Surgical Ventricular Restoration for Patients With Ischemic Heart Failure: Determinants of Two-Year Survival

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1 Surgical for Patients With Ischemic Heart Failure: Determinants of Two-Year Survival Tomasz G. Witkowski, MD, Ellen A. ten Brinke, MD, Victoria Delgado, MD, Arnold C.T. Ng, MBBS, Matteo Bertini, MD, Nina Ajmone Marsan, MD, See H. Ewe, MBBS, Dominique Auger, MD, Kelvin H. Yiu, MBBS, Jerry Braun, MD, Patrick Klein, MD, Paul Steendijk, MD, PhD, Michel I.M. Versteegh, MD, Robert J. Klautz, MD, PhD, and Jeroen J. Bax, MD, PhD Departments of Cardiology and Cardiothoracic Surgery, Leiden University Medical Center, Leiden, The Netherlands Background. Surgical ventricular restoration (SVR) improves left ventricular (LV) systolic function by partially restoring the normal geometry of the left ventricle. However, the beneficial effects of this surgical procedure on long-term clinical outcome remain controversial. The present study aimed to evaluate the independent determinants of 2-year morbidity and mortality rates after SVR. Methods. Seventy-nine patients with ischemic heart disease and LV ejection fraction of 0.35 or less were included. All patients underwent SVR and additionally coronary artery bypass grafting or mitral valve surgery if clinically indicated. Clinical and echocardiographic examination was performed before SVR and at 6 months follow-up. The primary end point was a composite of all-cause mortality and hospitalizations for heart failure. Results. At 6 months follow-up a significant improvement in heart failure symptoms was noted. In addition, LV ejection fraction increased from to (p < 0.001). During a median follow-up of 2.7 years, the primary end point was recorded in 22% of the patients. Baseline New York Heart Association functional class IV and a 6-month follow-up LV endsystolic volume index of at least 60 ml/m 2 were independently associated with worse outcome (hazard ratio, 5.4; 95% confidence interval, 1.9 to 15.2; p < 0.001; hazard ratio, 2.7; 95% confidence interval, 1.3 to 5.6; p < 0.001, respectively). Conclusions. Advanced heart failure status at baseline and large residual postsurgery LV end-systolic volume index were independently associated with increased mortality and heart failure hospitalization rates at 2 years follow-up after SVR. (Ann Thorac Surg 2011;91:491 8) 2011 by The Society of Thoracic Surgeons Ischemic heart disease is the most frequent cause of heart failure (HF) in the contemporary population [1]. Chronic ischemia and acute ischemic events lead to changes in left ventricular (LV) geometry, from the natural elliptical shape toward a more spherical shape that ultimately reduces systolic function. During the last few years, several advances in medical and device-based therapies have attempted to prevent LV remodeling and improve long-term survival of HF patients [2]. In addition, different surgical techniques have been developed to restore the normal shape of the dilated left ventricle and to improve LV function. Surgical ventricular restoration (SVR) in ischemic HF patients has yielded beneficial short-term effects on functional status, exercise performance, and quality of life [3]. Several series have also shown improved long-term outcome, with 5-year survival rates of 70% and 5-year Accepted for publication Sept 29, Address correspondence to Dr Bax, Department of Cardiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands; j.j.bax@lumc.nl. freedom from HF hospitalization rates up to 80% [4]. Despite these beneficial effects demonstrated in numerous single-center trials [3], the recent results of the multicenter, randomized Surgical Treatment for Ischemic Heart Failure (STICH) trial have shown no incremental survival benefit of SVR and revascularization versus revascularization alone [5]. Patient selection issues and hemodynamic effects of LV volume reduction have been proposed to explain these contradictory results [5]. Ongoing research to elucidate the independent determinants of long-term survival in HF patients undergoing SVR may improve our knowledge on the pathophysiologic mechanisms of this therapeutic approach [5]. Therefore, the aim of the present study was to identify clinical and echocardiographic determinants of 2-year Dr Bax discloses that he has financial relationships with Biotronik, Medtronic, Boston Scientific, BMS Medical Imaging, Edwards Lifesciences, St. Jude Medical, and GE Healthcare by The Society of Thoracic Surgeons /$36.00 Published by Elsevier Inc doi: /j.athoracsur

2 492 WITKOWSKI ET AL Ann Thorac Surg SVR: DETERMINANTS OF SURVIVAL 2011;91:491 8 morbidity and mortality in patients with ischemic cardiomyopathy undergoing SVR. Patients and Methods Patient Population Patients with coronary artery disease, LV ejection fraction of 0.35 or less, and LV aneurysm who underwent SVR between 2002 and 2008 were included in the present study. The inclusion criteria were previous anterior myocardial infarction, akinetic or dyskinetic ventricular aneurysm, and symptoms of angina, congestive HF, or life-threatening ventricular arrhythmias. The exclusion criteria included patients with recent myocardial infarction, concomitant severe aortic valvular disease, and associated comorbidities resulting in an increased operative risk or reduced life expectancy. In addition, patients who died within the 30 days after SVR were excluded from further analysis. All the patients underwent baseline clinical and echocardiographic evaluation. The recorded clinical variables included demographics, cardiovascular risk factors, comorbidities, medical therapy, and clinical status (New York Heart Association [NYHA] functional class, 6-minute walk distance, and quality of life score according to the Minnesota Living With Heart Failure Questionnaire). Conventional echocardiography and tissue Doppler imaging techniques were performed to evaluate LV volumes and mass, LV systolic and diastolic function, and severity of mitral regurgitation. Clinical and echocardiographic evaluations were repeated at 6 months follow-up after surgical procedure, and at 2 years follow-up the all-cause mortality and hospitalizations for HF were recorded. Finally, baseline and 6 months follow-up changes in clinical and echocardiographic variables were related to survival at 2 years. The study was conducted with the approval of the Leiden University Medical Center Institutional Review Board with specific waiver of the need for individual patient written informed consent. Echocardiographic Evaluation Transthoracic echocardiography was performed at baseline and at 6 months follow-up with a commercially available system (Vivid 7; GE-Vingmed, Horten, Norway). The images were obtained with a 3.5-MHz transducer in the parasternal and apical views and digitally stored for off-line analysis (EchoPAC ; GE- Vingmed). From the parasternal long-axis view, LV diameters and septal and posterior wall thicknesses were measured; LV mass was calculated according to Devereux s formula and corrected for the body surface area [6]. Left ventricular end-diastolic and end-systolic volumes were calculated from the two- and four-chamber apical views using Simpson s method and were indexed for body surface area [7]. Left ventricular ejection fraction was subsequently calculated and expressed as a value between 0 and 1. The assessment of LV diastolic function included the measurement of early (E-wave) and late (A-wave) diastolic peak velocities, E/A ratio, E-wave deceleration time, and isovolumetric relaxation time from the pulsed-wave Doppler recordings of the transmitral inflow [8]. In addition, using color-coded tissue Doppler imaging, early diastolic mitral annular velocity (E=) was obtained by placing the sample volume at the septal and lateral mitral annulus. The averaged E= value was obtained, and the E/E= ratio was derived as a measurement of LV filling pressures. Mitral regurgitation was evaluated semiquantitatively from color-flow Doppler images in the four-chamber apical view according to current guidelines [9]. At 6 months follow-up, the echocardiography was repeated to evaluate LV volumes and function and mitral valvular function. Particularly, patients were screened for showing a midterm LV end-systolic volume index (LVESVI) of at least 60 ml/m 2 as this cutoff value has been related to poor outcome in patients with ischemic heart disease [10]. Clinical Evaluation Routine clinical evaluation was performed before surgery and at 6 months follow-up. New York Heart Association functional class, quality of life (Minnesota Living With Heart Failure Questionnaire), and exercise tolerance (6- minute walk test) were evaluated [11, 12]. The long-term outcome included the composite end point of all-cause mortality and hospitalization for decompensated HF. Clinical follow-up was performed by an independent physician at the outpatient clinic or by telephone contact with the patient or patient s relative. The information about patient s death was obtained during telephone contact with family member. Surgical Procedures and Early Postoperative Course The procedures were performed under cardiopulmonary bypass with antegrade warm-blood cardioplegia for myocardial protection. After median sternotomy, SVR was performed by the endoventricular circular patch plasty as previously described by Dor and colleagues [13]. The left ventricle was opened through the infarcted area. An endocardial encircling suture was placed at the transitional zone between scarred and normal tissue. A balloon (TRISVR; Chase Medical, Richardson, TX) containing 55 ml/m 2 body surface area saline solution was introduced into the left ventricle, and the encircling stitch was tightened to approximate the ventricular wall to the balloon. A polyethylene terephthalate fiber (Dacron) patch was used to close the residual orifice. The excluded scar tissue was closed over the patch to ensure hemostasis. Care was taken to eliminate all septal scarring and to delineate a new apex with the goal to restore the normal elliptical shape. Patients with at least grade 2 mitral regurgitation underwent concomitant restrictive mitral annuloplasty (two sizes smaller than measured) by means of an atrial transseptal approach using a Carpentier Edwards Physio ring (Edwards Lifesciences, Irvine, CA) with surgical technique described in a previous publication [14]. Patients who showed increased mitral regurgitation to at least grade 2 on intraoperative

3 Ann Thorac Surg WITKOWSKI ET AL 2011;91:491 8 SVR: DETERMINANTS OF SURVIVAL 493 transesophageal echocardiography performed immediately after SVR after discontinuation of extracorporeal circulation underwent a restrictive mitral annuloplasty, which was performed during a second period of aortic cross-clamping. In patients with severe tricuspid annular dilatation ( 4.0 cm) or regurgitation (grade 2), a concomitant tricuspid annuloplasty using an Edwards MC3 annuloplasty ring (Edwards Lifesciences) was performed. If indicated, patients underwent conventional coronary artery bypass grafting, and internal mammary arteries were used if possible. Statistical Analysis Distribution of the continuous data was tested with Komolgorov Smirnov one-sample test and Shapiro Wilk test. Normally distributed variables were presented as mean standard deviation, whereas nonnormally distributed variables were presented as median and interquartile range (IQR). Categorical variables were presented as numbers and percentages. Comparisons of repeated measurements were performed with paired Student s t test, Wilcoxon signed-rank test, and McNemar test, as appropriate. The study population was divided according to the midterm indexed LVESVI volume ( 60 ml/m 2 versus 60 ml/m 2 ). Comparisons between these two groups were performed with the nonparametric Mann-Whitney test, and the validity was confirmed with the Monte Carlo method (resampling technique). In addition, freedom of composite end point survival was explored with Kaplan- Meier curves with right-censoring at 2 years follow-up. Mantel-Cox test was used to compare the survival distributions of two samples. The determinants of the composite end point of all-cause mortality and HF hospitalization were evaluated with univariate and multivariate Cox proportional hazard analysis. Clinical (age, sex, NYHA functional class, comorbidities) and echocardiographic (LV ejection fraction, indexed LV volumes, and diastolic function) at baseline, concomitant surgical procedures, and surgical end points (indexed LV endsystolic volume and LV mass) were introduced in the univariate analysis. The variables with a probability value of less than 0.15 at univariate analysis were used in the multivariate stepwise backward logistic regression analysis. Validity of the assumption of proportionality for the Cox regression analysis was confirmed with scaled Schoenfeld residuals for continuous variables, and with log-minus-log plots for categorical variables. For all statistical tests, a probability value of less than 0.05 was considered significant. All statistical analyses were performed with SPSS version 17.0 (SPSS, Inc, Chicago, IL). Results Study Population Seventy-nine patients (mean age, years; 80% men) met the inclusion criteria and formed the study population. Baseline characteristics of the study population are summarized in Table 1. All patients had HF of ischemic origin, mostly in NYHA functional class II and Table 1. Baseline Patient Characteristic Before Surgical Characteristic Result Age (y) Men, n (%) 63 (80%) NYHA functional class, n (%) I 2 (3%) II 32 (40%) III 37 (47%) IV 8 (10%) Body surface area (m 2 ) Hypertension, n (%) 32 (40%) Diabetes, n (%) 12 (15%) COPD, n (%) 5 (6%) CVA, n (%) 9 (11%) Medical therapy ACEI/ARB, n (%) 71 (89%) -blockers, n (%) 66 (83%) Loop diuretics, n (%) 53 (67%) Digoxin, n (%) 9 (11%) Statins, n (%) 70 (88%) ACEI angiotensin-converting enzyme inhibitor; ARB angiotensin receptor blocker; COPD chronic obstructive pulmonary disease; CVA cerebrovascular accident; NYHA New York Heart Association. III (40% and 47%, respectively). Comorbidities included hypertension (40%), diabetes mellitus (15%), chronic obstructive pulmonary disease (6%), and previous stroke (11%). Patients were optimally treated according to current guidelines and at maximal tolerated doses (Table 1). Baseline Echocardiography Baseline mean LV ejection fraction was , and LV end-diastolic volume index and LVESVI were 105 ml/m 2 (IQR, 83, 139) and 71 ml/m 2 (IQR, 57, 82), respectively. Diastolic function analysis showed a median E/A ratio of 0.9 (IQR, 0.6, 1.4), median deceleration time of 191 ms (IQR, 157, 240), and median isovolumetric relaxation time of 75 ms (IQR, 55, 95). The E/E= ratio was 17 (IQR, 14, 22). Most patients (n 47; 60%) had moderate to severe mitral regurgitation (Table 2). Surgical Procedures All patients underwent SVR, and concomitant coronary artery bypass grafting, restrictive mitral valve annuloplasty, and tricuspid valve annuloplasty were performed in 51 (65%), 46 (58%), and 22 (28%) patients, respectively. Perioperative variables are presented in Table 3. A total of 61 (77%) patients showed a midterm LVESVI less than 60 ml/m 2. The remaining 18 (23%) patients had a midterm LVESVI of at least 60 ml/m 2. Changes in Clinical Status After Surgical At 6 months follow-up after surgical procedure, there was a significant improvement in NYHA functional class (from to ; p ). Thirty-two (41%)

4 494 WITKOWSKI ET AL Ann Thorac Surg SVR: DETERMINANTS OF SURVIVAL 2011;91:491 8 Table 2. Baseline Echocardiographic Variables Variable Result LV ejection fraction LVEDVI (ml/m 2 ) 105 (IQR, 83, 139) LVESVI (ml/m 2 ) 71 (IQR, 57, 82) LV mass index (g/m 2 ) 148 (IQR, 135, 197) Mitral regurgitation grade, n (%) (40%) 2 34 (43%) 3 13 (17%) E/A 0.9 (IQR, 0.6, 1.4) DT (ms) 191 (IQR, 157, 240) IVRT (ms) 75 (IQR, 55, 95) E/E= 17 (IQR, 14, 22) DT deceleration time; E/A ratio of peak Doppler velocities of early (E) and late mitral diastolic flow (A); E/E= ratio of E and early mitral annulus peak velocity (E=); IQR interquartile range; IVRT isovolumic relaxation time; LV left ventricular; LVEDVI left ventricular end-diastolic volume index; LVESVI left ventricular end-systolic volume index. patients improved by one point in NYHA functional class, and 13 (16%) patients improved more than one point (Fig 1). The distance covered in the 6-minute walk test increased significantly from 315 m (IQR, 180, 413) to 405 m (IQR, 343, 450; p ; Fig 2A), and the quality of life improved from 33 points (IQR, 23, 53) to 18 points (IQR, 10, 29; p ; Fig 2B). At 6 months follow-up, patients with a midterm LVESVI less than 60 ml/m 2 showed a significantly superior NYHA functional class compared with patients with an LVESVI of at least 60 ml/m 2 ( versus ; p 0.013). In contrast, both groups of patients showed similar improvements in the quality of life scoring (18 points; IQR, 9, 26 versus 24 points; IQR, 14, 46; p 0.132) and the 6-minute walked distance (420 m; IQR, 360, 465 versus 350 m; IQR, 330, 390; p 0.066). Fig 1. Change in New York Heart Association (NYHA) functional class in patients with heart failure after surgical ventricular restoration. ml/m 2 ; IQR, 83, 139; to 71 ml/m 2 ; IQR, 57, 82; p 0.001), LVESVI (from 75 ml/m 2 ; IQR, 57, 103; to 45 ml/m 2 ; IQR, 35, 55; p 0.001), and LV mass index (from 148 g/m 2 ; IQR, 135, 197; to 134 g/m 2 ; IQR, 114, 157; p 0.001; Fig 3). Left Changes in Echocardiographic Variables After Surgical At 6 months follow-up after SVR there were significant reductions in LV end-diastolic volume index (from 105 Table 3. Surgical and Perioperative Characteristics Variable Result Coronary artery bypass grafting, n (%) 51 (65%) Restrictive mitral valve annuloplasty, n (%) 46 (58%) Tricuspid valve annuloplasty, n (%) 22 (28%) Cardiopulmonary bypass (min) 199 (IQR, 133, 224) Aortic cross-clamp (min) 135 (IQR, 89, 162) Coronary vessels bypassed, n 2 (IQR, 0, 3) Reoperation for bleeding, n (%) 5 (6%) Postoperative intra-aortic balloon pump, 13 (16%) n (%) Higher-dose inotropic support, n (%) 5 (6%) Prolonged intensive care unit stay, n (%) 11 (14%) IQR interquartile range. Fig 2. Changes in distance covered in 6-minute walk test (A) and quality of life (B) at 6 months after surgical ventricular restoration. (IQR interquartile range.)

5 Ann Thorac Surg WITKOWSKI ET AL 2011;91:491 8 SVR: DETERMINANTS OF SURVIVAL 495 Fig 3. Changes in echocardiographic variables at 6 months after surgical ventricular restoration. (A) Changes in left ventricular end-diastolic volume index (LVEDVI). (B) Changes in left ventricular end-systolic volume index (LVESVI). (C) Changes in left ventricular (LV) ejection fraction. (D) Changes in left ventricular mass index. (IQR interquartile range.) ventricular ejection fraction increased significantly ( versus ; p 0.001; Fig 3). In addition, significant changes in LV diastolic function were noted, with an increase in E/A ratio (from 0.9; IQR, 0.6, 1.4; to 1.5; IQR, 0.9, 2.8; p 0.001), reduction in isovolumetric relaxation time (from 75 ms; IQR, 55, 95; to 63 ms; IQR, 55, 85; p 0.01), and increase in E/E= ratio (from 17; IQR, 14, 22; to 31; IQR, 17, 46; p 0.001). At 6 months follow-up there was a significant reduction in severity of mitral regurgitation, and the majority of the patients (n 74; 94%) showed none or trivial mitral regurgitation (p ). The median reduction of LVESVI in the overall population was 41% (IQR, 25, 52). Importantly, the mean reduction in LVESVI was significantly greater in the group of patients with a midterm LVESVI less than 60 ml/m 2 as compared with the patients with an LVESVI of at least 60 ml/m 2 (43%; IQR, 30, 58 versus 30%; IQR, 16, 44; p 0.002). This may be explained by significantly larger baseline LVESVI in patients with a midterm LVESVI of at least 60 ml/m 2 compared with patients with an LVESVI less than 60 ml/m 2 (93 ml/m 2 ; IQR, 78, 121 versus 68 ml/m 2 ; IQR, 52, 90; p 0.002). Morbidity and Mortality After Surgical During a median follow-up of 2.7 years (IQR, 1.7, 3.7) that was 100% complete, 17 patients (22%) presented with the composite end point of all-cause mortality and HF hospitalization. The cumulative event-free survival at 2 years was 83% (95% confidence interval, 78 to 88). Baseline NYHA functional class IV was associated with worse prognosis after SVR (3.6-fold increase of risk for poor outcome in univariate analysis). In addition, midterm LVESVI of at least 60 ml/m 2 was a strong determinant of outcome at 2 years follow-up, with almost eightfold risk increase for composite end point (all-cause mortality and HF hospitalization; Fig 4). In addition, NYHA functional class and LV mass index, both at 6 months follow-up, and baseline E/A ratio were significantly related to allcause mortality and HF rehospitalization at the univariate analysis (Table 4). Those univariate significant determinants of 2-year morbidity and mortality were introduced in a multivariate Cox regression model. Midterm LVESVI of at least 60 ml/m 2 and NYHA functional Fig 4. Cox cumulative hazard function in patients with residual postsurgical ventricular restoration left ventricular end-systolic volume index (LVESVI) of at least 60 ml/m 2 (solid line)or less than 60 ml/m 2 (dotted line). (CI confidence interval; HF heart failure; HR hazard ratio.)

6 496 WITKOWSKI ET AL Ann Thorac Surg SVR: DETERMINANTS OF SURVIVAL 2011;91:491 8 Table 4. Predictors of 2-Year Morbidity and Mortality Rates Outcome (All-Cause Mortality and Hospitalization Owing to Heart Failure) in Patients With Ischemic Heart Failure Who Underwent Surgical Univariate Analysis Multivariate Analysis Variable 2 HR a (95% CI) p Value HR a (95% CI) p Value Age, years ( ) 0.4 Men ( ) 0.5 NYHA functional class at baseline ( ) ( ) Hypertension ( ) 0.65 Diabetes ( ) 0.90 Baseline echocardiographic variables LV ejection fraction ( ) LVEDVI, ml/m ( ) 0.02 LVESVI, ml/m ( ) E/A ( ) 0.02 Concomitant surgical procedures CABG ( ) 0.70 MVP ( ) 0.18 TVP ( ) 0.75 Postsurgical LVESVI 60 ml/m ( ) ( ) Postsurgical LV mass index, g/m ( ) a Hazard ratio is expressed per NYHA functional class, per g/m 2 of LV mass index, per unit of E/A. CABG coronary artery by-pass grafting; CI confidence interval; E/A ratio of peak Doppler velocities of early (E) and late mitral diastolic flow (A); HR hazard ratio; LV left ventricular; LVEDVI left ventricular end-diastolic volume index; LVESVI left ventricular end-systolic volume index; MVP restrictive mitral valve annuloplasty; NYHA New York Heart Association; TVP tricuspid valve annuloplasty. class assessed at baseline remained in the model as strong predictors of 2-year morbidity and mortality in patients who underwent SVR (Table 4). Patients with a midterm LVESVI of at least 60 ml/m 2 had lower eventfree survival at 2 years than patients with LVESVI less than 60 ml/m 2 (59%; 95% confidence interval, 47 to 71 versus 91%; 95% confidence interval, 87 to 95; p 0.001; ; Fig 5). to 410 m [5]. In addition, the multicenter Reconstructive Endoventricular Surgery returning to Torsion Original Radius Elliptical shape of the left ventricle (RESTORE) trial, including 1,980 postinfarction patients, showed an improvement in NYHA functional class from 2.9 to 1.7 [4]. Comment The main findings of the present study can be summarized as follows: (1) SVR is an efficient therapy for ischemic HF patients with apical LV aneurysm and provides significant improvement in exercise performance, quality of life, and LV function; and (2) baseline NYHA functional class IV and residual postsurgery LVESVI of at least 60 ml/m 2 were associated with poor outcome at 2 years follow-up. Clinical and Echocardiographic Benefits of Surgical Surgical ventricular restoration is a feasible and effective therapy for ischemic HF patients, providing significant improvements in clinical symptoms and LV systolic function [3 5, 15 18]. This has been recently demonstrated in the large-scale STICH trial, including 501 patients with ischemic HF [5]. Heart failure symptoms improved by an average of one NYHA functional class, and the distance covered in the 6-minute walk test increased from 358 m Fig 5. Kaplan-Meier curves with the cumulative survival rate for the composite end point (death and hospitalization owing to heart failure) in patients (pts) with ischemic heart failure with residual postsurgical left ventricular end-systolic volume index (LVESVI) of at least 60 ml/m 2 (solid line) or less than 60 ml/m 2 (dashed line).

7 Ann Thorac Surg WITKOWSKI ET AL 2011;91:491 8 SVR: DETERMINANTS OF SURVIVAL 497 Similarly to these multicenter trials and many other single-center experiences [15, 16, 18], the present study confirms the beneficial effect of SVR on clinical status with improvement of NYHA functional class, quality of life, and exercise performance. This beneficial effect of SVR on clinical status is accompanied by a significant improvement in LV systolic function. As previously demonstrated in HF trials, favorable LV reverse remodeling (reduction in LV volumes) and improvement in LV systolic function were related to superior long-term survival [19]. The goal of this surgical procedure is to restore the spherical shape of the dilated left ventricle and to reduce LVESVI to a residual volume of 50 to 60 ml/m 2 [20]. In the majority of the studies, the mean reduction in LVESVI was nearly 30% with a mean increase in LV ejection fraction of 0.10 [4, 16, 18, 21]. Similarly, in the present study a significant reduction in LVESVI of 41% was observed, and more important, in as much as 77% of the patients a midterm LVESVI of less than 60 ml/m 2 was achieved. In addition, LV ejection fraction increased significantly from to (p 0.001). This improvement in LV systolic function may explain the improvement in clinical symptoms. However, it has been suggested that the reduction in LVESVI may induce an increase in LV filling pressures [15, 17, 22]. This increase can be more pronounced in those patients in whom concomitant restrictive mitral annuloplasty is performed [23]. In the present study, LV filling pressures increased significantly but did not have any negative impact on clinical symptoms because most of the patients showed an improvement in NYHA functional class and exercise performance. Therefore, the potential negative effects of increased LV filling pressures after SVR are exceeded by the beneficial effects on LV systolic function, resulting in improved clinical status. Determinants of Long-Term Survival After Surgical Beyond clinical and echocardiographic improvements, it would be more interesting to evaluate the efficacy of SVR in terms of long-term survival. The largest series have shown that patients undergoing SVR have a long-term survival rate of 70% [4, 5]. In the present study, the cumulative event-free survival at 2 years follow-up was 78%. The determinants of long-term survival after SVR have not been extensively explored or remain unclear. Several clinical and echocardiographic variables such as age, NYHA functional class, LV ejection fraction, and other surgical procedures performed in addition to SVR have been related to poor outcome after SVR [4, 24, 25]. However, a recent pooled analysis of 62 studies reporting early and long-term outcome after SVR has questioned the real impact of these factors on long-term prognosis [3]. The meta-analysis including a total of 1,231 patients has shown that clinical or echocardiographic variables did not have any significant influence on long-term survival. In contrast, the performance of coronary artery bypass grafting in addition to SVR improved long-term survival, whereas concomitant restrictive mitral annuloplasty was related to poor outcome [24, 26]. These results are in contrast to the recently published STICH trial in which combined SVR and coronary artery bypass grafting did not provide a superior survival benefit than revascularization alone [5]. One of the technical issues that may influence the survival benefits of SVR is the mid-term LVESVI. As demonstrated in previous studies, LV dimensions are important prognostic determinants in ischemic HF patients [10, 27]. In the STICH trial, the mean reduction in LVESVI was 19% [5]. This relative reduction in LVESVI was significantly smaller as compared with that of other series [28]. Indeed, Di Donato and associates [28] have recently demonstrated that a residual postsurgical LVESVI of at least 60 ml/m 2 was an independent predictor of mortality. The present study confirms and extends previous results by showing that a residual postsurgical LVESVI of at least 60 ml/m 2 determined a fivefold increase of death and HF rehospitalization during follow-up. In addition, baseline NYHA functional class was an independent determinant of survival at 2 years follow-up, with increased mortality risk in patients with NYHA functional class IV. These findings suggest that SVR might be considered as a therapeutic option for patients with HF in less-advanced stages of the disease. Study Limitations Some limitations should be acknowledged. First, the study population includes a relatively small sample size. In addition, a control group matched by various clinical and echocardiographic variables undergoing CABG (alone or associated with mitral valve repair and tricuspid annuloplasty) would be desirable to demonstrate the prognostic benefits of SVR. However, the aim of the present study was to explore the baseline and 6 months follow-up clinical and echocardiographic variables that are related to long-term survival rather than corroborate the results of the STICH trial. Second, the cause of death was not considered in the analysis. Left ventricular sphericity index was not evaluated in the present study population. Although it may be of interest, the measurement of this index with two-dimensional echocardiography relies on geometric assumptions that may result in methodological errors. The advent of real-time threedimensional echocardiography may provide meaningful insights into this regard. 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