Introduction. CLINICAL RESEARCH Pacing and resynchronization therapy. Hermine R. Poghosyan* and Smbat V. Jamalyan. Aims

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1 Europace (2012) 14, doi: /europace/eur415 CLINICAL RESEARCH Pacing and resynchronization therapy Comparison of pacing algorithms to avoid unnecessary ventricular pacing in patients with sick sinus node syndrome: a single-centre, observational, parallel study Hermine R. Poghosyan* and Smbat V. Jamalyan Arrhythmology Cardiology Center of Armenia, Yerevan, Armenia Received 14 September 2011; accepted after revision 11 December 2011; online publish-ahead-of-print 23 May 2012 Aims Reduction of unnecessary ventricular pacing (uvp) is an essential component in the treatment strategy in any pacing population in general. The aim of this study was to evaluate the efficacy of different algorithms to reduce uvp in an adult population with sick sinus syndrome (SSS) treated outside of clinical trials. Evaluation of the relationship between different types of pacing algorithms and clinical outcomes is also provided.... Methods This was a single-centre, observational, parallel study, based on retrospective analysis of the Arrhythmology Cardiology Center of Armenia electronic clinical database. This study evaluated atrial pacing percentage (AP%), ventricular and results pacing percentage (VP%), and the incidence of atrial high rate episodes in 56 patients with SSS using three different pacing strategies: managed VP, search atrioventricular (AV), and fixed long AV. We did not find statistically significant differences in the amount of VP between the groups. Although the atrial high rate percentage (AHR%) tended to be higher in the fixed long AV group, this difference was not statistically significant. Mean VP% and AP% were similar in all three groups.... Conclusions In our study, all three programmed strategies produced the same mean AP% and VP%, and were equally efficient in uvp reduction. There was no relationship between chosen algorithms and the incidence of pacemaker syndrome, hospitalizations, or change in New York Heart Association class. The percentage of AHR was not associated with pacing strategy or co-morbidities but showed borderline correlation with left atrial size Keywords Unnecessary ventricular pacing MVP algorithm Search AV Fixed long AV Atrial high rates Introduction Transvenousventricularpacing (VP) has been traditionally performed from the right ventricular apex because of the long-term pacing stability and the relative ease of pacing electrode positioning. Previous studies (DAVID, MOST, Danish II, and CTOPP) established that unnecessary VP (uvp) could have adverse haemodynamic consequences by worsening cardiac function, precipitating clinically symptomatic heart failure (HF), and predisposing to atrial fibrillation (AF). 1 4 Since the publication of these studies, reduction of uvp has become a standard strategy in pacing populations. Each manufacturer has developed its own algorithm(s) to minimize VP in current pacemakers (PMs) and implantable defibrillators. 5,6 In general, the underlying principles of these algorithms are based on either length of the atrioventricular (AV) interval or AA interval (AAI) with back-up VP. In the INTRINSIC RV trial, the lowest incidence of death or hospitalization for heart failure occurred in the DDD group, in which the AV Search Hysteresis algorithm had been enabled with an 11 19% prevalence of VP. 7 The SAVE-Pace trial has shown that dual-chamber minimal VP devices [managed VP (MVP), search AV] compared with conventional dual-chamber pacing, offered a 40% reduction in the relative risk of the development of persistent AF. The percentage of VP was significantly decreased in the intervention group compared with controls (9.1 vs. 99%). 8 * Corresponding author. Titogradyan 14, EMC, 4th Floor, ACCA Clinic, Yerevan, Armenia. Tel: ; fax: , hermine.poghosyan@acg.am Published on behalf of the European Society of Cardiology. All rights reserved. & The Author For permissions please journals.permissions@oup.com.

2 1484 H.R. Poghosyan and S.V. Jamalyan Similar data in patients with sick sinus syndrome (SSS) treated outside of clinical trials are sparse. The aim of this study was to compare three different algorithms to reduce the amount of uvp in an adult population with SSS who received Medtronic devices in the daily clinical practice of Arrhythmology Cardiology Center of Armenia (ACCA). We assessed the efficacy of each programming algorithm offered by Medtronic, in order to minimize uvp and to improve outcomes in the SSS population. The research questions of the study are as follows: 1. Is there any difference between algorithms in terms of efficacy in reducing uvp? 2. Is there any impact on the amount of atrial pacing (AP) related to the pacing algorithm? 3. Is there any difference in the percentage of time spent in atrial high rate (AHR%) during long-term follow-up related to the pacing algorithm? Methods This was a single-centre, observational, parallel study, based on retrospective analysis of patient records from the ACCA electronic clinical database. To evaluate the efficacy of each programming algorithm to minimize unnecessary VP, we compared the performance of three pacing algorithms in terms of percentage of ventricular pacing (VP%), percentage of AP (AP%), and AHR% based on follow-up charts and information retrieved from the devices. The following inclusion criteria were applied: (i) age.18 years; (ii) SSS; (iii) dual-chamber Medtronic devices; with (iv) at least one algorithm activated to reduced uvp; (v) intact or abnormal AV conduction but not concomitant complete AV block; (vi) no permanent AF; and (vii) no cardiac resynchronization therapy. For this study, to allow for database searches, the SSNS was defined as: average heart rate,50 b.p.m. on ambulatory electrocardiogram (ECG) monitoring with symptomatic pauses over 2 s and/or symptomatic chronotropic incompetence revealed during the treadmill test. Chronotropic incompetence was diagnosed after individuals failed to reach at least 85% of their age-predicted maximal heart rate during the exercise test or had a calculated chronotropic index,0.8. The degree of AV block was determined by ambulatory ECG monitoring before device implantation, and during follow-up by device interrogation and ambulatory ECG monitoring. Device programming: The choice of algorithm was at the discretion of the treating physician. All devices remained programmed to dual-chamber pacing mode (DDD or DDDR), and the same algorithm to diminish unnecessary VP remained unchanged during the follow-up period. In patients with fixed long AV, the AV interval was programmed to 230 ms. Permanent AF was defined as either the inability to restore sinus rhythm by cardioversion, or the recognition that attempts to do so were likely to fail. Using the inclusion criteria, 61 patients were identified in the ACCA database with SSNS and a device either implanted or replaced between November 2007 and November No single patient was missed because of AV interval criteria (SAV or PAV) or SSNS definition. The following exclusion criteria were applied: (i) any sustained complete AV block for.3 months (n ¼ 1); (ii) atrial electrode position rather than right atrial appendage or high atrial septal position (n ¼ 0); (iii) changes in AV intervals or algorithms to avoid uvp in device programming during the last 6 months of follow-up period (n ¼ 2) or (iv) changes in AV intervals or algorithms to avoid uvp during the whole follow-up for those patients with,6 months of follow-up duration (n ¼ 1); (v) changes in antiarrhythmic drug therapy after the first 3 months of follow-up period (n ¼ 1); and (vi) activation of any preventive pacing or antitachycardia pacing algorithm in the atrium during the entire followup period (n ¼ 0). Thus, 56 patients were included in final analysis. Diagnostic data were retrieved from the implanted devices using a Medtronic 2090 programmer. Device implantation was performed according to current recommendations. 9,10 Atrial high rate episodes were defined as five beats above 180 b.p.m. Left atrial (LA) dimension was measured on transthoracic echocardiograms from the parasternal long axis view using Philips Ultrasound HP Sonos The mean LA diameter obtained from all echocardiograms collected during the follow-up period. Study endpoints The primary endpoints of the study were mean VP%, AP%, and AHR%. Secondary endpoints were heart failure worsening by New York Heart Association (NYHA) class, hospitalization for any cardiovascular reason, pacemaker syndrome, and association of AHR% with the following parameters: VP%, AP%, underlying disease, and mean LA diameter. Study groups Medtronic has developed the following algorithms to reduce uvp: Managed VP: The MVP operates during atrial-based pacing (AAI/R) with back-up VP during AV block. When AV conduction is lost for two out of four atrial to atrial depolarization intervals, the device switches to DDD/R mode with pre-programmed SAV and PAV intervals. Then, periodical checks for AV conduction are performed. 11 Search AV algorithm operates in DDD/R mode with automatic extension of AV interval. The search AV operates in DDD/R mode as well as in DDI/R, DVI/R, or VDD mode with automatic extension of PAV and SAV intervals as needed to promote intrinsic ventricular activation. If AV conduction is not found within the range of maximally extended AV intervals, the device reverts to the programmed AV intervals and suspends search AV operations for progressively longer periods. Fixed long AV interval:we defined a fixed long AV interval as PAV and SAV interval.230 ms. The study population was divided into the following three groups: MVP group, search AV group, and fixed long AV group. We also combined patients from the MVP group and the search AV group in a C+ group.

3 Pacing algorithms in patients with sick sinus node syndrome 1485 Statistical analysis All analysis had been performed using STATA 10 statistical software. Due to the small sample size, non-parametric Fisher s exact test was used to test for differences between groups for categorical variables. Distributions of all continuous variables were examined by the help of QQ plots to test for normality. Kruskal Wallis analysis of rank test and Wilcoxon Mann Whitney test were used to test differences between groups for continues variables. Simple linear regression analysis was used to test for associations between continuous variables. Ethical considerations The study was approved by the Institutional Review Board on Human Research within the College of Health Sciences at the American University of Armenia. Results Baseline patient demographic characteristics device programming, and pacing parameters of the study population are shown in Table 1. The mean age was 62.9 years. The mean follow-up duration was months. There were no statistically significant differences in baseline parameters between the groups. Using the maximal target dose of the drug recommended by guidelines, we compared doses of b-blocker therapy and found no statistically significant difference between groups. The use of other antiarrhythmic drugs was similar in all four groups. There were statistically significant differences in follow-up duration only between the C+ and the fixed long AV groups (P, 0.03), and we performed comparison with adjustment for differences in follow-up duration. There were no differences in other parameters. Percentage of ventricular and atrial pacing, and atrial high rate episodes Analyses are summarizes in Table 2. We did not detect any statistically significant difference in VP% that was similarly low in all three groups. Although the mean AHR% was higher in the fixed long AV group, it did not reach statistical significance. Atrial pacing percentage did not differ between groups. We compared algorithms in patients with VP% over 40%. Most of these patients had VP amount of,30%, and the groups were not different on this point as well. There was no statistically significant difference between the C+ group and the fixed long AV group in terms of VP% and/or AHR% and/or AP% with or without adjustment of follow-up duration. Heart failure and New York Heart Association class Changes in NYHA class and the incidence of HF hospitalizations are shown in Table 2. There was no hospitalization for HF during the follow-up. Both baseline NYHA class and changes in NYHA class in all three groups were similar. In total, seven patients had HF improvement in NYHA class, and seven patients had HF worsening by NYHA class in the study population. However, these changes were not associated with a device algorithm for reduction of uvp. Hospitalization for any cardiac reason In total, five patients had 10 hospitalizations for a cardiac reason. All hospitalizations were for electrical or pharmacological cardioversions. In the MVP group, one patient had five cardioversions during the follow-up period, whereas in the search AV group there was only one cardioversion, and in the fixed long AV group three patients underwent five cardioversions (Table 2). Pacemaker syndrome Diagnosis of PM syndrome was based primarily on the patient s symptoms, such as anxiety, weakness, chest pain, syncope or near-syncope, dyspnoea, cough, and increased jugular vain pressure. Temporary VVI pacing or pacemaker-mediated tachycardia (PMT) were also used for diagnosing PM syndrome. Four PM syndrome episodes had been suspected based on the above-mentioned criteria: one in the MVP group, one in the fixed long AV group, and two in the search AV group. Association of atrial high rates, percentage of atrial and ventricular pacing, underlying disease, and left atrial diameter Linear regression analysis was used to test the correlation between AHR% and VP%/AP%. We did not find any correlation between AHR% and VP% or AHR% and AP%. The AHR% showed a marginally significant correlation with LA diameter. LA size of mm showed no correlation (r ¼ 3.7, P ¼ 0.1), whereas LA.48 mm had a strong correlation with AHR% (r ¼ 4, P, 0.05), although there was no correlation between AHR% and co-morbidity. Discussion The general concern about conventional DDD pacing is that there is a high probability of uvp in patients with an intact AV conduction, as the nominal programmed AV interval is similar to the native PR interval. 8,12 In the study reported by Nielson et al. in patients with intact AV conduction, the fixed extension of AV intervals has been proved to be ineffective in reducing VP and is associated with a high risk of arrhythmias caused by repetitive retrograde ventriculo-atrial conduction. 13 Managed VP has been proved to be superior to search AV algorithm in minimizing VP, particularly in patients with first degree AV block. 14 We did not confirm these findings in our study. However, the purpose of our study was not to find the best algorithm for pacing in the SSS population but to compare randomly used algorithms to diminish uvt in daily clinical practice. The mean VP% in our study was low in all groups, but, surprisingly, it was not lower in the MVP group compared with the search AV and/or fixed long AV groups. Noticeably, fixed long AV appears to be as efficient as more complex algorithms, especially as this would be the most battery-preserving option. Sick sinus node syndrome definition in our study differs from those in the guidelines. The definition of SSS is always a difficult

4 1486 H.R. Poghosyan and S.V. Jamalyan Table 1 Baseline characteristics and pacing settings Variables All MVP Search AV Fixed long AV P value (n 5 56) (n 5 13) (n 5 12) (n 5 31) Age (years, mean + SD) a Male gender [n (%)] 28 (50.00) 7 (12.5) 4 (7.14) 17 (30.4) 0.51 b LVEF (%, mean + SD) a LA (mm, mean + SD) a Co-morbidity [n (%)] Valvular diseases 9 (16.07) 3 (5.36) 0 (0) 6 (6.67) 0.58 b Coronary artery disease 12 (21.43) 2 (3.57) 3 (5.36) 7 (12.5) 0.83 Cardiomyopathy 8 (14.55) 2 (3.64) 2 (3.64) 4 (7.27) 1.00 Hypertension 38 (67.86) 9 (16.07) 8 (14.29) 21 (37.5) 1.00 Diabetes mellitus 7 (12.5) 2 (3.57) 1 (1.79) 4 (7.27) 1.00 a CHF history 8 (14.29) 3 (5.36) 1 (1.79) 4 (7.27) 0.59 a AT/AF history 28 (50.0) 6 (10.71) 3 (5.36) 19 (33.93) 0.12 a Medication [n (%)] b-blockers 43 (76.78) 12 (23.21) 9 (8.93) 22 (21.43) 0.33 b Low dose 14 4 (7.14) 4 (7.14) 6 (10.7) Intermediate dose 21 4 (7.14) 5 (8.93) 12 (21.4) High dose 8 4 (7.14) 0 (0) 4 (7.14) Class I/III antiarrhythmics 16 (28.57) 5 (8.93) 1 (1.79) 10 (17.86) 0.20 Digoxin 2 (3.57) 0 (0.00) 2 (3.57) 0 (0) 0.04* Calcium-channel blockers 20 (35.71) 6 (10.71) 5 (8.93) 9 (16.07) 0.45 ACE-I/ARBs 37 (66.07) 9 (16.07) 6 (10.71) 22 (39.29) 0.48 SSS as a primary indication for PM 42 (75.0) 10 (23.81) 8 (19.05) 24 (57.15) 0.78 Concomitant AV block grade (%) None 25 (44.64) 7 (12.5) 5 (8.93) 13 (23.21) 0.77 First degree AV block 15 (26.79) 3 (5.36) 3 (5.36) 9 (16.07) 1.00 Second degree AV block 5 (8.93) 0 (0) 2 (3.57) 3 (5.36) 0.30 Advanced AV block vs. non-sustained third degree AV 10 (17.86) 2 (3.57) 2 (3.57) 6 (10.71) 1.00 block Follow-up duration (months, mean + SD) * Pacing parameter settings by groups Lower rate (b.p.m., mean + SD) a Upper tracking rate (b.p.m., mean + SD) a Upper sensor rate (b.p.m., mean + SD) a Rate response on [n (%)] 10 (76.9) 6 (50.0) 21 (67.7) 0.39 b Automatic PVARP on [n (%)] 7 (53.8) 8 (66.7) 13 (41.9) 0.35 b Mode switch on [n (%)] 5 (41.6) 4 (33.3) 17 (54.8) 0.40 b Lead impedance trend on [n (%)] 13 (100.0) 12 (100.0) 31 (100.0) 1.00 b NCAP [n (%)] 3 (23.1) 4 (33.3) 6 (19.3) 0.64 b PMT intervention [n (%)] 5 (41.6) 4 (33.3) 8 (25.8) 0.68 b a Wilcoxon Mann Whitney test was used for the continuous variables. b Fisher s exact test was used for the categorical variables. *95% confidence interval. ACE, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; AT, atrial tachycardia; AV, atrioventricular; CHF, congestive heart failure; LVEF, left ventricular ejection fraction; NCAP, non-competitive atrial pacing; PMT, pacemaker-mediated tachycardia; PVARP, post-ventricular atrial refractory period; SD, standard deviation; SSS, sick sinus syndrome. task because it refers to a broad array of abnormalities in the sinus node and atrial impulse formation/propagation. The definition used in this study was adapted to our clinical setting, making it possible to introduce the exact criteria for the database filters to select the target population. Unfortunately, in our case, we cannot use standard guidelines definitions as a criterion for database searching. However, all patients in the ACCA database with PM and SSS were included in the initial population group of the study, so no patients were missed before applying exclusion criteria. The IDEAL RVP study is the first prospective cross-over study that performed a head-to-head assessment of MVP and search AV to minimize uvp% in the same individuals. This study included

5 Pacing algorithms in patients with sick sinus node syndrome 1487 Table 2 Outcomes Outcome variables Mean + SD P value... MVP Search AV Fixed long AV (n513) (n512) (n531) VP% a AP% a AHR% a 40% VP burden VP%, 40% n (%) 12 (92.3) 9 (75.0) 28 (90.3) 0.42 b VP%. 40% n (%) 1 (7.7) 3 (25.0) 3 (9.7) NYHA class No change n (%) 9 (69.2) 10 (83.3) 23 (74.2) 0.69 a Improvement n (%) 2 (15.3) 0 (0.0) 5 (16.1) Worsening n (%) 2 (15.4) 2 (16.7) 3 (9.6) Hospitalizations for any cardiac reason (n patients/number of hospitalizations) Cardioversion 1/5 1/1 3/ /0.08 HF decompensation 0/0 0/0 0/ Combined MVP and search AV groups Fixed long AV (n525) (n531) VP% c AP% c AHR% c a Kruskal Wallis equality-of-populations rank test results. b Fisher s exact test. c Mann Whitney U test results. AHR, atrial high rates; AP, atrial pacing; HF, heart failure; VP, ventricular pacing. 127 patients in 14 centres. The main finding was that the MVP algorithm offered a further VP% reduction compared with the search AV algorithm in patients with dual-chamber PM, except for the population diagnosed with a persistent loss of AV conduction. 15 Although differences between programs to diminish uvp in groups (based on type of AV conduction) were statistically significant in the IDEAL RVP study, the follow-up in each arm was only 1 month. 16 Owing to the small number of patients, we did not compare VP% in patients with a different degree of AV block. However, we found a relatively low amount of VP% (close to 30%) in all groups, and there was no difference in mean VP% or AV conduction type between groups. We did not find any statistically significant difference in AHR%, AP%, VP%, or worsening heart failure between the combined MVP search AV algorithms (C+) group and the fixed long AV group. In our study, patients received more or less equal medical treatment. There was no statistically significant difference in the use of class I/III antiarrhythmic drugs: 15 patients received sotalol or amiodarone, and one patient in the MVP group received propafenon. The use of b-blocker agents and doses were similar across the groups (Table 1). In the SAVE-Pace trial, reduction in the occurrence of persistent AF showed a linear correlation with VP%. 8 The most recently published MinVPACE study showed a significant reduction in the rate of persistent AF with minimal VP (9%) when compared with conventional DDDR pacing (42%). 17,18 We used mean AHR% to evaluate atrial arrhythmia, and found no difference in mean AHR% between groups. A comparison of the C+ group and the fixed long AV group showed similar results. For evaluation of AHR% we used PM telemetry data only, which is a limitation. However, in the study by Kristensen et al. the specificity and sensitivity of PM telemetry for detection of atrial tachyarrhythmias was 100 and 90%, respectively, and the false-positive rate was 0%. 19 The mean AHR% was higher in the fixed long AV group, but there was no statistically significant difference in AHR% between the groups. This finding may be partly explained by the assumption that AHR% correlates with the amount of VP% as observed in SAVE PACE. However, in our study with a small sample size we could not determine a correlation between AHR% and VP%/AP%. Risk factors for AF are well established and validated. 20,21 We found a linear correlation between AHR% and LA diameter. The association between LA size and AF has previously been reported. 22,23 Whether these atrial arrhythmias are due to SSS (as a tachy-component of disease) or are related to co-morbidities is questionable owing to the small size of our study. However, we did not find a statistically significant association between mean AHR% and co-morbidities. All three algorithms to diminish uvp are different not only in their underlying principles, but also in their behaviour in different clinical conditions. In clinical practice, it will be useful to have evidence-

6 1488 H.R. Poghosyan and S.V. Jamalyan Table 3 Comparison of current algorithms for minimizing ventricular pacing Clinical settings AAI(R) DDD(R) Adaptive AV Fixed long AV First degree AV block Continued functional AAI pacing with Immediate VP at the appropriate or VP with fixed long AV interval inappropriate long AV interval inappropriate AV delay AAIR pacemaker syndrome Intermittent second degree AV block Repeated pauses, inappropriately short or long AV intervals. Manufacturers AAI(R) DDD(R) Adaptive AV Maximum AV Medtronic MVP (for detail see below) Search AV (for detail see below) Up to 440 ms St Jude AICS/VIP a Up to 350 ms (Accent DR) ElA AAIsafeR algorithm b Up to 450 ms Biotronik VP suppression w algorithm c AV hysteresis (I-Opt) d 300 ms (Talos, Cylos, Phylos) Boston Scientific AVSH algorithm e 300 ms (Altrua/Insigna/Nexus/ Vitality/Vitality I) based guidelines in order to better select algorithms to reduce VP. Comparison of the advantages and disadvantages of these algorithms from different manufacturers is summarized in Table 3. It is also important to highlight that prolongation of the AV interval leads to a high probability of endless loop tachycardias We observed only two cases of documented PMT from device recordings, and both patients were in the fixed long AV group. Additionally, it is important that long AV delay programming can limit the upper rate in cardiac stimulation. It is important to evaluate the upper rate in patients with SSS and long AV interval using not only clinical data or PM telemetry, but also Holter monitoring and exercise stress-test. It is highly recommended to analyse the upper rate behaviour in a future prospective study. Pacemaker syndrome is typically seen in patients with retrograde VA conduction and prolonged AV interval. In our study, it occurred in all three groups in different circumstances. Limitations and strengths Our findings could be compromised by the small sample size and retrospective design of the study. However, this criticism may be offset by the relatively long follow-up with unchanged device programming and drug regimen. We have not done power calculations Immediate VP VP with fixed long AV interval Pause-dependent VT High likelihood 27,28 Not possible Not possible Diagnostic Event and histogram cannot dissect MVP Search AV + histogram Ventricular rate histogram behaviour Fusion beats Less possible More possible Possible Current algorithms for minimizing VP offered by different manufacturers a AICS/VIP (St Jude) in devices starting with Affinity, the algorithm is called Auto Intrinsic Conduction Search (AICS). It was modified and improved in Victory pulse generators and is now called ventricular intrinsic preference (VIP). b AAIsafeR algorithm (ELA) is programmable with maximum AV delay up to 450 ms to prevent the potential marked pauses. It also incorporates a variety of event counterdiagnostics, including a tabulation of the number of times the device has exited the AAIsafeR algorithm, the reasons for exiting, and examples captured on electrogram snapshots. c VP suppression w algorithm (Biotronik): the advanced VP Suppression w algorithm, the Estella pacemaker series significantly minimizes VP. Ventricular pacing suppression switches to ADI(R) mode when intrinsic rhythm is present and operates in DDD(R) mode when intrinsic rhythm is absent. d AV hysteresis (Biotronik) is programmable as a repetitive or scan option. e AV search hysteresis (AVSH) algorithm (Boston Scientific): every N number of cycles (programmable), the algorithm would extend the programmed AV delay by a percentage (also programmable) of the programmed AV delay searching for intact AV conduction. AV, atrioventricular; VT, ventricular tachycardia. because of the retrospective design of this study; instead we used non-parametric statistics to enhance the statistical accuracy. The study population is not the best one to be treated with MVP (the second degree AV block was too low, being completely absent in the MVP group). In our study, we did not evaluate fused or pseudo-fused VP. These beats have normal or near normal ventricular contraction and do not affect cardiac function or count for adverse VP. Fused ventricular beats are more likely to be created by the search AV algorithm and to some extent can happen in any of our three initial groups. We have no means to adjust VP amount relative to fusion. Adjusting for PM syndrome had little effect, as the diagnosis of this syndrome relies on patients complaints exclusively. We cannot rule out possible endless loop tachycardia episodes that might account for PM syndrome because device programmable settings to prevent these arrhythmias [non-competitive atrial pacing (NCAP), PMT intervention] were not always activated. However, we had only two patients in the study with documented endless loop tachycardia and both were among the four patients diagnosed with PM syndrome. These two patients remained minimally symptomatic even after activation of PMT intervention. However, except for these four patients there was no other patient with clinical symptoms suggestive of PM syndrome.

7 Pacing algorithms in patients with sick sinus node syndrome 1489 We did not evaluate quality of life in the study population because it was not within the scope of the study and the groups were not homogeneous, showing a wide distribution of age, underlying disease, and co-morbidities. However, it would be highly recommended to take into consideration quality of life for any prospective study. Conclusion This study evaluated mean AP%, VP%, and AHR% in patients with SSS using three different strategies to diminish uvp in daily clinical practice: AAI/R mode with back-up VP during AV block of MVP, automatic extension of AV interval of search AV and fixed long AV interval. We did not find a significant differences in VP%, AHR%, or AP% related to the pacing strategy. AHR% had a marginal correlation with LA diameter but not co-morbidities. All three strategies were equally effective in reducing uvp. There was no statistically significant difference in NYHA class change, PM syndrome, or cardiac hospitalizations related to pacing strategies. It would be useful to have evidence-based guidelines in order to better select algorithms to reduce VP. Further prospective studies will be necessary to determine efficient algorithms to reduce uvp in patients with SSS. Acknowledgements We would like to express our thanks to Karapet L. Davtyan MD, MPH. Conflict of interest: none declared. References 1. Wilkoff BL, Cook JR, Epstein AE, Greene HL, Hallstrom AP, Hsia H et al. Dualchamber pacing or ventricular backup pacing in patients with an implantable defibrillator: the Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial. JAMA 2002;288: Sweeney MO, Hellkamp AnS, Ellenbogen KA, Greenspon AJ, Freedman RA, Lee KL et al. 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