Transcatheter Aortic Valve Implantation in Very High-Risk Patients With EuroSCORE of More Than 40%

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1 Transcatheter Aortic Valve Implantation in Very High-Risk Patients With EuroSCORE of More Than 40% Thorsten Drews, MD, Miralem Pasic, MD, PhD, Semih Buz, MD, Guiseppe d Ancona, MD, PhD, Stephan Dreysse, MD, Marian Kukucka, MD, Alexander Mladenow, MD, Roland Hetzer, MD, PhD, and Axel Unbehaun, MD Deutsches Herzzentrum Berlin, Berlin, Germany Background. Transcatheter aortic valve implantation (TAVI) is a new method for the treatment of high-risk patients with aortic valve stenosis. Although a logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) of more than 40% has been considered a contraindication for this new procedure, we routinely perform this procedure in this very high-risk patient group. We analyzed the results of TAVI patients with a EuroSCORE of over 40%. Methods. Between April 2008 and January 2012, 514 consecutive patients underwent TAVI. In the study group (group I, EuroSCORE > 40%) of 186 patients the EuroSCORE was 63% 16% (range 40 to 98) and the Society of Thoracic Surgeons predicted risk of mortality score was 23% 14% (range 4 to 90); there were 26 (14%) patients in cardiogenic shock. The mean age was 81 8 (range 36 to 99) years and there were 122 women and 64 men. Group II (the control group, EuroSCORE < 40%) consisted of 328 patients. In this group the EuroSCORE was significantly lower (23% 9%, range 2% to 40%). The STS mortality score was 11% 8% (1% to 48%). In this group were 196 men and 132 women with a mean age of 78 8 (range 29 to 97) years. Results. Technically, in group I the valve was successfully implanted in 99.5% (185 of 186). In 25 (13%) patients the procedure was performed on the heart-lung machine and in 25 (13%) patients an elective percutaneous coronary intervention was performed in the same session. Postoperative echocardiography showed a low transvalvular gradient (mean 4.5% 2.5%, range 2 to 15) and a low rate of paravalvular regurgitation (grade 0 in 97, less than grade I in 49, less than grade II in 38 patients, and grade II in 2 patients). The overall 30-day mortality in patients with EuroSCORE of over 40% (group I), including that in patients in cardiogenic shock, was 6.5%, and in patients with EuroSCORE of over 40% (group I) and without cardiogenic shock it was 5.7%; the 1-year survival was 67% and 71%, respectively, and the 2-year survival was 54% and 56%, respectively. Conclusions. Patients with comorbidities, as mirrored by a EuroSCORE of more than 40% should not be refused for TAVI. On the contrary, this is a supreme indication for the TAVI procedure. (Ann Thorac Surg 2013;95:85 93) 2013 by The Society of Thoracic Surgeons Transcatheter aortic valve implantation (TAVI) has become a standard procedure in multiple centers for high-risk patients with severe aortic stenosis [1 10]. In order to justify this cost-intensive new procedure with unknown durability of the prosthesis, the use of risk scores showing an expected risk of mortality of over 10% and over 15% for conventional surgery has been recommended by Medtronic (Medtronic Inc, Minneapolis, MN) and Edwards Lifesciences (Irvine, CA), respectively, and over 20% by several authors [1, 2, 11]. The European System for Cardiac Operative Risk Evaluation (EuroSCORE), introduced in 1999, is used by several European centers in order to have a scoring Accepted for publication Aug 22, Presented at the Forty-eighth Annual Meeting of The Society of Thoracic Surgeons, Fort Lauderdale, FL, Jan 28 Feb 1, Address correspondence to Dr Pasic, Deutsches Herzzentrum Berlin, Augustenburger Platz 1, Berlin, Germany; pasic@dhzb.de. system for the prediction of early mortality on the basis of objective risk factors [12 14]. Because this scoring system seems to overestimate the risk of mortality, a new model, EuroSCORE II, was introduced in 2011 [15]. Additionally, with the aid of the Society of Thoracic Surgeons (STS) National Adult Cardiac Surgery Database (STS NCD) in the late 1980s, the STS developed several different risk models for death and major morbidities that were first applied in 1994 [16]. The latest model, introduced in 2008, was developed using data collected between 2002 and Whether the EuroSCORE or the STS predicted risk of mortality score is the more useful to predict perioperative mortality has been discussed by several authors [16 18]. Drs Pasic, Drews, Buz, Unbehaun, and Dreysse disclose financial relationships with Edwards Lifesciences by The Society of Thoracic Surgeons /$36.00 Published by Elsevier Inc

2 86 DREWS ET AL Ann Thorac Surg TAVI IN HIGH-RISK PATIENTS WITH EUROSCORE MORE THAN 40% 2013;95:85 93 Although Walther and colleagues [1, 2] showed in 2007 that transapical aortic valve implantation might reduce the risk of conventional surgical aortic valve replacement in very high-risk patients, some authors recommend performing TAVI only in patients with an STS mortality score less than 20% and a EuroSCORE less than 40%, and in those with expected survival of over 1 year [19]. The prognosis of patients who are not candidates for TAVI or for conventional aortic valve replacement is grave [20, 21]. Their mortality rate at 6 months is 31.8% and at 2 years 53.4%. Therefore, we routinely perform this procedure in this very high-risk patient group with a EuroSCORE greater than 40%, in patients with an expected survival of less than 1 year and in patients with significantly reduced left ventricular function (less than 25%) [21, 22]. An alternative is to perform TAVI on cardiopulmonary bypass (CPB) [23]. Thus the procedure can be performed in patients with severely depressed left ventricular function with or without cardiogenic shock. Additionally, previous heart surgery in this high-risk patient group will not increase the perioperative risk [24]. In this study, we examine the surgical procedure and the postoperative course of patients undergoing transcatheter aortic valve implantation presenting with a EuroSCORE of over 40%. Patients and Methods Patients Transcatheter aortic valve implantation was performed between April 2008 and January 2012 in 593 patients at the Deutsches Herzzentrum Berlin. In 514 patients, transapical implantation of an Edwards SAPIEN valve (Edwards Lifesciences) was conducted. All 514 were multimorbid (with peripheral vascular disease, diabetes mellitus, pulmonary hypertension, etc) and presented with severe aortic valve stenosis in advanced age ( 70 years of age) or high preoperative risk assessment (logistic EuroSCORE 20%). None of the evaluated very high-risk patients were refused treatment regardless of comorbidities and clinical status (eg, profound shock; except patients with active endocarditis) if, technically, it was possible to perform the procedure in terms of the annular size. Especially in patients undergoing reoperation, the transapical route for aortic valve implantation was chosen because it enables more precise valve handling and positioning due to the antegrade approach with shorter access to the aortic annulus [24]. The total group of 514 patients was divided into 2 subgroups according to whether the EuroSCORE was higher or lower than 40%. Table 1. Patient Data ([n]/% or Mean SD, Range) Variable Group I Group II Test Number of patients [n] Gender [female/male] 122/64 196/132 NS a Age [years] 81 8 (36 99) 78 8 (29 97) p b Weight [kg] (40 122) (37 147) p b Body mass index 26 5 (17 43) 28 6 (17 59) p b Comorbidity Peripheral vascular disease 158 (85%) 217 (66%) p a Coronary heart disease 133 (72%) 179 (55%) p a Chronic obstructive pulmonary disease 122 (66%) 165 (50%) p a Pulmonary hypertension (systolic 50 mm Hg) 117 (63%) 76 (23%) p a Stroke 79 (42%) 48 (15%) p a Diabetes mellitus 53 (28%) 113 (34%) NS a Previous surgery CABG 52 (28%) 38 (12%) p a AVR 18 (10%) 11 (3%) p a MVS 10 (5%) 2 (1%) p a Other 7 (4%) 4 (1%) NS a Cardiogenic shock 26 (14%) 2 (1%) p a Laboratory data Creatinine (mg/dl) ( ) ( ) p b Pro-BNP (pg/ml) 9,093 11,245 (97 77,019) 2,827 4,061 (10 34,898) p b Preoperative risk score EuroSCORE [logistic, %] (40 98) 23 9 (2 40) p b STS PROM score [%] (4 90) 11 8 (1 48) p b a Fisher exact test. b Mann-Whitney U test. AVR aortic valve replacement; BNP B-type natriuretic peptide; CABG coronary artery bypass grafting; EuroSCORE European System for Cardiac Operative Risk Evaluation; MVS mitral valve surgery; NS not significant; STS PROM Society of Thoracic Surgeons Predicted Risk of Mortality.

3 Ann Thorac Surg DREWS ET AL 2013;95:85 93 TAVI IN HIGH-RISK PATIENTS WITH EUROSCORE MORE THAN 40% Group I (study group, EuroSCORE 40%) consisted of 186 patients (122 women and 64 men) with a mean age of 81 8 (range 36 to 99) years (Table 1). The EuroSCORE was 63% 16% (range 40% to 98%) and the STS mortality score was 23% 14 % (4% to 90%). The left ventricular ejection fraction was in the mean (range 0.10 to 0.70). Twenty-six (14%) patients presented with cardiogenic shock (low cardiac output with preoperative use of inotropes and critical preoperative state in EuroSCORE classification) and in 25 (13%) patients the CPB was used due to severely impaired heart function (Table 2). Group II (the control group, EuroSCORE 40%) consisted of 328 patients in whom the TAVI procedure was performed (Table 1). In this group the EuroSCORE was significantly lower: 23% 9% (range 2% to 40%). The STS mortality score was 11% 8% (1% to 48%). In this group were 196 women and 132 men with a mean age of 78 8 (range 29 to 97) years. The LV ejection fraction was in the mean (range 0.10 to 0.70); in 10 patients (3%) the procedure was performed with CPB (Table 2). Methods: Preoperative and Postoperative Evaluation The preoperative and postoperative examinations included clinical and laboratory examinations, electrocardiogram, chest X-ray, transesophageal echocardiography, and multislice computed tomography of the chest and pelvis followed by vascular three-dimensional reconstruction. This allowed us to choose the antegrade or retrograde approach and, in the case of cannulation for the heart lung machine, to identify the optimal vessel [23]. Preoperative coronary angiography and ultrasound examinations (Doppler) of the arteries and veins of the lower extremities, and of the carotid arteries, were performed. The Doppler examination allowed the detection of severe peripheral vascular disease. The echocardiographic data, the postoperative course, potential complications, and the late outcome were followed. The preoperative and postoperative clinical examination included registration of the neurologic status. As the mean age of the patients was 79 8 (range 29 to 99) years, their general condition was mostly seriously impaired (EuroSCORE 38% 23%, range 2% to 98%; STS risk calculator 15% 12%, range 1% to 90%) and 25% (127 of 514) of them had a history of stroke, strict neuropsychologic examination could not be performed. However, the following were recorded: vigilance; orientation toward time and location; oculomotoric movements; field of vision; motor function; sensibility; dysarthria, and neglect, in accordance with the criteria of the National Institutes of Health Stroke Scale [25]. The echocardiographic data, the postoperative course, potential complications, and the late outcome were followed (Tables 3, 4, and 5). Additionally, a routine checkup was performed 1 month and 1 year after the operation. The data were compared between the 2 groups. Methods: Procedural and Technical Considerations Immediately before the procedure, the whole team analyzed the diagnostic workup and discussed possible technical difficulties and complications and means to prevent them, as well as the use of the heart-lung machine. The elective use of cardiopulmonary bypass was considered in patients with reduced ejection fraction (below 0.20), if the patient presented in cardiogenic shock 87 Table 2. Operative Data (Mean SD, Range) Variable Group I Group II Test Number of patients [n] Technical success rate 185 (99.5%) 324 (99%) NS a On-pump surgery 25 (13%) 10 (3%) p a Intraaortic balloon pump 12 (6%) 1 (0.5%) p a Size of the valve: 23/26/29 mm 69/101/16 88/209/31 p 0.02/p 0.04/NS a Percutaneous coronary intervention Elective/urgent 25/- 32/4 NS a Pacemaker implantation DDD/VVI 3 (2%)/8 (4%) 9 (3%)/8 (2%) NS a Duration of hospitalization [days] Length of stay on ICU (0.1 59) (0.1 32) p b Total length of stay (1 110) (0.3 46) p b Mortality 30-day mortality 12 (6.5%)/9 (5.7%) d 11 (3.4%) p c Survival 6-month survival 73%/78% d 90% 1-year survival 67%/71% d 89% 1.5-year survival 64%/67% d 86% 2-year survival 54%/56% d 80% a Fisher exact test. b t test. c Log-rank test (p 0.05). d Without cardiogenic shock. ICU intensive care unit; NS not significant.

4 88 DREWS ET AL Ann Thorac Surg TAVI IN HIGH-RISK PATIENTS WITH EUROSCORE MORE THAN 40% 2013;95:85 93 (eg, catecholamine dependence, organ failure, artificial ventilation), in cases of patients with relevantly enlarged right ventricle with pulmonary hypertension, or when a concomitant conventional surgical procedure was planned [23]. Elective coronary artery stent implantation was considered in patients with concomitant coronary artery disease. Only the most relevant coronary artery stenosis was considered to be a target for stent implantation [22]. The procedures were performed in a hybrid operating room in a completely sterile environment and under fluoroscopic imaging with a monoplane angiography system. All patients were under general anesthesia. The surgical technique of transcatheter valve implantation was based on the procedure described by several authors [1 4], with the modification of transcatheter valve positioning and liberation under simultaneous angiography with contrast medium in order to find the optimal valve position and to reduce the risk of paravalvular leakage [10]. The procedure was monitored by fluoroscopy, angiography, and intraoperative transesophageal echocardiography. The study was approved by the Institutional Review Board. All patients provided written informed consent. Statistical Evaluation All data analyses were performed using PASW Statistics, version 18.0 (SPSS, Inc, Chicago IL). The Gaussian distribution of the data was tested by the Kolmogorov-Smirnov test. Depending on the result, the measurements were analyzed by the Levene test for variance, and by the Mann-Whitney U test and the unpaired sample t test to find significances. For survival analysis (Kaplan-Meier curves) the log-rank test was used. A Cox proportional hazards model was used to investigate possible risk factors for mortality. A univariable approach for all possible risk factors was evaluated. Proportional hazard assumptions were checked. For several parameters, multivariable Cox proportional hazards models with all combinations were performed. The best model was chosen according to Akaike information criterion. A value of p less than 0.05 was considered to indicate statistical significance. Results Procedural and Postprocedural Course In all patients the technical procedure was performed using the standard technique [22]. The technical suc- Table 3. Echocardiographic Data (Mean SD, Range) Variable Group I Group II Test Number of patients [n] Preoperative Left ventricular 51 9 (33 80) 48 7 (30 73) p a End diastolic diameter [mm] Left ventricular ejection fraction ( ) ( ) p a Aortic valve Insufficiency [degree] (0 4) (0 4) p a Orifice area [cm 2 ] ( ) ( ) NS b Diameter of aortic annulus [mm] (15 28) (18 29) NS b Gradient max [mm Hg] (15 125) (14 140) p a Gradient mean [mm Hg] (8 90) (7 100) p a Mitral valve Insufficiency [degree] (0 3) (0 3) p a Tricuspid valve Insufficiency [degree] (0 4) (0 3) p a Postoperative Central AVI (degree) 20 (11%) 32 (10%) NS c Grade 0 I Grade I 6 12 Grade I II 2 Grade II Paravalvular AVI (degree) 69 (37%) 114 (35%) NS c Grade 0 I Grade I Grade I II 8 12 Grade II 2 2 Aortic valve gradient Max [mmhg] (3 29) 9 5 (0 40) NS a Mean [mmhg] (2 15) (1 20) NS a a Mann-Whitney U test. b t test. c Fisher exact test. AVI aortic valve implantation; NS not significant.

5 Ann Thorac Surg DREWS ET AL 2013;95:85 93 TAVI IN HIGH-RISK PATIENTS WITH EUROSCORE MORE THAN 40% Table 4. Predictive Factors of Cumulative Survival (Univariable Cox Regression Analysis) Variable Hazard Ratio 95% CI p Value Gender Age NS Weight NS Body mass index NS Peripheral vascular disease NS Coronary heart disease NS Pulmonary hypertension (systolic NS 50 mm Hg) Chronic obstructive pulmonary NS disease Diabetes mellitus NS Stroke NS Previous CABG NS Previous AVR NS Previous MVS NS Previous other cardiac surgery NS Cardiogenic shock Kidney failure Pro-BNP EuroSCORE STS PROM score On-pump surgery NS Size of the valve (Edwards NS Sapien valve) Intraprocedual PCI NS Pacemaker implantation NS Left ventricular end diastolic NS diameter Left ventricular ejection fraction NS Aortic valve insufficiency NS Orifice area NS Diameter of aortic annulus NS Mean valve gradient NS Mitral valve insufficiency NS Tricuspid valve Insufficiency NS Central regurgitation (Edwards NS SAPIEN valve) Paravalvular regurgitation NS (Edwards SAPIEN valve) Mean aortic valve gradient (Edwards SAPIEN valve) NS AVR aortic valve replacement; BNP B-type natriuretic peptide; CABG coronary artery bypass grafting; CI confidence interval; EuroSCORE European System for Cardiac Operative Risk Evaluation; MVS mitral valve surgery; NS not significant; PCI percutaneous coronary intervention; STS PROM Society of Thoracic Surgeons Predicted Risk of Mortality. cess rate was 99.5% (185 of 186) in group I and 99% (324 of 328) in group II. One patient in group I had apical bleeding due to fragile myocardial muscle (92-year-old patient with previous coronary artery bypass grafting), and in group II two had annulus rupture making conversion to conventional surgery necessary, 1 had valve dislocation, and 1 had type A dissection. This last adverse event could be treated successfully by placement of an uncovered aortic endostent [26] and the patient s postoperative course was completely uneventful. In group I, 69 patients received a 23-mm, 101 patients a 26-mm, and 16 patients a 29-mm Edwards SAPIEN valve. In group II, 88 patients received a 23-mm, 209 a 26-mm, and 31 a 29-mm Edwards SAPIEN valve. There were no statistically significant differences (Table 2). In group I, significantly more patients needed cannulation for CPB (25 patients [13%] in group I, 10 patients (3%) in group II). Additionally, in group I, 26 (14%) patients were in cardiogenic shock preoperatively and in 12 patients (6%) IABP [intraaortic balloon pump] implantation became necessary at the end of the procedure, whereas in group II only 2 (1%) patients were in cardiogenic shock and 1 patient needed an IABP (p 0.001) (Tables 1 and 2). Echocardiographic Data Preoperatively, the echocardiographic data showed significant differences in left ventricular function between the 2 groups (Table 3). In group I the left ventricular end diastolic diameter was significantly higher than in group II (LVEDD: group I: 51 9mm [range 33 to 80], group II: 48 7 mm [range 30 to 73] [p 0.001]), and the ejection fraction was significantly lower (group I, [range 0.10 to 0.70]; group II, [range 0.10 to 0.70] [p 0.001]. Although the aortic valve orifice area did not differ between the groups, the transvalvular aortic valve gradient did differ between the groups due to the fact that in group I the ejection fraction was significantly lower (Table 3). Additionally, the degree of mitral valve and tricuspid valve insufficiency was significantly higher in group I because the patients with higher EuroSCORE more often had pulmonary hypertension and reduced left ventricular function (Tables 1 and 3). Postoperatively, the transvalvular gradient was low, due to the special design of the valve, and did not differ between the 2 groups (Table 3). Central and paravalvular regurgitation are special characteristics in transcatheter valve implantation. Therefore, it is not surprising that postoperative echocardiographic examinations showed slight central incompetence in 20 patients in group I (11%) and in 32 patients in group II (10%). Minimal paravalvular leakage was seen in 69 (37%) patients in group I and in 114 (35%) in group II (not significant). The paravalvular regurgitation was Table 5. Predictive Factors of Cumulative Survival (Multivariable Cox Regression Analysis) Variable Hazard Ratio 95% Confidence Interval p Value Gender Cardiogenic shock Kidney failure

6 90 DREWS ET AL Ann Thorac Surg TAVI IN HIGH-RISK PATIENTS WITH EUROSCORE MORE THAN 40% 2013;95:85 93 mostly of grade I or less; in only a few patients was it between grades I and II. Length of Stay Due to the multimorbidity of the patients, they needed a long postoperative in-hospital stay. The mean length of stay on the intensive care unit was in group I days (range 0.1 to 59) and in group II days (range 0.1 to 32) (Table 2). The total length of inhospital stay was in group I days (range 1 to 110) and in group II days (range 0.3 to 46). The length of stay on the intensive care unit and the in-hospital stay differed between the 2 groups (p 0.001). Preoperative and Postoperative Stroke Rate Preoperatively, in group I, 79 patients (42%) had a history of stroke compared with 48 patients (15%) in group II. The difference was significant (p 0.001). Postoperative clinical examination showed that in group I, 1 patient had a new stroke and in group II, 3 patients had a stroke and 1 patient presented with signs of a transient ischemic attack. Postoperatively, there was no statistical difference between the 2 groups. Cardiac Pacemaker In the case of postoperative atrioventricular block degree III for more than 3 days, a cardiac pacemaker was implanted. In group I, 11 patients (6%) needed pacemaker implantation and in group II 17 patients (5%). There was no statistically significant difference between groups I and II (Table 2). Survival The overall 30-day survival in group I (EuroSCORE 40%) was 6.4%. Reflecting that patients in cardiogenic shock have a higher perioperative risk, group I was divided into 2 subgroups: group Ia consists of 159 patients with EuroSCORE greater than 40% without cardiogenic shock with a 30-day mortality of 5.7% and subgroup Ib consists of 27 patients with EuroSCORE greater than 40% with cardiogenic shock with a 30-day mortality of 6.5% (Fig 1; Table 2). In group II (Euro- SCORE 40%) the 30-day mortality was 3.4%. The overall 1-year survival in subgroup Ia was 67%, in subgroup Ib was 71%, and in group II was 89%. The difference was statistically significant (Fig 1; Table 2). The reasons for death in group I during the first 30 days were myocardial failure in 6 patients, septicemia in 3, intraoperative death in 1 patient (92-year-old patient with previous coronary artery bypass grafting), and other reasons in 2 patients (basilic vein thrombosis and pneumonia). Three of these 10 patients presented with preoperative cardiogenic shock. In group II, 11 patients died during the first 30 days. The reasons were mostly septicemia (4), followed by myocardial failure (3), intraoperative death in 3 patients Fig 1. Survival (Kaplan-Meier curves, log-rank test: 0.05). (cum cumulative; pts patients; ES EuroSCORE.) (annulus rupture in 2 and myocardial perforation in another), and one other reason (rupture of an abdominal aortic aneurysm). Predictive Factors of Cumulative Survival In patients with a EuroSCORE of over 40%, female gender, cardiogenic shock, kidney failure, and elevated pro-bnp (B-type natriuretic peptide) were observed to negatively influence late survival (Tables 4 and 5). Age, body mass index, and previous heart surgery did not influence the long-term survival. Additionally, preoperative reduced myocardial function or mitral and tricuspid valve insufficiency did not influence the late outcome. Comment In patients with advanced heart failure, the operative risk is elevated during conventional aortic valve replacement. The mortality ranged from 3% to 30% [7 9, 20]. Transcatheter aortic valve implantation has been introduced to reduce the surgical risk in patients with increased perioperative mortality. Several risk scores have been introduced [12 16] and their relevance for patients undergoing TAVI has been shown [27]. In the Partner B trial of inoperable patients in the United States, the mean logistic EuroSCORE of patients treated by TAVI and standard therapy was 26.4% and 30.4%; the STS PROM score was 11.2% and 12.1%, respectively [28]. By comparison, in the German TAVI registry of 1,365 patients undergoing TAVI the mean EuroSCORE was 20.6% 13.7% [29]. The France 2 registry published a study of 2,107 patients undergoing TAVI with a mean EuroSCORE of and a

7 Ann Thorac Surg DREWS ET AL 2013;95:85 93 TAVI IN HIGH-RISK PATIENTS WITH EUROSCORE MORE THAN 40% mean STS PROM score of 15.6% 12.4% [30]. In fact, our patient cohort of 514 consecutive patients had a higher mean EuroSCORE (37.5% 22.7%). We recognized early a different population of patients who had been referred for this type of treatment in our institution. Some of them were very old and polymorbid patients, most of whom had earlier received only conservative treatment; eg, nonagenarians and persons with reduced mobility. Therefore our philosophy has been, since the beginning of our experience, to propose TAVI even to patients with extremely complex comorbid profiles, including cardiogenic shock [31]. None of the very high-risk patients evaluated were refused treatment regardless of comorbidities and clinical status (eg, profound shock), except patients with active endocarditis, if technically it was possible to perform the procedure in terms of the annular size. This is, of course, reflected by the higher STS score and Euro- SCORE of our TAVI cohort and is to some extent an indicator of the patient referral pattern of our institution. Since its establishment, the Deutsches Herzzentrum Berlin has been a referral center for the treatment of extreme cardiovascular pathologies and conditions. Only within its structured environment were we able to design a TAVI program and to enroll a plethora of complex candidates. Since the beginning of our TAVI experience in 2008, we have learned from the masters of this innovative technique including experience from Leipzig, Germany (Professor Mohr/Professor Walther), Rouen, France (Professor Cribier), and Siegburg, Germany (Professor Grube/Professor Gerckens). We also recognize the importance of their initial proctorship for the present success of our program [4]. Some authors recommend performing TAVI only in patients with an STS mortality score of less than 20% and a EuroSCORE of less than 40%, and in those with expected survival of over 1 year [19]. In our institution 36% of patients (186 of 514) undergoing TAVI had a EuroSCORE of over 40%. Corresponding to the recommendation of Figulla and colleagues [19], these patients would be given conventional surgery or medical therapy only. We were able to show that transcatheter aortic valve implantation can be performed also in patients with high perioperative risk. Although the perioperative mortality was elevated (group I, overall 30-day mortality 6.5%; patients without cardiogenic shock, 5.7%) and therefore significantly higher than for patients with lower perioperative risk (group II, 3.4%), the long-term results are good (1-year survival 67%, 2-year survival 54%, and 1-year survival 71%; 2-year survival 56% for patients without cardiogenic shock). As shown in an earlier publication [27] the Euro- SCORE and the STS PROM score are not strong predictors for short-term survival. In our group, female gender, cardiogenic shock, kidney failure, and elevated pro-bnp were observed to negatively influence late survival (Tables 4 and 5). Most interestingly, age, body mass index, and previous heart surgery, preoperative reduced myocardial function or mitral and tricuspid valve insufficiency do not influence the long-term survival. Tamburino and colleagues [32] showed that a high incidence of moderate to high-grade regurgitation gives reason to expect worse outcome. Applying our modified technique of performing simultaneous angiography during slow and gradual valve deployment enables perfect visualization of the aortic root and the coronary arteries, and fine adjustment of the position of the new valve allows the rate of paravalvular regurgitation to be reduced [10]. Therefore in the group of patients analyzed, the rate of paravalvular regurgitation was not seen as a risk factor for late outcome; the mid-term and long-term survival in patients with a EuroSCORE of less 40% is determined by comorbidities after the elimination of aortic valve stenosis. Leon and colleagues [28] and Reiss and Smith [33] concluded in the PARTNER trial that TAVI should be the new standard of care for patients with aortic stenosis who are not suitable candidates for surgery. Additionally, we presented in an earlier publication our view that TAVI can be performed successfully in patients with advanced heart failure [21]. Our group showed the postoperative course in multimorbid patients with coronary disease, peripheral vascular disease, pulmonary hypertension, chronic obstructive pulmonary disease, or history of stroke, and in patients with reduced left ventricular function. In the cohort analyzed, 36% of patients had a significantly increased risk score (EuroSCORE 40%) and they had a 1-year survival of 67%. Nevertheless the perioperative risk is elevated, especially for patients in cardiogenic shock; 13% of these very high-risk patients needed CPB during valve implantation. A CPB is rarely necessary for transcatheter aortic valve implantation but it is a prerequisite for the procedure to have the heart-lung machine ready for use in the operating room and it is an important part of the safety net [23], although not all patients put on CPB during the procedure need the support. Nevertheless, its elective use increases the safety in critically ill patients in order to maintain hemodynamic stability during the phases of rapid pacing and to prevent manual cardiopulmonary resuscitation because the postoperative course of these patients is unfavorable. Therefore, the following are our guidelines on how to act in particular situations with regard to very high-risk patients: (1) No exclusion policy: all patients with STS PROM score of 10/EuroSCORE of 40% or higher are evaluated as candidates for treatment regardless of comorbidities and clinical status; for example, profound shock (except patients with active endocarditis), if it is technically possible to perform the procedure in terms of the annular size. (2) Elective femoro-femoral CPB is considered in patients with severe cardiogenic shock, poor left ventricular function (LVEF 0.10 to 0.20), or enlarged right ventricle with severe pulmonary hypertension. 91

8 92 DREWS ET AL Ann Thorac Surg TAVI IN HIGH-RISK PATIENTS WITH EUROSCORE MORE THAN 40% 2013;95:85 93 (3) The intraaortic balloon pump is considered in very high-risk patients with depressed hemodynamic condition. From our initial experience in very high-risk patients, TAVI seems to provide much better results than medical treatment or conventional aortic valve replacement, which carries a relatively high operative mortality in these specific patients (7 9, 14, 12, 20, 21). Therefore, all patients with STS PROM score of 10/ EuroSCORE of 40% or higher should be evaluated as candidates for treatment if it is technically possible to perform the procedure in terms of the annular size. Nevertheless, it must be noted that female gender, cardiogenic shock, and kidney failure represent an elevated risk in this multimorbid subgroup. The predictive score systems do not correlate with the data of early mortality in patients undergoing TAVI and should not be used to exclude patients from this new therapeutic option. In fact, a high score is the real indication for TAVI. Other members of the team are Tom Gromann, MD, Guna Tetere, MD, Ekatarina Ivanitskaja-Kühn, MD, and Natalia Solowjowa, MD, Christoph Klein, MD, and Katrin Schäfer. We thank Ms. Anne Gale, Editor in the Life Sciences, for editorial assistance and Mrs. Julia Stein for statistical analysis. References 1. Walther T, Simon P, Dewey T, et al. Transapical minimally invasive aortic valve implantation: multicenter experience. Circulation 2007;116(suppl 11):I Walther T, Dewey T, Borger MA, et al. Transapical aortic valve implantation: step by step. Ann Thorac Surg 2009;87: Webb JG, Altwegg L, Boone RH, et al. Transcatheter aortic valve implantation: impact on clinical and valve-related outcomes. Circulation 2009;119: Pasic M, Unbehaun A, Dreysse S, et al. 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