doppler echocardiographic parameters and NT-BNP levels was unexpectedly weak. This implies that in elderly patients with SHF, the noninvasive assessment of the cardiac filling state may be less accurate than previously thought and factors other than cardiac performance are likely to importantly influence NT-BNP levels. P2153 Usefulness of 2D speckle tracking echocardiography in carcinoid heart disease N. Mansencal, E. Mitry, P. Rougier, O. Dubourg. APHP - Hopital Ambroise Pare, Boulogne, France Background: Carcinoid heart disease (CHD), which is mainly defined as a valvular heart disease, may occur in patients presenting with digestive endocrine tumor and carcinoid syndrome. The most frequent presentation of CHD is a right-sided CHD and may be associated with right ventricular enlargement. Velocity vector imaging (VVI) is a new echocardiographic technology that measures myocardial velocity and deformation using 2D speckle tracking. The aim of this study was to compare the pattern of VVI in pts with CHD and in healthy pts. Methods: We prospectively studied 60 pts divided in 2 groups: 30 pts with CHD (group 1) and an age- and sex-matched control group (n=30, group 2). All pts with CHD had histologically proven digestive endocrine tumor and carcinoid syndrome. Quantification of CHD severity was performed according to a previous validated scoring system (score between 0 and 20). We systematically performed transthoracic echocardiography in all patients, with the use of VVI technology, allowing to measure systolic peak velocity (V), peak strain (S) and peak strain rate (SR) in basal, mid and apical right ventricular free wall in apical 4-chamber view. Right ventricular systolic function was also assessed by the right ventricular fractional area change (FAC) measured in apical 4-chamber view. Results: Values of V, S and SR in basal, mid and apical right ventricular free wall (FW) were significantly lower in group 1 as compared to control group (p<0.02 for basal FW and p<0.01 for mid and apical FW). Mean CHD score of severity was 10.7±4.6. In patients with lowest tertile of CHD score, no significant difference occurred between group 1 and group 2, concerning global values of V, S and SR, whereas patients with highest tertile of CHD score presented with the most

44 344 Echocardiography in cardiomyopathy important right ventricular systolic dysfunction. Strong correlation was found between CHD score of severity and global values of V (r=0.90, p<0.0001), whereas correlation between CHD score and FAC was weak (r=0.42, p=0.04). Conclusion: Our study suggests that VVI could be of interest in patients with CHD, allowing to quantify right ventricular systolic function. Right ventricular systolic dysfunction in CHD is related to the degree of valvular severity. P2154 Characterization of myocardial deformation in hypertrophic cardiomyopathy using speckle tracking: a comparison with physiological hypertrophy H. Badran 1, M. Saber 2, A. El-Sherif 2, A. Farhan 2,Y.Nassar 2, S. Moktar 2, M. Yacoub 3. 1 Menoufiya University, Shebin, Egypt; 2 Cairo University, Cairo, Egypt; 3 Imperial College London, London, United Kingdom Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disorder that is characterized not only by the growth of cardiomyocytes, but also by changes in cardiac architecture and cellular metabolism and, finally, by myocardial dysfunction. strain (ε)/strain rate (SR) imaging, using speckle tracking, has been shown to be a more sensitive technique for quantifying regional myocardial deformation (RMD). Objective: This study was designed to characterize global and regional myocardial deformation using 2-dimensional strain and SR imaging in HCM and compare it to physiological hypertrophy in athletes. Methods: The study population comprised 21 patients with HCM (mean age 26.2±6 years) with asymmetric septal hypertrophy (IVS = mm) and 34 age matched athletes with IVS >12 mm. Apical four -chamber view was displayed; 2D RMD using speckle tracking was used to measure longitudinal peak systolic strain (εsys), peak systolic SR [SRsys], time to peak (ε) [TTP], post systolic strain (εpss) and intra-ventricular systolic delay (intra-v delay). These parameters were quantified in basal, mid and apical segments of septal and lateral walls of the left ventricle. Results: RMD of LV segments was significantly reduced in HCM patients in comparison to corresponding segments in athletes, (p <0.001). (εsys) and SRsys of the basal (-8.5±5.5%, -0.7±0.5 sec-1) and mid (-4.8±7.5%,-0.57±0.5 sec-1) segments were significantly lower than apical septal (21.6±21%, 1.62±0.6 sec-1) and all lateral segments [-14.4±6.9%, -1.1±0.4 sec-1, -11.7±5%, -0.77±4.2 sec- 1, 12.3±6.4%, -0.75±0.5 sec-1 respectively (p <0.001) in HCM patients, while myocardial deformation was normal and almost homogenous in athletes. εpss was detected in more than one segment in 67% of HCM patients but not in athletes. The latter showed homogeneous systolic activation of the ventricular walls. Furthermore, HCM group, showed significant increase of the intra-v systolic delay between segments which is more prominent in septal than in lateral wall. The standard deviations (SD) of intra-v delay obtained from septal segments were greater in HCM compared to athletes (42±12 versus 7±3 ms in septal segments and 51±10 versus 3±2 ms, in lateral segments respectively, p <0.001). Conclusion: The non uniform distribution and magnitude of LV hypertrophy in patients with HCM, is associated with disorganized contraction and regional heterogeneity of myocardial systolic function. Deformation analysis using speckle tracking is a novel ultrasonic technique that helps to differentiate mechanical dysfunction in HCM from myocardial adaptation in physiologic hypertrophy. P2155 Usefulness of contrast echocardiography in Tako-Tsubo cardiomyopathy N. Mansencal, A. Lamar, A. Beauchet, R. El Mahmoud, R. Pilliere, O. Dubourg. APHP - Hopital Ambroise Pare, Boulogne, France Background: Assessment of left ventricular (LV) dysfunction in Tako- Tsubo cardiomyopathy (TTC) is of importance. Biplane LV angiography wellcharacterizes this dysfunction, but is invasive. The aim of this prospective study was to assess the reliability of contract echocardiography in TTC. Methods: We prospectively studied 50 women divided into 2 groups: 25 consecutive patients with TTC (group 1) and 25 patients with proved coronary artery disease (CAD) (group 2). Groups 2 was age- and sex-matched with group 1. All patients underwent coronary arteriography, biplane LV angiography, conventional transthoracic echocardiography and contrast transthoracic echocardiography less than 24 hours after the onset of symptoms. Gold standard for LV systolic function assessment was LV angiography. Results: Mean age of patients with TTC was 73±11 years. Mean angiographic LVEF was 38±9%. LV segments were well-classified as having (or not) wall motion abnormalities in 70% and 88% by observer 1 using conventional and contrast echocardiography, respectively (p < ), and in 91% and 99% by observer 2 using conventional and contrast echocardiography, respectively (p < ). In patients with TTC, LVEF was 42±11% assessed by conventional echocardiography (versus 38±9% by LV angiography, p < ) and 38.2±8.5% using contrast agent (p = 0.42, as compared to LV angiography). Sensitivities and specificities for the diagnosis of TTC by observer 1 were respectively 56% and 64% using conventional echo versus 88% and 84% using contrast agent. Sensitivities and specificities for observer 2 were respectively 72% and 88% using conventional echo versus 96% and 96% using contrast agent. Accuracy for the diagnosis of TTC was significantly improved using contrast echocardiography for both observers, whereas interobserver agreement was excellent using contrast agent (kappa = 0.85 versus 0.34 using conventional echocardiography). Conclusion: We demonstrated that contrast echocardiography is an accurate imaging method for a non-invasive assessment of left ventricular systolic function in TTC. P2156 Incremental value of subclinical left ventricular systolic dysfunction for the identification of patients with obstructive coronary artery disease G. Nucifora, J.D. Schuijf, M. Bertini, V. Delgado, A.J.H.A. Scholte, J.M. Van Werkhoven, J.W. Jukema, E.R. Holman, E.E. Van Der Wall, J.J. Bax. Leiden University Medical Center, Leiden, Netherlands Purpose: Diastolic and subclinical systolic dysfunction may indicate coronary artery disease (CAD) even in asymptomatic patients. However, whether these characteristics can improve prediction of obstructive CAD is still unknown. Methods: A total of 182 consecutive outpatients (54±10 years, 59% males) without known CAD and with LV ejection fraction 50% underwent 64-slice MSCT coronary angiography and echocardiography. MSCT angiograms showing atherosclerosis were classified as showing obstructive ( 50% luminal narrowing) CAD or not. Conventional echocardiographic parameters of LV systolic and diastolic function were obtained; in addition, speckle tracking echocardiography was performed to assess LV global longitudinal strain (GLS). The relation between this parameter of LV systolic function and obstructive CAD was explored using multivariate and ROC analyses. Results: Based on MSCT, 32% patients were classified as having no CAD, whereas 33% showed non-obstructive CAD and the remaining 35% had obstructive CAD. Multivariate analysis of clinical and echocardiographic characteristics showed that only high pre-test likelihood of CAD (OR 3.21, 95% , p=0.046), GLS (OR 1.97, 95% CI , p<0.001), and diastolic dysfunction (OR 3.72, 95% CI , p=0.006) were associated with obstructive CAD. A value of GLS yielded high sensitivity and specificity in identifying patients with obstructive CAD (83% and 77%, respectively), providing a significant incremental value over pre-test likelihood of CAD and diastolic dysfunction (Figure). Incremental value of GLS Conclusions: GLS impairment in patients without overt LV systolic dysfunction, expressing subclinical LV dysfunction, aids detection of patients with obstructive CAD. This information may be useful for selection of appropriate further diagnostic tests. P2157 Effects of cardiac resynchronization therapy on subepicardial and subendocardial left ventricular twist M. Bertini 1, N. Ajmone Marsan 1, G. Nucifora 1, V. Delgado 1,R.J.Van Bommel 1, C.J.W. Borleffs 1, G. Boriani 2,M.Biffi 2, M.J. Schalij 1, J.J. Bax 1. 1 Leiden University Medical Center, Leiden, Netherlands; 2 Univ. di Bologna - Istituto di Cardiology, Bologna, Italy Purpose: Subepicardial and subendocardial layers have different orientation of myofibers: right and left hand orientation, respectively. Subepicardial layer leads the direction of left ventricular (LV) twist, having larger radius of rotation. Minimal data are available on subepicardial and subendocardial LV twist and cardiac resynchronization therapy (CRT) in heart failure (HF) patients. The aim of the study was to explore the effects of CRT on LV twist in both layers. Methods: A total of 75 HF patients scheduled for CRT were included. Realtime three-dimensional echocardiography was performed and repeated within 48 hours after CRT, to assess LV volumes, LV ejection fraction (EF) and systolic dyssynchrony index (SDI). Speckle tracking analysis was applied to LV basal and apical short axis images to assess subepicardial and subendocardial LV apical and basal rotation. LV twist was defined as the net difference at isochronal time point between apical and basal rotation. Consequently, subepicardial and subendocardial LV twist were calculated at baseline and within 48 hours after CRT (immediately after CRT). Results: The mean age was 65±10 years, 49 men. Ischemic aetiology of HF was present in 38 (51%) patients. At baseline LVEF was 26±6% and improved to 31±7% immediately after CRT (p<0.001). At baseline SDI was 7.6±2.4% and improved to 5.8±2.3% immediately after CRT (p<0.001). Peak subepicardial LV twist increased from 2.3±1.9 to 3.4±2.1 (p=0.001) and peak subendocardial LV

45 Echocardiography in cardiomyopathy 345 twist from 4.5±3 to 5.5±3.2 (p=0.003). The acute change ( ) of LVEF was significantly related to LV end-systolic volume, SDI, SDI, subepicardial LV twist, subepicardial LV twist, subendocardial LV twist and subendocardial LV twist. At multivariable linear regression analysis the strongest determinant of LV systolic improvement immediately after CRT was subepicardial LV twist (β=0.54, p<0.001). Conclusions: An immediate improvement of subepicardial LV twist after CRT is the best reflector of the positive effect of CRT on LV systolic function P2158 Two-dimensional speckle tracking strain echocardiography in heart transplant patients B. Syeda, P. Hoefer, P. Pichler, M. Vertesich, S. Roedler, S. Mahr, S. Graf, J. Bergler-Klein, D. Glogar, T. Binder. Medical University of Vienna, Vienna, Austria Background: Longitudinal strain determined by 2 dimensional speckle tracking is a sensitive parameter to detect early systolic left ventricular dysfunction. However, it is unclear if heart transplant (HTX) patients exhibit reduced longitudinal strain compared to healthy individuals. Methods: Transthoracic echocardiography (TTE) and multidetector computed tomographic angiography (MDCT, dual source 2x32x0.6mm, Siemens Definition) was performed in 31 HTX patients (126.8±67.6 months [10.6 years] post transplantation) and in 42 asymptomatic healthy subjects. Grey-scale apical 2-, 3- and 4-chamber views were recorded and stored for automated offline speckle tracking for longitudinal strain analysis (EchoPAC 7.0, GE). The presence of coronary artery disease (CAD) and left ventricular ejection fraction (LVEF%) was assessed by MDCT. Results: Nine of the 31 transplant patients had significant allograft CAD. Mean global longitudinal peak systolic strain (GLPSS) was significantly lower in the transplant recipients than in the healthy population (-13.9±4.2% vs ±5.8%, respectively, p<0.01). This was still the case after excluding the 9 transplant patients with CAD (-14.1±4.4% vs ±5.8%, respectively, p<0.02). LVEF% was 60.7±10.1% in transplant recipients vs. 64.8±6.4% in the healthy population (p=ns). There was no significant age difference within the two groups 62.9±10.7 years vs. 60.4±11.6 years, respectively (p=ns). Conclusion: GLPSS is reduced in heart transplant recipients compared to healthy subjects despite equal LVEF%. This difference is independent of age. Longitudinal strain analysis could allow the early detection of subclinical left ventricular dysfunction in heart transplant recipients. P2159 Differences in the cardiomyopathy progression of female and male fabry patients. implications for monitoring and treatment M. Niemann 1, S. Herrmann 1, F. Breunig 1,M.Beer 2, C. Wanner 1, W. Voelker 1,G.Ertl 1, F. Weidemann 1. 1 Medizinische Klinik I, Wuerzburg, Germany; 2 Radiologische Klinik, Wuerzburg, Germany Background: The established disease model for the Fabry cardiomyopathy is based mainly on data from male patients. In this model the cardiomyopathy progression starts with left ventricular hypertrophy and reduced regional myocardial function and progresses towards myocardial fibrosis. Whether it is similar in female patients was never systematically investigated. Methods: 115 patients with genetically proven Fabry disease (64 females and 51 males) were investigated with standard echocardiography (for the assessment of left ventricular hypertrophy), strain rate imaging (for regional myocardial deformation) and magnetic resonance imaging (MRI) using the late enhancement (LE) technique for the detection of fibrosis. Results: Female Fabry patients (n=64; age 43±10 years, range from 10 to 83 years) had a left ventricular wall thickness (LVWT) range from 5 to 16 mm. Thirtyfour percent of the female patients (n=22) had at least one LE positive segment. LE was first seen at a LVWT of 9 mm. In the female patients being non hypertrophic (LVWT < 13 mm) 11 patients had already LE positive segments. Above 13 mm LVWT all females showed LE in MRI. In the 51 male Fabrys (age 43±7 years, range from 7 to 66 years) the LVWT ranged from 6 to 20 mm. Forty-nine percent of the male patients (n=25) had at least one LE positive segment. LE occurred first at 12mm LVWT. All male patients having a LVWT of more than 16 mm (n=6) showed at least one LE positive segment. The youngest female with LE was 36 and the youngest male patient with LE was 23 years old. The presence of LE was associated with low strain rate values in male and female patients. In female patients showing LE the reduction of strain rate values were independent of left ventricular wall thickness (peak systolic strain rate lateral in hypertrophic patients with LE = -0.7±0.2 s -1 ; in non hypertrophic patients with LE = -0.7±0.2 s -1 ;p>0.05). Conclusion: In contrast to male patients, the loss of function and the development of fibrosis in female Fabry patients do not necessarily require hypertrophy. Thus, the cardiomyopathy progression in female and male Fabry patients is different which should have implications for monitoring and treatment of Fabry female patients. P2161 Regional distribution of entity of strain and time to peak strain of right ventricle in normal individuals and in heart failure patients A. Meris 1,C.Conca 1,C.Klersy 2, A. Evangelista 1, J. Klimusina 1, M. Averaimo 1, A. Auricchio 1, F. Faletra 1. 1 Fondazione Cardiocentro Ticino, Lugano, Switzerland; 2 Fondazione IRCCS Policlinico San Matteo, Pavia, Italy Purpose: Assessment of right ventricular (RV) function is of paramount importance in many cardiovascular diseases. RV strain by using 2D speckle tracking has been used to a limited extent in the evaluation of RV function. Methods: We prospectively enrolled 100 normal subjects and 76 patients with RV dysfunction defined as tricuspid annular plane systolic excursion (TAPSE) < 2 cm. Longitudinal peak strain (LPS), defined as percentage of maximum shortening in systole (negative values) for 6 RV segments (basal, mid, and apical segments of the RV free wall and septum), global RV strain (GS), defined as the average of LPS in the 6 segments, and time-to-peak strain (TPS) defined as the time from the beginning of QRS to LPS, were measured from 4-chamber apical view. Results: LPS and GS in normal subjects and in patients with RV dysfunction are shown in the Figure. Normal subjects have a significantly (p <0.05) higher LPS and GS and a shorter TPS than patients with RV dysfunction. A significant correlation between LPS and TAPSE (r = -0.83, p <0.001) was found. Considering TAPSE as the reference parameter, the ROC curve showed that the highest sensitivity/specificity cut-off to identify normal LPS is -19% [sensitivity of 95% (95%CI 87% to 98%) and a specificity of 85% (95%CI 77% to 91%)]. Conclusions: 2D speckle tracking may be a useful tool to evaluate global and regional RV function. Greater differences are noted in the regional distribution of the amount of mechanical dyssynchrony rather than in the timing. P2162 Left ventricular dysfunction during right ventricular pacing: volumetric analysis with real-time three-dimensional echocardiography T. Wolber, C. Brunckhorst, F. Duru. University Hospital Zurich, Zurich, Switzerland Background: Chronic right ventricular apical (RVA) pacing has been associated with increased risk of heart failure and adverse outcome. RVA pacing induces abnormal electrical activation patterns of the left ventricle. However, few data exist on the acute effects of RVA pacing on three-dimensional ventricular function. We performed three-dimensional (3D) echocardiography with volumetric analysis to assess global and regional left ventricular function during RVA pacing. Methods: 26 patients with implanted cardiac devices and normal intrinsic atrioventricular conduction were included in the study. Three-dimensional echocardiography was performed during intrinsic sinus rhythm and during RVA pacing. Time-volume analysis of 16 myocardial segments was performed offline. A systolic dyssynchrony index (SDI) was calculated to assess regional variation in systolic function. Longitudinal function was assessed by sequential time-volume analysis of apical, mid-ventricular and basal segments. Results: During RVA pacing, a reversed apical-to-basal longitudinal contraction sequence was observed in 58% of all patients. RVA pacing was associated with 3D echo contraction front mapping

46 346 Echocardiography in cardiomyopathy increased LV dyssynchrony and reduced LV ejection fraction (LVEF). SDI increased from 4.4±2.2 to 6.3±2.4 percent (P=0.001).Three-dimensional left ventricular ejection fraction (LVEF) declined from 53±13 to 47±14 percent (P=0.05). Conclusion: RT3DE volumetric assessment of left ventricular function provides evidence that pacing from the RVA results in acute alterations in LV contraction sequence and increased LV dyssynchrony. Further studies are warranted to assess the potential of RT3DE to identify patients who might be at increased risk of pacing-induced heart failure or who might benefit from alternate-site or multisite pacing. P2163 Contrast enhancement has no additional value in RV volumetric measurements with real-time 3D echocardiography D.H.F. Gommans 1, A.P.J. Van Dijk 2, M.A. Brouwer 2,M.J.Van Der Vlugt 2. 1 Radboud University Medical Centre, Nijmegen, Netherlands; 2 Radboud University Medical Centre Nijmegen, Nijmegen, Netherlands Purpose: Real-time 3D echocardiography (RT3DE) has the potential to substitute cardiac MRI for RV volumes. The purpose of this study was to assess accuracy and reproducibility of RT3DE for RV volumes with and without the use of contrast. Methods: RT3DE images (IE-33, Philips) were obtained from the apical view before and after contrast agent-injection (Sonovue) in 40 healthy males. Using on board software (Qlab 5, GI view) RV and LV volumes were divided into 7 shortaxis and 7 long-axis slices. Endocardial contours were manually traced for enddiastolic and end-systolic volumes. Accuracy for LV measurement was confirmed by comparison to a validated standard (Qlab 5, CV view, 3DQ ADV). Accuracy of RT3DE RV measurement was determined by comparison of LV SV with RV SV. Volumes were traced twice and compared to obtain intraobserver variability. Results: Obtained with RT3DE, mean LV EDV and ESV were 127.5±21.4 and 50.5±12.7 ml, LVEF was 60.4±7.7% with excellent comparison to the standard (mean difference -0.02, p=0.99). Mean RV EDV and ESV were 108.7±21.8 and 44.6±14.5 ml, RVEF was 59.3±8.0%. In the short-axis view with and without contrast the mean difference between RV and LV SV was -7.4±17.6 ml, p<0.05 and -11.2±11.4 ml, p<0.05. In the long-axis view with and without contrast mean difference between RV and LV SV was -5.0±17.1 ml, p<0.07 and -10.6±12.5 ml, p<0.05 (Figure). In short-axis view Pearson correlations between RV and LV SV with and without contrast were 0.50 and 0.77, p< In the long-axis view correlations with and without contrast were 0.51 and 0.75, p< Reproducibility was good (r = 0.971, SEE = 10.1). Conclusion: RT3DE underestimates RV volumes, but it is a feasible and reproducible method. Contrast has no additional value for volumetric measurements. P2164 Assessment of right ventricular systolic function: validation of six echocardiographic methods versus cardiac magnetic resonance imaging M. Pavlicek, A. Wahl, K. Wustmann, F. Praz, S. De Marchi, M. Schwerzmann, T. Rutz, C. Eigenmann, B. Meier, C. Seiler. Inselspital Bern, Berne, Switzerland Purpose: Systolic right ventricular (RV) function is an important predictor in the course of various congenital and acquired heart diseases. Numerous parameters are routinely employed, namely peak systolic tricuspid annular velocity by Doppler tissue imaging (DTItv), tricuspid myocardial acceleration during isovolumetric contraction (IVA), tricuspid annular plane systolic excursion (TAPSE), myocardial performance index (MPI) and fractional length and area change (FAC), without knowing the most accurate one for systolic RV function assessment. We prospectively compared these parameters with cardiac magnetic resonance (CMR) as reference method. Methods: 72 patients underwent both CMR and transthoracic echocardiography within 11±32 days. The RV was imaged by CMR from the base towards the apex during short end-expiratory breath-holds using contiguous short axis slices in 8mm increments. Volumes were calculated from the area within the manually traced contours and the slice thickness (disk summation). Echocardiographic values were obtained by 2D-, M-Mode-, Doppler-echocardiography, and pulsed wave DTI. Results: 17 (24%) patients showed normal biventricular systolic function, 32 (44%) predominant left ventricular dysfunction, 14 (19%) predominant RV dysfunction and 9 (13%) pulmonary hypertension. RV ejection fraction (EF) as determined by CMR ranged from 25 to 80%. It correlated with DTItv (r=0.42, p<0.0001), TAPSE (r=0.42, p<0.0001), IVA (r=0.31, p=0.009), fractional length change (r=0.34, p=0.03), FAC (r=0.32, p=0.007) and MPI (r=-0.25, p=0.04). The accuracy of the methods for the detection of RVEF<50% is shown in the table. Table 1 p-value Area under the curve Sensitivity, Specificity, Cut off value % % DTItv, cm/s < TAPSE, mm < FAC, % IVA, m/s RV length change, % MPI, no unit Conclusions: The echocardiographic methods most accurately detecting impaired RV ejection fraction <50% are those measuring tricuspid annular free wall motion in the long axis. P2165 Right ventricular function in asymptomatic patients with systemic sclerosis C. Dumitrascu, A. Dumitrascu, C. Draghici, M. Grigore, C.M. Tanaseanu. Sf Pantelimon Emergency Hospital, Bucharest, Romania Cardiopulmonary involvement in patients with systemic sclerosis (SSc) carries a poor prognosis, mainly due to pulmonary hypertension and rightheart failure. Subclinical cardiac involvement has a higher frequency. Aim Of The Study: to assess the right ventricular (RV) myocardial function in patients with systemic sclerosis and related the findings to the clinical features of the disease. Methods: Twenty-six patients with SSc (mean age, 56±15 years [± SD]) and 25 healthy, age-matched control subjects were studied. The patient underwent clinical exam, routine lab tests, determination of anti SCL and anti centromere antibodies, Doppler echocardiography. Results: Compared with control subjects, RV free wall thickness (5.6±1.4 mm vs 3.9±1.2 mm, p < 0.001) and end-diastolic dimensions were increased in patients with SSc, The mean value of Tr E/A in SSc was lower than in controls (0.9±0.2 vs. 1.2±0.2, p=0.03). The mean value of Tei index for the RV was higher in SSc patients than in controls (0.34±0.08 vs. 0.29±0.02, p <0.001) The isovolumic relaxation time corrected to RR interval was increased (6.5±2.9 versus 4.5±2.5%). TAPSE measurements were significantly different between SSc and control patients (2.4±0.43 vs. 1.9±0.39 cm with P < ). LVEF was similar, but RVEF was lower in the SSc group (RVEF: 49.6±6.8 vs. 39.2±6.7% with P < ). Contrary to expectation, pulmonary artery systolic pressure (PASP) did not correlate well with RV function (r = 0.260, r2= 0.063, P = 0.015). Conclusions: In progressive systemic sclerosis, RV systolic dysfunction is common and appears to be a result of pulmonary hypertension, disturbance of myocardial microcirculation, and myocardial fibrosis. Pulmonary hypertension was not well correlated with RV dysfunction; it suggested pulmonary hypertension was not the only cause of RV failure. Primary right heart involvement was the other possible cause. In evaluation of the patients with SSc echo appeared to be the most useful among the noninvasive tests, mainly due to the high specificity. P2166 Left ventricular untwisting in restrictive and pseudo-restrictive left ventricular filling; novel insights into diastology B.M. Van Dalen, O.I.I. Soliman, W.B. Vletter, F.J. Ten Cate, M.L. Geleijnse. Erasmus MC - Thoraxcenter, Rotterdam, Netherlands Objectives: Conceptually, an ideal therapeutic agent should target the underlying mechanisms that cause left ventricular (LV) diastolic dysfunction. The objective of our study was to gain further insight into the mechanics of diastology by comparison of LV untwisting measured by speckle tracking echocardiography (STE) in young healthy adults with normal and pseudo-restrictive LV filling, and dilated cardiomyopathy (DCM) patients with true restrictive LV filling. Methods: The study comprised 20 healthy volunteers with a Doppler LV-inflow pattern compatible with restrictive LV filling but an E/Em ratio <8 ( pseudorestrictive ), 20 for age and gender matched healthy volunteers with normal LV filling and an E/Em ratio <8, and 10 DCM patients with true restrictive LV filling and an E/Em ratio >15. LV untwisting parameters were determined by STE.

47 Echocardiography in cardiomyopathy 347 Results: Compared to healthy subjects, DCM patients had decreased peak diastolic untwisting velocity (-62±33 degrees/s vs. -113±25 degrees/s, P <0.01) and untwisting rate (-15±9 degrees/s vs. -51±24 degrees/s, P <0.01) (Figure 1). Compared to healthy subjects with normal LV filling, healthy subjects with pseudo-restrictive LV filling had increased peak diastolic untwisting velocity (- 123±25 degrees/s vs. -104±30 degrees/s, P <0.05) and untwisting rate (-59±23 degrees/s vs. -44±22 degrees/s, P <0.05) (Figure 1). Conclusion: Faster LV untwisting plays a pivotal role in the rapid early diastolic fillingoccasionally seen in young healthy individuals. In contrast, in DCM patients untwisting is severely delayed and this impairment to utilize suction may reduce LV filling. P2168 Noninvasive estimation of left ventricular filling pressure in patients with heart failure independent of systolic function F.L. Dini 1, P. Ballo 2, L. Badano 3, P. Barbier 4, M. Galderisi 5,S.Ghio 6, A. Rossi 7, P.L. Temporelli 8. 1 Azienda Ospedaliero - Universitaria Pisana, Pisa, Italy; 2 Sant Andrea Hospital, La Spezia, Italy; 3 Santa Maria della Misericordia Hospital, Udine, Italy; 4 Centro Cardiologico Monzino, Milan, Italy; 5 Azienda Ospedaliera Universitaria Federico II, Naples, Italy; 6 Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; 7 University of Verona, Verona, Italy; 8 Istituto Scientifico - Fondazione Salvatore Maugeri IRCCS, Veruno, Italy Background: Using Classification And Regression Tree (CART) analysis, we sought a noninvasive estimation of left ventricular (LV) filling pressure in patients with heart failure (HF) by decision models based on single or combined echo- Doppler parameters. Methods and Results: HF patients (n=258) with a wide range of LV ejection fraction (EF= 43±16%) underwent echo-doppler and hemodynamic evaluation. Elevated LV filling pressure was defined by a pulmonary capillary wedge pressure >15 mmhg. Patients were classified according to: E wave deceleration time (EDT) <150 ms, mitral-to-myocardial early velocities (E/e ) >15, 15 >E/e >8, left atrial (LA) volume index >40 ml/m 2, E wave-to-color M-mode propagation velocity >2, difference in duration of pulmonary vein flow and mitral velocities at atrial contraction >30 ms. A classification tree was developed using CART analysis (derivation cohort: n=178). Using this model, E/e >15 or EDT <150 ms as a first decisional node allowed identification of presence of elevated LV filling pressure in 71 patients. As further steps, 15 >E/e >8 as a second node followed by one of the remaining criteria as a third node permitted prediction of raised filling pressure in 79 more patients (92% sensitivity, 74% specificity). Models were validated in a testing group of 80 patients. With respect to standard criteria, the best performance of CART analysis was found in patients with EF >50%, with a 9.5% relative increase in accuracy. P2167 Can 3D echocardiography be used to investigate the dynamics of cardiac function? A functional data analysis K.K. Poppe, G.A. Whalley, R.N. Doughty, C.M. Triggs. The University of Auckland, Auckland, New Zealand Background: Cardiac motion is a continuum, depending on the relationship between systolic and diastolic phases. Real-time 3-dimensional echocardiography (RT3DE) allows left ventricular volumes (LVVs) to be calculated for each frame of an imaging sequence. By converting the repeated volume measurements to a function of time, functional data analysis techniques can be applied. We explore the representation of LV dynamics using the 1st and 2nd derivatives of LVV throughout the cardiac cycle. Method: RT3DE loops (Philips ie33) were captured from 15 normal and 15 postacute coronary syndrome (ACS) subjects. For each subject, LVVs (proportional to end-diastolic volume) were converted to a function of time (R software). The 1st derivative of the function is the velocity (vel) of volume change; the 2nd derivative is acceleration (acc). Plots showing 2 dynamic dimensions (LVV vs vel, and vel vs acc) and 3 dimensions (LVV vs vel vs acc) were created. Results: Normal/ACS subjects: 60%/80% male, median age 24/64yrs, median ejection fraction (LVEF) 60%/36%. In all subjects, LVV vs vel and vel vs acc plots evolved closed curves that frequently crossed themselves, suggesting the 2D plot was an inadequate summary of LV dynamics. The apparent loops on the 2D plots were unravelled in the 3D plots, revealing the changing directions of vel and acc through the cardiac cycle. While the appearance of curves was similar across subjects, the area within the curve appears reduced with low LVEF. a) LVV vs time, b) 2D plot, c) 3D plot Conclusion: This pilot study graphically displayed the dynamics of LVV through the cardiac cycle. As motion is assessed throughout systole and diastole, the area within the curve may prove a more sensitive measure of function than LVEF. Further evaluation of the technique is required and should involve 3D not 2D curves. CART Analysis Conclusions: These classification rules may be used to build up ease-of-use pathways for predicting elevated LV filling pressure in patients with HF. P2169 Arterial stiffness and coronary flow reserve are independent determinants of LV untwisting in untreated patients with essential hypertension. A speckle tracking echocardiography study I. Ikonomidis, C. Papadopoulos, J. Lekakis, I. Paraskevaidis, H. Triantafyllidi, S. Tzortzis, C. Tsitlakidis, P. Trivilou, D.T. Kremastinos. University of Athens, Athens, Greece LV utwisting is a novel marker of myocardial relaxation and LV diastolic suction. Arterial stiffness and impaired coronary microcirculation may determine left ventricular (LV) function. We investigated the association of the above parameters with LV twisting and untwisting. Methods: We studied 60 untreated consecutive patients (mean age: 54±11 years), with newly diagnosed essential hypertension (clinic blood pressure >140/90 mmhg and >125/80mmHg in 24hour ambulatory BP monitoring) and 30 healthy controls matched for atherosclerotic factors. Exclusion criteria were diabetes, familiar hyperlipidemia, CAD, and pulmonary disease. We measured a) Carotid to femoral artery pulse wave velocity (PWV) b) Coronary flow reserve (CFR) after adenosine infusion. c) Peak Twisting (ptw-deg) and Untwisting (Utw) at mitral valve opening (UtwMVO) and at the end of LV early filling defined as the end of the mitral inflow E wave (UtwE-deg) using speckle tracking imaging. We calculated the percentage difference between Peak twisting and untwisting at MVO [%difference (ptw UtwMVO)] and end of mitral E wave [%difference (ptw UtwE)] and the corresponding untwisting rates. Results: Patients had higher PWV (10.5±1.8 vs 8.2±1.5, p<0.01) and lower CFR, (2.5±0.6 vs 3.2±0.6, p<0.01) than normals. Compared to controls, hypertensives had increased peak twisting (15.7±3.6 vs.13.8±4.3 deg p<0.05) and decreased %difference ptw-utwmvo (29±8 vs. 38±7%, p<0.05) %difference ptw-utwe 67±9 vs. 73±8%, p<0.05), untwisting rate at MVO (0.34±0.1 vs. 0.55±0.1 deg/sec p<0.05) and end of mitral E wave (0.19±0.1 vs. 0.24±0.1 deg/sec p<0.05)). Increasing PWV and decreasing CFR were related to reduced %difference ptw-utwmvo (r=-0.48 and r=0.43, p<0.01), %difference ptw-utwe (r=-0.37, r=0.47, p<0.01), untwisting rate at MVO (r=-0.64 and r=0.43, p<0.01) and end of LV early filling (r=-0.38 and r=0.42, p<0.01). By regression analysis,

48 348 Echocardiography in cardiomyopathy the above relations remained significant after adjustment for age, sex, BMI, LV mass and blood pressure (p<0.01). By ROC analysis a PWV>10.5 and CFR<2.5 were significant predictors of an untwisting rate at MVO >0.30%/sec (median of the study population) [AUC=82%, 95% CI: 70-90% p<0.01 and AUC=71%, 95% CI: 56-87% p=0.013]. Conclusions: Increased arterial stiffness and abnormal coronary microcirculation are independent determinants of impaired LV untwisting in never-treated patients with essential hypertension. patients with normal glucose tolerance. Using logistic regression model adjusting for age, gender, site and size of AMI, and blood pressure, newly diagnosed DM (odds ratio 3.0) and a history of DM (odds ratio 9.0) remained significant predictors of CFVR < 2 whereas impaired glucose tolerance (IGT) was not. Conclusions: The study shows that CFVR is decreased in patients with known or newly diagnosed DM even after adjustment of possible confounders, whereas patients with IGT have preserved CFVR compared to those with normal glucose metabolism. P2170 Intima media-thickness of the common carotid artery in major vascular surgery patients: a predictor of postoperative and late cardiovascular events W.J. Flu 1,J.P.VanKuijk 1, S.E. Hoeks 1,R.Kuijper 2, O. Schouten 2, D. Goei 2,T.Winkel 2,Y.VanGestel 2,J.J.Bax 3, D. Poldermans 4. 1 Erasmus MC, Rotterdam, Netherlands; 2 Erasmus, Rotterdam, Netherlands; 3 Leiden University Medical Center, Leiden, Netherlands; 4 Erasmus MC - Thoraxcenter, Rotterdam, Netherlands Purpose: Cardiovascular complications are the leading cause of postoperative and late morbidity and mortality in vascular surgery patients. The Revised Cardiac Risk (RCR) Index is commonly used for preoperative risk stratification. This study evaluated the incremental prognostic value of the common carotid artery intima media-thickness (CCA-IMT) in predicting cardiovascular events, next to the prognostic value of the RCR Index. Methods: In 508 vascular surgery patients the following risk factors were recorded; ischemic heart disease, heart failure, stroke, diabetes mellitus and renal dysfunction. Troponin T measurements and ECG s were performed postoperatively on day 1, 3 and 7. The CCA-IMT was analysed using high-resolution B- mode ultrasonography. The study endpoint was the composite of 30-day cardiac ischemia and late cardiovascular mortality. The optimal predictive value of CCA- IMT was calculated using ROC curve analysis. Multivariable regression analyses were used to assess the additional value of CCA-IMT to predict cardiac events. Results: 30-day cardiac ischemia and late cardiovascular mortality was noted in 117 (23%) and 81 patients (16%), respectively. The optimal predictive value of CCA-IMT was 1.25mm (sens.70%, spec.80%). Multivariable analysis showed that the RCR Index was predictive for 30-day cardiac ischemia (OR=2.6 95%CI ) and late cardiovascular mortality (HR %CI ). An increased CCA-IMT on top of the RCR Index was independently associated with 30-day cardiac ischemia (OR 2.5, 95%CI ) and late cardiovascular mortality (HR %CI ) (Figure). P2172 Implication of dynamic variation of left ventricular vortex flow morphology on left ventricular function: a quantitative vorticity imaging study using contrast echocardiography G.R. Hong, I.W. Song, S.H. Lee, J.S. Park, D.G. Shin, Y.J. Kim, J.H. Chio. Yeungnam University, Daegu, Korea, Republic of Background: We hypothesized that the dynamic changes of LV vortex flow morphology optimizes LV fillingand ejection. The aim ofthisstudy wastocharacterize dynamic changes in LV vortex flow morphology during cardiac cycle in normals and patients with systolic (SHF) and diastolic heart failure (DHF). Methods: 17 normals and 20 patients (13 with SHF and 7 with DHF) underwent 2-D contrast echocardiography. LV vorticity was estimated by particle image velocimetry. We measured maximal and minimal vortex flow size (TVS,%) and phasic variation in the vortex flow size (PV-TVS,%) and time to maximum vortex formation (t-mv). Results: Max-TVS was significantly larger in normals than SHF (p<0.001) but there was no significant difference between normals and DHF. Min-TVS was significantly larger in normals than in patients with SHF and DHF (p<0.001). PV-TVS was greater in normals than SHF (p<0.01) but there was no significant difference between normals and DHF. T-MV during diastole was significantly longer in DHF than normal and SHF (p<0.001). Quantitative LV vortex size Max-TVS (%) Min-TVS (%) PV-TVS (%) t-mv (ms) Normal 86±12 32±11 57±25 89±27 SHF 50±14 12±7 35±19 95±35 DHF 78±18 8±5 61±31 185±56 TVS, total vortex size; PV, phasic variation; t-mv, time to maximal vortex size; SHF, systolic heart failure; DHF, diastolic heart failure. Cumulative Long Term Survival Conclusions: The present study shows that an increased CCA-IMT has prognostic value in vascular surgery patients to predict cardiovascular events, incremental to the prognostic value of the RCR Index. P2171 Influence of abnormal glucose metabolism, on coronary microvascular function after a recent myocardial infarction B.B. Loegstrup 1, D.E. Hoefsten 1, T.B. Christophersen 1, J.E. Moeller 2, H.E. Boetker 3, P.A. Pellikka 4,K.Egstrup 1. 1 Svendborg Hospital, Svendborg, Denmark; 2 Department of Cardiology, Copenhagen, Denmark; 3 Aarhus University Hospital, Aarhus, Denmark; 4 Mayo Clinic Division of Cardiovascular Diseases, Rochester, United States of America Objectives: To assess the association between abnormal glucose metabolism and depressed coronary flow velocity reserve (CFVR) in patients with acute myocardial infarction (AMI). Background: Mortality and morbidity after AMI is high among patients with abnormal glucose metabolism independent of other risk factors. Methods: Study population consisted of 183 patients with a first AMI. 161 patients with no history of diabetes mellitus (DM) performed an oral glucose tolerance test. After coronary angiography and revascularization a transthoracic echocardiography and non-invasive assessment of CFVR was performed. CFVR was assessed in the distal part of left descending artery. Adenosine was administered by intravenous infusion (140 μg/kg/min) to obtain the hyperaemic flow profiles. The CFVR was the ratio of hyperaemic to baseline peak diastolic coronary flow velocities. Results: Median CFVR was 1.9; 109 patients (60%) had a CFVR 2. CFVR was depressed in 22 patients with a history of DM, and in 39 patients with newly diagnosed DM, whereas CFVR did not differ in 58 patients with abnormal and 62 Conclusion: Phasic changes in vortex flow morphology correlates with global LV function and maybe a sensitive indicator of intracardiac hemodynamics in SHF and DHF P2173 Comparative effects of levosimendan and dobutamine on left ventricular diasolic function and brain natriuretic peptide in patients with decompansated advanced heart failure D. Duman, F. Palit, E. Simsek, O. Yildiz. Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey Background: In this randomized prospective trial, we we compared the effects of levosimendan and dobutamine on left ventricular diastolic cardiac modifications and brain natriuretic peptide in patients with decompansated advanced heart failure (AHF).

49 Echocardiography in cardiomyopathy 349 Methods: Sixty-three patients (mean age 65±9.0 yrs) refractory to conventional theraphy with left venicular (LV) ejection fraction (EF) 0.35 and diastolic LV dysfunction due to idiopathic or ischemic cardiomyopathy were enrolled and were randomized to levosimendan (n= 33) or dobutamine (n= 30). All patients were in sinus rhythm and had pseudonormal (21%) or restrictive filling (79%) pattern by echo Doppler method. Conventional echo Doppler was used to assess LV EF, LV volumes, peak velocities of transmitral early (E) and late (A) diastolic LV filling, the ratio of transmitral early to late LV filling velocity (E/A), and deceleration time of E (DT). The E/e ratio was also evaluated using the tissue Doppler imaging together with plasma B-type natriuretic peptide (BNP) levels measurements before and after drug infusion. Results: The improvement of LV EF and LV volumes were smilar in both levosimendan and dobutamine groups. However, levosimendan but not dobutamine group showed a significant increase of A wave (p<0.05), DT (p<0.005), and a significant reduction of E wave (P< ), E/A (P< ) and E/e ratio (P<0.001). The levosimendan group had also a greater decrease in BNP at 24 hours compared with dobutamine group (p<0.005). The percent change of BNP in levosimendan group was significantly correlated with the percent change of E/e and DT (r=-0.42, p<0.01 and r=0.58, p<0.005, respectively). Conclusions: In patients with decompansated AHF, levosimendan and dobutamine both improve LV systolic function. However, levosimendan also improves LV diastolic function which was associated with a greater decrease of neurohormonal activation in these patients. P2174 Cardiovascular risk factors and early left ventricular longitudinal systolic dysfunction assessed by TDI in asymptomatic subjects with normal ejection fraction G. Di Salvo, S. Carerj, A. Salustri, F. Antonini-Canterin, S. La Carrubba, L. Cossu, P. Caso, A. Pezzano, R. Calabro, V. Di Bello on behalf of SIEC Italian Society of Cardiovascular Echography. Italian Society of Cardiovascular Echography (SIEC), Milan, Italy Background: In asymptomatic subjects with cardiovascular (CV) risk factors early diagnosis of left ventricular (LV) dysfunction is still a major challenge. Tissue Doppler imaging (TDI) is an important tool with a demonstrated clinical relevance in several cardiac diseases. Aim of this study were: 1. To evaluate the ability of TDI in detecting early longitudinal ventricular dysfunction; 2. To study the relationship between TDI and CV risk factors; 3. To assess the prognostic ability of TDI in a large group of asymptomatic subjects with preserved LV systolic function and normal diastolic function. Methods: A total of 1371 subjects (median age 60 years, 595 males) formed our study population: Controls, 265 healthy subjects; Group I, 434 subjects with one CV risk factor; Group II, 401 subjects with two CV risk factors; Group III, 271 subjects with 3 CV risk factors. A comprehensive standard echo-doppler evaluation, including PW-TDI study was performed in all patients. Follow up data were available on 554 subjects (mean age 55±13 years, 39% men). Results: Diastolic parameters (such as E/A, A wave, Em/Am; E/Em) were able to discriminate the number of CV risk factors. LV global longitudinal systolic function (Sm) was the only systolic parameter inversely related with the number of CV risk factors (p<0.0001). At multivariate analysis, Sm confirmed as the only functional parameter able to predict the increasing number of CV risk factors (p<0.001). Upon follow-up (mean 28±16 months), 18 individuals (3.2%) developed a first overt CVD event. The presence of an Sm value <7.5 cm sec showed a significant additional predictive value compared to the presence of CV risk factors. Conclusions: TDI is able to identify early longitudinal LV systolic abnormalities in presence of apparently normal systolic and diastolic function and progressively impairs with increasing CV risk factors, demonstrating a significant additional prognostic value compared to the simple presence of coexisting CV risk factors. P2175 Myocardial ejection velocities and strain underestimate electrical dyssynchrony during left bundle branch block (LBBB) K. Russell 1, A. Opdahl 1,O.Gjesdal 1,E.W.Remme 2,H.Skulstad 1, E. Kongsgaard 1, T. Edvardsen 1, O.A. Smiseth 1. 1 Rikshospitalet University Hospital, Oslo, Norway; 2 Institute of Surgical Research, Oslo, Norway Background: The clinical value of assessing LV intraventricular dyssynchrony prior to cardiac resynchronization therapy is controversial. This study investigated if peak myocardial ejection velocity (S), peak systolic strain (εs) and peak strain including post systole (ε) reflect electrical conduction delay in LBBB. Methods: In 5 anaesthetized dogs with LV micromanometers we measured myocardial segment lengths by sonomicrometry and intramyocardial-emgs (IM- EMG) by implanted electrodes. Onset of R in IM-EMG defined onset of regional electrical activation, and reference method for onset of true mechanical activation was first sign of active force generation (AFG) by LV pressure-segment length loop analysis. Time delay for lateral wall with respect to septum was quantified for each index during LBBB induced by RF-ablation. Results: During LBBB there was marked delay in electrical activation of the lateral wall by 50±7 ms (mean±sd) and similar delay in mechanical activation measured as onset AFG by 51±13 ms (p=ns). Mechanical activation measured as Figure 1 S, εs and ε, however, showed time delays of -30±25, 26±38 and -38±26 ms, respectively, indicating that these indices underestimated electrical dyssynchrony (Figure 1). Furthermore, peak S and peak εs suggested erroneously that the lateral wall was activated prior to septum. Similar finding were found by echocardiography. Conclusions: As predicted, LBBB was associated with marked delay in electrical activation between the LV lateral wall and septum and similar delay in true mechanical activation. Velocity and strain indices, however, were inaccurate measures of electrical delay, suggesting that these indices may lead to erroneous conclusions regarding magnitude of electrical delay and direction of the electrical activation sequence in LBBB. P2176 Apical untwist: an integral component of early diastolic left ventricular function U. Gustafsson, P. Lindqvist, M.Y. Henein, A. Waldenstrom. Heart center, Umeå University Hospital, Umeå, Sweden Background: Cavity twist is proven to be an important contributor to systolic left ventricular (LV) function and untwist to its filling. We aimed in this study to assess the exact relationship between LV apical untwist and early diastolic events of the cardiac cycle. Method: Short axis images of LV cavity at apical and basal levels were studied using echo speckle tracking in 43 healthy subjects, all in sinus rhythm, mean age 63 years, 22 females. Degrees of untwist were measured at 4 time points during early diastole (aortic valve closure, mid isovolumic relaxation, mitral valve opening and peak E velocity) at each level as well as globally. Peak LV E wave velocities were measured using conventional spectral Doppler. Studied individuals were divided into two groups according to the degree of apical untwist occurring during early filling (>2.5 degrees and <2.5 degrees). Results: The group with apical untwist >2.5 degrees in the early filling phase had significantly higher peak E velocities, 0.68m/s vs 0.58m/s (p=0.015), and significantly later onset of apical untwist with respect to AVC (p=0.05). The degree of global untwist during the isovolumic relaxation period inversely correlated with peak E wave velocity (R=-0.3 p=0.05), whereas that occurring during early filling phase directly correlated with peak E wave velocity (R=0.5 p<0.001). Conclusion: Global and especially apical untwist is an important integral component of early diastolic left ventricular function. The inverse relationship between the degree of global untwist during isovolumic relaxation and early diastolic filling velocities is in agreement with the known knowledge of shape change during this period. These findings highlight the important role of LV apical diastolic function in maintaining overall cavity performance. P2177 2D echo speckle tracking-assessed left ventricular torsion in healthy volunteers is gender but not age dependent C.J. Finn, L. Zhong, L.K. Tan, L.H. Chua, Z.P. Ding. National Heart Centre, Singapore, Singapore Background & Aim: Left ventricular (LV) torsion plays an important role in LV performance. However, the impact of age and gender on this measurement has not been extensively studied. We aimed to study the relationship between LV torsion, other conventional echo parameters, and age and gender. Methods: We performed echo studies (IE33, Philips) on normal healthy volunteers. LV torsion - defined as the instantaneous net difference of LV basal and apical rotations - was measured by off-line 2D echo speckle tracking analysis (QLab software) of LV basal and apical short-axis slices. Results: There were 69 healthy volunteers (mean age 42±11 years, range 26 to 72 years). ANOVA analysis revealed that there was no significant difference for LV torsion and rotation parameters among the age categories (table). Independent sample t-test revealed that females (n=36) had significantly greater values of peak LV torsion/diastolic length (1.9±0.7 degree/cm versus 1.5±0.4 degree/cm, P<0.001), untwisting rate (74.2±40.7 degree/sec versus 58±22.4 degree/sec, P<0.001) and peak diastolic untwisting velocity (-154±77 degree/sec versus - 115±46 degree/sec, P<0.001) than males (n=33). There was significant correlation between LV ejection fraction and LV torsion (r=0.23, P<0.05) but not for peak apical rotation (P=0.07) and peak basal rotation (P=0.16). Conclusion: The magnitude of LV torsion was independent of age in healthy volunteers. Peak LV torsion normalized to diastolic length, untwisting rate and

50 350 Echocardiography in cardiomyopathy LV rotation & torsion in normals by age Age (years) < >60 (n=13) (n=20) (n=13) (n=19) (n=4) P Value Peak LV torsion (degree) 14.8± ± ± ± ± Peak apical rotation (degree) 11.5± ± ± ± ± Peak basal rotation (degree) -4.0± ± ± ± ± Twist rate (degree/sec) 54.8± ± ± ± ± Untwist rate (degree/sec) 81.3± ± ± ± ± Peak systolic twisting velocity (degree/sec) 99.4± ± ± ± ± Peak diastolic untwisting velocity (degree/sec) -161± ± ±36-140±77-114± Peak LV torsion/diastolic length (degree/cm) 1.9± ± ± ± ± peak diastolic untwisting velocity were significantly higher in females compared to males. P2178 Sub-clinical and clinical high altitude pulmonary edema: an ultrasound lung comets study L. Pratali 1, M. Cavana 2,R.Sicari 1, E. Picano 1. 1 Fondazione G Monasterio, Pisa, Italy; 2 UB Rianimazione e Ambulatorio medicina di montagna, Aosta, Italy Background: The Ultrasound Lung Comets (ULCs) detected by chest sonography are a simple, non invasive, semiquantitative sign of increased extravascular lung water. High altitude pulmonary edema (HAPE)may occur in climbers,withan estimated frequency at %. Aim: to correlate the occurrence of HAPE with ULCs in a group of recreational climbers Methods: We evaluated 18 healthy subjects (mean age 45±10 years, 10 males) participating to a high altitude trekking in Nepal. We performed chest and cardiac sonography in all subjects, at sea level and at different altitudes during the ascent. ULCs were evaluated on anterior chest at 28 pre-defined scanning sites. Results: At individual patient analysis ULCs during ascent appeared in 15/18 subjects (83%) at 3440 height m s.l. and in 18/18 subjects (100%) at 4790 m s.l. in presence of normal left and right ventricular function and pulmonary artery systolic pressure rise (sea level= 24±5 mmhg vs peak ascent= 42±11 mmhg, p<0.001). The mean values of ULCs is shown in the figure. An ULCs score showed a negative correlation with O2 saturation (R=-0.7; p<0.0001). Conclusions: In recreational climbers, chest sonography reveals a high prevalence of clinically silent pulmonary edema, mirrored by reduction of O2 saturation and increase in pulmonary artery systolic pressure. P2179 Evaluation of non-invasive parameters for estimation of left ventricular filling pressures in heart failure patients after restrictive mitral annuloplasty and surgical ventricular restoration E.A. Ten Brinke, M. Bertini, R.J. Klautz, M.L. Antoni, J.J. Bax, P. Steendijk. Leiden University Medical Center, Leiden, Netherlands Purpose: Doppler echocardiography including tissue Doppler imaging (TDI) is widely used to assess diastolic left ventricular (LV) function. In particular, E/E is used as a non-invasive estimate of LV filling pressures. However, it is not established whether E/E is a good index for LV filling pressures in heart failure patients after extensive cardiac surgery and especially after restrictive mitral annuloplasty (RMA) and surgical ventricular restoration (SVR). Global diastolic strain rate during isovolumic relaxation (SRIVR) obtained with 2-dimensional speckle tracking analysis was recently proposed as an alternative approach to estimate LV filling pressures. Methods: We analyzed heart failure patients 6 months after RMA and/or SVR. Diastolic function was assessed invasively in the catheterization room. In addition, echocardiography including TDI and speckle tracking analysis was performed. Invasively measured indices included relaxation time constant Tau, dp/dtmin, and LV end-diastolic pressure (LVEDP). Invasive indices were correlated with a range of echocardiographic indices including E/A, IVRT, DT, E/E, SRIVR, and E/SRIVR. Results: A total of 23 heart failure patients were analyzed (RMA+SVR, n=11; RMA, n=8; SVR, n=4).the strongest correlation with invasive indices, in particular LVEDP, was found for SRIVR (r=-0.76, p<0.001). E/E did not correlate significantly with any of the invasively obtained diastolic indices (see Table). Correlations (r) tau -dp/dtmin LVEDP Mitral flow doppler E/A r 0.38 (p = 0.07) (p = 0.04) 0.65 (p < 0.001) IVRT r 0.33 (p = 0.12) (p = 0.18) 0.18 (p = 0.42) DT r (p = 0.70) 0.35 (p = 0.10) (p = 0.01) Tissue Doppler E/E r (p = 0.76) 0.08 (p = 0.71) (p = 0.58) Speckle tracking SRIVR r (p = 0.07) 0.46 (p = 0.03) (p < 0.001) E/SRIVR r 0.47 (p = 0.02) (p = 0.09) 0.46 (p = 0.03) Conclusions: In heart failure patients investigated 6 months after RMA and/or SVR, E/E correlated poorly with invasively obtained diastolic indexes. Global SRIVR, however, correlated well with LVEDP and dp/dtmin. Our data suggest that global SRIVR is a promising non-invasive index to assess left ventricular filling pressures in patients after extensive cardiac surgery. P2180 Can feature tracking correctly detect motion patterns as they occur in blood inside heart chambers? Validation of Echocardiographic Particle Image Velocimetry using moving phantoms R. Faludi 1,A.Walker 2,G.Pedrizzetti 3, J. Engvall 4, J.U. Voigt 5. 1 Heart Institute, University of Pecs, Pecs, Hungary; 2 Department of Clinical Physiology, Central Hospital, Vasteras, Sweden; 3 Dipartimento di Ingegneria Civile, University of Trieste, Trieste, Italy; 4 Department of Clinical Physiology, University Hospital, Linköping, Sweden; 5 Department of Cardiology, University Hospital Gasthuisberg, Catholic University Leuven, Leuven, Belgium Background: Echo Particle Image Velocimetry (PIV) is a new, feature tracking based approach to visualize and quantify blood flow patterns in heart chambers. In vivo, the flow velocity and direction of contrast enhanced blood is estimated by echocardiographic feature tracking algorithms and motion patterns, like vortices, are quantified. In this study we validated this new technique in moving phantoms. Methods: A linearly moving string phantom and a rotating agar phantom with graphite scatterers, both moving according to different, computer controlled speed patterns (range cm/s), were imaged at varying insonation angels (0-90 ) and frame rates (60-200/s). Over 80 different ultrasound image loops were analyzed for motion velocity and direction as well as for motion patterns of the scatterers in the phantoms using a dedicated prototype software. Measurement results were post-processed and analyzed with dedicated, custom made, MATLAB based tools and compared to the true values. Results: The new algorithm was able to estimate motion velocity with high accuracy (r=0.98, mean difference 1.6±1.9cm/s). Already at very low velocities, estimates became stable. Maximally detectable velocity was dependent on frame rate (r=0.65, p<0.001) and insonation angle (r=0.58, p<0.01) and reached 39 cm/s under optimal conditions. At higher velocities, estimates became random. Direction estimates were highly accurate in 80-90% of the samples (mean diff 1.4, n.s.). Interestingly, the accuracy of the direction estimate did not depend on motion velocity. Motion patterns (vortex size and position) were correctly identified. Conclusion: The new method of Echo-PIV appears feasible. Velocity estimates are accurate, the maximally detectable velocity, however, depends on imaging settings. Motion direction estimation works well, even at high velocities. We conclude, that Echo PIV may be used as a tool to analyze flow inside the heart, particularly if flow patterns are investigated. P2181 Intraoperative real-time 3D transesophageal echocardiography reliably assess left ventriuclar stroke volume: Direct comparison with thermodilution technique H. Yoshitani 1, M. Takeuchi 1,H.Nakai 1, K. Otani 1, N. Haruki 1, K. Kaku 1,Y.Nishimura 1, G. Ohara 1, R.M. Lang 2,Y.Ostuji 1. 1 University of Occupational and Environmental health, Kitakyushu, Japan; 2 The University of Chicago Medical Center, Chicago, United States of America Purpose: Accurate assessment of left ventricular (LV) volume by 2D transesophageal echocardiography (TEE) is often difficult, because imaging plane does not cut true apex. Although intraoperative assessment of LV volume is usually estimated stroke volume (SV) by thermodilution, we hypothesized that full volume datasets obtained from real-time 3DTEE could encompass whole part of the LV, thus allowing accurate determination of LV volume and SV in the operating room. Methods: To validate this hypothesis, we performed following 2 protocols. In protocol 1, full-volume datasets of 3D transthoracic echocardiography (3DTTE), as a reference standard, were acquired either before or after 3DTEE examination in 28 patients. LV volume was compared between two methods using quantitative software (QLab). In protocol 2, volumetric measurement of 3DTEE and 2DTEE were performed in 28 patients during cardiac surgery at different loading conditions. The values of SV obtained by 3DTEE (SV3D) and 2DTEE (biplane Simpson s

51 Echocardiography in cardiomyopathy 351 methods; SV2D) were compared to SV simultaneously acquired by thermodilution (SVT). Results: In protocol 1, excellent correlation of LV volumes (EDV: r=0.99, ESV: r=0.99). In protocol 2, a total of 53 datasets were obtained. Correlation between SV3D and SVT (r=0.73) was better compared to that between SV2D and SVT (r=0.35). 95% limits of agreement were lower in 3DTEE (±11 ml) compared to 2DTEE (±33 ml). SV2D (34±13 ml) was significantly smaller compared to SV3D (52±14 ml, p<0.001) and SVT (55±16 ml, p<0.001). Long-axis diameter from the mitral annulus to the LV apex was also significantly longer in 3DTEE compared to 2DTEE. Conclusions: Real-time 3DTEE allows accurate assessment of LV volume status, and could be another alternative for the determination of stroke volume during cardiac surgery. P2182 Routine performance of 3-dimensional transesophageal echocardiography: is there incremental value over 2-dimensional transesophageal echocardiography? S. Kort, B. Pulipati, D.L. Brown. Stony Brook University Medical Center, Stony Brook, United States of America Purpose: Three-dimensional transesophageal echocardiography (3D TEE) can provide additional information to that obtained by 2D TEE for specific indications. However, incremental value of 3D TEE over 2D TEE for routine use regardless of the indication has not been evaluated and is the aim of this study. Methods: We compared the data obtained from 3D and 2D TEE studies of 66 consecutive patients performed for various indications by the same operator. The time required for completion of 3D and 2D image acquisition and 3D reconstruction was compared to the time required for 2D acquisition performed alone for similar indications. Results: 3D TEE provided additional information to that obtained by 2D TEE in 55% of patients. 3D TEE revealed more detailed anatomy of the mitral valve and prosthetic valves in the mitral and aortic positions, offered enhanced visualization of the entire length of intracardiac catheters and was therefore most helpful in the assessment of valvular heart disease, evaluation of endocarditis involving native, prosthetic valves and intracardiac wires, delineation of complications related to endocarditis and guidance of percutaneous procedures. 3D TEE also provided additional information for other indications (exclusion of cardiac source of emboli and assessment prior to cardioversion). Adding 3D acquisitions and reconstructions to the routine 2D TEE protocol significantly prolonged the procedure time (41.28±17.58 vs 24.31±13.3 minutes, p<0.01). Conclusion: 3D TEE provides additional information to that obtained by conventional 2D TEE in the majority of patients regardless of the indication for the study. Because the additional imaging and reconstructions prolong the procedure time, development of specific protocols for efficient integration of 2D and 3D imaging is indicated before recommending this modality for routine clinical use. P2183 Does ventriculo-arterial coupling change during the course of normal pregnancy? An echocardiographic study R.O. Jurcut 1,O.R.Savu 1,S.Giusca 1,I.L.Gussi 2, R. Enache 1, B.A. Popescu 1, J. D Hooge 3, J. Deprest 3, J.U. Voigt 3, C. Ginghina 1. 1 Institute of Cardiovasc.Diseases C.C.Iliescu/Inst. De Boli CV, Bucharest, Romania; 2 Carol Davila University of Medicine and Pharmacy, Bucharest, Romania; 3 Catholic University of Leuven (KULeuven), Leuven, Belgium Purpose: Pregnancy is a physiologic condition associated with significant intravascular volume expansion and progressively decreased systemic vascular resistance due to the low impedance utero-placental circulation as well as associated vasodilatation. The aim of the study was to assess the evolution of ventriculoarterial coupling during the course of normal pregnancy. Methods: Twenty-seven pregnant women (30.7±2.9 years) and 14 age and sexmatched non-pregnant controls (30.2±4.4 years) were included. Echocardiography with conventional 2D and Doppler was performed longitudinally at 11-14, and 32 weeks during pregnancy, and at inclusion for the control group. Total vascular resistance (TVR), aortic distensibility (ADis) and arterial elastance (Ea) were calculated to characterize vascular adaptation. Left ventricular (LV) endsystolic wall stress (ESWS) and end-systolic elastance (Ees) were calculated. Ventriculo-arterial coupling index was derived as the arterial to end-systolic ventricular elastance ratio, as previously reported. Repeated measurements ANOVA was used to assess parameters evolution during pregnancy, and t-test was used for comparisons with the non-pregnant controls. Results: During pregnancy we found a progressive increase in LV end-diastolic volume (93.8±7.0 vs 88.8±6.0 ml in 3rd vs 1st trimester, p<0.01) and stroke volume (78.7±14.8 vs 68.7±12.5 ml, p<0.05), associated to a decreased TVR (982.7±284 vs ±158 dyne.s/cm5, P<0.05), which was significantly lower than in controls (1372.9±212 dyne.s/cm5, p<0.01). Aortic distensibility increased during pregnancy, reaching its peak during 3rd trimester (7.55±2.5 vs 6.25±2.1 mmhg -1,p<0.05). This change was present even after adjusting for maternal age (p<0.01), heart rate (p<0.01), and mean arterial pressure (p<0.01), known determinants of ADis. End-systolic wall stress was lower than in controls, and decreased significantly during pregnancy with a nadir at 3rd trimester (29.4±5.6 vs 41.9±9.6 g/cm 2,p<0.01). With a non-significant trend for increase of both Ea and LV Ees, the ventriculo-arterial coupling index was stable throughout pregnancy (0.79±0.11 vs 0.75±0.11, NS). Conclusions: Pregnancy is an increased preload state associated with progressively decreased total vascular resistance and increased aortic compliance, decreased end-systolic wall stress and increased cardiac output, leading to preserved ventriculo-arterial coupling P2184 Comparison between arterial wave intensity and arterial elastance to end-systolic ventricular elastance ratio as indices of ventricular-arterial coupling F. Antonini-Canterin 1, R. Caruso 2, R. Enache 3, B.A. Popescu 4, C. Ginghina 4,O.Vriz 5,D.Pavan 6, E. Leiballi 1, S. Carerj 2, G.L. Nicolosi 1. 1 Azienda Ospedaliera S. Maria Degli Angeli, Pordenone, Italy; 2 Policlinico Universitario, Messina, Italy; 3 Institute of Cardiovasc.Diseases C.C.Iliescu/Inst. De Boli CV, Bucharest, Romania; 4 Carol Davila University of Medicine and Pharmacy, Bucharest, Romania; 5 Cardiology, San Daniele Del Friuli, Italy; 6 Cardiology, San Vito Al Tagliamento, Italy Background: The ventricular arterial coupling is a key determinant of cardiovascular performance. One reliable index of this coupling is the ratio of arterial elastance (Ea) to end-systolic ventricular elastance (Ees). Recently, carotid artery wave intensity (WI) has been used as a new index which provides information Abstract P2182 Table 1 Indication # of Patients # of Patients with Additional Information Provided by 3D MTEE Additional Data by 3D MTEE Pre-cardioversion 17 8 (47.1%) LAA thrombus excluded in technically difficult studies, malcoaptation of MV leaflets with central regurgitant orifice, mild P2 prolapse, incidental mobile fibroelastoma attached to the atrial surface of A2, better delineation of MV annular ring, better delineation of LAA clot, tethering of MV leaflets, excluded MV prolapse, retained MV chordae Source of Cardiac Emboli 16 6 (37.5%) LAA thrombus excluded in technically difficult studies, malcoaptation of the MV leaflets, MV anterior leaflet thickening with no prolapse, Lambl s excrescence, mobile atheroma in mid aortic arch, better definition of an LV thrombus with multiple extensions, better visualization of bioprosthetic MV and AV leaflets and struts, exclusion of paravalvular leak in the presence of eccentric AI, incidental torn chordae Endocarditis 12 6 (50%) Precise localization of MV leaflet perforation and attachment of vegetations, retained MV chordae, delineation of MV anatomy and extent of vegetations, excellent delineation of pacing leads for exclusion of vegetations, better visualization of AV struts Mitral Valve (78.6%) A2 and P2 prolapse, central malcoaptation and tethering, precise localization of partially dehisced prosthetic MV, retained posteromedial papillary muscle and chordae, better delineation of a partially ruptured papillary muscle and a torn chordae, better visualization of flail and partially flail MV Aortic Valve 5 3 (60%) Better visualization of prosthetic valve, residual VSD post AVR and VSD repair, incidental A2 prolapse ASD/PFO closure 2 2 (100%) Better delineation of ASD location and size, visualizing deployment of both arms of Ampulatzer device in the LA, better delineation of relationship between device and other structures, fenestrated septum identified

52 352 Echocardiography in cardiomyopathy / New or improved: angiogenesis and remodeling about the interaction of the heart and vascular system, as the first peak (W1) represents the forward compression wave and reflects left ventricle (LV) contractile function. We aimed to compare these two indices of ventricular-arterial coupling and to assess their correlations with parameters of LV function. Methods: We enrolled 77 consecutive patients (pts) without significant aortic or mitral valve disease referred to our echocardiographic laboratory. An echocardiographic and carotid ultrasound study (using a Prosound Alfa 10 Aloka machine) was performed, assessing LV function and ventricular-arterial coupling. The Ea/Ees ratio was determined, where Ea was calculated from stroke volume (SV) and end-systolic pressure as Systolic BP 0.9/SV and Ees was calculated by a modified single-beat method, as previously described, using an estimated normalized ventricular elastance at arterial end-diastole (ENd): Ees = [Diastolic BP (ENd(est) Systolic BP 0.9)]/(ENd(est) x SV). We determined WI as (dp/dt) (du/dt) at the level of right common carotid artery. A cut-off value for Ea/Ees ratio of >1.3 was considered for a pathologic ventricular-arterial coupling. Results: The clinical characteristics of pts were: mean age 64±15 years; 51 men. Hypertension was present in 33.3% of pts, coronary heart disease in 35.1%, non-ischemic dilated cardiomyopathy in 10.4%. Mean LV ejection fraction was 52±14%. Mean value of Ea/Ees was 1.43±0.72 and of W1 was 14130±9940 mmhg m/s3. Ea/Ees ratio and W1 showed a statistically significant negative correlation (r = -0.43, p <0.001). Considering the cut-off value of 1.3 for Ea/Ees ratio, W1 was significantly lower in patients with an Ea/Ees ratio >1.3 as compared with those with a normal ratio (10160±6500 vs 16800±11100 mmhg m/s3, p =0.002). Ea/Ees ratio and W1 were significantly correlated with parameters of LV systolic function: LV ejection fraction (r = and 0.56 respectively) and systolic mitral annular velocity, S-wave (r = and 0.66 respectively) (all p <0.001). Conclusions: The arterial WI significantly correlates with Ea/Ees ratio, a previously validated index of ventricular-arterial coupling. Both indices are strongly correlated with echocardiographic parameters of LV systolic function. The clinical value of these findings remains to be determined. Purpose: Non-ischemic diabetic cardiomyopathy may be due to myocardial steatosis. We evaluated left ventricular (LV) multidirectional strain/strain rate (SR) using 2D speckle tracking in patients with truly uncomplicated type 2 diabetes mellitus (DM) and documented myocardial steatosis on magnetic resonance spectroscopy. Methods: One hundred male subjects (47 with and 53 without DM) were recruited. Exclusion criteria for DM patients included HbA1c >8.5%, known cardiovascular disease or DM related complications, hyperlipidemia, blood pressure >150/85 mmhg. Myocardial ischemia was excluded by a negative dobutamine stress test. Healthy controls were matched for age, body mass index and body surface area. Results: Mean age was 57±6yrs. Median DM diagnosis duration was 4yrs, and mean HbA1c was 6.4±0.7%. There were no differences in LV end-diastolic volume index (41±9 vs44±8ml/m 2, p=ns), end-systolic volume index (16±5 vs 18±4mL/m 2, p=ns) and ejection fractions (61±6 vs60±5%, p=ns). Transmitral E/A (0.95±0.21 vs 1.12±0.32, p=0.007) and pulmonary S/D ratios (1.45±0.28 vs 1.25±0.27, p=0.001) were more impaired in diabetics. Diabetic patients had impaired longitudinal but preserved circumferential and radial functions (Table). Presence of DM was an independent predictor for longitudinal strain, systolic SR and early diastolic SR on multiple linear regressions (all p<0.001). Table 1. Strain and Strain Rate Parameters Between Patients with Diabetes Mellitus and Healthy Subjects Variable DM Patients (n=47) Controls (n=53) p value Mean global longitudinal strain (%) -18.3± ±1.9 < Mean global longitudinal systolic SR (s -1 ) -0.99± ± Mean global longitudinal early diastolic SR (s -1 ) 1.04± ±0.26 < Global circumferential strain (%) -22.7± ±3.2 NS Global circumferential systolic SR (s -1 ) -1.40± ±0.23 NS Global circumferential early diastolic SR (s -1 ) 1.79± ±0.61 NS Mean radial strain (%) 40.6± ±12.1 NS Mean radial systolic SR (s -1 ) 1.71± ±0.48 NS Mean radial early diastolic SR (s -1 ) -1.98± ±0.70 NS DM: diabetes mellitus; SR: strain rate; NS: not significant. Conclusions: In uncomplicated type 2 DM patients with documented myocardial steatosis, LV longitudinal systolic and diastolic functions were impaired but circumferential and radial functions were preserved. P2185 Uric acid level is an independent marker of left ventricular hypertrophy and impaired early diastolic relaxation in never treated hypertensives P. Xaplanteris, C. Vlachopoulos, K. Aznaouridis, A. Bratsas, I. Dima, K. Baou, G. Vyssoulis, C. Stefanadis. Hippokration General Hospital of Athens, Athens, Greece Background: Elevated levels of serum uric acid (UA) have emerged as a risk factor for cardiovascular disease in patients with essential hypertension (HT). We investigated the relationship between UA level and echocardiography indices in never treated subjects with essential HT. Methods: The study included 1100 newly diagnosed, never treated hypertensives (651 males, mean age 52.7±11.8 years, mean systolic blood pressure 164.8±9.1 mmhg, mean diastolic blood pressure 100.6±7.4 mmhg) naive to anti-ht medications. Left ventricular function was assessed by means of echocardiography, as part of the initial diagnostic work up; left ventricular mass index (LVMI), ejection fraction (EF), peak E- and A- velocity, E/A ratio, Tei index and left ventricular midwall fractional shortening (MWFS) were accordingly calculated.the relations between UA and echocardiographic indices were assessed using Pearson s correlation coefficient and univariate linear regression analysis, after adjusting for age, smoking, systolic/diastolic blood pressure, body mass index, fasting glucose and total cholesterol. Results: In our study population mean UA level was 5.3±1.7 mg/dl, LVMI 115.2±13.1 g/m 2, EF 64.9±4.9%, peak E-velocity 0.69±0.12 m/s, peak A- velocity 0.73±0.14 m/s, E/A ratio 0.96±0.22, Tei index 0.61±0.06, MWFS 21.7±3%. UA was correlated with LVMI (r=0.26, P<0.01), EF (r=-0.14, P<0.01), peak E-velocity (r=-0.132, P<0.01), E/A ratio (r=-0.07, P<0.05) and Tei index (r=0.113, P<0.01) but not with peak A-velocity or MWFS. In univariate linear regression analysis, UA emerged as as independent predictor of LVMI (β=0.574, P<0.05, adjusted R2 change 0.003) and E/A ratio (β=-0.008, P<0.05, adjusted R2 change 0.003). Conclusion: UA levels independently predict left ventricular hypertrophy and impaired early diastolic relaxation, as assessed by LVMI and E/A ratio in never treated HT. The mechanism responsible for the detrimental effect of uric acid on myocardial performance in hypertensives requires further investigation. P2186 Differential effects of type 2 diabetes mellitus with intensive glucose control on left ventricular myocardial functions C.T.A. Ng 1, V. Delgado 1, R.W. Van Deer Meer 1,M.Bertini 1, G. Nucifora 1, D.Y. Leung 2,N.R.VanDeVeire 1,H.J.Lamb 1, M.J. Schalij 1,J.J.Bax 1. 1 Leiden University Medical Center, Leiden, Netherlands; 2 The University of New South Wales, Sydney, Australia NEW OR IMPROVED: ANGIOGENESIS AND REMODELING P2187 Whole genome expression analysis in patients with chronic total coronary occlusion confirms negative correlation of interferon-beta with coronary collateralization S.H. Schirmer 1, A.M. Van Der Laan 2, J.O. Fledderus 3, O.L. Volger 4, M. Boehm 1, A.J.G. Horrevoets 4,J.J.Piek 2,N.VanRoyen 2. 1 Universitaetsklinikum der Saarlandes, Homburg, Germany; 2 Academic Medical Center, Amsterdam, Netherlands; 3 University Medical Center Utrecht, Utrecht, Netherlands; 4 VU University Medical Center, Amsterdam, Netherlands Purpose: Recently, we reported increased interferon (IFN)-beta signaling in patients with single vessel subtotal coronary stenosis and insufficient coronary collateral artery development, and showed that IFNbeta attenuated arteriogenesis in mice. Here, we investigated whole genome RNA expression analysis of stimulated monocytes from patients with chronic total occlusion (CTO) of a coronary artery and different degrees of collateralization. This patient group would benefit most from a pro-arteriogenic therapy as both the primary intervention as well as long-term results show lower rates of success than in patients with non-total coronary narrowings. Methods: 50 patients with CTO scheduled for elective PCI underwent intracoronary wedge-pressure measurements and assessment of pressure-derived collateral flow index (CFI). Monocytes were isolated from peripheral blood by negative isolation, and stimulated with 10 ng/ml lipopolysaccharide (LPS) for 3h. From 10 patients with highest and 10 with lowest CFI, RNA was isolated, amplified and hybridized to whole-genome bead-chip arrays (Illumina ). After normalization, differential expression was analyzed and Gene Set Enrichment Analysis (GSEA) was performed. Real-time RT-PCR was performed to validate gene expression in the whole patient group (n=50). Results: Baseline characteristics did not differ between patients with high (0.27±0.06) or low (0.47±0.08) CFI. After correcting for multiple testing, 120 genes were found to be differentially expressed in the LPS-stimulated monocytes between patients with low and patients with high CFI, of which 65 genes were more strongly induced in the group with a low CFI. Pathway analysis (GSEA) showed a highly significant enrichment of several interferon-related pathways in patients with a low CFI. Individual genes of these pathways were upregulated, and analysis of their promoter sequences confirmed the strong enrichment for IFNbeta response elements. Real-time RT-PCR analysis of the whole patient group (n=50) confirmed increased expression of IFNbeta regulated genes in stimulated monocytes from patients with low CFI, showing significant negative correlations of CFI with expression of the IFNbeta-regulated genes CXCL11, CCL8, IL27 and IL15RA. Conclusion: We provide evidence of increased IFNbeta signaling in a patient group with chronic total coronary artery occlusion and a hampered arteriogenic response. The data suggest inhibition of anti-arteriogenic IFNbeta-signaling as a potential therapeutic option for the stimulation of arteriogenesis in a patient group that would particularly benefit from pro-arteriogenic strategies.

53 New or improved: angiogenesis and remodeling 353 P2188 Endothelial microparticles and endothelial repair: identification of biological pathways in microparticle-mediated endothelial repair N. Werner, N. Heiermann, G. Nickenig. Universitaetsklinikum Bonn, Bonn, Germany Background: Apoptosis of endothelial cells leads to the development of endothelial dysfunction, which itself is one of the earliest pathophysiological correlates of atherosclerosis and strongly associated with an impaired cardiovascular prognosis. Endothelial cell apoptosis can be quantified using flow-cytometry based enumeration of the circulating endothelial cell-derived microparticles (EMP) within peripheral blood. Bone marrow derived endothelial progenitor cells (EPC) are an important cellular risk predictor. The vasculoprotective action of EPC seem to be mediated by an enhanced reendothelialization process after endothelial cell damage e.g. in endothelial dysfunction. We postulate that the apoptotic endothelial cell interact with the circulating EPC via EMP. Methods and Results: EMP were obtained from human coronary arterial endothelial cells (HCAEC) after serum starvation and isolated using ultracentrifugation. Flow cytometric analyses confirmed that EMP were positive for annexin V, CD31 (PECAM), CD49e (Integrin α5), CD51 (Integrin αv), CD51/61 (Integrin αvβ3), CXCR2, and CXCR4. Co-cultivation experiments demonstrated that cultivated HCAEC co-cultured with fluorescent-labelled EMP incorporate these membrane vesicles. Incubation of cultured mononuclear cells with EMP lead to an enhanced conversion of mononuclear cells into acdi-ldl/lectin positive EPC-like cells, co-cultivation of EPC with EMP prevented TNF-alpha induced cell apoptosis, and migration of EPC was enhanced in response to EMP. Proteomic analysis confirmed that several proteins involved in apoptosis, proliferation, and migration are carried by EMP. Finally, we measured EPC liberation from bone marrow into peripheral blood in C57bl6 mice. Intravenous treatment of mice with EMP enhanced the number of circulating sca-1/flk-1 positive EPC within peripheral blood compared to vehicle treated mice. The number of circulating CD31+/Annexin+ EMP and CD34+/KDR+ EPC was determined in 40 patients with coronary artery disease using flow cytometry. The number of circulating EMP correlated with EPC function (p<0.001, r=0.601). Conclusion: EMP and circulating EPC seem to substantially interact in rodents and humans. EMP influence conversion, migration, and apoptosis of EPC in vitro. EMP mobilize EPC in vivo after intravenous treatment of wildtype mice with EMP. We speculate that the described interaction of EMP with EPC enhance the homing process of EPC within the area of endothelial cell damage. Further studies will elucidate the underlying molecular mechanisms of the interaction between apoptotic and regenerating cells. P2189 The neuropeptide catestatin acts as angiogenic cytokine in vitro and in vivo M. Theurl 1, W. Schgoer 1, P. Schratzberger 1, M. Egger 1, A. Beer 1, D. Vasiljevic 1, J. Patsch 1, S. Mahata 2, R. Kirchmair 1. 1 University Hospital for Internal Medicine I, Innsbruck, Austria; 2 University of California, San Diego, United States of America Introduction: Catestatin (Cat), a biologically active fragment of Chromogranin A was initially described as a nicotinic antagonist inhibiting catecholamine release from adrenal medulla. Recently, also other biological effects for this peptide were described like release of histamine or activation during cutaneous wounds. We found that Cat induces chemotaxis on a variety of cells including endothelial cells (EC) and therefore hypothesized that Cat might act as a novel angiogenic cytokine. Results: To investigate the effect of Cat on EC differentiation into vascular structures in vitro, we performed a matrigel tube formation assay in the absence or presence of different concentrations of Cat. Cat at a concentration of 10-9M was most effective in promoting tube formation (1.77±0.079 vs. ctr.; n=4, P<0.01). This effect could be blocked by a Cat antibody (Ab) (0.87±0.1 vs. ctr; n=4, P<0.01 vs. Cat). The migratory response of ECs toward Cat was measured with a modified boyden chemotaxis chamber. Cat dose-dependently induced chemotaxis of EC (max. 10-9M: 1.67±0.034 vs. ctr; n=6, P<0.01). Additionally, Cat specifically induced proliferation of EC as measured by cell numbers of starved EC (1.86±0.13 vs. ctr., n=4, P<0.01; Cat-Ab 0.97±0.06 vs. ctr; n=4, P<0.05 vs. Cat). Western blot analysis revealed stimulation of ERK by 10-9M Cat indicating activation of this signal transduction pathway by Cat. We tested for angiogenic effects in vivo by using 2 different mouse models. In the mouse cornea neovascularization model Cat induced significant growth of new blood vessels. In the unilateral limb ischemia model injection of Cat (10 μg every other day for 2 weeks) into adductor muscles increased capillary (475±31 vs. 303±28/mm 2 ; n=7, P=0.003) and arteriole (10.1±0.8 vs. 5.2±1.0/mm 2 ;n=7, P=0.001) density, and accelerated perfusion recovery as shown by LDPI (LDPI ratio ischemic/control leg after 28 days of ischemia) 0.94 vs. 0.74; n=10, P= Conclusion: Our observations demonstrate that the neuropeptide Cat induces angiogenesis in vitro and in vivo inducing direct effects on EC. Beneficial effects in the limb ischemia model indicate that Cat might be a useful agent inducing therapeutic angiogenesis. P2190 Metallothionein enhances angiogenesis and arteriogenesis by modulating smooth muscle S. Zbinden 1,J.Wang 2, M. Adenike 2,H.Morsli 2,S.E.Epstein 2, M.S. Burnett 2. 1 Inselspital Bern, Berne, Switzerland; 2 Washington Hospital Center, Washington, United States of America Introduction: Metallothionein (MT)is a potent immunomodulatory molecule known to play a protective role incardiac and cerebral ischemia. Previously, we have shown that MT is highly upregulated following the induction of acute hindlimb ischemia in a mousemodel. The objectives of this study were to determine if MT is important incollateral development, and to investigate the mechanisms by which MTcontributes to flow recovery following the induction of acute hindlimb ischemia. Methods: Laser Doppler perfusion imaging andmatrigel plug assays were used to assess both collateral flow recovery andangiogenesis in MT knockout mice, compared to wildtype animals. Smooth muscle cells (SMCs) were isolated from MT knockout mice, and proliferation, migration and invasion assays were performed. Geneexpression of MMP9, PDGFR, VEGF in SMCs were measured by real time PCR. CD11b+ cells were isolated from MT knockout and wildtype animals and tested for invasiveness using an ECISassay. Results: We found that blood flow recovery (arteriogenesis) measured by Laser Dopplerwas reduced in MT KO mice (p=0.017). Furthermore, angiogenesis was impaired in MT knockout micewith significantly fewer vessels in the matrigel plugs from the MTKO animals compared to the plugs from the wildtype mice (6.19±0.916 vs 0.333±0.161, p=0.004). MTKO SMCs showed impaired proliferation using an MTT assay (p<0.05). Migratory capacity ofaortic SMCs from MTKO mice was significantly impaired compared to wildtype SMCs (O.D. units, 2.38±0.02 vs. 2.76±0.06, p=0.004). A similar pattern was observed in the invasion assay, with reduced invasiveness in the MTKO vs.wildtype cells (O.D. units, 0.700±0.02 vs ±0.05, p=0.008). MTKO SMCs had significantly lower expression levels of matrix metalloproteinase-9 (MMP9), (2% of wildtype, p=0.006). Likewise, MMP9 protein levels were decreased in MTKO cells, as demonstrated by ELISA. VEGF mrna levels were significantly lower in MTKO SMCs, (43% of wildtype, p=0.0006), as were VEGF-(p=0.015) and PDGF protein levels (54% of wildtype, p=0.005). CD11b+ cells from MT knockout mice were more invasive than wildtype cells (p<0.05). Conclusion: Both collateral flow recovery and angiogenesis are impaired in MTknockout mice. Possible mechanisms contributing to these deficiencies includeendothelial, SMC, and macrophage dysfunction in the MT knockout animals. P2191 Beta 2 adrenergic receptor improves the endothelial progenitor cells angiogenic function R. De Rosa, G. Galasso, F. Piscione, G. Santulli, A. Pierri, D. Sorriento, G. Iaccarino, B. Trimarco, M. Chiariello. Azienda Ospedaliera Universitaria Federico II, Naples, Italy Background: Endothelial progenitor cells (EPC) are present in the systemic circulation and home to sites of ischemic injury where promote neo-angiogenesis. We recently showed that β2 Adrenergic Receptors (β2ar) play a critical role in vascular tone regulation and neo-angiogenesis. To date, no data are available on the role of β2ar on EPC biology. Aim: To evaluate the role of β2ar on EPC angiogenic function. Methods: β2ar deficient mice (KO) and wild type (WT) mice in a C57/BL6 background, subjected to unilateral hindlimb ischemic surgery were used for this study. Circulating mouse EPC were harvested 5 days after ischemic hindlimb surgery and cultured according to previously described techniques. Fluorescence-activated cell sorter (FACS) analysis was used to detect the cell surface expression of the endothelial cell antigen Flk-1 on cultured EPC. β2ar expression on EPC was evaluated by Western blot (WB) analysis. EPC migration was performed using a modified Boyden chamber assay, while vascular network formation was assessed with an in vitro matrigel assay. To evaluate in vivo the EPC angiogenic function mice hindlimb blood flow was measured using a Doppler flow analyzer immediately before surgery and up to 3 weeks. Results: WB showed the expression of β2ar on EPC derived from WT mice. Stimulation of EPC derived from WT mice with isoproterenol (ISO), a potent β2ar agonist, induced a 4fold increase of Flk-1 expression on EPCs as assessed by FACS (p<0.05 vs basal condition) indicating a role of β2ar on EPC differentiation. Furthermore, ISO stimulation of WT derived EPC induced a 3fold increase mobilization (p<0.05 vs basal condition) and significantly increased EPC related vascular network formation as confirmed by tubules formation on matrigel assay (60±5 ISOvs10±3, p<0.05). Since KO mice are compromised in hindlimb reperfusion after ischemia, we investigated EPC levels after culture in WT and KO mice. Five days after the induction of ischemia, the number of EPC derived from WT mice increased 3fold compared to KO in response to ischemic surgery (p<0.05 vs EPC derived from KO mice), while no differences were noted before surgery. Finally, rescue experiments were performed comparing WT and KO EPCs. Interestingly, the impairment in limb reperfusion in KO mice was rescued by intravenous infusion of WT EPCs but not of KO EPCs as confirmed by Doppler analysis. Conclusion: The present study provides the first evidence that β2ar stimulation improves the in vivo and in vitro EPC angiogenic function.

54 354 New or improved: angiogenesis and remodeling P2192 Stimulation of transmural capillary endothelialization of small-diameter synthetic vascular grafts through local overexpression of a novel recombinant VEGFR2-ligand VEGF-A109 J. Hytonen 1, O. Leppanen 1, P. Korpisalo 1, S. Laidinen 1, D. Bergqvist 2, K. Alitalo 3, T.T. Rissanen 1, S. Yla-Herttuala 1. 1 A.I.Virtanen- Institute, University of Kuopio, Kuopio, Finland; 2 Uppsala University Hospital, Uppsala, Sweden; 3 University of Helsinki, Helsinki, Finland Background: Endothelialization of prosthetic vascular conduits through transmural capillarization is a theoretically appealing way to increase biocompatibility and ultimately improve the currently dismal patency rates of small-diameter prosthetic bypass grafts. However, in sharp contrast to non-human primates, in which highporosity PTFE vascular grafts are consistently endothelialized through transmural capillarization, human results have been discouraging, which may be caused by inadequacy of angiogenesis. Recently, we have shown in normal and ischemic skeletal muscle that transient overexpression of VEGF-A promotes capillary arterialization and sprouting angiogenesis, and induces supraphysiological blood flow. We hypothetized that transfection of perigraft tissues at the time of graft implantation would augment transmural capillarization and luminal endothelialization of high-porosity PTFE grafts. Methods: 52 NZW rabbits received 87 eptfe (30mm, 2.0mm ID, 60μm internodal distance) carotid end-to-end interposition grafts, and were randomized to local therapy with adenoviruses (Ad) encoding 1) VEGF-A165; 2) novel recombinant VEGF-A109 with identical ligand-induced VEGF-receptor-2 dimerization properties; or 3) control protein (nuclear-targeted β-galactosidase [LacZ]). At 6 or 28d after surgery contrast-enhanced CPS Doppler ultrasound data were obtained from target area and vessels were explanted for histology and expression studies. Results: AdVEGF-A165 and AdVEGF-A109 dramatically increased perfusion in perigraft tissues at 6d, a time point close to peak transgene expression (14.2±3.6 or 16.7±2.6 fold increase vs. baseline, P<0.01). At 28d the effect was attenuated but still significantly higher than baseline (2.9±1.0 or 3.6±1.3 fold increase, P<0.05). At 6d no luminal endothelial cells were observed in any of the groups. Three weeks later, at 28d, animals that had received AdVEGF-A165 or AdVEGF- A109 displayed an increase in luminal endothelialization through transgraft growth (9.8±3.3% or 7.9±3.4% luminal endothelial coverage at mid-graft vs. 0% in controls, P<0.01). No signs of increased pannus formation at anastomotic regions or luminal stenosis were observed in the treatment groups as compared to LacZ controls. Conclusions: This study suggests that local delivery of AdVEGF-A165 or AdVEGF-A109 introduced to the surgical wound at the time graft implantation - with no additional delay or morbidity associated with procedures such as autologous cell harvest - is a promising novel strategy to increase endothelialization of high-porosity synthetic vascular grafts. P2193 Angiopoietin-like 2 is a pro-angiogenic factor with potent vasodilator and hypotensive activity in mice N. Farhat, N. Thorin-Trescases, A. Drouin, B. Allen, A. Mamarbachi, M.A. Guillis, E. Thorin. Montreal Heart Institute, Montreal, Canada Angiopoietin-like 2 (Angptl2) is an orphan circulating 57 kda protein with predicted vascular activity. Our objectives were to study the pro-angiogenic activity of Angptl2 and its effect on vasomotor tone and blood pressure regulation in mice. We purified an Angptl2-GST fusion protein from the media of stably transfected HEK 293 cells by affinity chromatography on glutathione Sepharose. Migration and tube-like structure formation of cultured human umbilical vein endothelial cell (HUVEC) was studied in the presence of Angptl2 (250 nm). Migration was increased 5 times by Angptl2 (P<0.05), while tube-like structure formation was increased in Matrigel from 16±4 tubes to 67±13 (n=3, P<0.05). For comparison, VEGF (26 nm) increased tube formation to 72±14. In vitro, exogenous addition of purified Angptl2 (1 nm) induced 64±7% relaxation (n=10) of preconstricted (U46619, 30 nm; thromboxane A2 analog) isolated mesenteric arteries from C57BL6 mice. This response was endothelium-independent (62±13%; n=4), while acetylcholine-induced relaxation was abolished in denuded arteries (P<0.05). In intact arteries, while the nitric oxide synthase inhibitor N-nitro-Larginine (L-NNA, 100 μm) magnified Angptl2-induced relaxation to 82±5% (n=9, P<0.05), this response was fully prevented by ODQ (1 μm; n=4, P<0.05), an inhibitor of the soluble guanylate cyclase. In vivo intra-carotid injection of Angptl2 (6 μg/kg, 200 μl bolus) induced a rapid drop in systolic blood pressure from 89±3 (n=9) to 70±3 mmhg(p<0.05). The time to recover 50% of the pre-injection blood pressure (t50%) value was 250±63 sec. In the presence of L-NNA (5 mg/kg) baseline blood pressure increased (P<0.05) from 86±1 to111±3 mm Hg, but was unaffected by ODQ (1 mg/kg; 87±7 mm Hg); the hypotensive effect of Angptl2 (-19±2 mm Hg) was potentiated (P<0.05) by L-NNA (-33±3 mm Hg), but prevented by ODQ (-2±2 mmhg; P<0.05). In conclusion, Angptl2 is a pro-angiogenic factor with new vasodilatory and hypotensive activities. P2194 Tissue factor gene silencing contributes to inastabilization of neo-vessels formation G. Arderiu, E. Pena, L. Badimon. Barcelona Cardiovascular Research Center, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain Purpose: Accumulating evidence has transformed our view of tissue factor (TF) from a protease coreceptor triggering coagulation and thrombus formation into a multi functional transmembrane signaling receptor involved in angiogenesis and inflammation. Since atherosclerotic plaques seem to increase their risk in association to its neovascularization, we sought to investigate whether TF could trigger neovessel formation and confer risk to atherosclerotic plaques. Methods: We have used a three-dimensional co-culture system with human microvascular endothelial (HMEC-1), human vascular smooth muscle cells (HVSMC) and an in vivo model of xenograft implantation in mouse. HVSMC obtained by the explant technique from coronary arteries of heart explants during transplantation surgery and HMEC-1 were mixed and then plated together onto basement membrane-like gel (Matrigel). To discriminate each cell type, cells were labeled with two different fluorescent membrane dyes, PKH2 and PKH26. Analysis of capillary-like network formation was performed by time lapse video microscopy (Leica TCS SP2-AOBS). Chemotactic migration was measured in a modified Boyden chamber. Low expression of TF was induced with sirna, the delivery of TFsiRNA into the cells was done by a Nucleofactor device. For the in vivo studies cells were injected with the matrigel plugs subcutaneously in the dorsal midline region of nude mice. After seven days post injection, mice were euthanized and tumor tissue was analyzed. Results: We observed by confocal microscopy, that direct contact between HMEC-1 and HVSMC promoted branching morphogenesis in 3D BM cultures. VSMC localize around endothelial cells promoting migration (74±7.3 vs 23±5.4) of endothelial cells. The induction of this mechanism of formation of complex tubelike structures was inhibited by the inhibition of TF expression (sirna). Low levels of TF (75%±6.5 inhibition vs control) in HMEC-1 resulted in reduced cellular migration as well as upregulation of HAND2 (three folds up), and downregulation of CCL2 (four folds down) gene expression. Importantly, inhibition of TF expression in either HMEC-1 or HVSMC decreases their shared ability to form new capillaries in vivo ±15.70 pixels main tub HMEC-1, ±20.45 pixels main tub HVSMC vs ±15 pixels control). Conclusion: Our results demonstrate that TF has a key role in coordinating the formation of stable neovessels. These results indicate that TF, in addition to triggering intraluminal thrombosis, may contribute to atherosclerotic plaque complication by inducing medial neovascularization. Funded by SAF2006/10091, Fundacion Jesus Serra P2195 Evidence of novel vasculoangiogenic effect of cilostazol T.-H. Chao 1, S.-Y. Tseng 1,Y.-H.Li 1,P.-Y.Liu 1,G.-Y.Shi 1, H.-L. Wu 1,C.-L.Cho 2, J.-H. Chen 1. 1 National Cheng Kung University College of Medicine and Hospital, Tainan, Taiwan; 2 National Sun Yat-Sen University, Kaohsiung, Taiwan Background: Cilostazol is an antiplatelet agent with vasodilating effect working through increasing intracellular cyclic adenosine monophosphate (camp) levels. It has been recently reported to have some cellular effects, suggesting that it may promote angiogenesis. In this study, we investigated the in-vitro and in-vivo effects of cilostazol in promoting angiogenesis and vasculogenesis. Methods: Colony-forming units of early human endothelial progenitor cells (EPC) treated with cilostazol were counted 7 days after isolation. Cell proliferation, chemotactic motility and capillary-like tube formation in human umbilical vein endothelial cells (HUVEC) were examined. Eight-week-old male ICR mice were treated intraperitoneally with cilostazol (1, 5, 10 mg/kg) and saline 2 times per day since day 1 to day 7 after hindlimb ischemia and flow recovery in ischemic limb was measured by a Laser Doppler perfusion image analyzer. Quantification of circulating stem cells was performed and capillary density over ischemic limb was examined by counting anti-mouse CD31+ capillaries. Assays of endothelial NO synthase (enos) and Akt phosphorylation and vascular endothelial growth factor (VEGF) in ischemic muscle were performed by immunoblotting. Results: Colony-forming units of EPC were significantly increased with cilostazol, an effect mediated through camp/protein kinase A-dependent pathway. Cilostazol stimulated proliferation, chemotactic motility and capillary-like tube formation in HUVEC as a NO-mediated downstream event through activation of camp/protein kinase A and phosphatidylinositol 3-kinase/Akt-dependent pathways. Cilostazol also stimulated endothelial cell expression of matrix metalloproteinase, which mediated extracellular proteolysis, leading to endothelial cell invasion and migration during angiogenesis. Blood flow ratio (ipsilateral/contralateral) recovery and capillary density after 14 days in the ischemic hindlimb were significantly improved in cilostazol-treated mice (10mg/kg) than vehicle control, which were attenuated by L-NAME. Circulating CD34+ cells was also significantly higher in cilostazoltreated mice. Cilostazol increased VEGF protein levels, and up-regulated enos phosphorylation and Akt phosphorylation in ischemic muscle. Conclusions: Cilostazol enhanced the vasculo-angiogenic response in vitro and in vivo, providing a unique mechanism for beneficial effect of this drug in limb ischemia, partly mediated by activation of enos and VEGF. Accordingly, further

55 New or improved: angiogenesis and remodeling 355 preclinical and clinical studies of cilostazol on the other ischemic situations such as myocardial infarction will be justified. P2196 Impact of erythroblasts in bone marrow cells on limb salvage after cell implantation in patients with critical limb ischemia Y. Iso 1, T. Soda 1,T.Sato 1,R.Sato 1, T. Kusuyama 1,Y.Omori 1, M. Shoji 1, S. Koba 1, Y. Kobayashi 1, H. Suzuki 2. 1 Showa Univ. Hospital, Tokyo, Japan; 2 Showa Univ. Fujigaoka Hospital, Yokohama, Japan Objective: Therapeutic angiogenesis with bone marrow mononuclear cells (BMCs) has recently been developed as a less invasive intervention for patients with chronic critical limb ischemia (CLI). There have been no earlier findings, however, on which factors affect the long-term outcome after BMC implantation (BMI). The aim of this study is to identify which factors influence limb salvage after BMI. Methods: Fifteen no-option CLI patients treated with BMI were enrolled in the present study. Limb ischemia was assessed with the use of the ankle-brachial index (ABI), transcutaneous oxygen tension (TcO2), and rest pain score. The cell populations among the implanted cells were determined by May-Giemsa staining and flow cytometry. Results: The limb salvage rate after BMI was approximately 53% (n= 7 in the amputation group and n= 8 in the salvage group). There were no significant differences between the groups in clinical characteristics, or in the ABI, TcO2 level, or rest pain score before implantation. The number of implanted BMCs was the same in the two groups. In the cytological studies, the percentages of erythroblasts and neutrophils in the salvage group were significantly higher and significantly lower, respectively, than those in the amputation group (p= 0.02, p= 0.03, respectively). There were no significant differences, however, in the percentages of myeloblasts, myelocytes, monocyte, or lymphocytes. The calculated erythroblast count was significantly higher in the salvage group than in the amputation group (p= 0.03), and the number of CD34-positive cells was somewhat greater in the salvage group than in the amputation group (p= 0.06). Logistic regression analysis revealed that the percentage of erythroblasts was significantly associated with limb salvage (95%CI , p= 0.03). In vitro angiogenesis assay demonstrated that CD235a (erythroid marker)-positive cells from BMCs significantly promote endothelial proliferation compared with the CD235a-negative cells (p< 0.05). Conclusions: The cellular composition of the BMCs injected into the ischemic limbs may contribute more to long-term limb outcome after the implantation than the severity of limb ischemia or background factors. The favorable effects of BMI appear to reflect the impact of the erythroblast doses. P2197 The initial down-regulation of collateral shear force allows perivascular macrophage accumulation and enhances collateral proliferation H. Sager, H. Schunkert, W.D. Ito, J. Weil. Universitaet zu Luebeck, Luebeck, Germany Purpose: Elevated shear force (SF) and increased perivascular macrophage accumulation are believed to be hallmarks of collateral growth (arteriogenesis). NOS expressions and activations are SF dependent. Endothelial monocyte/macrophage adhesion, however, is counteracted by increased NO availability and has been observed under low SF conditions. Methods: In order to resolve this paradox we first investigated the time course of SF and NOS expressions in growing rat collateral vessels after femoral artery occlusion. Secondly we examined the interdependency of SF, macrophage recruitment and collateral proliferation 1) after increasing collateral blood flow using peripheral nitroglycerin (GTN) infusions and 2) after enhancing macrophage recruitment under NO depletion (oral L-NAME). Results: (values are given as mean ± SEM, * p<0.05): SF was significantly down-regulated post occlusion (SF in dyn/cm 2 :pre-20±2.5 vs. post-occlusion 14±3.7*; n=10) correlating to reduced inos and enos expression (12 h after occlusion). Acute peripheral application of GTN led to a rise of collateral SF to pre-occlusion levels (SF in dyn/cm 2 :pre-20±2.5 vs. post-occlusion + GTN 22±2.8; n=10). Ongoing low SF conditions (continuous peripheral GTN infusion) reduced collateral macrophage recruitment (macrophages per collateral section: post- 42.5±4.4 vs. post-occlusion + GTN 26.3±1.9*; n=10) and diminished collateral proliferation (proliferative index: post- 0.54±0.04 vs. post-occlusion + GTN 0.19±0.08*; n=10) 3 days after occlusion. Chronic NO depletion led to a significant increase in pericollateral macrophage amounts (macrophages per collateral section: post ±7.3 vs. post-occlusion + L-NAME 164.6±14.7*; n=19) but not in proliferation (proliferative index: post- 0.6±0.06 vs. post-occlusion + L-NAME 0.59±0.08; n=19) 7 days after occlusion. Conclusions: Based on these results we propose following resolution of the Monocyte/NO Paradox : An initial phase characterized by low SF conditions allows the recruitment of circulating cells that are locally activated during a second phase of elevated hemodynamic forces. P2198 Fibrin improves human peripheral blood endothelial progenitor cells stemness and paracrine function A. Magera 1, R. Di Stefano 1,C.Armani 1,M.C.Barsotti 1, F. Chiellini 2, A. Minnocci 3, M. Alderighi 4, R. Solaro 4, G. Soldani 5, A. Balbarini 1. 1 Cardiac, Thoracic and Vascular Department, University of Pisa, Pisa, Italy; 2 BIOLab-Dept. of Chemistry and Industrial Chemistry,University of Pisa, Pisa, Italy; 3 BIO Labs-Polo S.Anna Valdera-SSSUP S.Anna, Pisa, Italy; 4 Dept. of Chemistry and Industrial Chemistry, University of Pisa, Pisa, Italy; 5 Laboratory for Biomaterials and Graft Technology-Inst. of Clinical Physiology, CNR, Massa, Italy Purpose: Fibrin is a natural biopolymer appealing for cell-based regenerative therapies, supporting growth, migration and differentiation of several cell types. Endothelial progenitor cells (EPC) can be easily isolated from peripheral blood, eliminating donor morbidity and used to promote in vivo angiogenesis. Aim of this study was to investigate if fibrin is a good alternative to traditional matrices for EPC growth and function. Methods: Fibrin was obtained from fibrinogen (9 mg/ml) and thrombin (25 U/ml). Ultrastructure was investigated by scanning electron microscopy (SEM), cryogenic SEM (CRYO-SEM) and atomic force microscopy (AFM). EPC were obtained from peripheral blood and cultured on fibrin ( cell/cm 2 ) for 7-14 days. Fibronectin was used as a control. Metabolic activity was assessed by WST1 assay and viability by confocal microscopy (calcein incorporation). The expression of endothelial (CD31, KDR, vwf, Ve-Cadherin) and embryonic stem cell markers (nanog, oct-4) was assessed by flow cytometry, confocal microscopy and Real Time RT-PCR. For NANOG gene oligos unable to recognize the sequences encoded by pseudogenes were used. Angiogenesis was assessed on matrigel by incorporation of EPC into HUVEC tubules. Finally, the release of 50 cytokines was evaluated by a multiplexable bead system. Results: SEM and AFM revealed a nanometric fibrous structure, with mean fiber diameter of 165±4 nm and mean density of 95.9±0.2%, while CRYO-SEM showed micropores of different size ( μm).wst1 assay showed an increased metabolic activity of EPC cultured on fibrin as compared to fibronectin (fibrin: 0.519±0.06 a.u. vs. fibronectin: 0.243±0.06, n=5, p 0.01), up to 14 days. Flow cytometry showed no difference on the expression of endothelial markers (CD31=24±9%; vwf=28±11%; KDR=57±20%; VE-Cadherin=24±7%) as compared to fibronectin. Interestingly the culture on fibrin elicited a marked induction of Oct 4 and Nanog mrna levels, being 5.5±1.3 and 20.5±3.1 fold enriched on fibrin than fibronectin, p< Angiogenesis assay revealed no significant difference between EPC grown on fibrin or fibronectin. Finally, a significative release of the following cytokines: IP-10, PDGF-bb, IL-8, IL-16, MIG, MIF, SDF-1 α, GRO-α, MCP-1, M-CSF and HGF was detected only from EPC grown on fibrin. Conclusions: Fibrin is a suitable scaffold for EPC growth, viability and differentiation. The paracrine release of cytokines involved in cell recruitment suggests that EPC grown on fibrin might accelerate blood vessel formation. The stemness more expressed by EPC grown on fibrin adds a surplus value to EPC-based therapies. P2199 Composite scaffolds for a controlled delivery of bioactive pro-angiogenetic growth factors E. Briganti 1, D. Spiller 1, C. Mirtelli 1,P.Losi 1,S.Kull 1, S. Tonlorenzi 1, R. Di Stefano 2, G. Soldani 1. 1 IFC CNR - Ospedale Pasquinucci, Massa, Italy; 2 Azienda Ospedaliero - Universitaria Pisana, Pisa, Italy Purpose: The aim of this study was to develop a novel composite scaffold that, combining good mechanical properties with a controlled and sustained release of bioactive pro-angiogenetic growth factors, should be useful for regenerative medicine applications in which a significant tissue distensibility is necessary, such as myocardial infarction. Methods: The scaffold, constituted by a synthetic biocompatible material, the polyetherurethane-polydimethylsiloxane (PEtU-PDMS), and a biological polymer, the fibrin, was fabricated by spray phase inversion in an original way. In brief, the thrombin solution was sprayed simultaneously to the PEtU-PDMS solution and then incubated overnight at 37 C with the fibrinogen solution at 10 or 20mg/ml, to reach a deep permeation of fibrin into wall thickness. During the fibrin polymerization vascular endothelial growth factors-165 (VEGF165), basic fibroblast growth factors (bfgf), and 5 or 10μg of heparin were incorporated in the fibrin layer. Structural-mechanical properties of scaffolds and the effect of fibrinogen and heparin concentration on growth factors release were evaluated. The in vitro VEGF and bfgf bioactivity was assessed using HUVEC culture. Finally, mrna expression of IL-8, L-SEL, LFA-1 and inos in human monocytes was measured to determine the immune response induced by scaffolds. Results: Morphological analysis of scaffolds surface showed an homogeneus fibrin layer, constituted by a network of randomly oriented nanofibers, firmly adherent onto the synthetic material. Tensile tests highlighted isotropy, handling and elasticity of the scaffolds. The rate of growth factors release from scaffolds was controlled by the fibrinogen concentration (20mg/ml of fibrinogen determined the slowest release rate), whereas it was not affected by heparin concentration; in addition, bfgf was retained for a longer time than VEGF and thus delivered more slowly. The biological activity of the released growth factors was maintained. Finally, scaffolds induced a slight immune response in vitro as showed by low mrna expression levels of inflammatory markers. Conclusion: The results of the present work suggest that the new developed composite scaffold once implanted, providing a co-localization and temporal dis-

56 356 New or improved: angiogenesis and remodeling tribution of bioactive VEGF and bfgf in addition to handling and elasticity, may be able to stimulate new vessels formation in the target tissue. Implants of composite scaffolds in ischemic hindlimb and in the dorsal subcutaneous tissue of Wistar rats are under investigation to assess their potential to induce angiogenesis. P2200 The impact of erythropoietin on local balance of angiopoietins and VEGF in a murine model of hind-limb ischemia G. Vogiatzi, D. Tousoulis, A. Briassoulis, A. Valatsou, C. Antoniades, D. Perrea, N. Papageorgiou, K. Marinou, D. Konstantinidis, C. Stefanadis. University of Athens, Athens, Greece Purpose: Angiopoietin (Ang) -1 and -2, their receptor Tie-2, and vascular endothelial growth factor (VEGF) regulate angiogenesis and may be important in myocardial collateral development. Ang-2 and VEGF act synergistically to produce a stable and functional microvasculature while Ang-1 can also be antiangiogenic, offsetting VEGF-induced angiogenesis. We investigated whether erythropoietin (EPO) alters the local balance of the angiopoietins and VEGF in a murine model of hind limb ischemia. Methods: Wild type C57BL/6 male mice were anesthetized and underwent surgically induced unilateral hind-limb ischemia with ligation and excision of the left femoral artery. Mice were divided in a randomised blinded manner in two groups and received either EPO (400IU/kg for 5 days in 0.2ml solution, IM) or normal saline (0.2ml for 5 days, IM). At day 28 they were sacrificed and muscle tissues from the both limbs were snap frozen in liquid N2 for RNA extraction. Mice underwent laser Doppler perfusion imaging after surgery on days 1, 7 and 28 for the estimation of the bilateral hind-limb perfusion. Quantitative real time RT-PCR was performed to analyze the differential gene expression between these two models of several angiogenic factors such as VEGF, Ang-1 and Ang-2. Results: There was no significant difference in the expression of Ang-1 and VEGF between the ischemic (13.2±1.0 and 8.4±0.6 RLU) and non-ischemic (13.4±2.39 and 8.0±0.8 RLU, p=ns for both) limb of control animals. However, the ischemic limb expressed significantly lower Ang-2 (9.1±1.5 RLU) compared to the non-ischemic limb (11.6±1.5RLU, p=0.004) in the control animals. On the contrary, EPO induced a significant elevation of VEGF expression in the nonischemic limb (10.4±1.0 RLU) compared to the ischemic limb (7.6±1.1 RLU, p=0.008). Importantly, erythropoietin prevented the elevation of Ang-2 in the nonischemic limb (6.0±1.9RLU) compared to the ischemic (7.6±3.1RLU, p=ns) limb. The expression of Ang-1 was still not significantly different between the two limbs in the erythropoietin-treated animals (12.5±2.3 RLU in ischemic vs 11.3±1.0 RLU in the non-ischemic limb). Conclusion: Erythropoietin treatment increases VEGF and decreases Ang-2 expression at the non-ischaemic limb in animals with unilateral limb ischaemia. This finding suggests that erythropoietin may play a critical role in neoangiogenesis by interfering in the mechanisms regulating remote post-conditioning. P2201 Development of a 3D nanostructured scaffold with angiogenic potential in cardiovascular applications R. Di Stefano 1, A. Magera 1, E. Briganti 2,C.Ristori 1, M.C. Barsotti 1, D. Spiller 2, C. Mirtelli 2, P. Losi 2, G. Soldani 2, A. Balbarini 1. 1 Cardiac, Thoracic and Vascular Department, University of Pisa, Pisa, Italy; 2 IFC CNR - Ospedale Pasquinucci, Massa, Italy Purpose: Medical devices realized with a biocompatible polymer, the poly(ether)urethane-polydimetilsiloxane (PEtU-PDMS), may have important cardiovascular applications such as vascular prostheses or cardiac patches. Fibrin is an optimal matrix to promote the in situ release and maintaining of cells widely used in tissue engineering. Endothelial progenitor cells (EPC) are bone marrow cells able to contribute to the vascular repair. Aim of this work was to realize a nanocomposite 3D scaffold composed by PEtU-PDMS, coated with fibrin, able to support EPC growth and differentiation and to promote in vivo angiogenesis. Methods: Scaffolds were fabricated by spray-phase inversion technique (Advanced Spray Machine Technology). Surface morphology was analysed by stereo-microscopy (Ponceau Red staining) and scanning electron microscopy (SEM). EPC obtained from peripheral blood of healthy donors were cultured on scaffold (1x106 cell/cm 2 ) in endothelial culture medium containing 5% FBS and specific growth factors. Fibronectin coating was used as control. Cell viability (Calcein-AM incorporation) and endothelial markers expression was assessed by confocal microscopy. VEGF and bfgf release was evaluated by Elisa assay. Four types of scaffolds (A: PEtU-PDMS, B: PEtU-PDMS and fibrin, C: PEtU-PDMS, fibrin and growth factors, D: PEtU-PDMS, fibrin and EPC) were implanted subcutaneously in the dorsal right and left side (angiogenesis model) or in the unilateral hindlimb (ischemia model) of female nude rats for up 14 days. In vivo neo-angiogenesis was evaluated by histology and immunohistochemistry (CD31 staining) and by Laser Doppler imaging. Results: Pounceau staining showed that fibrin coating was homogeneous and tightly bound to the synthetic polymer surface. SEM showed a well organized layer of fibrin fibres in a nanometric scale (mean diameter 140 nm). EPC viability and the endothelial markers expression was as high as on fibronectin. VEGF and bfgf release was maintained until 14 days. The histological analysis of implanted scaffolds revealed a well organized network of neovessels around the scaffolds C and D as compared with controls (A and B). In the hindlimb ischemic model Laser Doppler blood perfusion was significantly higher with scaffold C implantation. Conclusions: The spray technology can realize a nanostructured 3D scaffold made of a biocompatible polymer and fibrin as matrix to allows EPC adhesion and differentiation. This new biodegradable support has the potential of an angiogenic sticker able to promote neo vessels formation in vivo. P2202 In vivo characterization of the angiogenic properties of T-cadherin D. Pfaff 1,M.Philippova 1,M.B.Joshi 1, E. Kyriakakis 1,P.Erne 2, T.J. Resink 1. 1 University Hospital Basel, Basel, Switzerland; 2 Kantonspital, Luzern, Switzerland Purpose: T-cadherin (T-cad) is an atypical GPI-anchored member of the cadherin superfamily which is upregulated in endothelial cells of vasa vasorum in atherosclerotic lesions and in endothelial cells of tumor-derived blood vessels. Pro-angiogenic properties for T-cad have been demonstrated in vitro using the endothelial cell spheroid model and the Nicosia heart model. Myoblast-mediated delivery of soluble T-cad to mouse skeletal muscle in vivo was shown to facilitate VEGF-induced angiogenesis, and T-cad gene ablation in a mouse mammary tumor model was shown to limit tumor angiogenesis. The effects of T-cad on angiogenesis in vivo remain poorly characterized. In this study we aim to exploit two in vivo models to further investigate and characterize the angiogenic potency of T-cad expressed on endothelial cells. Methods: We have generated an array of lentiviral vectors to overexpress native T-cad protein, to express different domain-deletion mutants of T-cad protein, and to downregulate T-cad protein. The first in vivo angiogenesis model constitutes a human vasculature in mice engineered by implanting primary human endothelial cells as spheroids embedded within a matrigel-fibrin matrix. In this model endothelial cells are transduced with lentivirii prior to preparation of spheroids. The second in vivo model is the shell-less chick embryo chorioallantoic membrane and here the vasculature is directly infected with lentivirii. Results: All engineered lentiviral vectors have been tested for efficient and reproducible modulation of T-cad protein in primary endothelial cells (EC s) and a variety of cell lines (endothelial cells, keratinocytes, squamous cell carcinoma cells, melanoma cells). Spheroids composed of T-cad overexpressing EC s or T-cadsilenced EC s (and corresponding control EC s) have been implanted into mice and the relevance of T-cad to building a new vasculature in mice is under analysis. Spheroids composed of EC s transduced with domain-deletion mutants of T-cad have been analysed for sprout outgrowth in vitro. Domains relevant to the ability of T-cad to either stimulate angiogenesis or inhibit angiogenesis in a dominant negative manner) have been identified and investigations on their relevance to vessel development in vivo are under way. Conclusion: Different in vivo models are being successfully used to characterize the angiogenic impact of T-cad expressed on endothelial cells. This underestimated molecule might be of use as a potential future target for several therapeutic approaches, e.g. during tumor angiogenesis. P2203 Gene therapy with AdPDGF-C and -D induces proliferation of fibroblasts and impairs cardiac function P. Korpisalo 1, H. Karvinen 1, M. Ryhanen 1, M. Merentie 1, J. Huusko 1, M. Hedman 2, S. Laidinen 1, J. Kilpijoki 1, U. Eriksson 3, S. Yla-Herttuala 1. 1 Department of Molecular Medicine, A.I. Virtanen Institute, Kuopio, Finland; 2 Department of Cardiology, Kuopio University Hospital, Kuopio, Finland; 3 Ludwig Institute for Cancer Research, Stockholm, Sweden Platelet derived growth factors (PDGFs) are a family of proteins that regulate pericyte proliferation and stabilisation of vessels. Recently two new members of the family PDGF-C and PDGF-D were identified and reported to have angiogenic potential. Thus, they might be useful in revascularisation of ischemic tissues with gene therapy. We have created adenoviruses encoding PDGF-C and PDGF-D, and tested the angiogenic potential of these growth factors in rabbit skeletal muscle and mouse myocardium. An AdLacZ marker-gene was used as a control. An ischemia model consisting of the ligation of the superficial femoral artery was used in rabbit hindlimb. Closed-chest, trans-thoracic myocardial injections were used in mice. High resolution CPS-ultrasound was used to evaluate changes in blood flow noninvasively in both models. High frequency ultrasound was used to quantify ejection fraction and other cardiac measures in mice. Histology was used in both models for the assessment of microvascular changes. AdPDGF-C and PDGF-D were found to induce proliferation of fibroblasts and inflammatory cells in the rabbit hindlimb six days after gene transfer. In mice myocardium a similar expression of the growth factors was found to impair cardiac function, such as ejection faction and fractional shortening. Additionally, an increase in the left-ventricular inner-volume was detected implicating possible cardiac insufficiency. The angiogenic changes induced by the growth factors in either model were quite modest compared to the fibrotic and inflammatory changes and functional defects. In conclusion, PDGF-C and PDGF-D have angiogenic potential in some models but hinder the function of target tissues after gene therapy in mice and rabbits. In

57 New or improved: angiogenesis and remodeling / Markers and monitors of endothelial function 357 the light of these results, the potential of AdPDGF-C and -D for therapeutic agents in tissues where impaired function can be life-threatening seems to be limited. P2204 Collateral vessel formation in patients with documented coronary occlusion: role of gender, smoking and of their combination F. Mouquet 1, F.J. Cuilleret 1,S.Susen 1, P.V. Ennezat 1, T. Letourneau 1, P.A.M. Doevendans 2, J. Dallongeville 3, M.E. Bertrand 1,B.Jude 1,E.VanBelle 1. 1 Hopital Cardiologique CHRU de Lille, Lille, France; 2 UMCU - Cardiology Department, Utrecht, Netherlands; 3 Institut Pasteur de Lille, Lille, France In case of coronary occlusion, development of coronary collaterals is an important adaptive mechanism: it can reduce the size of myocardial infarction (MI), preserve left ventricular function, and reduce the risk of death. Women and smokers have an increased risk of cardiovascular events after MI. Preclinical studies have suggested that these patients might exhibit a less developed collateral circulation. The present study was designed to evaluate the impact of gender, smoking and their combination on collateral circulation development in the clinical setting. 387 consecutive patients with at least one coronary occlusion of a major coronary vessel at diagnostic angiography were prospectively enrolled. The duration of coronary occlusion was recorded. Collateral development was graded with a previously validated angiographic method. In the population, 19% were women and 75% were smokers. Smoking was less frequent in women (23%) than in men (88%, p=0.0001). Multivariable analysis adjusted for age, cholesterol level, diabetes, severity of coronary artery disease, and duration of coronary occlusion, found that female gender (p=0.003) and smoking (p=0.003) were independently associated with a less developed collateral circulation (Figure). Among the 4 smoking/gender combination groups, smoking/women was the group with the least developed collateral circulation (CFG=1.84±0.55) while non-smoking/men was the group with the most developed collateral circulation (CFG=3.04±0.29, p=0.0001, Figure). Conclusion: In patients with coronary occlusion, collateral circulation is less developed in women and in smokers. The combination of female gender and smoking is particularly detrimental. This could partly explain the worse cardiovascular prognosis observed in these groups of patients after MI. P2205 Effects of endogenous NO and of NO-donors in arteriogenesis K. Troidl 1,S.Tribulova 1, H. Wustrack 2, I. Eitenmueller 1, W. Schierling 1,W.J.Cai 3,C.Troidl 1, W. Schaper 1. 1 Max-Planck- Institut fuer Herz und Lungenforschung, Bad Nauheim, Germany; 2 Klinikum der J.W. Goethe Universitaet, Frankfurt am Main, Germany; 3 Dept. of Anatomy, Central South Univ. Changsha, Xiansha, China, People s Republic of Purpose: Previous studies showed that targeted enos disruption in mice with femoral artery occlusion does not impede and transgenic enos overexpression does not stimulate collateral artery growth following femoral artery occlusion (FAL), suggesting that NO from enos does not play a role in arteriogenesis. However, pharmacological NOS inhibition with L-NAME markedly blocks arteriogenesis, suggestive of an important role of NO. Methods: In order to solve the paradox we studied targeted deletion of inos as well as enos (n=12 each) with respect to collateral growth. A subset of mice lacking enos received additionally L-NIL to block all sources of NO (n=5). Next we quantified time course of mrna expression of different NOS isoforms in a high fluid shear stress arteriogenesis model in rats (n=3 for each time point). Finally we evaluated the therapeutic effect of NO donors on arteriogenesis by determination of collateral conductances and by immunohistological investigations in rabbits (n=6). Results: We found that only inos knockout could partially inhibit arteriogenesis. However, the combination of enos knockout plus treatment with the inos inhibitor L-NIL completely abolished arteriogenesis. This resulted in severe consequences: Two animals had to be sacrificed because of pedal self-amputation, two died from ischemia provoked necrosis (gangrene), and only one animal survived the observation period. enos and especially inos (but not nnos) become up-regulated in shear stress-stimulated rat collateral vessels. This was strengthened by the observation that the NO-donor DETA NONOate strongly stimulated collateral artery growth, activated perivascular monocytes and increased proliferation markers. This resulted in a significantly increased collateral conductance of 235±31 ml/min/100mmhg (control FAL 133±12 ml/min/100mmhg). Conclusion: NO is necessary for arteriogenesis but inos plays an important part. P2206 Calcium-dependent gene regulation plays a critical role during shear stress induced arteriogenesis C. Troidl 1,H.Nef 1,S.Voss 1,A.Schilp 1,S.Kostin 2,K.Troidl 2, T. Schmitz-Rixen 3,C.W.Hamm 1,A.Elsaesser 4, H. Moellmann 1. 1 Kerckhoff Klinik GmbH, Bad Nauheim, Germany; 2 Max-Planck- Institut fuer Herz und Lungenforschung, Bad Nauheim, Germany; 3 Klinikum der J.W. Goethe Universitaet, Frankfurt am Main, Germany; 4 Klinikum Oldenburg, Oldenburg, Germany Purpose: Recently we could show that an activation of the transient receptor potential cation channel, subfamily V, member 4 (TRPV4) is an early and important event during fluid shear stress (FSS) induced arteriogenesis. The aim of the present study was to investigate calcium-dependent transcriptional regulation using a clinical relevant animal model in the hind limb of pigs, to uncover possible molecular mechanisms of collateral growth. Methods: Domestic pigs (n=18, 40±1 kg) were assigned to the following groups (each n=6): (1) sham operated pig served as controls, (2) ligature of the A. femoralis, (3) ligature of the A. femoralis combined with an arterio-venous shunt distal to the occlusion, which leads to chronically increased FSS. Pigs were euthanized after 7 days. Collateral arteries and muscle tissue of the M. quadriceps were isolated and analysed using quantitative real-time PCR, Western Blot analysis and immunohistochemistry. Investigations were carried out with special focus on Kv channel interacting protein 3, (KCNIP3), camp responsive element binding protein 1 (CREB1), nuclear factor of activated T-cells, cytoplasmic, calcineurindependent 1 (NFATC1), C-JUN protein (c-jun) and myocyte enhancer factor 2C (MEF2C). Results: In shunt treated pigs a strong growth of collateral arteries results in an increased collateral flow index. Western Blot analysis showed increased protein levels of KCNIP3 in the cytoplasmic fraction after shunt treatment. This was confirmed by immunohistochemical staining. Increased phosphorylation was found for NFATC1 after shunt treatment using Western Blot analysis. Accordingly, immunohistochemistry showed decreased cytoplasmic fluorescence signals of NFATC1. CREB- as well as c-jun-positive nuclei were increased in shunt treated pigs. For MEF2C no significant changes were observed between ligature and shunt treatment. Conclusion: Western Blot results showed that of the three most important calcium-dependent transcription factors (KCNIP3; NFATC1 and MEF2C) two are activated after shunt treatment. This was confirmed by immunohistochemistry and mrna abundance. In addition the increased expression of CREB and c-jun, which are also indirectly activated by calcium point towards the pivotal role of TRPV4-triggerd increase of cytosolic calcium during arteriogenesis. Our results demonstrate the important role of calcium as a central mediator of FSS-induced arteriogenesis by activation of the mechanosensitive Ca 2+ -channel TRPV4. MARKERS AND MONITORS OF ENDOTHELIAL FUNCTION P2207 A multicenter study to assess flow-mediated dilation variability L. Ghiadoni 1,F.Faita 2,L.DeSiati 3,A.Biggi 4,G.Ambrosio 5, G.A. Lanza 6, M.L. Muiesan 7,M.Volpe 3, S. Taddei 1, F. Cosentino 3 on behalf of the Working Group on Peripheral Circulation of the Italian Society of Cardiology. 1 Azienda Ospedaliero - Universitaria Pisana, Pisa, Italy; 2 CNR Istituto di Fisiologia Clinica, Pisa, Italy; 3 2nd Faculty of Medicine, University La Sapienza, Rome, Italy; 4 Azienda Ospedaliero Universitaria di Parma, Parma, Italy; 5 Università di Perugia, Ospedale Silvestrini, Perugia, Italy; 6 Catholic University of the Sacred Heart, Rome, Italy; 7 University of Brescia, Brescia, Italy Purpose: Endothelial dysfunction is associated to cardiovascular risk factors and plays a pivotal role in prediction of cardiovascular events. Endothelial vasomotor testing may be performed non-invasively by assessment of flow-mediated dilation (FMD). Despite large efforts to standardize the technique, there are technical limitations related to its reproducibility.the aim of this multicentre study was to standardize the procedure for FMD assessment among different research centres and evaluate FMD variability over time in healthy volunteers. Methods: Seventy-five healthy subjects (aged 20-60years) were recruited in 6 italian university hospitals. FMD was assessed as dilation of the brachial artery secondary to 5 minutes wrist ischemia by trained operators using a clamp to held the ultrasound probe. Sequences of B-mode images of the brachial artery were VCR recorded for baseline FMD (time0) and repeated 1 hour after maintaining the probe in the same position (time1). A third sequence was obtained 1 month apart (time 2). Endothelium-independent vasodilation to glyceril trinitrate (25 mcg,

58 358 Markers and monitors of endothelial function sublingual) was also evaluated at time 1 and 2. FMD and response to GTN were measured blindly as percentage changes in brachial artery diameter by an automatic edge detection system at the coordinating centre. The intra- (time 0 versus 1) and inter-session (time 0 versus 2) coefficients of variation were calculated for the 6 different research centres and overall to assess FMD and GTN variability over time. Results: All recordings were suitable for analysis. FMD was 7.5±3.2% at time 0, 7.3.±3.3% at time 1 and 7.4±2.9% at time 2. Overall, the intra-session FMD variability was 10.2±12.1% ranging from 7.1 to 10.9% in the different centres. Inter-session FMD variability was 13.0±8.9%, ranging from 12.2% to 13.8% in the different centres. GTN response was 13.9±4.1% at time 0 and 12.8±4.8% at time 2. Overall inter-session variability of GTN response was 12.9±9.8%, ranging from 10.1% to 17.1% Conclusions: This multicenter study shows that intersession FMD coefficient of variation (1 month apart) results to be similar to the intra-session one (1 hour apart), which would represent the intrinsic variability in the endothelial response. Thus, a standardized procedure including operator training, defined experimental settings and automatic brachial artery measurements, ensures an adequate FMD reproducibility over time and it can be routinely used for the assessment of endothelial function in clinical studies. P2208 Endothelium function and intima-media thickness (IMT) changes in hypertensive patients under the influence of pharmacogenetically determined treatment in relation to five genes polymorphisms L. Sydorchuk 1,K.M.Amosova 2, V.P. Pishak 1, R.I. Sydorchuk 1, I.I. Sydorchuk 1. 1 Bukovinian State Medical University, Chernivtsi, Ukraine; 2 National State Medical University, Kyiv, Ukraine Objective: To evaluate endothelium function (EF) and IMT changes in patients with essential arterial hypertension (EAH) under influence of antihypertensive treatment during 9-12 months depending on I/D polymorphism in ACE gene, A1166C; in AGTR1 gene, T894G in enos gene, Pro12Ala in PPAR-γ2, Arg389Gly in ADRβ1 gene. Design/Methods: 249 patients (EAH I 26.5%; EAH II 45.8%; EAH III 27.7%; women 48.2%, men 51.8%, mean age 50.5±10.4 yrs) underwent combination therapy depending on genes polymorphism ((hydrochlorothiazide (HCTZ)+angiotensin II receptor (ARB) blocker), HCTZ+β1- blockers (BB), HCTZ+ACE inhibitors (ACEI), calcium antagonists (CA)+ARB, CA+BB, CA+ACEI). EF evaluated by Flow mediated brachial artery dilation Celermajer-test (FMD). Carotid artery IMT by Ultrasound. Efficacy criteria of treatment were FMD >10.0%, IMT <0.9mm (ESC/ESH 2007). Results: Number of patients with target IMT (<0.9mm) and FMD (>10.0%) increased by 15.9% and 29.3% after treatment, p< HCTZ+ARB increased percentage by 13.3% and 23.3%, p<0.001: reliable in ACE gene II-genotype (p 0.002), AGTR1 gene A-allele (0.001 p 0.05), enos gene G-allele carriers (0.006 p 0.023), PPARγ2 gene Pro-allele (0.005 p 0.028) and ADRβ1 gene Arg-allele (0.003 p 0.028). HCTZ+BB combo caused an 8.8% IMT increase (p=0.007): reliable in ID-genotype of ACE gene and TG-genotype of enos gene (p=0.045), without significant changes of FMD. Target IMT and FMD patients increased under HCTZ+ACEI by 18.0% and 36.0%, p<0.001: reliable in ACE gene ID-genotype (p<0.001), enos gene G-allele (0.001 p 0.046), PPARγ2 gene Pro-allele and ADRβ1 gene Arg-allele (0.001 p 0.014). 13.3% and 33.3% increase under CA+ARB, p<0.001, certainly in DD-genotype of ACE gene. CA+BB associated increase by 20.0% (p=0.011) and 53.3% (p<0.001): reliable in DDgenotype of ACE gene (p 0.011), independent on genotypes of AGTR1 gene (p 0.024), TG-genotype of enos gene, ProPro-genotypes of PPARγ2 gene and Gly-allele of ADRβ1 gene (p<0.001). CA+ACEI combo caused increase by 25.9% and 33.3%, p<0.001, certainly in DD-genotype carriers of ACE gene (p<0.001), A-allele of AGTR1 gene, G-allele of enos gene, Pro-allele of PPARγ2 gene and Arg-allele carriers of ADRβ1 gene (0.001>p 0.023). Conclusions: The reliable advantage in endothelial function improvement observed in all combinations of CA (better CA+ACEI), than with HCTZ (p<0.05) in D-allele carriers of ACE gene. Combos of CA+ARB and CA+ACEI are better than HCTZ+BB (p<0.05) in D-allele of ACE gene. P2209 Arterial wave reflections and determinants of endothelial function in erectile dysfunction patients: a hypothesis based on peripheral mode of action D. Terentes-Printzios, C. Vlachopoulos, N. Ioakeimidis, K. Baou, K. Aznaouridis, G. Antoniou, K. Rokkas, A. Askitis, C. Stefanadis. Hippokration General Hospital of Athens, Athens, Greece Purpose: Erectile dysfunction (ED) is associated with endothelial dysfunction. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthase is a determinant of endothelial dysfunction and C-type natriuretic peptide (CNP) which is highly expressed in the vascular endothelium is likely to exert a strong antiatherogenic activity that might be a key in compensating for deficiencies in NO. A possible interplay between ADMA and CNP with functional changes in penile and peripheral arteries was examined. Methods: ADMA and N-terminal fragment CNP (NT-proCNP) levels were measured in 85 ED patients and 37 subjects with normal erectile function matched for age and risk factors. Peak systolic velocity (PSV) of penile arteries below 25 cm/sec was considered to indicate severe arterial insufficiency (SAI). Augmentation Index (AIx) was measured as an index of wave reflections. Results: Patients with SAI (n=21) had significantly increased AIx (31 vs 23 vs 24%, P<0.001) and decreased NT-proCNP levels (left plot) as compared to subjects without SAI (PSV>25cm/s) and to controls. ADMA levels in patients with SAI were similar to those of men without SAI and significantly higher as compared to controls (middle plot). In ED patients, AIx exhibited a significant correlation with NT-proCNP (r=-0.19, P<0.05) and ADMA levels (r=0.17, P<0.05). Furthermore, CNP was inversely associated with ADMA (right plot). ADMA, CNP and penile arterial function Conclusions: Our data indicate that higher ADMA and lower CNP levels are unfavourably associated with a significantly decrease in penile vascular inflow and an increase in arterial wave reflections, most likely due to a markedly impaired NO and CNP activity in small arteries and arterioles. P2210 Dynamic reactivity of micro-circulation is less pronounced in type 2 diabetic subjects than in BMI and aged matched controls following a glucose challenge: potential implications for future CVD M.S.V. Chittari Macharotu, P.G. McTernan, N. Bawazeer, K. Lois, P.J. O Hare, M. Ciotola, S. Kumar, A. Ceriello. University of Warwick, Coventry, United Kingdom Purpose: Post meal hyperglycemia is an independent risk factor for retinopathy, macro vascular disease and cardiovascular disease (CVD). As limited data are available on the effects of post meal hyperglycemia on micro vascular reactivity, the aim of this study is to assess the effect of post meal hyperglycemia on both macro vascular and micro vascular reactivity simultaneously using flow mediated dilatation of brachial artery (FMD) and retinal vessel analysis (RVA) using a retinal vessel analyser. Methods: Subjects with type 2 diabetes (T2DM: Age: (mean±sd) 9.74 yrs; BMI: (mean±sd) 5.07 kg/m 2 ; n=22) and without type 2 Diabetes (ND: Age: 41.58±9.85 yrs and BMI: 30.11±4.96 kg/m 2 ; n=22) were recruited into this study, using strict criteria. Ethical approval was obtained from the Local Research Ethics Committee and all patients gave written consent. After overnight fast, a baseline FMD measurement of the right brachial artery and a measure of RVA as well as baseline blood markers were obtained. Subjects consumed 75 grams of glucose (OGTT) and plasma and serum markers, FMD and RVA were recorded every hour for 3 hrs. Results: OGTT confirmed ND and T2DM status. FMD and RVA analysis identified significant changes over time with both ND and T2DM subjects. Sub-cohort analysis determined that baseline arterial reactivity was significantly lower in T2DM subjects compared with ND subjects (P<0.05). In ND subjects, glucose challenge produced a gradual reduction of the FMD, reaching significance by 2 hr (P<0.01), no change was noted with RVA analysis. In T2DM subjects, hyperglycemia had a significant effect on FMD, (at an earlier time of 1hr) than noted in the ND subjects (P<0.05). Micro vascular reactivity in the T2DM subjects also showed a significantly different trend. Retinal arterial reactivity seems to increase initially due to rising blood glucose levels before showing reduced activity at a later stage. The dynamic range in the reactivity appears to be blunted compared with ND group, with statistically significant changes noted both at 1 and 2 hrs post glucose load (P<0.05). Conclusion: These novel data highlight that an acute increase in blood glucose can affect the arterial reactivity both at micro vascular as well as macro vascular level in T2DM patients. The blunted change in the micro circulation in T2DM could be due to either impaired auto regulation or impaired endothelial function or both. In conclusion, these findings may help to explain why postprandial hyperglycemia seems to be a risk factor for both CVD and retinopathy, indicating a possible link between CVD and retinopathy in T2DM. P2211 Non-invasiv measurement of local, regional and systemic arterial function in assessment of cardiovascular risk B. Gaszner 1, L. Priegl 1,I.Horvath 1, M. Illyes 2,A.Cziraki 1. 1 University of Pecs, Heart Institute, Pecs, Hungary; 2 TensioMed, Budapest, Hungary Purpose: Arterial stiffness parameters are commonly used to determine the development of atherosclerosis. The aim of our study was to compare local, regional and systemic arterial functional parameters measured by different non-invasiv examination methods for the assessment of cardiovascular risk.

59 Markers and monitors of endothelial function 359 Methods: The regional velocity of the pulse wave (PWVao), which shows the flexibility of the aortic wall, the local PWVcar at carotid artery measured by Doppler ultrasound, and the augmentation index (AIx), which varies proportionately with the resistance of the small arteries, were used for this purpose. Specification of the above mentioned parameters in healthy volunteers (control, n=99), in patients with either type II diabetes mellitus (DM, n=51), or ischemic heart disease (IHD, n=115) underwent diagnostic coronary angiography were performed. Measurements were simultaneously done using combined carotis Doppler echo-tracking system (Aloka SSD-5500) and oscillometric TensioClinic Arteriograph equipment. Results: The oscillometric AIx and PWVao values in control group (-39,3±31,9% and 8,5±1,6 m/s) significantly (p<0,05) increased in IHD and DM groups (Aix: -8,4±31,3% and -4,3±29,1%; PWVao: 10,2±2,3 m/s and 9,9±2,2 m/s). Echotracking PWVcar data showed similar significant tendency (PWVco 6,3±1.5 m/s; PWVIHD 7,5±1,6 m/s; PWVDM 7,4±1,3 m/s; p<0,05). Changes in echo-tracking Aix values were notable, but not significant. As a result of simultaneously conducted oscillometric and echo-tracking measurements a strong correlation of Aix, PWVcar and PWVao parameters (RAix=0,68 és RPVW=0,70) were found. Conclusions: According to the ESC 2007 guidelines in assessment of cardiovascular risk the arterial stiffness parameters were determined as part of the prognostic factors. Our results show that the increased cardiovascular risk could be assessed by the same extent with the local, regional and systemic arterial stiffness parameters using userfriendly oscillometric and echo-tracking methods. P2212 The role of asymmetric dimethylarginine in lighten the links between low-grade inflammation, endothelial and cardiorenal dysfunction in essential hypertension K. Dimitriadis, C. Tsioufis, C. Thomopoulos, D. Syrseloudis, E. Andrikou, I. Andrikou, V. Tzamou, D. Tousoulis, I. Kallikazaros, C. Stefanadis. First Cardiology Clinic, University of Athens,Hippokration Hospital, Athens, Greece Purpose: Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of the nitric oxide synthase, emerges as a marker of cardiovascular risk. Microalbuminuria, hypoadiponectinemia and subclinical inflammation are associated with atherosclerosis progression. We investigated the relationships of urinary albumin excretion, expressed as the albumin to creatinine ratio (ACR), with high-sensitivity C-reactive protein (hs-crp), adiponectin and ADMA in essential hypertensives. Methods: Our population consisted of 158 newly diagnosed untreated nondiabetic patients with stage I to II essential hypertension [106 men, mean age=49 years, office blood pressure (BP)=151/97 mmhg]. According to the ACR values determined as the mean of two non-consecutive morning spot urine samples, the study population was divided into microalbuminurics (n=32) (mean ACR= mg/g) and normoalbuminurics (n=126) (mean ACR<30 mg/g). Moreover, in all patients venous blood sampling was performed for estimation of lipid profile and hs-crp, adiponectin and ADMA concentrations. Results: Microalbuminurics compared to normoalbuminurics were older (53±7 vs 49±6 years, p<0.05), had higher 24-h systolic BP (144±11 vs 133±12 mmhg, p=0.001), while did not differ regarding sex, smoking status and metabolic profile (p=ns for all). Moreover, microalbuminurics compared to normoalbuminurics exhibited higher levels of ADMA (0.61±0.04 vs 0.55±0.03 μmol/l, p=0.001) and hs-crp (4.5±1.7 vs 2±1.1 mg/l, p<0.0001), whereas had lower adiponectin values (5.8±1.5 vs 9±2.6 μg/ml, p=0.019). In the total population, ACR was positively related to body mass index (r=0.319, p<0.0001), 24-h systolic BP (r=0.263, p<0.0001), ADMA (r=0.366, p<0.0001), hs-crp (r=0.318, p<0.0001) and negatively related to adiponectin (r=-0.169, p=0.004). Regarding ADMA, it was associated with 24-h pulse pressure (r=0.404, p<0.0001), hs-crp (r=0.221, p<0.0001) and adiponectin (r=-0.222, p<0.0001). Multiple regression analysis revealed that 24-h systolic BP, hs-crp and ADMA were the independent predictors of ACR (R2=0.58, p<0.0001). Furthermore, analysis of covariance showed that ADMA, adiponectin and hs-crp values were significantly different between groups even after adjustment for confounders (p<0.05). Conclusion: Microalbuminuric hypertensives exhibit pronounced inflammatory activation, endothelial dysregulation and hypoadiponectinemia. Moreover, the close association of ADMA with hs-crp and adiponectin, further establishes endothelial dysfunction as an integrative factor in the interpretation of ACR-related risk. P2213 Exercise induced gene-expression of DDAH-1 improves retinal microcirculation in obesity H. Hanssen 1,T.Nickel 2,V.Drexel 1,G.Hertel 1, I. Emslander 2, A. Schmidt-Trucksaess 1,M.Weiss 2,M.Halle 1. 1 Department of Prevention and Sports Medicine, Technische Universitaet Muenchen, Munich, Germany; 2 Department of Cardiology, Ludwig-Maximilians-Universitaet, Munich, Germany Purpose: Endothelial dysfunction is involved in the development of retinal microvascular changes in metabolic disorders. Retinal arteriolar narrowing and venular dilatation are associated with long-term risk of cardiovascular disease. ADMA (asymmetric dimethylarginine), a NO inhibitor, is metabolized by DDAH (dimethylarginine dimethylaminohydrolase). This study aimed to investigate the effect of regular endurance exercise on the arteriolar to venular diameter ratio (AVR) and the impact of the ADMA/DDAH-pathway. Methods: 46 male marathon runners aged were divided into the following groups: 15 obese (OR) (waist >102 cm, training distance/week (TD) 40km) and 14 lean runners (LR) (TD 40km) were compared to 17 lean athletes (LA) (TD 70km). AVR was assessed with a static vessel analyzer and blood samples were collected before and after a 10 week training program. Peripheral mononuclear cells (PBMC) were isolated by ficol gradient. DDAH-1-gene-expression in PBMC was analyzed by real time PCR. ADMA serum levels were detected by ELISA. Results: At baseline, AVR in obese runners was impaired (0.81). Endurance training improved AVR significantly in all groups (post-training: OR 0.86, LR 0.91, LA 0.96; p<0.001 for all). Training induced arteriolar dilatation was most pronounced in OR. Baseline ADMA-levels in OR were higher compared to lean subjects and decreased significantly during training (p<0.05; baseline 0.57 pg/ml to 0.46 pg/ml post-training). Associated with the ADMA decrease, we found an increase in DDAH-1 gene-expression in PBMC in OR (+220%; p<0.01). ADMA levels and DDAH gene expression were not altered in lean subjects compared to baseline. Conclusion: Obesity is associated with an impairment of the retinal microcirculation. Intensified endurance training normalizes AVR in obese runners. The amelioration of AVR in obese subjects seems to be caused by an exercise-induced improvement of endothelial function in retinal arterioles. The associated decrease in systemic ADMA levels is most probably induced by an enhanced DDAH expression. Our data suggest that endurance training improves endothelial microvascular function through modulation of the nitric oxide synthase pathway, generated by alterations of ADMA/DDAH signalling. P2214 Asymmetric dimethylarginine regulates endothelial progenitor and endothelial function via the vasodilator stimulated phosphoprotein VASP protein family F. Fleissner, J. Fiedler, J. Widder, G. Ertl, J. Bauersachs, T. Thum. Julius-Maximilians University, Wurzburg, Germany NO plays a vital role in endothelial vessel homeostasis. The NO synthase inhibitor asymmetric dimethylarginine (ADMA) reduces endothelial progenitor cell (EPC) number, differentiation and function. Migration assays using modified Boyden chambers revealed a significant reduction in migratory capacity of EPCs after treatment with increasing doses of ADMA. This effect could be rescued by adding the non-enzymatic NO donator pentaerythrithyltrinitrate (PETriN). Microarray analysis revealed deregulation of a variety genes involved in the regulation of NO bioavailability, such as vasodilator activated phosphoprotein (VASP). At the leading edge of lamellipodia and the tips of filopodia, VASP localizes to regions with dynamic actin reorganization and therefore plays an important role in cell migration. We therefore investigated the influence of ADMA on VASP expression and phosphorylation in EPC. Western Blots showed a significant reduction in VASP phosphorylation at the Ser239 site, whereas total VASP remained unchanged. Treatment with PETriN significantly increased phosphorylated VASP. Confocal imaging revealed a similar reduction in VASP phsophorylation. Interestingly, animal experiments using VASP-/- knockout mice showed improved nachrelated relaxation in organ bath experiments. Accordingly, an aortic sprouting assay showed significantly improved endothelial sprouting as well as increased numbers of circulating EPC in VASP-/- mice (90.2% increase in VASP-/- vs. wt, p<0.001). We therefore demonstrate improved endothelial function in VASP- /- mice suggesting possible compensative effects of other VASP protein family members. Indeed, the Ena/Vasp like protein (ENA) was upregulated in VASP-/- mice. SiRNA-mediated functional knockdown of ENA but not VASP in endothelial cells significantly attenuated migration capacity. Thus, ENA, a member of the VASP protein family is involved in the ADMAmediated impairment of vascular function. P2215 An optimized protocol for analysis of circulating angiogenic monocytes and endothelial progenitor cells by flow cytometry M. Hristov 1,S.Schmitz 1, T. Leyendecker 2, C. Schuhmann 3, P. Von Hundelshausen 1,F.Kroetz 3, H.Y. Sohn 3, F. Nauwelaers 4, C. Weber 1. 1 RWTH Aachen University, IMCAR, Aachen, Germany; 2 RWTH Aachen University, Department of Cardiology, Aachen, Germany; 3 LMU Munich, Department of Cardiology, Munich, Germany; 4 BD Biosciences Europe, Erembodegem, Belgium Purpose: Circulating adult endothelial progenitor cells (EPCs) have been shown to differentiate into mature endothelial cells, thus contributing to vascular homeostasis. Resident CD14dimCD16+ monocytes expressing the angiopoietin-1 receptor Tie2 functionally differ from classical inflammatory CD14bright monocytes and have also been implicated in angiogenesis. However, clinically applicable protocols for flow cytometric quantification of EPCs and Tie2+ monocytes in peripheral blood and a consensus on reference values remain elusive. Methods: The number of Tie2+CD14lowCD16+ proangiogenic monocytes and CD34+VEGFR2+CD45dim EPCs was assessed in peripheral venous blood of 58 consecutive patients (48 male, 10 female; mean age 66±11 years) with angiographically documented stable coronary artery disease by three-color flow cytometry using specific monoclonal antibodies conjugated to PerCP, PE, PE-Cy7,

60 360 Markers and monitors of endothelial function APC and APC-Cy7. Strict exclusion criteria (ACS within the last 6 months, current inflammation, autoimmune disease, ongoing or recidivated malignant disease, renal insufficiency with indication for dialysis, severe peripheral arterial occlusive disease with rest pain, atrial fibrillation and LVEF 45%) were applied to avoid confusing co-morbidity. In case of scheduled cardiac catheterization blood was drawn before the catheter intervention. Acquisition and analysis were performed on digital flow cytometers. Double- and back-gating was used to dissect complex mononuclear cell populations including a variety of overlapping phenotypes. This assessment was further refined by matching bright fluorochromes (PE-Cy7, PE) with dimly expressed markers (CD34, VEGFR2) and by automatic compensation to minimize fluorescence spillover. Results: Presuming a Gaussian distribution, we obtained average values (mean±sd) of 2.7±0.4% for Tie2+CD14lowCD16+ monocytes (range: %, CV: 14.6%) and 0.008±0.001% for CD34+VEGFR2+CD45dim EPCs (range: 0.006%-0.011%, CV: 15.8%). The intra- and inter-assay variability was 2.5% and 9.8%, respectively. Conclusions: We have developed a fast, highly sensitive and optimized assay for the flow cytometric quantification of circulating proangiogenic monocytes and EPCs in cardiovascular medicine. This protocol may represent a basis for standardized analysis and monitoring of these cell subsets to define their normal range and prognostic/diagnostic value in clinical use. P2216 Endothelial dysfunction after percutaneous coronary intervention -Is it different according to the kind of stent?- H. Teragawa, K. Nishioka, N. Mitsuba, S. Mikami, Y. Fujii, J. Soga, N. Fujimura, Y. Higashi, Y. Kihara. Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan Background: Several reports have shown that endothelial function is an important index of long-term prognosis, even in patients with coronary artery disease (CAD). However, it has not been fully elucidated how the kind of stent affects endothelial function in the long term. Therefore, we investigated endothelial function of the brachial artery before and 6 months after PCI in patients with CAD. Methods: The subjects were 160 patients (122 men, mean age 66 y) with CAD who underwent successful PCI for stenotic lesions. In each patient, brachial artery diameter responses to hyperemic flow (flow-mediated dilatation, FMD) and nitroglycerin (NTG) spray were measured by high-resolution ultrasonography just before and 6 months after stenting. Angiographic restenosis was defined as >50% diameter reduction at follow-up coronary angiography. Results: Seventy-eight patients were treated with bare metal stents (BMS), and 82 with drug-eluting stents (DES; 57 sirolimus-eluting stents, [SES] and 25 paclitaxel-eluting stents [PES]). The characteristics of the patients did not differ in the two groups except for the presence of diabetes mellitus (BMS, 27%; DES, 44%; p<0.05). The restenosis rate was significantly lower in patients with DES (BMS, 41%; DES, 10%; p < ). Brachial artery diameter at baseline and the percent increase in blood flow did not differ in the two groups before and after stenting. Before stenting, FMD (BMS, 3.7±0.4%; DES, 3.6±0.4%) and NTGinduced dilatation (BMS, 13.7±0.7%; DES, 13.7±0.6%) did not differ significantly in the two groups. Six months after stenting, the change in FMD was different in the two groups (BMS, 1.0±0.5%; DES; 1.3±0.5%; p<0.001), whereas the difference in NTG-induced dilatation was not significant in the two groups (BMS, 1.6±0.8%; DES, 0.4±0.7%; NS). The difference in FMD was similar in patients with SES ( 1.6±0.5%) and PES ( 0.9±0.8%; NS). Multivariate analysis demonstrated that DES (p<0.001, t = 3.68) affected FMD after PCI. Conclusions: These results suggest that endothelial function had deteriorated 6 months after implantation of a DES compared with PCI using a BMS, although the use of a DES markedly reduced restenosis. This finding may confirm the need for careful follow-up of patients with CAD, especially after implantation of a DES. P2217 Assessment of endothelial function in patients with Takayasu s arteritis by flow mediated vasodilatation and reactive nitrogen intermediates N. Senguttuvan, S. Jain, V. Dhawan, N. Khandelwal, A. Bahl, S. Verma. Post Graduate Institute of Medical Education and Research, Chandigarh, India Introduction: Takayasu s arteritis (TA) is among the commonest causes of renovascular hypertension in young. Endothelial function can be assessed by flow mediated vasodilatation (FMD) of the brachial artery. The dual role of nitric oxide (NO) has been well described in the pathogenesis of diseases like SLE, RA etc. The purpose of our study was to assess the endothelial function in patients with TA. To the best of our knowledge, there is no study that has been conducted to assess the endothelial function in patients with TA. Methods: We studied 20 patients with TA and 20 age and sex matched controls. After getting their informed consent, a detailed clinical examination and appropriate laboratory investigations were done to assess disease activity (active and inactive groups as per ACR criteria), FMD (measured as per the guidelines) and reactive nitrogen intermediates (RNI) levels (measured by the Green LC method). Those with hypertensive crisis and those who had undergone angioplasty and vascular surgery were excluded. Results: We used Mann Whitney U test, Fisher exact test and Kruskal Wallis test with posthoc pairwise analysis appropriately (p<0.05 was considered as significant). Mean (95% CI) of RNI level of patients with TA was 22.54μM ( ), which was significantly higher than that of controls 5.53μM ( ) (p<0.0001). It was also found that mean RNI level was significantly higher in patients with active TA 26.97±17.43μM ( ) when compared to patients with inactive TA 12.21±11.82μM ( ) or controls 5.53±5.42μM ( ). However, the posthoc analysis of RNI levels did not demonstrate any statistically significant difference between patients with inactive disease and controls (p=0.36). The mean flow mediated vasodilatation (95% CI) in patients with TA was found to be 25.72% ( ) as compared to 24.83% ( ) in controls (p>0.05). Similarly, no statistically significant difference was seen between patients with active TA and those with inactive TA. We further analyzed the effect of RNI levels in patients with TA in relation to FMD and found that all the subjects belonging to the abnormal category of FMD belonged to patients with TA irrespective of their RNI levels. Conclusion: The endothelial function, as measured by FMD, showed no difference between patients with TA and controls while mean RNI level was significantly elevated in patients with TA.Patients with active TA had significantly higher RNI levels than those with inactive disease. Hence, we put forth that RNI levels can be used to identify the disease activity levels in patients with TA. P2219 Correlations between the cardiovascular risk and disease activity in rheumatoid arthritis on the arterial stiffness in hypertensive patients R. Musetescu 1,E.Belu 1, A.E. Musetescu 2, D.-D. Ionescu 1. 1 Cardiology Center, Craiova, Romania; 2 University of Medicine, Craiova, Romania Background: Rheumatoid arthritis may be associated with an increased risk of cardiovascular disease and accelerated atherosclerosis. Chronic inflammation may impair arterial function and lead to the increase of their stiffness reflected by Augmentation Index (AIx) changes. However, it is unknown the degree of impairment of the arterial stiffness in hypertensive patients with RA and the relationship with the disease activity. Objective: The aim of this study was to assess the vascular status of hypertensive patients with RA using the arteriographic method and to evaluate the relationship with the disease activity. Methods: We examined 78 hypertensive patients with RA (mean age 43.2±12.4 years), and 62 controls (mean age 45.6±11.5 years). All patients underwent standard clinical and biological (CRP, ESR) evaluation, with disease activity quantification by DAS28,4v. Augmentation index (AIx) was measured using Sphygmocor (AtCorMedical) device after standardised blood pressure measurement. The augmentation index was measured using applanation tonometry methods from radial artery. The study population was devided into two groups, the first group included patients with low disease activity (DAS28<3.2, n=21), meanwhile the second group included patients with moderate and high disease activity (DAS28>3.2, n=57). Results: study group analysis and comparison of means have shown that AIx was significantly higher in hypertensive RA patients compared to controls (28.64±10.16 vs ±2.46, p <0.001), as well as between the two study groups, in patients with moderate and high disease activity scores (26.32±8.26 vs ±2.84, p <0.001). Multiple regression analysis has also revealed that the presence of RA is an independent predictor for AIx (R2=0.716, p<0.001). Conclusions: The study revealed an increased augumentation index in hypertensive patients with RA especially in those with high disease activity scores. RA is associated with early increase of arterial stiffness and can be considered as an independent risk factor for cardiovascular morbidity. If these data are confirmed, aggressive prevention strategies for reducing the cardiovascular risk should be tested for persons with rheumatoid arthritis. P2220 Association of endothelial function and nitrooxidative stress with speckle tracking myocardial deformation in patients with rheumatoid arthritis. Effects of chronic inhibition of interleukin-1 I. Ikonomidis, S. Tzortzis, J. Lekakis, I. Paraskevaidis, I. Andreadou, M. Nikolaou, T. Kaplanoglou, G. Skarantavos, P. Soukakos, D.T. Kremastinos. University of Athens, Athens, Greece Inhibition of Interleukin-1 activity improves nitrooxidative stress, endothelial and coronary function. We investigated a) the association of nitrooxidative stress and endothelial function with myocardial deformation b) the effects of anakinra, an interleukin-1a receptor antagonist on myocardial deformation in rheumatoid arthritis (RA) patients. Methods: We compared 42 RA patients to 23 normal controls. 23 patients received anakinra (150mg s.c. o.d) and 19 patients prednisolone for 30 days. At baseline and post-treatment we assessed a) the LV longitudinal, circumferential and radial strain and strain rate, using speckle tracking echocardiography b) the coronary flow reserve (CFR) c) the flow-mediated endothelial-dependent dilation of the brachial artery (FMD) and d) nitrotyrosine (NT) blood levels. Results: Patients had impaired baseline myocardial deformation indices compared to controls (p<0.05). Baseline CFR and NT were related with longitudinal strain (r=0.436, r=0.359), systolic strain rate (r=0.487, r=0.479) and early diastolic

61 Markers and monitors of endothelial function 361 strain rate (r=-0.367, r=-0.384), circumferential strain (r=0.439) and systolic strain rate (r=0.452) (p<0.05). FMD was related with longitudinal and circumferential diastolic strain rate (r=0.554, r=0.547, p<0.01). Compared to baseline, anakinratreated patients increased the longitudinal strain, systolic and early diastolic strain rate and circumferential strain and strain rate (p<0.05 for all comparisons). No significant changes were observed among prednisolone-treated patients. There was a parallel improvement in FMD (5.3±3.0%, vs. 10.5±4.1%, p<0.01), CFR (2.4±0.6 vs. 3.08±0.5, p<0.01) and NT (median 787 vs. 388 nm p<0.05) after 30 days of anakinra treatment. Table 1. Chronic effects of anakinra on Longitudinal LV deformation parameters versus prednisolone-treated patients Anakinra (n=23) Prednisolone (n=19) P Baseline 30-days Baseline* 30-days Long. strain (%) -17.8± ± ± ± Long. systolic sr (1/s) -1.02± ± ± ± Long. early diastolic sr (1/s) 0.96± ± ± ± Conclusions: Myocardial deformation is impaired in RA patients and is related with nitrooxidative stress and endothelial dysfunction. Chronic inhibition of IL-1 improves LV deformation in parallel with endothelial function and nitrooxidative stress. P2221 Regulation of endothelial thrombogenic activity under static and dynamic conditions by modulating alternative Splicing of tissue factor U. Rauch, A. Eisenreich, A. Zakrzewicz, A. Pries, H.-P. Schultheiss. Charite - Campus Benjamin Franklin, Berlin, Germany Background: The regulation of alternative splicing provides a powerful mechanism to control the protein diversity. The Cdc2-like kinases (Clk) and DNA topoisomerase I (DNA topo I) control alternative splicing by regulating the phosphorylation of serine/arginine-rich (SR) proteins. We recently showed Clks and DNA topo I to regulate alternative splicing of human tissue factor (TF) and cellular TF activity of TNF-α-induced HUVEC. This study investigated the impact of the SR proteins SRp75 and SF2/ASF on TF isoform expression and the regulation of thrombogenicity; and the role of Clks and DNA topo I in regulating the endothelial thrombogenicity under pro-inflammatory and dynamic conditions. Methods: HUVEC were pre-incubated with inhibitors of Clks and DNA topo I or sirnas against SRp75 or SF2/ASF before stimulation with TNF-α. TF expression was determined by Real-Time PCR and Western blotting and the thrombogenicity was measured by a chromogenic TF activity assay and a FXa generation assay. Results: Stimulation of HUVEC with TNF-α led to a 6-fold increased expression of alternatively spliced human (ash)tf and full length (fl)tf 1 h post induction (p<0.0001, n=5). Inhibition of SF2/ASF by specific sirnas led to a 2.5-fold increased in ashtf expression (p<0.05). The fltf mrna was reduced by 70% (p<0.0001). Combined inhibition of SRp75 and SF2/ASF by sirnas reduced the ashtf expression by 50% (p<0.0001) and fltf by 60% (p<0.01) in this static system (n=5). Moreover, we showed TNF-α to 5-fold increase the TF activity (p<0.0001, n=5). Inhibition of SF2/ASF reduced the TF activity by 50% and inhibition of SRp75 reduced the TF activity by 40% in HUVEC (p<0.01, n=5) 8h post TNF-α stimulation. These data demonstrate SF2/ASF and SRp75 to influence the regulation of TF isoform expression and cellular thrombogenicity under static conditions. Under dynamic flow conditions we found TNF-α to 3-fold increase the FXa generation in HUVEC (p<0.0001) 10 as well as 15 min post perfusion start (n=6). Inhibition of Clks significantly reduced the TNF-α-induced increase in FXa by 25% (p<0.0001) 10 and 15 min post perfusion start. Inhibition of DNA topo I led to a reduction of FXa generation by 70% 10 min (p< 0.001) and by 55% 15 min post perfusion start (p<0.0001). These data correspond to the expression of fltf, the main contributor to TF activity in HUVEC under the same conditions. Conclusion: These observations indicated that modulating alternative splicing of TF by the inhibition of SR proteins and the corresponding kinases influences the thrombogenicity under static and dynamic conditions in TNF-α-stimulated HU- VEC. P2222 Effect of nitric oxide on the AT-2 receptor expression in-vivo V.T. Dao, T. Suvorava, O. Kocgirli, S. Agouri, M. Oppermann, V. Balz, G. Kojda. Heinrich Heine University, Institute of Pharmacology and Clinical Pharmacology, Duesseldorf, Germany Purpose: We hypothesized that pentaerythritol tetranitrate (PETN) and endothelial nitric oxide (NO) might impact on the expression of angiotensin (AT) type 1 (AT-1) and type 2 (AT-2) receptors. Methods: We generated mice with an endothelial-specific overexpression of endothelial NO -synthase (enos) using the Tie-2 promotor and backcrossed these mice to the C57BL/6 background. Two of these lines were characterized by enos-western blot analyses and blood pressure measurements in comparison to transgene negative littermates. In addition, C57Bl/6 mice were fed with either 6 or 60 mg PETN/kg body weight/day for 4 weeks. Results: Analysis of line 1 of transgenic enos mice (1-eNOS++) showed a 2.3±0.15 fold higher aortic expression of enos and a reduction of blood pressure to 109.6±2.0 mmhg (P<0.01, n=4-6). Analysis of line 2 of transgenic enos mice (2-eNOS++) showed a 3.3±0.3 fold higher aortic expression of enos and a reduction of blood pressure to 105.0±3.0 mmhg (n=6, p<0.01). Treatment of 2- enos++ with the NOS-inhibitor L-nitroarginine (L-NAME) for 30 days completely inhibited the difference in blood pressure suggesting that the reduction of blood pressure in transgenic mice was caused by an increased bioavailability of endogenous NO. In lungs and left ventricular myocardium of 2-eNOS++ the expression of AT-1-receptors was similar to transgene negative littermates (P>0.05, n=8). In striking contrast, the expression of AT-2 receptors was increased by endothelial overexpression of enos in a gene-dose-dependent manner in the myocardium. In 1-eNOS++ and 2-eNOS++ this increase was significantly higher vs. control (P<0.05 and P<0.01, respectively). In lung tissue the AT-2 receptor expression was significantly increased in both lines vs. control (P<0.05). In addition the AT-2 receptor expression of L-NAME-fed mice was decreased in heart tissue of enos transgenic mice (n=4, P<0.05). Furthermore, in-vitro studies with the NO-Donor S-Nitroso-N-Acetyl-D,L-Penicillamin incubated porcine aortic endothelial cells resulted in significant higher expression levels of the AT-2 receptor (P<0.05). Preliminary experiments with PETN-fed mice showed a significant increase in AT-2-receptor expression in myocardial tissue (P<0.05) whereas the expression of the AT-1 receptors did not change (P>0.05) neither in myocardial nor in aortic tissue. Conclusion: These results show that endogenous NO and NO-Donors can upregulate vascular AT-2 receptor in-vivo. This newly discovered regulation might contribute to vasoprotective effects of NO. P2223 Humoral changes, expression of endothelial selection ligands and bubble grade following SCUBA (self contained underwater breathing apparatus) dive D. Glavas 1,A.Markotic 1,Z.Valic 1,N.Kovacic 2, I. Palada 1, R. Martinic 1,T.Breskovic 1,D.Bakovic 1, A.O. Brubakk 3, Z. Dujic 1. 1 Split University Hospital, Split, Croatia; 2 University of Zagreb-School of Medicine, Zagreb, Croatia; 3 Norwegian University of Science and Technology, Trondheim, Norway SCUBA (S) diving has diverse risk to health. The decompression sickness (DCS) is initiated by gas bubbles. Since CD15 and CD15s are leukocytes antigens recognised as ligands by endothelial selectins, we assumed they could be markers for impaired vasodilatation following diving. Aim: To evaluate humoral changes, expression of endothelial selection ligands (CD15 and CD15s on leukocytes) and formation of gas bubbles following open sea S dive. Methods: We performed an analysis of peripheral blood samples to detect the leukocytes that carries CD15 and CD15s and flow cytometry analysis of CD15 and CD15s to estimate any alteration in the membrane expression of those markers. The blood samples of 8 divers were collected 30 mins before and 50 mins after a dive to 54 m for 20 mins bottom time. The number of gas bubbles in the heart was monitored by ultrasound (according to Eftedal-Brubakk method). Results: Gas bubbles were observed in the right side of the heart in all 8 divers. The maximal mean bubble grade was 1.9±1.9 bubbles/cm 2. There was a significant increase in total white blood cells after the dive (before 6.4±1.6:after 8.0±1.9 (x10 9/l) and neutrophils (3.8±1.4:5.7±1.9), the monocytes slightly but not significantly increased (0.3±0.2:0.4±0.2), while lymphocytes significantly decreased (2.3±0.5:1.8±0.6). There were no significant changes in the red blood cells and platelet counts. There was a significant increase in LDH (175.3±39.5: 206.1±44.8 (IU/l)), CK (158.0±55.1:242.3±75.4), CKMB fraction (4.0±2.1:11.3±2.1), Na (137±1.0:139.5±1.1 (μm)) and decrease in K (4.8±0.2:4.3±0.3). There were no significant changes in glucose, laktate, CRP and troponin. The proportion of CD15+monocyte increased significantly after the dive (before dive 38.4±19.3 (mean±sd):after 67±34.2 (P<0.01; t-test) as well as the CD15s monocyte (CD15s high) (3.2±1.4:6.7±4.0 (P<0.05; t-test). The expression of the CD15 and CD15s was continously low on lymphocites (CD3+CD19+).There were no correlation between CD15+monocyte expression and average bubble formation (r=-0.56; P=0.17), as well as with CD15s+monocytes (r=0.43;p=0.29). Conclusion: The study suggests that biochemical changes, induced by SCUBA diving, primarily activate existing monocytes, rather that increase their number. The significant change of CD15+ monocytes and CD15s+high monocytes is not critical for bubble formation but may be involved in endothelial dysfunction. In addition, there were signs of muscle injury what supports the idea that inflammation may be part of decompression injury. The specific mechanisms involved in bubble formation await further examination.

62 362 Endothelial dysfunction: clinical studies ENDOTHELIAL DYSFUNCTION: CLINICAL STUDIES P2224 The incremental effect of sleep apnea on sub-clinical inflammation and asymmetric dimethyl-arginine levels in hypertensives: a nighttime partner of cardiovascular risk C. Thomopoulos, C. Tsioufis, A. Kasiakogias, D. Tsiachris, V. Tzamou, A. Mazaraki, I. Andrikou, I. Darladimas, T. Makris, C. Stefanadis. First Cardiology Clinic, University of Athens,Hippokration Hospital, Athens, Greece Objectives: Apart from the established role of high sensitivity C-reactive protein (hs-crp), diverse cytokines like IL-6, IL-18 and TNF-α promote a wide range of atherogenic effects in various domains of the vasculature. Asymmetric dimethyl arginine (ADMA) has been recognized as a marker of endothelial dysfunction in diverse clinical settings. In the present study, we investigated the possible associations of sleep apnea (SA) with the above mentioned serological markers in hypertensives. Methods: We studied 62 untreated hypertensives with SA documented by positive polysomnography (aged 48±7 years, 79% men, office systolic/diastolic blood pressure: 150±8/97±7mmHg), and 70 hypertensives without SA (negative polysomnography), matched for age, sex, smoking status, body mass index and 24 hour pulse pressure. All subjects underwent polysomnography, 24 hour ambulatory blood pressure monitoring, echocardiographic examination, while routine metabolic profile and serological markers were estimated in a single morning venous sample. Results: Hypertensives with SA compared to those without SA did not differ regarding waist circumference (0.92±0.1 vs. 0.92±0.1, p=ns) and 24h systolic BP (140±9 vs. 138±7 p=ns) while 24h diastolic BP was higher in hypertensives with SA (87.22±6.88 vs ±7.18mmHg, p=0.034). Furthermore, the former group with respect to the latter had significantly increased levels of log hs-crp by 28%, log TNF-α by 69%, logil-6 by 75% and logil-18 by 26% (p< for all cases). Similarly ADMA was increased in SA hypertensives by 13% (p<0.0001). Metabolic profile and left ventricle mass index resulted similar between the groups (p=ns, in all cases). In diverse ANCOVA study models, these differences remained statistically significant even after adjustment for confounders (p< for all cases). In the total study population all studied inflammatory markers plus ADMA were correlated with logahi and minsato2 (p< in all cases), while body mass index and 24 hour pulse pressure with all studied serological markers (p<0.05 in all cases). Conclusions: Hypertensive subjects with SA demonstrated increased levels of hs-crp, IL-6, IL-18, TNF-α and ADMA independently of confounders, including body size and 24h pulsatile load. The close association of apnea severity indexes with these serological markers further supports the incremental effect of SA on the cardiovascular risk duet of subclinical inflammation and endothelial dysfunction. P2225 The relation between endothelial dependent flow mediated dilation of the brachial artery and coronary collateral development A. Ongun 1, S. Gulec 1,N.Uslu 2, C. Tulunay Kaya 1, C. Ozdol 1, S. Turhan 1,Y.Atmaca 1,T.Altin 1,C.Erol 1. 1 Ankara University School of Medicine, Ankara, Turkey; 2 Baskent University Faculty of Medicine, Ankara, Turkey Background: Endothelial dysfunction is thought to be a potential mechanism for the decreased presence of coronary collaterals. The aim of the study was to investigate the association between endothelial function and the extent of coronary collaterals. Methods and Results: We investigated the association between endothelial function assessed via flow mediated dilation (FMD) following reactive hyperemia and the extent of coronary collaterals graded from 0 to 3 according to Rentrop classification in a cohort of 171 patients who had high grade coronary stenosis or occlusion on their angiograms. Mean age was 61 years and 75% were males. Of the 171 patients 88 (51%) had well developed collaterals (grades 2 or 3) whereas 83 (49%) had impaired collateral development (grades 0 or 1). Patients with poor collaterals were significantly more likely to have diabetes (p=0.001), but less likely to have used statins (p=0.083). FMD measurements were not different among good and poor collateral groups (11.5±5.6% vs. 10.4±6.2% respectively, p=0.214). Conclusions: No significant association was found between the extent of angiographically visible coronary collaterals and systemic endothelial function assessed by FMD. Table 1. Characteristics of the subjects Variables Poor collateral (n=83) Goodcollateral (n=88) pvalue Age (years) 61±10 61± Gender, males (%) 65 (78) 64 (73) Diabetesmellitus (%) 46 (55) 27 (31) Hypertension (%) 49 (59) 56 (64) Current smokers (%) 41 (49) 39 (44) Previous MI (%) 55 (66) 53 (60) LDL-C, mg/dl 109±34 107± Triglycerides, mg/dl 152±91 165± Ejectionfraction, % 46±13 49± Aspirin 72 (87) 74 (84) Beta-blockers 57 (69) 56 (64) Calcium channel blockers 5 (6) 11 (13) ACE-Is or ARBs 57 (69) 62 (71) Nitrates 28 (34) 35 (40) Statins 50 (60) 64 (73) nisms for the increased risk are poorly known. In this study we assessed whether children of pts with p-ami had abnormalities in plt and endothelial function. Methods: We studied 21 children (16±3 yrs, 9 M) of pts with p-ami ( 50 yrs old; Group 1) and 18 age and sex-matched children of healthy subjects (15±3 yrs, 9 M; Group 2). Blood samples were collected at rest and at peak treadmill exercise stress test (EST). Plt reactivity was assessed by monocyte-plt aggregates (MPA) and CD41 and PAC1 plt expression by flow cytometry with and without ADP stimulation (10-7 M). Peripheral vascular function was assessed by measuring brachial artery dilation during post-ischemic forearm hyperemia (flow mediated dilation, FMD) and after 25 μg of sublingual nitrates (nitrate-mediated dilation, NMD). Results: There were no differences in basal cytometry variables between groups. ADP and EST induced a higher percentage increase of flow cytometry markers in Group 1 compared to Group 2 (Table). FMD was significantly reduced in GROUP-1 compared GROUP-2 (7.7±3.0% vs 11.1±7.7% respectively; p=0.002), whereas no difference was found in NMD between the two groups (13.4±4.5% vs 15.2±3.5%; p=0.21). Children Children p of AMI patients of healthy subjects MPA pre/mpa at peak (%)* 9.5± ± MPA at peak/mpa at peak ADP (%)* 12.1± ± MPA preadp/mpa at peak ADP (%)* 10.6± ±4.9 <0.001 CD41 pre/cd41 at peak (%)* 5.5± ±3.6 <0.001 CD41 at peak/cd41 at peak ADP (%)* 14± ±5.5 <0.001 CD41 pre ADP/CD41 at peak ADP (%)* 10.1± ±1.1 <0.001 PAC1 pre/pac1 at peak (%)* 24.7± ±6 <0.001 PAC1 at peak/pac1 at peak ADP (%)* 154.4± ± PAC1 pre ADP/PAC1 at peak ADP (%)* 158.3± ±4.9 <0.001 *Data were expressed as pertentage variation of platelet indexes before (pre) and at peak of EST. CT = closure time, MPA = monocyte-platelet aggregates. Conclusions: Our results show that both plt and endothelial function have a less favourable profile in children of young AMI pts compared to controls. The pathophysiologic and clinical implications of these findings deserve appropriate investigations. P2227 Vascular endothelial function predicts mortality risk in patients with advanced ischemic chronic heart failure M. Shechter, S. Matetzky, M. Arad, M.S. Feinberg, D. Freimark. Chaim Sheba Medical Center, Tel Hashomer, Israel Background: Endothelial function is impaired in advanced chronic heart failure (CHF) patients. Aims: To explore the association between endothelial function and subsequent mortality risk in advanced CHF (ACHF). Methods and Results: We prospectively assessed brachial flow-mediated dilation (FMD) in 82 consecutive New York Heart Association (NYHA) class IV ischemic ACHF patients with left ventricular ejection fraction (LVEF) 22±3%. Following overnight fasting and discontinuation of all medications for 12 hours, percent improvement in FMD (%FMD) and nitroglycerin-mediated vasodilation (%NTG) were assessed using linear array ultrasound. All patients were followed for 14±2 months for pre-specified combined adverse cardiovascular events, including death, hospitalization for CHF exacerbation or myocardial infarction. Subjects were divided into 2 groups: (n=41) and > (n=41) the median %FMD of P2226 Platelet reactivity and endothelial function in children of patients with premature acute myocardial infarction L. Barone, G. Scalone, I. Coviello, A. Delogu, A. De Nisco, A. Di Monaco, R. Nerla, F. Infusino, G.A. Lanza, F. Crea. Catholic University of the Sacred Heart, Rome, Italy Background: Family history of premature acute myocardial infarction (p-ami) is associated with an increased risk of AMI in first degree relatives. The mecha- Kaplan-Meier Survival Plot

63 Endothelial dysfunction: clinical studies %. Both groups were comparable regarding cardiovascular risk factors, LVEF and concomitant medications. During follow-up 22 (53.6%) patients with FMD had composite adverse cardiovascular events compared with only 8 (19.5%) with FMD > the median (p<0.01). Furthermore, 5 deaths (12.1%) occurred in patients with FMD, compared with no deaths in FMD > the median (p<0.03) (Figure). Cox regression analyses revealed that FMD was an independent predictor for these events. Conclusion: Brachial artery FMD is associated with increased mortality risk in ischemic NYHA class IV ACHF patients. P2228 Smoking induces lipoprotein-associated Phospholipase A2 (Lp-PLA2) in cardiovascular disease free adults: the ATTICA study D. Panagiotakos 1, A. Tselepis 2,C.Pitsavos 3, C. Tellis 2, C. Chrysohoou 3, J. Skoumas 3, C. Stefanadis 3. 1 Harokopio University, Athens, Greece; 2 University of Ioannina, Ioannina, Greece; 3 University of Athens, Athens, Greece Background: Data from large Caucasian population studies have demonstrated an independent association between plasma Lipoprotein-associated Phospholipase A2 (Lp-PLA2) and the risk of future cardiovascular events. We studied the association of smoking habits on Lp-PLA2 levels, in a sample of CVD free adults. Methods: During we randomly enrolled 3042 men and women (18-89 years) from the Attica region, Greece. Several socio-demographic, lifestyle (including current, former smoking or passive smoking), clinical and biological factors, were assessed in all participants. Lp-PLA2 activity in total plasma and in apob-depleted plasma, after the sedimentation of all apo B-containing lipoproteins with dextran sulfate-magnesium chloride (HDL-Lp-PLA2 activity), was determined by the trichloroacetic acid precipitation procedure using [3H]-PAF (100 μmol/l final concentration) as a substrate. Results: The total plasma Lp-PLA2 activity and mass were higher in current smokers compared to non-current smokers (p<0.05); similarly people reported exposed to second-hand smoke had also higher levels of Lp-PLA2 activity and mass compared to those who were not exposed to others cigarette smoke (p<0.05). Importantly, the molar ratio of Lp-PLA2 mass to apo B is higher in active smokers as compared to non-current smokers (2.8±1.4 vs. 2.0±1.1, p=0.03), and higher in secondhand smokers compared to non-current smokers (2.7±1.1 vs. 2.0±1.1, p=0.05). Moreover, Lp-PLA2 activity was positively associated with current or passive smoking (all p-values < 0.05) and this association was independent of various potential confounders. Conclusion: The present study shows for the first time that the plasma Lp-PLA2 activity or mass is strongly positively associated with active or secondhand smoking among healthy individuals. expression. This novel cytoprotective mechanism provides a mechanistic explanation how aspirin prevents acute coronary events at low plasma concentrations not related to its antiplatelet activity. P2230 Improved vasoreactivity following spironolactone therapy in chronic haemodialysis patients P. Flevari, S. Kalogeropoulou, D. Leftheriotis, F. Panou, S. Katsoudas, D. Bacharaki, D. Vlahakos, D. Kremastinos. Athens University Hospital Attikon, Athens, Greece Purpose: Cardiovascular mortality is the major cause of death in haemodialysis (HD) patients (pts). Endothelial dysfunction is commonly observed and precedes cardiovascular complications, including arrhythmias and sudden death. Although aldosterone directly affects endothelial function, the impact of its inhibition on HD pts has not yet been fully appreciated. Therefore, our goal was to study the vasoactive effect of spironolactone in HD pts, as evidenced by forearm venous occlusion plethysmography. Methods: Fourteen stable HD pts were studied, 9 male/5 female, mean aged 62±3 years. Pts with predialysis K + >6 meq/l were excluded. After an initial 4- month period of placebo treatment, all pts received spironolactone (25 mg thrice weekly) after each HD session for the next 4 months. Systemic blood pressure (BP), heart rate, and parameters of endothelial function were collected at baseline, after placebo administration, and following spironolactone treatment. We assessed forearm blood flow (FBF) i) at rest (baseline), ii) during reactive hyperaemia. Hyperaemic FBF corresponded to the mean value of the first 4 measurements observed after arterial occlusion release. The max % difference in reactive FBF (relative to baseline) was assessed. The duration of hyperaemia was the time (sec) at which FBF returned to 50% of its maximal increase relative to baseline flow. ANOVA for repeated measures was used for statistical analysis. Data are expressed as mean±se. Results: All patients completed the study without serious side effects. None of the above mentioned parameters were significantly changed during placebo administration. Following spironolactone treatment, predialysis K + increased from 4.4±0.2 to5.5±0.3 meq/l (p<0.01), while BP decreased [systolic BP from 148±4 to 122±3 mmhg(p<0.01) and diastolic BP from 74±3 to66±5 mmhg(p<0.01)]. After spironolactone administration, no significant differences were observed in baseline FBF values, while a significant increase was noted regarding the % difference in reactive FBF (from 51±12 to 152±46%, p<0.05). The duration of hyperaemia was also increased by treatment (from 35±8 to48±5 sec,p<0.01). Conclusion: In clinically stable HD pts, spironolactone administration is associated by favorable endothelial responses. Further studies are required in order to elucidate the pathophysiologic mechanism(s) and evaluate the clinical relevance of such treatment. P2229 Low-dose aspirin protects against coronary endothelial damage by inhibiting LOX-1-dependent uptake of electronegative L5 in acute myocardial infarction P.-Y. Chang, S.-C. Lu, J.-K. Lee, Y.-J. Chen, Y.-T. Lee. National Taiwan University Hospital, Taipei, Taiwan Purpose: Patients with coronary heart disease benefit from low-dose aspirin therapy through uncharacterized cytoprotective mechanisms independent of aspirin s antiplatelet effect. The electronegative low-density lipoprotein (LDL), named L5, is a naturally-occurring oxidized-ldl which exhibits a spectrum of atherogenic effects on cultured vascular cells. We hypothesized that low-dose aspirin protects against L5-induced coronary cell damage by inhibiting uptake of L5 through lectin-like oxidized LDL receptor-1 (LOX-1). Methods: Plasma LDL was isolated from patients with acute ST-elevation myocardial infarction and divided by ion-exchange chromatography into 5 subfractions, L1 L5, with increasing electronegativity. Cell proliferation was assessed by trypan blue exclusion and 3H-thymidine incorporation in human coronary artery endothelial cells (HCAECs) treated with each LDL subfractions. Fibroblast growth factor 2 (FGF2) expression was analyzed by ELISA and real-time PCR. Transcriptional regulation of FGF2 promoter was investigated using Luciferase reporter gene assay. The uptake of L5 by HCAECs was directly visualized by DiI fluorescence. LOX-1 expression was detected by immunochemical staining. Results: Aspirin had a biphasic effect on cell proliferation and intracellular FGF2 expression in HCAECs: a modest increase in both when aspirin concentrations were less than 0.2mmol/l (low-dose) and a concentration-dependent decrease when aspirin concentrations were higher than 0.2 mmol/l. The L5 specimens isolated from patients with acute myocardial infarction were able to induce HCAEC apoptosis and inhibit EC proliferation by down-regulating FGF2 expression. In contrast, L1-L4 hadno effects. Co-incubation of the cells with 50 ug/ml L5 and low-dose aspirin 0.2 mmol/l resulted in a significant attenuation of the inhibitory effects of L5. Imaging studies showed that the entry of DiI-labeled L5 into HCAECs was selectively inhibited by monoclonal antibody against LOX-1. Addition of lowdose aspirin decreased cellular LOX-1 expression, prevented DiI-L5 uptake and improved DNA synthesis. These changes were accompanied by maintenance of FGF2 gene promoter activity which was transcriptionally repressed by L5. Conclusions: This study showed that low-dose aspirin improved coronary cell survival by inhibiting L5 uptake through LOX-1 and maintained intracellular FGF2 P2231 Relation of digital vascular function and endothelial function by flow-mediated dilation with carotid atherosclerosis in hypertension A. Tatasciore, R. Tommasi, F. Santarelli, M. Zimarino, G. Renda, S. Gallina, R. De Caterina. Universita G. D Annunzio, Chieti, Italy Background and Aim: Systolic blood pressure (BP) has been related to arterial stiffness and the wave reflection phenomenon, in turn leading to atherosclerosis. We hypothesized that endothelial dysfunction, as assessed by flow-mediated dilation (FMD), might be a key mediator of this relationship. Here we tested the relationship of new tools to assess vascular function - the digital pulse amplitude augmentation (PAT) and the PulsePen - to assess arterial stiffness, with carotid artery intima-media thickness (IMT), as an index of atherosclerosis. Methods: In a cohort of 134 hypertensive patients we evaluated the relationship of several parameters assessing vascular function, including the peripheral vasodilatory function in response to hyperemia through the PAT, the pulse wave velocity (PWV, using the PulsePen) and FMD (by echo of the brachial artery, to assess endothelial dysfunction) with carotid artery IMT as a marker of atherosclerosis. Results: Systolic (S) BP, SBP variability, and all the 3 techniques assessing vascular function here studied had some relation with IMT at univariable regression analysis. At multivariable regression analysis, however, only PAT and PWV remained significantly related to IMT (Table), indicating that changes in vascular function explored by these techniques traduce the detrimental effects of SBP and SBP variability. Variables IMT Univariable Analysis, P (r) Multivariable Analysis, P SBP (mmhg) (0.203) NS SBP variability (mmhg) (0.202) NS FMD % (-0.211) PWV (0.219) PAT (0.380) Conclusions: Digital vascular dysfunction, assessed by the PAT hyperemic response, and arterial stiffness, evaluated as PWV, are directly and - at least in part - independently related to vascular atherosclerotic damage in hypertensive patients.

64 364 Endothelial dysfunction: clinical studies P2232 Graded association of arterial stiffness with asymmetric dimethylarginine, endothelin-1 and osteoprotegerin levels in essential hypertensive patients K. Dimitriadis, C. Tsioufis, E. Andrikou, D. Syrseloudis, C. Thomopoulos, I. Andrikou, A. Mazaraki, D. Tousoulis, I. Kallikazaros, C. Stefanadis. First Cardiology Clinic, University of Athens,Hippokration Hospital, Athens, Greece Purpose: Arterial stiffening is a marker of atherosclerosis, whereas increased levels of asymmetric dimethylarginine (ADMA), osteoprotegerin (OPG) and endothelin-1 (ET-1) are associated with endothelial dysfunction states. In this study we examined the relationships of arterial stiffness with ET-1, OPG and ADMA levels in essential hypertensive patients. Methods: One hundred sixty-five newly diagnosed untreated non-diabetic patients with stage I to II essential hypertension [110 men, mean age=49 years, office blood pressure (BP)=151/97 mmhg] were divided into three groups according to carotid to femoral pulse wave velocity (PWV) values, assessed by means of a computerized method (Complior SP): Group A (PWV<7.4 m/sec), group B (PWV= m/sec) and group C (PWV>8.7 m/sec). Additionally, venous blood samples were drawn for estimation of lipid profile, ET-1, OPG and ADMA concentrations. Results: Patients in group A (n=61) compared to subjects in group B (n=53) and C (n=51) had lower office systolic BP (147±12 vs 150±14 vs 158±13 mmhg, respectively; p<0.05 for all cases) and left ventricular mass index (101.4±13 vs 115.2±15 vs 121.2±12 g/m 2, respectively; p<0.05 for all), while did not differ regarding metabolic profile (p=ns). Moreover, patients in group C compared to group B and A, exhibited higher levels of ADMA (0.63±0.04 vs 0.57±0.04 vs 0.52±0.03 μmol/l, respectively; p<0.05 for all), OPG (5.8±0.3 vs 4.3±0.5 vs 3.8±0.4 pmol/l, respectively; p<0.05 for all) and ET-1 (1.13±0.28 vs 0.65±0.17 vs 0.45±0.19 fmol/ml, respectively; p<0.05 for all). In the entire population, PWV was related to age (r=0.279, p<0.0001), office systolic BP (r=0.314, p<0.0001), ET-1 (r=0.236, p<0.05), OPG (r=0.314, p=0.03) and ADMA (r=0.193, p<0.05). Regarding ADMA, it was correlated with waist to hip ratio (r=0.209, p<0.05), office systolic BP (r=0.430, p<0.0001), whereas ET-1 exhibited a positive relationship with office systolic BP (r=0.214, p<0.05) and OPG (r=0.229, p<0.05). By multiple regression analysis it was revealed that age, office systolic BP, OPG and ADMA were independent predictors of aortic stiffness (R 2 =0.49, p<0.0001). Furthermore, analysis of covariance showed that ET-1, OPG and ADMA values remained significantly different between groups after adjustment for confounders (p<0.05). Conclusions: In essential hypertensives, aortic stiffness is gradually related to ET-1, OPG and ADMA levels, advocating common pathophysiological pathways of endothelial dysfunction and progressive atherosclerosis. Moreover, these findings further support the role of PWV as a tool to estimate vascular status in hypertension. P2233 Low 25-hydroxyvitamin D levels are associated with elevated plasma ADMA and C-reactive protein concentrations: nexus with cardiovascular disease D.T.M. Ngo 1,A.L.Sverdlov 1, J.J. Mcneil 2,J.D.Horowitz 1. 1 University of Adelaide, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia; 2 Monash University, Melbourne, Victoria, Australia Background: Low plasma vitamin D concentrations are associated with significant increases in incidence of obesity, hypertension, diabetes; myocardial infarction; cardiovascular and all-cause mortality. However, the mechanism(s) underlying association between vitamin D status and cardiovascular risk remains uncertain. In the current study, we evaluated possible relationships between vitamin D status, endothelial dysfunction and inflammation. Methods: Studies were performed in a normal population cohort (n=253) aged 51 to 77 years (mean 63.4±6 years). Plasma concentrations of 25-hydroxyvitamin D3 (25(OH)D3) were determined by radioimmunoassay after extraction. Plasma concentrations of asymmetric dimethylarginine (ADMA), a marker/mediator of endothelial dysfunction, were determined by HPLC. High-sensitivity C-reactive protein (hs-crp) levels were utilized as a marker of inflammatory activation. Putative correlations were evaluated by univariate and multivariate analyses. Results: On univariate analyses, low 25(OH)D3 levels were inversely correlated with ADMA concentrations, hs-crp levels; and body mass index. Presence of hypertension, and treatment with an ACEi/ARB were also associated with low 25(OH)D3 levels. On backward multiple linear analyses, both ADMA (β=-0.19, p=0.003) and hs-crp (β=-0.14, p=0.03) concentrations were inverse correlates of plasma 25(OH)D3 concentrations; other significant correlates were: male gender (β=0.19, p=0.003, calcium levels (β=0.14, p=0.03), and use of angiotensinconverting enzyme inhibitor (β=-0.17, p=0.007). Table 1. Variables independently associated with high 25(OH)D3 levels β coefficient P value Male gender Calcium levels (mmol/l) Presence of ACEi/Ang IIi Hs-CRP (mmol/l) ADMA concentrations (μm) Conclusions: In this ageing population cohort, plasma 25(OH)D3 concentrations are inversely related to markers of endothelial dysfunction and inflammation. It remains to be determined whether this represents the mechanism(s) underlying the association between vitamin D status and cardiovascular risk. P2234 Exercise-training restores endothelium-dependent vasorelaxation and reverses endothelial NOsynthase uncoupling in Spontaneously Hypertensive Rats S. Thioub 1, C. Goanvec 1, F. Guerrero 1, J.-C. Cornily 2, J. Mansourati 2. 1 EA 4324, Université de Bretagne Occidentale, Brest, France; 2 University Hospital of Brest, Université de Bretagne Occidentale, Brest, France Many cardiovascular diseases are associated with oxidant stress involving uncoupling of endothelial nitric oxide synthase (enos). We sought to evaluate the effect of exercise training on enos coupling/uncoupling in Spontaneously Hypertensive Rats (SHR). Male SHR and Wistar-Kyoto (WKY) rats were divided into sedentary (n=20) and exercise (n=20) groups. Exercise group was submitted to a treadmill training protocol (20m/min, 60 min/day, 5 days/week, 9 weeks and 10 incline). Systolic Blood Pressure (SBP) was measured before training, 6 h (acute effects) and 72 h (chronic effects) after the last exercise bout. Responses to vasoactive compounds were examined in vitro in rings prepared from femoral artery. Dose-response curves to ACh (10-9 to 10-4 mol/l) alone or in the presence of either Nω-nitro-Larginine methyl esther (L-NAME, mol/l) or tetrahydrobiopterin (BH4, 10-5 mol/l), a cofactor for enos activity, were studied in rings precontracted with PE (10-7 mol/l). Sedentary life-style and training exercise did not alter SBP in WKY. In SHR, SBP increased significantly 6 h and 72 h (158±6 vs 184±4 mmhg and 184±4 mmhg) post-sedentary life-style (p= ). In trained SHR, SBP was significantly reduced 6 h post-exercise as compared to reference value (140±3 vs 161±3 mm Hg; p = 0.002). SBP was also decreased 72 h post-exercise as compared to postsedentary life-style (166±3 vs 184±4 mm Hg; p = 0.023). Results on femoral artery rings are summarized in the table. Emax (maximal relaxation) and EC50 (half-maximal effective dose) in response to ACh alone or in presence of BH4 ACh ACh+BH4 Emax (%) EC50 (μm) Emax (%) EC50 (μm) SHR sedentary (n=10) 33.60± ±0.54* 26.81± ±0.06 WKY sedentary (n=10) 48.50± ± ± ±0.15 SHR exercise (n=10) 95.68± ± ± ±0.06 WKY exercise (n=10) 86.87± ± ± ±0.05 Percent relaxation = percent reduction in force from PE. Training has acute and chronic hypotensive effects in SHR. Endothelial dysfunction associated with hypertension involves enos uncoupling. Endotheliumdependent vasorelaxation is improved by exercise training in normotensive rats. In hypertensive animals, exercise training restored ACh-induced vasorelaxation by coupling enos. P2235 Relevance of homocycteine on brachial flow-mediated vasodilation and carotid and femoral intima media thickness in sibling of hypertensive patients M.F. Elnoamany, H. Badran, H. Ebraheem, A. Reda, N. Elsheekh. Menoufyia Faculty of Medicine, Shebeen Elkom, Menoufyia, Egypt Background: Mild hyperhomocysteinaemia, a risk factor for vascular disease, is common in the general population. Offspring of hypertensive parents, have been reported to have endothelial dysfunction compared with the offspring of normotensive parents. This does not occur simply as a consequence of increased blood pressure but may rather be a cause of the condition. Carotid intima-media thickness (CIMT) is the second valid marker of generalized atherosclerosis. Aim of the work: We studied the relation of sonographically determined carotid & femoral intima-media wall thickness and enothelial function to serum homocysteine (Hcy) concentrations in offsprings of hypertensive parents. Methods: Plasma homocysteine levels were measured in normotensive siblings for hypertensive patients (n=78) and normotensive controls (n=30). All the subjects were non-diabetic, had no past history of myocardial infarction, stroke or peripheral vascular disease and had normal renal functions. Brachial artery flow-mediated (FMD) and nitroglcerine mediated vasodilatation (NTGMD) were measured to assess endothelial function. Also carotid and femoral intima-media thickness that reflect vascular disease were examined. Results: Hcy level were found to be significantly higher in normotensive siblings when compared to controls {13.7±4.5 versus 7.8±2.7 micromol/l (p<0.001)}. CIMT and femoral IMT were significantly increased in siblings in comparison to control (0.72±0.1 versus 0.59±0.1 and 0.71±0.1 versus 0.58±0.1 mm P<0.01) respectively. FMD and FMD% that reflect endothelial dysfunction but not NT- GMD & NTGMD% were significantly lower in siblings compared with control (0.7±0.1 versus 1.6±0.1mm and 20% versus 55%, P<0.001). Conclusion: Plasma homocysteine levels are significantly elevated in normotensive siblings for parents with essential hypertension. Increased carotid and

65 Endothelial dysfunction: clinical studies 365 femoral IMT in addition to endothelial dysfunction may serve as results of hyperhomocysteinaemia that create the potential cardiovascular risk. P2236 Intermittent airway obstruction and atherogenesis in hypertension. Risk stratification depends on disease severity A. Kasiakogias, C. Tsioufis, C. Thomopoulos, A. Mazaraki, P. Tolis, E. Andrikou, I. Andrikou, V. Tzamou, I. Kallikazaros, C. Stefanadis. First Cardiology Clinic, University of Athens,Hippokration Hospital, Athens, Greece Purpose: The adverse effect of obstructive sleep apnea (OSA) on the cardiovascular system may be partially explained by the action of inflammatory and atherogenic mediators. The aim of our study was to investigate the effect of disease severity on markers of atherosclerosis in hypertensive patients. Methods: 91 consecutive subjects with stage I-II hypertension and OSA confirmed by polysomnography were divided into two groups- of moderate (N=36) and severe disease (N=55) respectively- according to their apnea hypopneas index (AHI) (cut-off value= 30 episodes/hour). All patients underwent ambulatory blood pressure monitoring, while blood sampling was performed for routine laboratory testing and measurement of asymmetric dimethyl arginine (ADMA) and interleukin-18 (IL-18) levels. The albumin to creatinine ratio (ACR) was determined on two non-consecutive urine morning samples. Results: The two groups exhibited similar 24hr systolic and diastolic BP values (141±11 vs 140±7, 88±6 vs. 86±7mmHg, p=ns for both). There were also no significant differences regarding the body mass index, the metabolic profile and GFR. The severe OSA group exhibited higher levels of logadma (-0.23±0.1 vs ±0.08μmolŁ, p=0.02), logil-18 (2.5±0.13pg/ml vs. 2.4±0.109pg/ml, p=0.001) and logacr (1.13±0.31 vs. 0.97±0.28mg/g, p=0.032). In the entire population, the AHI was correlated with the logacr (r=0.23, p=0.05), logil-18 (r=0.32, p=0.003) and logadma (r=0.356, p=0.001). In a model of multiple regression analysis (adjusted r 2 =0.21), the AHI was independently predicted by the logil-18 (p=0.05) and the logadma (p=0.02). Inversely, in another model (adjusted R 2 =0.18) logadma was independently predicted by minimum O2 saturation during sleep (b=-0.29, p=0.017). Conclusions: OSA is accompanied by raised biomarkers of atherogenesis reflecting a condition of diffuse vascular damage. Apnea severity should be considered when estimating the cardiovascular risk profile in patients with concurrent hypertension. P2237 Coronary flow reserve is impaired in patients with migraine G. Kaynar, L.E. Sade, B. Yetis, H. Bozbas, S. Eroglu, B. Pirat, V. Simsek, B. Ozin, H. Muderrisoglu. Baskent University Faculty of Medicine, Ankara, Turkey Purpose: Migraine is a common neurovascular disorder characterized by attacks of severe headache, autonomic and neurological symptoms. To test the hypothesis that migraine can be associated with systemic endothelial and microvascular dysfunction we investigated coronary flow reserve (CFR) as a means of coronary microvascular function in patients with migraine. Methods: Sixty one patients (35 with migraine and 26 healthy controls) without coronary artery disease, hypertension or diabetes mellitus were included. Coronary diastolic peak flow velocities were measured at baseline and after dipyridamole infusion (0.56 mg/kg/4 minutes). CFR was calculated as the ratio of hyperemic to baseline diastolic peak velocities. CFR 2 was considered normal. Results: Patients with migraine were younger than controls (Mean age: 30±7,5 vs 36±7,9 years; P=0,002). There were no significant differences regarding other clinical characteristics. Left ventricular systolic function was decreased in patients with migraine as compared with controls (Ejection fraction: 56,8±4,5% vs 60,4±3,2%; P < 0,001, mean mitral annular systolic velocity: 10,2±2.0cm/s vs 13.0±1.9cm/s; P<0.0001). Mean diastolic peak velocities at baseline and during hyperemia were 31,1±5,9 and 60,3±8,7 cm/s for migraine, 27±2,8 and 78,4±15,5 cm/s for healty controls. CFR values were significantly lower in subjects with migraine than in the control group (1,98±0,38 versus 2,96±0,62; P<0,001). Impaired CFR was observed in 45,7% of migraine patients as compared with 0% of healthy controls (P<0.0001) Conclusions: CFR which reflects coronary microvascular dysfunctions is impaired in a considerable proportion of patients with migraine suggesting subclinical atherosclerosis and increased cardiovascular risk in these patients. P2238 Pentaerithrityltetranitrate enhances reactive hyperemia in patients with coronary artery disease. A subanalysis of the randomized, double-blind, clinical PENTA study M.A. Ostad, B. Schnorbus, R. Schiewe, C. Medler, D. Wachtlin, T. Munzel, A. Warnholtz. University Medical Center, Mainz, Germany Purpose: Chronic treatment with nitroglycerin is characterized by the induction of tolerance and deterioration of endothelial dysfunction. Pentaerithrityltetranitrate (PETN) differs from nitroglycerin by the lack of tolerance induction and by antioxidative properties. Previously, we have reported the results of the PENTA study which revealed no deterioration of endothelial dysfunction in conduit arteries in patients with coronary artery disease (CAD). Reactive hyperemia depends on microvascular dilation in response to ischemia. Recent data from a clinical study have identified an association of lower reactive hyperemia with increased cardiovascular risk in patients with peripheral arterial disease. Yet it is unknown whether PETN has an impact on reactive hyperemia. Therefore we have analysed the hyperemic response to ischemia in the PENTA study. Methods: In a prospective, double-blind trial, 80 patients with CAD were randomly assigned to treatment for 8 weeks with oral PETN 80mg t.i.d. (PETN) or placebo (C), respectively. Brachial arterial endothelial function was measured as flow-mediated dilation before and after treatment. Peak reactive hyperemia was evaluated by pulsed doppler analysis of blood flow volume and mean shear stress within the first 5 seconds upon cuff release. Heart rate, blood pressure and hematokrit were monitored at all visits. Data monitoring and statistic analysis were independently performed by the coordination centre of clinical trials (KKS), Mainz. The trial was registered as ISRCTN Results: Both treatment groups were comparable regarding age, gender, distribution of cardiovascular risk factors, concomitant medication, baseline arterial diameter, hematokrit and hemodynamic status. Peak increases in blood flow volume and mean shear stress upon 5 minutes of ischemia were comparable at baseline. After treatment, the peak increases in blood flow volume (mean±sd: PETN: +173±420%; C: -8±503%, p=0.04) and mean shear stress (mean±sd: PETN: +123±374%; C: -71±462%, p=0.01) were significantly enhanced in the PETN group vs. C compatible with enhanced reactive hyperemia. Changes in peak reactive hyperemia did not correlate with changes in FMD. Conclusions: We conclude from our data that chronic PETN treatment of patients with CAD improves microvascular function. With respect to the prognostic significance of an enhanced reactive hyperemia the results of our study generate the hypothesis that chronic PETN treatment lowers the cardiovascular event rate in patients with atherosclerosis. This hypothesis should be prospectively investigated in a randomized trial. P2239 Early therapy with n-3 Polyunsaturated Fatty Acids improve endothelial function ultrasound parameters and diastolic function index in patients with acute myocardial infarction M. Haberka, K. Mizia Stec, M. Mizia, K. Gieszczyk, A. Chmiel, Z. Gasior. Slaski Uniwersytet Medyczny w Katowicach, Katowice, Poland Body of evidence suggests pleiotropic effects of n-3 Polyunsaturated Fatty Acids (n-3 PUFA) on several clinical endpoints in patients with acute myocardial infarction (AMI). Purpose: Our aim was to assess influence of early n-3 PUFA therapy on vascular function and left ventricular (LV) diastolic function in patients with AMI. Methods: Forty consecutive patients with AMI and successful coronary stent implantation were randomized to the study group (n=20; F/M=4/16; age=58±8; STEMI=70%; TIMI 3=100%; standard therapy + Omacor 1g daily) and the control group (n=20; F/M=4/16; age=62±10; STEMI=65%; TIMI 3=100%; standard therapy). All the patients were given pharmacotherapy according to the actual ESC recommendations. The study group patients were given n-3 PUFA therapy (Omacor 1g daily) starting from the 3rd day of AMI. The following non-invasive imaging methods were performed in the 3rd and 30th day after AMI: transthoracic echocardiography (TTE) and high-resolution ultrasound to measure: flow mediated dilatation (FMD), nitroglycerin-mediated vasodilatation (NMD) and intima-media thickness (IMT). Results: Baseline patients characteristics (standard laboratory parameters, MI localization, clinical risk factors, concomitant diseases and drugs therapy), ultrasound vascular parameters and TTE parameters did not differ significantly between both groups. Mean FMD (8.4±7.2 to 15.3±10.6%; p=0.019), but not NMD (26.9±12.1 to 30.2±14.0%;p=ns) values increased significantly after 1- month therapy with PUFA. FMD and NMD values did not change significantly among control patients (FMD: 9.9±6.4 to 10.2±9.0%; NMD: 25.1±11.4 to 25.8±14.0%;p=ns). Evaluation of TTE baseline and control parameters revealed significant decrease of E/E (E early diastolic maximal mitral ring movement velocity) index (12,1±3,6 to 10,7±2,7;p=0.02) in the PUFA group patients without significant changes in other diastolic function parameters (E and A wave, E/A ratio, E and A wave, isovolumetric relaxation time, deceleration time) and no significant changes in control patients. We found no correlation between FMD and E/E index values. Conclusions: Patients with AMI benefit from an early introduction of n-3 PUFA therapy revealing improvement in vascular function parameters and sensitive diastolic LV function index (E/E ) evaluated after one-month therapy.

66 366 Endothelial dysfunction: clinical studies / Lipids and statins P2240 Effect of long-term L-thyroxine treatment on endothelial function and carotid intima media thickness in young adults with congenital hypothyroidism M. Arcopinto, A.M. Marra, T. Lettiero, V. Apuzzi, G. Bosso, A. Valvano, F. Calabrese, M.C. Salerno, U. Oliviero, A. Cittadini. Azienda Ospedaliera Universitaria Federico II, Naples, Italy Background: Overt and subclinical hypothyroidism are associated with increased risk for atherosclerotic cardiovascular disease. Patients with Congenital Hypothyroidism (CH) display subtle abnormalities of the cardiovascular system that appear to be related to non physiological fluctuations of TSH levels and occur despite careful replacement therapy. Objective: Aim of the present case-control study was to assess arterial carotid intima-media thickness (CIMT) in conjunction with endothelial function by flowmediated vasodilation (FMD) in patients with CH in order to evaluate the effects of long-term levothyroxine (L-T4) replacement therapy. Patients and methods: Thirty young adults with CH aged 18.1±0.2 years and 30 age and sex-matched controls underwent IMT measurement by carotid Doppler ultrasound and brachial artery reactivity evaluation by flow-mediated dilatation (FMD) at the time of the study. Hypothyroidism was diagnosed by neonatal screening and L-T4 treatment was initiated within the first month of life and adjusted to maintain TSH levels in the normal range and free thyroxine in the highnormal range. Results: see table below. Stepwise regression analysis revealed that pubertal and total mean TSH was an independent determinant of FMD (p<0.0001) and IMT (p<0.0001), respectively. In addition, the number of episodes of subclinical hypothyroidism (TSH>5.0 mu/l with normal FT4) during puberty (r=-0.53, p< 0.003) was an additional risk factor for endothelial dysfunction. FMD and IMT values in CH and Controls Controls CH p FMD (%) 14.5± ±0.9 < NMD (%) 22.1± ±1.3 n.s. Mean CCA-IMT (mm) 0.62± ±0.003 < Mean ICA-IMT (mm) 0.61± ±0.004 < Mean ECA-IMT (mm) 0.63± ±0.003 < Data are expressed as mean ± SEM; FMD: flow mediated dilation; NMD: nitroglycerin mediated dilation; IMT, intima-media thickness. Conclusions: Young adults with CH, treated with long-term L-T4 replacement therapy, display endothelial dysfunction and increased CIMT predicted by indexes of L-T4 under-treatment. Therefore, long-term L-T4 therapy may induce increased risk of atherosclerosis and of acute cardiovascular events. P2241 Vascular dysfunction in HIV infected patients receiving highly active antiretroviral therapy I. Ikonomidis 1,J.Palios 1, J. Lekakis 1, L. Rallidis 2, S. Tsiodras 2, G. Poulakou 2, P. Panagopoulos 2, A. Papadopoulos 2, H. Giamarellou 2, D.T. Kremastinos nd Cardiology Department, Attikon Hospital, University of Athens Athens, Greece; 2 University of Athens, Athens, Greece Background: A high risk of atherosclerosis and cardiovascular disease has been described in HIV-1 positive individuals receiving highly active antiretroviral therapy (HAART). Reactive hyperemia is an endothelial dependant vascular reaction to ischemia in order to prevent tissue damage. We investigated whether HIV-1 positive individuals receiving HAART and patients who where naïve to medication had differences in their vascular function. Methods: We compared measurements of forearm reactive hyperemia using venous occlusion strain gauge plethysmograrhy (Hokanson AI6 Arterial Inflow System) in HIV individuals receiving HAART with patients naïve to treatment with similar risk factors. Mean carotid imtima media thickness of the right, left common carotids and carotid bulbs was measured in all subjects using B-mode ultrasonography Results: Forty four (N=44) HIV patients receiving HAART were compared to twenty six (N=26) naïve to therapy HIV patients with similar clinical characteristics. Patients exposed to treatment had worse reactive hyperemia results since they had lower % change in the blood flow between the maximum hyperemic blood flow and the baseline blood flow at rest (690±256 vs. 903±320, p<0,01). The maximum hyperemic flow in HAART receiving patients was lower comparing to HAART naïve patients (37,7±11,1 vs. 31,9±11,0, p<0.05). The baseline flow was similar between the two groups. In multivariate analysis the % change in the forearm blood flow during maximum hyperemia was independently correlated with treatment with HAART (p<0.01), total cholesterol (p<0.05), triglycerides (p<0.05), carotid IMT (p<0.05), a marker of subclinical atherosclerosis (p<0,05 respectively) among blood pressure, glucose levels, smoking, BMI, age, disease duration, viral load and CD4 lymphocyte count. Conclusions: Patients with HIV infection receiving HAART present functional abnormalities of arterial microcirculation as assessed by the reactive hyperemia parameters in comparison with naïve patients. This vascular dysfunction is determined by HAART treatment and metabolic parameters, is related with the carotid atherosclerosis and may thus increase the risk of cardiovascular events in these subjects P2242 Endothelial dysfunction in diabetic patients with myocardial perfusion abnormalities in absence of obstructive epicardial coronary disease R. Djaberi, J.D. Schuijf, J. Op T Roodt, A.J. Scholte, T.J. Rabelink, E. De Koning, E.E. Van Der Wall, J.J. Bax, J.W. Jukema. Leiden University Medical Center, Leiden, Netherlands Purpose: In patients with diabetes mellitus (DM) myocardial perfusion defects are often observed in absence of significant epicardial coronary artery stenosis. We hypothesized that these perfusion abnormalities may be explained by endothelial dysfunction. Methods: Prospectively, a total of 135 asymptomatic patients with DM (mean age 51±13yrs, 68 men), underwent cardiovascular screening by multi-slice computed tomography (MSCT) coronary angiography and myocardial perfusion imaging (MPI) by SPECT at rest and during adenosine stress. MSCT images were evaluated for the presence of significant coronary artery stenosis ( 50% luminal narrowing). To quantify size and severity of perfusion defects on SPECT images, the summed stress score (SSS) based on a 17 segment, 5 point model, was determined for each patient. Presence of any myocardial perfusion defect was defined as SSS>2. In all patients, flow mediated dilation (FMD) of the brachial artery, a marker of endothelial function, was determined using ultrasonography. Results: In 35 (27%) patients, significant coronary artery stenosis was observed on MSCT and these patients were excluded from further analysis. In the remaining 95 patients, abnormal myocardial perfusion was observed in 30 (32%) of patients. FMD was significantly lower in patients with myocardial perfusion defects (3.6±2.4), as compared to those without perfusion defects (6.4±2.6) (p<0.001) (Figure 1). Importantly, after correction for age and other cardiovascular risk factors, FMD remained the only predictor of the presence of abnormal myocardial perfusion (p<0.001). Conclusions: In patients with DM, myocardial perfusion abnormalities in absence of significant epicardial coronary artery stenosis are associated with endothelial dysfunction. LIPIDS AND STATINS P2243 The influence of statins on late cancer mortality in vascular surgery patients with chronic obstructive pulmonary disease Y.R.B.M. Van Gestel 1,S.E.Hoeks 1,D.D.Sin 2,V.Huzeir 1,H.Stam 1, F.W. Mertens 1,J.J.Bax 3, H.J.M. Verhagen 1,R.T.VanDomburg 1, D. Poldermans 1. 1 Erasmus Medical Center, Rotterdam, Netherlands; 2 University of British Columbia & The James Hogg icapture Center, St. Paul s Hospital, Vancouver, Canada; 3 Leiden University Medical Center, Leiden, Netherlands Purpose: Chronic obstructive pulmonary disease (COPD) is associated with an increased incidence of lung cancer, independently of smoking. Since at least 20 to 25% of the patients with COPD die from cardiovascular disease, medical treatments that confer cardiovascular risk reduction such as statins may reduce mortality in these patients. However, contradictory results exist regarding the effect of statins on cancer. Consequently, we investigated the association between COPD and cancer mortality and whether the use of statins modified this relationship. Methods: The study included 3371 patients with peripheral arterial disease who underwent vascular surgery between 1990 and The diagnosis of COPD was made according to the guidelines of the Global Initiative for Chronic Obstructive Lung Disease (GOLD). The endpoints were 10-year total cancer mortality, lung cancer mortality and extra-pulmonary cancer mortality. Results: COPD was associated with increased risk of total cancer mortality (Hazard Ratio, HR 1.61; 95%CI ). The risks for lung cancer (HR 2.06; 95%CI ) and extra-pulmonary cancer deaths (HR 1.43; 95%CI ) were both elevated in patients with COPD. The excess risk was mostly driven by patients with moderate and severe COPD. There was a trend towards lower cancer mortality risk among COPD patients who used statins (HR 0.57; 95%CI ). Interestingly, statins were significantly associated with reduced cancer mortality from sites other than the lungs (HR 0.49; 95% CI ).

67 Lipids and statins 367 Statins and cancer in COPD patients Conclusions: COPD was associated with increased lung and extra-pulmonary cancer mortality in this large cohort of peripheral arterial disease patients. Furthermore, statin may reduce the risk for (extra-pulmonary) cancer mortality in patients with COPD. P2244 Colesevelam added to a stable combination of a maximally tolerated statin and ezetimibe in patients with heterozygous familial hypercholesterolemia; the TRIPLE trial R. Huijgen 1,M.D.Trip 1, E. Bruckert 2, A.F.H. Stalenhoef 3, B.P.M. Imholz 4, P.N. Durrington 5, M. Eriksson 1, F.L.J. Visseren 6, J.R. Schaefer 7, J.J. Kastelein 1 on behalf of TRIPLE investigators. 1 Karolinski University Hospital, Huddinge, Sweden; 2 Hôpital Pitié-Salpêtrière, Paris, France; 3 Department of Internal Medicine, University Medical Centre Nijmegen, Nijmegen, Netherlands; 4 Department of Internal Medicine,Tweesteden Ziekenhuis, Waalwijk, Netherlands; 5 The University of Manchester, Manchester, United Kingdom; 6 Vascular Medicine, University Medical Centre Utrecht, Utrecht, Netherlands; 7 Philipps University Hospital Marburg, Marburg, Germany Objectives: Guidelines for treatment of patients with familial hypercholesterolemia (FH) advise to reduce LDL-C levels below 100 mg/dl. However, a considerable proportion of FH patients are not at goal despite potent combination therapy. We studied if adding Colesevelam (COL) 3.75 g/day to a stable combination therapy is safe and can effectively reduce LDL-C. Methods: Heterozygous FH patients on maximally tolerated statin and ezetimibe 10 mg for at least 3 months with LDL-C >100 mg/dl and LDL-C variability 10% over 4 weeks were eligible. Patients continued their statin and ezetimibe and were randomized to COL or placebo (PBO) as add-on therapy for a 12 week double blind period and continued for another 40 weeks on open label active treatment. Results: Between August 2007 and September 2008 in 8 lipid clinics in 5 European countries 138 patients were screened. 52 Patients were excluded; 6 (4%) LDL-C below target, 31 (22%) too high (>10%) LDL-C variability, 15 (11%) excluded for other reasons. 86 (62%) Patients were randomized, 41 on PBO and 45 on COL. LDL-C at baseline was 3.7 mmol/l (PBO) and 3.9 mmol/l (COL). Changes in lipid parameters for patients having at least one lipid assessment (ITT) are given in the table. A LDL-C reduction from baseline of 15% or more was seen in 14 patients (33%) on COL and in 0 on PBO (P<0.0001). COL was well tolerated. Percentage change in Lipid parameters Least Square mean % change Placebo Colesevelam Treatment from baseline (N=39) (N=43) Difference (95% CI) LDL-C 6 weeks (-25.7, -11.8)* LDL-C 12 weeks (-17.7, -6.0)* Tot-Chol 12 weeks (-12.2, -2.5)* HDL-C 12 weeks (-3.0, 8.6) Triglycerides 12 weeks (-10.0, 16.9) ApoB/ApoA1 ratio 12 weeks (-19.2, -3.0)* *P< CI = Confidence Interval, LDL-C = Low Density Lipoprotein Cholesterol, Tot-Chol = Total Cholesterol, HDL-C = High Density Lipoprotein Cholesterol. Least square mean % change from baseline, based on ANOVA with site and treatment as co-factor. Conclusions: The 6 week primary endpoint was met, with a mean TD for LDL- C of up to 18.7%. In hefh patients not at goal, COL added to a combination of maximal tolerated statin and ezetimibe, significantly improved LDL-C, Tot-Chol and ApoB/ApoA1 ratio s. P2245 The role of conventional risk factors in explaining residual risk in statin-treated post myocardial infarction patients. Results from the IDEAL study A.G. Olsson 1, C. Lindahl 2,R.Fayyad 3,I.Holme 4 on behalf of IDEAL Investigators and Steering Committee. 1 University Hospital, Linköping, Linköping, Sweden; 2 Pfizer Sweden, Sollentuna, Sweden; 3 Pfizer Inc, New York, United States of America; 4 Ullevaal University Hospital, Oslo, Norway Background: We have previously described significant relations between Apolipoprotein B (apob), apob/apoa1 ratio and non-hdl-cholesterol and cardiovascular events (CVE) in statin-treated patients reaching the goals of 2.0 and 2.5 mmol/l in the IDEAL study. Methods: Patients were allocated to either 20 to 40 mg of simvastatin (n=4449) or atorvastatin 80 mg (n=4439) daily for 5 years. The study had an open-label randomized design (PROBE) and had no run-in phase. In this post-hoc subanalysis, for subjects who reached the LDL-C goals of 2.5 mmol/l or 2.0 mmol/l at 3 and 6 months, risk factors for CVE were investigated by Cox regression analysis including sex, age, systolic blood pressure, coronary heart failure at baseline, hypertension, diabetes, smoking, and prior statin use, and each of mean apob, mean apob/apoa1 and mean non-hdl at months 3 and 6. In addition, net reclassification analysis (NRI) was performed by logistic regression with cross-classification of CVE risk into 4 groups based on a model including apob/apoa-1 and excluding it over and above the adjustment factors defined above. A similar analysis was performed by comparing the model with and without smoking. Results: For subjects who reached LDL goals of <2.5 mmol/l, apob, apob/apoa1 and non-hdl-c significantly predicted CVE risk. The hazard ratios (HR) and 95% confidence intervals of 1 standard deviation increase in apob, apob/apoa1 and non-hdl were: 1.13 ( ), 1.16 ( ), and 1.11 ( ), respectively. Neither inclusion of the apob/apoa1 ratio or inclusion of smoking over and above the standard factors had much influence on the NRI for CVE. For apob/apoa-1, the index was 2.6% for goal <2.5 mmol/l, and 2.0% for goal <2.0 mmol/l. Similar numbers for smoking were 2.3% and 1.9%. Conclusion: For subjects who reached LDL goal, even though there are are still significant relations between conventional risk factors and outcome in post myocardial infarction patients, on-study apob/apoa1 did not provide further prediction of CVEmeasured by NRI. This does not diminish the need of paying attention to these factors in long term cardiovascular prevention. The causes of the residual risk in statin treated patients in a 5-year perspective may be related to more short-term factors such as thrombogenic and inflammatory factors or to other lipoproteins e.g. HDL. P2246 Combination niacin extended-release and simvastatin treatment causes greater reduction in atherogenic particles compared to atorvastatin monotherapy W. Insull Jr 1,P.P.Toth 2, H.R. Superko 3,R.Thakkar 4, P. Jiang 4, R. Parreno 4, R.J. Padley 4. 1 Baylor College of Medicine and Methodist Hospital, Houston, United States of America; 2 University of Illinois School of Medicine, Peoria, United States of America; 3 St. Joseph s Research Institute, Atlanta, United States of America; 4 Abbott, Abbott Park, United States of America The numbers of lipoprotein particles, in addition to their cholesterol content, may be of importance in determining cardiovascular risk. Previous studies have shown that statins can reduce LDL-particle numbers, but have little effect on LDL size. The purpose of this study was to compare the effects of a once-daily combination tablet of niacin extended-release (NER, Niaspan, Abbott) and simvastatin (NER/S, Simcor, Abbott) vs atorvastatin monotherapy on lipid particle sizes and total numbers in patients with dyslipidemia from the SUPREME study. Patients with dyslipidemia who were either not previously receiving statin therapy, or who discontinued any lipid-altering treatment for 4-5 weeks prior to the study, received 1000/40-mg/d NER/S for 4 weeks, followed by 2000/40-mg/d for 8 weeks; or atorvastatin 40-mg/d monotherapy for 12 weeks. Changes in nuclear magnetic resonance (NMR) lipoprotein subclasses from baseline to week 12 were compared using Wilcoxon rank-sum test and proportion of patients were compared using Fisher s exact test. The median percent changes in particle number and size from baseline to week 12 were calculated from 137 patients in the modified intentto-treat (mitt) population (NER/S treatment, n=74; atorvastatin monotherapy, n=63). There was no significant difference in LDL-cholesterol (LDL-C) levels in response to treatment with NER/S vs. atorvastatin monotherapy. However, NER/S treatment resulted in greater percent reductions in calculated particle numbers for LDL (51.6% vs. 42.7%; p=0.022), small LDL (55.0% vs. 44.7%; p=0.011), very low-density lipoprotein (VLDL) and chylomicrons (63.4% vs. 39.2%; p<0.001), compared to atorvastatin monotherapy, respectively. A greater proportion of patients in the NER/S group achieved an LDL-particle number of less than 1000 nmol/l (46% vs. 21%; p=0.002). NER/S treatment also resulted in greater increases in particle size for LDL (2.7% vs. 1.0%; p=0.007) and VLDL (9.3% vs. 0.1%; p<0.001), compared to atorvastatin monotherapy, respectively. Compared to atorvastatin monotherapy, NER/S treatment resulted in a greater reduction in the number of small LDL particles, VLDL and chylomicron particles were reduced, and the mean size of LDL and VLDL particles increased. This suggests that NER/S treatment may result in a shift towards a less atherogenic population of lipoprotein subclasses despite similar effects on total LDL-C levels.

68 368 Lipids and statins P2247 Reduction in cardiovascular events and associated cost after treatment initiation with niacin extended-release plus simvastatin combination therapy versus simvastatin plus ezetimibe fixed dose therapy R. Simko 1,R.Quimbo 2, M.J. Cziraky 2,S.Balu 1. 1 Abbott Laboratories, Abbott Park, United States of America; 2 HealthCore, Inc., Wilmington, United States of America Purpose: To compare annual cardiovascular disease (CVD) event risk and attributable-health care costs between patients initiating niacin extended-release (NER) plus simvastatin (NER/S) and simvastatin plus ezetimibe (S/E) fixed-dose therapy among patients with prior CVD. Methods: A retrospective analysis of patients aged 18 years newly initiating S/E or NER/S therapy (initial therapy of NER added to existing simvastatin therapy) between 1/1/2001 and 6/30/2006 (index date) was performed using a the HealthCore Integrated Research Database. Patients with a minimum of 12 months pre- and post-index date follow-up and CVD during the12 months prior to index date were included. CVD event risk was estimated using Kaplan-Meier survival analysis while adjusted post-index date mean annual CVD-attributable total health care costs [sum of inpatient, emergency room, and outpatient visit costs] were compared through a multivariate generalized linear model. Model covariates included treatment group, age, gender, pre-index CVD costs, Deyo-Charlson comorbidity index (DCI), and prior type 2 diabetes and hypertension. Results: A total of 7,065 study patients were identified initiating S/E (n=6,513) or NER/S (n=552). NER/S patients were significantly younger (58.5±9.2 years vs. 61.3±10.2 years; p<0.0001) and more likely to be male (85.1% vs. 67.9%; p<0.0001) compared to S/E patients. Pre-index date comorbidity burden (1.3±1.3 vs. 1.4±1.6; p=0.1018) was similar between the two groups. Patients initiating NER/S therapy were 32% [Hazard Ratio (HR): 0.68 ( )] less likely to experience a post-index CVD event versus S/E patients. Multivariate analysis demonstrated a 25% ($568, 95% CI: $443-$730 vs. $760, 95% CI: $710-$815; p=0.0289) reduction in mean annual CVD costs among NER/S patients compared to S/E patients. Conclusion: High risk patients with prior CVD treated with NER/S were associated with lower CVD event risk and total annual CVD-attributable costs compared to S/E patients. Higher utilization and early initiation of NER/S therapy which emphasizes the reduction of residual risk would seem to be beneficial as compared to an LDL-C centric treatment strategy. P2248 Increased cholesterol absorption in patients treated with strong statins M. Eto, M. Akishita, T. Akiyoshi, H. Ota, K. Nomura, K. Yamaguchi, S. Ogawa, K. Iijima, Y. Ouchi. Department of Geriatric Medicine, University of Tokyo, Tokyo, Japan Serum cholesterol levels are determined by both synthesis and absorption. Administration of statins effectively reduces serum cholesterol levels through inhibition of its synthesis and subsequent LDL receptor upregulation in liver, but compensatory increase in cholesterol absorption from small intestine might limit statin s beneficial effect. At present, mechanisms underlying cholesterol absorption remain largely unknown. Therefore, we conducted this cross-sectional study to clarify predictive factors for cholesterol absorption, especially focusing on types of statins. In this study, 141 patients were enrolled from our ambulatory clinic (73.7±9.4 yo., yo., 59 menand 82 women). Twenty-nine (21%) patients had a history of coronary artery disease and 39 (28%) had a history of ischemic stroke. Ninety-six (68%) patients had hypertension, 53 (38%) had diabetes, 71 (50%) were receiving strong statins and 34 (24%) were receiving standard statins. No patient received any cholesterol absorption inhibitors. Serum sitosterol and lathosterol levels were measured for an absorption marker and a synthesis marker, respectively. As expected, sitoserol levels were significantly higher (2.68±0.14 vs 1.78±0.15micro-g/mL, p<0.01) and lathosterol levels were lower (0.8±0.04 vs 1.56±0.17 micro-g/ml, p<0.01) in patients receiving any types of statins compared with those in patients not receiving statins. Interestingly, strong stain group had significant higher sitoserol levels (2.90±0.18 vs 2.23±0.19 micro-g/ml, p<0.01) and lower lathosterol levels (0.67±0.05 vs 1.08±0.15 microg/ml, p<0.01), although serum total cholesterol levels were comparable between these 2 groups. Multiple regression analysis using age, sex, risk factor profile, history of ischemic disorders and types of statins as variables, demonstrated that treatment with strong statins was the only one independent predictive factor for cholesterol absorption (p<0.01). In conclusion, cholesterol absorption is enhanced in patients treated with strong statins. These results provide clinical implications for cholesterol management to prevent atherosclerotic vascular disease. P2249 Cardiovascular event reduction after treatment initiation with simvastatin plus niacin extendedrelease combination therapy versus statin monotherapy among managed care dyslipidemia patients R. Simko 1,R.Quimbo 2,M.Cziraky 2,S.Balu 1. 1 Abbott Laboratories, Abbott Park, United States of America; 2 HealthCore, Inc., Wilmington, United States of America Purpose: To compare annual cardiovascular disease (CVD) event risk between patients initiating any statin monotherapy (SM) and niacin extended-release [NER] + simvastatin (NER/S) combination therapy among patients with dyslipidemia in a managed care setting. Methods: A retrospective analysis of patients aged 18 years newly initiatingsm or NER/S therapy (initial therapy of NER added to existing simvastatin therapy) between 1/1/2001 and 6/30/2006 (index date) was performed using the Health- Core Integrated Research Database. Patients with a minimum of 12 months preand post-index date follow-up and prior cardiovascular disease 12 months prior to initiation of therapy were included. Unadjusted and adjusted annual CVD event risk was estimated using Kaplan-Meier survival analysis and Cox proportional hazards model, respectively. Model covariates included treatment group, age, gender, Deyo-Charlson comorbidity index (DCI), and prior type 2 diabetes and hypertension. Results: A total of 26,051 study patients were identified initiating SM (n=25,499) or NER/S (n=552). NER/S patients were significantly younger (58.5±9.2 years vs. 60.4±11.8 years; p<0.0001) and more likely to be male (85.1% vs. 60.1%; p<0.0001) as compared to SM patients. NER/S patients were healthier at baseline than SM patients (pre-index DCI score: 1.3±1.3 vs. 1.5±1.6; p=0.001), though a higher percent of NER/S patients had hypertension (88.6% vs. 73.7%; p<0.0001). Patients initiating NER/S therapy were 39% [Hazard Ratio (HR): 0.61 ( ); p=0.0005] less likely to experience a post-index CVD event versus SM patients, while the adjusted rate was 32% [HR: 0.68 ( ); p=0.0078]. Conclusion: Treatment with NER/S among dyslipidemia patients was associated with lower CVD event risk compared to SM treated patients. Early initiation of NER/S therapy emphasizing reduction of residual risk would seem to be beneficial as compared to an LDL-C only focused treatment strategy. Further research on the impact of the individual lipid parameters on clinical outcomes in a real-world population is warranted. P2250 Attainment of normal lipid levels in french patients receiving er niacin/laropiprant added to statin therapy B. Ambegaonkar 1,G.Davies 2, H. Phatak 1, T. Souchet 3, V. Sazonov 1. 1 Merck and Co., Inc., Whitehouse Station, Nj, United States of America; 2 Merck and Co., Inc., Upper Gwynedd, Pa, United States of America; 3 MSD France, Paris, France Purpose: To project attainment of goal/normal levels of low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), and triglycerides (TG) following addition of ER niacin/laropiprant (ERN/LRPT) to ongoing statin therapy vs. continuation of current statin therapy in French patients at high risk for coronary heart disease (CHD). Methods: A model based on an iterative process used patient-level data from a French cohort identified from BKL-THALES database and individual patient lipid responses from a clinical trial of ERN/LRPT (2 g), to estimate normal lipid level attainment based on current European Society of Cardiology guidelines on Cardiovascular Disease Prevention in Clinical Practice. This process utilized the empirical response data from the trial that accounted for individual variability in treatment responses and correlation between treatment responses for the 3 lipid parameters. Gender-stratified analyses were conducted for high-risk groups, including CHD or CHD risk equivalents, with LDL-C>2.5 mmol/l. Results: Among 238 high-risk patients, mean age was 65 years; 77% were male; mean LDL-C, HDL-C, and TG levels (mmol/l) were 3.64, 1.21, and 2.27 respectively. Among women receiving ERN/LRPT added to statin vs. statin only, 38.4% vs. 3.0% reached LDL-C goal, 39.1% vs. 10.6% achieved 2 normal lipid levels, and 18.2% vs. 0.3% attained all 3 normal lipid levels. Similar patterns for goal/normal level attainment were observed in men with ERN/ LRPT added to statin vs. statin only: 31% vs. 4.6% for LDL-C, 40.4% vs. 17.7% for 2 lipids, 16.4% vs. 0.5% for all 3 lipids. Conclusions: In this projection of goal/normal lipid level attainment in French clinical practice, addition of ERN/LRPT to statin in high risk patients not at optimal lipid levels allows an additional 25% male patients and about one-third more female patients to achieve LDL-C goal. Among those with ERN/LRPT added to statin compared to statin only, additional 25% and up to 18% more patients attain 2 and all 3 normal lipid levels respectively. P2251 Beneficial effect of statin treatment on carotid atherosclerosis in patients with stable coronary artery disease stratified by renal function T. Ishizu, Y. Seo, N. Murakoshi, S. Watanabe, K. Aonuma. University of Tsukuba, Tsukuba, Japan Background: Chronic kidney disease (CKD) is common in patients with coronary

69 Lipids and statins 369 artery disease (CAD), and such patients have adverse outcomes. The purpose of the present study was to investigate the efficacy of cholesterol lowering treatment with a statin in modifying carotid atherosclerosis in patients with stable CAD stratified by glomerular filtration rate (GFR). Methods: One-hundred eleven patients with stable coronary artery disease were stratified into 3 baseline GFR groups: normal or increased ( 90 ml/min/1.73m 2 ; n=41 patients), mild reduction (60 to 89 ml/min/1.73m 2 ; n=58 patients), and moderate or severe reduction (<60 ml/min/1.73m 2 ; n=14 patients). Patients underwent carotid ultrasonography at baseline, 1-year and 2-year after statin treatment, and mean intima-media thickness (IMT) of the distal common carotid artery was measured using manual tracing software by a single sonographer blinded to patient clinical background. Results: LDL cholesterol and CRP levels were similar in the three groups at baseline and after statin treatment. Compared with patients with normal GFR, significant reductions in mean IMT were observed in moderate or severe CKD at 1-year (p=0.014) and in mild CKD at 2-year follow up (p=0.009) after adjustment for LDL cholesterol reduction. Conclusion: Among stable CAD patients, those with CKD benefited more from statin treatment than did patients without CKD. However, this benefit may not be attributed to the reduction of LDL cholesterol by statin treatment. P2252 Evidence of myocardial adrenergic innervation abnormalities in hyperlipidemic subjects: the beneficial effect of statins E.A. Zacharis 1,M.E.Marketou 1, S.I. Koukouraki 2, V.K. Prassopoulos 2,I.Karalis 1,G.F.Diakakis 1, F.I. Parthenakis 1, N.S. Karkavitsas 2, P.E. Vardas 1. 1 Cardiology Dept. Heraklion University Hospital, Heraklion, Greece; 2 Dept. of Nuclear Medicine, Heraklion, Greece Purpose: Hyperlipidemia results in endothelial dysfunction and myocardial perfusion abnormalities even in the absence of any organic heart disease. We investigated the association of dyslipidemia with myocardial adrenergic innervation disturbances using 123 I-meta-iodobenzylguanidine ( 123 I-MIBG) and assessed the effect of statin therapy thereupon. Methods: We examined 30 hyperlipidemic subjects (20 men, aged 57±10 years, total cholesterol >240 mg/dl, LDL-C >16 0mg/dl), while 19 healthy volunteers served as a control group. None had any disease that may have affected myocardial adrenergic innervation. All subjects underwent a planar and a SPECT myocardial imaging of the heart after an intravenous infusion of 5mCi 123 I-MIBG. Heart to mediastinum ratio (H/M) was used for quantitative assessment of adrenergic innervation, 10 minutes and 4 hours after drug infusion, while SPECT scintigraphy evaluated the regional distribution of adrenergic activity. Twenty of the hyperlipidemic subjects received 20 mg/day rosuvastatin for 6 months, while the remaining ten received placebo. An 123 I-MIBG study was repeated at 6 months. Results: Total cholesterol and LDL-C levels were significantly reduced (from 312±135 mg/dl and 184±79 mg/dl to 195±72 mg/dl and 98±37 mg/dl respectively, p<0.05). The H/M ratio in hyperlipidemics at 10 min and 4 hours was 1.80±0.22 and 1.73±0.26 respectively; significantly lower than that in normals (2.30±0.9 and 2.14±0.10 respectively, p<0.05 for both) and was improved under rosuvastatin treatment (1.98±0.8 and 1.95±0.25 respectively, p<0.05). During SPECT scintigraphy, 19 hyperlipidemic subjects (68%) showed defects in the inferior wall, nine (32%) displayed additional regional disturbances in myocardial adrenergic activity in the anterior wall and ten subjects (33%) in the apex. These defects were ameliorated mostly in the inferior and anterior wall on re-evaluation, but only in those receiving rosuvastatin. No regional disturbances were detected in healthy subjects. Conclusions: This is the first study to show a high prevalence of myocardial adrenergic innervation disturbances in hyperlipidemic subjects, while the rosuvastatin further intensifies the cardioprotective effect of statins. Background: The majority of patients with dyslipidemia in Germany are treated with a statin. However, many patients do not achieve recommended lipid targets. Methods: DYSIS enrolled consecutive outpatients 45 years-old, on statin therapy for 3 months with available lipid values. We investigated whether in Germany patients with sedentary lifestyle (SL) differ in cardiovascular disease risk factor profile and LDL-C target achievement from patients without SL. Results: Patients with SL had a higher prevalence of cardiovascular risk factors, heart failure, cerebrovascular disease, and peripheral artery disease, compared to those without SL. There was no difference between both groups with regards to coronary heart disease. Logistic regression analysis adjusting for patient characteristics, heart failure and lipid lowering therapy identified SL as independent predictor of LDL not at goal (OR 1.25, 95%-CI ). Patients with SL Patients without SL P-value* n=1,822 (42.9%) n=2,422 (57.1%) Age (years, ±SD) 67.4± ± Female [%] BMI 30 mg/m 2 [%] < Hypertension [%] < Diabetes mellitus [%] < Metabolic syndrome (ATP III) [%] < Ischemic heart disease [%] Cerebrovascular disease [%] < Heart failure [%] < mg/day Simvastatin equivalent [%] mg/day Simvastatin equivalent [%] Ezetimibe [%] LDL-C not at goal [%] < LDL-C = low-density lipoprotein cholesterol; HDL-C = high-density lipoprotein cholesterol /70 mg/dl (CHD/CHD equivalent), 130 mg/dl (2+ RF), 160 mg/dl (0-1 RF). Conclusion: SL was an independent determinant for not being at recommended lipid targets for secondary prevention in patients already treated with statins. These results demonstrate the urgent need for life style changes and a more intensive and comprehensive lipid management in these patients. P2254 Comparative efficacy of ezetimibe added to atorvastatin vs uptitration of atorvastatin in attainment of recommended lipid targets in patients at high risk of coronary heart disease (CHD) L. Leiter 1,H.Bays 2, S. Conard 3,J.Lin 4, M. Hanson 4,A.Shah 4, A.M. Tershakovec 4. 1 University of Toronto, Toronto, Canada; 2 Louisville Metabolic and Atherosclerosis Research Center, Louisville, Ky, United States of America; 3 University of Texas Southwestern Medical School, Dallas, Tx, United States of America; 4 Merck & Co, Inc, North Wales, Pa, United States of America Purpose: LDL-C has been identified by European and Canadian treatment guidelines as a major target for treatment of patients at high risk of CHD. Some guidelines also identify total C, total C/HDL-C ratio and Apo B as additional targets, and hs-crp as a potentially useful risk indicator. The purpose of this post hoc analysis was to compare the efficacy of ezetimibe 10 mg (E) added to atorvastatin (A) 40 mg to uptitration of A 80 mg on attainment of various lipid targets and hs-crp levels. Methods: After stabilization of A 40 mg therapy, patients with hypercholesterolemia at high risk of CHD were randomized to receive A 40 mg + E (n=288) or uptitration to A80 mg (n=291) for 6 weeks. This analysis assessed the attainment of various lipid and hs-crp targets set for the purpose of this study. Results: At baseline mean LDL-C was 2.3 mmol/l, mean total C was 4.3 mmol/l, mean Apo B was 1.0 g/l, and mean hs-crp was 1.7 mg/dl in both treatment groups. Mean total C/HDL-C ratio was 3.6 and 3.7 in the A 40 + E and A80 groups, respectively. Compared with doubling the dose of A to 80 mg, patients had greater odds of achieving LDL-C<2 mmol/l, total C<4.0 mmol/l, total C/HDL-C ratio<4.0, or Apo B<0.85g/L when treated with E added to A. In addition, patients achieving LDL-C<2 mmol/l had greater odds of also achieving total C<4.0, total C/HDL-C ratio<4.0 mmol/l, Apo B<0.85 g/l, or hs-crp<1 mg/dl with E added to A treatment compared with patients whose A dose was doubled to 80 mg (Figure). P2253 High prevalence of persistent lipid abnormalities in patients with sedentary lifestyle treated with statins in Germany: results of the dyslipidemia international study A.K. Gitt 1, C. Juenger 1, K. Bestehorn 2, F. Chazelle 3,W.Smolka 2, J. Senges 1, J.P.P. Kastelein 4 on behalf of DYSIS Study Group. 1 Institut fuer Herzinfarktforschung Ludwigshafen, Ludwigshafen am Rhein, Germany; 2 Merck Sharp & Dohme, Haar, Germany; 3 Merck, Paris, France; 4 Academic Medical Center, Amsterdam, Netherlands Conclusions: Adding E to A 40 mg was more effective at reducing LDL-C, Apo B, total-c, total C/HDL-C ratio, and hs-crp levels than doubling the dose of A to 80 mg (the highest recommended dose) in statin-treated patients with hypercholesterolemia at high risk of CHD. The relative clinical outcomes benefits await further study. P2255 Influence of coenzyme Q10 supplementation in statin treated patients on left ventricular diastolic dysfunction. Results of randomised double-blind clinical study J. Fedacko, D. Pella, R. Rybar. Kosice University Medical School, Kosice, Slovak Republic Inhibition of HMG-CoA reductase by statins leads to decreased synthesis of

70 370 Lipids and statins cholesterol and coenzyme Q10 (CoQ10), because they share the same biosynthetic pathway. Background of our double-blind randomized, single centre prospective 3-months study (CoQ10 200mg/day vs. placebo) administered to statin treated patients was to evaluate possible benefits of coenzyme Q10 supplementation on left ventricular diastolic dysfunction. Methods: Sixty eligible patients were enrolled in the study. All patients underwent physical, laboratory, and echocardiographic examinations at the beginning and at the end of the study. Physical and laboratory examinations were performed also after 1 month. Results: Two of three observed parameters of the diastolic dysfunction were significantly improved in the CoQ10 treated patients - peak E/A ratio increased from 0.818±0.20 to 1.034±0.21 (p=0,0001) and isovolumetric relaxation time decreased from ±16.35ms to 86.40±13.53 ms (p=0.0001) while the third one remained statistically unchanged - deceleration time at baseline ±51.21 ms compared with final visit ±34.49 ms (p=0.2629). In the placebo group of patients the E/A ratio decreased from 1.175±0.37 to 1.107±0,34 (mild worsening, although the value 1.107±0.34 is still in reference values of E/A ratio, but this worsenig was close to achieving statistical significance (p=0.0857) statin therapy was continuous in all study patients during the whole study period. Isovolumic relaxation time remained nearly unchanged. The value moved from 84.79±16.42 to 88.91±20.49 (p=0.2747). Deceleration time also did not change significantly (from ±39.60 to172.00±39.27; p=0.2805). In conclusion, our results showed that supplementation of statin treated patients with coenzyme Q10 may improve left ventricular dysfunction. More randomised clinical studies are needed to address this issue to confirm this possible benefit. Purpose: Decreased 24-h heart rate variability (HRV) is associated with increased risk of cardiovascular morbidity and mortality. The objective of this study is to examine the relation between plasma lipids and HRV in hypercholesterolaemic subjects without coronary artery disease (CAD) before and after treatment with 10 mg rosuvastatin. Methods: We included 48 hyperlipidaemic subjects (32 men, aged 59±10 years). Inclusion criteria were hypercholesterolaemia (TCHOL >240 mg/dl) and low density lipoprotein (LDL-C) cholesterol>160 mg/dl. All had a normal echocardiogram and no signs of coronary artery disease. Holter recording and fasting blood samples were performed in all subjects. The subjects were randomized to receive 10 mg/day rosuvastatin (n=35 or placebo n=13) for 1 year and reevaluated. Results: Total cholesterol and LDL-C levels were significantly reduced (from 289±101 mg/dl and 172±67 mg/dl to 192±64mg/dl and 97±26mg/dl respectively, p<0.05). Heart rate variability indices at baseline and after 12 months of treatment with 10 mg/day of rosuvastatin in hypercholesterolaemic patients are showed in Table 1. Rosuvastatin placebo before 1 year before 1 year SDNN 51.32±14.7* 63.84± ±14.8** 51.14±13.1 SDANN ±19.3* 170.8± ±15.6** ±14.5 PNN ±1.8* 9.6± ±1.4** 7.46±1.7 RMSSD 28.67±12.7* 49.67± ±12.4** 29.32±13.5 *P<0.05 before vs 1 year, **P<0.05 vs patients before treatment. Conclusions: Treatment with rosuvastatin is associated with an increased 24-h HRV in hypercholesterolaemic patients without coronary artery disease. P2256 Understanding the awareness of hypercholesterolemia and the adherence to lipid-lowering treatment in Brazil: the CORE project A.C. Sposito, J.E. Dos Santos, F.A. Fonseca, J.R. Faria-Neto, R.D. Santos, J.A.F. Ramires, M.C. Bertolami, O.R. Coelho, E. Tutihashi, F.H.Y. Cesena on behalf of CLACC - Latin-American Council for Cardiovascular Care. CLACC, Sao Paulo, Brazil Purposes: to evaluate the proportion of adults with measured blood cholesterol, the prevalence of self-reported hypercholesterolemia (HCHOL), the rate of adherence to lipid-lowering treatment, and factors associated with non-adherence in Brazil. Methods: Part 1: 2000 individuals were interviewed in 70 cities. The sample was representative of the voting population. The margin of error of the survey was 3% at a 95% confidence interval. Part 2: 35 to 65 year-old patients (pts) from the two upper economic classes with self-reported HCHOL were interviewed. They were considered adherent (n=418) if on statins for more than one year, and nonadherent (n=417) if had withdrawn statins in the previous 12 months, without medical counselling. A segmentation analysis was performed to classify the pts into mutually exclusive groups, according to their attitudes. The chi-square test was used for statistical analyses. Results: Part 1: 53% of the interviewed individuals informed to have never had their blood cholesterol determined. Among those with measured blood cholesterol, 22% said that the level was high, meaning a prevalence of self-reported HCHOL of 10%. Among the individuals with presumed HCHOL, 33% informed to be on treatment and had always treated, 17% said that they had not been on treatment but started treating, 23% reported that they had treated but quitted, and 28% informed that they had never treated the HCHOL. Part 2: compared to the adherent pts, the non-adherent group reported a lower prevalence of arterial hypertension (39% vs. 29%, p=0.002) and diabetes mellitus (14% vs. 7%, p=0.001); a higher rate of smoking (27% vs. 36%, p=0.005); shorter, less detailed appointments; a lower level of trust in the physician; to be aware of HCHOL for a shorter time; to consider HCHOL less severe; to search information about HCHOL less frequently (54% vs. 40%, p <0.001) and alternative treatments more often (35% vs. 59%, p <0.001). Three behavioural profiles were characterized: undisciplined, misinformed/pleased, and worried (16%, 29%, and 55% of the sample, respectively). Adherence rates were 28%, 34%, and 65% in these groups, respectively (p <0.001). Conclusions: based on the prevalence of self-reported HCHOL (10%), the high proportion of non-measured blood cholesterol, and the low adherence to lipidlowering treatment, it is mandatory to improve the strategies targeting detection of HCHOL and treatment compliance. Among multiple factors that contribute to treatment non-adherence, behavioural patterns may be identified in the pts and help establish specific measurements to overcome barriers to adherence. P2257 Heart rate variability and plasma lipids before and after treatment with rosuvastatin in hypercholesterolaemic patients without coronary artery disease E.A. Zacharis 1, M.E. Marketou 1, E.I. Skalidis 1,I.Karalis 1, A.P. Patrianakos 1,K.Stokkos 1, E. Ganotakis 2, F.I. Parthenakis 1, P.E. Vardas 1. 1 Cardiology Dept. Heraklion University Hospital, Heraklion, Greece; 2 Dept. of Internal Medicine, Heraklion, Greece P2258 Sex differences in the effect of hypertension on lipid profiles in Chinese patients X. Fan, Y. Wang, K. Sun, H. Wang, X. Song, W. Song, W. Zhang, H. Wu, X. Zhou, R. Hui. Cardiovascular Institute & FuWai Hospital, Chinese Academy of Medical Sciences and Peking Union Medi, Beijing, China, People s Republic of Purpose: Differences in blood pressure and lipid profiles are well known between sexes. However, little is known about whether hypertension influences the sexrelated differences in serum lipid and lipoprotein levels. The present study aimed to examine the effect of hypertension on sex-related differences in lipid profiles in Chinese. Methods: We conducted a community-based cross-section study composed of 5389 hypertensive patients (3555 women and 1834 men) and 1285 normotensives (833 women and 452 men), aged years, from 7 rural communities in China. Dyslipidemia (including high- triglycerides, high- total cholesterol, highlow-density lipoproteins, and low- high-density lipoproteins) were diagnosed according to Adult Treatment Panel III guideline. Results: After adjustment for body mass index and fasting blood glucose, women showed higher levels of high-density lipoproteins than men before and after 55 years of age in either normotensives or hypertensive patients, while total cholesterol and low-density lipoproteins rose in women with aging and exceeded men significantly after 55 years of age. The level of triglycerides was lower in hypertensive or normotensive women than in men before 55 years of age. However, hypertensive women over 55 years of age showed significantly higher triglycerides level than did men (mean differences: 20.2 mg/dl, P<0.001), but no sexdifferences in triglycerides level were found in normotensives (mean differences: 2.4 mg/dl, P>0.05). Dyslipidemia was more common in men than in women in either normotensives (28.7% vs. 22.2%, P=0.042) or hypertensives (40.6% vs. 35.1%, P=0.027) before 55 years of age. However, this sex-related difference in dyslipidemia disappeared in normotensives (24.3% vs. 31.6%, P>0.05) and reversed in hypertensive patients (30.0% vs. 42.4%, P<0.001) after 55 years of age. Central obesity was more common in women than in men throughout the age span, and no effect of hypertension was found on this sex-related difference. Conclusions: Sex-related differences in lipid profiles can be influenced by age and hypertension. P2259 Beneficial modulation of heart rate variability indices after rosuvastatin treatment in type 2 diabetic patients E.A. Zacharis 1, M.E. Marketou 1, E.I. Skalidis 1,I.Karalis 1, K. Stokkos 1, A.P. Patrianakos 1, G.F. Diakakis 1, E. Ganotakis 2, F.I. Parthenakis 1, P.E. Vardas 1. 1 Cardiology Dept. Heraklion University Hospital, Heraklion, Greece; 2 Dept. of Internal Medicine, Heraklion, Greece Purpose: Diabetic autonomic neuropathy is a frequent and serious complication of diabetes mellitus (DM). The reduction in parameters of heart rate variability (HRV) seems not only to carry negative prognostic value in patients with diabetes but also to precede the clinical expression of autonomic neuropathy. The objective of this study was to examine the effect of rosuvastatin treatment on HRV indices in patients with type 2 DM. Methods: We included 52 subjects with type 2 DM (18men, aged 65±10 years) with low density lipoprotein (LDL-C) cholesterol<130 mg/dl. All had a normal echocardiogram and no signs of coronary artery disease. Holter recording and fasting blood samples were performed in all subjects. The subjects were random-

71 Lipids and statins / Other topics 371 ized to receive 10 mg/day rosuvastatin (n=28) or placebo (n=24) for 6 months and were reevaluated. Results: LDL-C levels was significantly reduced (from 108±52 mg/dl to 89±34mg/dl, p<0.05). Heart rate variability indices at baseline and after 6 months of treatment are showed in Table 1. Table 1 Rosuvastatin Placebo before 6 months before 6 months SDNN 48.3± ±17.6* 45.6± ±18.9 SDANN ± ±16.5* 115.9± ±16.5 pnn ± ±5.7* 6.93± ±4.7 rmssd 32.4± ±9.5* 35.4± ±2.5 *p<0.05 compared to baseline. Conclusions: Treatment with rosuvastatin is associated with an increased 24- h HRV in type 2 diabetic patients. The clinical significance of this finding needs further investigation. OTHER TOPICS P2261 Identification of an electronegative LDL as potential novel biomarker for acute coronary syndrome P.-Y. Chang 1, J.-K. Lee 1, Y.-J. Chen 1,S.-C.Lu 1, Y.-T. Lee 1, K.-C. Chang 2,P.-Y.Pai 2, C.-H. Chen 3. 1 National Taiwan University Hospital, Taipei, Taiwan; 2 China Medical University, Taichung, Taiwan; 3 Baylor College of Medicine, Houston, United States of America Purpose: L5, a highly electronegative LDL originally isolated from hypercholesterolemic human plasma, exhibits a spectrum of atherogenic effects on cultured vascular cells. To evaluate its clinical implication, we assess its prevalence in patients with acute coronary syndrome (ACS), coronary artery disease (CAD) or CAD risk factors in comparison with subjects without these risk factors. Methods: Fasting blood samples were collected from adult patients with angiographically evidenced (coronary artery stenosis 50%) ACS (n=20) or stable angina (n=20), asymptomatic hypercholesterolemia (LDL cholesterol 160 mg/dl; n=20), type 2 diabetes mellitus (HbA1c 8.0; n=20), history of chronic smoking (n=20), and healthy subjects without these risk factors (n=20). Plasma LDL was divided by ion-exchange chromatography and all detectable LDL subfractions were collected. The most electronegative LDL subfraction, L5, was quantitated and the ratio of L5 to total LDL was calculated. Significant elevation of plasma L5 levels was defined as a percentage ratio of L5/LDL higher than 1.0%. Results: Plasma LDL was divided by ion-exchange chromatography into 5 subfractions, L1 L5, with increasing electronegativity, in all hypercholesterolemic samples (n=20/20;l5/ldl= %). In contrast, ion-exchange chromatography failed to yield L5 in any of the healthy subjects without CAD risk factors. Irrespective of the plasma cholesterol concentrations, L5 was found in all ACS patients (n=20/20; L5/LDL= %) and most CAD patients with stable angina (n=14/20; L5/LDL= %). L5 was also found in most diabetic (n=16/20;l5/ldl= %) and most chronic smokers (n=14/20; L5/LDL= %). Patients with ACS had significantly higher L5/LDL ratio than patients with stable angina (5.9±2.2 vs. 1.8±1.3, p<0.05). Regardless of their origins, all L5 specimens were able to induce human coronary arterial endothelial cell apoptosis and inhibit EC proliferation by inhibiting fibroblast growth factor-2 expression. L1-L4 had no effects. Conclusions: We have identified a naturally-occurring oxidized LDL in human plasma named L5 as potential biomarker for ACS. The significant presence of L5 in patients with ACS, CAD or CAD risk factors but not in risk-free healthy subjects implicates a clinical correlation. Large-scale epidemiological survey and prospective investigations are warranted to confirm L5 s atherogenic role and hence identifying it as a novel therapeutic target. P2262 Significant impact of chromosomal locus 1p13.3 on serum LDL cholesterol and on angiographically characterized coronary atherosclerosis A. Muendlein 1, S. Rhomberg 1,C.H.Saely 1, T. Winder 2, G. Sonderegger 1,P.Rein 1,S.Beer 1, A. Vonbank 1,H.Drexel 1. 1 VIVIT Institute, Feldkirch, Austria; 2 Private University in the Principality of Liechtenstein, Triesen, Liechtenstein Objectives: Recently, a significant impact of a new locus on chromosome 1p13.3 on serum LDL cholesterol and clinical events of coronary artery disease (CAD) was described. Potential associations between variants on this locus and angiographically characterized coronary atherosclerosis are unknown. We therefore aimed at investigating the association of variants of locus 1p13.3 with coronary atherosclerosis. Methods: We performed genotyping of variants rs599839, rs646776, and rs on chromosome 1p13.3 in a large cohort of 1610 consecutive Caucasian patients undergoing coronary angiography, where lesions of 50% or more were classified as significant. Results: Compared to the homozygous common allele the rare alleles of variants rs599839, rs646776, and rs were significantly associated with decreased serum LDL cholesterol (132±40 vs. 125±36 mg/dl, p = 0.003, 132±40 vs. 124±36 mg/dl, p <0.001, and 131±40 vs. 125±37 mg/dl, p = 0.005, respectively). Further, carriers of the rare alleles of variants rs and rs were at a significantly lower risk of significant coronary stenoses than subjects who were homozygous for the frequent allele, with odds ratios (OR) of 0.78 [ ]; p = and 0.74 [ ]; p = 0.004, respectively. After multivariate adjustment including LDL cholesterol, the protective effect of the rare allele of variant rs646776, but not of variant rs599839, on CAD risk remained significant (OR = 0.77 [ ], p = 0.034). Conclusion: We conclude that chromosomal locus 1p13.3 is significantly associated with both, serum LDL cholesterol and coronary atherosclerotic lesions. P2263 Relationships between modulation of functional characteristics of plasma lipoproteins and changes in their size and composition by short-term exercise in patients with metabolic syndrome A.C.F. Casella-Filho, F.H.Y. Cesena, I.C. Trombetta, V. Monteiro- Silva, C. Denardi, C.C. Magalhaes, C.E. Negrao, R.C. Maranhao, P.L. Daluz, A.C.P. Chagas. Heart Institute (InCor) HC.FMUSP, Sao Paulo, Brazil Purpose: To verify whether modulation of functional properties of lipoproteins by short-term exercise training (ExT) is associated with changes in size and composition of LDL and HDL subfractions in patients with metabolic syndrome (MetS). Methods: Forty sedentary persons (30 with MetS, 10 controls) were evaluated. Twenty of those with MetS were subjected to a 3 times/week controlled training load (45 min/day) for 3 months on a bicycle ergometer. LDL and HDL subfractions were obtained by plasma ultracentrifugation before and after ExT, and their compositions were analysed. HDL particle size was determined by laser-light scattering method. In vitro resistance of LDL to oxidation with CuSO4 was determined. In another assay, LDL from control subjects was incubated with HDL2a or 3b from MetS patients (before and after ExT) and the resistance to oxidation was verified. Results: ExT did not alter plasma levels of total cholesterol (TC), LDL-c, HDL-c, apoa1 and apob, but significantly decreased the concentration of triglycerides (TG). LDL resistance to oxidation markedly increased (+91%) after ExT, which was associated with a significant decrease in the content of apob (-16%) and TG (-14%), but not of TC, free cholesterol, cholesterol ester, total protein or phospholipids, in the LDL particle. Oxidizability of control LDL decreased when mixed with HDL2a or 3b from patients with MetS after ExT, compared with coincubation with HDL2a or 3b from these patients before ExT (-23% for HDL2a and -18% for HDL3b). This was associated with a significant decrease in the content of TC and TG in HDL3b (-7% and -12%, respectively) and HDL3c (-13% and -15%, respectively). ExT did not significantly modify concentrations of TC and TG in HDL2a, 2b and 3a, and total protein content was unchanged in all HDL subfractions. HDL particle size did not change with ExT (10.23±1.10 vs 10.26±1.09 μm before and after ExT, respectively, p >0.05). Conclusions: in subjects with MetS, short-term ExT does not change plasma LDL-c concentration but reduces LDL vulnerability to oxidation, associated with a significant decrease in lipid (TG) and protein (apob) content in LDL, indicating a change from small, dense to larger, less dense particles. ExT does not change HDL size and plasma HDL-c concentration, but promotes early enhancement of anti-oxidative properties of HDL subfractions, associated with a decrease in TC and TG content in the smallest subfractions. P2264 Low HDL - high inflammatory markers in heart failure induced by high frequency pacing in minipigs B. Pennato 1, V. Lionetti 1, F. Bigazzi 2, M. Puntoni 3, A. Simioniuc 1, M. Campan 1, F.A. Recchia 1, T. Sampietro 3. 1 Scuola Superiore Sant Anna, Pisa, Italy; 2 Fondazione Toscana Gabriele Monasterio, Pisa, Italy; 3 CNR Istituto di Fisiologia Clinica, Pisa, Italy Background: Clinical, experimental and in vitro studies suggest a major role for high-density lipoproteins (HDL) in the vascular homeostasis regulation, not necessarily related to pro- or anti-atherosclerotic mechanisms. Low HDL, together with a pro-inflammatory state, seem to be associated with left ventricular dysfunction in the absence of coronary atherosclerotic lesions, as occurs in idiopathic dilated cardiomyopathy. Aim: To test possible correlations between the development of non-ischemic cardiac failure and altered levels of HDL and ApoAI, inflammatory markers C3, alpha- 2-macroglubulin and ceruplasmin, in a pig model of pacing-induced dilated cardiomyopathy. Material and Methods: 8 adult male minipigs were chronically instrumented with a pacemaker connected to the left ventricular (LV) wall. Blood samples were collected at baseline, i.e. before starting the pacing protocol, and after three weeks of pacing at 180 beats/min, when LV ejection fraction was <35% and end-diastolic pressure was >18 mmhg. Statistical analysis was performed with paired Student s t-test. Results: After three weeks of pacing there were no significant changes in total cholesterol and triglycerides compared to baseline (57±7.50 vs 53.88±13.79 mg/dl and 23.67±9.31 vs 28.43±4.50 mg/dl respectively). Conversely, HDL and

72 372 Other topics ApoAI levels were dramatically decreased (21.63±2.45 vs 9.63±3.62 mg/dl, p=0.0004, and 16.86±0.97 vs 9.76±3.41 mg/dl, p=0.002, respectively). Among the inflammatory markers, alpha-2-macroglubulin and ceruplasmin levels were significantly increased (107.14±15.65 vs ±26.04 mg/dl, p=0.0314, and 26.51±3.37 vs 36.45±5.92 mg/dl, p=0.0096, respectively), while C3 levels were not significantly changed (14.66±4.59 vs 17.88±8.30 mg/dl). Conclusion: Our results suggest a novel association between development of cardiac dysfunction and decrease in circulating HDL, even in the absence of other co-morbidities and alterations of total cholesterol and triglycerides. P2265 The role of lipoprotein-a on major cardiovascular events in patients with familial combined hyperlipidemia and metabolic syndrome C. Masoura, I. Skoumas, C. Pitsavos, K. Aznaouridis, V. Metaxa, L. Papadimitriou, F. Platsouka, T. Tsokanis, N. Giotsas, C. Stefanadis. Hippokration General Hospital of Athens, Athens, Greece Purpose: To evaluate the role of lipoprotein-a (Lp-a) on cardiovascular risk in familial combined hyperlipidemia (FCH) patients with metabolic syndrome (MetS). Methods: We studied prospectively 323 FCH patients with MetS (mean age 51 y, 208 males) for 9.8±3.4 years. Demographic and biochemical parameters were recorded at enrolment. Diagnosis of MetS was made according to the modified ATPIII criteria. Hard cardiovascular end-points, like acute myocardial infarction (AMI) and cardiovascular death, were recorded. Results: Overall 9% of the patients (29 patients, 10.6% males vs. 6.1% females, P=0.17) presented with outcomes. We observed no difference (P=NS) between patients with and without cardiovascular endpoints, in regard to total cholesterol (289±51 vs. 287±57 mg/dl), LDL-cholesterol (194±55 vs.189±58 mg/dl), triglycerides (317±140 vs. 340±176 mg/dl), HDL-cholesterol (37±8 vs. 38±9 mg/dl), apolipoprotein-a1 (137±20 vs.139±25 mg/dl) and apolipoprotein-b levels (180±41 vs. 172±41 mg/dl). In contrast patients with AMI and/or cardiovascular death were older (55.8±8.3 vs. 50.3±10.3 years, P=0.006) and they had higher waist/hip (0.942±0.084 vs ±0.066, P=0.069) and higher Lp-a levels (40.3±44.9 vs. 28.2±29.6 mg/dl,p=0.049) at enrolment. After Cox regression analysis, Lp-a at enrolment and age were the significant predictors for AMI and/or death (hazard ratio per 1 mg/dl-increase of Lp-a, 95% CI , P=0.011). Conclusions: Lp-a level represents an independent predictor of major cardiovascular events in FCH patients with metabolic syndrome. P2266 Characterization and validation of a combined oral triglyceride and glucose tolerance test in patients with coronary artery disease C.M. Werner, A. Filmer, M. Fritsch, S. Groenewold, M. Boehm, U. Laufs. Universitätsklinikum des Saarlandes - Klinik für Innere Medizin III, Homburg, Germany Background: Retrospective analyses of epidemiologic studies suggest an association of postprandial TG levels with the risk of cardiovascular events, whereas fasting TG levels may be less predictive. The aim of our study was to develop a combined oral triglyceride and glucose tolerance test (OTT/OGT) in order to measure postprandial triglyceride and glucose tolerance at the same time. Methods and Results: Pilot experiments in 25 healthy volunteers and cross-over studies in patients with CAD and metabolic syndrome showed that a sequential test protocol with a 75g fat load test applied 3 hours prior to a glucose tolerance test showed no significant differences in the triglyceride kinetics compared to the OTT alone. N = 300 consecutive patients with stable coronary artery disease (CAD) were subjected to the OTT->OGT protocol, patients with diabetes received the OTT alone (mean age 66 y.). In addition, 40 age-matched subjects without CAD were examined. Within the CAD patients, individuals without metabolic syndrome (MS) and normal glucose tolerance (n=54) showed the lowest triglyceride values (fasting TG 103±5 mg/dl, TG at maximum 183±11 mg/dl). Patients with CAD and metabolic syndrome and impaired glucose tolerance (IGT) or diabetes mellitus (DM) had the highest triglyceride values (n=132, fasting 198±11 mg/dl, at maximum 335±17 mg/dl). CAD patients with MS but no IGT/DM (n=57, fasting 130±7 mg/dl, at maximum 248±5 mg/dl) and patients with IGT/DM but no MS (n=57, fasting 122±7 mg/dl, at maximum 233±16 mg/dl) showed a significantly lower postprandial TG increase. The group of IGT/DM patients was the only group to show a further TG increase between 4 and 5 hours post OTT, suggesting a delayed triglyceride clearance in diabetic CAD patients. The triglyceride maximum did not significantly differ between CAD patients without MS and IGT/DM and control subjects without CAD. Interestingly, in all patient groups with CAD, the relative TG increase did not correlate to the absolute TG increase. Conclusions: TG tolerance and glucose tolerance can be simultaneously measured in CAD patients using a simple sequential test protocol. As expected, patients with metabolic syndrome and diabetes exhibit elevated fasting and postprandial TG. However, CAD patients show striking differences between their absolute and relative postprandial triglyceride increase. Follow-up examinations in over 500 patients will be performed to elucidate whether the postprandial triglyceride kinetics correlate with future cardiovascular events and whether this test protocol identifies patients with TG-associated cardiovasular risk. P2268 Postprandial lipemia in familial combined hyperlipidemia, familial hypercholesterolemia and healthy subjects A. Pavlidis, G. Kolovou, K. Anagnostopoulou, P. Petrou, K. Sorodila, A. Valaora, K. Salpea, D. Cokkinos. Onassis Cardiac Surgery Center, Athens, Greece Purpose: Familial combined hyperlipidemia (FCH) is the most common familial dyslipidemia among patients who suffer early myocardial infarction. Familial hypercholesterolemia (FH) is a monogenic disorder of lipid metabolism secondary to low density lipoprotein receptor mutations that has been strongly linked to premature coronary artery disease (CAD). Postprandial hypertriglyceridemia is also associated with CAD. The purpose of this study was to evaluate postprandial lipemia after an oral fat tolerance test (OFTT) in men with FCH and compare them to FH and healthy subjects. Methods: The study population consisted of 83 subjects. OFTT was given to 34 men with FCH, 29 men with FH and 20 healthy men. The FCH and FH groups were further divided according to the lipid phenotype, on the basis of Fredrickson s classification, into five subgroups: FCH IIA (n=13), FCH IIB (n=10), FCH IV (n=11), FH IIA (n=21) and FH IIB (n=8). TG concentrations were measured before, 2, 4, 6 and 8 h after OFTT and the postprandial response was evaluated by the areas under the curve (AUC) for TG concentrations. Results: The TG levels after OFTT were significantly higher in FCH compared to FH and healthy groups (AUC in mg/dl/h; 2678±1415 vs. 1503±1147 and 1011±652 respectively, p<0.001). The postprandial TG levels were significantly increased in FCH IV and FCH IIB groups compared to FCH IIA at 2h (p=0.002 and p=0.001 respectively), 4h (p=0.004 and p<0.001 respectively), 6h (p=0.002 and p<0.001 respectively) and 8h (p<0.001 and p<0.001 respectively). There were no significant differences between FCH IV and FCH IIB groups and among FH and FCH subgroups with the same lipid phenotype (FH IIA vs FCH IIA and FH IIB vs FCH IIB). Fasting TG levels were the only significant predictor of the AUC (Spearman s rank correlation; r = 0.907, p < 0.001). Conclusions: Fasting TG concentration is the main determinant of postprandial lipemia. FCH and FH patients demonstrate an exaggerated postprandial response that could partially contribute to the high cardiovascular risk. This abnormal response is even more pronounced in FCH subjects with a prevalent hypertriglyceridemic phenotype. These patients should be identified and treated promptly with the appropriate hypolipidemic regime. P2269 Improvement in the control of hypercholesterolemia in coronary heart disease patients over the decade from 1997 to 2007 S. Surowiec 1, P. Jankowski 1, R. Wolfshaut 2,M.Loster 1,K.Batko 2, A. Pajak 2, K. Kawecka-Jaszcz 1. 1 I Department of Cardiology and Hypertension Jagiellonian University Collegium Medicum, Krakow, Poland; 2 Faculty of Health Sciences Jagiellonian University Collegium Medicum, Krakow, Poland Background: Effective treatment of hypercholesterolemia improve prognosis in coronary heart disease patients. However, the control of hypercholesterolemia was found insufficient. Purpose of the present analysis was to assess changes in effectiveness of the hypercholesterolemia treatment in coronary patients under care of general practitioners (GP) and cardiologists in hospital outpatient clinics (HO). Methods: Consecutive patients after hospitalization due to myocardial infarction, unstable angina, PCI or CABG at age years, residents of Cracow province (1.2 mln. inhabitants), were examined 6-18 months after discharge in Cracovian Program of Secondary Prevention Ischemic Heart Disease ( ) and in Polish component of Euroaspire III ( ). Results: There were 365patients (188 treated in HO and 177 treated by GPs) examined in and 363 patients (228 and 135 respectively) examined in No significant differences in age and sex distribution were found between the studied groups. The use of the lipid lowering drugs was 18,6% in in patients treated by GPs and 48,9% in patients treated in HO (p<0,0001). After ten years the rates increased to 88,2% and 86,8% respectively. At baseline cholesterol concentration <4.5 mmol/l was found in 9,0% patients treated by GPs and 19.5% patients treated in HO (p<0,001) and at the end of the study in 52,3% and 52% of patients respectively. In LDL-Cholesterol <2,5 mmol was found in 8.3% patients treated by GPs and 18,8% treated in HO (p<0,001) and in in 59.9% of patients in both groups. At baseline HDL-cholesterol >1.0 mmol/l (men) or >1.2mmol/l (women) was found in over 80% of patients in both sites at baseline and at the end of the study Triglycerides concentration <1,7 mmol/l was found in 54,6% patients treated by GPs and in 59,0% patients treated in HO at baseline and at the end of the study in 71.9% and 60,9%, respectively (p<0.05). Conclusion: Differences in the lipid lowering treatment between patients treated in GPs and in HO found in , were no longer observed ten years after. Improvement e was achieved in both sites but it was more pronounced in patients treated by GPs.

73 Other topics 373 P2270 Postprandial triglycerides and postprandial inflammation are significantly reduced by eight weeks of eccentric endurance exercise P. Rein 1, C.H. Saely 2, A. Vonbank 1, S. Beer 1,V.Kiene 1,S.Aczel 1, T. Bochdansky 3,H.Drexel 1. 1 VIVIT-Institute, Feldkirch, Austria; 2 Private University in the Principality of Liechtenstein, Triesen, Liechtenstein; 3 Rankweil State Hospital, Rankweil, Austria Purpose: Postprandial triglyceridemia is considered to be a substantial risk factor for cardiovascular disease. The atherogenicity of postprandial hypertriglyceridemia may in part be driven by inflammatory mechanisms. We hypothesised that eccentric endurance exercise lowers both, postprandial triglyceride excursions and the postprandial inflammatory response. Methods: Over a training period of 8 weeks, 51 healthy non-diabetic subjects (16 men and 35 women, mean age 50.7 years) 3 to 5 times per week performed eccentric endurance exercise by hiking downhill a path in the Austrian alps covering a difference in altitude of 540 meters; for the upward way a cable car was used, where compliance was measured electronically. The area under the triglyceride curve according to Patsch was measured after a standardized oral fat load; together with postprandial trigylcerides also postprandial leukocytes were measured. Results: Both postprandial triglyceridemia (from 1762±880 mg*dl 1h 1at baseline to 1417±664 mg*dl 1h 1; p <0.001) and postprandial leukocytes (from 68.8±11.6 G*L 1h 1 to 66.5±13.6 G*L 1h 1; p = 0.023) were reduced significantly with 8 weeks of eccentric endurance exercise. Conclusions: Eight weeks of modestly strenuous eccentric endurance exercise significantly reduce postprandial triglyceridemia and postprandial inflammation. P2271 Coronary obstruction detected by computerized tomography angiography in familial hypercholesterolemia is associated with Achilles tendon xanthomata and coronary artery calcification M.H. Miname, J. Parga, J. Avila, A.P. Chacra, W. Salgado, C.E. Rochitte, R.D. Santos. Heart Institute InCor University of Sao Paulo, Sao Paulo, Brazil Familial hypercholesterolemia (FH) is characterized by early coronary heart disease (CHD) onset. Multidetector computed tomography (MDCT) angiography has been proposed as a non-invasive test to determine asymptomatic coronary obstruction presence and might be useful as a screening tool in this population at high risk of CHD. However, MDCT use is implicated with elevated cost, high radiation and contrast exposures. On the other hand, coronary artery calcification (CAC) quantification, an accepted measure of plaque burden and a marker of CHD events, can be easily obtained by computerized tomography with no contrast injection, low radiation exposure and at a lower cost. Our objective was to evaluate determinants of coronary obstruction assed by MDCT angiography in asymptomatic FH subjects. Seventy-nine FH subjects (38% men) underwent routine clinical, laboratory and 64-slice MDCT angiography evaluations. Achilles tendon xanthomas were found by clinical examination in 19% of subjects. The presence of CAC determined by Agatston s method (CAC socres > 0) and stenosis defined as 50% obstruction of vessel lumen were found respectively in 42% and in 16% of study subjects. There were no differences between the groups regarding: age (47±12 vs. 44±14 years, p=0.43), male gender (56% vs. 50%, p=0.15), LDL-C (295±47 vs. 279±52 mg/dl, p=0.24), cholesterol-year score (17.721±5.187 vs ±6.298, p= 0.26), HDL-C (46±8 vs. 47±11mg/dL, p=0.78), Lipoprotein(a) (median: 42 vs. 54 mg/dl, p= 0.58), and C reactive protein levels (median: 1.7 vs. 1.6 mg/l, p=0.14) in those presenting or not stenosis respectively. No differences were also found in those with or without stenosis respectively in the prevalence of smoking (0% vs. 14%, p=0.19), hypertension (31% vs. 32%, p=0.97), previous statin use (31% vs. 30%, p= 0.96) and in the presence of the metabolic syndrome (25% vs. 40%, p=0.39). However, those with stenosis had a greater CAC prevalence 100% vs. 32%, p<0.0001, and higher median CAC scores 49 vs. 0, p< The presence of Achilles tendon xanthomas was also more frequent in those with stenosis (47% vs. 13%, p=0.0084). In conclusion the presence of Achilles tendon xanthomata and CAC were associated with coronary stenosis. The presence of either CAC and Achilles tendon xanthomata might be useful in determining in whom MDCT angiography might be used as a screening tool to detect luminal obstruction in FH. Prospective data are necessary to evaluate the role of MDCT angiography in predicting CHD events in these subjects. Background and objective: In spite of statin therapy, the incidence of cardiovascular (CV) events is high. Whilst LDL-C goal is sometimes not reached, other lipid abnormalities can also contribute to CV risk. The objective of DYSIS study was to assess the prevalence of lipid abnormalities (LDL-C, HDL-C and triglycerides) in patients treated with statins. Methods: Analysis of 3721 Spanish patients included in DYSIS, a cross-sectional study carried out in Europe and Canada on 20,916 patients 45 years-old treated with statins for at least 3 months. Data were recorded from patient s clinical charts. We used the ATP-III recommendations to define patient risk, LDL-C goal and the normality or not of the HDL-C and triglycerides. Results: In 3721 patients (median age 65 year-old, 47.3% women, 61.2% highrisk patients), LDL-C was not at goal in 50.4% (men:51.4%, women: 49.1%, p=0.19). Lack of goal attainment was more frequent in high (58.8% [goal<100 mg/dl], 89.8% considering <70 mg/dl) and moderate risk (48.9% [goal <130 mg/dl]) vs low risk patients (21.3% [goal <160 mg/dl] p<0.001). Low HDL was present in 29.8% of the patients (men:25.0% [<40 mg/dl], women: 35.1% [<50 mg/dl], p<0.001) and in respectively, 34.8%, 37.1% and 2.1% of those at high, moderate and low CV risk. Triglycerides were 150 mg/dl in 37.6% (men: 41.4%, women: 33.8%, p<0.001), and respectively, in 40.7%, 42.0% and 20.8% (high, moderate or low CV risk). 36.8% had two or more abnormalities (6.4% abnormal LDL-C + low HDL-C, 13.1% abnormal LDL-C + triglycerides and 9.7% had abnormal values of the three parameters). Only 28.4% of patients had the three lipids within the recommended range or the range considered normal in the NCEP APT III guideline. Conclusions: Despite statin therapy, a large amount of patients show lipid abnormalities, not only abnormal LDL-C but also low HDL-C and/or abnormal triglycerides, especially those at higher CV risk. An integrated approach to the treatment of dyslipidaemia may be of interest in order to reduce the risk of CV complications even further in patients treated with statins. P2273 Controlling lipids in a high risk population with documented coronary artery disease for secondary prevention: are we doing enough? M. Singh 1,S.Chin 2,P.Giles 2, D. Carothers 2, K. Al-Allaf 2, J. Khan 2. 1 Rosalind Franklin University of Medicine & Science, Chicago Medical School, Illinois., North Chicago, United States of America; 2 Walsall Hospitals NHS Trust, Walsall, West Midlands., Walsall, United Kingdom Purpose: Prevalence of low HDL-C in patients who have achieved LDL-C targets in the current era of universal statin therapy for secondary prevention remains unknown. We conducted a study to determine the prevalence of low HDL-C in patients with documented coronary artery disease, and the lipid lowering treatment patterns in secondary prevention of CAD. Methods: In this retrospective cohort analysis, data were captured from 1999 to The Joint British Society 2 criteria were used for defining low HDL-C as <1.0 in males and <1.2 in females. We compared the prevalence of low HDL-C across the following categories of LDL-C: < 2 mmol/l, mmol/l, and > 2.5 mmol/l. Table 1 Variables LDL-C < 2 LDL-C: LDL-C > 2.5 No of patients Age 65.23± ± ±11.54 TC 3.38± ± ±0.78 HDL 1.16± ± ±0.33 LDL 1.50± ± ±0.63 P2272 Percentage lipid abnormalities in statin treated patients. The dyslipidemia international survey study (DYSIS-SPAIN) J.R. Gonzalez-Juanatey 1, J. Millan 2,C.Guijarro 3, E. Alegria 4, J.V. Lozano 5, V. Inaraja 6,G.Vitale 6,L.Cea-Calvo 6 on behalf of Spanish DYSIS investigators. 1 Hospital Clinico Universitario de Santiago de Compostela, Santiago de Compostela, 2 Hospital General Universitario Gregorio Maranon, Madrid, 3 Hospital Fundación Alcorcón, Madrid, 4 Clinica Universitaria de Navarra, Pamplona, 5 Centro de Salud Serrería 2, Valencia, 6 Clinical Research Department, Merck Sharp & Dohme, Madrid, Spain Results: 2087 patients with a mean age of 64.34±11.94 years constituted the study sample. 36.6% of patients in this study were found to have low HDL-C. Irrespective of gender, low HDL-C was prevalent across all levels of LDL-C, but interestingly most prevalent in patients with a LDL-C <2 mmol/l (43.06%). There was no correlation between the LDL-C and HDL-C levels implying their independent relationship and, thus, the need to treat them independently.

74 374 Other topics P2274 Body mass index independently predicts the variation in plasma levels of triglycerides and the triglycerides/hdl-cholesterol ratio after short-term red wine consumption F.H.Y. Cesena, A.C.M. Andrade, S.R. Coimbra, A.M. Benjo, P.L. Da Luz. Heart Institute (InCor), University of Sao Paulo Medical School, Sao Paulo, Brazil Purpose: To determine predictive factors of variations in plasma levels of triglycerides (TG), TG/HDL-c ratio, and plasma glucose after short-term red wine consumption. Methods: 42 individuals (64% men, 46±9 years) were given red wine (250 ml/day) for 14 days. Plasma concentration of lipids and glucose were measured before and after red wine consumption. Paired t test, analysis of variance and linear regression were used for statistical analyses. Results: Baseline characteristics included body mass index (BMI) 25.13±2.76 kg/m 2, LDL-c 156±39 mg/dl, and HDL-c 53±14 mg/dl. Red wine increased plasma levels of TG from 105±42 mg/dl to 120±56 mg/dl (p=0.001) and the TG/HDL-c ratio from 2.16±1.10 to 2.50±1.66 (p=0.014). In a linear regression model adjusted for age, gender, baseline BMI, blood pressure, lipids, and glucose, only BMI was independently predictive of the variation in plasma TG after red wine (beta coefficient 0.593, p <0.001). Similar results were found for the correlation between BMI and the variation in TG/HDL-c ratio (beta coefficient 0.529, p <0.001, adjusted model). When individuals were divided into 3 categories, according to their BMI, the average percent variation in TG after red wine was 4%, 17%, and 33% in the lower, intermediate, and higher quartiles, respectively (p=0.001). The respective numbers for the variation in the TG/HDL-c ratio were 5%, 18%, and 32% (p=0.007). The table shows the mean plasma levels of TG and TG/HDL-c ratio, according to BMI quartiles (Q), before and after red wine intake. Red wine also increased the plasma concentration of glucose from 92±9 mg/dl to 96±9 mg/dl (p=0.002). This variation was inversely correlated to baseline plasma glucose (beta coefficient 0.437, p=0.006) in a linear regression model adjusted for age, gender, baseline BMI, blood pressure and lipids. Q1 (n=14) Q2 (n=14) Q3 (n=14) BMI kg/m 2 BMI kg/m 2 BMI kg/m 2 Before After Before After Before After TG (mg/dl) 100±41 97±47 107±41 124±53 108±46 139±63 TG/HDL-c 1.91± ± ± ± ± ±1.93 Conclusions: Individuals with higher BMI are at greater risk for adverse metabolic effects of short-term red wine consumption, regarding elevation in plasma TG levels and the TG/HDL-c ratio. P2275 Cholesterol metabolism and hepatic function in cardiovascular patients aged 75 years and older T. Strandberg 1, M.H. Hovinen 2, K.H. Pitkala 2,T.A.Miettinen 2, R.S. Tilvis 2. 1 University of Oulu, Oulu, Finland; 2 University of Helsinki, Helsinki, Finland Purpose: One of the paradoxes in old age is that low serum cholesterol is often associated with better survival in epidemiological studies. We investigated hepatic function and cholesterol metabolism in a group of patients with stable cardiovascular disease (CVD) aged 75 years and older and related these to 7-year mortality Methods: In the DEBATE study mailed questionnaires, sent to a random sample of individuals aged 75 and over, were used to retrieve 400 home-living CVD patients. At baseline in 2000, they underwent clinical examinations and laboratory testing. 15D score was used to measure general function. Serum alanine aminotransferase (ALT, divided in quartiles) level was taken to reflect hepatic function, cholesterol metabolism was assessed with serum noncholesterol sterols (assessed in 374 individuals) of which lathosterol reflects hepatic cholesterol synthesis and cholestanol and plant sterols (campesterol, sitosterol) reflect cholesterol absorption. Total mortality up to 2006 was collected from national registers. Results: Average age at baseline was 80 years and 65.3% (n= 261) were women. Of the patients, 80.8% (n= 323), 36.5% (n=146) and 13.8% (n=55) had a history of coronary heart disease, cerebrovascular disorders, or peripheral artery disease, respectively. Median BMI was 26.1 kg/m 2 (interquartile range ). Median ALT level was 19 IU/L, (interquartile range 14-25; max 131). Although baseline 15D score was not significantly different between ALT quartiles, 7-year mortality (n=151, 40.4%) was inversely related to ALT quartile (mortality 51.1, 44.2, and 30.1% from the lowest to highest quartile, P=0.0007). Baseline comparisons were adjusted for age, sex and statin use. Both BMI and glucose were significantly higher with increasing ALT, while serum lipids including LDL-cholesterol were more inconsistent. However, marker of cholesterol synthesis significantly decreased (P=0.001) and markers of absorption significantly increased (P=0.04) with decreasing ALT quartiles. Conclusions: Lower ALT concentration and lower cholesterol synthesis reflected poorer prognosis in older CVD patients. LDL-cholesterol remained unaltered probably because cholesterol absorption still was reciprocally increased in these home-living inviduals with stable condition. P2276 Familial hypercholesterolaemia - an oportunity for preventive medicine A.M. Medeiros, A.C. Alves, V. Francisco, S. Silva, M. Bourbon on behalf of on behalf of the investigators of the Portuguese FH Study. Instituto Nacional de Saude Dr Ricardo Jorge, Lisbon, Portugal Cholesterol is a well known cardiovascular risk factor. Individuals with genetic disorders of lipid metabolism have an increased cardiovascular risk. Patients with Familial Hypercholesterolaemia (FH) have a 100 times greater risk of developing premature CHD than the population in general. OMS estimates that Portugal should have about cases of FH, but this disorder is severely under diagnosed in our country. It is essential that these patients are identified at a young age, so they can receive counseling and treatment according their condition. This is the main aim of Portuguese FH Study. The present study analyses the cardiovascular events, fatal and non fatal, on this population that could be avoided if these patients had been identified and treated at young age. Since 1999, a total of 302 index patients and 676 relatives have been received at our lab, from all over country, for the molecular study of FH. The molecular analysis identified 314 definite FH patients (index and relatives) which correspond to 1,6% of all cases estimated to exist in Portugal. Only 43% of the clinical diagnosed index patients had their diagnosis confirmed. About 16% (21/129) of the index cases and 9% (17/185) of the relatives genetically identified, already had a cardiovascular event (age index/years 45,31±12,89 and age relatives/years 44,23±11,04). In these 129 familes 45 premature deaths occurred (age/years 55,73±13,99). About 12% (21/175) of the index cases with clinical diagnosis of FH but in whom no mutation was found, also presented premature CHD (age/years 46,86±13,40) what seems to indicate that another gene defect, not yet known, must be the cause of such a severe phenotype. Clinical identification is possible but only the genetic diagnosis correctly identifies the pathway affected. This is important for disease prevention allowing for a more personalized counseling and treatment in order to decrease the elevated cardiovascular risk in these patients. Efforts must concentrate in the early identification of these patients so they can adopt a healthier life style and receive counseling and pharmacological treatment to prevent an early death, as already happen in so many families. These deaths could probably been avoided in these patients had been identified and treated at young age. Genetic identification allows the early diagnosis of this disorder, what is especially important for the prognosis of children and adolescents. The future must be centered in prevention and not in the treatment of the serious cardiovascular complications associated to this disorder. P2277 The correlation of the long pentraxin 3 (PTX3) to lipids in patients hospitalized with acute chest pain T. Brugger-Andersen 1,V.Ponitz 1,F.Kontny 2,H.Staines 3, H. Grundt 4,K.Miyamoto 5,C.Miyazawa 5, T. Matsuura 5, M. Sagara 5, D.W.T. Nilsen 1. 1 Department of Cardiology, Stavanger University Hospital, Stavanger, Norway; 2 Department of Cardiology, Volvat Medical Center, Oslo, Norway; 3 Sigma Statistical Services, Balmullo, United Kingdom; 4 Department of Medicine, Stavanger University Hospital, Stavanger, Norway; 5 Perseus Proteomics Inc., Tokyo, Japan Background: The long pentraxin 3 (PTX3) is a recently identified member of the pentraxin protein family that also includes C-reactive protein. PTX3 is produced by the major cell types involved in atherosclerotic lesions in response to inflammatory stimuli, and elevated plasma levels are found in the acute coronary syndromes (ACS). However, currently available clinical data on the relation of PTX3 to lipids in a population hospitalized with acute chest pain is sparse. The aim of this study was to assess these variables. Methods: PTX3 was measured with a new, high-sensitive ELISA method (PPMX, Tokyo, Japan) in EDTA plasma in admission samples from 795 patients. The patients were followed for 24 months for clinical outcome. A multiple regression model was fitted for the total population. Results: PTX3 was related to total cholesterol but not to high-density lipoprotein cholesterol or triglycerides for the total population (r= 0.213, p<0.001) (Table I). Table 1. The relationship between PTX3 and lipids for patients hospitalized with acute chest pain B (p-value) R Multiple regression Groups Total cholesterol HDL cholesterol Triglycerides model p-value All patients (n=795) (<0.001) 0.67 (0.304) (0.066) <0.001 HDL cholesterol, high-density lipoprotein cholesterol. Conclusion: In patients with acute chest pain PTX3 is correlated with total cholesterol. P2278 Cigarette smoking blocks the protective expression of Nrf2/ARE pathway in blood cells of young heavy smokers favouring inflammation: relation to endothelial function and carotid intima-media thickness C. Mozzini, A. Fratta Pasini, U. Garbin, A. Pasini, S. Manfro, C. Stranieri, L. Cominacini. University of Verona, Verona, Italy Purpose: Cigarette smoking constitutes a major risk factor for atherosclerotic

75 Other topics 375 vascular disease. Since cigarette smoking promotes oxidative stress and oxidative stress is an inductor of inflammation through activation of the redox-sensitive transcription factor NF-kB, as well as of the counteracting protective NF-E2- related factor 2 (Nrf2)/antioxidant related elements (ARE) pathway, this study was aimed to evaluate: 1) the balance between these two inducible elements in peripheral blood mononuclear cells (PBMC) derived from young healthy smokers and 2) the relationship with systemic indexes of oxidative stress, inflammation, endothelial function and carotid intima media thickness (IMT). Methods: 124 healthy volunteers (aged 26±4 years, 74/50 males/females) participated in the study. Smokers were described as individuals who smoked 5 10 (light smokers: LS) or (heavy smokers: HS) cigarettes per day for at least 3 years, whilst non-smokers (C) included those who had never smoked or those who had not smoked for at least 3 years. In PBMC were evaluated: NFkB activation (ELISA), Nrf2/ARE gene expression (Real time PCR and Western blotting), membrane oxidized phospholipid 1-palmitoyl-2-arachidonyl-sn-glycero- 3-phosphorylcholine (ox-papc), (HPLC/mass spectrometry) and GSH (HPLC). Morever high-sensitivity C reactive (hs-crp), carotid IMT and flow-mediated vasodilation (FMD) of the brachial artery in response to hyperemia were measured. Results: LS showed significantly higher expression of Nrf2/ARE genes than HS and C in PBMC(p<0.001). On the contrary nuclear NF-kB activation in PBMC was significantly higher in HS than in LS and C (p<0.001).activation of NF-kB positively correlated (p<0.001), while the expression of the Nrf2/ARE negatively correlated with the degree of oxidative stress, as evaluated by membrane ox- PAPC and GSH in PBMC. Hs-CRP was significantly higher in HS than in LS and C (p<0.001) and was directly correlated with NF-kB activation in PBMC (p<0.001). FMD resulted significantly impaired in HS and LS than in C (p<0.01). Moreover FMD was significantly impaired in HS than in LS (p<0.01). Similarly there was an increased carotid IMT in both HS and LS when compared with C (p<0.001), but carotid IMT was higher in HS than in LS (p<0.001). Conclusions: Excessive oxidative stress induced by cigarette smoking abolishes the protective antioxidant response of the Nrf2/ARE pathway in PBMC of healthy young HS, favouring the activation of NF-kB and the systemic inflammation. These findings are associated with an impairment of FMD and an increase of carotid IMT. P2279 Genetic variant rs C>T in the nicotinic acetylcholine receptor gene cluster on chromosome 15q24 significantly predicts smoking severity in coronary artery disease patients C.H. Saely 1, A. Muendlein 1, A. Vonbank 1,P.Rein 2,S.Beer 1, J. Breuss 1, B. Gaensbacher 1,H.Drexel 1. 1 VIVIT Institute, Feldkirch, Austria; 2 Private University in the Principality of Liechtenstein, Triesen, Liechtenstein Objectives: Smoking is a major cause of preventable premature death, mainly due to its strong and dose-dependent impact on coronary artery disease (CAD). Recently, genetic determinants of nicotine dependence (which correlates with the amount of smoked cigarettes rather than with the smoker status per se) have been suggested. No data are available for patients already affected by CAD. Methods: We genotyped variant rs C>T in the nicotinic acetylcholine receptor gene cluster on chromosome 15q24 in a large cohort of 1303 consecutive Caucasian patients with angiographically proven CAD. Results: From our patients, 62.1% had a history of smoking (n = 809; 226 current and 581 past smokers). Genotype distributions of variant rs were not significantly different between patients with a history of smoking and those who had never smoked (ptrend across genotypes = 0.471). However, the variant among smokers proved strongly predictive for the average amount of cigarettes smoked per day (24/d, 23/d, and 30/d for subjects with the AA, the AT, and the TT genotypes; p <0.001 for those with the TT genotype vs. carriers of the A allele). This association remained significant after adjustment for age and gender (F = 12.4; p <0.001). Conclusions: Genetic variant rs C>T in the nicotinic acetylcholine receptor gene cluster significantly predicts smoking severity in patients with angiographically proven CAD. P2280 Synergistic effect of smoking and early-stage pulmonary dysfunction on abnormal pressure wave reflection in men K. Shiina, H. Tomiyama, C. Matsumoto, M. Odaira, M. Yoshida, A. Yamashina. Tokyo Medical University, Tokyo, Japan Objective: This cross-sectional study was conducted to clarify whether pressure wave reflection, as assessed by the augmentation index (AI), might be increased in the presence of early-stage pulmonary dysfunction and, if so, whether smoking modifies this relationship. Methods: In 6112 clinically healthy Japanese subjects {i.e., forced expiratory volume at 1 second/forced vital capacity (FEV1.0/FVC) ratio >70%, with no known history of pulmonary disease or cardiovascular disease}, pulmonary function, the radial augmentation index (rai) and second peak of radial systolic pressure wave form (SBP2), a surrogate marker of central systolic pressure, were measured. Results: The FEV1.0/FVC ratio and smoking status were found to show significant correlation with the augmentation index (AI) as assessed by radial pressure wave analysis with significant interaction between the two {B (95% confidence interval = ( ), t-value = -2.01, p = 0.03} in the 3351 men (49±9 years old), but not the 2761 women (46±10 years old) in this study. In men, the adjusted values of radial AI, SBP2 and the prevalence rate of subjects with elevated plasma levels of CRP were significantly higher in current smokers with early-stage pulmonary dysfunction than in the other 3 categories (Figure). AI, SBP2 and CRP in four groups Conclusion: In men, early-stage pulmonary dysfunction and current smoking may synergistically increase micro-vascular dysfunction and the increase in CV risk related to pressure wave reflection, and inflammation may contribute, at least in part, to such synergistic effects. P2281 Smokers benefit more from early invasive treatment of acute myocardial infarction than non-smokers E. Aune 1, J. Hjelmesaeth 1, K. Endresen 2, J.E. Otterstad 1. 1 Vestfold Hospital Trust, Toensberg, Norway; 2 Rikshospitalet University Hospital, Oslo, Norway Purpose: The aim of this study was to investigate whether a previously shown survival benefit of early invasive treatment of acute myocardial infarction (AMI) may differ according to smoking status. Methods: Prospective observational cohort study on consecutive patients admitted for AMI in 2003 (conservative cohort) (n = 311) and 2006 (invasive cohort) (n = 307). Patients were subdivided into current smokers at admission, including those who stopped within the last 3 months, and non-smokers (including ex-smokers). Statistics: Cox proportional hazards regression analysis. Results: A total of 27% (invasive cohort) and 32% (conservative cohort) of the patients were categorized as current smokers, respectively. Current smokers had a 72% increased risk (HR 1.72, 95% CI , p = 0.021) for death after one year, adjusted for treatment cohort, age, gender, prior AMI, prior stroke, and diabetes. Smokers and non-smokers in the invasive cohort had a 70% and 30% lower one-year mortality compared with the conservative cohort, respectively (Kaplan-Meier plots are presented in the figure). Non-smokers were significantly older than smokers both in the conservative (median age 77 vs. 60 years, p<0.001) and invasive cohort (median age 79 vs. 58 years, p = 0.001). We found a significant interaction (p = 0.039) between treatment cohort and smoking status supporting a larger survival benefit in smokers. Survival according to smoking status Conclusions: The survival benefit following introduction of early invasive management of unselected AMI patients was higher among smokers than nonsmokers. P2282 Smoking cessation increases serum adiponectin levels in an apparently healthy greek population S. Efstathiou 1, I. Skeva 1,C.Dimas 2, A. Panagiotou 2,K.Parisi 2, L. Janoumis 1, A. Kafouri 1, K. Bakratsas 1, T. Mountokalakis 1. 1 Hygeias Melathron, Athens, Greece; 2 Athens University Hospital Attikon, Athens, Greece Purpose: Smoking has been associated with low serum levels of adiponectin, an adipocytokine with insulin-sensitizing, anti-inflammatory and anti-atherogenic properties. However, no data are available so far in regard to the short-term impact of smoking cessation on serum adiponectin concentration. The objective of this study was to assess the early effect on serum adiponectin levels of smoking cessation supported by bupropion, a well-established pharmaceutical aid.

76 376 Other topics Methods: Apparently healthy smokers of both sexes with no additional cardiovascular risk factors were administered 150 mg sustained-release bupropion twice daily for 9 weeks. Quitters constituted the active group and non-quitters the control group. Sandwich enzyme-linked immunosorbent assays were employed for the measurement of serum adiponectin and serum cotinine, the major proximate metabolite of nicotine, which is widely used as a biomarker of tobacco exposure. Participants self-reported abstinence was confirmed by a serum cotinine level below 15 ng/ml. Results: Among the 106 Greeks of Caucasian origin who completed the study (mean age 44.5±11.3 years, 57 females, body mass index [BMI] 26.7±4.9 kg/m 2, daily cigarettes 27.1±10.6, Fagestrom score 7.4±1.8, Brinkman index 512.2±98.4, basal adiponectin 7.2±1.5 μg/ml, basal cotinine 381.4±191.1 ng/ml), 45 (42.5%) had quitted smoking at week 9. Quitters did not differ from non-quitters in terms of baseline characteristics. Quitters post-cessation adiponectin levels were significantly increased (mean difference from baseline 1.9±0.8 μg/ml [95% CI 1.2, 2.3], p < 0.001), while non-quitters adiponectin concentration remained unaltered (mean difference from baseline 0.1±0.4 μg/ml [95% CI -0.2, 0.3], p = 0.164). Cotinine levels at week 9 were lower in quitters (3.8±3.4 ng/ml) as compared to non-quitters (211.2±96.5 ng/ml; p < 0.001). Weight gain was non-significant in quitters (1.7±1.0 kg [95% CI -1.6, 2.4], p = 0.511) as well as in non-quitters (1.5±1.2 kg [95% CI -1.9, 2.5], p = 0.598). A multiple regression model including female gender (standardized β coefficient = 0.480, p = 0.002), age (0.355, p = 0.003), BMI (-0.308, p = 0.005), waist circumference (-0.276, p = 0.008), smoking status (-0.255, p = 0.010), and cotinine levels (-0.233, p = 0.021) explained about two thirds of the variation in adiponectin levels (adjusted R 2 = 0.656). Conclusions: Serum adiponectin levels appear to increase considerably within two months after smoking cessation. This finding may provide further insight into the mechanisms related to the detrimental effects of smoking and the benefits of quitting. P2283 Passive smoking is associated with masked hypertension in clinically normotensive non-smokers: cross-sectional results in a smoke-filled environment C. Thomopoulos, D.P. Papadopoulos, S. Massias, E. Michalopoulou, A. Bratsas, O. Papazachou, T.H. Makris. Department of Cardiology, Elena Venizelou General & Maternity Hospital, Athens, Greece Purpose: Clinical and experimental data indicate that passive smoking exerts detrimental effects on vascular homeostasis; however, its association with blood pressure (BP) levels especially in the clinically non-hypertensive range is still lacking. We investigated ambulatory BP levels among clinically normotensive nonsmokers exposed (PS) and not exposed (SF) to passive smoking aiming to evaluate the relative prevalence of masked hypertension (MH). Methods: From 790 consecutive never treated subjects who were referred to an outpatient hypertensive clinic, we excluded active smokers, nonsmokers not exposed to workplace smoking and those having a mean clinic BP>140/90mmHg (mean BP of three separate measurements with elapsing time of one week). In the remaining population echocardiographic examination and metabolic profile assessment was performed while all the clinically normotensives eligible to participate (112 PS and 100 SF) underwent to ambulatory BP monitoring. In all participants haemodynamic reaction to standing was assessed, while by appropriate questionnaires salt intake, type of followed diet, coffee and alcohol consumption and physical activity were registered; lastly, in the PS group the daily and overtime exposure to passive smoking were entered in our analysis. Results: SF with respect to PS group resulted older by 3±5 years, followed a more hygienic diet and consumed less alcohol (p<0.05 for all). PS with respect to SF group demonstrated higher 24h systolic BP and clinic heart rate (125±4 vs. 122±5mmHg, p<0.001 and 79±4 vs. 73±4 beats/min, p=0.009, respectively), while the prevalence of MH was higher in the former group (n=18, 16%) with respect to the latter (n=8, 8%), p=0.02. In a logistic multivariable regression model (R 2 adjusted=0.28, p=0.001) determinants (adjusted odds ratio, 95% confidence interval) of MH were passive smoking (1.22, ), daily (1.34, ) and over-time (1.34, ) duration of smoke exposure, male gender (1.32, ), younger age (0.64, ), adverse lifestyle attitudes, mean clinic systolic/diastolic BP (1.17, /1.21, ) and both standing diastolic BP and heart rate (1.31, and 1.24, , respectively) (p<0.05 for all). Conclusions: MH is associated with passive smoking in clinically prehypertensive non-smokers and adverse lifestyle attitudes may represent potential accelerators of this phenomenon. This finding underscores the need for the amelioration of smoking status assessment in combination with other demographic and lifestyle markers along with the routine clinical BP evaluation. P2284 Smoking is related to subclinical inflammation and impairment of thrombosis/fibrinolysis system in essential hypertensive subjects: an insight into the tobacco-related vascular disease K. Dimitriadis, C. Tsioufis, A. Kasiakogias, A. Miliou, E. Andrikou, A. Mazaraki, C. Thomopoulos, D. Tsiachris, D. Tousoulis, C. Stefanadis. First Cardiology Clinic, University of Athens,Hippokration Hospital, Athens, Greece Purpose: Despite the fact that smoking has numerous effects that promote atherosclerosis, the data regarding its association with inflammatory processes and thrombosis/fibrinolysis system in the setting of untreated essential hypertension are rather scarce. In the present study we investigated the interrelationships between smoking, high-sensitivity C-reactive protein (hs-crp), fibrinogen and plasminogen-activator inhibitor type 1 (PAI-1) levels in essential hypertensive subjects. Methods: 295 newly diagnosed untreated non-diabetic patients with stage I to II essential hypertension [192 men, mean age=50 years, office blood pressure (BP)=148/95] were classified according to their smoking habits as current smokers ( 1 cigarette/day, n=127) and the remaining subjects as non-smokers (n=165). All subjects underwent ambulatory BP monitoring and venous blood sampling was performed for estimation of metabolic profile, hs-crp fibrinogen and PAI-1 concentrations. Results: Hypertensive current smokers compared to non-smokers had increased office diastolic BP (96±9 vs 94±7 mmhg, p<0.05) and 24-h diastolic BP (84.7±10 vs 80.8±9 mmhg, p=0.001), whereas did not differ regarding age, sex, body mass index (BMI), and left ventricular mass index (p=ns for all). Although groups exhibited no difference regarding metabolic profile (p=ns), smokers compared to non-smokers were characterized by higher levels of hs-crp (3.18±0.95 vs 2.29±0.48 mg/l, p<0.005), fibrinogen (316.2±62.6 vs 292.7±66.9 mg/dl, p=0.01) and PAI-1 (38.08±9.54 vs 25.5±23.9 ng/ml, p=0.002). In the entire population, hs-crp was associated with BMI (r=0.281, p<0.0001), pack-years index (r=0.184, p<0.005), 24-h systolic BP (r=0.144, p<0.05), and fibrinogen (r=0.138, p<0.05), whereas PAI-1 exhibited a positive correlation with pack-years index (r=0.248, p<0.005) and 24-h diastolic BP (r=0.220, p=0.006). Regarding fibrinogen, it was related to pack-years index (r=0.176, p<0.05) and daytime pulse pressure (r=0.185, p<0.005). Analysis of covariance revealed that hs-crp, fibrinogen and PAI-1 concentrations remained significantly different between the two groups after adjusting for confounding factors (p<0.05 for all). Conclusions: Smoking in essential hypertension is accompanied by increased inflammatory processes and impairment of thrombosis/fibrinolysis system, as reflected by hs-crp, fibrinogen and PAI-1 levels. These findings may partially elucidate the complex mechanisms linking smoking with increased cardiovascular risk, in this setting. P2285 Chewing tobacco produces coronary vasoconstriction S. Ramakrishnan, R. Thangjam, A. Roy, S. Singh, S. Seth, R. Narang, B. Bhargava. All India Institute of Medical Sciences (AIIMS), New Delhi, India Background: The acute hemodynamic and coronary vasomotor effects of chewing tobacco are not known. Methods: Ten patients who are habitual tobacco chewers (age yrs) undergoing elective coronary angiography and consenting to be part of the study were included. Patients with unstable angina or advanced coronary artery disease were excluded. The study was approved by the institutional ethics Committee. Following coronary angiography, a right heart study was performed through right femoral vein using 8F sheath. A 7F thermodilution Swan Ganz continuous cardiac output pulmonary artery catheter was used to measure the cardiac output continuously and right heart pressures were measured from the respective ports of the catheter. Having obtained the baseline hemodynamic data, 1g of tobacco was given orally to be chewed. Subsequently, the hemodynamic data were obtained periodically till a period of 60 minutes. A repeat left coronary injection was obtained 15 minutes after giving tobacco, in the RAO view for estimation of the diameter of left anterior descending artery by QCA. Results: Chewing tobacco leads to a significant acute increase in heart rate, systemic blood pressure and cardiac output (from 3.64±0.45 lit/min to 4.44±0.68 lit/min p 0.04) peaking at 15 min. There were no significant changes in the right atrial, pulmonary artery and wedge pressures and hence no change in the pulmonary vascular resistance. More importantly, chewing tobacco was associated with coronary vasoconstriction (proximal LAD diameter 3.42±0.52 mm to 2.71±0.48; p value 0.04). Conclusion: Chewing smokeless tobacco leads to coronary vasoconstriction and also produces significant hemodynamic alterations. P2286 Smoking is associated with subclinical inflammation, impairment of thrombosis/fibrinolysis system and increased osteoprotegerin levels in essential hypertensives K. Dimitriadis, C. Tsioufis, E. Andrikou, D. Syrseloudis, C. Thomopoulos, I. Andrikou, A. Mazaraki, V. Tzamou, I. Kallikazaros, C. Stefanadis. First Cardiology Clinic, University of Athens,Hippokration Hospital, Athens, Greece Purpose: Despite the fact that smoking has numerous effects that promote atherosclerosis, the data regarding its association with biological markers of risk in the setting of untreated essential hypertension are rather scarce. In the present study we investigated the interrelationships between smoking, high-sensitivity C- reactive protein (hs-crp), osteoprotegerin (OPG), fibrinogen and plasminogenactivator inhibitor type 1 (PAI-1) levels in essential hypertensives.

77 Other topics / Population trends 377 Methods: 245 newly diagnosed untreated non-diabetics with stage I to II essential hypertension [172 men, mean age=51 years, office blood pressure (BP)=148/95] were classified according to their smoking habits as current smokers 1 cigarette/day, n=115) and the remaining subjects as non-smokers (n=130). All subjects underwent ambulatory BP monitoring and venous blood sampling was performed for estimation of metabolic profile, hs-crp, OPG, fibrinogen and PAI-1 concentrations. Results: Hypertensive current smokers compared to non-smokers had increased office diastolic BP (97±8 vs93±7 mmhg, p<0.05) and 24-h diastolic BP (85±10 vs 80±8 mmhg, p=0.001), whereas did not differ regarding age, sex, body mass index and left ventricular mass index (p=ns). Although groups exhibited no difference regarding metabolic profile (p=ns), smokers compared to non-smokers were characterized by higher levels of hs-crp (3.25±1.1 vs 2.33±0.84 mg/l, p<0.005), OPG (5.8±0.7 vs 4±0.5 pmol/l, p<0.005), fibrinogen (318.5±56.6 vs 289.3±67.3 mg/dl, p=0.02) and PAI-1 (40.02±7.56 vs 24.5±22.7 ng/ml, p=0.004), independently of confounding factors. In the entire population, hs-crp was associated with pack-years index (r=0.175, p<0.05) and 24-h systolic BP (r=0.188, p<0.05), whereas PAI-1 exhibited a correlation with pack-years index (r=0.248, p<0.005) and 24-h diastolic BP (r=0.220, p=0.006). Regarding OPG, it was associated with age (r=0.228, p<0.05), waist to hip ratio (r=0.345, p<0.05), 24-h systolic BP (r=0.286, p<0.0001) and pack-years index (r=0.348, p<0.05), while fibrinogen was related to pack-years index (r=0.176, p<0.05) and daytime pulse pressure (r=0.185, p<0.005). Conclusions: Smoking in essential hypertension is accompanied by increased inflammatory processes, atherosclerosis progression and impairment of thrombosis/fibrinolysis system, as reflected by hs-crp, OPG, fibrinogen and PAI-1 levels. These findings may partially elucidate the complex mechanisms linking smoking with increased cardiovascular risk, in this setting. P2287 Aspirin use does not affect lipid efficacy of niacin extended-release treatment R. Thakkar 1,H.A.Punzi 2,M.H.Davidson 3,S.Krause 1, P. Jiang 1, C. Lovell 1, R.J. Padley 1. 1 Abbott, Abbott Park, United States of America; 2 Texas Woman s University, Dallas, United States of America; 3 University of Chicago, Chicago, United States of America Niacin is the most effective agent available for increasing high-density lipoprotein cholesterol (HDL-C), and has been shown to decrease low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels and improve cardiovascular outcomes. However, some patients have difficulty tolerating niacin because of flushing, the most common adverse event associated with niacin therapy. Aspirin (ASA) is commonly used to decrease flushing, but its impact on the lipidaltering effects of niacin is not well-defined. The effect of ASA on the lipid efficacy of niacin extended-release (NER, Niaspan, Abbott) was evaluated in patients from a double-blind, placebo-controlled trial. Dyslipidemic patients were randomized (1:1:1) to 1 of 3 treatment groups: NER and ASA (NER + ASA); NER and ASA placebo (NER + ASA PBO); NER placebo and ASA placebo. NER or NER placebo was titrated as follows: 500 mg week 1, 1000 mg week 2, and 2000 mg weeks 3-6. Patients took ASA or ASA placebo 325 mg 30 minutes prior to NER or NER placebo dosing. Lipid efficacy was similar for patients treated with or without ASA after 6 weeks (Table). % Change from baseline to final visit n NER +ASA n NER + ASA PBO p-value Total-C a (1.5) (1.5) HDL-C a (2.2) (2.2) Non-HDL-C a (2.0) (2.0) LDL-C a (2.3) (2.2) TG b [-51.7, -8.7] [-52.0, -4.0] Lp(a) b [-35.1, 0.0] [-36.3, 0.0] a ANCOVA analysis of percent change from baseline to final visit: LS Mean (SE). b Non-parametric analysis of percent change from baseline to final visit: Median [Q1, Q3]. Over the course of the study, mean maximum flushing intensity decreased more (59% during week 6; 33% overall; p<0.001) in the group receiving NER + ASA than the group receiving NER + ASA PBO. Overall the adverse event (AE) profile was not higher in the NER + ASA group vs the NER + ASA PBO group, particularly, gastrointestinal AEs were experienced by 8.8% vs 12.2% of patients, respectively. This study quantitatively demonstrates that aspirin, when taken to reduce the severity of niacin extended-release-induced flushing in patients with dyslipidemia, does not compromise the lipid efficacy of niacin extended-release. P2288 Prediction of cardiovascular events by MMP-9 in elderly men T.W. Weiss, E.B. Furenes, M. Troseid, S. Solheim, I. Seljeflot, H. Arnesen. Oslo University Hospital (Ulleval), Oslo, Norway Purpose: Matrix metalloproteinase-9 (MMP-9) is thought to play a crucial role in the progression of atherosclerosis. Experimental data suggests interactions between MMPs and lipid metabolism, triglyceride hydrolysation and adipocyte maturation. We investigated the importance of MMP-9, its inhibitor tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) and MMP-9/TIMP-1- ratio on cardiovascular events in elderly men at high risk for cardiovascular disease with respect to lipid levels. Methods: We prospectively studied 563 elderly men at high risk for cardiovascular disease. The variables were measured at inclusion and cardiovascular events were recorded over 3 years. MMP-9 levels were grouped by quartiles and related to cardiovascular event rate. Results: Cardiovascular events were recorded in 68 individuals. Higher circulating levels of MMP-9 (p = 0.046) but not triglycerides, total cholesterol, HDL, LDL or oxidised LDL were associated with cardiovascular events. Univariate regression revealed a significant association between higher MMP-9 levels (>75th percentile; 543 ng/ml) and cardiovascular events (OR 1.93; CI ; p = 0.016). When calculated in a multivariate model, the significance was lost (adjusted OR 1.59; CI ; p = 0.108). Analysing MMP-9 together with plasma lipid levels, it appeared that elevated MMP-9 levels are stronger predictors of cardiovascular events (OR 3.69; CI ; p=0.001) in individuals with hypertriglyceridaemia (>1.7 mmol/l). In a multivariate regression model, the prediction of cardiovascular events by MMP-9 was still significant in patients with hypertriglyceridaemia (adjusted OR 3.17; CI ; p = 0.009). Conclusions: MMP-9 is associated with cardiovascular events in elderly men. In the presence of hypertriglyceridaemia, elevated MMP-9 levels (>543 ng/ml) are a strong predictor of cardiovascular events. Even though not suitable as an independent marker for atherosclerosis, taking into account hypertriglyceridaemia, MMP-9 could be a useful tool to identify elderly men at particular high risk for cardiovascular events. POPULATION TRENDS P2289 Economic status and cardiovascular risk factors in rapidly developing country: Comparison between 1998 and 2005 in South Korea S.J. Ahn 1, S.Y. Jang 2,J.I.Park 3,S.Y.Park 1,S.J.Park 1,J.H.Cho 1, J.O. Jeong 1,Y.K.Kim 1,S.Y.Kim 1,Y.J.Kim 1. 1 National Police Hospital, Seoul, Korea, Republic of; 2 Seoul National University, Seoul, Korea, Republic of; 3 Seoul Veterans Hospital, Seoul, Korea, Republic of Purpose: South Korea is rapidly developing country which Gross National Income (GNI) pre capita in 1998 and 2005 were each 7,355 and 16,413 US dollars. This study examines the association between economic status and risk factors of CV disease in rapidly developing country, South Korea, and their changes according to economic growth. Methods: We analyzed data from the 1998 and 2005 Korea National Health and Nutrition Examination Survey (KNHANES). Total 7,353 and 5,192 persons of each KNHANES, who were 25 years and over and took health examination, were included. Risk factors included hypertension (HT), diabetes mellitus (DM), obesity, total cholesterol (TC), smoking and regular exercise (RE). Economic status was divided into quartiles, as equivalent income which is household income divided by the number of family in the same house. We compared odds ratios of CV risk factors in both 1998 and 2005 according to economic status. Results: 1) Using 1998 KNHANES data, for men, compared with the highest income quartile, those in the bottom quartile had odds ratios of 1.06 ( ) for HT, 1.32 ( ) for DM, 1.42 ( ) for smoking, 1.14 ( ) for TC, 0.61 ( ) for RE, 0.58 ( ) for obesity. 2) Using 2005 data, for men, those in the bottom quartile had odds ratios of 1.38 ( ) for HT, 0.61 ( ) for DM, 1.55 ( ) for smoking, 0.90 ( ) for TC, 0.49 ( ) for RE, 0.87 ( ) for obesity. 3) Using 1998 data, for women, those in bottom quartile had odds ratios of 1.12 ( ) for HT, 0.82 ( ) for DM, 2.13 ( ) for smoking, 1.00 ( ) for TC, 0.45 ( ) for RE, 0.96 ( ) for obesity, as compared with highest income quartile. 4) Using 2005 data, for women, those in bottom quartile had odds ratios of 1.35 ( ) for HT, 1.06 ( ) for DM, 2.55 ( ) for smoking, 0.90 ( ) for TC, 0.42 ( ) for RE, 1.53 ( ) for obesity. Conclusions: According to the increase of GNI per capita, more than double, some of the CV risk factors were changed in their inequalities. For men, inequality of HT and DM became clear but that of obesity was blunted with economic growth. RE and smoking shows more vivid changes of odds ratios. There were no significant inequalities in TC even no changes with economic growth. For women, Inequality of obesity became clear and smoking showed slightly increase of odds ratios. Inequality of RE continued according to increase of GNI per capita. There were no significant inequalities in HT, DM and TC. Further studies of the change of CV risk factors as larger economic growth are needed. P2290 The time course of risk of death following acute myocardial infarction and diabetes M.L. Norgaard 1, S.S. Andersen 1,T.K.Schramm 2, G.H. Gislason 2, F. Folke 1, M.L. Hansen 1,D.M.Bretler 1, L. Koeber 2,C.Torp- Pedersen 1. 1 Gentofte Hospital, Hellerup, Denmark; 2 Rigshospitalet (The Heart Centre), Copenhagen, Denmark Purpose: To examine long-term trends in risk of death in individuals with incident diabetes or incident myocardial infarction (MI) in a nationwide cohort of the Danish population (3.2 million individuals).

78 378 Population trends Methods: All residents in Denmark 30 years of age were followed for up to 10 years (1997 to 2006) by individual-level linkage of nationwide administrative registers. Patients either hospitalized with first-time myocardial infarction (MI) or patients with incident diabetes claiming a first prescription of a glucose lowering medication (GLM) were identified. Multivariable Cox proportional hazards model adjusted for age and gender was employed to analyse the risk of death over time in patients with diabetes compared with patients with a MI using the background population as a reference. Results: The total population included 3.2 million individuals. In the ten year period, patients were diagnosed with incident MI and were identified with incident diabetes. Patients with a MI had a particular high risk of death in the initial period. However over time the risk in MI patients declined and was surpassed by a higher risk in patients with diabetes after 5 years (Figure 1). P2292 Trends in cardiovascular risk factors in switzerland, : data from the national health surveys P. Marques-Vidal 1, A. Chiolero 2, F. Paccaud 1. 1 Centre Hopitalier Universitaire Vaudois, Lausanne, Switzerland; 2 McGill University, Québec, Canada Objective: to assess the prevalence and trends of the main cardiovascular risk factors (CVRF) in the adult population of Switzerland. Methods: data from the national health interview surveys conducted in 1992, 1997, 2002 and 2007 (28,692 men and 35,090 women overall) were used. Selfreported data on height, weight, smoking, high blood pressure, high cholesterol, diabetes, antihypertensive and hypolipidaemic drug treatment were used. Results: smoking decreased whereas the prevalence of the other CVRF increased during the study period (table, all trends p<0.001). The amount of cigarettes smoked per day decreased from 18±12 (mean±sd) in 1992 to 14±11 in 2007 in men, and from 14±10 to 11±9 in women (p<0.001). In subjects with high cholesterol, hypolipidaemic treatment increased from 18% in 1997 to 40% in 2007 (p<0.001), while in hypertensive subjects antihypertensive treatment increased from 52% to 64% (p<0.001). -: not available. Trends in CVD risk factors Figure 1 Conclusions: Acute myocardial infarction being an acute illness has a high shorttime risk of death, whereas diabetes being a chronic disease has a high long-term risk, exceeding that of MI after 5 years. P2291 Control of dyslipidemia in western switzerland: a long way to go P. Marques-Vidal 1, M. Firmann 1,F.Paccaud 1, V. Mooser 2, N. Rodondi 3, G. Waeber 1, P. Vollenweider 1. 1 Centre Hopitalier Universitaire Vaudois, Lausanne, Switzerland; 2 GlaxoSmithKline, Philadelphia, United States of America; 3 Polyclinique Médicale Universitaire (PMU), Lausanne, Switzerland Objective: assess the prevalence, treatment and control levels of dyslipidaemia in Lausanne, Switzerland. Methods: population based study of 3,238 women and 2,846 men aged Dyslipidaemia prevalence, treatment and control were defined according to PROCAM guidelines adapted to Switzerland. Results: 35% of the sample had dyslipidaemia, of which 33% were treated, and 57% of those treated were adequately controlled (23% near control ), see table. Among 710 subjects with personal history of CVD or diabetes, 89% had dyslipidaemia, of which 44% and 21% were treated and adequately controlled, respectively (11% near control ). On multivariate analysis, treatment was positively related with age, body mass index (p for trend <0.001), alcohol consumption (p for trend <0.05), family history of MI (OR=1.47, ) and personal history of hypertension (OR=2.38, ), CVD or diabetes (OR=3.93, ), and negatively related with female gender (OR=0.70, ) and educational level (p for trend <0.05). Adequate control of lipid levels was negatively related with body mass index and alcohol drinking (p for trend <0.05). Dyslipidaemia Treated Control among treated Poor control Near control In control All subjects (n=6,084) 2,111 (34.7) 692 (32.8) 137 (19.8) 161 (23.3) 394 (56.9) Gender Men (n=2,846) 1,129 (39.7) 401 (35.5) 81 (20.2) 89 (22.2) 231 (57.6) Women (n=3,238) 982 (30.3) 291 (29.6) 56 (19.3) 72 (24.7) 163 (56.0) Test 58.35*** 8.25** 0.62 NS Risk category (adapted PROCAM) High (n=1,109) 1,029 (92.8) 322 (31.3) 110 (34.2) 78 (24.2) 134 (41.6) Intermediate (n=806) 680 (84.4) 122 (17.9) 20 (16.4) 50 (41.0) 52 (42.6) Low (n=699) 244 (19.4) 157 (64.3) 7 (4.5) 24 (15.3) 126 (80.2) Very low (n=3,470) 158 (5.4) 91 (57.6) 0 (0.0) 9 (9.9) 82 (90.1) Test 3920*** 51.41*** *** Results are expressed as number of subjects and (percentage). Statistical analysis by chi-square: NS, not significant; **p<0.01; ***p< Conclusion: circa one third of the population presents with dyslipidaemia, one third of dyslipidaemic subjects is treated and one half of treated subjects is adequately controlled. Implementation of guidelines is urgently needed Men 6,575 5,537 8,563 8,017 Current smoking (%) Hypertension (%) High cholesterol (%) Obesity (%) Diabetes (%) Women 7,946 6,937 10,343 9,862 Current smoking (%) Hypertension (%) High cholesterol (%) Obesity (%) Diabetes (%) Results are expressed in percentages. Conclusion: the decrease in smoking is encouraging; the increase in hypertension and high cholesterol might reflect more frequent screening and lower threshold for treatment. The increase of obesity and diabetes is of concern. P2293 Change in medical treatment of European patients included in the REACH registry: comparison between the disease territories C. Suarez 1,U.Zeymer 2, T. Limbourg 2, J. Rother 3, P.G. Steg 4, D.L. Bhatt 5 on behalf of REACH Registry investigators. 1 Hospital Universitario de la Princesa, Madrid, Spain; 2 Institut fuer Herzinfarktforschung Ludwigshafen, Ludwigshafen am Rhein, Germany; 3 Johannes Wesling Klinikum Minden, Minden, Germany; 4 Bichat-Claude Bernard Hospital (AP-HP), Paris, France; 5 Brigham and Women s Hospital, Boston, United States of America Purpose: The REACH Registry is an international prospective registry of outpatients with multiple risk factors for atherothrombotic events or with symptomatic atherothrombosis, with 67,888 patients enrolled in 44 countries worldwide. Baseline REACH data showed a substantial gap between guideline recommendations and clinical practice. Methods: We compared medication (antithrombotic agents, lipid lowering agents [LLA], antihypertensive agents [AHA] and antidiabetic agents [ADA]) use at baseline and at 2-year follow-up in European REACH patients, using McNemar s test. Disease territory groups were compared using the chi-squared test. Results: Of patients enrolled in the REACH Registry in Europe, completed the 2-year follow-up suffered single arterial disease (CAD, 65.1%; CVD, 23.9% & PAD, 10.9%). The use of all medications increased, except for 1 AHA in hypertensives, ADAs in diabetics, other antiplatelet agents in CAD, and ACE-I/ARBs in CVD patients. At both baseline and at two years, there were differences between territories in the use of each medication (all P<0.0001, except 1 ADA [P<0.01]). Medication use in REACH Patients: Europe CAD alone (n, 9308) CVD alone (n, 3421) PAD alone (n, 1561) Baseline (%) 24m (%) Baseline (%) 24m (%) Baseline (%) 24m (%) ASA Other antiplatelet agents * Oral anticoagulants antithrombotic agents * Statins Other LLA * 1 LLA ACE/I ARBs (%) Hypertensive patients with 1 AHA (%) Hypertensive patients with 3 AHA (%) Diabetic patients with 1 ADA (%) * *P<0.05, P<0.01, P<0.001, P<0.0001; Baseline vs 24 months.

79 Population trends 379 Conclusions: The improvement in medical treatment of single arterial disease was greatest in PAD patients. However, secondary prevention therapy is still suboptimal, particularly for PAD. This improvement may be due to increasing adherence to guidelines, but an educational effect of REACH is also likely. Conclusions: The occurence of CAD in PHC users in Portugal is strongly associated with cardiovascular risk factors, namely with HT, DM and obesity. Moreover, even after correction for all variables under analysis, MS remained a significant risk factor for CAD. P2294 Ireland Improved survival of incident dialysis patients with coronary disease in the United States: A.N. Nealon 1, I. Yousif 1, C.A.M. Wall 2, A.G. Stack 1. 1 Regional Kidney Centre, Letterkenny General Hospital, Letterkenny, Ireland; 2 Meath and Adelaide Hospitals, Trinity College Dublin, Dublin, Purpose: Coronary Disease (CAD) is a major risk factor for death in dialysis patients. Whether improved end-stage kidney disease care (ESKD) has impacted on annual mortality rates from coronary disease in successive cohorts is unclear. Methods: We hypothesized that improved ESKD care has led to improved coronary management and reduced mortality for patients with known coronary disease at dialysis onset. Data on all new ESKD patients between were obtained from the US Renal Data System and linked with all-cause mortality. Patients (N=1,003,305) were followed until 4/10/2006. Annual Mortality was calculated for those with and without coronary disease by year of incidence from Cox regression was used to estimate 1-year and 2-year mortality hazard (RR) ratios for each calendar year (with 2000 as referent) in sequentially adjusted models. The final multivariable model was adjusted for demographic, socioeconomic, comorbid and laboratory markers (n=21). Analysis were conducted using SAS V Conclusions: Although coronary disease remains a common diagnosis at dialysis initiation, mortality rates in these patients have declined from Improved survival in successive cohorts suggests improved coronary disease management in this high-risk population. P2295 Prevalence and risk factors for coronary artery disease in the primary health care. Insights of the VALSIM study M.M. Fiuza 1,N.Cortez-Dias 1,S.Martins 1,A.Belo 2. 1 Hospital Santa Maria, Lisbon, Portugal; 2 Portuguese Society of Cardiology, Lisbon, Portugal Purpose: To determine the prevalence of coronary artery disease (CAD) and to identify its association with gender, age, body mass index (BMI), waist circumference (WC), metabolic syndrome (MS), hypertension (HT) and diabetes mellitus (DM) in Primary Health Care (PHC) users in Portugal. Methods: Cross-sectional study performed in PHC setting, involving 721 general practitioners (GP) representative of all regions of Portugal. The first two adult patients scheduled for an appointment on a given day were invited to participate, irrespective of the reason for consultation. The inclusion criterion was the existence of laboratory results for HDL cholesterol, triglycerides and fasting glucose performed up to one year prior to the consultation. A questionnaire on sociodemographic, clinical and laboratory data was completed by the GP. WC and BMI were measured and two blood pressure (BP) measurements were obtained after a 5-minute seated rest. CAD was defined by angina pectoris or previous myocardial infarction; DM by fast glycaemia 126mg/dL or antidiabetic agents; HT by previous diagnosis or BP 140/90mmHg; and MS by NCEP-ATP III criteria. Logistic regression multivariate analysis was used to assess the association of age, BMI, WC, MS, HT and DM with the occurrence of CAD. Results: The study included 16,856 individuals (58.1±15.1 years; 61.6% women). The prevalence of CAD adjusted for gender and age was 5.1%, higher in men (M: 5.8%; W: 4.6%) and increased with age. The variable with the strongest link to CAD was age, being 76 times more frequent in individuals aged 80 years than in those aged years. Although the prevalence of CAD was 71% higher in men (OR: 1.71; 95%CI ), male gender ceased to be an independent risk factor when WC, HT and DM were introduced into the model. After correction for these variables, CAD prevalence was higher in women (OR: 1.40; 95%CI ), 2.5 times higher in those with HT, 42% higher in those with DM. Risk for CAD increased with BMI, reaching statistical significance for severe obesity (OR: 2.5; 95%CI ). Even after correction for all variables under analysis, MS remained a significant factor (OR:1.16; 95%CI ), but not WC. Based on the variables analysed in the model predicting occurrence of CAD, the area under the ROC curve was 0.76 (95%CI ; p<0.001). P2296 Young adults positively changed their cardiovascular risk over 16 years - a prospective registry with good news P.J. Sousa 1, M. Miranda 2, B. Monteiro 1, J. Ferreira 3, M. Mendes 3, J.C. Monge 1, H. Nunes 1, J. Varandas 1. 1 Centro de Medicina Aeronautica - FAP, Lisbon, Portugal; 2 Hospital de Curry Cabral, Lisbon, Portugal; 3 Hospital de Santa Cruz - CHLO, Lisbon, Portugal Purpose: Cardiovascular (CV) disease is the leading cause of death worldwide. Abnormalities in blood pressure (BP), lipid profile, smoking habits and body mass index (BMI) can lead to atherosclerosis manifestations more than 30 years later. The purpose of this registry is to study the changes of CV risk in similar samples of healthy young adults over a period of 16 years. Methods: Prospective registry of applicants to military careers in 1991/2 (G1), 1996/7 (G2), 2001/2 (G3) and 2006/7 (G4). Temporal evolution of CV risk factors and CV risk at 65 years (calculated using the Heart Score and Framingham Score) were assessed. Results: The registry included 923 applicants, 94% male gender, with mean age of 19.2±2.3 years and BMI 22.4±2.5. G2 was slightly older (19.8±3.0;p=0.04,IC:0.95) and no differences were found on BMI and percentage of male gender. Excepting mean BP, which raised over the registry period (p<0.05,ic:0.05: G1 vs others), there was an improvement in CV risk: Lower total cholesterol (p<0.05,ic:0.05: G4 vs others) and LDL cholesterol with elevation of HDL cholesterol (p<0.05,ic:0.05: G1 vs G2 and G2 vs G4) Lower fasting glucose from G1 to G3 with a slight increase thereafter (p<0.05,ic:0.05: G1 vs others and consecutive groups) Lower ratio of smokers (p<0.05,ic:0.05: G4 vs others). Risk scores raised initially (p<0.05,ic:0.05: G1 vs G3 in Heart Score) and decreased afterwards (p<0.05,ic:0.05: G2 vs G3 and G3 vs G4 in Framingham Score). Temporal evolution of CV risk factors 1991/2 1996/7 2001/2 2006/07 All population (n=190) (n=133) (n=258) (n=342) (N=923) SBP (mmhg) 122.3± ± ± ± ±11.7 Total Cholesterol (mg/dl) 169.5± ± ± ± ±30.9 LDL (mg/dl) 116.1± ± ± ± ±29.2 HDL (mg/dl) 46.1± ± ± ± ±10.5 Fast Glucose (mg/dl) 87.2± ± ± ± ±7.8 Smokers (%) Heart Score 3.0± ± ± ± ±1.4 Framingham Score 12.9± ± ± ± ±5.1 Mean ± Standard Deviation. Conclusions: In these 16 years, there was an improvement in global CV risk and individual CV risk factors, except for BP levels, which suffered an increase and demands specific measures. Global CV risk remains important, justifying new control strategies. P2297 Cardiovascular profile of years old adolescents T.M.R. Rocha, E. Paixao, A.C. Alves, V. Francisco, A.M. Medeiros, T. Santos, S. Silva, M. Bourbon. Instituto Nacional de Saude Dr Ricardo Jorge, Lisbon, Portugal Health promotion and cardiovascular disease (CVD) prevention should start in childhood and not only in adult age. It is difficult to motivate young people to have healthy life styles and that depends partially on their risk perception. The aim of this study was to evaluate the cardiovascular risk profile of high school students More than 800 adolescents have been studied to determine the prevalence of cardiovascular risk factors in this population. Until now the results from 542 students, age 16,2±0.9 yrs (52% male), from 6 different schools in the Lisbon area have been analyzed. Decimal balance/metric scale, digital sphygmomanometer and auto-analyzers for fasting biochemical determination were used to Abstract P2294 Table 1. Mortality Trends by Calendar Year Year Coronary disease prevalence (%) Annual mortality (%) With coronary disease (%) Without coronary disease (%) Year Relative Risk Death Unadjusted 0.91** 0.95** (ref) ** 0.92** Adjusted all factors ** 1.04* (ref) *** 0.90*** 2-Year Relative Risk Death Unadjusted 0.95** (ref) *** 0.92*** Adjusted all factors ** 1.07** 1.05** 1.04* 1.00 (ref) *** 0.89*** ***P<0.0001, **P<0.001, *P<0.01. Ref = referent group year.

80 380 Population trends determine/measure: age, sex, smoking habits, diabetes, BMI, blood pressure, cholesterol, triglycerides, and blood glucose. Absolute risk and relative risk were calculated by the Score System. Statistic analysis tested differences using Pearson Chi-Square and Fisher s Exact Test. According to the European Cardiology Society and NCTP consensual cut-offs for the ages in question, the results obtained were as follows: 29,5% with hypercholesterolaemia (>75 percentile (170mg/dl), being 8,7% >95 percentile (190mg/dl)), 14,5% overweight/obese (BMI>25), 13% smokers, 12% with potential hypertension (>95 percentile but 30% had >90 percentile or >120/80), 12% with blood glucose above 100 mg/dl and 10% with hypertryceridaemia (>95 percentile (150 mg/dl)). Gender differences are significant (p<0.001) for triglycerides and cholesterol, higher in girls; BMI and blood pressure higher in boys. About 33% presented 1 risk factor, 10% had 2 and 3% presented 3 cardiovascular risk factors. Absolute risk did not exceed 1%. Projecting risk estimation for age 60, did not reach 5%, nevertheless levels of 2%, 3% and 4% were estimated, respectively in 34%, 5% and 1% of participants. Relative risk of 2, 3 and 4 was calculated on 25%, 3% and 0.2%. In boys, risk was significantly higher (p<0.001) in either assessment. The prevalence of characteristics associated to CVD risk in young students is high, predominantly in males: Since relative risk is higher it should be a better option in the attempt to motivate behavior changes. It is essential that health promotion namely cardiovascular prevention, start in childhood to prevent that our adolescents reach adult age already with an increased cardiovascular risk. The adoption of healthy life styles and the early detection of adolescents at risk should be the priority of heath policies. These measures will hopefully decrease the mortality rates in adult age. P2298 Trends in Q-wave myocardial infarction case-fatality from 1978 to 2006 C. Sala 1,M.Grau 2, J. Vila 2,R.Masia 3, J. Aboal 3, A. Sureda 3, J. Marrugat 2,J.Sala 3,R.Elosua 2 on behalf of REGICOR Study. 1 ABS Manresa IV, Manresa, Spain; 2 Institut Municipal d Investigació Mèdica, Barcelona, Spain; 3 Hospital Universitari Josep Trueta, Girona, Spain Purpose: To analyze the trends in first Q-wave myocardial infarction (MI) casefatality from 1978 to 2006 and determine the variables related to these changes. Methods: Population-based hospital registry including patients with first Q-wave MI aged 25 to 74 years admitted between 1978 and Sociodemographic and clinical characteristics (medical history, severity variables) along with treatments used during hospital stay were recorded. Thirty-day case-fatality was also collected. Seven 4-year periods were analyzed. We used logistic regression for the multivariate analysis. Results: The study included 3845 patients. In the 29-year period, 30-day casefatality was 9.8% and showed a decreasing trend over time (p for trend<0.001). Age, sex (women), diabetes, hypertension, anterior MI, and KillipIII-IVwere associated with higher case-fatality, whereas smoking, reperfusion, beta-blockers and aspirin use were associated with lower case-fatality. The adjusted associations between the defined periods and case-fatality are shown in the table. Table 1. Crude case-fatality and multivariate adjusted ORs of case-fatality for different periods Crude case-fatality Model 1 Model 2 Model 3 (%) OR (95% CI) OR (95% CI) OR (95% CI) ( ) 0.9 ( ) 0.9 ( ) ( ) 0.5 ( ) 0.7 ( ) ( ) 0.4 ( ) 1.1 ( ) ( ) 0.3 ( ) 1.1 ( ) ( ) 0.2 ( ) 0.8 ( ) ( ) 0.1 ( ) 0.7 ( ) Conclusion: A dramatic decrease in 30-day case-fatality occurred over this 29- year period, and was mainly related to the use of aspirin and beta-blockers. P2299 Increased risk of acute myocardial infarction in patients with epilepsy: a nationwide study J.B. Olesen 1, P.R. Hansen 1, G.H. Gislason 2, C. Torp-Pedersen 1, P. Weeke 1,D.M.Bretler 1, C.H. Jorgensen 1,S.Z.Abildstrom 3. 1 Department of Cardiology, University Hospital Gentofte, Copenhagen, Denmark; 2 Department of Cardiology, University Hospital Rigshospitalet, Copenhagen, Denmark; 3 Cardiovascular Research Unit, Department of Internal Medicine, University Hospital Glostrup, Copenhagen, Denmark Purpose: Patients with epilepsy have increased risk of acute myocardial infarction (AMI), but it is unclear whether this is related to a common pathophysiological substrate, i.e., atherothrombotic disease. We investigated this association in a nationwide study. Methods: A cohort consisting of the total Danish population 10 year on January 1, 1997 was examined by individual-level linkage of nationwide registries. Patients with epilepsy were identified by code at discharge. The risk of AMI associated with epilepsy was estimated by Cox proportional-hazard analysis, adjusted for sex, age, prior AMI or cerebrovascular disease, concomitant medication, socioeconomic status, and comorbidity. Results: We included 4,614,807 individuals in the cohort, of which 54,693 (1.2%) had epilepsy. Previous cerebrovascular disease was identified in 85,073 (1.8%) patients, from these 6091 (7.2%) had epilepsy. Their mean age was 44.2 years (standard deviation: 19.9) and 49.1% were men. During the 10 year follow-up period ( ), 175,984 (3.8%) subjects experienced an AMI. The Cox regression analyses were stratified for cerebrovascular disease because of a significant interaction with epilepsy. In patients with cerebrovascular disease, we observed no association between epilepsy and AMI (hazard ratio [HR] 0.98; 95% confidence interval [CI] ). In patients without cerebrovascular disease, epilepsy was associated with increased risk of AMI (HR 1.20; CI ). Conclusions: Epilepsy is associated with increased risk of AMI in patients without previous cerebrovascular disease. The results indicate an association between epilepsy and AMI independent of a shared atherothrombotic etiology. Further investigations of cardiac risk factors among patients with epilepsy are warranted. P2300 Trends in management and outcome of acute myocardial infarction in Portugal, Switzerland and the United States P. Marques-Vidal 1, N. Rodondi 2,C.MatiasDias 3,F.Paccaud 1. 1 Centre Hopitalier Universitaire Vaudois, Lausanne, Switzerland; 2 Polyclinique Médicale Universitaire (PMU), Lausanne, Switzerland; 3 National Institute of Health (INSA), Lisbon, Portugal Background: little information exists whether trends in thrombolysis, coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) are similar between countries. This study assessed trends in thrombolysis, CABG, PCI and outcome of acute myocardial infarction (AMI) in Portugal, Switzerland and the US. Methods: trends in coronary interventions and 7-day in-hospital mortality rates were assessed for each country by analysis of national hospital discharge data between 1998 and 2003 (67,489 patients in Portugal, 62,067 in Switzerland and 5,680,241 in the US). Results: the number of subjects admitted with AMI increased by 4% in the US, 40% in Portugal and 50% in Switzerland. In all countries, mean age at admission increased for both genders. Average length of stay decreased in Portugal and Switzerland, whereas no clinically significant decrease was found in the US. PCI increased in Portugal (9.5% to 21.7%), Switzerland (8.9% to 26.8%) and the US (20.5% to 24.7%). Thrombolysis increased in Portugal (1.5% to 10.3%) but less in Switzerland (0.5% to 3.9%) or the US (1.9% to 2.1%). CABG decreased significantly in the US (9.6% to 6.7%), with a nonsignificant decrease in Portugal (2.1% to 1.6%) or Switzerland (4.5% to 2.9%). Unadjusted seven-day in-hospital mortality rates decreased in Portugal (12.9% to 11.5%) and the US (11.1% to 10.3%), but increased in Switzerland (7.6% to 9.8%). Conclusions: the number of subjects with AMI increased considerably in Portugal and Switzerland. Management and outcome of patients with AMI also changed substantially between 1998 and P2301 Efficacy evaluation of the national program of arterial hypertension monitoring A.D. Deev, S.A. Shalnova, V.V. Konstantinov on behalf of study participants. State Research Center for Preventive Medicine, Moscow, Russian Federation Objectives: The National Program of Arterial Hypertension (AH) Monitoring in Russia was established in It is research-practical program based of stratified random sample of households on the territorial plot of existing health care system. The Program design consists in 3 cross-sectional independent screenings in participating Region (42 Regions of RF are participating) in 4-5 year interval with mortality follow up of subjects from the 1st screening. To the end of 2008 two Regions performed 2 screenings and additional 4 all 3 screenings which were recognized as representative. Efficacy variables for those 6 Regions are presented. Methods: Efficacy variables are: hypertension prevalence (HP), awareness of hypertension (AWH), treatment of AH (TH) and treatment efficacy (TE) together with usage of AH drug classes (ACE inhibitors, beta-blockers (BB), Ca-antagonists (CAA), diuretics (DIU), still rare used drugs (angiotensin receptor antagonists and alpha-blockers) and other antihypertensive drugs (OAHD)). All data are ageadjusted with direct standardization (euro-standard). Results: Data on subjects were analyzed ( on the 1st screening, on the 2nd, 6858 on the 3rd). HP did not changed in women to the 3rd screening (46.3±0.5 vs. 46.7±0.6) and slightly decreased in men (41.7±0.9 vs. 39,7±1.1, p<0.08). At the same time AWH was increased in both sexes: (71.9±1.6 vs. 86.1±1.6, p< in men and 73.7±1.5 vs. 88.2±1.6, p< in women). TH was also increased (58.1±1.5 vs. 71.2±2.2, p< in men and 71.1±1.5 vs. 80.5±1.9, p< in women) together with TE (18.7±1.9 vs. 27.0±2.8, p<0.01 in men and 26.1±1.9 vs. 35.2±2.5, p<0.01 in women). This probably occurs due to increased ACE inhibitors prescription (intake) on 26.0%, DIU on 19.4%, still rare used new drugs on 29.0% and BB - on 27.2% in men (no trend in women) while OAHD prescription decreased 30.1%. For TH women the number of prescribed drugs were decreased (1.90±.03 vs. 1.77±.05,p<0.01). Additionally among hypertensives systolic BP mean dropped

81 Population trends / Coronary surgery Valvular heart disease mm Hg(p<0.0001), diastolic BP 2.5 mm Hg (p<0.0001), total cholesterol level 0,6 mmol/l (p<0.0001), stroke prevalence 4,3 percent (p<0.0001), retinopathy 3,4 percent (p<0.0001), kidney diseases 5.5 percent (p<0.0001). At the same time CHD prevalence among hypertensives increased 3.0 percent (p<0.01), diabetes mellitus percent (p<0.01) while left ventricular hypertrophy and creatinemia prevalence did not changed significantly. Conclusion: the data demonstrated slow but steady improvement in situation with AH for Regions which are participating in the Program successfully. P2302 Russian multicentral epidemiological survey: morbidity, mortality, quality of diagnostics and management of acute CHD (RESONANCE) S.A. Boytsov 1, N.N. Nikulina 2, S.S. Yakushin 2,R.A.Liferov 3, G.I. Furmenko 4, S.A. Akinina 5 on behalf of RESONANCE study group. 1 Russian Cardiology Research-and-Production Complex, Moscow, Russian Federation; 2 Academician I.P.Pavlov Ryazan State Medical University, Ryazan, Russian Federation; 3 Ryazan Regional Clinical Cardiology Center, Ryazan, Russian Federation; 4 Voronezh State Medical Academy, Voronezh, Russian Federation; 5 Region Clinical Hospital, Khanty-Mansiysk, Russian Federation Purpose: Acute coronary heart disease (CHD) represents the most common cause of morbidity and mortality in the world. Relative epidemiologic data for Russia are sparse. The aim of the study was to determine the acute CHD incidence and mortality, especially out-of-hospital cases. Methods: The fatal and nonfatal cases of acute CHD were actively revealed among representational cohort ( population, 76.4% of them 18 years) of three Russian regions for 12 months by review of symptoms, medical out-patient cards, hospital medical histories, ambulance reports and in cases of death - also by using of civil status acts, autopsy reports. Then refined data has been compared with official diagnosis and causes of death in death certification. Results: According to official data mortality from acute CHD among studied population amounted per male and per female. The results of acute CHD-induced deaths detection demonstrated that true death-rate from acute CHD exceeded officially registered level at the least in 2.13 times for males ( per , p<0.001) and in 2.28 times for female ( per , p<0.001). All unregistered cases of fatal acute CHD were revealed among out-of-hospital deaths. Thus, out-of-hospital mortality from acute CHD increased from 70.67% to 87.98% (p<0.01) for male patients and from 39.58% to 78.68% (p<0.001) for female patients. The incidence of acute CHD increased by 26% for male population (from to per , p<0.01) and by 32% for female population (from to per , p<0.01). Conclusions: The study results revealed detestability of acute CHD as cause of deaths, especially in out-of-hospital death cases. As a consequence, a realistic acute CHD incidence is higher than officially registered value. CORONARY SURGERY VALVULAR HEART DISEASE P2303 Prosthesis patient mismatch after mitral valve replacement is associated with persistent pulmonary arterial hypertension A. Tugcu 1,O.Kose 1, O. Yildirimturk 1,Y.Tayyareci 1,V.Aytekin 2, I.C.C. Demiroglu 1,S.Aytekin 2. 1 Florence Nightingale Hospital, Istanbul, Turkey; 2 T.C. Istanbul Bilim University, Florence Nightingale Hospital, Istanbul, Turkey Purpose: We aimed to determine the impact of prosthesis patient mismatch (PPM) on postoperative pulmonary arterial (PA) pressure after mitral valve replacement (MVR). Methods: Hundred patients who underwent isolated MVR with a preserved left ventricular ejection fraction were enrolled. Mitral valve effective orifice area (EOA) was determined by continuity equation and indexed for body surface area. Because atrioventricular compliance (Cn) has been shown to influence PA pressure in patients with mitral stenosis, it was also determined by echo-doppler measurements. Results: Thirty-three patients (33%) had PPM defined as indexed EOA 1.2cm 2 /m 2. Postoperative systolic PA pressure was significantly higher in patients Figure 1 with PPM compared to patients with no PPM (Figure 1). Patients with an Cn 4 ml/mm Hg had a significantly higher (p < 0.001) postoperative systolic PA pressure (37.2±8.8 mmhg) compared to those with Cn > 4.0 ml/mm Hg (31.6±7.4 mm Hg). Postoperative systolic PA pressure levels correlated well with indexed EOA (r=-0.537, p<0.001), mean transprosthetic gradient (r=0.433, p<0.001) and Cn (r=-0.422, p<0.001). In multiple stepwise linear regression analysis, the independent determinants of postoperative PA hypertension were: indexed EOA (β=-0.430, p<0.001), age (β=0.249, p=0.01), Cn (β=-0.197, p=0.025) and atrial fibrillation (β=0.186, p=0.013). An indexed EOA 1.2cm 2 /m 2 had a sensitivity of 89% and a specificity of 84% to predict PA hypertension. Conclusion: PPM after MVR is not uncommon. It is associated with persistent postoperative PA hypertension. In order to minimize the risk of PPM, a systematic estimation of the indexed EOA and planning a specific surgical strategy targeted towards each patient should be accomplished before the operation. P2304 Speckle-tracking correlates better than traditional parameters with the long-term systolic function decrease after mitral valve replacement J.A. De Agustin Loeches, J. Zamorano, L. Perez De Isla, C. Almeria, J.L. Rodrigo, A. Aubele, D. Herrera, C. Fernandez-Golfin, P. Marcos-Alberca, C. Macaya. Hospital Clinico San Carlos, Madrid, Spain Background and aim: The long-term development of left ventricular (LV) dysfunction after mitral valve replacement is frequent in patients with chronic severe mitral regurgitation (MR). Strain and strain rate analysis have emerged, as quantitative variables to accurately estimate the myocardial contractility. Our aim was to compare preoperative strain and strain rate obtained by 2D-echo based speckletracking with the traditional parameters to predict postoperative LV dysfunction after mitral valve replacement. Methods: Thirty four consecutive patients with chronic severe MR scheduled for mitral valve replacement were prospectively enrolled. Preoperative longitudinal strain (S) and strain-rate (SR) at the level of the interventricular septum (IVS) was performed by speckle-tracking. LV dimensions and ejection fraction (LVEF) was assessed by 3D-echocardiography. Preoperative examinations were performed within 48 hours before surgery, and postoperative ones 6 months after surgery. Results: Mean age of patients was 59.9±11.3 years and ten patients (29.4%) were men. Longitudinal Strain rate at the level of the basal IVS showed the better correlation with the LVEF decrease (see table). LV dimensions and Dp/dt also correlated well. Nevertheless, preoperative LVEF had not correlation with the LVEF decrease. Table 1 r p EDV (3D) ESV (3D) LVEF (3D) Dp/Dt Long. S basal IVS Long. SR basal IVS Long. S mid IVS Long. SR mid IVS Strain and strain rate obtained by 2D-echo based speckle-tracking compared with the traditional parameters to predict postoperative LV dysfunction. Conclusions: Longitudinal speckle-tracking-derived strain and strain-rate of IVS allows us to accurately detect early abnormalities of LV contractile function. This new tool may assist the clinician in the optimal timing of surgery in patients with chronic severe MR. P2305 Clinical and echocardiographic long term follow up of patients undergoing Ross procedure according to the predominant aortic valve lesion M. Delgado Ortega, M. Ruiz Ortiz, M. Mesa Rubio, E. Romo Penas, F. Toledano Delgado, M.C. Leon Del Pino, M. Anguita Sanchez, J.C. Castillo Dominguez, J. Casares Mediavilla, J. Suarez De Lezo Cruz Conde. Hospital Universitario Reina Sofia, Cordoba, Spain Aim: To study the clinical and echocardiographic long-term follow up of patients (pts) undergoing Ross procedure according to the predominant aortic valve lesion. Patients and Methods: We analyzed 79 pts who underwent Ross procedure since November/97 until January/09. Two subgroups were distinguished: a) Aortic Stenosis (AS) (n = 25, 32%) b) Aortic Regurgitation (AR) (n = 54, 69%). All echocardiographic measures were standarized by body surface area. Results: No significant difference in age was found between groups (29±13 years in AS versus 30±11 in AR). In AR group males predominated (77% versus 40%, p <0.05). The etiology of the lesion was congenital in 92% of AS compared to 61% of AR group (p <0.05). Echocardiographic parameters of both groups and their evolution after surgery are detailed in Table 1. After 67±32 months of clinical follow-up there was no significant difference in the need of autograft surgery between both groups (5% reoperations in AS versus 6.5% in AR). At least moderate regurgitation of the autograft was detected in 10% of pts with AS versus 13% in the AR group (p=0.78). Five percent of pts suffered an autograft endo-

82 382 Coronary surgery Valvular heart disease Table 1 AS p value AR p value p value pre follow pre follow AR vs AR vs AS pre AS follow Diastolic diameter, mm/m Sistolic diameter, mm/m < Septum, mm/m < Posterior wall, mm/m Ejection fraction, % < Mean aortic gradient, mmhg < Aortic ring diameter, mm/m AS: Aortic stenosis. AR: Aortic regurgitation. carditis in AS group compared to 2% in AR group (p =0.51). Most patients remained asymptomatic during follow-up: 94% in AS group and 93% in AR group (p =0.83). Conclusions: 1)Patients with aortic regurgitation as predominant aortic lesion have a worse ejection fraction and larger left ventricular diameters, which normalized after surgery. 2)Most of the pts who underwent Ross procedure are asymptomatic in long-term follow up. 3) Regurgitation of the autograft may appear over time, although the need for reoperation is low, regardless the type of valvular lesion. P2306 Autograft failure in the follow-up of Ross operation: a descriptive study and predictive factors in a prospective series M. Ruiz Ortiz, M. Delgado Ortega, D. Mesa Rubio, E. Romo Penas, F. Toledano, C. Leon, A. Lopez Granados, J.M. Arizon Del Prado, P. Alados Arboledas, J. Suarez De Lezo. Hospital Universitario Reina Sofia, Cordoba, Spain Purpose: Failure of the autograft in aortic position is one of the complications that can appear in the follow-up of patients after Ross operation. Our aim is to analyze the incidence of this complication in our series and to study factors associated with it. Methods: Out of 102 patients consecutively operated of Ross intervention at our centre between November 1997 and January 2009, we selected 83 patients (age 32±11 years, range 6 to 54 years, 60 males -72%) who were discharged without significant autograft regurgitation and had at least one follow-up echocardiogram. Autograft failure was defined as the presence of at least moderate regurgitation by echocardiography, judged according to the guidelines of the American Society of Echocardiography. We studied the frequency of this complication and tried to find predictive factors. Results: After 56±36 months of follow-up, 8 patients (9.6%) developed autograft failure: four severe regurgitation (three of whom underwent valve replacement), one moderate-severe insufficiency and three moderate regurgitation. The probability of autograft failure-free survival was 99% at one year and 90% at 5 years. In univariate analysis, autograft failure was associated with operation in the first 6 months of the learning curve (42% versus 4%, p <0.001), aetiology other than congenital (19% versus 4% in congenital aetiology, p = 0.024), a lower ejection fraction (60±7% versus 68±10%, p = 0.018) and a larger pulmonary annulus size -normalized by body surface area- (15±1 mm/m 2 versus 13±2 mm/m 2,p= 0.015) as measured by the echocardiogram prior to surgery. Patients with autograft failure presented larger autograft annulus size normalized by body surface area- (17±1 mm/m 2 versus 14±4 mm/m 2 ) in the last follow-up echocardiogram, but this difference did not reach statistical significance (p=0.13). In multivariate analysis, only operation in the first period of the learning curve (HR 9.1, 95% CI , p = 0.021) and larger normalized pulmonary annulus size (HR 1.4, 95% CI , p = 0.04) were independent predictors of this complication. Conclusions: Late autograft failure presents a low incidence after Ross procedure. In our experience, intervention in the first period of the learning curve and a larger pulmonary annulus size were independent predictors of this complication. P2307 When repair, when rather replacement for chronic ischemic mitral regurgitation-medium term results of undersized ring annuloplasty with echocardiographic follow-up D. Puszczewicz, R. Przybylski, S.Z. Pawlak, T. Niklewski, J. Pacholewicz, T. Kukulski, A. Kowalczuk, M. Zembala. Silesian Center for Heart Disease, Zabrze, Poland Background: Mitral valve annuloplasty is the standard surgical technique for the management of chronic ischemic mitral regurgitation (IMR). However up to 1/3 of patients develop recurrent IMR after surgical annuloplasty. Material and Methods: In a series of consecutive 284 patients with CAD undergoing CABG with mitral valve repair, first 134 were evaluated: 90 male (67,2%), mean age 63,1, mean EuroSCORE 6,6±2,6 and 106 pts with history of acute MI. Transthoracic echocardiography (TTE) with quantitative Doppler measurements revelaled moderate MR in 62 pts (46,3%) and severe in 72 pts (53,7%). Undersized ring was implanted in all pts (Ring diameter ranged 24-30mm, but sizes 26, 27, 28 were used in 93,7% of pts). Patients were observed for 4-20 months (Median 7,2±3,0). TTE was performed in all pts. Results: Severe MR occured in 8 pts (5,9%). 2 pts of them required reoperation. Statistical analysis revealed that length of coaptation (LC) (p=0,0002), NYHA class (p=0,034), CCS class (p=0,027), Euroscore (p=0,021) are the predictors of postoperative MR. Cox regression showed independent predictors of recurrent MR are: age (OR 0,9 p=0,041), post-op IABP (OR 3,4 p=0,023), BSA (OR 0,084 p=0,041), EROA (OR 154,4 p=0,001), LVEDVI (OR 1,024 p=0,011), LVESVI (OR 1,020 p=0,044) and LC (OR 0,011 p=0,014). Results depend on: LC (cut off 6, 3mm, sensitivity 94,0%, specificity 85,0%, p<0,05) and left ventricular geometry and function LVEDVI (cut off 82,6 ml/m 2, 60,0%, 61,3%, p<0,05), LVESVI (cut off 54,2ml/m 2, 60,0%, 68,8%, p<0,05), LVEF (cut off 35%, 75,0%, 65,0%, p<0,05). Risk of IMR recurrence-cox multivariate analyzes - if four predictors are present: LC 6,0mm, IMR severe preop, LVEF 35% pre-op, BSA 1,9 pre-op - 84,33%, for three predictors - LC, IMR and LVEF - 50,13%, for three predictors - LC, IMR, BSA - 60,08% respectively. Conclusions: We identified clinical and echocardiographic parameters associated with repair failure, that suggests some patients with IMR might be better served by MV replacement than repair. P2308 Decellularization reduces inflammatory reaction, calcification and extracellular matrix degeneration in pulmonary heart valve allografts P. Akhyari 1,H.Kamiya 1, P. Mambou 2, R. Tschierschke 2,M.Barth 3, S. Schilp 4, I. Berger 5, W.W. Franke 3,M.Karck 2, A. Lichtenberg 1. 1 Universitaetsklinikum Jena, Jena, Germany; 2 Universitaetsklinikum Heidelberg, Heidelberg, Germany; 3 Helmholtz Group for Cell Biology, German Cancer Research Center, Heidelberg, Germany; 4 Phys. Chemistry, University of Heidelberg, Heidelberg, Germany; 5 Dept. of Pathology, Klinikum Kassel, Kassel, Germany Purpose: Aortic or pulmonary allografts are used in adult and pediatric patients. However, functional graft deterioration may be reduced by decellularization through elimination of immunogenic cellular antigens and proinflammatory components. Methods: Fresh (fpv, n=5) or detergent-decellularized pulmonary allografts (dpv, n=5) were implanted for 4 months in juvenile sheep. Echocardiography, haemodynamic measurements, immunohistological analysis for endothelial, interstitial, and inflammatory cells, von Kossa and Movat staining, scanning and transmission electronmicroscopy, western blot analysis of ECM proteins, endothelial markers and Poly (ADP-ribose) polymerase (PARP), and DNA content were obtained upon explantation. Results: After 4 months in vivo no significant stenosis or insufficiency occurred, but a trend towards smaller valve area and increasing peak gradients were noted in fpv. Furthermore, significantly higher total DNA, elastin and slightly increased laminin content were observed in fpv, although electronmicroscopical evaluation proved signs of architectural matrix disintegration. Histologically, interstitial hyperplasia and leaflet thickening were accompanied by increased numbers of apoptotic cells, infiltration of (CD3+) inflammatory cells and disseminated micro foci of calcium deposition in fpv as compared to dpv. In the decellularized group partial re-endothelialization and beginning interstitial repopulation at the base of the cusps were present with negligible calcium deposition and inflammatory infiltration. Conclusions: Despite comparable haemodynamic performance at 4 months, on the ultra-structural level higher rate of graft degeneration are present in fpv at this early stage. In contrast, dpv retain functional capacity and exhibit minor adverse matrix remodelling, particularly reduced inflammatory response and calcification. These changes are most likely responsible for late degeneration and chronic graft failure and deserve particular attention when novel heart valve prosthesis are developed for clinical application. P2309 Surgical coronary artery revascularization versus medical management before high risk non-cardiac surgery: a meta-analysis P. Singh, S. Adigopula, U. Bedi, M. Singh, J. Molnar, R. Arora, S. Khosla. Rosalind Franklin University of Medicine and Science, North Chicago, United States of America Purpose: Previous studies comparing pre-operative coronary artery bypass grafting (CABG) with medical management in patients undergoing elective high risk non-cardiac surgery have shown conflicting results. Hence, a meta-analysis was performed to evaluate the incidence of all-cause mortality and myocardial infarction (MI). Methods: A systematic review of literature identified six retrospective studies involving 1345 patients. As the studies were homogenous for both outcomes, combined relative risks (RR) and the 95% confidence intervals (CI) were computed using the Mantel-Haenszel fixed-effect model. A two-sided alpha error <0.05 was considered statistically significant. Results: There were no differences in baseline demographics of patients in both groups. Compared to control group, the risk of all-cause mortality (RR: 0.38, CI: ; p<0.001) and MI (RR: 0.26, CI: ; p<0.001) was significantly lower in patients who had previous CABG. Conclusions: Pre-operative CABG before elective high risk non-cardiac surgery

83 Coronary surgery Valvular heart disease 383 may be superior to medical management in reducing the incidence of all-cause mortality and MI. P2310 Association between C-reactive protein, systemic inflammatory response syndrome and adverse outcomes in cardiac surgery H. Cohen Arazi, S.V. Waldman, R. Poggio, L.R. Carrizo, R. Spampinato Torcivia, H. Grancelli, M. Carnevalini, W. Rodriguez, C.E. Pensa, C. Nojek. FLENI Institute, Buenos Aires, Argentina Purpose: It is not fully established whether baseline blood levels of inflammatory markers may identify patients at risk for Systemic Inflammatory Response Syndrome (SIRS) and adverse outcomes in cardiac surgery. Methods: One hundred sixty-nine consecutive patients (77.3% men, age 61.1 years ± 15.9, Euroscore median 4.3 (IC )) who underwent cardiac surgery between April 2007 and December 2008, were prospectively included. SIRS was defined as described by the American College of Chest Physicians/Society of Critical Care Medicine Consensus, plus a norepinephrine infusion >0.5μg/kg/min. Cutoff values for high intermediate - sensitivity CRP were established in >2.0mg/dL. A combined end point included SIRS associated with atrial fibrillation (AF), shock, renal failure (RF) or death. Logistic regression was used for multivariate analyses. Results: Eighty-seven patients (54%) developed SIRS after cardiac surgery, and 50 (31%) patients had the combined end point. Nine patients (5.6%) died during the in-hospital stay. Eighty-one patients had preoperative CRP >2.0 mg/dl (50.3%). A univariate analysis demonstrated that CRP >2.0 mg/dl was associated with SIRS (OR 3.17-IC95% , p<0.0001), and the combined end point (OR 3.58-IC95% , p<0.001). An association was found between CRP and: SIRS associated with RF (OR 6.36-IC95% , p<0.0001), SIRS and Shock (OR 7.49-IC95% , p<0.004), SIRS and AF (OR 4.13-IC95% , p<0.006). As well as independent association among CRP and RF (OR 2.96-IC95% , p<0.002) and shock (OR 3.97-IC95% , p<0.020). Adjusted by preoperative variables (gender, age, diabetes, hypertension, crossclamp time, left ventricular diastolic diameter, BUN, creatinine, history of RF, history of myocardial infarction), CRP >2.0 mg/dl independently predicted: SIRS (OR IC95% , p<0.000), combined end point (OR 2.95-IC95% , p<0.018), SIRS and RF (OR IC95% , p<0.010), SIRS and shock (OR 6.50-IC95% , p<0.005), SIRS and AF (OR 3.51-IC95% , p<0.028), RF (OR 2.91-IC95% , p<0.019) and shock (OR 4.13-IC95% , p<0.020). Conclusions: Intermediate - sensitivity CRP levels >2.0 mg/dl might be useful in the identification of patients at risk for SIRS and adverse outcomes. P2311 Redox state in arterial grafts predicts left ventricular functional restoration after coronary artery bypass grafting C. Antoniades 1, T. Van-Assche 1, A.S. Antonopoulos 2, D. Tousoulis 2, C. Stefanadis 2, D. Taggart 1, K.M. Channon 1, P. Leeson 1. 1 University of Oxford, Oxford, United Kingdom; 2 University of Athens, Athens, Greece Myocardial oxidative stress is a critical parameter in left ventricular functional restoration after coronary bypass graft (CABG) surgery. Aim: We examined the effect of vascular redox state in CABG grafts, on patients functional rehabilitation post-surgery. Methods: In this study 147 coronary artery disease (CAD) patients who underwent CABG were recruited. We determined NYHA class before surgery and 6 weeks post-cabg. Paired segments of left internal mammary arteries (LIMA) and saphenous veins (SV) were harvested during CABG. Superoxide (O 2 - )production in the LIMA arterial wall was estimated by lucigenin chemiluminescence. SV vasomotor responses to acetylcholine (ACh) and sodium nitroprusside (SNP) were determined ex-vivo. Results: Patients NYHA-class pre-cabg was independent of total O2- production in LIMA grafts (Fig. A). However patients in NYHA II at 6 weeks post-cabg, had higher O 2 - in LIMA grafts at the rime of surgery, compared to those in NYHA class I (Fig. B). In multivariate analysis overall O2- in the LIMA was the sole independent predictive factor of NYHA-class at 6 weeks post surgery (β(se): (0.015), p=0.02). None of the other peri-operative factors (SV vasorelaxations to ACh, demographic characteristics etc) were correlated with NYHA-class at 6 weeks post-cabg. Conclusions: Graft redox state is not correlated with severity of heart failure before CABG, but constitutes an independent predictive factor of left ventricular functional restoration and clinical rehabilitation post-surgery. Arterial graft redox state may affect graft vasomotor function and myocardial perfusion post-cabg. P2312 Coronary surgery: does patient risk profile change over years? B. Mihajlovic, S. Nicin, N. Cemerlic Adjic, K. Pavlovic, S. Dodic, M. Fabri. Institute of cardiovascular diseases of Vojvodina, Sremska Kamenica, Serbia Background: In current era of widespread use of PCI, it is debatable if CABG patients are of higher risk. The aim of the study is to evaluate risk profile of CABG patients. Methods: By analyzing the EuroSCORE and its risk factors, we reviewed a consecutive group of 4675 isolated CABG patients operated during the last 8 years ( ) at our Clinic. The number of PCI patients was compared to the number of CABG patients. For statistical analyses the Pearson Chi-square and ANOVA tests were used. Results: The number of PCI increased from 159 to 1595 (p<0.001), and the number of CABG from 557 to 656 (p<0.001). The mean EuroSCORE increased from 2.74 to 2.92 (p=0.06). The frequency of the following risk factors did not change over years: female gender (p=0.614), previous cardiac surgery (p=0.175), serum creatinine >200μmol/l (p=0.256), preoperative ejection fraction 30% (p=0.065), systolic PA pressure > 60 mmhg (p=0.473) and postinfarct septal rupture (p=0.275). Chronic pulmonary disease, neurological dysfunction, critical preoperative care and unstable pectoral angina decreased significantly (p<0.001). The mean age increased from 56.8 to 60.7 (p=0.001) and extracardiac arteriopathy increased from 9.2% to 22.9% (p<0.001). Recent preoperative myocardial infarction increased from 11% to 15.1% (p=0.021), while emergency operations increased from 0.9% to 4.0% (p=0.001). Conclusion: The number of CABG increases despite the enlargement of PCI. The risk for isolated CABG given by EuroSCORE increases over years. The risk factors, significantly contributing to higher EuroSCORE are: older age, extracardiac arteriopathy, recent myocardial infarction and emergency operation. P2313 Proinflamatory cytokines and the risk of perioperative myocardial infarction in patients undergoing coronary artery bypass grafting M. Sniezek-Maciejewska 1, E.L. Stepien 2, A. Undas 1,K.Sztefko 3, B. Kapelak 1,J.Sadowski 1. 1 Institute of Cardiology, Jagiellonian University School of Medicine, Krakow, Poland; 2 Krakowski Szpital Specjalistyczny im. Jana Pawlall, Krakow, Poland; 3 Polish-American Institute of Pediatrics, Jagiellonian University School of Medicine, Krakow, Poland Perioperative myocardial infarction (PMI) in patients undergoing coronary artery bypass grafting (CABG) implies negative prognostic consequences. In search for risk markers of this complication, various clinical and biochemical factors, including proinflammatory cytokines, Interleukin 6 and Tumor Necrosis Factor (IL-6 and TNFalpha) have been evaluated. The aim of the study was to evaluate the usefulness of preoperative measurements of proinflammatory cytokines IL 6 and TNFalfa in patients undergoing CABG. Material and methods: 176 patients undergoing elective CABG were evaluated, aged (mean, 61) years, 139 men and 34 women. Using our own algorithm (haemodynamic state, ECG, CK, CK-MB, ctn I and echocardiography) and ESC criteria to diagnose PMI, the patients were divided into 3 groups: group I patients with uncomplicated course; group II patients with minimal myocardial damage (MMD); group III patients with PMI. TheIL 6 and TNFalfa levels were measured using ELISA assays. Results: Mean IL 6 values for groups I III were: 2.96±3.01; 2.34±1.42 and 3.44±3.56 pg/ml, respectively. Mean TNFalfa values for I III group were: 2.55±3.1; 2.38±2.12; 3.27±4.43 pg/ml. There were no statistic differences for mean values (test t). Using ROC curve for sensitivity and specificity analysis we found a statistically significant difference for group I and III (p<0.005) at the cut-off level for IL 6 of 2.37 pg/ml. There was no such difference for TNFalfa.

84 384 Coronary surgery Valvular heart disease Patients Mean no. of grafts Occluded grafts Per patients irresp. of no. of grafts Number (no./all, %) (no., %) Arterial Venous All patent All occluded Mixed a M, n= ±0.9 40/244 (16.4) 105/465 (22.6) 129 (52.5) 13 (5.3) 105 (42.5) F, n= ±0.9* 5/41 (12.2) 32/92 (34.8)** 26 (49.1) 5 (9.4) 22 (41.5) *p<0.05 F vs M (ANOVA), **p<0.05, chi-square. a Mixed means patent and stenosed or occluded. all grafts patent (52%). In the remaining patients at least 1 of 2-5 conduits was occluded. Differences between females and males are presented in table 1. Conclusions: A noninvasive visualization of by-pass grafts by means of a 64- MDCT appears an attractive alternative to invasive method. Use of this method confirmed a lower patency rate of venous grafts compared to arterial conduits. Occlusion rate of venous grafts was found to be gender-related, being higher in females. Conclusion: Mean value IL 6 and TNFalfa measured preoperatively are higher in patients with PMI; the IL 6 cut-off level of 2.37 pg/ml discriminates patients with risk of PMI with 68% sensitivity and 52% specificity. Measurements of proinflamatory cytokines mainly IL 6 before CABG surgery may be useful for predicting the risk of PMI. P2314 Risk-prediction models for major postoperative morbidity in coronary surgery P.E. Antunes, J.F. Oliveira, M.J. Antunes. University Hospital, Coimbra, Portugal Purpose: There are several risk-prediction models for perioperative mortality but models for morbidity are not used. A prospective study of patients undergoing coronary artery bypass graft surgery (CABG) was conducted to identify the preoperative risk factors and to develop and validate risk prediction models for major causes of postoperative morbidity. Methods: Data on 4,567 patients who underwent isolated CABG surgery over a 10-year period were extracted from our prospectivelygenerated clinical database. Five major postoperative complications (cerebrovascular accident, mediastinitis, acute renal failure, cardiovascular failure and respiratory failure) were analysed. A composite morbidity outcome (presence of two or more major morbidities) was also entered in the analysis. A risk model was developed for each of these endpoints and validated by means of logistic regression and bootstrap analysis. Discrimination and calibration were assessed by using the under the receiver operating characteristic (ROC) curve area and the Hosmer-Lemeshow (H-L) test, respectively. Results: The hospital mortality was 0.96%. The specific morbidity rates were: cerebrovascular accident (2.5%), mediastinitis (1.2%), acute renal failure (5.6%), cardiovascular failure (5.6%) and respiratory failure (0.9%). The composite morbidity rate was 9.0% The risk models developed demonstrate an acceptable discriminatory power (ROC curve area for cerebrovascular accident, 0.715; mediastinitis, 0.696; acute renal failure, 0.778; cardiovascular failure, 0.710; respiratory failure, 0.787; and composite morbidity outcome, 0.701) (Figure). The results of the H-L test showed that models predict morbidity accurately, both on average and across the ranges of patient deciles of risk, thus can be used clinically. Conclusions: As a complement to a previously reported mortality risk-prediction model, we developed a set of risk-prediction models that can be used as an instrument to provide information to clinicians and patients about the risk of postoperative major morbidity in our patient population anticipating isolated CABG. P2315 Coronary artery graft patency on a 64-MDCT angiography: single centre experience in 300 patients M. Sosnowski 1,A.Gola 2,K.Chromik 2,A.Sobczak 2, R. Bachowski 1, A. Bochenek 1, P. Buszman 1,Z.Gasior 1, M. Trusz-Gluza 1, M. Tendera 1. 1 Slaski Uniwersytet Medyczny w Katowicach, Katowice, Poland; 2 Gornoslaski Osrodek Kardiologii, Katowice, Katowice, Poland A visualization of coronary by-pass grafts on multi-detector computed (MDCT) coronary angiography focuses increasing interests as an alternative to invasive by-pass angiography. This method is totally noninvasive, relatively simple, with ambulatory accessibility and less complications. We reviewed results of a 64-MDCT coronary angiography in 300 consecutive patients with a history of coronary artery by-pass graft surgery (3 months to 8 years after surgery, median 6 months). There were 53 females (mean age 65±8ys) and 247 males (mean age 61±9ys, p<0.05). Among females, 7 had 1 arterial graft, 12 had only venous grafts and the remaining 34 - mixed (both arterial and venous). Among males, 12 had 1 arterial graft, 30 - venous grafts, and mixed grafts. Number of grafted vessels was 1 in 23 patients (7F, 16M), 2 in 82 (16F, 66M), 3 in 144 (24F, 120M) and 4 or more in 51 patients (6F, 45M). The total number of arterial grafts was 285 in 258 patients and of the venous grafts was 557 in 281 patients. Results: Out of 285 arterial grafts 45 (15.8%) were occluded. Total occlusion was found in 137 out of 557 venous grafts (24.6%, p<0.01, Chi-square). On patients basis, in 18 out of 300 (6%), all grafts were occluded, while 155 patients had P2316 Long term (7-to-20-year) patency of the radial artery as a coronary bypass conduit assessed by computed tomographic angiography R. Boutekadjirt 1, D. Toledano 1, P. Achouh 2,K.OuldIsselmou 2, P. Goube 3, B. Lancelin 4, R. Fouquet 5,C.Acar 1. 1 Pitie-Salpetriere Hospital (AP-HP), Paris, France; 2 European Hospital George Pompidou (AP-HP), Paris, France; 3 Centre Hospitalier Sud-Francilien, Corbeil, France; 4 Clinique Alleray-Labrouste, Paris, France; 5 Centre Hospitalier de Versailles, Le Chesnay, France Purpose: The radial artery (RA) as a coronary bypass conduit offers excellent mid-term results but its durability remains unknown. The aim of this study was to assess the long term RA patency using CT angiography. Methods: Sixty-four-slice CT angiography was performed in 115 patients having undergone coronary bypass with the RA. Follow-up extended from 7 to 20 years (mean: ). Age ranged form 48 to 88 years (mean:69 + 8). Five patients were in atrial fibrillation. Twenty one patients had evidence of myocardial ischemia and 94 were asymptomatic. The conduits used were: RA (129), left IMA (108), right IMA (15) and veins (43). RAs were anastomosed to: marginal (56%), diagonal (16%) and right coronary (28%) whereas IMAs were mostly anastomosed to the LAD (85%). Medications included antithrombotics: aspirin (71%), clopidogrel (23%), oral anticoagulant (15%) and vasodilators: nitrates (10%), beta-blockers (71%), Ca 2+ blockers (41%) and ACE inhibitors (49%). PTCA was required in 15 patients at years involving: 5 RAs, 1 IMA and 13 coronary arteries. Results: CT scanner allowed a reliable evaluation of graft patency in all cases for a mean radiation exposure of mgray.cm. The 11-year patency of RAs was 82.9%. It was lower than IMAs (94.3% p<0.01) and similar to veins (79.0% p=0,45). All graft patency was lower in case of myocardial ischemia than in asymptomatics (77.1% vs 89.5% p<0.01) and in non-lad than in LAD grafts (84.2% vs 95.3% p<0.01). RA graft patency appeared to be improved by aspirin (87.9% vs 71.0% p=0.02) and beta-blockers (87.0% vs 72.2% p=0.04). No other medication seemed to affect either RA or all graft patency. All dilated (2) or stented (3) RA conduits were patent. Conclusion: In this study the RA-to-coronary bypass conduit provided an excellent long term patency. CT angiography allowed a non-invasive and reliable method for assessing graft function. P2317 Predictors of early outcome after coronary artery bypass grafting in the elderly S.M. Oliveira, A. Goncalves, R. Almeida, A. Azevedo, P. Dias, P. Pinho. Hospital S Joao, Porto, Portugal Introduction: Improved life expectancy led to an increasing number of elderly patients (pts) submitted to coronary artery bypass graft surgery (CABG). As comorbidities are more prevalent in geriatric patients, a critical evaluation of cardiac surgical outcome is needed. The aim of this study was to identify predictors of in-hospital mortality in elderly patients undergoing CABG. Methods: We retrospectively analyzed records of pts aged 75 years submitted to CABG from January 2002 to December 2006 at our center. Demographic data, cardiovascular risk factors, postoperative complications and additive EuroSCORE classification were analyzed. High risk was defined as EuroSCORE 6 points. Results: A total of 115 pts 75 years were included. Mean (standard deviation (SD)) age at time of surgery was 78 (2) years and 80 (69.6%) were men. Sixty-six (57.4%) pts had arterial hypertension, 64 (55.7%) had dyslipidemia, 40 (34.8%) were diabetic and 21 (18.3%) were obese. Pre-operative co-morbidities (defined in EuroSCORE), were common: 34 (29.6%) pts had extracardiac arteriopathy, 9 (7.8%) had cerebral vascular disease, 8 (7.0%) had chronic pulmonary obstructive disease and 3 (2.6%) presented with renal insufficiency. Fifty-six (48.7%) pts had records of recent myocardial infarction, 22 (19.1%) had moderate to severely depressed left ventricular (LV) function and 5 (4.3%) presented a critical preoperative state. Ten (8.7%) pts were submitted to a combined carotid artery surgery. Mean EuroSCORE was 7.16 (range 4 to 19) points, and 84 (73.0%) pts were classified in the high risk group. Mean (SD) hospital stay was 12.6 (12.3) days and overall in-hospital risk of death was 6.1% (7 pts). In univariate analysis, significant predictors of hospital mortality were moderate to severely depressed LV function (18.2% vs. 3.3%, p=0.034), combined carotid artery surgery (30% vs. 3.8%,

85 Coronary surgery Valvular heart disease 385 p=0.009), hemodialysis after CABG (71.4% vs. 0.9%, p<0.001), major bleeding (40% vs. 3.7%, p=0.012) and prolonged orotracheal intubation (30% vs. 2.9%, p=0.004). EuroSCORE was not predictor of in-hospital mortality. Conclusion: CABG procedure in the elderly was associated with an in-hospital mortality rate of 6.1%. EuroSCORE is a validated risk stratification system for the prediction of cardiac surgical outcome, however it was not predictor in our patients. In addition to postoperative complications, LV function and associated carotid artery surgery were the only pre-operative predictors of early mortality. P2318 Impact of diabetes in elective on-pump and off-pump coronary artery bypass surgery in patients with multivessel coronary artery disease and preserved ventricular function E.G. Lima 1,R.D.Vieira 1, N.H. Lopes 1,F.S.Paulitsch 1,R.Rahmi 1, A. Hueb 1, A.C. Pereira 1, J.A.F. Ramires 1, M. Farkouh 2,W.A.Hueb 1. 1 Heart Institute of University of Sao Paulo, Sao Paulo, Brazil; 2 Mount Sinai Hospital, New York, United States of America Background: Diabetes mellitus (DM) is recognized as an important cardiovascular risk factor in patients submitted to on-pump coronary artery bypass graft (CABG). The development of off-pump CABG has been contributed to minimize the non physiological effects of on-pump CABG. There are few randomized and prospective studies with diabetic subjects comparing on-pump and off-pump surgery. Methods: Patients with multivessel coronary artery disease, stable angina, preserved ventricular function and cardiovascular surgeon s agreement that revascularization could be attained by either strategies, were randomized to on-pump or off-pump CABG. The primary end-points were cardiovascular death, stroke or unstable angina requiring revascularization. DM was defined in according of American Diabetes Association criteria. Results: In MASS III study 308 subjects were randomized to intervention, 153 were submitted to on-pump and 155 to off-pump surgery. There were 54 and 56 diabetic patients in on-pump and off-pump surgery groups, respectively. DM patients showed higher triglycerides level more hypertension and lesser tabagism. Baseline characteristics were similar among diabetic patients randomized to both strategies. There were no differences in the incidence of mortality, stroke, and refractory angina in diabetics patients submitted to on-pump or off-pump CABG along five-year follow-up. Conclusion: In MASS III study, the surgery strategy did not confer differences in primary end-points in diabetics patients. P2319 Myocardial bridge: Surgical outcome and midterm follow up A. Sajjadieh Khajouei 1,R.Parvizi 2. 1 Shahid Chamran Heart Hoapital, Isfahan, Iran (Islamic Republic of); 2 Shahid Madani Heart Hospital, Tabriz, Iran (Islamic Republic of) Myocardial bridge consists of muscle fiber bundle lining on epicardial coronary artery for variable distance. Although myocardial bridge associates with benign prognosis, their presence has also been considered a cause of angina, myocardial infarction, malignant arrhythmia and sudden death. There is not a general consensus about therapeutic strategies in symptomatic patients whit myocardial bridge (medical therapy, coronary artery bypass surgery, coronary stenting, supra arterial myotomy).we report results of surgery and long-term follow up in 26 patients who had disabling symptoms due to myocardial bridge refractory to medical therapy. From among more than coronary angiography which was performed in our centre 290 (1.5%) cases had the angiographic diagnosis of myocardial bridge out of them 26 (9%) patients underwent surgical myotomy for treatment of myocardial bridge causing significant systolic arterial compression. The patients (19 male-7 female) had history of typical chest pain and positive exercise test. All of them were examined with radionucleotide study preceding angiography that was positive for ischemia in 20 cases (76%). Coronary angiography and left hear catheterization in all patients revealed impaired blood flow due to myocardial bridge in left anterior descending artery and there was additional atherosclerotic stenosis of coronary arteries in 6 and mitral valve disease in one patient. supra arterial myotomy was performed in all patients. There was no mortality or major intraoperative complication. Post operative scintigraphic and angiographic studies demonstrated restoration of coronary blood flow and myocardial perfusion without significant residual compression of the artery. Except in one patient who had recurrent anginal chest pain after operation and coronary angiography showed residual narrowing in LAD despite myotomy and underwent CABG of LIMA to distal LAD. During 7-81 month of follow-up (mean: 34.2±21) only two patients had symptoms of angina that was not shown significant residual compression and symptoms controlled by medical treatment. In conclusion surgy of myocardial ischemia due to myocardial bridge can be accomplished with very low operative risk and excellent prognosis. P2320 Effects of surgical technique options in the mid-term results of coronary revascularization in octogenarians M. Serrao 1,F.Graca 2, M. Marques 2, M. Abecasis 2, J. Calquinha 2, R. Rodrigues 2,J.Neves 2, A. Moradas 2, J. Queiros E Melo 2. 1 Hospital Central do Funchal, Funchal, Portugal; 2 Hospital de Santa Cruz, Lisboa, Portugal Introduction: As surgical revascularization is becoming more frequent in octogenarians, we reviewed our data to analyze if complete revascularization and off-pump technique had impact in early and mid-term results. Methods: Retrospective study of 85 consecutive patients, aged 80 years or older, submitted to coronary artery bypass in a single thoracic center, between January 2003 and December We analyzed if off-pump technique (OPT) 69% vs. cardio-pulmonary bypass (CPB) 31% and complete revascularization (CR) 57,1% vs. uncomplete revascularization (UR) 42,9% had impact prognosis early and up to 5 years after surgery. Results: Baseline characteristics were similar between groups and follow-up was 91% complete.the groups had no significant differences in their mean age (CPB=82,8±2,3 years vs. OPT=82,6±1,8; p=ns) and in Logistic Euroscore (CPB=8,7±5,9 vs. OPT=11,4±13,1; p=ns). However, CPB group had longer mean hospital stay (CPB=12,1±7,7 vs. OPT=8,9±5,2 days; p=0,03) and more complete revascularization (CPB=84,6% vs OPT=15,4%, p=0,001). When comparing the revascularization there was no significant differences in mean age (CR=82,5±1,9 years vs. UR=82,9±2, p=ns) and in Logistic Euroscore (CR=11,6±13,8 vs. UR=9,2±6,6, p=ns). At 5-year follow-up, off-pump surgery patients had the same late prognosis (total mortality: OPT=22.6% vs. CPB=21,7%, p=ns; cardiovascular mortality: OPT=15,5% vs. CPB=15,4%, p=ns) as well as complete revascularization (total mortality: CR=20% vs. UR=25,8%, p=ns; cardiovascular mortality: CR=14,6% vs. UR=16,7%, p=ns). Conclusion: In octogenarians, off-pump technique, even though may imply to perform a less complete revascularization, leads to a shorter hospital stay and has the same 5 year results as of those patients operated under cardiopulmonary bypass. We conclude that off-pump technique should be the approach of choice to perform coronary revascularyzation in octogenarians P2321 Long-term clinical outcomes after drug-eluting stent implantation versus surgical treatment in patients with a single vessel disease C. Patsa 1, K. Toutouzas 1,E.Tsiamis 1, C. Tsioufis 1, A. Spanos 1, I. Chlorogiannis 2,E.Pattakos 3, M. Panagiotou 4, D. Iliopoulos 4, C. Stefanadis 1. 1 Hippokration General Hospital of Athens, Athens, Greece; 2 Euroclinic of Athens, Athens, Greece; 3 Hygeia Hospital, Athens, Greece; 4 Athens Medical Center, Athens, Greece Purpose: Patients with an isolated lesion in the proximal segment of left anterior descending artery (plad) present a challenging clinical problem for interventionists. The optimal revascularization strategy using either drug-eluting stent (DES) or left internal mammary artery (LIMA) remains controversial. We investigated the long-term clinical outcomes of DES versus LIMA in patients with isolated plad lesion and chronic stable angina. Methods: We enrolled 412 patients with plad lesion: 302 underwent DES implantation and 110 LIMA grafting. Patients undergoing DES implantation were scheduled to receive double antiplatelet therapy for 12 months. Primary end points were the occurrence of major adverse cardiac events (MACE). MACE was defined as: Death, myocardial infarction and target lesion revascularization (TLR). Results: There was no difference regarding the demographic and angiographic characteristics between the two cohorts. The incidence of MACE was similar between the two groups (p=0.57) during the 29.31±9.78 months follow-up period. The incidence of death was 1.65% in DES group versus 1.81% in LIMA group (p=0.99). The rate of myocardial infarction was 0.66% in DES versus 0.90% in LIMA group (p=0.99). TLR was 2.31% in DES and 0% in LIMA group (p=0.19). Five patients (1.65%) from DES group underwent percutaneous coronary intervention and 2 patients (0.66%) underwent coronary artery by pass grafting. The event-free survival curve was similar in both groups: 95.36% (DES) versus 97.27% (LIMA) (p = 0.42) (Figure). Conclusion: The overall survival rate was similar between the two groups of patients during the long-term follow-up period. Hence, it seems that both revas-

86 386 Coronary surgery Valvular heart disease / Heart transplantation and left-ventricular assist devices cularization modalities can be used effectively and safely to treat this particular group of patients. P2322 Tissue engineering: optimal coating of inflow cannulae from cardiac assist devices placed in the apex of the left ventricular cavity J. Mueller 1, B. Kapeller 2, K. Brandes 1,K.Macfelda 2. 1 Berlin Heart, Berlin, Germany; 2 Medical University of Vienna, Vienna, Austria Purpose: To find the optimal coating for implantable material is a callenge for. The movement of the inflow cannula in the apex of the left ventricle stimulates the proliferation of fibroblasts around the cannula inside the left ventricle in patients with cardiac assist devices (VADs) to variable degrees. Moreover, the cannula is responsible for unfavourable flow conditions in the left ventricle which may induce thrombus formation around the cannula. VADs generate a negative pressure in the left ventricular cavity in order to induce a flow into the pump. To avoid suction of thrombi or uncontrolled grown tissue into the pump, the surface of the cannula should see for a proper adhesion of cells and potential thrombi to the surface of the inflow cannula. We investigated the degree of adhesion of fibroblast to different titanium surfaces under in vitro and invivo conditions lateron with the optimal coated surface. Materials and Methods: Seven titanium discs (25 mm diameter, 5mm thickness) served as samples and were coated with seven different biomaterials: silicone, spongy silicone, polished titanium, sintered titanium (150 and 300 μm roughness), velour, silver coated velour, plasma injected titanium and Ti/HA. Polystyrole served as control. Human cardiofibroblasts were isolated by using published methods. Cells were cultured under standard conditions (5% CO2, 95% humidity) in DMEM-culture medium supplemented with foetal calf serum and antibiotics. Test series were carried out in 6 well Ultra Low Attachments plates by using 1x104 cells per well and per material sample. After 2 weeks specimens and on growing cells were fixed with glutaraldehyde and prepared for electron microscopical analysis. The cell layer grown on the discs was exposed to different degrees of shears stress in order to test to adhesion of the cells to the surface. Results: Only silver coated velour did not show any cell cover. The cellular overgrowth of the other materials was of varying intensity. The most densely cell layer was observed on polished titanium followed by sintered titanium. Under shear stress conditions the best cell growth and optimal adhesion of the cell to the surface was obtained on sintered titanium (300) followed by plasma injected titanium and Ti/HA compared to the control. Conclusion: According to the test series carried out with and without exposure to shear stress conditions sintered titanium (300) can be suggested as appropriate biomaterial for optimizing adhesion of cells and thrombi to the surface and ingrowth of cannulas into the ventricle, which has been clinical confirmed in more than 9 patients. Table 1 EC no CsA EC w 400 ng/ml CsA Glycosaminoglycans [μg/10 6 cells] 2.8± ±0.2 Prostacyclin [pg/10 6 cells] 78±3 75±7 TGF-β [pg/10 6 cells] 864± ±167 Conclusions: MEEC are powerful regulators of vascular injury in pigs. Allogeneic MEEC failed to induce a significant Th1-driven alloimmune response but induced differentiation of splenocytes into Th2-cytokine producing cells. This induction and the therapeutic efficacy of allogeneic MEEC were alleviated by a concomitant 12- day course of CsA. Adventitial MEEC transplants even of allogeneic sources and without immunosuppressive treatment- may be useful in decreasing luminal narrowing in a clinical setting. P2324 Custodiol-n, a novel organ preservation solution, reduces ischemia/reperfusion injury in a rat heart transplantation model S. Loganathan, T. Radovits, K. Hirschberg, A. Koch, S. Korkmaz, P. Neugebauer, M. Karck, G. Szabo. Universitaetsklinikum Heidelberg, Heidelberg, Germany Custodiol (HTK-solution) is a widely used cardioplegic solution. The newly developed Custodiol-N additionally consists of intra- and extracellular ironchelators that have been reported to reduce free radical species which play a central role in ischemia/reperfusion injury. In the present study we investigated the effects of Custodiol-N in a rat transplant model. Heterotopic transplantation was performed in Lewis rats. Ischemia was standardized to 1h. 4 groups were assigned: 2 Custodiol-N groups and 2 Custodiol control groups with a reperfusion time of 1h and 24h, respectively. Coronary blood flow (CBF), left ventricular pressure (LVP), its first derivative (dp/dt), endotheliumdependent vasodilatation to bradykinine and endothelium-independent vasodilatation to sodiumnitroprusside as well as ATP-content were measured. TUNEL staining was performed to detect apoptotic cardiomyocytes. After 1h, CBF (3.99±0.24 vs. 2.86±0.35ml/min/g;p<0.05), LVP (117±18 vs. 82±4mmHg;p<0.05) and dp/dt (3453±577 vs. 1740±116mmHg/s;p<0.05) were significantly higher in the Custodiol-N group in comparison to the corresponding control. Vasodilatatory response to sodiumnitroprusside did not show differences between the groups. Bradykinine resulted in a significantly higher increase in CBF in the Custodiol-N group (92±4 vs.60±5%;p<0.05) as well as myocardial ATP-content (9.84±0.68 vs. 1.86±0.41μmol/g;p<0.05). TUNEL staining showed a significantly reduced apoptosis (21.58±1.59 vs ±1.54%;p<0.05). After 24 hours, there was no difference between the groups in CBF, LVP, dp/dt, LVEDP. HEART TRANSPLANTATION AND LEFT-VENTRICULAR ASSIST DEVICES MINIMALLY INVASIVE AND ROBOTIC SURGERY P2323 Cyclosporine A modifies immune-mediating and therapeutic efficacy of allogeneic perivascular porcine endothelial cell implants H. Methe 1, M. Nanasato 2, A.-M. Spognardi 2, A. Groothuis 2, E.R. Edelman 2. 1 Klinikum der Universitaet Muenchen-Grosshadern, Munich, Germany; 2 Massachusetts Institute of Technology, Cambridge, United States of America Objectives: Non-syngeneic endothelial cells (EC) embedded within threedimensional matrices (MEEC) when placed in the vascular adventitia control lumenal inflammation, occlusive thrombosis and intimal hyperplasia. Host immunity directed against engrafted allogeneic tissue is a predominant T helper (Th)1- driven immune response and is a major impediment for short- and long-term success of grafts. We therefore aimed to identify if cyclosporine A (CsA) would enhance immune compatibility and therapeutic efficacy of perivascular allogeneic MEEC. Methods: Pigs (n=4/group) underwent balloon injury of both carotid arteries and received a 12 days course of CsA (group 1), perivascular implants of porcine MEEC (group 2), combination of CsA and MEEC (group 3) or were left untreated (group 4). Host immune reactivity (EC-specific Abs, activation of splenocytes) was analyzed after 28 and 90 days in 2 pigs/group respectively. Results: In vitro CsA was without effect on biosecretion by EC (table). No immune reactivity against allogeneic EC was observed in treatment groups 1 and 4. MEEC treatment alone (group 2) induced formation of IgG1 antibodies specific for the allogeneic EC and differentiation of host splenocytes into Th2 but not Th1 cytokine-producing cells. Concomitant CsA-therapy reduced the frequency of IgG1 antibodies and Th2-cytokine producing splenocytes upon MEEC treatment. Compared with groups 1 and 4 treatment with MEEC (group 2) significantly inhibited luminal occlusion 28 and 90 days after balloon injury. Concomitant CsAtreatment reduced the ability of MEEC to inhibit luminal occlusion. TUNEL staining after 1h and 24h Our current results demonstrate the benefits of custodiol-n especially during the critical early phase of reperfusion after heart transplantation. We believe custodiol-n is a novel promising approach in the developement of cardioplegic solutions. P2325 Pretransplantation cytomegalovirus mismatch serology (D+/R-) is a risk factor for four year mortality after heart transplantation E. Bollano, B. Rundqvist, B. Andersson, U. Nystrom, V. Sigurdardottir, F. Nilsson, N. Selimovic. Sahlgrenska University Hospital, Gothenburg, Sweden Purpose: The aim of this study was to evaluate association between cytomegalovirus (CMV) serology in donors and recipients regarding outcome after heart transplantation. Methods: Retrospective analysis of all heart transplanted adult patients at University Hospital from January 1988 through December Risk factors tested were recipient age, sex, blood group, pretransplant CMV serology, allograft ischemic time, diagnosis, donator age, sex and blood group and donor CMV serology. Primary outcome was mortality during the first 4 years after transplantation. Results: During this period 362 adults underwent heart transplantation with a mean age at transplantation of 46±12 (mean ± SD), 79% were males. The diagnoses were: cardiomyopathy (n=226), coronary artery disease (n=110), retransplantation because of cardiac allograft vasculopathy (n=7), valvular disease (n=8) and others (n=11). The study population was devided into 2 groups according to

87 Heart transplantation and left-ventricular assist devices Minimally invasive and robotic surgery 387 Survival stratified by CMV serology donor and recipient serology at the time of transplantation [(D+/R+; D-/R+; D-/R- = low risk group) and D+/R- = high risk group]. By univariate analysis allograft ischemic time and CMV serology were associated with increased mortality but not recipient age, donator age and diagnosis. In multivariate analysis independent predictor of mortality was only mismatch of pretranslant CMV serology (D+/R-) (HR 0.55; 95% CI ; p = 0.035). Conclusion: In adults, mismatch of pretransplant CMV serology is an independent predictor for early and midterm mortality after heart transplantation. P2328 Cyclosporine A decreases muscular mitochondrial energetics by the effects of its vehicle without significant long term toxicity in the heart and muscle of heart transplant patients B. Mettauer 1, B. N guessan 2,J.Zoll 3, E. Epailly 4, J.P. Mazzucotelli 4, E. Lampert 3, F. Piquard 3,X.Bigard 5,B.Geny 3, R. Ventura-Clapier 6. 1 Hôpitaux Civils de Colmar, Colmar, France; 2 Institut de Physiologie, Université D Abidjan, Abidjan, Côte d Ivoire; 3 Institut de Physiologie, Faculté de Médecine, Université de Strasbourg, Strasbourg, France; 4 Hopital Civil de Strasbourg, Strasbourg, France; 5 Département des facteurs Humains CRSSA, Grenoble La Tronche, France; 6 INSERM U769, Châtenay Malabry, France Ciclosporine A (CSA), still the keystone of most immunosuppressive regimens, has been suspected to have muscular toxicity at the mitochondrial level, potentially impairing heart and skeletal muscle function after heart transplantation (HTR). We examined the maximal O2 consumption (Vmax, μmolo2/min/g dry weight) of skinned muscular fibers from right ventricular (RV) and vastus lateralis (VL) biopsy samples in an oxygraphic chamber, at the time of HTR and 10 months after HTR as effect of chronic CSA treatment, and after adjunction within the oxygraphic chamber of 1, 10 and 100 μm of respectively CSA in Vehicle (Sandimmune), vehicle alone (Cremophor EL), CSA in ethanol (EOH) and EOH alone as representing acute effect of CSA. Values represent the means ± SEM of 10 patients. Patients chronically under CSA did not exhibit a decrease of Vmax (RV:10.8±0.6,13.9±0.9; VL:3.0±0.5,4.9±02 before and after 10 months following HTR respectively, all p=ns). Acutely CSA in Vehicle decreased Vmax in both RV and VL in a dose dependant manner, mainly by the effects of Vehicle alone and not due to CSA per se (figure). Acute effects of CSA and its vehicle We conclude that CSA has no clinically significant chronic muscular mitochondrial toxicity but may decrease mitochondrial oxidative capacity during acute intravenous administration by the effects of its vehicle, potentially affecting acutely skeletal and cardiac muscular energetics. S. Lemoine, M. Angioi, S. Mattei, C. Sirbu, N. Benzaghou, H. Aloui, O. Marcon, J.P. Carteaux, E. Aliot, J.P. Villemot. CHU de Nancy - Hopital de Brabois, Vandoeuvre les Nancy, France Purpose: The development of cardiac allograft vasculopathy (CAV) is the main long term complication of cardiac transplantation and has a very deleterious effect on its prognosis. We therefore aimed to determine long-term predictors of the occurence of a CAV in heart transplant defined by the occurence of a significant coronary lesion (>50% in reduction of diameter stenosis) diagnosed on systematic follow-up angiogram. Methods: Monocenter retrospective study. All 1-year survivors among hearttransplanted patients between January 1991 and December 2005 extracted from our propective database were included in this study. In our institution, a policy of systematic serial coronary angiography is usually applied to detect CAV. Patients were considered to have a CAV if a coronary stenosis >50% by visual analysis was evidenced. Probabilities of CAV occurence was assessed by Kaplan-Meier (KM) analysis and univariate and multivariate Cox analysis were performed to determine univariate and independent predictors of CAV. Results: 174 patients (mean age 50±10 years, male gender 77%) were included and followed during a median period of 2961 days (interquartiles ). Before transplantation, 45% of the patients suffered from ischaemic cardiomyopathy. During follow-up (FU), a CAV was evidenced in 33 patients (19%) after a median delay of 1961 days ( ). KM probabilty of being free of CAV at FU was 64%. Univariate predictors of the occurence of CAV were: absence of smoking cessation (p<0.003), total serum cholesterol level (p<0.028) and the number of previous episodes of acute rejection (p<0.0001). By multivariate analysis, absence of smoking cessation (OR % CI ( ), p<0.005) and the number of previous episodes of acute rejection (OR %CI ( ), p<0.001) were found to be independently correlated to the occurence of a CAV. At the end of FU, KM probability of being free of CAV was 72% in smokers and 59% in non-smokers, 94% in patients with less than 2 previous acute rejection episodes and 54% in those with more than 2. Conclusion: In heart-transplanted patients, the occurence of CAV is strongly correlated to previous episodes of acute rejection and absence of smoking cessation. A special effort has to be done to obtain smoking cessation in these patients. P2330 Circulating anti-heart autoantibodies are non-invasive markers of high cellular rejection burden in heart transplantation A.L.P. Caforio 1,A.Angelini 2,S.Bottaro 3,F.Tona 1, G. Thiene 2, G. Gerosa 4,S.Iliceto 1. 1 Cardiology,Dept Cardiological Thoracic and Vascular Sciences, Padua University, Padova, Italy; 2 Cardiac Pathology, Padua University, Padova, Italy; 3 Clinical Pharmacology, Padua University, Padova, Italy; 4 Cardiac Surgery, Dept Cardiological Thoracic and Vascular Sciences, Padua University, Padova, Italy Purpose: Autoimmune response may occur after solid organ transplantation. In autoimmune disease autoantibodies provide non-invasive early markers for active phases of immune-mediated inflammation in the target organ. We aimed at assessing frequency and potential predictive role of serum antiheart-autoantibodies (AHA) for acute rejection (AR) after heart transplantation (HTx). Methods: We studied 44 stable HTx patients (32 male, aged 51±16 years at HTx, at 100±72 months post-htx). Serum at last follow-up was assessed for anti-heart autoantibodies (AHA) by indirect immunofluorescence on cryostat sections of normal O blood group human myocardium and skeletal muscle, blindly from clinical features. AHA of the organ-specific type reacted with myocardium, but were unreactive with skeletal muscle, AHA of the partially organ-specific type were weakly reactive with skeletal muscle. Control groups included sera from patients with non-inflammatory cardiac disease (n=160, 80 male, aged 37±17), with ischemic heart failure (n=141, 131 male, age 51±12) and normal blood donors (n=270, 123 male, aged 35±11). A rejection score was assigned based on a modification of the ISHLT grading on follow-up endomyocardial biopsy as follows:1a=1, 1B=2; 2=3; 3A=4; 3B=5; 4=6. The following scores were calculated for each patient: RS in the total follow-up (TRS); RS in the 1st year (RS 1yr); TRS including only severe grades (greater or = 3A) (sev TRS); 1styr RS including only severe grades (sev RS 1yr). All scores were normalised for the number of biopsies taken in each patient. Antibody status was related to clinical and diagnostic features by univariate analysis. Results: The frequency of AHA was higher in HTx than in non-inflammatory cardiac disease (34% vs 1% respectively, p=0.0001), ischemic heart failure (34% vs 1% respectively, p=0.0001) or normal subjects (34% vs 2.5% respectively, p=0.0001). Positive AHA status was not associated with age at HTx, gender, pre- HTx diagnosis, time from HTx, type of immunosuppressive therapy. AHA positive patients had higher sev TRS compared to those who were AHA negative (1.3±0.1 vs. 0.46±0.4, p=0.006). Conclusion: The finding of AHA provides a non-invasive predictor of high acute cellular rejection burden after heart transplantation. P2329 Absence of smoking cessation: a major predictive factor of chronic allograft vasculopathy in heart-transplanted patients P2332 Detection and prognostic impact of echocardiographically assessed diastolic dysfunction in heart transplant recipients P. Jung, K. Berlinger, J. Rieber, F. Kroetz, M. Leibig, A. Koenig, P. Schneider, H. Gross, H.Y. Sohn, V. Klauss. Klinikum der Universitaet Muenchen, Munich, Germany Diastolic dysfunction represents a prognostically important finding during echocardiography. In patients undergoing cardiac transplantation (HTX) the anastomosis of graft and host atria alters the echocardiographic parameters commonly used to characterize diastolic function. Aim of the present study is to identify an

88 388 Heart transplantation and left-ventricular assist devices Minimally invasive and robotic surgery echocardiographic method for the assessment of diastolic function in HTX patients and to calculate its prognostic value. Methods: In 28 HTX patients (60.5±10 years, 20 male) the enddiastolic filling pressure of the left ventricle (LVend) was measured during routine cardiac catheterization. A LVend<16mmHg was considered normal. Within 2 days, a complete echocardiographic examination was performed including measurement of left atrial (LA) and left ventricular (LV) size, ejection fraction (EF), early (Em) and late diastolic mitral inflow (Am), deceleration time of the mitral E wave (Dt), systolic and diastolic pulmonary vein flow (PVs and PVd) and isovolumic relaxation time (IVRT). In addition, the TVI based early (Ea) and late diastolic (Aa) movement of the mitral annulus was assessed. The ratio Em/Am and Em/Ea was calculated in each patient. In 281 HTX patients clinical events (cardiac and non cardiac death, coronary intervention, re-transplantation) were registered during a follow-up period of up to 2.5 years after the initial echocardiogram. Results: 9 of 28 patients had a LVend >16mmHg and revealed a significantly higher Em (1.2 vs. 0.8m/s, p=0.006), Em/Am ratio (2.9 vs. 1.9, p=0.008) and Em/Ea (9.0 vs. 6.1, p=0.038). No significant differences were present regarding all other echocardiographic parameters. Clinical events occurred in 38 (13.5%) of the 281 follow-up patients (0.4% cardiac death, 1.4% non-cardiac death, 11.7% coronary intervention). Of all echocardiographic parameters only Em/Ea was able to predict an elevated clinical event rate using a threshold value of 8 (20 vs. 9%, p=0.057). Conclusion: The echocardiographic estimation of the diastolic function is feasible in HTX patients and provides prognostic information. P2333 Cardiac allograft vasculopathy (CAV) is different in CMV high-risk patients after heart transplantation T.H. Oberndorfer 1,M.Frick 1, C.H. Mussner-Seeber 1, D. Hoefer 2, H. Antretter 2, G. Poelzl 1. 1 Department of Internal Medicine III - Cardiology, Innsbruck, Austria; 2 Department of Cardiothoracic Surgery, Innsbruck, Austria Purpose: Cardiac allograft vasculopathy (CAV) is the leading cause of late mortality after heart transplantation (HTX). High-risk cytomegalovirus (CMV) mismatch constellation (D+/R-) has been repeatedly associated with increased mortality and accelerated CAV. Recently, investigation of coronary plaque composition in vivo has become possible with the introduction of intravascular ultrasound virtual histology (IVUS-VH). In this study we compared the plaque composition of high and low-risk CMV-missmatch patients using IVUS-VH. Methods and Materials: 7 patients (median age 62 years, range 34-65; median time after HTX 4 years, range 1-8) with high-risk CMV-mismatch and 26 patients (median age 52 years, range 25-65; median time after HTX 5 years, range 1-9 years) with low-risk CMV-mismatch (D+/R+, D-/R-, D-/R+) were included into this study. In all patients at least one coronary artery was investigated using IVUS-VH. Data were obtained using a continuous pullback (0.5mm/s) and a commercially available mechanical sector scanner (Eagle Eye Gold, Volcano Therapeutics). A region of interest (10-15mm) was selected at the side with the highest amount of plaque and analyses were done offline with pcvh-review software (Volcano Therapeutics). Four histological plaque components (fibrous, fibrolipid, necrotic and calcified) were correlated with a specific spectrum of the radiofrequency signal, which was assigned to different colour codes (green, greenish-yellow, red and white). Results: Patient characteristics between groups with regard to diabetes, hyperlipidemia, and hypertension were comparable. Also, total plaque burden was not significantly different (high-risk: mm 3 vs. low-risk: mm 3 ;p=ns).on the contrary, IVUS-VH demonstrated significantly higher necrotic plaque mass in high risk patients (18% vs. 11%; p<0.05) whereas fibrous (66% vs. 68%; p=ns), fibrolipid (10% vs. 12%; p=ns), and calcified (5% vs. 5.5%; p=ns) plaque tissue was comparable. Conclusion: Although total plaque burden of CAV is comparable between groups IVUS-VH reveals a significant higher proportion of necrotic plaque mass in CMV-high-risk patients. Increased necrotic plaque mass may indicate augmented plaque vulnerability and thus may explain excess mortality in these patients. P2334 Resting and exercise haemodynamic and metabolic responses to acute reduction of continuous-flow left ventricular assist device support D. Jakovljevic 1, R.S. George 2,G.Donovan 1, D. Nunan 1, R.S. Bougard 2, M.H. Yacoub 3,E.J.Birks 2,D.A.Brodie 1. 1 Research Centre for Society and Health, Buckinghamshire New University, Buckinghamshire, United Kingdom; 2 Royal Brompton and Harefield NHS Trust, London, United Kingdom; 3 Magdi Yacoub Institute, Harefield Heart Science Centre, London, United Kingdom Purpose: The present study assessed the effect of acute reduction of continuousflow left ventricular assist device (LVAD) support on resting and peak exercise cardiac power output and other haemodynamic and metabolic measurements. Methods: Twelve male patients (age 37±10 yrs) implanted with continuous-flow LVADs, visited the exercise laboratory twice during the same day with at least four hours rest between the two visits. During the first visit, LVAD support was optimal with speeds ranging from 9,000 to 9,600 revolutions per minute. During the second visit the LVAD support was reduced at 6,000 revolutions per minute. Measurements at rest and at the peak exercise of the modified Bruce protocol were undertaken using non-invasive, inert gas, rebreathing haemodynamic and respiratory gas procedures. Cardiac power output, expressed in watts (W), was calculated from cardiac output and mean arterial blood pressure as previously suggested. Results: In response to reduced LVAD support, resting cardiac power output decreased by 21% (from 0.87 to 0.69 W, p=0.068) as was cardiac output by 13% (from 5.3 to 4.6 l min -1, p=0.141) and mean arterial pressure by 9% (from 74.1 to 67.3 mm Hg, p=0.123). Resting stroke volume decreased by 18% (from 71.4 to 58.2 ml.beat-1, p=0.072) while resting heart rate increased by 5% (from 74 to 79 beats min -1, p=0.126). At peak exercise most of the measured haemodynamic and metabolic variables decreased significantly in response to reduced device support. Cardiac power output decreased by 39% (from 2.31 to 1.40 W, p<0.001), cardiac output by 30% (from 12.2 to 8.6 l min -1,p<0.001), mean arterial pressure by 13% (from 85.4 to 74.3 mm Hg, p=0.006), stroke volume by 24% (from 88.4 to 67.5 ml beats -1, p=0.039) and heart rate by 9% (from 138 to 126 beats min -1, p=0.046). Peak oxygen consumption reduced by 23% (from 18.2 to 14.1 ml kg -1 min -1, p=0.004) whereas exercise time decreased by 18% (from 628 to 516 seconds, p=0.032). Conclusion: The present study suggests that cardiac power output is more sensitive to acute reduction of LVAD support than conventionally measured peak oxygen consumption, and therefore should probably be used in the management of LVAD patients. P2335 Subclinical Ebstein-Barr virus (EBV) infection is frequent in long-term cardiac transplant recipients C.H. Mussner-Seeber 1,M.Frick 1,H.Antretter 2, D. Hoefer 2, G. Weiss 3, G. Poelzl 1. 1 Department of Internal Medicine III - Cardiology, Innsbruck, Austria; 2 Department of Cardiothoracic Surgery, Innsbruck, Austria; 3 Department of Internal Medicine I, Innsbruck, Austria Introduction: Viral infections account for substantial morbidity and mortality in solid organ transplantation. In heart transplant recipients viral infections have been associated with acute rejection, cardiac allograft vasculopathy (CAV), posttransplant lymphoproliferative disease (PTLD), and graft loss. The frequency of subclinical viral infections in the long-term course after heart transplantation (HTX) is unclear. It was the goal of our study to investigate the prevalence of various types of viral infections in stable heart transplant recipients. Patients and methods: From June to December consecutive heart transplant recipients (21% female) were tested for viral infection. All patients were on stable doses of immunosuppression and free from acute infection or rejection for at least 3 months before entry into the study. Mean patient age was 61±11 years (range 23-81). Median time after HTX was 8 years (range 1-24). Patients were tested for cytomegalovirus (CMV), Ebstein-Barr virus (EBV), parvovirus B19 (PV B19), herpes simplex virus (HSV) 1/2, human herpes virus (HHV) 6/8, and hepatitis C using qualitative PCR in peripheral blood. In addition, serologic antibody screening was applied for all the above viruses including hepatitis A and B. Results: Reliable test results were available in 98 patients, of which 30 (30,9%) were tested positive (EBV 26,3%, HSV1/2 2,7%, HHV6 2,6%, HHV8 1,3%, HVC 1,2%). Co-infection with EBV and HSV1/2 was found in one patient. There was no difference between virus-positive and virus-negative patients with regard to age, gender, time after HTX, CMV- and gender-mismatch at time of transplantation, and type of immunosuppression. Of note, no differences were seen either in graft function and laboratory parameters such as ALT, AST, GGT, LDH, leucocytes, lymphocytes, monocytes and haemoglobin. Conclusion: Subclinical EBV infections are unlike other viruses - frequent in stable heart transplant recipients. EBV infections were not correlated with donor a/o recipient related parameters and did not impact on blood count and liver function tests. Since the long-term consequences of subclinical EBV infections are unknown, effectiveness of routine viral testing in heart transplant recipients remains unclear and has to be addressed in a follow-up study. P2336 Effects of left ventricular assist devices on heart rate and Vo2 recovery trends following peak exercise: optimal vs reduced unloading speed G.C. Donovan 1, R.S. George 2, D.J. Jakovljevic 1, D. Nunan 1, R.S. Bougard 2, M.H. Yacoub 3,E.J.Birks 2,D.A.Brodie 1. 1 Buckinghamshire New University, Chalfont St Giles, United Kingdom; 2 Royal Brompton and Harefield NHS Trust, London, United Kingdom; 3 Magdi Yacoub Institute, Heart Science Centre, London, United Kingdom Purpose: This study assessed heart rate and Vo2 recovery trends following peak exercise in patients recently implanted with a left ventricular assist device (LVAD). Methods: Fourteen non-paced patients (2 females) age 35±8 yrs implanted with continuous-flow LVADs (mean duration of support 45±8.5 days), undertook two modified Bruce continuous progressive exercise tests during the same day. The first test took place with the LVAD on optimal unloading speed, pump-on, and the second at a reduced speed where there was minimal contribution from the device into the circulation, pump-down. There were at least four hours rest between the two testing conditions. Heart rate and metabolic measurements were

89 Heart transplantation and left-ventricular assist devices Minimally invasive and robotic surgery 389 continuously recorded. Repeated measures ANOVA and paired t-tests were used to assess individual and group change scores at rest, peak exercise and throughout five minutes of a seated recovery. Delayed heart rate recovery, post peak exercise, was defined as < 18 by minute one, for this recovery position. Results: There was a significant reduction in total exercise time for the pumpdown test, 683±131 vs. 617±151 seconds (p = 0.03), although three patients exercised for longer during the pump-down test. Change scores in heart rate, Vo2, RER, and perceived exertion were similar between tests at rest, during peak exercise, and during the recovery period. Four patients (29%, males) demonstrated a reduced heart rate recovery during the first two minutes (mean 15±1.1 by minute one; 22±1.3 by minute two), in both pump-on and pump-down tests. A further two patients demonstrated a delayed recovery (< 15bmin -1 by minute one) in the pump-down test. A post-exercise rise in Vo2 (3.6±0.7 ml kg -1 min -1 ) during minute one in the pump-down test was observed in four patients (29%, one female). In two of these patients, a smaller increase was also observed in the pump-on test. Interestingly, three of the patients (21%, males) showed a trend towards delayed heart rate and Vo2 recovery in both tests. Conclusion: This study shows that trends in heart rate and Vo2 recovery appear to be similar, despite an acute reduction in LVAD speed. However, withinindividual data suggest that further investigation is warranted in order to assess whether continued LVAD support improves post-exercise heart rate and Vo2 responses in those patients demonstrating a delayed recovery pattern. Purpose: The purpose of the study was to detect predictors of all-cause mortality in heart transplant patients. The influence of basic recipient characteristics as well as different biomarkes and histopathological rejection grades after HTx were investigated. The usefulness of inflammatory or myocyte damage markers as noninvasive method to monitor cellular rejection was examined. Methods: The patients enrolled had mean age of 48,7±12,4 years, the median follow-up was 26 months, in which 397 biopsy specimens were obtained. Troponin T,NT-proBNP,CRP,creatinine,urea and lipid profile were serially determined in 42 de novo and chronic heart transplant recipients at the time of routine endomyocardial biopsy. General patient records prior to HTX were collected, including age, gender, BMI, etiology of heart disease, preexisting diabetes, pulmonary vascular resistance, pulmonary artery pressure, cardiac output, and variables for period after HTx were included, such as hypertension, renal failure, BMI, steroid diabetes, CMV infection, rejection index. Results: NT-proBNP values posttransplant and CRP values 3 months after HTx in comparison between stable and deceased patients (NT-proBNP: vs ,p=0.005; CRP: 37.4 vs. 2.9,p=0.004) correlated significantly with mortality. Renal failure raised the mortality hazard ratio five times. Other variables showed no correlation to mortality. No correlation was found between NT-proBNP, CRP and troponin T values and grade of rejection. Higher NT-proBNP levels, as well as CRP, were observed in early posttransplant period, with declining trend over time. Mortality rate 2 years posttransplant was 18%. Conclusions: NT-proBNP mean values in early and late postransplant period and CRP values in late posttransplant period proved to be significant predictors of allcause mortality. CRP in the first 3 months showed no significance as predictor of survival, probably due to great oscillations associated with frequent infection episodes. Preserving normal renal function correlated with a lower rate of complications and mortality, so the significance of preventing steroid diabetes and strict control of cyclosporin levels and toxicity proved to be of great importance. Our results also implicate that NT-proBNP, CRP and troponin T are not useful markers for monitoring slight or moderate rejection episodes. The levels of NT-proBNP and CRP are highest in the first months with progressively decreasing trend during the first year in stable patients, reaching almost reference values in patients with no complications. P2338 Percutaneous left ventricular assist devices versus intra-aortic balloon pump counterpulsation for treatment of cardiogenic shock: a meta-analysis of controlled trials J.M. Cheng, C.A. Den Uil, S.E. Hoeks, M. Van Der Ent, L.S.D. Jewbali, R.T. Van Domburg, P.W. Serruys. Erasmus MC - Thoraxcenter, Rotterdam, Netherlands Aims: Studies have compared safety and efficacy of percutaneous left ventricular assist devices (LVADs) with intra-aortic balloon pump (IABP) counterpulsation in patients with cardiogenic shock. We performed a meta-analysis of randomized controlled trials to evaluate potential benefits of percutaneous LVAD on hemodynamics and 30-day survival. Methods: In two trials, the TandemHeart was evaluated and, recently, a study on the Impella device was published. Results: After device implantation, LVAD patients had a higher cardiac index (mean difference (MD) 0.35, 95%CI 0.14;0.55), higher mean arterial pressure (MD 13.1, 95%CI 6.3;17.9) and lower pulmonary capillary wedge pressure (MD -5.3, 95%CI -9.4;-1.2) compared to IABP patients. The pooled relative risk estimate revealed no significant difference in 30-day mortality using mechanical support by percutaneous LVAD compared to IABP (RR 1.06, 95% CI 0.68; 1.66). Leg ischemia (p<0.01) and bleeding (p<0.001) were observed more freqently in TandemHeart patients than in IABP patients. P2341 Perioperative asymptomatic troponin release after endovascular abdominal aneurysm repair is associated with poor long-term outcome O. Schouten 1,T.A.Winkel 1, S.E. Hoeks 1, J.P. Van Kuijk 1,W.J.Flu 1, Y.R.B.M. Van Gestel 1,J.J.Bax 2, D. Poldermans 3. 1 Erasmus MC, Rotterdam, Netherlands; 2 Leiden University Medical Center, Leiden, Netherlands; 3 Erasmus, Rotterdam, Netherlands Background: Endovascular abdominal aortic aneurysm (AAA) repair is considered as treatment of choice in high-risk cardiac patients. However, endovascular AAA repair is not associated with long-term survival benefit. The aim of the current study was to assess the impact of perioperative asymptomatic troponin release after endovascular AAA repair on long-term prognosis. Methods: In 228 patients undergoing elective endovascular AAA repair routine sampling of cardiac troponin T (ctnt) and ECG recording was performed on days 1, 3, 7, and at the day of discharge. Elevated ctnt was defined as serum concentrations 0.01 ng/ml. Asymptomatic cardiac damage was defined as ctnt release without chest pain complaints or ECG changes. The median follow-up was 2.9 years and survival status was obtained by contacting the civil service registry. Results: A total of 29/228 patients had ctnt release, median 0.08 ng/ml, of who 24 (83%) were asymptomatic. Patients with asymptomatic ctnt release had an increased mortality rate after 2.9 years as compared to patients without perioperative ctnt release (56% vs 18%, p<0.001, figure). Also after adjustment for clinical risk factors and medication use applying multivariate Cox regression analysis, asymptomatic cardiac damage was associated with a 3.6 fold increased risk for mortality (HR 3.6, 95% CI ) while statin use was associated with a reduced risk for long-term mortality (HR 0.58, 95% CI ). Conclusion: Although percutaneous LVAD provides superior hemodynamic support in patients with cardiogenic shock compared to IABP, the use of these more powerful devices did not improve early survival. Yet, these results do not support the use of percutaneous LVAD as the approach of first choice in the mechanical management of cardiogenic shock. P2340 Predictors of mortality and clinical usefulness of NT-proBNP, troponin T and C-reactive protein in follow-up after heart transplantation D. Milicic, J. Ljubas, B. Skoric, I. Gornik, D. Jelasic, J. Samardzic. University of Zagreb School of Medicine, Zagreb, Croatia Conclusion: Asymptomatic cardiac damage in patients undergoing endovascular AAA repair is associated with poor long-term outcome. Routine perioperative cardiac screening after endovascular AAA repair might be warranted. P2342 Quality of Life Threee Years after MIDCAB versus Isolated RIVA-Stenting M. Breuer, B. Georgii, M. Ferrari. Universitaetsklinikum Jena, Jena, Germany Purpose: Studies regarding long-term follow-up of patients after MIDCAB versus isolated RIVA-stenting, in particular focused on quality of life, are rare. We present the results of a retrospective long-term follow-up in 330 patients comparing health status and quality of life 1 to 7 years after surgical/interventional therapy. Methods: The study was performed in 172 patients (28.5% female) after MID- CAB compared to 158 patients where stent-grafting of the LAD (27.2% female)

90 390 Heart transplantation and left-ventricular assist devices / Non-coronary cardiac interventions was the therapy. After an initial interview by phone postoperative quality of life was examined by short-form 36 questionnaire (SF-36). Mean follow-up was 38 months. MIDCAB group contained n=137 single-vessel (79.7%), n=23 doublevessel (13.4%), n=12 triple-vessel (7.0%) diseases. In the stent-grafted group were n=125 (79.1%) single-vessel, n=23 (14.6%) double-vessel, n=10 (6.3%) triple-vessel diseases. Results: Six of eight subscales were rated remarcably better after MIDCAB. Significantly better estimated was general health perception (p<0.04). Stentgrafted patients showed favourable results in role emotional functionning and mental health. Regarding subgroups with up to 2, 3-4, 5-7 years of follow-up there were no significant differences. Stent grafted patients >80 years showed better results in all eight sub- and summscales, with significant differences in role function and role emotional functionning (p<0.05). MIDCAB-patients <80 had significantly better results in general health perception and standardized physical summscale (p<0.02). Conclusions: Refering long-term results for quality of life, MIDCAB-patients <80 years seem to profit more than stent-grafted patients, in particular for physical reasons. In patients >80 years however quality of life is higher after stent-grafting. P2343 The role of echocardiography parameters in monitoring of patients treated with Transcatheter Heart Valve Implantation procedures (THVI) T. Niklewski, R. Przybylski, K. Wilczek, M. Krason, P. Chodor, P. Nadziakiewicz, S.Z. Pawlak, J. Glowacki, M. Zembala. Slaskie Centrum Chorob Serca, Zabrze, Poland Purpose: Echocardiography is one of the most important tools used for qualification and monitoring of high risk patients (pts.) with severe aortic valve stenosis (AS) for transapical and transfemoral valve implantation procedures (THVI). Precise measurement of aortic valve annulus diameter, severity and symmetry of calcifications, transvalvular gradients, LVOT narrowing, ejection fraction (EF) and aortic valve valve area (AVA), degree of regurgitation (AR) after balloon predilatation, Effective Orifice Area (EOA) of implanted prostheses, cusps opening, gradient and degree of perivalvular leakage are detrimental values assessing correct preprocedural valve selection and optimal placement after implantation. Material and method: Using transoesophageal echocardiography (TEE) our first 9 THVI patients were analyzed (8 females and 1male) with mean age 78,16 years, BSA 1,72m 2, logistic Euro Score and STS Score were 20,56% and 18,7% The mean preoperative EF was 50,5%, aortic valve area (AVA): 0,68cm 2, mean transvalvular gradient 65,9mmHg and mean annulus diameter 22mm In 3 pts. with 20mm we used 23mm and in 4pts with annulus larger than 22mm Edwards SAPIEN 26mm balloons and valves. Two of patients received only percutaneous balloon valvuloplasty because of intraoperative technical contraindications. Results: The intraoperative TEE revealed mean post balloon AV area extension over +0,28 cm 2 to 0,96cm 2 (NS) with mild AR and without significant decrease of transvalvular gradients. After valve implantation mean prosthesis annulus relaxation using the 23 and 26mm prostheses were 20 and 23mm measured in long axis view. We observed only trivial perivalvular leakage in 2 pts. Mean gradient decreased to 12,5mmHg (p=0,0001), EOA increased to 1,47cm 2,(p<0,05) mean EOAindex of all our group was 0,836cm 2 /m 2 (0,73cm 2 /m 2 for 23mm and 1,08cm 2 /m 2 for 26mm prostheses respectively). Mean postprocedural EF was 48,5%. Conclusions: Our echocardiography data shown that despite of significant improvement of mean AVA and decreased transvalvular gradient, implanted valves expanded only to preoperatively measured annular diameter, what may result in moderate patient prosthesis mismatch (0,85-0,60cm 2 /m 2 ), which could influence on left ventricular function and mass reduction in the future. Transcatheter-based balloon dilatation of stenotic, severely concentric calcified aortic valve did not improve the sufficient aortic valve opening in our material. P2344 Endoscopic removal of dislocated atrial septal closure devices and ASD repair T. Schachner, N. Bonaros, D. Wiedemann, S. Mueller, T. Bartel, A. Daburger, O. Pachinger, G. Laufer, J. Bonatti. Innsbruck Medical University, Innsbruck, Austria Purpose: Percutaneous closure of a patent foramen ovale or atrial septum defect is nowadays applied in the majority of the cases with acceptable results. Device displacement or incomplete closure of the interatrial communication may lead to residual shunt, hemolysis and recurrent neurological events. We report on our experience with 5 patients who underwent totally endoscopic removal of an insufficient atrial septal closure device at our institution. Methods: Between March 2003 and January patients (aged 37 (16-60) years, 13 (33%) male) underwent totally endoscopic ASD closure. Out of theses 40 patients between May 2007 and January patients (3 males and 2 females, age: 40 (30-57) years) with a displaced atrial septal closure device (Amplatzer Septal Occluder, or PFO Star Occluder) were referred to our department of cardiac surgery. All patients were operated in a completely endoscopic fashion using the Da Vinci Telemanipulator (Intuitive Surgical, Sunnyvale CA), intraaortic balloon endoocclusion and remote access perfusion via the right femoral vessels. Device removal was performed by means of Endo Catch 15 mm retrieval device Covidien (Norwalk, CT). Results: All 5 procedures were succesfully completed in a totally endoscopic fashion. The Amplatzer Septal Occluder and the PFO Star Occluder were removed in 3 and 2 cases respectively. Median size of the removed devices was 24 (22-26) mm. The entire procedure was completed in 319 ( ) min. Cardiopulmonary bypass time was 167 ( ) min, cross clamp time was 108 (88-169) min. All but one defects were closed using a Dacron patch. There was no patient with a rest shunt in the intraoperative transesophageal echocardiography, no interatrial communication was detected at the echocardiography before discharge. All patients had an uneventful postoperative course and were discharged home on the 5th or 6th postoperative day. No residual shunt was detected in the follow up period of 9 (1-19) months. Conclusions: Removal of a dislocated atrial septal closure device can be successfully performed in a totally endoscopic approach using the robotic system and remote access perfusion with balloon endoocclusion. Operative times are acceptable and intermediate results are not compromized by the endoscopic technique. P2345 NON-CORONARY CARDIAC INTERVENTIONS Transcatheter therapy of tricuspid regurgitation by heterotopic valve implantation: experimental results A. Lauten, M. Ferrari, C. Willich, H. Schubert, S. Bischoff, H.-R. Figulla. Universitaetsklinikum Jena, Jena, Germany Objective: Tricuspid regurgitation (TR) reduces cardiac output (CO) and increases central venous pressure with secondary organ dysfunction, e.g. leading to liver cirrhosis and portal hypertension. To date, the surgical approach is the only option to treat TR. Here we report the first experience of interventional treatment by percutaneous implantation of valved stents into the inferior (IVC) and superior vena cava (SVC) to replace tricuspid valve function in acute insufficiency. Methods: In nine sheep (54-75kg) acute TR grade III-IV was created by papillary muscle and chordae avulsion using a 0.07-inch retrograde wire blade. Successful creation of TR was confirmed by angiography and by a prominent ventricular wave in central venous pressure recording. Two self-expanding nitinol stents containing a porcine pulmonary valve where then implanted in the IVC and SVC in a transcatheter approach. Implantation was performed through the right jugular vein by means of a 21F catheter and guided by fluoroscopy. Hemodynamics where recorded throughout the experiment, valve function was verified by angiography and epicardial echocardiography. Results: TR grade III-IV was successfully created in nine animals and resulted in a reduction of CO from 5.15±1.69/min to 2.9±1.16/min. Right atrial and central venous systolic pressure increased to 12.9±3.14mmHg and 16.2±2.82mmHg, respectively. After deployment of the IVC- and the SVC-valve, systolic venous pressure decreased and cardiac output significantly increased to 4.20±0.84l/min. At autopsy correct device positions where verified in all successfully implanted animals. No macroscopic damage, central venous perforation or thrombus formation was observed by venous stents in the acute model. Conclusion: In high-grade TR implantation of valved stents in central venous position reduces venous regurgitation and improves hemodynamics in the acute experiment. Implantation of one or two valves in central venous position is technically feasable and partially or fully replaces tricuspid valve function in the animal model. These techniques could expand the therapeutic options for patients with relevant TR but high risk for open heart surgery. P2346 Italian patent foramen ovale survey (I.P.O.S.): early results G. Butera 1, G. Sangiorgi 2, A. Aprile 3, G. Ussia 4, I. Spadoni 5, E. Onorato 6, L. Caputi 7,A.Benassi 8,G.Anzola 9, M. Carminati 1 on behalf of IPOS Investigators. 1 policlinico san donato irccs, San Donato Milanese, Italy; 2 department of cardiology- Modena University, Modena, Italy; 3 department of cardiology, Bergamo, Italy; 4 ospedale ferrarotto, Catania, Italy; 5 ospeale apuano, Massa, Italy; 6 department of cardiology, Brescia, Italy; 7 istituto besta, Milan, Italy; 8 hesperia hospital, Modena, Italy; 9 department of neurology, Brescia, Italy Purpose: Percutaneous defect closure is well established in patients with a symptomatic patent foramen ovale (PFO). However, real-word practice derived from large patient populations are lacking. IPOS is a web-based, prospectic, observational, multi-centric real-world registry designed to analyze the current standards of PFO closure in Italy. Aims of the study were: (a) to analyse clinical practice regarding PFO closure; (b) to study indications, devices used, results of percutaneous PFO closure; (c) to evaluate follow-up of large series of patients treated by percutaneous closure. Methods: The survey lasted 12 months. Follow-up evaluations will be recorded yearly up to 5 years after procedure. Between November 2007 and October 2008, 50 centres accepted to participate. One thousand and ninety patients were included in the registry (58% females; median age 45 years (range 5-75 years). The large part of subjects were treated due to a previous history of TIA/Stroke (85% of pts). Fifteen percent of subjects had an associated migraine with aura. Results: Procedures were monitored by using trans-esophageal echocardiography and fluoroscopy in 70% of subjects while 30% were monitored by using intracardiac echocardiography. Procedures were performed under general anesthesia

91 Non-coronary cardiac interventions 391 in 54% and under local anesthesia/conscious sedation in 46%. An aneurysm of the interatrial septum was associated in 41% of patients. Devices used for PFO clusore were PFO/Cribriform Amplatzer devices in 68%, Cardiastar devices in 8%, Starflex/Biostar in 7%, Premere in 11%, Helex in 2%, other in 4%. Early complications occurred in 27 subjects (2.5%): 7 experienced transient atrial fibrillation, 1 had pericardial effusion, 2 needed vascular surgery due to the occurrence of femoral artero-venous fistula, 1 developed blood effusion due to oro-tracheal intubation, in 2 subjects a device was removed due to device malposition, 1 patients needed surgery due to device malposition, other minor complications in 13 subjects. Conclusions: Early results of the IPOS study shows that percutaneous PFO closure is a safe procedure. Long-term Follow-up will be available at the time of the meeting. P2347 Patent foramen ovale closure limits recurrence of cryptogenic stroke: MRI-based long-term follow-up study P. Guerin 1, T. Manigold 1, B. Guillon 2, H. Desal 3, E. Auffray-Calvier 2, J.M. Langlard 4, B. Delasalle 1, R. Fressonnet 1, N. Piriou 1, D. Crochet 1. 1 INSERM, UMR915, l institut du thorax, Nantes, France; 2 CHU Nantes, Service de Neurologie, Nantes, France; 3 CHU Nantes, Service de Neuro-radiologie, Nantes, France; 4 Nantes. L Institut du Thorax, Nantes, France Background and purpose: Patients with cryptogenic stroke and patent foramen ovale (PFO), especially when associated with atrial septal aneurysm (ASA), are at risk of recurrent cerebrovascular events. This study seeks to assess long-term outcome in cryptogenic stroke patients, based on clinical and MRI evaluation, because transient ischemic attacks (TIA) or stroke may be asymptomatic. Method: 72 consecutive patients, under 55 years of age, with ischemic stroke and PFO and associated ASA or large PFO with spontaneous right-to-left shunts, closed percutaneously, were assessed at least one year after closure. Follow-up included cardiac and neurological assessment, contrast transthoracic echocardiography (TTE), contrast transcranial doppler (TCD) and cerebral MRI. Results: Data were available in 71 patients (40.5±9.0 years; sex ratio: 1.5). Percutaneous PFO closure was successful in all patients; ASA was observed in 90.1%. At a mean follow-up of 17.8±8 months, no stroke recurrence was noted, clinically or on MRI. Residual shunt was absent on contrast TTE in 83.8% of cases, and in 65.6% after Valsalva, dropping to 65.2% and 24.6% respectively using TCD, with a majority of small shunts. Final clinical follow-up, at 3.0±1.1 years, found no stroke recurrence. Conclusion: In selected patients, younger than 55 years, PFO closure associated with antithrombotics after a first cryptogenic stroke is safe and prevent symptomatic or silent recurrent cerebral ischemic events, although residual shunt remained. To the best of our knowledge, this is the first study to assess ischemic stroke recurrence from clinical signs and MRI follow-up. MRI was more sensitive in detecting symptomatic or silent stroke. No closure complications were detected over at least one year after the procedure, as described in most studies using these new devices P2348 Cardiac veins and coronary arteries: relevant data for percutaneous indirect annuloplasty R. Del Valle Fernandez, V. Jelnin, G. Panagopoulos, C.E. Ruiz. Lenox Hill Heart and Vascular Institute, New York, United States of America Background: In percutaneous indirect mitral annuloplasty techniques, a cinching device is deployed in the coronary sinus (CS)-great cardiac vein (GCV) in an attempt to indirectly cinch the mitral annulus (MA). Prior reports showed that the coronary arteries may lie between these structures and that coronary flow may therefore be compromised. The aim of this study is to describe the anatomy of the cardiac venous system and its relations to the coronary arteries. Methods: Retrospective analysis of 50 patients (30% males) studied with 64 slices computed tomography angiography for coronary artery evaluation, between January-May, Data was analyzed using SPSS Results: Age was 67±14 years and ejection fraction 60±12%. Left and balanced coronary artery dominance were present in 6% and 4% of the patients (p), respectively. Length of the CS-GCV was ±11.42mm. Maximum vein dimensions were found at the CS ostium, with a progressive decrease in size along the CS/GCV trajectory (p<0.001). There was one CS/GCV-arterial intersection in 14p, two in 23p and three or more intersections in 13p. Mean distances from the CS ostium to the first and second arterial intersections were 83.7±19.8mm and 106.2±17.0mm, respectively. The CS/GCV crossed above an artery at least once in 41 patients (82%) and twice in 19 patients (38%). The artery crossed above was: the left circumflex (LCX) in 39 intersections (proximal LCX in 33, mid in 5 and distal in 1), the 1st and 2nd marginal branches in 4 and 1 intersections, respectively, and the intermediate ramus in 7. In one patient the vein crossed above the proximal left anterior descending artery. Tributary veins: a marginal vein crossed over a coronary artery in 23p and the middle cardiac vein crossed over the posterior descending artery or the posterolateral artery in 31p. Vein anatomy at crux cordis was Von Ludhinghausen type I in 16% and tipe III in 6%. Mean number of posterior veins (PV) was 1.5 and of marginal veins (MV) was Mean distances from the CS ostium to the origin of the PV1, PV2, PV3, MV1, MV2 and MV3 were 18.8±13.0, 25.6±11.5, 45.1±11.2, 62.3±15.1, 74.3±21 and 96.5±24.7mm, respectively. Conclusions: In most patients the CS/GCV crosses over a coronary artery at least once before reaching the interventricular groove and therefore, assessment of the individual anatomy may be worth prior to indirect annuloplasty interventions. Prospective studies analyzing the clinical implications of these findings are essential. P2349 Migraine evolution after percutaneous closure of patent foramen ovale A. Wahl, F. Praz, T. Tai, M. Schwerzmann, S. Windecker, H.P. Mattle, B. Meier. Inselspital Bern, Berne, Switzerland Background: Patent foramen ovale (PFO) has been linked to migraine, and retrospective studies reported an improvement in migraine prevalence and frequency after PFO closure for other reasons. We sought to identify predictors of migraine improvement after PFO closure. Methods: Of 497 patients undergoing PFO closure using the Amplatzer PFO Occluder for secondary prevention of paradoxical embolism, 125 (25%; aged 51±11 years; 57% male) suffered from migraine (63% with aura) according to the criteria of the International Headache Society. Clinical outcome was retrospectively assessed for up to 9 years. We used scales to evaluate the frequency (<1 /month, 1 /month, 2 3 /month, 1 /week, 2 6 /week, 1/day, >1 /day), the duration (<4hr, 4 72 hr, >72 hr), and the intensity (from 0 to 10) of headache episodes. Patients also self-rated the overall improvement or worsening in quartiles. Results: All implantation procedures were successful. There were no device related complications. No patient was lost during 5±2 years of follow-up. At 6 months, complete PFO closure as assessed by contrast TEE was achieved in 91%, whereas a minimal, moderate, or large residual shunt persisted in 6%, 2%, and 1%, respectively. One patient (1%) experienced a recurrent transient ischemic attack 4 years after PFO closure. Following the intervention migraine headaches totally disappeared in 43 patients (34%), and improved by at least 50% in 57 additional patients (46%); 8 patients (6%) reported a decrease of 25%. While headache remained unchanged in 11 patients (9%); 6 patients (5%) experienced worsening headaches. Mean subjective improvement was 74±32%. Overall, mean headache frequency (from 2-3 /month to 1 /month; p<0.001), duration (from 4-72 hr to <4hr; p<0.001), and intensity (from 7±2 to 2±3; p<0.001) improved significantly. There was a significant decrease of any migraine headaches (from 100% to 60%; p<0.001), of migraine with aura (from 63% to 18%; p<0.001), and of the number of patients taking any migraine medication (from 89% to 51%; p<0.001). In the responder group ( 50% improvement) the initial prevalence of migraine with aura was higher (40% vs. 68%; p=0.01). The presence of aura (Odds ratio 5; CI ; p=0.03) and high pain intensity (Odds ratio 1.6; CI ; p=0.02) were both independent predictors of response to treatment. Conclusions: These results suggest that percutaneous PFO closure durably alters the spontaneous course of migraine. Presence of aura and higher pain intensity at baseline are independent predictors of response to closure. P2350 Catheter closure of large atrial septal defects associated with deficient aortic and posterior rims using the greek maneuver B.D.T. Thanopoulos 1, P.D. Dardas 2, N.E. Eleftherakis 1, E.K. Karanasios 1, N.V. Ninios 2. 1 Aghia Sophia Children s Hospital, Athens, Greece; 2 Agios Loukas Hospital, Thessaloniki, Greece Objectives: In patients with large atrial septal defects (ASDs) and deficient aortic and/or posterior rim successful deployment of the Amplatzer septal occluder (ASO) is challenging and several times impossible. In this report we describe a modification of the technique (Greek maneuver) of ASD closure using the ASO to circumvent this problem. Methods and Results: During the last 3 years 65 patients (median age 14.8 years, range 4 to 52 years)with large ASDs and deficient aortic and/or posterior rim underwent catheter closure with the ASO using the Greek maneuver. The Greek maneuver is applied when protrusion of the aortic edge of a deployed (using the standard of ASD closure technique) device in to the right atrium is detected by echo. To circumvent this problem the sheath is advanced into the left atrium where the left disk and 2/3 rds of the right disk are deployed. Then the whole delivery system is pushed inward and leftward gently against the left atrial wall. This trick changes the orientation of the left disk which becomes parallel to the septum preventing protrusion of the device into the right atrium. The ASO was successfully implanted and was associated with complete closure in 62/65 (95.3%) patients. There were no early or late complications related to the procedure. Conclusions: The Greek maneuver is a quite useful trick that works well in preventing the protrusion of the aortic edge of the ASO in patients with large ASDs and deficient aortic and/or posterior rim.

92 392 Non-coronary cardiac interventions P2351 Clinical results of large secundum atrial septal defect closure in adult using percutaneous cocoon atrial septal occluder K. Lairakdomrong, S. Srimahachota, P. Lertsapcharoen, J. Chaipromprasit, S. Boonyaratavej, P. Kaewsukkho. King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand Background: Atrial septal defect (ASD) is a common congenital heart disease in adult. Amplatzer septal occluder is one of the most common devices used for transcatheter closure due to its high success rate and ease to implant. Cocoon atrial septal occluder is a new nitinol-based device, its shape resembles Amplatzer septal occluder but coated with platinum to prevent nickel release. Little is known about clinical results of large ASD closure using Cocoon atrial septal occluder. Objective: To review our experience in closure of secundum ASD in adult by Cocoon septal occluder and to compare the clinical and results of the pts who had ASD closure with the device 30mm and <30 mm. Methods: Between November 2005 and October 2008, 63 consecutive pts underwent transesophageal echocardiography (TEE)-guided transcatheter closure of secundum ASD at our institution. The patients were divided into Group 1 and 2 according to device diameter 30 mm (n=31) and <30 mm (n=32), respectively. Clinical outcomes, complications and transthoracic echocardiography (TTE) before hospital discharge, 1-3 month and 1 year were analyzed. Results: Device implantations were successful in 27 pts (87.1%) in group1 and 32 pts (100%) in group 2 (P=0.053). The maximum size of secundum ASD in group 1 determined by TTE, TEE and balloon sizing diameter (BSD) were 22.6±5.0 mm (range 15-32), 28.1±4.8 mm (range 19-39) and 31±3.5 mm (range 23-38) respectively. The maximum size of secundum ASD in group 2 determined by TTE, TEE and BSD were 19.7±4.4 mm (range 12-31), 20.4±3.4 mm (range 13-26) and 23.1±2.9 mm (range 15-30) respectively. The mean device size in group 1 and 2 were 33.5±3.1 and 24.6±3.3 mm, respectively. Four pts (12.9%) in group 1 had unsuccessful implantation. All of them were in the first 15 cases of using large device ( 30 mm) and two of them had device embolization requiring surgical removal. The patients in both groups were gradually improved in clinical symptoms and decreased in RV systolic pressure and RV size with complete ASD closure at 1 year. Conclusion: Transcatheter closure of large secundum ASD by Cocoon septal occluder is feasible with hemodynamic benefit. However, complication rates are higher with large ASD closed with device size 30 mm especially during the early learning curve period. With experience, the complication rate declines and the success rate is not different from the group with smaller device size. P2352 Long-term outcome of percutaneous balloon mitral valvotomy using multi-track technique in Kenya G. Yonga 1, P. Bonhoeffer 2,C.Jowi 3. 1 Aga Khan University Hospital, Nairobi, Kenya; 2 Great Ormond Street Hospital for Children, London, United Kingdom; 3 University of Nairobi, Nairobi, Kenya Purpose: To determine the outcome of up to ten years of follow-up of patients done percutaneous balloon mitral valvotomy (PBMV) using multitrack technique in Kenya. Method: Prospective and retrospective follow up study of post PBMV utilizing clinic visits, hospital records and telephone calls at three main cardiac catheterization laboratories in Nairobi. 702 patients aged 9-67yrs who underwent PBMV between 1994 and Results: 702 patients have so far been reported to have undergone PBMV by multitrack technique in Kenya. Age range is 9-67yrs. Mean age is yrs. Weights range 18-78kg. Mean echo score Mode NYHA functional class III. Immediate outcome MVA changed from to There was success rate of 97% and mortality rate of 0.5%. A significant proportion of patients was lost to follow up, therefore only 422 (60%) are reported in this study. Restenosis was encountered in 34 (8.1%) patients mostly occurring within 5yrs of PBMV. Immediate MVA outcome <1.8cm 2 and Wilkins score > 10 were significantly associated with Restenosis (95%CI). Event free survival at 3, 5 and 10 years were 94%, 91%, and 80%. Echo score, age, and MVA >1.8cm 2 were predictors of event free survival. The total cost of procedure was average of 1,600/= euros per patient. Conclusions: PBMV by multi-track technique offers our patients with severe mitral stenosis a safe, effective and relatively inexpensive option for therapy. The long term results are good especially amongst those with good post PBMV valve area. Follow up has been a major problem in our set-up but is improving. P2353 Clinical and hemodynamic results in percutaneous mitral valvuloplasty with mitral stenosis and pulmonary hypertension L. Abid, I. Trabelsi, D. Abid, M. Hadrich, R. Hammami, S. Krichene, S. Mallek, F. Triki, M. Hentati, S. Kammoun. cardiology departement of Hedi Cheker Hospital, Sfax, Tunisia Purpose: Percutaneous mitral valvuloplasty (PMV) became the procedure of choice of mitral stenosis with favorable morphology. It is also useful in cases of elevate operative risk, at the aged people and patients with a NYHA class IV or at that with severe pulmonary hypertension. The development of pulmonary hypertension (PH) is a known after- affect at patients with mitral stenosis. However its impact on PMV results at such patients is little described. our objective is to determine the impact of pulmonary hypertension on immediate and long term results of the PMV. Patients and methods: a retrospective study that spreads on 6 years ( ) including all patients undergoing PVM for the first time. Clinical, radiologic, echocardiographic and hemodynamic data of patients have been collected. 72 patients among 289 had PH > 60 (H group), whereas 217 patients had PH < 60 (N group). We compare the immediate and belated results of PVM between the 2 groups. Results: compared to the group without pulmonary hypertension, patients of the H group were younger (28,1 years versus 34,15 years, p<0,05), were presented more often with an acute pulmonary edema (18,6% versus 5% p=0,002), and have more often an echocardiographic wilkin score > 8 (29% versus 19% p=0,05). The mitral area before PVM was 0,8cm 2 against 1,01 cm 2 in the N group (p<0,05). A bad result was noted in 13% of H group against 6% of the N group (p=0,04). Post procedural complications were similar in the 2 groups except for the severe mitral regurgitation which was more often in the H group. The mitral area after PVM was 1,9cm 2 in the N group whereas it was 1,8 cm 2 in the H group (p=0,03). After the PVM, the NYHA class was improved in the 2 groups. During a mean follow up of 92 months, the rate of the cumulative survival was 34% in H group versus 30% in the N group (p=0,03). The NYHA class I or II were met more often in the N group. Conclusion: the PMV is a sure and an efficient procedure even in presence of pulmonary hypertension in spite of the pejorative character that confers the last parameter on the immediate on the long term prognosis. P2354 Safety and efficacy of biostar bioadsorbable atrial septal device for percutaneous patent foramen ovale closure G. Gioffre, M. Iamele, A. Giardina, R. Licitra, S. Rossi, L. Befani, G. Stefanini, G. Pendenza, C. Iani, A. Gaspardone. Divisione di Cardiologia, Ospedale S. Eugenio, Rome, Italy Purpose: The present study was aimed at assessing the feasibility, safety and efficacy of a novel bioadsorbable atrial septal repair device for percutaneous patent foramen ovale (PFO) closure in a single center experience. Methods: Between september 2007-august 2008, 46 consecutive patients (pts) (30 women, mean age 47±11 yrs, range 18-74) underwent percutaneous PFO closure with a bioadsorbable atrial septal repair device. Indications for closure were the presence of significant basal or Valsalva-induced right-to-left atrial shunt at transthoracic echocardiography (TTE) (>grade 1 defined as >10 bubbles during the first 5 cardiac cycles of contrast entering the right atrium) associated with cryptogenic stroke (S, 25 pts), repeated transient ischemic attacks (TIA, 11 pts), severe migraine ( 4 attacks/montly resistant to triple pharmacologic therapy) associated with multiple cerebral ischemic lesions at magnetic resonance imaging (7 pts), decompression illness (2 pts) and platypnea-orthodeoxia syndrome (1 pt). In 6 pts a septal aneurysm (>10 mm excursion) was present. Aspirin 100 mg per day for 6 months and clopidogrel at the dose of 75 mg per day for the 3 months was the standard discharge treatment. Results: The device was successfuly delivered and implanted in all patients. Fluoroscopy time was 5.9±3.5 min. Devise size was 23 mm in 10 pts, 28 mm in 30 pts and 33 in 6 pts. Median hospital stay was 1.6 nights. Four pts had intermittent fever <38 C within 10 days after discharge requiring anti-inflammatory drugs; 5 pts had transient Holter-detected atrial arrhythmias in the first 3 months after discharge and 1 pt only required pharmacological treatment; 4 pts complained atypical transient chest pain within 30 days after discharge. At 9.4±3.8 month follow-up, TTE revealed significant (>grade 1) Valsalva-induced residual shunt in 3 pts (6.5%). No recurrent cerebro-vascular episodes occurred in stroke and TIA pts. Migraine was abolished/improved in 6 pts and unchanged in 1. Conclusions: PFO closure by bioadsorbable device is safe and effective resulting in a high rate of early and complete shunt closure PBMV by Multi-track technique

93 Non-coronary cardiac interventions 393 P2355 Midterm follow-up after percutaneous closure of patent foramen ovale in patients with cerebral ischemia - experience with the Amplatzer PFO Occluder system D. Fischer, A. Schaefer, M. Fuchs, G. Klein, B. Schieffer, G.P. Meyer. Medizinische Hochschule Hannover, Hannover, Germany Background: Prevalence of patent foramen ovale (PFO) with detectable rightto-left shunt is high in patients with TIA/cerebral infarction and is associated with increased risk for recurrent paradoxical thrombembolism. Percutaneous closure represents a promising therapeutic concept since it avoids surgical closure or life-long anticoagulation with coumadin. In our experience, the Starflex occluder system in comination with anticoagulation (coumadin and aspirin) may be associated with an increased prevalence of bleeding complications and thrombus formation on the occluder system. Therefore, this study analysed the midterm follow-up after implantation of Amplatzer occluder with an antithrombotic regimen with clopidogrel and aspirin. Methods and Results: In the present study 114 patients (60 men; age: 47±13 years) with 1 TIA/stroke documented by CCT or MRI were included. All had PFO with significant right to left shunt (Valsalva: >50% of left atrium filled with contrast during TEE) and/or PFO with atrial septum aneurysm, since it has recently been demonstrated that particularly these conditions are associated with increased risk of recurrent stroke. Other sources of embolism were excluded. Implantation of the Amplatzer occluder system was performed under fluoroscopic and TEE guidance PFO-closure was successfull in all patients. Patients were treated for 6 months with an antithrombotic regimen (clopidogrel 75 mg/d and aspirin 100 mg/d). Follow-up included contrast-enriched TEE with Valsalva manoeuvre after 6 and 12 months and a health questionnaire. After a mean TEE follow-up of 10.7 months, PFO was completely closed in 93% of the patients, in 7% a minimal residual shunt was detected. None of the patients showed local thrombus formation on the occluder system. The mean follow-up with the health questionnaire is 17.7±9 months (range 3 to 37), completed in 100% of patients and revealed recurrent neurological symptoms in 5 patients (in these patients, the PFO was completely closed): 1 re-stroke, 2 TIA s and 2 epileptic seizures. One patient suffered from a gastrointestinal bleeding. Conclusion: Percutaneous closure of patent foramen ovale with the Amplatzer occluder system represents a safe and effective therapy for appropriately selected patients to prevent recurrent cerebral ischemic events. Six months of aspirin and clopidogrel prevented the occurrence of thrombi on the occluder. P2356 Atrial septostomy in patients with end-stage pulmonary hypertension. Novel approach to trans-septal puncture R. Baglini. IsMeTT, University of Pittsburgh, Palermo, Italy Purpose: Atrial septostomy in patients with end-stage pulmonary hypertension (PI) is a clinically useful procedure with high intra and periprocedural mortality mainly due to cardiac perforation and tamponade. Aim of this study was to develop a new method of septal perforation in order to reduce the risk of cardiac perforation and mortality during AS. Patients and methods: Five patients (3 males, 2 females, mean age 42,3±12,4 years) with severe, drug resistant PI, NYHA class III/IV and right ventricular failure, were selected to undergo elective atrial septostomy. Pre-procedure echocardiography and cardiac catheterization data were coherent with the clinical assessment. Left atrial dimension was significantly reduced (8,3±2,4 scm) and the interatrial septum was displaced toward the left atrial lateral wall in all patients. After mild sedation, a 9F, 9MHz ICE catheter (Boston Scientific ) was positioned into the right atrium by the left femoral venous route. A 5 F pigtail catheter was inserted through the right femoral artery to the ascending aorta as a mark point. An 8 F Mullins sheath, preloaded with an inner dilator and a 0,018 with a tip equipped by a radiofrequency energy erogator (Bayliss Medical Company )was inserted from the right femoral vein to the right atrium and pointed to the fossa ovalis region on ICE guidance. The Bayliss generator delivers high-voltage continuous radio-frequency energy at a fixed frequency in a high impedance range to create the desired perforation, causing minimal collateral damage to surrounding tissue. Following these steps, after a weight-adjusted heparin iv bolus, a short train of radiofrequency energy at 5 W was erogated during three seconds, to allow the septal perforation. The entire system was then passed through the septum to the left atrium and a balloon septostomy was performed with 5.0 to 10 mm diameter balloons. Results: Procedural immediate success was 100%. No patient developed cardiac tamponade or pericardial effusion. Septal perforation was successful at the first attempt in all patients but one in whom four attempts were needed. Procedure related complications were: a ventricular sustained tachycardia after 30 minutes from the end of the procedure in the fifth patient and a transient cerebral ischemia in the third patient. Closure of the septostomy was shown in the first patient after 20 days and a new septostomy with larger balloons was successfully performed. Conclusion: Radiofrequency perforation of the interatrial septum under ICE guidance seems to be a safe and feasible method for trans-septal catheterization and atrial septostomy in these patients. P2357 Percutaneous closure of large patent ductus arteriosus in adult patients F. Hernandez, J. Garcia-Tejada, M.T. Velazquez, I. Gomez, T. Bastante, L. Unzue, A. Gonzalez, M. De Riva. Hospital 12 de Octubre, Madrid, Spain Percutaneous closure of patent ductus arteriosus (PDA) using occluders and coils is well established. However, closure of very large PDA by surgery or with devices is still a matter of controversy. We describe our experience with percutaneous closure of very large PDA in adult patients using Amplatzer devices. Methods: Ten patients (9 female), mean age 30,6±8 years, with a diagnosis of PDA and left-to-right shunt, underwent right and left cardiac catheterization prior to PDA closure. Anatomical evaluation of PDA was performed with a 90 lateral aortography. Minimal and maximal internal diameters were measured, and size and type of device was chosen according to the anatomy. Results: All 10 patients were successfully treated with Amplatzer devices (eight with the Amplatzer Duct Occluder, two with the Amplatzer Post-MI Ventricular Septal Defect Occluder). Mean diameter of the PDA was 10,4 mm (4-19 mm). Three patients had severe pulmonary hypertension (mean >40 mmhg), that decreased immediately during transient balloon occlusion of the PDA. Echocardiographic follow-up at 9 months showed complete closure in all patients. There were no significant complications related to the procedure, and all patients were discharged after 24 hours. Mean follow-up has been 30±9 months, with no relevant events. PDA patients characteristics n=10 Sex Age PDA size Pulmonary hypertension Device Follow-up Closure (mm) (months) 1 Female 19 8 NO PDA 10/8 55 YES 2 Female 35 9 YES PDA 12/10 51 YES 3 Female YES POST-MI VSD YES 4 Female NO PDA 14/12 45 YES 5 Female 49 8 NO PDA 10/8 32 YES 6 Male NO PDA 14/12 26 YES 7 Female 36 9 NO PDA 10/8 15 YES 8 Female 19 4 NO PDA 6/4 11 YES 9 Female 49 7 NO PDA 10/8 11 YES 10 Female YES POST- MI VSD 18 4 YES Conclusions: Percutaneous closure of very large PDA in adults can be successfully and safely performed with Amplatzer devices. In cases anatomically not amenable for the duct occluder, other devices such as the ventricular septal defect occluder are a good therapeutic alternative. P2358 Transvenous removal of pacing and defibrillating leads using mechanical dilatation: a single center long term experience M.G. Bongiorni, E. Soldati, G. Zucchelli, A. Di Cori, L. Segreti, R. De Lucia, G. Solarino, G. Coluccia. Azienda Ospedaliero - Universitaria Pisana, Pisa, Italy Purpose: Transvenous Pacing (PL) and Defibrillating Lead (DL) extraction is a highly effective technique. Device related complications are currently rising the need of Transvenous Lead Removal (TLR). Aim of this report is to analyse the longstanding experience performed in a single Italian center. Methods: since January 1997 to November 2008, 1365 consecutive patients (1023 men, mean age 65.5 years, range 3-95) with 2413 leads (mean pacing period 68.9 months, range 1-336) were managed. PL were 2101 (1146 ventricular, 843 atrial, 112 coronary sinus leads), DL were 312 (297 ventricular, 2 atrial, 13 superior vena cava leads). Indications to TLR were class I in 33% and class II in 67% of the leads. We performed mechanical dilatation using the Cook Vascular (Leechburg PA, USA) polypropylene sheaths and, if necessary, other intravascular tools (Catchers and Lassos, Osypka, Grentzig-Whylen, G); a Internal Trans- Jugular Approach (ITA) through the internal jugular vein was performed in case of free-floating leads or failure of standard approch. Results: Removal was attempted in 2409 leads because the technique was not applicable in 4 PL (0.2%); 2369 leads (2057 PL, all the 312 DL) were completely removed (98.2%), 20 (0.8%) partially removed, 20 (0.8%) not removed. Among 2329 exposed leads, 353 were removed by manual traction (15.1%), 1754 by mechanical dilatation using the venous entry site (75.3%), 14 by femoral approach (FA) (0.6%) and 168 by ITA (7.2%). All the 80 free-floating leads were completely removed, 23.7% by FA and 76.3% by ITA. Major complications occurred in 8 cases (0.58%): cardiac tamponade (7 cases, 2 deaths), hemotorax (1 death). Conclusions: our experience shows that TLR using mechanical dilation has a high success rate and a low incidence of serious complications in centers provided with wide experience. The use of the ITA allows a very high effectiveness and safety in case of free-floating or difficult exposed leads.

94 394 Non-coronary cardiac interventions / Imaging and intervention in congenital heart disease P2359 Biodegradable magnesium stents in emergency interventions in critically ill babies. First clinical experiences P.A. Zartner 1,M.Sigler 2, D. Schranz 3, M.B.E. Schneider 1. 1 Deutsches Kinderherzzentrum, Sankt Augustin, Germany; 2 Universitätsklinikum, Goettingen, Germany; 3 Universitaetsklinikum Giessen und Marburg GmbH, Giessen, Germany With good early results and superior to balloon dilation only, stents have found its place in interventions in children with a congenital heart disease, but solutions are needed to cover early infancy and the neonatal period. Under compassionate care regulations we implanted absorbable metals stents (AMS, Biotronik, Berlin, Germany) in three patients (bodyweight 1,7 kg, 7 kg, 2 kg) with severe pulmonary vessel obstructions and critical clinical conditions. The AMS was made of an alloy of over 90% of magnesium and some rare earth elements. Projected degradation time was 4 to 8 weeks after implantation; intravascular stability of the stent was 1 to 3 weeks. All stents and the implantation procedures were well tolerated and follow-up was not noticeably influenced by the stent degradation. All three children recovered and could be dismissed home from the hospital. After 4 weeks all stents had lost its stability and gave room to further procedures. One patient died 5 months after implantation due to pneumonia not related to the stent. Autopsy and histopathology revealed a patent vessel at the stented area, with the stent dissolved completely. Biodegradable metals stents offer new strategies in the therapy of congenital heart diseases especially for newborns and small infants. Depending on the implantation site stent diameters of 6 mm and larger are needed. A prolonged degradation time may help to avoid early reintervention. To evaluate the possible domain of biodegradable metal stents in patients with congenital heart diseases is an important challenge to come. P2360 Papillary muscle rupture after percutaneous extraction of pacemaker leads P. Rucinski 1,A.Tomaszewski 1, A. Kutarski 1,B.Malecka 2, A. Zabek 2. 1 Medical University of Lublin, Lublin, Poland; 2 Jagiellonian University, Krakow, Poland Percutaneous leads removal due to cardiac device related infective endocarditis (CDIE) is complex however seems to be safe and effective. Mechanical extraction systems are widely used. Variety of complications and tricuspid valve injury had been described, however no one reported papillary muscle rupture. We performed an analysis of complications of 215 lead extraction procedures looking for tricuspid apparatus injuries. Methods: We analyzed procedures in patients subjected for percutaneous removal of leads with at least one lead was older than 1 year. In 215 patients we extracted 383 leads, (1-6; mean 1,78 per patient). Mean patients age was 64,6 years (5-91), and 29 (69%) were male. The methods of extraction were: extorsion and traction, mechanical (locking stylets, telescopic sheaths) and other mechanical devices (femoral work station, basket, snare, lasso). Transthoracic (TTE) and transespophageal (TEE) echocardiography were performed before and after procedure. Results: Mild to moderate tricuspid regurgitation (TR) was diagnosed in all patients with ventricular lead before and after procedure. In three patients we found new severe TR after extraction. In the first patient round structure connected to chordae and moving between right atrium (in systole) and right ventricle (RV) (in diastole) was observed and was characterized as complete rupture of papillary muscle. In the second patient in place of distal papillary muscle (near free wall of RV) hazy, swollen structure with some chaotic movement in RV (only) was visible and TEE confirmed incomplete. Those two pts had no significant heart failure exacerbation both in short and long term observation what is differentiating form other causes of acute TR. Third patient experienced complete RV papillary muscle rupture but the symptoms were so severe that she was subjected for cardiosurgery. Conclusion: For the first time we described the papillary muscle ruptures as a consequence of lead extraction procedure. This severe complication in some cases may be clinically silent. P2361 Percutaneous leads extraction using mechanical system in 188 patients - single centre experience A. Kutarski 1, B. Malecka 2, P. Rucinski 1, A. Zabek 2. 1 Medical University of Lublin, Lublin, Poland; 2 Jagiellonian University, Krakow, Poland Introduction: The growing problem with pacing system infections and leads excess made the percutaneous lead removal technology widespread. The aim of the study was to analyze efficacy and complications of mechanical percutaneous extraction of pacing and ICD leads in a single reference centre. Methods: In 188 pts (119 male) aged 4-90 years (mean age 64.5), we extracted 342 leads that were at least 12 (PM) or 6 months (ICD) old. Most leads (262) were active and 80 abandoned, 68.9% bipolar, 74.5% passive fixation, 49% - atrial, 48% - RV, 3% LV. Mean age of lead 86±57 months. In 40% of pts. single lead was extracted, 45% - two, 15% - 3 or more (max. 6). The most common indication was local pocket infection (41%); endocarditis (23%) and the necessity to remove abandoned lead (36%). Strategy: mechanical extraction, cardiosurgery in case of failure or complications. Results: Mean procedure time 114 min. Superior approach 95%, femoral 3%, combined 2%. Simple extorsion and traction used in 19.5% cases, mechanical (locking stylets, telescopic sheaths) 76.3%, other mechanical devices (femoral work station, basket, snare, lasso) used in 4,2%. Extraction success rate 98.2%. No peri-operative deaths reported. Complications: 7 pts (cardiac tamponade 2, pulmonary embolism 2, severe tricuspid regurgitation 2, persistent endocarditis requiring cardiosurgery 1). In 3 cases of tearing of extracted lead remained distal part of broken lead was extracted via femoral approach and in 1 case broken distal free part of extracted lead was removed from pulmonary artery via femoral approach using lasso catheter. Conclusions: Percutaneous lead removal using mechanical techniques in experienced centre is safe and has a high success rate. Simple mechanical techniques and subclavian approach are sufficient in most cases and advanced techniques are necessary to complete the procedure in less than 10% of patients. IMAGING AND INTERVENTION IN CONGENITAL HEART DISEASE P2362 High intensity transient signals measured by transcranial Doppler during transcatheter closure of atrial septal defect K. Suda 1,Y.Kudo 1, Y. Tananari 2,S.Itoh 2,H.Ishii 1,H.Nishino 1, M. Iemura 1, Y. Maeno 1, H. Yasunaga 2,T.Matsuishi 2. 1 Kurume University School of Medicine, Kurume, 2 St. Mary s Hospital, Kurume, Japan Purpose: To determine the frequency and nature of high intensity transient signals (HITS) measured by transcranial Doppler (TCD) during transcatheter closure of atrial septal defect (ASD) using Amplatzer septal occluder (ASO). Methods: During closure of ASD in 17 patients, we measured HITS using TCD. Procedure time was divided into 5 periods; Period 1, right heart catheterization; Period 2, left heart catheterization; Periods 3, left heart angiocardiography; Period 4, sizing and long sheath placement; Period 5, device placement and release. We compared HITS among the 5 periods and identified factors that correlated with HITS. Results: Mean patient s age was 19±10 years old and mean size of ASO was 17±5 (10 to 28) mm in diameter. Total number of HITS was 34±28 (3-113). HITS in period 2, 4, and 5 were not significantly different one another but were significantly higher than those in period 1 and 3, (period 2, 11.7±11.2; period 4, 9.3±11.0; period 5, 10.4±12.5 vs. period 1.4±3.6, and period 3, 1.4±1.6 HITS, p<0.05, respectively). Importantly, the time for device manipulation strongly correlated with HITS in period 5 (r=0.83, p<0.0001) and total HITS (r=0.77, p<0.0005). Conclusions: Closure of ASD using ASO produces certain number of microemboli. To decrease the number of microemboli, we have to decrease the time for device manipulation. P2363 Left ventricular twist and untwisting in patients undergoing transcatheter closure of secundum atrial septal defect L.L. Dong, X.H. Shu, D.X. Zhou, L.H. Guan, H.Y. Chen, C.Z. Pan, H.Z. Chen. Zhongshan Hospital of Fudan University, Shanghai, China, People s Republic of Objective: Transcatheter closure of atrial septal defect (ASD) has become a routine procedure. However, no data are available on the impact of overload relief on left ventricular (LV) torsional deformation of ASD. This study sought to evaluate LV twist and untwisting before and early after device closure of ASD using the new speckle tracking imaging (STI) method. Methods: We acquired basal and apical LV short-axis images in 30 patients (29±9 years, 9 males) with normal pulmonary pressure before and 1-day after transcatheter ASD closure (defect diameter 23.7±6.8mm). All data were offline analyzed. LV twist was defined as the difference between LV apical and basal rotation. Results: LV end-diastolic volume (69.6±6.3 ml vs. 62.1±5.0 ml, P = 0.007) and LV ejection fraction (69.3±5.7% vs. 65.9±5.2%, P = 0.007) was increased significantly after successful transcatheter closure of ASD while end-systolic volume was unchanged (22.4±5.0 ml vs. 22.5±4.7 ml, P = NS). After transcatheter ASD closure, there was no significant difference in peak apical rotation and time to the peak (P > 0.05 for both). However, an significantly improved basal rotation was recorded in patients with ASD after the procedure, including significantly increased peak clockwise rotation (-7.1±3.2 vs. -5.4±2.9, P = 0.014), decreased initial counterclockwise rotation (2.0±1.8 vs. 5.1±3.2, P < 0.001) and shortened time to peak clockwise rotation (105.5±16.5% vs ±18.5% of systolic period, P = 0.001). LV twist was significantly improved in patients with ASD after the device closure (16.1±6.7 vs. 12.2±6.3, P = 0.001), whereas there was no significant difference in untwisting rate, time to peak untwisting rate and untwisting during IVRT (all P > 0.05). Conclusions: LV systolic twist could be significantly improved but diastolic untwisting remained unchanged after successful transcatheter closure in patients

95 Imaging and intervention in congenital heart disease 395 with ASD. This improvement was mainly attributed to the improved LV basal rotation rather than the unchanged apical rotation. P2364 Intracardiac ultrasound imaging during percutaneous atrial septal defect or patent foramen ovale closure. Comparison with transesophageal ultrasound findings before the procedure M. Vavouranakis 1, C. Kavouras 1,I.Vlasseros 1, S. Vaina 1, T. Papaioannou 1, E. Sanidas 1, K. Speggos 2,D.Flessas 1, I. Kalikazaros 1, C. Stefanadis 1. 1 Hippokration General Hospital of Athens, Athens, Greece; 2 Areteio General Hospirtal, Athens, Greece Purpose: Transesophageal ultrasound (TEE) has been traditionally used for the diagnosis and guidance of percutaneous atrial septal defect (ASD) and patent foramen ovale (PFO) closure. Intracardiac echocardiography (ICE) has been proposed as an alternative technique to guide these procedures. Methods: In the study we enrolled patients with ASD or PFO. Before the procedure all patients underwent TEE interrogation to image the defect and to study the anatomical characteristics. During closure ICE was performed with an 8Fr ultrasound tipped catheter. After the procedure all patients received aspirin 100 mg for 6 months and clopidogrel 75mg for 3 months. Results: In the study we included in total 65 patients (26 males, mean age 35±4), 40 with ASD (mean Qp/QS ratio: 2.5) and 25 with PFO (20 patients with stroke and 5 with transient ischemic attack). Mean procedural time was 44±23 min. The mean sizes of secundum defects as measured by ICE were larger compared with the respective sizes as measured by TEE (20mm vs. 17.5mm). ICE revealed a chiari network with thrombus in one patient and additional septal defects in two other patients that were not seen by the TEE performed the day of the procedure. Additionally, in 2 patients after microbubbles infusion, ICE showed that there was no PFO present, as it was suggested by TEE imaging. In 63 patients (97%) immediate complete closure was achieved, whereas in two patients a small residual shunt remained. There were no complications observed during or after the procedure. Conclusion: ICE seems to provide superior images of the atrial communications to those obtained by TEE. ICE tends to replace TEE as an imaging tool for ASD and PFO closure, since it can be very useful and more effective imaging technique for detecting details and guiding closure procedures, simultaneously eliminating the need for general anesthesia. P2366 The effect of percutaneous atrial septal defect closure on echocardiographic parameters of the left and right heart O.J. Monfredi, M. Luckie, H. Buckley, B. Clarke, V.S. Mahadevan. Manchester Royal Infirmary, Manchester, United Kingdom Introduction: Percutaneous device closure is an established treatment for secundum atrial septal defects (ASDs), though little is known about its effects on complex echocardiographic parameters. Methods: 26 consecutive patients undergoing percutaneous ASD closure underwent prospective echocardiography at baseline, 24 hours post-, and 6-8 weeks post-closure. Echo parameters were analysed by a single blinded operator. Results: Mean age of the study population was 46 years (±17.8). 69% were female. Mean device size was 27mm (range 11-40mm). Right atrial (RA) area fell by 4.2cm 2 over 8 weeks (p<0.05), whilst mean right ventricular (RV) diameter fell by 0.9cm (p<0.05). RV diastolic and systolic areas also fell by statistically significant amounts. Fractional area change (FRAC) of the RV decreased by a mean of 6.6% on day 1 post-asd closure, and by a total of 11.7% at 8 weeks (p<0.05). Mean RV tricuspid annular plane systolic excursion (TAPSE) decreased by 0.24cm on day 1, and by 0.49cm at 8 weeks (p<0.05). Mean septal mitral annular E/E ratio increased from 12.4 to 16.4 on day 1, and to 20.3 at 8 weeks (p<0.05). Mean lateral mitral annular E/E ratio showed similar statistically significant increases. P2365 Efficacy of percutaneous closure of patent foramen ovale: comparison between three commonly used devices R. Thaman, G. Faganello, M. Nelson, G.V. Szantho, G.R. Gimeno, S. Curtis, R. Martin, M. Turner. Bristol Royal Infirmary, Bristol, United Kingdom Purpose: For patients with stroke due to paradoxical embolus, percutaneous closure of patent foramen ovale (PFO) has become standard therapy with many occluders available. Studies examining the efficacy of the various occluders are lacking. We evaluated short/medium term PFO closure rates of 3 occluders used in a single centre. Methods: One hundred and fifty six adults aged 47±12 (18-81 years) undergoing PFO closure using transoesophageal echocardiography at the Bristol Royal Infirmary, UK were evaluated with transthoracic bubble contrast study before and 6 monthly after PFO closure. The PFO was considered small if <15, moderate if and large if 30 bubbles were counted in the left heart after valsalva. Only large PFO s were included. Results: Indications for PFO closure were: one or more transient ischaemic events/stroke (n=144, 87%), peripheral embolism (n=2, 1%), decompression illness (n=18, 11%) and orthodeoxia (n=2, 1%). Mean balloon PFO size was 8±3.3 (3-17mm), 45 (27%) had septal aneurysm, 29 (17%) had a long tunnel PFO. Three different occluders were used depending on anatomy: Amplatzer (AGA Medical Corporation, Golden Valley, MN) (n=80, 48%), Gore Helex septal occluder (n=48, 29%) and Premere TM (St Jude Medical) septal occluder (n=38, 23%). Complications occurred in 4 (2.4%) patients: pseudo aneurysm (n=1), arteriovenous fistula (n=1) and transient supraventricular tachycardia (n=2). One (0.6%) transient neurological event was recorded during follow up. At 6 months residual right to left shunting ( moderate) was highest in the Helex group [58.3% ( large 45.8%, moderate 12.5%], and lower for Premere [39.5% ( large 23.7%, moderate 15.8%)] and Amplatzer [32.5% ( large 17.5%, moderate 15%)]. Similarly at final follow up residual shunting remained higher in the Helex group [33.3% ( large 25%, moderate 8.3%)], compared to Premere [18.5% ( large13.2%, moderate 5.3%)] and Amplatzer [11% ( large7.5%, moderate 3.5%)]. The Amplatzer was associated with a significantly lower residual shunt rate compared to the Helex (p<0.05 for 6 months and final follow up). The Premere had intermediate residual shunt rate but was not significant in our sample. Multivariate predictors for residual shunts showed included the type of device (p<0.05 for amplatzer vs Helex) and septal aneurysm (RR 0.04, 95% CI ). Conclusions: PFO closure is a safe and efficacious treatment. PFO closure is progressive however closure rates depend on the device and presence of septal aneurysm. Echo changes post-closure Conclusions: The study confirmed that RV remodeling occurs following ASD closure. It demonstrates for the first time that certain echocardiographic effects are evident as early as the first post-procedural day. These effects are presumably related to decreases in RV volume loading consequent on ASD closure, and continue to at least 8 weeks post-closure. Further studies are in progress to elucidate whether certain pre-closure parameters can accurately predict favourable RV remodeling following ASD device closure. P2367 Results of transcatheter closure of unroofed coronary sinus defect J.-K. Wang, M.H. Wu. National Taiwan University Hospital, Taipei, Taiwan Purpose: Unroofed coronary sinus (CS) allows communication between left atrium and CS through the fenestration, resulting in increased pulmonary blood flow. We present the results of transcatheter closure of unroofed CS with Amplatzer septal occluder. Methods: Between January 2004 and May 2008, 9 patients (5 males and 4 females) with ages ranging from 26 to 65 years (median 39 years) underwent attempted transcatheter closure of unroofed CS defect. The procedure was performed under general anesthesia and transesophageal echocardiographic monitoring. Balloon sizing was performed in 8. The device size selected was within 2 mm larger than balloon sizing diameter. In the remaining 1 without balloon sizing, the device diameter selected was 6 mm larger than maximal diameter of CS ostium measured with transesophageal echocardiography. Results: No one had a persistent left superior vena cava. The mean Qp/Qs ratio is 2.4±1 and mean systolic pulmonary artery pressure was 35±19 mmhg. An Amplatzer septal occluder was deployed in all 9 patients of whom a device was deployed in the defect in 1 and at the CS ostium in 8. Four patients required 1-2 size larger devices to achieve success because of repeated pull through of the initially selected device. The mean device size used was 21±3.6 (16 28) mm. One patient in whom the device was deployed in the defect developed herniation of the left disk resulting in mild-to-moderate residual shunt. All patients were available for 3-month follow-up. No one had a residual shunt on the 3-month follow-up echocardiography. One patient who had uremia, hypertension and a history of laryngeal cancer died of a stroke 4.5 months after the procedure. Following a mean follow-up period of 31±15 months, symptomatic improvement was documented in the remaining 8 patients.

96 396 Imaging and intervention in congenital heart disease Conclusion: Transcatheter closure of unroofed CS defect in patients without a persistent left superior vena cava with Amplatzer septal occluder is safe and feasible. P2368 The effect of interatrial septal defect closure on migraine burden, five year single centre experience K.N. Asrress, O. Ormerod, N. Wilson, A.R.J. Mitchell. John Radcliffe Hospital, Oxford, United Kingdom Purpose: In patients with interatrial septal defect, in the form of patent foramen ovale (PFO) and atrial septal defects (ASD), the prevalence of migraine with aura is higher than the general population. This has led to the postulation that the presence of a shunt has a causal relationship with migraine, though there is no conclusive evidence that closure has an effect on migraine burden. We set out to prospectively assess the impact of interatrial device closure on migraine burden, in patients with migraine with aura. Methods: Data on all patients undergoing percutaneous PFO or ASD closure where there was also a prior diagnosis of migraine with aura was collected prospectively between 2003 and All patients were followed up at three months where they underwent transthoracic echocardiography to check for residual interatrial shunts. At follow up they were asked if there had been an impact on their migraine headaches. Responses were recorded and analysed. Results: 210 consecutive patients with PFO or ASD underwent percutaneous interatrial defect closure over the study period, of which 25 (12%) had a prior diagnosis of migraine with aura. Amongst patients with migraine with aura 21 (84%) were female. Mean age 40.2±10.2 years. Primary indication for device closure was cryptogenic stroke (28%), transient ischaemic attack not thought to be migrainous in origin (16%), systemic embolism (13%), decompression illness (8%) and dyspnoea (4%). In 32% severe migraine with aura was the primary indication for device closure. At three months follow up 20% of patients reported complete resolution of their migraine headaches, 44% reported improvement but not resolution in symptoms, 16% had no change and 20% had worsening of their symptoms. Therefore 16 (64%) had improved symptoms and 9 (36%) had no change or worsening symptoms (p<0.005). All 25 patients had well positioned devices with no evidence of a residual shunt at three months follow-up. Conclusions: Percutaneous closure of interatrial septal defects resulted in significant improvement in migraine burden three months post procedure, even in patients where the primary indication for closure was not migraine. Many patients in both groups reported an increase in migraine burden immediately post procedure, but this had improved in the majority by three months. This rebound phenomenon has been previously reported, and may reflect the presence of the device itself. At three months the device would have largely endothelialised coinciding with the improvement in symptoms. Despite the limitations of this small series, the results support ongoing trials. P2369 Usefulness of 64-slice cardiac computed tomography in the assessment of atrial septal defects in patients undergoing percutaneous occlusion S. Ojeda 1,M.PanAlvarez-Osorio 1,M.Romero 1, J. Suarez De Lezo 1, S. Espejo 1,R.Isamat 1,D.Mesa 1,D.Garcia 1, L. Burgos 2, A. Medina 2. 1 Hospital Universitario Reina Sofia, Cordoba, Spain; 2 Hospital Universitario Dr Negrin, Las Palmas De Gran Canaria, Spain During percutaneous closure of atrial septal defects (ASD) implantation failure may occur. We assess the usefulness of 64-slice computed tomography (CT) in patients with ASD submitted for cardiac catheterization and percutaneous closure of the defect. Methods: From June-93 to January-09, 297 patients with ASD were treated percutaneously at our center. Since March-08, 24 consecutive adult patients with ASD were evaluated by echocardiogram and CT before catheterization; 7 of them were referred to surgery due to unsuitable anatomy. The remaining 17 underwent catheterization with transesophageal echocardiographic (TEE) monitoring for percutaneous closure of the defect. Multiplanar reformation of the CT images were done using the same views as in the TEE (retroaortic, 4-chamber and caves projections). In all 3 views we assessed the entire atrial septum obtaining images at 1.5 mm intervals ( septal views per patient). We selected the size of the device according to the maximum ASD diameter on any plane and the minimum dimension of the interatrial septum, as measured by CT. No Balloon sizing of the defect was performed. Additional angiography (pulmonary and coronary) was avoided with CT information. Table 1 TEE (mm) CT (mm) r p< Posterior rim 12.05± ± AV rim 12.8± ± Inferior Cave rim 19±8 21± Superior Cave rim 19±7 14± Retroaortic rim 7.29± ± Superior rim 12.1±7.2 14± ASD Caves 13±4 20± ASD Retroaortic 17.7± ± ASD 4C 18.3± ± AV: Atrioventricular. Results: Amplatzer ASD occluders were used in all patients. Size was decided before catheterization. Primary success was obtained in all 17 patients. Correlations between TEE and CT measurements are summarized in table. Conclusion: Multiplane evaluation of the interatrial septum allows an accurate selection of occluder diameter and avoids the use of balloon sizing techniques and additional angiograms, simplifying the procedure. P2370 The influence of atrial septal defect percutaneous device on left ventricular mechanics: a bidimensional strain study B. Castaldi, F. Fratta, G. Di Salvo, G. Santoro, G. Gaio, C. Iacono, L. Baldini, G. Pacileo, M.G. Russo, R. Calabro. Ospedale Vincenzo Monaldi, Naples, Italy Atrial septal defect is one of the most frequent congenital heart disease. Today the percutaneous closure is feasible in the large majority of cases. Previous studies suggest that the imposition of a device could alter the longitudinal function of the left ventricular septum. The purpose of this study was to evaluate the mid-term effect of atrial septal occluder device on left ventricular mechanics in pediatric patients using 2D strain imaging. 70 subjects (aged 6 to 16 years) were studied: 35 patients 11±10 months after percutaneous closure of atrial septal defect and 35 healthy volunteers (CTRL) matched for age (mean age 9.7±3.5 vs 9.3±3.3 years), and BSA. In all subjects standard echocardiography was performed. Residual interatrial shunt and other cardiac abnormalities were excluded. Standard projections were acquired and stored for 2D strain off-line analysis. The analysis was performed with a dedicated software (Echopac PC 08). Of the 35 studied patients 25 had an Amplatzer Septal Occluder, 8 a Solysafe device and 2 a Helex device. Standard echocardiography failed to show any significant difference in left chamber volume and function between patients and CTRL (interventricular septum in diastole: 6.9±1.0 mm vs 7±1.0 mm; left ventricular diastolic dimension: 42.34±4.8 mm vs 42.0±6.0 mm; EF: 65±4% vs 65±4%; left atrial width 31.6±3.2 mm vs 30.5±5.0 mm; E/A: 1.89±0.4 vs 1.80±0.3; DecT 155±30 ms vs 151±15 ms; E/E 5.8±1.0 vs 5.5±1.0, respectively; p= ns for all data). Speckle tracking analysis showed a significant reduction in the mean basal circumferential strain (S) (-18.3±3% vs -23.3±4% p< ), strain rate (SR) (1.6±0.3 1/s vs -2.0±0.3 1/s; p=0.0002) and left ventricular torsion (10.5±4.2 vs 14.5±4.5 ; p=0.005) in ASD-treated group compared to CTRL. Conversely, radial SR values were reduced only in basal septal and basal antero-septal segments (1.84±0.57 1/svs2.33±0.68 1/s p=0.01 and 1.63±0.54 vs 2.09±0.67 1/s; p=0.01, respectively) in treated group, as was the longitudinal S of the basal septum (-17.8% vs -20.2%; p=0.003). However, the global longitudinal S was similar to CTRL (- 20.7±1.4% vs -21.2±1.4%; p=0.4). Not significant difference in longitudinal, radial and circumferential S and SR as well as in left ventricular torsion was found in the treated group according to the used device. In conlcusion percutaneous closure with atrial septal device causes abnormalities of the left ventricular mechanics. These abnormalities seems not to be related with the type of the device but probably they could be related to the device size. We need more patients to evaluate it. P2371 The safty and efficacy of transcatheter closure of perimembranous ventricular septal defect B. Han, L. Zhao, J. Zhang, Y. Wang, Y. Jin, Y. Yi. Provincial Hospital affiliated to Shandong University, Jinan, China, People s Republic of Purpose: We sought to evaluate the safety, efficacy, and followup results of transcatheter closure of perimembranous ventricular septal defect (pmvsd). Methods: During January 2005-January 2009, 118 patients underwent transcatheter closure of pmvsd in our Hospital. The mean age at closure was 9 years (range 2 to 31 years). Echocardiography and Electrocardiography were conducted at 1, 3, 6, and 12 months, and every year after VSD closure. The median follow-up time was 26 months (range 1 to 48 months). Results: 111 cases underwent transcatheter closure successfully (94.9%). 19 cases used eccentric VSD device and 92 cases used concentric VSD device. A total of 18 cases early complications occured (16.2%). 9 cases suffered from heart block after closure including 2 cases with complete right bundle branch block (CRBBB), 1 case with incomplete right bundle branch block (ICRBBB) and 6 cases with accelerated junctional tachycardia (AJT) and all of them recovered after 1 week to 3 months. 2 of 4 cases with residual shunt had mechanical hemolysis and resolved 3 days later after conservative therapy. Mild aortic valve regurgitation occurred in 2 cases and mild tricuspid regurgitation occurred in 3 cases. Conclusions: Transcatheter closure of pmvsd is safe and efficacious in excellent successful rate. Severe complications is rare. Heart block are the main complications after occlusion of pmvsd and recovered completely. The key point is selecting patients under strict indications.

97 Imaging and intervention in congenital heart disease 397 P2372 Transcatheter closure of the patent ductus arteriosus using the amplatzer duct occluder in symptomatic infants with low weight F. Godart, C. Francart, I. Bouzguenda, A. Richard, C. Rey. Hopital Cardiologique CHRU de Lille, Lille, France Purpose: Transcatheter closure of patent ductus arteriosus (PDA) using the Amplatzer duct occluder (ADO) is an effective treatment and a true alternative to surgical closure. However, closure of PDA in children with low weight remains a real challenge for the interventionist. Methods: From April 1999 to February 2009, 203 patients underwent percutaneous PDA closure. We focus here on the 17 infants weighing 6kgandin whom duct was closed using the ADO. All patients were symptomatic and indications included failure to thrive and/or shortness of breath and/or frequent respiratory infections. There were 15 females and 2 males; the mean age was 5.1±4 months, and the mean weight was 4.6±0.9 (range 2.8 to 6 kg). The procedure was realized under local anaesthesia (n = 14) and general anaesthesia (n = 3). In 5 of the 17 pts, implantation was performed from a sole venous femoral access without arterial puncture, and device release was controlled by transthoracic echocardiography. Size of the duct was 3.6±1.3 mm (range 1.7 to 6 mm) and systolic pulmonary artery pressure was 54±19 mm Hg (range 26 to 96 mm Hg). Implantation succeeded in all but one without any complication. Closure was realized by six 5/4 mm ADO, five 6/4 mm ADO, five 8/6 mm ADO, and one 10/8 mm ADO. One patient with failed procedure underwent subsequently surgical closure of the duct. During follow-up (0 to 58 months), Doppler echocardiography showed decrease in ductal residual shunt: complete occlusion was noticed in 5 pts at day one, 10 pts at one month, 14 pts at 3 months, and 16 pts at one year after implantation. No patient but one had persistent pulmonary hypertension and only one had a moderate stenosis on the left pulmonary artery due to device protrusion. One patient died 15 months after implantation from non cardiac related cause. Conclusions: In experienced hands, percutaneous closure of large PDA in symptomatic infants weighing 6 kg is safe, effective, and solves clinical problems. It offers a real alternative to the classic surgical treatment. P2373 Transcatheter closure of patent ductus arteriosus using the new Amplatzer duct occluder (ADO II). 1-year experience B.D.T. Thanopoulos, N.G.E. Elefterakis, S.L. Loukopoulou. Aghia Sophia Children s Hospital, Athens, Greece Objectives: The aim of this study was to report 1-year experience with 51 patients who underwent attempted transcatheter closure of a patent ductus arteriosus (PDA) using the new Amplatzer duct occluder (ADO II). Methods: The mean age of the patients was 7.5±7.8 years (range 0.3 to 45 years). The device is a modified Amplatzer duct occluder made of fabric-free fine Nitinol wire net in to 2 very low profile disks with an articulated connecting waist. Both disks are 6 mm larger than the diameter of the connecting waist. Connecting waist diameters and device lengths range from 3-6 mm and 4-6 mm, respectively. The ADO II is appropriate for closure of very small to moderate- large (up to 5.5 mm) PDAs of any morphological type. Results: The mean PDA diameter was 3.5±1.6 mm (range, 0.5 to 5.5 mm). The mean device diameter (waist diameter) was 4.2±1.3 mm (range 3 to 6 mm). The device was permanently implanted in 49 patients. Complete angiographic closure was observed in 47/49 (96%) patients. At 24 hours color Doppler flow imaging revealed complete closure in 48/49 (98%) patients. Major complications included device embolization and significant hemodynamic obstruction of the descending aorta in one patient, respectively. No other complications were observed. Conclusions: The ADO II is a highly effective prosthesis that can be safely applied in most patients with small to moderate-large PDA of any anatomical type. Further studies are required to establish long-term results in a larger patient population. P2374 Ductal stenting for duct-dependent pulmonary circulation: a multi-center experience N. Sreeram 1,H.Hamza 2, H. Agha 2,V.Kohli 3,M.Emmel 1, G. Bennink 1. 1 University Hospital, Cologne, Germany; 2 University Children s Hospital, Cairo, Egypt; 3 Apollo Hospital, New Delhi, India Background and Aims: Ductal stenting in neonates with pulmonary atresiavariants can potentially avoid the need for a surgical shunt. We report a multicenter experience with this therapeutic approach. Patients and Methods: 31 consecutive infants (17 female) from 3 centers, who were catheterised on an intention-to-treat are presented. They ranged in age from 3 to 120 days and in weight from 2.2 to 4.0 kg. The ductal morphology was horizontal and straight (n=22), tortuous (n=5), and vertical (n=4). Stenting was performed as an adjunct to RF perforation of the pulmonary valve in 16 patients. Prostaglandin E therapy was discontinued 6 hours prior to the procedure in 23 infants. Results: In 6 patients a stent was not implanted for the following reasons: failure to enter the duct (n=4), tortuous duct with concomitant stenosis of a branch PA (n=2). in the remainder, stents ranging from 3.5 to 4.5mm in diameter of varying lengths were implanted (retrogradely in 14, anterogradely in 11; 2 stents in series in 2). The procedure was uncomplicated in all; 1 infant in whom the initial stent did not cover the entire duct required a second ductal stent 3 days later. Following stent implantation, the systemic oxygen saturation at rest ranged from 75% to 88%. The duration of hospital stay ranged from 1 to 66 days. Patients were discharged from hospital taking aspirin 5mg/kg/day. Conclusions: Despite a learning curve, ductal stenting is relatively straightforward and provides adequate medium-term palliation. It is of particular relevance in centers with limited surgical backup. P2375 Percutaneous Closure of Hypertensive Ductus Arteriosus C. Zabal, J.A. Garcia Montes, A. Buendia, J. Calderon Colmenero, E. Patino Bahena, A. Juanico, F. Attie. National Institute of Cardiology Ignacio Chavez, Mexico City, Mexico Background: The Amplatzer duct occluder (ADO) has been used with success to close large patent ductus arteriosus (PDA), but some problems exist specially with hypertensive PDAs, such as incomplete closure, hemolysis, left pulmonary artery stenosis, obstruction of the descending aorta, and progressive pulmonary vascular disease. Methods and results: We analyze a group of 168 patients with isolated PDA and pulmonary artery systolic pressure (PSAP) 50 mmhg. Mean age was 10.3±14.3 years, PDA diameter was 6.4±2.9 mm, PASP was 63.5±16.2 mmhg, and Qp/Qs was 2.7±1.2. We used ADOs in 145 (86.3%) cases, Amplatzer muscular ventricular septal defect occluders (AMVSDO) in 18 (10.7%), Amplatzer septal occluders (ASO) in 3 (1.8%), and the Gianturco-Grifka device in 2 (1.2%) cases. Device diameter was 106.3±51% higher than PDA diameter. PASP decreased after occlusion to 42.5±13.3 mmhg (p< ). Immediately after closure, no or trivial shunt was present in 123 (74.5%) cases. Immediate complications were device embolization in five (3%) cases, and descending aortic obstruction in one case. The overall success rate was 98.2%. Follow-up in 145 (86.3%) cases for 37.1±24 months showed further decrease of the PASP to 30.1±7.7 mmhg (p<0.0001). Angio images of a hypertensive PDA Conclusions: Percutaneous treatment of hypertensive PDA is safe and effective. ADO works well for most cases, but sometimes other devices (MVSDO or ASO) have to be used. When cases are selected adequately, pulmonary pressures decrease immediately, and continue to fall with time. P2376 Echocardiographic determinants of successful balloon dilation in pulmonary atresia with intact ventricular septum A. Drighil 1,M.AlJufan 2,A.Slimi 2, S. Yamani 2. 1 Ibn Rochd university hospital, Casablanca, Morocco; 2 King faisal specialist hospital and research center, Riyadh, Saudi Arabia Pulmonary atresia with intact ventricular septum (PA-IVS) is a complex congenital heart malformation with multitude therapeutic approaches. Recently, balloon valvotomy has been used as an alternative to primary surgery. This study aimed to identify echocardiographic markers of balloon dilation success in PA-IVS. The echocardiograms of 26 patients diagnosed with PA-IVS who underwent primary pulmonary balloon valvotomy were reviewed. Tricuspid annulus Z score, pulmonary annulus Z score, right ventricular (RV) to left ventricular (LV) length ratio, RV to LV transverse diameter ratio and tricuspid valve (TV) to mitral valve (MV) annulus diameter ratio were measured. The tricuspid Z score, pulmonary Z score, RV/LV lenght ratio, RV/LV diameter ratio, and the TV/MV ratio were significantly different in the group which had successful balloon dilatation compared to the that failed. Based on decision trees using the Weka classifier package, only RV/LV diameter ratio > 0.76 predicts a 92.3% success rate. In contrast an RV/LV diameter ratio 0.76 associated with RV/LV lenght ratio 0.70 predicts 100% failure. In conclusion, successful balloon dilation in membranous type PA-IVS can be predicted by a scoring system using RV/LV diameter ratio and RV/LV length ratio.

98 398 Imaging and intervention in congenital heart disease P2377 covered stents for moderate-severe native aortic coarctation S. Abadir 1,S.Noble 2, G. Sarquella-Brugada 1, R. Ibrahim 2, N. Dahdah 1,J.Miro 1. 1 Hospital Sainte Justine, Montreal, Canada; 2 Montreal Heart Institute, Montréal, Canada Background: Covered stents (CS) have been suggested as an alternative to bare stents to decrease aortic complications in moderate-severe native coarctation (CoA). Methods: We retrospectively reviewed our 18 patients (26.7±14.6 yo; 12 to 58) who underwent CS implantation since 2003 (Cheatham-Platinium stent, 8 zig, length 22 to 45mm) for moderate-severe native CoA. Results: Preimplantation systolic blood pressure was 147.9±17.5 mmhg, with mean pressure gradient of 63.3 mmhg (41 to 103). 11/16 hypertensive patients were under medication, 8/11 had at least 2 medications. Significant collaterals were present in 15/18 patients. All attempts were successful. Lesion diameter/aortic diameter at diaphragm increased from 20.7%±11.0% to 90.2%±15.8%. Invasive gradient (under general anesthesia) decreased from 33.4±11.1 to 1.4±2.8 mmhg. One major complication occurred (mild cerebrovascular ischemic event in a 46.9 yo). Sub-clavian artery was partially jailed in 4/18, with none losing radial pulse. 4 patients had almost atretic lesion (< 1 mm), one needing radiofrequency perforation for acquired interruption. During follow up (mean 15.8 mo, 1 to 49.5), 13 patients have already undergone non invasive imaging, with one demonstrating a small (6 mm) aneurysm. No stent fracture was observed. Three of our 8 teenager patients underwent further dilatation to accommodate aortic growth. Normal blood pressure was obtained in 8/16 previously hypertensive patients. Only one patient has blood pressure gradient >20 mmhg, due to aortic arch hypoplasia. Conclusion: CS implantation is safe in moderate-severe native CoA, and provides excellent transcoarctation gradient relief. These results compare favorably to our previously reported experience with balloon dilatation and bare stents implantation in native CoA. P2378 Stent implantation for the treatment of aortic coarctation in children: Initial and five-year results N.G.E. Elefterakis, S.L. Loukopoulou, E.S.K. Karanasios, B.D.T. Thanopoulos. Aghia Sophia Children s Hospital, Athens, Greece Objectives: Long follow-up data following stent implantation (SI) for the treatment of coarctation of the aorta (CoA) in children are limited. This study reports initial and 5-year results following SI in children with CoA. Methods and Results: Fifty-four patients with CoA underwent SI (median age 9.2 years, range 7 14 years); 26 patients were treated for isolated native CoA and 28 for recurrent CoA. 60 stents were implanted. Palmaz 4014 stents were placed in 26 patients and Palmaz 308 in 28 patients. Excluded from the study were patients with significant hypoplasia of the distal aortic arch or aortic isthmus proximal to the CoA as well as those with complex CoA. Elective re-dilation of a previously implanted stent was performed in 28 patients. Immediately after SI the peak systolic pressure gradient (mean (SD)) fell from 60 (±17) mm Hg to 8.5 (±4.8) mm Hg (p< 0.05). The diameter of the CoA increased from 5.6 (±2.6) mm to 16.4 (±2.8) mm (p< 0.05). The most important procedural complications were proximal stent migration and stent fracture (after redilation) in 1 and 3 patients, respectively. There were no deaths, no evidence of aneurysm formation or any other complications related to SI throughout the follow-up period. At the 5-year follow-up no cases of recoarctation were identified on angiography, multislice CT, or MRI. In 91% (49/54) of the patients antihypertensive medication was either decreased or discontinued. Conclusions: SI is an effective and safe alternative to conventional surgical management for the treatment of selected children with CoA. P2379 Aortic valvuloplasty in children: impact of rapid ventricular pacing G. Sarquella Brugada 1, S. Abadir 1, J. Rodes Cabau 2, C. Houde 2, A. Dancea 3, N. Dahdah 1,J.Miro 1. 1 Hospital Sainte Justine, Montreal, Canada; 2 CHUL, Quebec, Canada; 3 McGill University, Montreal, Canada Introduction: Ventricular pacing for balloon stabilization in aortic valvuloplasty is increasingly used. We sought to evaluate its safety and benefits in a children population. Methods: Retrospective review of ten year experience in three pediatric centers. Control group was obtained based on age of patients and catheterizer in a match proportion of 2 non-paced to 1 paced procedure. Results: Overall, 140 procedures were performed in 130 patients with mean follow-up time of 32,07±34,98 months. There was male predominance (68,3%) with mean age of 5,6±6,97 years, and mean weight of 24,24±26,68 kg at procedure. Ventricular pacing has been used in 23 aortic valvuloplasties (16,4%) since Paced patients and control group were similar for procedure duration, radiation time and final gradient relief measured by echocardiography and catheterization. Non-paced procedures were much more associated with multiple (>3) balloon inflations (41,3% vs. 4,34%, X2 10,174 p=0,001), significant increase of aortic regurgitation at 1 year (28,2% vs. 4,34%, X2 5,42 p=0,017) and at last follow-up (30,4% vs. 4,34%, X2 6,133 p=0,011). Non-paced procedures were associated with a higher risk of reintervention (23,9% vs. 4,34%, X2 4,086 p=0,039). There was no difference in arrhythmia inducibilityduetoventricularpacing (13,4% vs. 8,69%, X2 0,87 p=0,7). Conclusion: Rapid ventricular pacing for aortic valvuloplasty does not increase the risk of arrhythmias, simplifies the procedure and is associated with lower rates of reintervention possibly by diminishing the number of balloon inflations needed. P2380 Japan Three-dimensional diagnosis of pulmonary-ductus descending aorta trunk in hypoplastic left heart syndrome and interrupted aortic arch with multi-slice CT for stent implantation I. Shiraishi Isao. National Cardiovascular Center, Suita, Osaka, Backgrounds: Recently, a combination therapy with pulmonary artery banding and stent implantation for patent ductus descending aorta-trunk (PDDT) has been approved as an initial interventional strategy of hypoplastic left heart syndrome (HLHS). However, it is hard to understand the precise 3-dimensional structure of PDDT by using conventional two-dimensional images with echocardiography and angiography because PDDT is sometimes bulge and tortuous. In this study, we evaluated the structure of PDDT in HLHS and IAA patients by using 3-D images with multi-slice (MS) CT. Patients and Method: We evaluated the shape and angle of the ascending aorta, main pulmonary artery, PDDT, anddescending aorta of neonatal patients with HLHS (n=13) and IAA (n=13) by using 64 detector-row MSCT. Results: The shape of PDDT in HLHS patients is divided into two groups, i.e., bulge (+) (n=7, angle between PDDT and descending aorta>20 degree) and bulge (-) groups (n=6, angle <20 degree). PDDT tilted to the left side of the body in 32.1±14.7 and 2.50±4.18 degree in bulge (+) and ( ) groups, respectively (p<0.05). The average angle of PDDT in the HLHS patients was 16.2±20.9 degree. In IAA patients, PDDT was bulged in only one of the 13 patients. Consequently, PDDT titled to the left side of the body in 1.54±5.5 degree (p<0.05 compared with HLHS). We also measured the angle of the ascending aorta, which showed that the ascending aorta tilted to the right side of the body in 16.1±14.8 and 1.31±12.5 degree in HLHS and IAA patients, respectively (P<0.05). Conclusions: In HLHS patients, 54% of the patients had bulged and tortuous PDDT. Three-dimensional diagnosis and measurement of PDDT with MSCT is recommended when the stent implantation is considered for HLHS patients. P2381 Cardiac catheterisation-related thrombosis in children with congenital heart disease is associated with 4G/5G polymorphism of PAI-1 gene M. Del Fiandra 1, V. De Lucia 2,N.Botto 2, I. Spadoni 2,S.Giusti 2, L. Ait-Ali 2, M.G. Andreassi 1. 1 IFC CNR - Ospedale Pasquinucci, Massa, Italy; 2 G. Monasterio Foundation, Massa, Italy Background: Vascular thrombotic complications are common adverse events during pediatric cardiac catheterization. Identification of acquired and genetic risk factors is essential in order to improve individual risk stratification. Aim: To examine the acquired and inherited risk factors associated with catheterrelated thrombosis in children with CHD. Methods: Within a case-only design, we enrolled 64 consecutive CHD in-patients (31 males, age=63.7±64.3 months) admitted to our pediatric cardiac surgery center for cardiac cath procedures. Hospital records of all patients were reviewed. Multiplex allele-specific PCR assay was used to analyze Factor V Leiden, prothrombin G20210A, MTHFR C677T, plasminogen activator inibitor-1 (PAI-1) 4G/5G, platelet glycoprotein IIIa Pl (A1/A2), cystationine beta synthase (CBS) 844ins68 genetic polymorphisms. Results: Five patients (7.8%) had thrombotic complication after cardiac cath procedures: 4 children (80%) had an arterial system thrombosis and 1 case (20%) had a venous system thrombosis. Children with thrombosis were younger (9.7±11.1 vs 68.3±64.9 months; p=0.04) and at lower weight (6.5±3.2 vs 21.9±20.0 kg; p=ns) than children without vascular complications. The carrier frequency of PAI-1 4G/4G variant was significantly higher in infants with thrombosis

99 Imaging and intervention in congenital heart disease 399 when compared to patients without (chi square=4.6, p=0.03). No statistical differences were found for other polymorphisms. Multivariate analysis showed that age [OR: 0.9, p=0.006] and homozygosity for 4G/4G PAI-1 variant [OR: 8.8, p=0.04] were independent risk factors for thrombosis. Conclusions: Patient age and PAI-1 promoter 4G/5G polymorphism are associated to catheter-related thrombosis. Other thrombophilic gene mutations do not have influence on vascular thrombotic complications. P2382 Neutrophil Gelatinase-Associated Lipocalin (NGAL): Is it a good predictor of radiocontrast nephrotoxicity in children undergoing angiography? D. Oguz, R. Olgunturk, F.S. Tunaoglu, C. Sanli, A. Eren. Gazi University School of Medicine, Ankara, Turkey Radiocontrast nephrotoxicity (RCN) is a common and important cause of hospitalacquired renal insufficiency and a well-recognized complication of cardiac angiography. RCN is generally mild and reversible but can lead to prolonged hospitalization, increased health care costs, and substantial morbidity and mortality. Neutrophil gelatinase-associated lipocalin (NGAL) is an early predictive biomarker of renal failure unlike serum creatinine levels. We prospectively enrolled 46 children (age 0 16 years, median: 3 yrs) with congenital heart disease (9 cyanotic, 37 acyanotic) undergoing elective cardiac catheterization and angiography with non-ionic contrast (IOPROMID 769mg/ml) administration in our study. Serial urine and plasma samples (baseline, 4 hr, 24 hr, and 48 hr after the procedure) were analyzed for NGAL and creatinine. The volume of contrast medium injected was 4.20±2.18cc/kg. (0,65-10,6cc/kg). RCN, defined as a 25% increase in serum creatinine from baseline, was found in 17 subjects (34%). However, in 36 patients (72%) serum NGAL levels were increased (in some up to 9 fold) after 4 hours of contrast administration. The volume of contrast medium injected between the patient group who had increased NGAL levels and who had not differed significantly (4,77±2,04 vs 3,00±2,01cc/kg, p<0,01). The dependency of creatinine to some factors like age, gender, muscle mass, muscle metabolism, medications, hydration status, and delayed response to renal function loss which make take several days are important disadvantages. Thus, plasma NGAL levels have emerged as sensitive, specific and highly predictive early biomarker of RCN in children. P2383 Anomalous origin of the Left Coronary Artery from the Pulmonary Artery (ALCAPA): clinical and echocardiographic aspects in 13 consecutive cases O. Milanesi 1, M.C. Baratella 2,A.Cerutti 1,E.Reffo 1, N. Maschietto 1, R. Biffanti 1, G. Stellin 3. 1 Department of Pediatrics- University of Padova, Padova, Italy; 2 Department of Cardiology- Dolo Hospital, Dolo (Ve), Italy; 3 Department of Pediatric Cardiovascular Surgery- University of Padova, Padova, Italy ALCAPA is a rare heart malformation, accounting for 0,5% of all the CHD. Asymptomatic at birth and during the firs days of life, it causes in the majority of the cases a progressive ischemic LV cardiomyopathy, frequently misdiagnosed as primitive. Aim of our work is to underline the most relevant clinical and echocardiografic features of such a disease. We reviewed the clinical records of all the patients with ALCAPA, observed at our Department during the period Dec 2004-Dec 2008, with special attention to the referring diagnosis, clinical presentation, ECG and echocardiographic typical aspects. During the study period 13 patients (7F), admitted in our Hospital, met this diagnosis. Mean age was 22 months (1-144) median 4. Referring diagnosis was dilated cardiomiopathy in 9, heart murmur in 3; one patient was already followed in our center after surgical coarctation repair. Overt congestive heart failure (CHF) was present in 8 cases, CHF controlled with anti-congestive therapy in 2. Three patients, 13, 44 and 141 months old were asymptomatic. In 12/13 cases ECG showed pathologic Q waves and/or ischemic S-T T changes. Two-D echocardiography showed severely dilated LV, with depressed pump function in 7, severe mitral regurgitation in 1, moderate in 5, mild in 4, absent in 3. Diagnosis was in every case established by means of the direct visualization of the inverted flow in the main left coronary artery (CA), obtained with a careful investigation of the origin of the CA in a short axis cut, at the base of the heart, using low PRF colour flow mapping, and confirmed detecting a low velocity diastolic flow in the pulmonary artery, due to the reverse flow in the ALCAPA. However, the warning light of the malformation was in 12/13 cases the ischemic sclerosis of the papillary muscles of the mitral valve, which appeared thin and bright, and the presence of colour flow spots into the interventricular septum due to the enhanced collateral vessels between the high pressure right and the low pressure left CA, present in all and more pronounced in the 3 older asymptomatic patients. All the patients were operated on with 1 death, due to post operative low cardiac output. The LV function totally recovered in the survivors. In conclusion ALCAPA is a rare malformation, lethal in natural history, but with a good surgical prognosis. In our series, the diagnosis was never suspected from the referring physicians. We believe that it is important to underline the echocardiographic warning lights, which can lead to a correct diagnosis and a prompt treatment. P2384 Do maternal cardiac structural abnormalities predispose to high resistance uterine artery Doppler indices? K. Melchiorre, G.R. Sutherland, A.T. Baltabaeva, B. Thilaganathan. St George s Healthcare NHS Trust, London, United Kingdom Objective: To compare the prevalence of previously undiagnosed cardiac abnormalities in women with normal and high resistance indices at midtrimester uterine artery Doppler screening. Methods: Maternal transthoracic echocardiography was undertaken in pregnant women after uterine artery Doppler screening for pre-eclampsia at weeks gestation. Women with a mean uterine artery pulsatility index above 95th centile (1.25) for the local population (multi-ethnic, socially diverse and migrant) were considered to have a high resistance uteroplacental blood flow indices. The prevalence of cardiac structural defects in these women was recorded. Results: A total of 210 women consented to have maternal echocardiography: 86 with high resistance and 124 with normal resistance uterine artery blood flow indices. There were five previously undiagnosed, functionally significant cardiac defects in this cohort, all in the high-resistance uterine blood flow group (p<0.05). The newly diagnosed cardiac defects included: large atrio-septal defects with unidirectional shunt, right/left heart disproportion and pulmonary hypertension (n=2), mitral valve disease possibly secondary to rheumatic heart disease (n=2) and bicuspid aortic valve with aortic regurgitation (n=1). Conclusions: The prevalence of previously undiscovered maternal cardiac structural malformations appears significantly increased in women with high midtrimester uterine artery Doppler resistance indices. This observation should be confirmed in a larger series of patients because it has important consequences for medical practice and the long-term care provided to these patients. P2385 Quantitative assessment of dynamic change of tricuspid valve geometry in hypoplastic left heart syndrome using real-time 3D echocardiography K. Takigiku, S. Yasukochi, K. Takei, I. Kajimura, Y. Nakano, N. Inoue, S. Tazawa. Nagano Children s Hospital, Nagano, Japan Background: Significant tricuspid valve (TV) regurgitation (TR) in the patients withhypoplastic left heart syndrome (HLHS) adversely affects on the outcome, however, the detail pathogenesisof TR is still unclear. The aim of study is to assess thedynamic change of tricuspid valve geometry in the patients with hypoplasticleft heart syndrome using real-time 3D echocardiography (RT3DE). Methods: We performed RT3DE (IE33,Phillips) in 11 patients with HLHS and 13 normal subjects (NL; 13 mitral valvesand 6 tricuspid valves). The full volume images were obtained with the apicalview using X7-2 matrix array transducer. We used recentry developed soft ware (Real View) to reconstruct the 3D morphology of annulus and leaflets automatically.the annular area (AA), annular height (AH), tentingvolume (TEV), tenting leaflet area (TEA) were calculated in early diastolic, mid systolic and end systolic phase. All thedata were corrected with body surface area. Results: In HLHS, The AA, TEV and TEA of TV markedly increased comparedwith those of MV and TV in normal subjects (p<0.01).throughout systole,while AA significantly decreased only in HLHS (p<0.01), AH increased only inmv. TEV decreased progressively during systole in three groups (p<0.01), however, TEA decreased only in HLHS (p<0.01). Conclusions: The newly developed quantitative software allows the identificationof dynamic geometrical differences between HLHS and NL. In HLHS, marked TV leaflettenting was reduced during systole by decrease in annular area, which results invalvular coaptation.

100 400 Imaging and intervention in congenital heart disease / Mitral, tricuspid and rheumatic valve disease P2386 Total isovolumic time relates to exercise capacity in patients with transposition of the great arteries after atrial switch E. Tay, M. Josen, D.G. Gibson, R. Inuzuka, R. Alonsa Gonzalez, G. Giannakoulas, W. Li, M. Bartsota, K. Dimopoulos, M.A. Gatzoulis. Royal Brompton Hospital, London, United Kingdom Introduction: Systemic right ventricular (RV) systolic dysfunction is a common sequelae amongst adult patients after undergoing atrial switch (AS) procedure for transposition of great arteries (TGA). Total isovolumic time (t-ivt) relates to exercise capacity in acquired systolic heart failure and may be a better predictor of response to cardiac resynchronization therapy (CRT) compared to markers of segmental dyssynchrony. We hypothesized that t-ivt is prolonged in patients after AS and relates to exercise capacity. Methods: We studied 29 consecutive adults with TGA who underwent transthoracic echocardiography and cardiopulmonary exercise testing. Clinical and demographic data were collected. Right ventricular size and function were assessed and t-ivt was measured by Doppler and calculated as: 60- (total ejection time + total filling time). Percentage predicted peak VO2 and VE/VCO2 slope were measured during maximal treadmill exercise. Results: Mean age was 30.3±7.3 years, 31.8% males. Mid RV diameter was 4.8±0.7cm. Ten patients (35%) had moderate to severe systolic dysfunction of the systemic RV and 5 (17%) had moderate to severe tricuspid valve regurgitation. Mean t-ivt was prolonged at 12.15±3.97s/min. Mean percent predicted peak VO2 and VE/VCO2 slope was 64.4±19.1% and 35.5±11.4 respectively. Total- IVT negatively correlated with % predicted peak VO2, (r=-0.53, p=0.0048). This correlation became stronger when patients with exercise induced cyanosis (n=8) were excluded, (r=-0.68, p=0.0016). Conclusion: Total IVT is prolonged in adult TGA patients after AS procedures and relates inversely to exercise capacity. Biventricular pacing with a view to shortening t-ivt may be a potential therapeutic option for these patients, which may be explored in prospective studies. P2387 Egypt Evaluation of pulmonary arterial anatomy in children with pulmonary atresia using non ECG gated MDCT M. Ghazy 1,M.ElSayed 1,A.ElFiky 1, G. El Shahed 1,H.Abd El Moniem 2, A. Roshdy 1, M. Abd El Kader 1, O. El Farouk 1. 1 Ain Shams University, Cairo, Egypt; 2 El Galaa Military Hospital, Cairo, Purpose: To evaluate the efficacy and safety of MDCT in establishing the pulmonary arterial anatomy in children with pulmonary atresia. Methods: The study was done using a 64 slices scanner. Younger patients received light sedation using oral chloral hydrate ( ml/kg) minutes before the scan. No sedation was needed for older cooperative patients. All the scans were done non-ecg gated after the injection of a low osmolar non ionic contrast material. Each study was reviewed by three operators; two cardiologists and a radiologist to assess the presence of pulmonary confluence, the size of pulmonary arteries, presence of peripheral pulmonary stenosis, and presence of MAPCAs and/or PDA. A study was considered successful if all these anatomical data could be reached clearly. The safety of the examination was evaluated by recording contrast related adverse effects and the overall well being of the patients after the study, also the amount of radiation exposure was calculated. Results: The study included 29 patients; the youngest was 17 days old while the oldest was 14 years old. Fifteen patients were below 2 years of age. The total amount of radiation delivered during the scans ranged from 0.75 msv to 3.48 msv (1.45±0.7). Only three studies (10%) were considered non successful, two of them were due to inadequate contrast opacification and the other due to excessive motion artifacts. In the remaining 26 studies (90%), all the pulmonary arterial anatomical data were obtained. Eighteen patients had confluent pulmonary arteries. In the eight patients with non confluent pulmonary tree the exact origin of the pulmonary arteries could be identified. The sizes of the pulmonary arteries were clearly measured in all patients. Twelve patients (46%) had peripheral pulmonary stenoses, six of which had origin stenoses of the left pulmonary artery. MAPCAs were clearly visualized in 50% of the patients. The PDA was also adequately visualized in 21 patients. The procedure was safe in all patients with no peri-procedural complications apart from one patient who had extravasation of the contrast from the injection site. Conclusion: Non ECG gated MDCT is a safe and effective approach for evaluating the pulmonary arterial anatomy in children with congenital pulmonary atresia as young as 17 days old with accurate data acquisition and low total radiation exposure. P2388 CMR tagging for measurements of the long axis function of the systemic right ventricular free wall S. Chen 1, J. Keegan 1,A.W.Dowsey 2,R.Wage 1,D.N.Firmin 1, G.Z. Yang 2,P.J.Kilner 1. 1 Royal Brompton Hospital, London, United Kingdom; 2 Imperial College London, London, United Kingdom Aim: The systemic right ventricle (RV) in transposition of the great arteries generally starts to fail later in life. Ejection fraction (EF) is used as a cardiovascular magnetic resonance (CMR) measurement of systemic RV function, but is time consuming and not reliably reproducible. We used CMR tagging of the free wall of the RV to measure systemic RV long axis function, comparing findings with EF. Methods: We studied patients with Mustard operation (OTGA), or unoperated congenitally corrected transposition of the great arteries (CCTGA), and controls. A breath-hold 4 chamber steady state free precession cine dataset was acquired, then a breath-hold cine gradient-echo echo-planar tagged acquisition in the same plane. Tagging was performed by a COMB prepulse, applied immediately after the R wave, which simultaneously tagged 2 short axis planes, a basal RV slice and another 40mm towards the apex. RV free wall systolic deformation (%) was calculated by measuring the difference between the tag lines at end-diastole and at peak myocardial displacement, and dividing the difference by the distance (40mm). RV end-diastolic and end-systolic volumes were measured by CMRTools (Imperial College, London). Results: Nineteen patients (13 OTGA + 6 CCTGA, age 30±7, 35±12 years) were studied and compared to 10 controls (31±9 years). Basal RV myocardial displacements in both OTGA and CCTGA were lower than controls (12±5 + 21±4 vs 26±3mm, p 0.001, p=0.01 respectively). Basal myocardial displacement in OTGA was more impaired than CCTGA, p= RV free wall systolic deformation tended to be lower in OTGA and CCTGA compared to controls (14±8 and 13±6 vs 22±9%, p=0.05, p=0.06 respectively). Compared to controls, CCTGA had higher EF, 65±10 vs 55±4%, p=0.02 but no EF difference between OTGA and controls, 55±9 vs 55±4%, p=0.7. Conclusion: RV free wall tagging showed lower RV free wall motion, and a trend towards lower systolic deformation in patients. Lower displacements in OTGA than CCTGA maybe due to surgery. EF is increased in CCTGA. Like patients with hypertrophic cardiomyopathy, high EF in CCTGA maybe due to approximation of endocardial borders as hypertrophied myocardial layers thicken. Deformation analysis suggest that high EF of CCTGA patients is not due to enhanced myocyte shortening, but to systolic elimination of blood spaces between the hypertrophied muscle layers, an effect that masks potential impairment of myocardial function if only EF is used. Therefore, RV free wall tagging may provide not only a quicker and simpler method for comparisons RV myocardial function, but also a more representative measurement. MITRAL, TRICUSPID AND RHEUMATIC VALVE DISEASE P2389 Early Results of the RHEUMATIC (Rheumatic Heart Echo Utilization and Monitoring Actuarial Trends in Indian Children) study A. Saxena 1, S. Ramakrishnan 1,A.Roy 1,S.Seth 1, A. Krishnan 1, S.K. Reddy 2,P.Misra 1, B. Bhargava 1, P.A. Poole-Wilson 1 on behalf of United Kingdom-India Education and Research Initiative. 1 All India Institute of Medical Sciences, New Delhi, India; 2 Carenidhi, New Delhi, India Purpose: Rheumatic Heart Disease (RHD) is estimated to affect over 20 million people worldwide, the vast majority being children in developing countries. Early detection of milder cases in asymptomatic children may prevent progression to severe valvular lesions by instituting secondary prophylaxis. Conventionally, auscultation has been used for diagnosing RHD, but echo-doppler is likely to be more sensitive and specific. We carried out a cross sectional survey to diagnose RHD in asymptomatic children aged 5-15 years, living in rural areas and crowded urban areas, using portable echocardiography. Methods: Children, aged 5-15 years, from government schools and private schools, in a pre identified rural area and from a crowded urban area were studied. After a history and physical examination, echo-doppler was performed, using a bedside portable echocardiography machine. A diagnosis of RHD was made by echo-doppler if one or more of the following were present: a) Mitral stenosis; b) Mitral regurgitation (MR) and/or aortic regurgitation (AR) with regurgitant jet length of more than 2 cm in at least two echo planes, along with abnormal valve morphology (a bicuspid aortic valve to be excluded in cases with AR); c) MR and/or AR with regurgitant jet length of 1-2 cm, and abnormal valve morphology, in the presence of a history suggestive of rheumatic fever. Results: A total of 859 children were screened, 458 from government schools, 175 from private schools and 226 from the crowded urban area. 452 were males. The mean age was years. All children were asymptomatic. History suggestive of rheumatic fever was obtained in 34 cases. MR was diagnosed by

101 Mitral, tricuspid and rheumatic valve disease 401 clinical examination in one case only (clinical prevalence of RHD 0.1%). Echo- Doppler diagnosed RHD in 28 cases, giving a prevalence of 3.2%. Thickening of the valve was present in all 28 cases. Doppler revealed MR in 25 and AR in four. Thirteen of these 28 cases had a history suggestive of rheumatic fever. Other cardiac lesions identified by echo-doppler were moderate sized atrial septal defect (one), bicuspid aortic valve, without stenosis or regurgitation (two) and mild left ventricular dysfunction, possibly due to dilated cardiomyopathy (one). Conclusions: This preliminary work demonstrates feasibility of echo screening in children for diagnosing RHD. In this study, the prevalence of RHD was found to be high, when screening echo-doppler was used. A larger study is necessary and is underway. P2391 Right ventricular pacing increases tricuspid regurgitation grade regardless the mechanical effect of the electrode placement M. Vaturi, J. Kuzniec, Y. Shapira, M. Perlmutter-Weiser, B. Strasberg, A. Sagie. Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel Background: The effect of RV pacing on tricuspid regurgitation (TR) is still debatable and is related to interference in valve closure by the electrode. The study aimed to determine the pacing impact on TR grade. Methods: Patients with permanent pacemaker (PM) (electrode at the RV apex) were studied. Exclusion criteria: PM dependence, atrial fibrillation and LV dysfunction. Each patient had a baseline echocardiography study followed by PM programming: if in sinus rhythm, the PM was set on a pacing mode ( 5 heartbeats of baseline rate) and vice versa. Echo study was repeated immediately thereafter. The TR was graded by vena contracta (TRvc). RV and LV areas (enddiastolic and systolic in the apical view) and the RV base systolic diameter (septum to free wall) were measured (arrow in Figure). Results: Twenty-one patients (12 males, 79±12 years, 81% with DDD pacing) were included. RV pacing was associated with increase in TRvc (from 0.2±0.2 to 0.4±0.2 cm, p<0.0001) and in the average TR grade (from mild to mild-moderate, p<0.0001). RV and LV areas and RV systolic pressure were not changed by the acute change in the pacing mode. However, RV base systolic diameter increased with pacing (3.3±0.7 vs. 2.9±0.5 cm, p=0.001) and was accompanied by visually leftward deviation of the basal septum (Figure). Patient characteristics Variable TR ERO = 0 TR ERO = 1-39 TR ERO 40 P value ERO, mm ± ±0.37 < Regurgitant Volume, ml ± ±17.9 < Annulus systolic diameter, cm 2.7± ± ±0.6 < Tenting Height 0.37± ± ± Tenting area 0.5± ± ±0.6 < RV length 7.7± ± ± RV basal diameter 3.1± ± ±0.7 < Conclusions: Isolated functional TR is not caused by valvular tenting but is associated with annular enlargement, consistent with the RV remodeling characterized by increased width rather than height. These mechanistic data may provide important clues on functional TR surgical correction. P2393 Left ventricular regional predictors of outcome post mitral valve repair in patients with functional ischemic mitral regurgitation T. Kukulski 1, A. Leopold 2,W.Streb 1, T. Niklewski 2, M. Zembala 2, Z. Kalarus 1. 1 Dpt of Cardiology Congenital Heart Disease and Electrotherapy, Zabrze, Poland; 2 Dpt of Cardiosurgery and Transplantology, Katowice, Poland Background: Although early and mid term outcome post valve repair using undersized mitral restrictive annuloplasty (UMRA)is satisfactory, the long term results might be compromised by recurrence of mitral regurgitation and poor reversed left ventricular remodeling (RLVR). It has been shown that morphologic indexes of mitral valve deformation can predict the success of surgical repair, however the role of LV functional parameters has to be still determine. The study was aimed to evaluate long term results post UMRA and to define LV functional predictors of poor outcome (combined end point: cardiac death and heart transplantation and hospitalization). Methods: 52 pts (61±7y, EF 40±11%, EDV 150±51, ESV 94±40 ml) with moderate-severe functional ischemic mitral regurgitation (FIMR) (MR degree 3,4±0,6) who underwent simultaneous UMRA (ring size 26,8±1,3mm) and CABG were evaluated retrospectively 40±8 months post surgery. Location of infarct was inferior in 50%, anterior in 21%,lateral in 13% of pts. Global LV function indexes and regional velocity (VEL sys) and deformation (S max)parameters were analysed at baseline and follow up. Mid-segment strain and velocity data were representative for each LV wall. Logistic regression was used to determine an impact of baseline LV function indexes and clinical variables on outcome. Results: 18/52 (34%)patients showed RLVR defined as EF increase by >5%. Inferior wall strain/esv and lateral wall velocity were found to be independent predictors of combined end-point (see table). Pacing effect on TR grade Discussion: RV pacing is associated with a small (but significant) increase in TR grade, independently of the electrode s presence. It is suggested that pacing increases TR via induction of dyssynchrony in RV contraction. P2392 Mechanism of functional,isolated tricuspid regurgitation A quantitative clinical study T.Y. Topilsky, M.E.S. Enriquez-Sarano. Mayo Clinic, Rochester, United States of America Background: Mechanism of functional tricuspid regurgitation (TR) remains unclear while recent studies suggested that functional mitral regurgitation is due valve deformation (tenting) rather than annular enlargement. Methods: To study the mechanism of functional, isolated (no valve disease, pulmonary hypertension, left heart disease, pacemaker, or congenital disease) TR we performed a triple quantitative (tricuspid valve deformation, regurgitation, right ventricular and atrial quantitation) study. We enrolled 141 patients with isolated functional TR, and 50 age- (71 vs. 70 years, p=0.54) sex- and ejection fraction- (63 vs 61% p=0.07) matched controls. Results: Patients with functional TR vs. controls had larger right atrial area (23.5±8.2 vs 15±3.3 cm 2,p<0.001) right ventricular (RV) area (27.8±9.4 vs. 22.7±5.9 cm 2,p<0.001) and lower RV area contraction (37±10 vs 44±13%, p<0.001). Patients were classified according to TR effective regurgitant orifice (ERO) as severe (ERO 40 mm 2 ), moderate (ERO 1-39 mm 2 ) and no TR (ERO 0mm 2 ) in Table 1. With increasing severity oftr, more valve and ventricular alterations were noted, but tricuspid tenting height was unchanged showing that the increasing tricuspid tenting area was due to annular enlargement. In multivariate analysis, the only independent predictor of ERO and regurgitant volume was systolic annular diameter. Importantly with increasing severity of TR, RV length did not increase while RV transversal diameter increased in parallel to annular dimension. Parameter Vel sys lat S max inf/esv Age EF baseline Estimate -3,70-4,29-1,54 2,57 p level 0,007 0,013 0,24 0,13 95%CI -6,35-7,63-4,17-0,83 +95%CI -1,06-0,94 1,08 5,97 chi square 8,16 6,82 1,43 2,35 p level 0,004 0,008 0,23 0,12 Odds ratio 0,02 0,01 0,21 13,06 95% CI 0,0017 0,0004 0,01 0,43 +95% CI 0,34 0,38 2,95 393,47 Conclusions: Regional LV function indexes can predict unfavourable outcome post mitral surgery in pts with FIMR P2394 Late referral of women for valve surgery - implications for complications and survival K. Zareba, R.O. Bonow, N. Akhter, B.R. Lapin, P.M. Mccarthy, V.H. Rigolin. Northwestern University, Chicago, United States of America Objective: Established guidelines for valve surgery are similar for men and women and include symptoms and left ventricular function. We sought to compare clinical and operative characteristics as well as outcomes in men and women referred for mitral valve (MV) surgery. Methods: An analysis of 758 patients (mean age 63±14, 48% females) admitted for MV surgery (replacement or annuloplasty) was conducted between April 2004 and July Patients undergoing concomitant aortic valve (AV), tricuspid valve (TV) or atrial fibrillation (AF) correction operations, coronary artery bypass grafting (CABG) and re-do operations were included. Clinical and operative variables were used to predict operative mortality and complications. Results: Compared to men, women were older (64±14 vs. 62±13, p=0.03), had more pre-op congestive heart failure (46% vs. 38%, p=0.04) and greater NYHA class III and IV symptoms (50% vs. 37%, p<0.0001) despite a higher mean ejection fraction (54±13 vs. 52±13, p=0.02). Women had more prior valve surgery (21% vs. 13%, p=0.004), and presented with more mitral and aortic stenosis. Women had more TV (36% vs. 17%, p<0.0001) and AF correction operations (40% vs. 33%, p=0.03). Equal numbers of men and women had concomitant AV

102 402 Mitral, tricuspid and rheumatic valve disease surgery while more men had CABG. Women also underwent more MV replacement (43% vs. 19%, p<0.0001), were given more blood products and required longer post-op ventilation and ICU stays. Mortality at 30 days post surgery was higher in women (6.1% vs. 3.0%, p=0.025), however operative mortality was not statistically different between women and men (3.3% vs. 1.8%, p=0.174). Multivariate regression analysis revealed that age (HR 1.09, p=0.003), concomitant TV operation (HR 1.65, p<0.001), and operative urgency (HR 1.43, p=0.034) were independent predictors of operative mortality or complications. Conclusions: Women present for MV surgery with more symptomatic heart failure. Women also undergo more complex operations, and have greater requirement for blood transfusions and mechanical ventilation. Therefore, earlier detection of symptoms in women is necessary, leading to earlier referral for MV surgery in appropriate patients. P2395 Comprehensive annular and subvalvular repair of chronic ischemic MR provides best long-term results with least ventricular remodeling C. Szymanski 1,A.Bel 1, I. Cohen 1, M.D. Handschumacher 1, M. Desnos 1, A. Carpentier 1, P. Menasche 1, A.A. Hagege 1, R.A. Levine 2,E.Messas 1. 1 European Hospital George Pompidou (AP-HP), Paris, France; 2 Massachusetts General Hospital, Cardiac Ultrasound Laboratory, Harvard Medical School, Boston, United States of America Background: In ischemic mitral regurgitation (IMR), leaflet tethering is caused by post-mi LV and annular remodeling. Severing second-order mitral chordae significantly decreases tethering and MR. We tested whether undersized ring annuloplasty can improve chordal cutting efficacy by reducing annulus-related tethering. Methods: Posterolateral MI created chronic remodeling and MR in 28 sheep. At 3 months, sheep were randomized to sham surgery vs isolated annuloplasty undersized by 2 sizes vs isolated bileaflet chordal cutting vs at the combined therapy (n=7 each). At baseline, chronic MI (3 months) and sacrifice (6.6 months) we measured LV volumes and ejection fraction (EF), wall motion score index (WMSi), MR Regurgitation fraction (MRRF) and vena contracta (VC), Mitral annulus area (MAA) and posterior leaflet (PL) restriction angle (PL to MAA) by 2D and 3D echo. Results: All groups were comparable at baseline and chronic MI, with mild- moderate MR (MRVC 4.6±1.0mm, MRRF 24±2.6%) and MA dilatation (p<0.01). At sacrifice, LV end-systolic volume (ESV) increased by 108% in controls vs 28% with ring + chordal cutting, less than with each intervention alone (p<0.01). Also, MR progressed to moderate-severe in controls but decreased to trace with ring + chordal cutting vs mild-moderate with ring alone and trace-mild with chordal cutting alone (MRVC 5.9±1.1mm in controls, 2.0±0.7 with ring, 1.0±0.9 with chordal cutting, 0.5±0.08 with both, p<0.01). Ring alone did not improve PL mobility (PL restriction angle 79.4±6.0 ), but chordal cutting did alone or with ring (PL restriction angle 54.2±5.0 with chordal cutting vs. 45.0±2.3 with both, p=ns). In multivariate analysis, LVESV and MAA most strongly predicted MR (r 2 =0.82, p<0.01). Conclusions: Comprehensive annular and subvalvular repair provides the most effective long-term reduction of both chronic ischemic MR and LV remodeling. Results: There were significant differences in the amount of left atrial fibrosis between group I and II (p=0.049) and group III and IV (p=0.008) (Table 1). The only clinical factors which significantly correlated with amount of atrial fibrosis were: patients age (p=0.048), left atrium diameter (p=0.024) and the degree of tricuspid regurgitation (p=0.004). Conclusion: Atrial fibrosis can provide pathophysiological substrate for atrial fibrillation in patients with mitral valve disease before and after mitral surgery. Atrial fibrosis is associated with patients age, left atrium diameter and the degree of tricuspid regurgitation. P2397 Long-term contribution of functional mitral regurgitation after a first non-st segment elevation acute coronary syndrome to left ventricular enlargement I. Nunez-Gil, J. Zamorano, L. Perez De Isla, C. Almeria, J.L. Rodrigo, C. Fernandez-Golfin, P. Marcos-Alberca, D. Herrera, A. Aubele, C. Macaya. Hospital Clinico San Carlos, Madrid, Spain Functional mitral regurgitation (MR) is frequent after an acute myocardial infarction. However, data about the long term influence of functional MR after a non-st segment elevation acute myocardial syndrome (NSTSEACS) are scarce. Our aim was to assess the relationship between functional MR after a first NSTSEACS and the development of LV enlargement. Methods: We prospectively studied 248 patients consecutively discharged from hospital in NYHA functional class I and II (74% men; mean age 65.1±12.3 years) after a first NSTSEACS. Every patient underwent an echocardiographic study during the first week after the NSTSEACS and were clinically and echocardiographically followed up between months later. Patients who were lost or died before were excluded. Results: One hundred and fifty eight patients were enrolled. MR was detected in 59 cases (38.3%). Patients were followed a median time of 1108 days (interquartile range: ). Onset mean LVEF was 55.76± LV diastolic (grade I: 12.7±40.7; grade II: 26.8±12.4; grade III: 46.3±50.9 cc, p=0.01) and systolic (grade I: 10.4±37.3; grade II: 10.12±12.7; grade III: 36.8±46.0 cc, p=0.02) mean volumes were higher after follow up in patients with MR, and the severity of the enlargement were related to the severity of the initial MR degree (See figure). In spite of LV remodeling no differences in revascularization were found between groups. Adverse events, including death, heart failure, unstable angina and infarction were more frequent in the MR group. P2396 Determinants and consequences of left atrial fibrosis in patients with mitral valve disease T. Mularek-Kubzdela, W. Seniuk, S. Grajek, A. Marszalek, A. Olasinska-Wisniewska, M. Jemielity, W. Stachowiak, W. Sarnowski, P. Breborowicz, M. Prech. Poznan University of Medical Sciences, Poznan, Poland The purpose of this study was to determine whether the amount of left atrial fibrosis is associated with development or persistence of atrial fibrillation before and after mitral surgery and to investigate which clinical factors are associated with increased fibrosis in patients with mitral valve disease. 101 consecutive patients (male 25, female 76) aged 23 to 71 (mean 52) with mitral valve disease admitted for mitral surgery were enrolled in the study. In all patients electrocardiography, echocardiography and clinical examination were performed before the operation. 36 patients were in sinus rhythm - group I, 65 had chronic atrial fibrillation- group II. Biopsies of the posterior wall of the left atrium were obtained during open heart surgery. Tissue was analyzed for percent of fibrosis using an image analyzer. 12 months after operation cardiac rhythm was checked. 8 patients died before 12- month-follow-up, 3 patients were lost to follow-up. Remaining 90 patients were divided into two groups according to the rhythm: group III - sinus rhythm (SR, 50 patients), group IV - atrial fibrillation (AF, 40 patients). Table 1 Group I Group II P SR before surgery AF before surgery N=36 N=65 Mean percent of left atrium fibrosis 32.1± ±10.7 P=0.049 Group III Group IV P SR one year after surgery AF one year after surgery N=50 N=40 Mean percent of left atrium fibrosis 32.8± ±10.4 P=0.008 Main results Conclusions: There is an increase in LV diastolic and systolic volumes in patients after a first NSTSEACS. Furthermore, the risk of LV enlergement is closely related to MR severity on admission. Thus, the remodelling could explain in part the worst prognosis observed regarding MR after a NSTSEACS. P2398 Subclinical left ventricular dysfunction in rheumatic mitral stenosis: correlation with high sensitivity C-reactive protein levels E. Khalifa. Dar Al Fouad Hospital, Cairo, Egypt Background: In pure rheumatic mitral stenosis (MS), varying degrees of left ventricular (LV) dysfunction occur. There is a controversy regarding whether this deterioration is result of functional or mechanical factors. Doppler tissue velocities of the mitral annulus correlate well with LV systolic and diastolic functions. C-reactive protein (CRP) is increased in patients with acute rheumatic fever but it is not known whether plasma levels increase in patients with chronic rheumatic valve disease and their impact on LV function. Objectives: To investigate left ventricular function by using pulsed wave Doppler tissue imaging (PWDTI) in rheumatic mitral stenosis and correlate this with high sensitivity (hs)-crp levels. Patients and methods: The current study enrolled 80 patients with chronic rheumatic mitral stenosis & 36 age and gender matched healthy volunteers as control group. PWDTI data (from each of 4 mitral annular sites, septal, lateral, inferior, anterior) were obtained. Mean peak annular systolic velocity (Sm), mean annular early (Em) and late (Am) diastolic velocities were calculated by averaging of values measured at each site. Precontraction time (PCT), ejection time (ET) and isovolumic relaxation time (IVRT) was estimated for calculation of the myocardial performance index (MPI).

103 Mitral, tricuspid and rheumatic valve disease 403 hs-crp levels were measured by rapid immunoassay and blinded to cardiologist making assessment of LV function. Results: Myocardial velocities of LV (Sm, Em, Am) were found to be significantly lower in MS patients compared to controls (8.1±0.61 vs 9.4±1.8 cm/s, 7.3±1.4 vs 14.4±0.28 cm/s, 9.2±2.1 vs 11.4±1.1 cm/s respectively, p<0.001 for all). MPI was higher in MS patients than control group (0.63±0.2 vs 0.47±0.3, p<0.001). Patients with MS were shown to have significantly higher plasma levels of hs-crp compared to controls (6.5±0.9 vs 2.2±0.8mg/L, p<0.001). Significant negative correlation could be established between hs-crp and Sm (r = -0.67), Em (r = -0.82), Am (r =-0.738) whereas significant positive correlation was established between hs-crp and MPI (r = 0.66) with p<0.001 for all correlations. Conclusion: Rheumatic mitral stenosis significantly impaired left ventricular long axis function evaluated by PWDTI, and this impairment was strongly correlated with hs-crp level. These results may be an evidence of ongoing low grade systemic inflammation in chronic phase of rheumatic heart disease. P2399 Does degenerative mitral regurgitation severity change during exercise echocardiography? J. Magne 1, M. Moonen 1, K. O Connor 1, P. Pibarot 2,L.A.Pierard 1, P. Lancellotti 1. 1 CHU de Liege - Domaine du Sart Tilman, Liege, Belgium; 2 Quebec Heart institute, Quebec, Canada Introduction: Recent studies revealed that mitral regurgitation (MR) severity may change during exercise in patients with functional MR. Significant exerciseinduced increases in MR is associated with poor outcome. By contrast, changes in MR severity during exercise remain undetermined in patients with degenerative MR. Method and results: Resting and symptom-limited semi-supine bicycle exercise Doppler-echocardiography were performed in 66 consecutive patients (61±15 years and 55% of male) with moderate to severe degenerative MR (i.e. mitral prolapse or flail). MR severity was evaluated, both at rest and during exercise, using vena-contracta (VC) width and effective regurgitant orifice (ERO) area calculated with the proximal isovelocity surface area (EROP) and the quantitative Doppler (EROD) methods. Systolic pulmonary arterial pressure (PAP) was derived from the peak regurgitant transtricuspid pressure gradient obtained at rest and during exercise. At rest, EROD was greater than EROP (52±16mm 2 vs. 31±17mm 2,p<0.0001). VC width (mean =5.3±1.5mm) was correlated with both EROP and EROD (r=0.57, p= and r=0.47, p=0.004, respectively). In addition, EROP and EROD were also correlated (r=0.51, p=0.0036). During exercise, VC, EROP and EROD increase in 71%, 54% and 54% of patients, respectively and there were good correlations between exercise VC and exercise EROP and EROD (r=0.42, p=0.035, r=0.47, p=0.017 and r=0.73, p<0.0001). Systolic PAP also increased during exercise (from 29±9 to52±16mmhg, p<0.0001) and changes in PAP during test were correlated with changes in EROP and EROD (r=0.33, p=0.04 and r=0.44, p=0.004). Moreover, patients with exercise peak PAP>60mmHg had higher exercise VC (6.2±1 vs. 7.8±3mm, p=0.04), EROP (33±21mm 2 vs. 45±22mm 2, p=0.04) and EROD (49±20mm 2 vs. 69±27mm 2, p=0.0047) and higher exercise-induced change in VC (0.6±2 vs. 2±1.6mm, p=0.04) and in EROD (-2.7±17 vs. 12±18 mm 2, p=0.006). After adjustment for age, sex and resting PAP, exercise-induced changes in EROD remained associated with changes in PAP (β=0.22, p=0.033) Conclusion: As in functional MR, degenerative MR can be dynamic and increases during exercise in more than 50% of patients. Changes in MR severity are associated with exercise-induced changes in systolic PAP, suggesting a potential impact on outcome. Further studies are needed to determine whether exercise-induced increase in MR has prognostic importance. compared with controls (112.19±15.45% and ±15.93% vs ±6.62% and ±10.08%, p<0.001 for both). With exercise, peak systolic twist increased in normals (18.44±6.24, p=0.002 vs. rest) but not in MR (16.74±5.4, p=ns). Times to onset and peak of untwisting both became earlier in MR (101.57±9.87 and ±15.76, p<0.02 vs. rest), but remained delayed compared with controls (93.46±8.03 and ±14.85, p<0.002 vs. MR). In the MR group, peak systolic twist on exercise correlated inversely with resting measures of left atrial volume (r=-0.402, p=0.03), regurgitant volume, and regurgitant fraction (r= and respectively, p<0.05 for both). Time to onset of untwisting on exercise correlated with resting LV end-diastolic volume (r=0.585, p=0.002), end-systolic volume on exercise, and the change in ejection fraction on exercise (r=0.562 and respectively, p=0.005). The change in time to peak untwisting from rest to exercise correlated inversely with left atrial volume (r= , p=0.049). Conclusion: In patients with chronic mitral regurgitation, abnormalities in LV twist on exercise worsen progressively with increased resting preload and with measures of exercise-induced systolic impairment. This provides further evidence that LV twist may play a role in the development of functional limitation with progressive disease. P2401 Functional mitral regurgitation and Non ST-segment elevation myocardial infarction: very long-term prognosis I. Nunez-Gil, J. Zamorano, L. Perez De Isla, C. Almeria, J.L. Rodrigo, C. Fernandez-Golfin, P. Marcoz-Alberca, M. Quezada, V. Serra, C. Macaya. Hospital Clinico San Carlos, Madrid, Spain Functional mitral regurgitation (MR) after an acute myocardial infarction is a frequent complication related with worse outcome. Nevertheless, data on MR after a Non-ST-segment elevation acute myocardial infarction (NSTEMI) is scarce in our environment. Our objective was to investigate the incidence, clinical predictors, and prognostic implications of MR in the setting of NSTEMI after a long term follow-up. Methods: We prospectively studied 255 consecutive patients admitted to our coronary care unit for a first NSTEMI. Every patient underwent an echocardiographic study during the first week after admission and was clinically and echocardiographically followed up (median 1011 days). Results: Mean age was 66.19±13 years (73.8%, men). MR incidence was 40% (75 patients, grade I; 15, grade II; 6, grade III and 3 grade IV). Only the age, diabetes mellitus, multivessel disease and MR (HR=2.17; , p=0.003) were independently related with long term worse outcome. The MR presence (see figure) and amount was proportionally related with more events. P2400 Left ventricular twist on exercise deteriorates with increased volume overload in chronic mitral regurgitation R.A. Argyle 1, R.P. Beynon 1, R. Aghamohammadzadeh 1, K.A. Pearce 1,A.N.Borg 2,S.G.Ray 1. 1 University Hospital of South Manchester, Manchester, United Kingdom; 2 Blackpool Victoria Hospital, Blackpool, United Kingdom Purpose: Left ventricular (LV) twisting and untwisting are important for normal systolic and diastolic function, and enhance on exercise in normal subjects. In chronic severe mitral regurgitation (MR), volume overload can result in LV dysfunction, initially apparent only on exercise. We studied how changes in LV twisting parameters on exercise relate to conventional markers of volume overload and LV function. Methods: Subjects underwent echocardiography at rest and during submaximal exercise on a supine bicycle ergometer. We used 2-dimensional speckle-tracking echocardiography in parasternal short axis views to assess LV twist by subtracting basal rotation from apical rotation. Times to onset and peak of untwisting were expressed as a percentage of systolic duration. Correlations with standard echocardiographic measures were carried out using the Spearman correlation coefficient. Results: 28 patients aged 60±14 years with asymptomatic chronic moderate to severe primary MR and 28 age-matched controls were included. At rest, peak systolic twist (degrees) was similar in both MR and controls (14.84±4.49 vs ±5.03 respectively). Both onset and peak of untwisting were delayed in MR Main results Conclusions: In our environment, MR is frequent after an NSTEMI. Its presence together with other negative factors establish a worse very long-term prognosis. In addition, this point seems to be proportionally related with MR degree. Therefore, the existence of MR should be specifically assessed and followed-up in every patient after an NSTEMI. P2402 Prospective single center registry of patients with ischemic mitral regurgitation considered for revascularization (PRAGUE 9 study registry) with one year clinical follow up V. Kocka, P. Widimsky, M. Penicka, H. Linkova, T. Budesinsky, J. Dvorak, L. Lisa, P. Tousek on behalf of Grant MSM Cardiac Center, Teaching Hospital Královské Vinohrady and 3rd Medical School of Charles University, Prague, Czech Republic Purpose: We aimed to characterize group of patients indicated for coronary revascularization, who have simultaneously ischemic mitral regurgitation (IMR). This was studied in population where primary percutaneous coronary intervention (PCI) is routine therapy of acute ST elevation myocardial infarction for at least 10 years. Best therapeutic approach to similar patients is not well established. Methods: 2408 patients undergoing cardiac catheterization at our institution from

104 404 Mitral, tricuspid and rheumatic valve disease 1.1. till were screened. 63 patients who were considered for coronary revascularization (percutaneous and/or surgical) and had at least mild to moderate (2+) ischemic mitral regurgitation were included. IMR was defined by detailed echocardiography evaluation of mitral valve morphology, excluding rheumatic heart disease, m.barlow and severe calcification. All patients were followed for one year. Population of Czech Republic is approx. 10 million and there were cardiac catheterizations performed in year Results: Clinical characteristics are: average age 69 years, 68% being of male sex, NYHA class 2.5, diabetes mellitus 44%, hypertension 78% (mean blood pressure at inclusion was 133/77mmHg, 2.2 antihypertensive medication per patient), positive troponin at inclusion 32%, prior revascularization 25%. In agreement with literature physical examination is not too helpful - 38% of patients have no detectable murmur, only 36% of patients have clearly audible murmur grade 2/6. Echocardiography showed mean left ventricle (LV) diastolic dimension 59mm, LV ejection fraction 41%, left atrium size 45mm. IMR severity was graded by experienced echocardiographer and there was statistically significant difference in LV diastolic dimension between mild to moderate (2+/4) and severe (4/4) IMR (p=0.01). Mean logistic Euroscore was patients underwent coronary revascularization (26 by PCI, 22 surgically with mitral valve repair in 13 cases), 14 were treated medically and 1 patient was referred for cardiac transplantation. There was no significant difference in mortality between patients treated medically (7%) and revascularized patients (19%) due to small sample size and small number of events, overall mortality was 16%. Conclusion: Incidence of patients with ischemic mitral regurgitation who are considered for coronary revascularization is 147 patients per 1 million per year, even in the era of primary PCI. These patients have high estimated surgical risk. One year mortality is also high at 16%. Our data might be useful for meta-analysis and planning future research. P2403 Pulmonary vascular resistances evaluation during exercise in patients with mitral valve stenosis A.R. Almeida, C. Cotrim, H. Vinhas, R. Miranda, S. Almeida, L.R. Lopes, I. Joao, P. Fazendas, M. Carrageta. Hospital Garcia de Orta, Almada, Portugal Background: Treadmill exercise echocardiography with Doppler evaluation during effort has been used for several years in our department. Purpose: Evaluate patients (pts) with mitral valve stenosis and sinus rhythm using Doppler parameters, during treadmill exercise test (TE), with assessment of pulmonary vascular resistances (PVR). Methods: From a total of 72 pts we have completed the study in 68 pts. The mean age was 50±10 years (27 to 74 years) and 59 were females. We evaluated the mitral functional area using pressure half-time method (PHT), the mean transmitral pressure gradient ( Pm), the stroke volume (SV) and cardiac output (CO) through aortic valve, and systolic pulmonary pressure (SPP) using the pressure gradient between right ventricle and right atria ( P RV/AD) in pts with tricuspid regurgitation in addition to right atrial pressure (assuming 5 mmhg at left lateral decubitus (LLD) and 0 mmhg at orthostatic position (OP)). We assessed these parameters with echocardiography at LLD and then at OP, during exercise (using the modified Bruce protocol), at peak workload (PW) before treadmill testing termination, and at early recovery (R) (first 90 seconds). To calculate PVR we assumed that pulmonary capillary wedge pressure (PCWP) is equal to Pm plus left ventricular telediastolic pressure (assuming it as 4 mmhg). The mean pulmonary pressure (MPP) was calculated with Chemla formula (MPP= 0,6 X SPP + 2 mmhg). We calculated PVR, in Wood units (WU), using the formula: PVR = (MPP-PCWP)/CO. Results: The mitral functional area was 1,46±0,35 cm 2 (0,8 to 2,5). The Pm at LLD was - 8,6±4 mmhg, at OP-6,2±3,5 mmhg (p<0,001 vs LLD), at PW - 23,3±9 mmhg (p< 0,0001 vs OP) and at R-15,3±5,6 mmhg (p<0,0001 vs PW). The mean SPP was at LLD - 44±11 mmhg, at OP - 31±11 mmhg, at PW- 63±20mmHg and at R- 56±15 mmhg (p<0,0001 vs PW). The mean PVR was at LLD - 4,2±2,8 UW, at OP - 2,8 UW (p<0,001 vs LLD) and at PW - 1,77 UW (p<0,001 vs OP). According to guidelines, the difference between SPP in PW and R lead to different indication to treatment (medical treatment vs mitral valvuloplasty or substitution with mechanical prosthesis) in 12 pts (18%). Conclusions: 1. The PVR decreased at OP and even more during exercise in treadmill in pts with mitral stenosis; 2. The Pm and the SPP decreased at orthostatic position; 2. The Pm and SPP increased significantly during exercise in studied population and were significantly higher at PW when compared to recovery; 4. The difference between SPP at PW and at R had influenced the clinical decision. P2404 The effect of severity of mitral regurgitation on ejection fraction and end-diastolic volume D.H. Maciver. Musgrove Park Hospital, Taunton, United Kingdom Purpose: Left ventricular ejection fraction (EF) and end-diastolic volume (EDV) are influenced by a complex interplay between pre- & after-load as well as the contractile function. In mitral regurgitation (MR) important clinical decisions, such as need for valve surgery, are influenced by the EF and EDV. Experimental animal studies show an initial increase in strain followed by a normalisation and finally a reduction in strain in severe MR. Therefore, a greater understanding and quantification of the effect of increasing mitral regurgitation on EF & EDV is crucial. Methods: A entirely new 2 shell three-dimensional mathematical model was used to assess the individual effect of increasing mitral regurgitation volume (0, 30, 60, 90 ml) on ejection fraction & end-diastolic volume. Net stroke volumes, left ventricular muscle mass, longitudinal stain & midwall circumferential strain (shortening) were fixed. Results: Increasing mitral regurgitation caused an increase in EDV but, unexpectedly, a fall in ejection fraction when myocardial shortening (strain) was unchanged. Conclusions: Mathematical modelling of ventricular contraction gives important insight into the complex changes that occur with increasing mitral regurgitation. Assuming no change in myocardial strain increasing mitral regurgitation resulted in an increase in EDV but a reduction in left ventricular EF. P2405 Three dimensional dobutamine stress echocardiography predicts the outcome of patients with functional mitral regurgitation K. Obase, N. Watanabe, N. Wada, A. Hayashida, Y. Neishi, T. Kawamoto, H. Okura, K. Yoshida. Kawasaki Medical School, Kurashiki, Japan Background: Dobutamine infusion improves functional mitral regurgitation (FMR) by its vasodilatory and inotropic effects. The aim of the study was to investigate the changes in geometry of mitral valve complex during dobutamine stress echocardiography (DSE) using transthoracic 3D echocardiography and to clarify its impact on the long-term prognosis of patients with FMR Methods: Thirteen patients with FMR underwent transthoracic 3D DSE (up to 40μg/kg/min). Effective regurgitant orifice (ERO) area of FMR was measured. The area of triangle formed by the tips of both papillary muscles and anterior annulus (PM area) was measured from the 3D data. The rate of change in ERO and PM area during DSE were calculated as following formula. % ERO = (ERO at baseline ERO at peak dose/ero at baseline); % PM area = (PM area at baseline PM area at peak dose)/pm area at baseline. Patients were divided into 2 groups according to the % PM area (% PM are a<10% and % PM area 10%). The long-term cardiac events, including cardiac death, valve and/or CABG surgery, percutaneous coronary intervention and congestive heart failure (CHF) were evaluated in both groups. Result: FMR improved in all the study patients during DSE. There was moderate correlation between % ERO and % PM area ( r =0.56). Incidence of cardiac event was significantly higher in group % PM area <10% than group % PM area 10 (p=0.021). Conclusion: Dynamic change in PM position during dobutamine infusion resulted in the reduction in FMR and is a strong predictor of cardiac events in patients with FMR. P2406 The association of natriuretic peptides to symptoms, severity and left ventricular remodelling in patients with organic mitral regurgitation M. Potocki 1,J.Mair 2, M. Weber 3, N. Jander 4,T.Burkard 1, P. Buser 1,C.H.Mueller 1. 1 University Hospital Basel, Basel, Switzerland; 2 Innsbruck Medical University, Innsbruck, Austria; 3 Kerckhoff Klinik GmbH, Bad Nauheim, 4 Herzzentrum Bad Krozingen, Bad Krozingen, Germany Background: Natriuretic peptides reflect cardiac stress and may therefore be useful in the management of patients with valvular heart disease.

105 Mitral, tricuspid and rheumatic valve disease / Prosthetic heart valves 405 Methods: We enrolled 144 patients with chronic moderate-to-severe organic mitral regurgitation (MR) in an international multicenter study to analyze the determinants of N-terminal pro-b-type natriuretic peptide (NTproBNP). NTproBNP levels were measured in a blinded fashion and we quantified symptoms, MR degree, left ventricular (LV) and left atrial (LA) remodelling. Results: NTproBNP levels (median 373 pg/ml [IQR pg/mL]) were associated with age, gender, NYHA functional class, atrial fibrillation, LV end-systolic dimension and LV ejection fraction. Independent predictors of increased NTproBNP levels were NYHA functional class (p<0.001), atrial fibrillation (p=0.008) and LV end-systolic dimension (p=0.026). Importantly, MR severity and LA dimension were not independently associated with NT-proBNP levels. NT-proBNP levels increased significantly with symptom class (p<0.001) but not with MR severity (p=0.144). The NT-proBNP levels were significantly higher in symptomatic patients than in asymptomatic patients (582pg/ml [IQR ] vs. 157pg/ml [64-256]; p <0.0001). The area under the receiver-operator-characteristic curve (AUC) to predict symptoms for NT-proBNP was 0.80 [95% CI, 0.71 to 0.88], which was significantly higher than for all echocardiographic measures (p<0.001 for all). The AUC for NT-proBNP to predict elevated LV end-systolic dimension (> 40mm) was 0.71[ ]. Receiver operating characteristic curves Conclusion: In patients with chronic moderate-to-severe organic MR NT-proBNP levels are determined by age, NYHA functional class, atrial fibrillation and LV endsystolic dimension. Thus, NTproBNP may be helpful in the clinical evaluation and management of patients with MR. PROSTHETIC HEART VALVES P2407 Platelet reactivity in patients with a history of obstructive prosthetic valve thrombosis E. Lev, T. Bouganim, Y. Shapira, M. Vaturi, A. Battler, R. Kornowski, A. Sagie. Rabin Medical Center, Petah Tikva, Israel Background and Purpose: One of the most serious complications of mechanical valves is obstructive prosthetic valve thrombosis (OPVT stuck valve ). Some patients develop OPVT despite an international normalized ratio (INR) in the therapeutic recommended range. We hypothesized that patients who develop OPVT have hyper-reactive platelets. We, therefore, aimed to examine platelet reactivity in patients who developed OPVT, despite therapeutic or neartherapeutic INR, compared with a matched control group. Methods: We compared platelet reactivity between patients who had an OPVT episode, despite therapeutic or near-therapeutic INR, during the years (n=19), and a matched group of patients with mechanical valves who did not develop this complication (n=19). Platelet reactivity was evaluated by platelet aggregation in response to various agonists, platelet deposition under flow conditions in the Impact-R system and plasma levels of platelet activation markers (soluble CD40-L and P-Selectin). Results: In the OPVT group the average INR during the index episode was 3.1±1.5, and 42.9±39 months have elapsed from the index episode to the current study. Both groups were matched for gender (63% women), age±10 yrs (mean yrs), valve position and type, active smoking and diabetes (15.8%). Patients with OPVT history had higher aggregation in response to collagen (P=0.05), higher platelet deposition in the Impact-R system (P=0.001), and tended to have higher levels of sp-selection and scd40l (P= ), than their control counter-parts. Platelet reactivity in the two groups Test Study Group (n=19) Control Group (n=19) P value Aggregation Collagen 1 μg/ml 67.2± ± Aggregation ADP 10 μmol/l 68.5± ± Impact-R: surface coverage % 9.1± ± Impact-R: average size (μm 2 ) 43.8± ± scd40-l (pg/ml) 193.3± ± sp-selectin (ng/ml) 3.0± ± Concluions: Patients with a history of OPVT appear to have increased platelet reactivity, which may contribute to an increased risk of thrombotic complications. These patients would, therefore, likely benefit from the addition of anti-platelet therapy to standard anti-coagulant treatment. P2408 Comparison of dabigatran, unfractionated heparin and low-molecular-weight heparin in preventing thrombus formation on mechanical heart valves, results of an in vitro study L. Maegdefessel 1,T.Linde 2, F. Krapiec 1, U. Steinseifer 2,J.Van Ryn 3, B. Hauroeder 4, U. Raaz 1, M. Buerke 1, K. Werdan 1, A. Schlitt 1. 1 Martin-Luther-Universitaet Halle, Halle, Germany; 2 Helmholtz Institute - RWTH, Aachen, Germany; 3 Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany; 4 Central Institute of the German Federal Armed Forces, Koblenz, Germany Purpose: Lifelong oral anticoagulation (OAC) therapy is required for the prevention of thromboembolic events after implantation of an artificial heart valve. Nevertheless, thromboembolic events occur in approximately 2-4% and bleeding complications in 2-9% of patients per year after mechanical valve replacement despite OAC. Thromboembolism and anticoagulant-related bleedings account for 75% of all complications experienced by heart valve recipients. Dabigatran etexilate, a new and orally available direct thrombin inhibitor, is currently investigated in a phase III trial in comparison to OAC in patients with atrial fibrillation. Dabigatran etexilate might also be an alternative to OAC in patients after mechanical heart valve replacement. The present study investigated the efficacy of dabigatran, in comparison to unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH; Enoxaparin) in preventing thrombus formation on mechanical heart valves in vitro. Methods: Blood (230 ml) from healthy young male volunteers was anticoagulated either by dabigatran (1 μm), UFH (150 IU), or LMWH (100 IU). Aortic valve prostheses (27 mm) were placed in a newly developed in vitro thrombosis tester and exposed to the anticoagulated blood samples under continuous circulation at a rate of 75 beats per minute. The total exposure time was 60 minutes. To quantify the thrombi that developed, electron microscopy was performed. Using a data acquisition unit (DAQ) flow and pressure differences were recorded before and after the heart valve and compared between the three groups. Finally, each valve was weighed before and after the experiment. Results: In whole blood with no anticoagulant, the apparatus completely clotted in minutes. When blood was treated with dabigatran, the mean thrombus weight was 168±92 mg, in the UFH group 162±98 mg, and in the LMWH group 194±117 mg (p-value: for comparison between all three groups via ANOVA). Electron microscopy showed no significant difference in thrombus formation in any group. The DAQ showed a decrease in flow and pressure curves when thrombi occurred in all three groups. Conclusions: Dabigatran was as effective as UFH and LMWH in preventing thrombus formation on mechanical heart valves in our in vitro investigation. Thus, we hypothesize that dabigatran etexilate might potentially be a useful and competitive orally administered alternative to UFH and LMWH for recipients of alloplastic heart valve prostheses. P2409 Twenty-years clinical outcome and hemodynamic performance of the HancockII bioprosthesis C. Valfre, G. Minniti, L. Salvador, V. Salandin, E. Cavarretta, F. Cesari, P. Ius. Treviso Hospital, Treviso, Italy Purrpose: The Hancock II (HII) is a second-generation of porcine bioprosthesis introduced into clinical use in The aim of this study is to evaluate the late clinical and echocardiographic outcome of this bioprosthesis. Methods: Between June 1985 and November 1993, 378 consecutive patients (pts) (234 male, mean age years, range 20-90) underwent valve replacement surgery with HII, respectively 250 (66.1%) in aortic (AVR) and 128 (33.9%) in mitral (MVR) position. Twenty-three year follow-up was complete for all pts at a median of 16 years (range 0-23). Results: Valve replacement was required in 53 patients (14%) after a mean of years ( ). Freedom from reoperation for any cause at 20-years was 77.8% (pts at risk 25). Among 325 pts who didn t undergo valve replacement, 87 pts (26.8%) were still alive with a mean follow-up of years (15-23) and echo data were collected on 45 of them (51.7%). In the whole population Table 1. Echocardiographic parameters Aortic valven=38 Mitral valven=7 Ejection Fraction (%) 59±8 56±9 End Diastolic Diameter (mm) 54±5 51±7 End Systolic Diameter (mm) 36±7 32±3 Valve Regurgitation None 29 (76%) 1 (14%) Trivial 5 (13%) 4 (58%) Mild 3 (8%) 1 (14%) Moderate Severe 1 (3%) 1 (14%) Paravalvular leak 1 (3%) 1 (14%)

106 406 Prosthetic heart valves the left ventricle function resulted preserved and none or trivial valve regurgitation was observed in 89% of the aortic patients and in 72% of mitral patients (Table 1). Conclusions: Based on the unusual high number of patients still alive and free from reoperation at 20-years, the HII bioprosthesis confirms excellent hemodynamic performance at very long-term observation. P2410 Clinical and echocardiographic study in patients reoperated for the prosthetic valve dysfunction M. Maciejewski, K. Piestrzeniewicz, A. Bielecka, M. Piechowiak, M. Lelonek, R. Jaszewski, J. Drozdz. Medical University, Lodz, Poland Introduction: Reoperation in patients with implanted artificial valves are still a serious problem; it is so mainly because of the higher early mortality rate. The incidence of reoperation (R) increases along with the increased number of implanted prosthetic valves (PV). Purpose: To analyse the risk factors of early and late mortality in patients undergoing the first R for prosthetic valve dysfunction (PVD) at the period Methods: Prospective study was performed in 194 consecutive pts (M-75, F- 119; mean age 53.2±11 years) with mechanical prosthetic valve (MPV: n=103 cases; 53%) or bioprosthesis (B: 91; 47%). The period since valve replacement to R was 6 days to 19 years. 22 pts were reoperated up to 30 days since PV replacement. 42 pts underwent urgent reoperation. III-IV NYHA functional class was observed in 105 pts. The types of PVD were: structural PVD in 82 pts (6 pts with MPV and 76 pts with B), endocarditis (IE) in 58 pts, PV blockade in 30 pts, periprosthetic leak in 17 pts, and other reasons in 7 pts. Univariate and multivariate Cox statistical analysis was performed to determine risk factors of early and late mortality. Results: The overall early mortality was 18.6%; 31.4% in pts with symptoms of III-IV NYHA functional class and 3.4% in pts with NYHA I-IIo. Univariate analysis revealed the following predictors of early mortality: urgent R (p<0.01), NYHA III-IVo (p<0.001), IE (p<0.001), R of MPV (p<0.005), plasma creatinine > 1.5 mg/dl (p<0.05), AF (p<0.02), hydropericardium (p<0.05) and EF<55% (p<0.01). Multivariate analysis identified symptoms of NYHA III-IV and IE as independent predictors of early mortality. The overall late mortality (> 30 days) was - 8.2% (0.62% year/patient). The next prosthetic valve replacement (rer) was performed in eight patients; three of these pts (26.3%) died at early period post rer. Univariate analysis revealed the following predictors of late mortality: age (p<0.05), male sex (p<0.05), R for IE (p<0.001), R for MPV (p<0.005), raised concentration of plasma creatinine > 1.5 mg/dl (p<0.05), atrial fibrillation (p<0.05) and left atrial enlargement >5.0 cm (p<0.01). Multivariate analysis identified age at the time of R as a strong independent predictor of late mortality. Conclusions: R in pts with PV, performed urgently espe