Department of Cardiothoracic Surgery, Cardiology and Medicine, St Vincent s Hospital, University of Melbourne, Melbourne, Victoria, Australia

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1 Surgical Ventricular Restoration Procedure: Single- Center Comparison of Surgical Treatment of Ischemic Heart Failure (STICH) Versus Non-STICH Patients Siew Goh, MBChB, David Prior, PhD, Andrew Newcomb, FRACS, Alexander McLellan, MBBS, Jane Mack, BA, Sue Callaghan, BAppSc, Jim Dimitriou, MBBS, Alexander Rosalion, FRACS, Ian Nixon, FRACS, and Michael Yii, MS, FRACS Department of Cardiothoracic Surgery, Cardiology and Medicine, St Vincent s Hospital, University of Melbourne, Melbourne, Victoria, Australia Background. Surgical ventricular restoration (SVR) was conceived to improve hemodynamic and clinical outcomes in ischemic cardiomyopathy. The Surgical Treatment of Ischemic Heart Failure (STICH) trial has conclusively shown no additional benefits of SVR when routinely combined with coronary artery bypass surgery. However, the STICH study did not include a registry arm for SVR-eligible patients who were not randomized. This study describes the SVR experience in a single center when participating in the STICH study, to better understand the role of SVR in current clinical practice. Methods. All patients receiving SVR between 2002 and 2006 were prospectively followed. Patients were divided into STICH SVR (SSVR) and non-stich SVR (NSSVR) groups. The SSVR patients received SVR as randomized in STICH. The NSSVR patients were evaluated for eligibility to participate in the STICH trial, and the reasons for not participating were analyzed. Baseline demographics, echocardiographic data, and clinical outcomes were compared. Results. Nine NSSVR patients were compared with 12 SSVR patients. Only 1 NSSVR patient did not fulfill entry criteria into the STICH trial for randomization. The main reason for performing SVR outside of the STICH study was dominant heart failure symptom associated with enlarged left ventricle. The NSSVR group had more anterior wall asynergy (60% vs 45%, p < 0.001), larger preoperative heart volumes (left ventricular end-diastolic volume index 108 ml/m 2 vs 69 ml/m 2, p < 0.05) and larger volume reductions (34% vs 11%, p 0.06). At 6.5-year follow-up, 83% SSVR and 89% NSSVR patients are alive. Conclusions. At our institution, patients eligible but not randomized into STICH, had larger preoperative heart volumes and larger volume reduction with SVR. The STICH study may not have included patients most likely to benefit from SVR. (Ann Thorac Surg 2013;95:506 12) 2013 by The Society of Thoracic Surgeons Heart failure as a consequence of coronary artery disease and subsequent ischemic cardiomyopathy is a major health problem with increasing prevalence, partly due to an ageing population, as well as more effective treatment for myocardial infarction. After an ischemic event, the infarcted myocardium, with an area of akinesia (when reperfusion occurs early) or dyskinesia (when there is transmural necrosis) can result in progressive dilatation of the remaining cavity [1]. The post infarction left ventricular (LV) dilatation, defined as greater than 20% increase in LV end-diastolic volume, Accepted for publication Oct 16, Presented at the Forty-eighth Annual Meeting of The Society of Thoracic Surgeons, Fort Lauderdale, FL, Jan 28 Feb 1, Address correspondence to Dr Yii, St. Vincent s Hospital Melbourne, Level 5, 55, Victoria Parade, Fitzroy, Victoria, Melbourne 3065, Australia; michael.yii@svhm.org.au. occurs in 20% of patients with myocardial infarction in less than 18 months [2]. This LV remodeling, characterized by increased LV end-diastolic volume, and changes in LV shape from elliptical to spherical is responsible for the development of congestive heart failure [3 8]. Surgical ventricular restoration (SVR) effectively reverses adverse LV remodeling and was conceived to improve the mechanical performance of the heart. This concept is based on the recognition that both akinetic and dyskinetic scars share similar mechanical defects [9, 10] and that increased LV volume is an important determinant of prognosis after successful revascularization [11, 12]. The international Reconstructive Endoventricular Surgery returning Torsion Original Radius Elliptical shape to the left ventricle (RESTORE) registry has consistently reported on the safety and efficacy of the SVR procedure [11 13]. These nonrandomized data have led to increasing application of SVR [14]. However, when the SVR 2013 by The Society of Thoracic Surgeons /$36.00 Published by Elsevier Inc

2 Ann Thorac Surg GOH ET AL 2013;95: SURGICAL VENTRICULAR RESTORATION 507 procedure was evaluated in a randomized manner in the Surgical Treatment of Ischemic Heart Failure (STICH) trial [15], it conclusively showed that there were no additional benefits of adding SVR to coronary artery bypass grafting (CABG) in patients with LV ejection fraction (EF) less than 0.35 and dominant anterior asynergy. However, the STICH study did not include a registry for SVR-eligible patients who were not randomized, but may confer additional valuable information to the negative findings of the trial. Our study aims to describe the SVR experience in a single center when participating in the STICH study, to better understand the role of SVR in current clinical practice. Material and Methods Patients Between July 2002 and January 2006 (STICH hypothesis 2 enrollment time period at our institute), 21 patients underwent SVR procedure. The patient cohort was differentiated into 2 groups: the STICH SVR (SSVR) group consisted of 12 patients who were randomized in the STICH trial and received SVR, and the non-stich SVR (NSSVR) group comprised 9 patients who were not in the trial yet still had SVR performed. Reasons for nonrandomization for patients in the NSSVR group were analyzed. Patients demographics were obtained from the computerized cardiac surgical database and follow-up was completed by reviewing patients clinical history and direct telephone contact. Determination of anterior wall asynergy was performed according to the STICH protocol for all patients. This study was approved by our Hospital Human Research Ethics Committee (approval number: HREC - A 54/03). Surgical Procedure Details of the surgical techniques have been reported previously [16, 17]. Briefly, the surgery was performed on the arrested heart with a combination of antegrade and retrograde tepid blood cardioplegia. Complete coronary revascularization was performed first using arterial and venous grafting. The SVR was then performed by endoventricular patch plasty as described by Dor and colleagues [16, 17]. Surgical ventricular restoration was performed using a mannequin (TRISVR; Chase Medical, Richardson, TX) filled at 50 to 60 ml/m 2 to optimize the size and shape of the new left ventricle. The endoventricular circular purse-string sutures (Fontan stitch) were placed at the transitional zone and tightened over the mannequin and the ventriculotomy was closed primarily using the ventricular wall if the opening of the ventricle was less than 3 cm or with a Dacron patch graft if it was more than 3 cm. Echocardiography Echocardiography was performed using the GE Vingmed VIVID7 echocardiograph (GE Medical Systems, Princeton, NJ), with data stored digitally. Data analysis was performed offline (EchoPAC, GE Medical Systems) by an echocardiologist who was blinded from the division of the 2 groups of patients. All patients had preoperative echocardiographic assessment. The left ventricular enddiastolic and end-systolic volumes were calculated from both 2-chamber and 4-chamber images using the biplane method of disks (modified Simpson rule) and were indexed to body surface area (ml/m 2 ). The LVEF was derived from the LV volumes using the formula: (EDV- ESV/EDV) 100%. Poor echocardiographic images that were unsuitable for assessment were excluded from the analysis. The same echocardiographic analysis was performed at less than 4 months and greater than 4 years postoperatively. Follow-Up The functional status of the patients was assessed at baseline, less than 4-months, and greater than 4-years followup, using the Canadian Cardiovascular Society angina class and New York Heart Association (NYHA) heart failure class. Follow-up was conducted by direct telephone calls with the patients and was completed in 100% of the patients. Survival was assessed on the basis of the occurrence of all-cause mortality during the follow-up. Statistical Analysis All data are expressed as median with 25th and 75th interquartile range. All statistical analyses are performed using nonparametric tests. Categoric data are compared with the Fisher exact test. Continuous variables at baseline and follow-up within both groups are compared with Wilcoxon signed-rank test. Intergroup comparison was made with the Wilcoxon rank-sum test. Statistical significance was assumed at a p value less than Results Patient Characteristics CABG was performed in 12 (100%) SSVR patients and 8 (89%) NSSVR patients. No valvular surgery was performed in any of these patients. Nine out of the 21 SVR patients were not in the STICH trial yet received SVR procedure; 8 out of those 9 were STICH-eligible but were not randomized. One patient did not meet the STICH criteria of LVEF less than He had a recent myocardial infarction with mural LV thrombus. SVR was deemed necessary in 3 NSSVR patients by consensus after discussions at a preoperative clinical conference and were therefore excluded from participation in the randomized STICH study. These 3 patients all had dominant heart failure symptoms. One patient had frank LV aneurysm, 1 patient had severely enlarged LV without frank aneurysm, and the remaining patient presented with progressive heart failure symptoms and an enlarging ventricle for SVR only without CABG. He had a completely recanalized left anterior descending and no LV aneurysm. On these bases, SVR was deemed necessary and these patients were not randomized. Of the remaining 5 NSSVR patients, 4 were eligible for STICH stratum C. One patient was not recruited in the

3 508 GOH ET AL Ann Thorac Surg SURGICAL VENTRICULAR RESTORATION 2013;95: STICH study because of language issues and received SVR because of a large aneurysm. Two patients had multisegmental infarcts and were deemed not ideal for SVR in the STICH study. Both patients had dominant heart failure symptoms and large LV volumes, and SVR was performed at the surgeon s discretion. One patient had consented for STICH stratum C but presented for urgent CABG without randomization. SVR was performed at the surgeon s discretion for advanced heart failure symptoms. The remaining NSSVR patient was randomized in STICH stratum B to receive medical therapy only, but re-presented with progressive heart failure symptoms and crossed over to receive CABG electively. SVR was performed at the surgeon s discretion predominantly because his worsening heart failure symptoms. Baseline Demographics and Operative Data The preoperative patient characteristics and operative data are shown in Tables 1 and 2, respectively. The 2 groups of patients were comparable in terms of the baseline demographics, medical history, number of diseased coronary arteries, number of grafts used for CABG, as well as the aortic cross-clamp and total bypass time. The NSSVR group had significantly larger preoperative LV end-systolic volume index (ESVI) compared with the SSVR group (71 ml/m 2 vs 51 ml/m 2, p 0.05) and more anterior asynergy (median 60% compared with 45% in the SSVR group, p 0.001). Although nonsignificant, there were more patients with advanced class III-IV heart failure symptoms in the NSSVR group compared with the SSVR group (67% vs 41%, p 0.39). Echocardiographic Assessment The LVEF increased from 27% to 38% at 4 months (p 0.05) and 35% at 4 years (p 0.05) for the SSVR group and from 32% at baseline to 39% (p 0.05) and 43% (p 0.05) at the same time points, respectively, for the NSSVR group (Table 3). There was no significant difference in the percentage increase in LVEF between the 2 groups (Fig 1). In terms of the LV volumes, the NSSVR group had a significantly larger preoperative LV end-diastolic volume index (EDVI) and LVESVI compared with the SSVR group (Table 3). The LVESVI reduction from baseline was significantly greater in the NSSVR group at both 4 months (45% vs 25%, p 0.05) and 4 years (50% vs 15%, p 0.005), as shown in Figure 2. The LVEDVI reductions were also greater in the NSSVR group, in a nonsignificant manner, compared with the SSVR group (Fig 3). Symptoms At baseline, 58% of SSVR and 34% of NSSVR did not have angina; 42% SSVR and 55% NSSVR patients had class III-IV angina (Fig 4). The proportion of patients with no angina increased and the proportion of patients with Canadian Cardiovascular Society class III-IV angina declined at 4-month and 4-year follow-up. All SSVR and 88% NSSVR patients were angina free at 4-year followup. Angina symptoms improved by 1.5 classes in the Table 1. Baseline Demographics and Clinical Characteristics Characteristic SSVR NSSVR (n 12) (n 9) p Value Demographic characteristics Age; year (median, IQR) 69 (63, 74) 65 (59, 73) 0.58 BMI, kg/m 2 (median, 27 (25, 30) 26 (24, 28) 0.43 IQR) Male, 9 (75) 8 (89) 0.60 Medical history Myocardial infarction, 9 (75) 9 (100) 0.26 Hyperlipidemia, 10 (83) 8 (89) 1.00 Hypertension, 11 (92) 8 (89) 1.00 Diabetes, 5 (42) 4 (45) 1.00 Ex-smoker, 7 (58) 7 (78) 0.64 Creatinine 0.2 mmol/l, 1 (8) 0 (0) 1.00 Stroke, 3 (25) 1 (11) 0.60 Previous PCI, 2 (17) 0 (0) 0.49 Left ventricular function Left ventricular ejection fraction, n (100) 8 (89) (0) 1 (11) 0.43 ESVI - ml/m 2 (median, 51 (45,73) 71 (59,102) 0.05 IQR) Akinesia/dyskinesia of anterior wall, % Mitral regurgitation, None/trace 4 (33) 2 (22) 0.66 Mild 8 (67) 6 (67) 1.00 Moderate 0 (0) 1 (11) 0.43 Severe 0 (0) 0 (0) NYHA heart failure class I-II, 7 (59) 3 (33) 0.39 III-IV, 5 (41) 6 (67) 0.39 CCS angina class No angina, 7 (58) 3 (34) 0.39 I-II, 0 (0) 1 (11) 0.49 III-IV, 5 (42) 5 (55) 0.67 Coronary anatomy No. of vessels with stenosis 50%, 1 1 (8) 0 (0) (34) 1 (11) (58) 7 (78) 0.64 Stenosis of left main coronary artery, 50% 74% 2 (17) 1 (11) % 0 (0) 1 (11) % of left anterior descending coronary artery stenosis, 12 (100) 7 (78) 0.17 BMI body mass index; CCS Canadian Cardiovascular Society; ESVI end-systolic volume index; IQR interquartile range; NSSVR non-stich surgical ventricular restoration group; NYHA New York Heart Association; PCI percutaneous coronary intervention; SSVR STICH surgical ventricular restoration group.

4 Ann Thorac Surg GOH ET AL 2013;95: SURGICAL VENTRICULAR RESTORATION 509 Table 2. Operative Data Variable SSVR (n 12) NSSVR (n 9) p Value CABG, 12 (100) 8 (89) 0.43 Number of grafts, 1 0 (0) 0 (0) 2 2 (17) 0 (0) (25) 4 (45) (58) 4 (45) 0.67 Cross-clamp time, 120 (102, 126) 112 (101, 119) 0.72 minutes (median, IQR) Total bypass time, 139 (126, 160) 156 (137, 167) 0.23 minutes (median, IQR) Operative 0 (0) 0 (0) mortality, Mitral valve surgery, 0 (0) 0 (0) CABG coronary artery bypass surgery; IQR interquartile range; NSSVR non-stich surgical ventricular restoration group; SSVR STICH surgical ventricular restoration group. SSVR group and 3 classes in the NSSVR group at 4 years (p 0.84). Similarly, there were more patients in the NSSVR group with class III-IV NYHA heart failure symptoms at baseline (67% vs 41%, p 0.39). The proportion of patients with class I symptoms increased and the proportion with class III-IV heart failure symptoms decreased during the interval from baseline to 4-month and 4-year follow-up. Heart failure symptoms improved by 1 class in SSVR and 1.5 classes in NSSVR groups at 4 years (p 0.47). Mortality and Survival Thirty-day and in-hospital mortality was zero for both groups of patients. At a median follow-up of 6.5 years, 10 of 12 (83%) SSVR and 8 of 9 (89%) NSSVR patients are alive. There was 1 early death from ventricular arrhythmia in the SSVR group at 5 weeks. The other death in the SSVR group Fig 1. Percentage change in left ventricular ejection fraction (LVEF) from baseline to 4-month and 4-year follow-up for SSVR (white bars) and NSSVR (black bars) groups. was 4 years post SVR due to progressive heart failure. There was 1 noncardiac death in the NSSVR group at 2 years. Four patients in each group had received a cardiac resynchronization therapy defibrillator device at latest follow-up for both primary and secondary prevention. Comment Surgical ventricular restoration has evolved from the early days of linear plication of anteroapical dyskinetic aneurysms to the introduction of endoventricular circular patch plasty repair for left ventricular aneurysm as described by Dor and colleagues [16, 17] in the 1980s. The Table 3. Echocardiographic and Clinical Outcomes; Median (25th, 75th IQR) Variable CCS NYHA LVEF EDVI (ml/m 2 ) ESVI (ml/m 2 ) SSVR Preop 0 (0,4) 2 (2,3) 0.27 (0.23,0.32) 69 (62,101) b 51 (45,73) b 4 month 0 (0,0) 2 (1,2) 0.38 (0.35,38) a 51 (42,67) a 37 (31,45) a 4 year 0 (0,0) 1 (1,1) a 0.35 (0.32,0.50) a 63 (57,67) 44 (37,48) a NSSVR Preop 3 (0,3) 3 (2,3) 0.32 (0.25,0.35) 108 (88,129) b 71 (59,102) b 4 month 0 (0,0) 2 (0,2) a 0.39 (0.26,0.51) a 79 (66,94) a 53 (31,69) a 4 year 0 (0,0) 1 (1,2) a 0.43 (0.37,0.47) a 72 (56,94) a 49 (31,62) a a Significant (p 0.05) compared with preop using Wilcoxon signed-rank test. b Significant (p 0.05) between SSVR and NSSVR group using Wilcoxon rank-sum test. CCS Canadian Cardiovascular Society; EDVI end-diastolic volume index; ESVI end-systolic volume index; IQR interquartile range; LVEF left ventricular ejection fraction; NYHA New York Heart Association; NSSVR non-stich surgical ventricular restoration group; preop preoperative; SSVR STICH Surgical Ventricular Restoration group.

5 510 GOH ET AL Ann Thorac Surg SURGICAL VENTRICULAR RESTORATION 2013;95: Fig 2. End-systolic volume index (ESVI) reduction expressed as median percentage change with 25th and 75th interquartile range (in brackets) for the SSVR (white bars) and NSSVR (black bars) groups at follow-up. The ESVI reductions were significantly greater in the NSSVR group at both 4-month and 4-year follow-up. SVR has been studied in many retrospective cohort studies and small nonrandomized trials [5, 11, 18 21]. Athanasuleas and colleagues [11 13] from the RESTORE group reported on the safety and efficacy of SVR in patients with ischemic cardiomyopathy. However, when this procedure was vigorously evaluated in the STICH trial, it found no benefit for the routine use of SVR in patients with LVEF less than 0.35 and dominant anterior asynergy [15], bringing into dispute the role of SVR in ischemic cardiomyopathy. The authors suggested that this negative result was more likely due to loss of diastolic distensibility as a result of SVR rather than selection bias. The registry arm of the STICH study for nonrandomized patients had been abandoned because of difficulty recruiting patients, thereby limiting the translation of the STICH results to contemporary practice. During the time frame our center was actively recruiting for the STICH trial, 43% of SVRs (9 out of 21) were performed outside of the trial. Eighty-nine percent of these patients would have been eligible for randomization, yet received SVR without participating in the study. The main reasons for performing SVR included dominant heart failure symptoms, LV aneurysm, and LV thrombus, associated with severe LV enlargement. Our SSVR cohort were comparable with the STICH trial in terms of anterior wall asynergy (45% in SSVR vs 50% in STICH), the proportion of patients with class III-IV heart failure symptoms preoperatively (42% in SSVR vs 49% in STICH) and preoperative EF (0.27 in SSVR vs 0.28 in STICH, Table 4). The LVESVI reduction was 19% in the STICH trial and 15% in our patients. This amount of volume reduction was generally below published series, which demonstrated an average LVESVI reduction of 40%, with a range of 30% to 58% [5, 8, 11, 18, 21]. The preoperative and postoperative LVESVI were smaller in our SSVR patients compared with the STICH trial. Residual LVESVI in the STICH trial was 67 ml/m 2. White and colleagues [5] showed that LVESVI greater than 60 ml/m 2 is associated with a fivefold increase in mortality compared with those with normal volumes post myocardial infarction. In contrast, our NSSVR group had a reduction of LVESVI from 71 ml/m 2 to 49 ml/m 2, an absolute reduction of 50% (Table 4). This is more comparable with the RESTORE [11 13] data, which reported a LVESVI reduction from 80 ml/m 2 to 56 ml/m 2, an absolute reduction of 30%. In addition to ventricular volumes, the RESTORE group documented preoperative NYHA class as one of the major risk factors for late mortality [13]. They reported a 5-year survival rate of 50% to 70% for class III-IV NYHA class compared with 87% to 95% for class I-II. Our NSSVR and RESTORE population had a larger proportion of patients with class III-IV symptoms. This is in contrast to the STICH trial where less than half of the patients had advanced heart failure symptoms. During the same time period, 9 patients were randomized to CABG only in STICH stratum B and C (SVR hypothesis) at our institution, and were all treated as per protocol. These patients had statistically similar baseline volume and percentage anterior asynergy to the SSVR Fig 3. End-diastolic volume index (EDVI) reduction expressed as median percentage with the 25th and 75th interquartile range (in brackets) for SSVR (white bars) and NSSVR (black bars) groups at follow-up. The EDVI reductions were greater in the NSSVR group at both 4-month and 4-year follow-up.

6 Ann Thorac Surg GOH ET AL 2013;95: SURGICAL VENTRICULAR RESTORATION 511 Fig 4. Canadian Cardiovascular Society (CCS) angina class and New York Heart Association (NYHA) heart failure symptoms at baseline and follow-up. (A) The non-stich surgical ventricular restoration (NSSVR) group had a larger proportion of patients with CCS class III-IV at baseline. The proportion of patients with no angina increased at 4-month and 4-year follow-up for both groups. (B) There were more patients in the NSSVR group with advanced class III-IV heart failure symptoms at baseline and the symptom class improved for both groups at both 4-month and 4-year follow-up. (Pre preoperative). patients, and also statistically smaller baseline and percentage anterior asynergy compared with the NSSVR patients. Two patients in stratum B were randomized to receive medical therapy alone, of which 1 died and the other crossed over to receive CABG and SVR during follow-up. Of these 11 STICH SVR-eligible patients, 3 patients have died (1 medical therapy only patient and 2 CABG only patients). Baseline LVESVI of the 3 STICH SVR-eligible patients who have died and did not receive SVR were 127, 139, and 179 ml/m 2. Our study compared the clinical and hemodynamic outcomes of patients who were randomized to receive SVR in the STICH trial in parallel with those who received SVR outside the trial. As anticipated, SVR improved LV function and the functional status in both groups of patients. However, the volume reductions were significantly greater in the NSSVR patient group, which had significantly larger preoperative LV volumes with more anterior asynergy, implying perhaps that STICH may not have included patients who were more likely to benefit from SVR. Study Limitations This study is based on a retrospective analysis of a small patient population in a single center participating in the STICH trial and may not be reflective of practices in other participating centers. Notwithstanding this, the marked differences between our 2 patient cohorts and the volume differences observed between the STICH trial and other registry data are highly suggestive that patients more likely to benefit from SVR may have not have been included in the STICH trial. The follow-up measure- Table 4. Comparison of Our Study With the STICH [15] Trial and the RESTORE [13] Study Our Cohort STICH Trial SSVR NSSVR RESTORE % Anterior wall asynergy 50% 45% 60% N/A Preop LVEF Preop EDVI (ml/m 2 ) N/A N/A NYHA III-IV 49% 42% 67% 67% ESVI reduction % (Preop 19% (82 to 67) 15% (51 to 44) 50% (71 to 49) 30% (80 to 56) to postop, ml/m 2 ) 30-day mortality 5% 0% 0% 5.3% Survival at follow-up Years 72% (5 years) 83% (6.5 years) 89% (6.5 years) 69% (5 years) EDVI end-diastolic volume index; ESVI end-systolic volume index; LVEF left ventricular ejection fraction; N/A Not available; NSSVR non-stich surgical ventricular restoration group; NYHA New York Heart Association; postop postoperative; preop preoperative; RESTORE Reconstructive Endoventricular Surgery, Torsion Original Radius Elliptical registry; SSVR STICH surgical ventricular restoration group.

7 512 GOH ET AL Ann Thorac Surg SURGICAL VENTRICULAR RESTORATION 2013;95: ments of LV volumes were not obtained at precisely the same postoperative interval. The 4-month measurements varied from intraoperative assessment to 4 months for the NSSVR patients. Likewise, the 4-year follow-up measurements were recorded between 4 years to the latest follow-up. Conclusions Our study demonstrated that the SVR procedure, when performed in appropriately selected patients, provides sustained clinical and hemodynamic improvements with minimal associated mortality. At our institution, patients receiving SVR outside of the STICH trial had worse heart failure symptoms and significantly larger LV volumes preoperatively. Despite this, both groups of patients benefitted symptomatically from the procedure with excellent long-term survival. We thank Dr Roman Kluger, Anesthetic Department at St Vincent s Hospital, Melbourne, for the statistical analysis and Ms Antoinette White for editing the manuscript. References 1. Klein MD, Herman MV, Gorlin R. A hemodynamic study of left ventricular aneurysm. Circulation 1967;35: Gaudron P, Eilles C, Ertl G, Kochsiek K. Compensatory and noncompensatory left ventricular dilatation after myocardial infarction: time course and hemodynamic consequences at rest and during exercise. Am Heart J 1992;123: Castelvecchio S, Menicanti L, Donato MD. Surgical ventricular restoration to reverse left ventricular remodeling. Curr Cardiol Rev 2010;6: Gaudron P, Eilles C, Kugler I, Ertl G. Progressive left ventricular dysfunction and remodeling after myocardial infarction. Potential mechanisms and early predictors. Circulation 1993;87: White HD, Norris RM, Brown MA, Brandt PW, Whitlock RM, Wild CJ. Left ventricular end-systolic volume as the major determinant of survival after recovery from myocardial infarction. Circulation 1987;76: Yamaguchi A, Ino T, Adachi H, Mizuhara A, Murata S, Kamio H. Left ventricular end-systolic volume index in patients with ischemic cardiomyopathy predicts postoperative ventricular function. Ann Thorac Surg 1995;60: Hamer AW, Takayama M, Abraham KA, et al. End-systolic volume and long-term survival after coronary artery bypass graft surgery in patients with impaired left ventricular function. Circulation 1994;90: Di Donato M, Castelvecchio S, Kukulski T, et al. Surgical ventricular restoration: left ventricular shape influence on cardiac function, clinical status, and survival. Ann Thorac Surg 2009;87: Di Donato M, Sabatier M, Dor V, Toso A, Maioli M, Fantini F. Akinetic versus dyskinetic postinfarction scar: relation to surgical outcome in patients undergoing endoventricular circular patch plasty repair. J Am Coll Cardiol 1997;29: Dor V, Sabatier M, Di Donato M, Montiglio F, Toso A, Maioli M. Efficacy of endoventricular patch plasty in large postinfarction akinetic scar and severe left ventricular dysfunction: comparison with a series of large dyskinetic scars. J Thorac Cardiovasc Surg 1998;116: Athanasuleas CL, Buckberg GD, Stanley AW, et al. Surgical ventricular restoration: the RESTORE Group experience. Heart Fail Rev 2004;9: Isomura T, Hoshino J, Fukada Y, et al. Volume reduction rate by surgical ventricular restoration determines late outcome in ischaemic cardiomyopathy. Eur J Heart Fail 2011;13: Athanasuleas CL, Buckberg GD, Stanley AW, et al. Surgical ventricular restoration in the treatment of congestive heart failure due to post-infarction ventricular dilation. J Am Coll Cardiol 2004;44: Hernandez AF, Velazquez EJ, Dullum MK, O Brien SM, Ferguson TB, Peterson ED. Contemporary performance of surgical ventricular restoration procedures: data from the Society of Thoracic Surgeons National Cardiac Database. Am Heart J 2006;152: Jones RH, Velazquez EJ, Michler RE, et al. Coronary bypass surgery with or without surgical ventricular reconstruction. N Engl J Med 2009;360: Dor V, Saab M, Coste P, Kornaszewska M, Montiglio F. Left ventricular aneurysm: a new surgical approach. Thorac Cardiovasc Surg 1989;37: Dor V. Left ventricular restoration by endoventricular circular patch plasty (EVCPP). Z Kardiol 2000;89(Suppl 7): Yamaguchi A, Adachi H, Kawahito K, Murata S, Ino T. Left ventricular reconstruction benefits patients with dilated ischemic cardiomyopathy. Ann Thorac Surg 2005;79: Vanoverschelde JL, Depré C, Gerber BL, et al. Time course of functional recovery after coronary artery bypass graft surgery in patients with chronic left ventricular ischemic dysfunction. Am J Cardiol 2000;85: Dor V. Reconstructive left ventricular surgery for postischemic akinetic dilatation. Semin Thorac Cardiovasc Surg 1997;9: Migrino RQ, Young JB, Ellis SG, et al. End-systolic volume index at 90 to 180 minutes into reperfusion therapy for acute myocardial infarction is a strong predictor of early and late mortality. The Global Utilization of Streptokinase and t-pa for Occluded Coronary Arteries (GUSTO)-I Angiographic Investigators. Circulation 1997;96: