Improved Functional Mitral Regurgitation After Off-Pump Revascularization in Acute Coronary Syndrome

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1 Improved Functional Mitral Regurgitation After Off-Pump Revascularization in Acute Coronary Syndrome Ho Young Hwang, MD, PhD, Jae Hong Lim, MD, Se Jin Oh, MD, Jin Chul Paeng, MD, PhD, and Ki-Bong Kim, MD, PhD Departments of Thoracic and Cardiovascular Surgery and Nuclear Medicine, Seoul National University Hospital, Seoul, Korea Background. We evaluated the effect of isolated offpump coronary artery bypass grafting on functional ischemic mitral regurgitation (IMR) associated with acute coronary syndrome. Methods. Of 1,419 acute coronary syndrome patients who underwent coronary revascularization between 2000 and 2010 (1,324 off-pump and 95 on-pump), 59 OPCAB patients had greater than mild degree functional IMR preoperatively (31 mild to moderate, 23 moderate, 5 severe). Clinical outcomes and results from echocardiography, angiography, and myocardial single-photon emission computed tomography performed early and 1 year postoperatively were analyzed. Results. Operative mortality was 5.1% (3 of 59). All survivors underwent early postoperative echocardiograms, which showed 0 patients with worsened IMR; 41 with less than or equal to mild degree residual IMR (NMR group); and 15 with greater than mild degree IMR (RMR group). Myocardial single-photon emission computed tomography revealed that RMR patients had more reversible ischemic myocardial segments preoperatively than NMR patients (p 0.009). Successful right coronary revascularization with proven graft patency was a predictor of early improvement of IMR (p 0.024). There were no differences in postoperative morbidities between the 2 groups. One-year follow-up echocardiograms demonstrated further improvement in 10 of 13 RMR patients. No patients experienced mitral valve-related events during follow-up. Overall survival and major adverse cardiac event-free survival rates at 5 years were 84.6% and 78.1%, respectively, with no intergroup differences. Conclusions. Most functional IMR associated with acute coronary syndrome, including severe degree IMR, improved during the first postoperative year after offpump coronary artery bypass grafting. (Ann Thorac Surg 2012;94: ) 2012 by The Society of Thoracic Surgeons Functional ischemic mitral regurgitation (IMR) results from abnormal function of normal mitral valve leaflets caused by changes in ventricular structure and function related to myocardial ischemia [1]. Causes of functional IMR vary from acute ischemic injury and left ventricular dysfunction to chronic left ventricular remodeling [2, 3]. Most previous studies demonstrated that treating chronic moderate to severe degree IMR at the time of coronary artery bypass grafting (CABG) was beneficial [4 8]. However, there has been no demonstration of a treatment strategy for functional IMR in patients with acute coronary syndrome (ACS). The aim of the present study was to evaluate whether mitral valve surgery is necessary in patients with ACS combined with functional IMR. We retrospectively reviewed our experience with isolated off-pump CABG (OPCAB) performed in patients with ACS and concomitant IMR greater than mild degree. Accepted for publication April 30, Presented at the Forty-eighth Annual Meeting of The Society of Thoracic Surgeons, Fort Lauderdale, FL, Jan 28 Feb 1, Address correspondence to Dr Kim, Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul , Korea; kimkb@snu.ac.kr. Material and Methods The study protocol was reviewed by the Institutional Review Board and approved as a minimal risk retrospective study (Approval Number: H ). It did not require individual consent based on the institutional guidelines for waiving consent. Patient Characteristics Of 1,911 patients who underwent isolated CABG between January 2000 and December 2010, 1,419 patients underwent CABG (1,324 off-pump and 95 on pump) for ACS. The spectrum of ACS included unstable angina, non-stsegment elevation myocardial infarction (NSTEMI) and ST-segment elevation myocardial infarction (STEMI) [9]. Seventy-one ACS patients (5.0%) had functional IMR greater than mild degree at the time of surgery. Among those, 59 patients who underwent isolated OPCAB based on our surgical strategies during the study period were enrolled in the present study. Preoperative echocardiograms revealed that grades of IMR were mild to moderate degree in 31 (52.5%), moderate degree in 23 (39.0%), and severe degree in 5 patients (8.5%). Twenty-five patients (42.4%) showed left ventricular dysfunction (left ventricular ejection fraction 0.35). Echocardiographic 2012 by The Society of Thoracic Surgeons /$36.00 Published by Elsevier Inc

2 1158 HWANG ET AL Ann Thorac Surg OPCAB IN ACS PATIENTS WITH FUNCTIONAL ISCHEMIC MR 2012;94: Table 1. Preoperative Characteristics and Echocardiographic Data of the Study Patients Variables n 59 Age (years) Male to Female 33:26 Recent myocardial infarction ( 2 weeks) 13 (22%) Risk factors, n (%) Smoking 23 (39%) Hypertension 40 (68%) Overweight (body mass index 25 kg/m 2 ) 24 (41%) Dyslipidemia 8 (14%) Chronic renal failure 13 (23%) History of stroke 12 (20%) Three-vessel disease 49 (83%) Left main disease 17 (29%) Emergent operation 9 (15%) Echocardiographic data LV ejection fraction LV end-systolic dimension (mm) LV end-diastolic dimension (mm) Grade of mitral regurgitation Mild to moderate 31 (53%) Moderate 23 (39%) Severe 5 (8%) Regional wall motion abnormality Left anterior descending coronary artery 30 (51%) Left circumflex coronary artery 20 (34%) Right coronary artery 45 (76%) LV left ventricular. evaluation months before ACS in 16 of the 59 patients showed no previous IMR. Cardiac presentations on admission were unstable angina in 39, NSTEMI in 11, and STEMI in 9 patients (Table 1). Emergent operations (operation carried out on referral before the beginning of the next working day) were performed in 7 patients (3 with unstable angina, 1 with NSTEMI, and 3 with STEMI) and urgent operation was performed in 17 patients. Twelve ACS patients were excluded from the study; 8 patients who underwent mitral annuloplasty during the early half of the study period based on the previous studies favoring mitral procedures [10, 11] and another 4 patients who underwent on-pump beating heart CABG because of impending cardiogenic shock during anesthetic induction. Operative Strategy The basic surgical procedures and principles of OPCAB have been previously described [12]. The left internal thoracic artery was used for revascularization in all patients except 1 in whom the right gastroepiploic artery graft was used for revascularization of the posterior descending coronary artery. Other conduits used included the right gastroepiploic artery (n 41), right internal thoracic artery (n 21), saphenous vein (n 15), and radial artery (n 1). The average number of distal anastomoses per patient was Complete revascularization, defined as at least 1 graft to each of the diseased 3 major coronary artery territories, was achieved in 48 patients (81.4%). Causes of incomplete revascularization were diffusely atherosclerotic small coronary arteries ( 1 mm diameter) in 3 patients and heavily calcified coronary arteries in 8 patients (7 right coronary artery territory, 3 left circumflex coronary artery territory, and 1 left anterior descending coronary artery territory). Our surgical strategies during the study period were the following: (1) performing off-pump revascularization while avoiding aortic manipulation; and (2) performing complete revascularization if possible, using a composite graft anastomosed to the in situ left internal thoracic artery. We used a free right gastroepiploic artery graft as a composite graft in most patients. When the right gastroepiploic artery was unavailable for grafting, or when the composite graft was too short to reach the target vessels, we harvested additional grafts from either other arteries or the saphenous vein to construct composite grafts. The most critical coronary artery territory (the left anterior descending coronary artery territory in almost all of the patients) was revascularized first to provide a backup to less critical territories. The left circumflex coronary artery territory was then revascularized, followed by the right coronary artery territory. Preoperative intraaortic balloon pump therapy during angiography or intensive care unit stay was performed in 21 patients (35.6%) because of hemodynamic instability or intractable resting angina. In another 10 patients, intraaortic balloon pump therapy was performed during OPCAB when acute hemodynamic instability occurred. Almost all of the acute hemodynamic instabilities during OPCAB were accompanied by aggravation of IMR. Intraaortic balloon pump therapy improved cardiac performance, reduced IMR, and facilitated completion of the procedure without conversion to cardiopulmonary bypass. Echocardiographic Evaluation Transthoracic echocardiography was performed preoperatively, prior to discharge, and 1 year postoperatively. The severity of IMR was graded as mild (area 0.20 cm 2 ), mild to moderate (0.20 to 0.29 cm 2 ), moderate (0.30 to 0.39 cm 2 ), and severe degree ( 0.40 cm 2 ) based on the effective regurgitant orifice area, which was calculated using the proximal isovelocity surface area method [13, 14]. Residual IMR was defined as IMR greater than mild degree as seen in echocardiography performed prior to discharge. Residual IMR at 1 year postoperatively included sustained or recurrent IMR greater than mild degree. Intraoperative transesophageal echocardiogram was performed in all patients. After anesthetic induction, mitral leaflet and subvalvular structure and eccentricity of regurgitation jet were evaluated, and degree of IMR was assessed as a baseline value for evaluation of further changes during surgery. In all 5 patients who had severe IMR on preoperative transthoracic echocardiogram, the degree of IMR remained severe even after anesthetic induction. Changes in IMR grade were assessed by

3 Ann Thorac Surg HWANG ET AL 2012;94: OPCAB IN ACS PATIENTS WITH FUNCTIONAL ISCHEMIC MR 1159 transesophageal echocardiogram after completion of each distal anastomosis. When all anastomoses were completed, IMR grade was reassessed. Mitral valve surgery was considered only if the grade of IMR had worsened or remained severe after completion of all anastomoses. Based on our off-pump revascularization strategy, however, none of the patients underwent mitral annuloplasty during the study period. Myocardial Single-Photon Emission Computed Tomography Study Thallium 201 rest/dipyridamole stress technetium 99m methoxyisobutylisonitrile-gated single-photon emission computed tomography (SPECT) was performed preoperatively and at 3 months and 1 year postoperatively, as previously described [15]. A 20-segment model was adopted for regional perfusion analysis. It was presumed that segments with a preoperative resting perfusion of 50% or less contained less viable myocardium and more fibrotic or necrotic myocardium than segments with a resting perfusion of greater than 50%. Therefore, probable nonviable segments with a preoperative resting perfusion of 50% or less were excluded. Reversibility score, an indicator of perfusion impairment reversibility, was calculated as rest minus stress perfusion values in each viable myocardial segment. To select perfusion-impaired segments, a reversibility score cutoff of 7 was used. Changes in left ventricular end-diastolic and end-systolic volume indices and ejection fraction were also calculated. Evaluation of Long-Term Clinical Outcomes Patients underwent regular postoperative follow-up through the outpatient clinic at 3- or 4- month intervals. Clinical and angiographic follow-up was completed on October 31, Follow-up was complete in 95% (53 of 56 survivors), with a follow-up duration of months. Operative mortality was defined as any death within 30 days, including deaths after hospital discharge. Cardiac death was defined as any death related to cardiac events, including sudden death during follow-up. Major adverse cardiac events included late cardiac death, acute myocardial infarction, coronary reintervention, congestive heart failure needing hospital readmission, and subsequent mitral valve procedures. Evaluation of Angiographic Patency Early and 1-year follow-up coronary angiograms were performed regardless of patients angina symptoms. Early postoperative angiograms were performed in 96.4% (54 of 56) of survivors on postoperative days. One-year ( months) coronary angiograms were performed in 92% (43 of 47) of patients who were followed for more than 1 year. Statistical Analysis Statistical analysis was performed using the IBM SPSS 19 (SPSS Inc, Chicago, IL) and SAS 9.1 (SAS Institute Inc, Cary, NC) software packages. Data were expressed as mean standard deviation, median and ranges, or proportions. Comparison between the 2 groups was performed with the 2 test or Fisher exact test for categoric variables and the Student t test or Mann-Whitney U test for continuous variables. Survival rates were estimated using the Kaplan-Meier method and comparisons between groups were performed using the log-rank test. Predictors of residual IMR were analyzed with univariate and multivariable logistic regression analysis. Variables with a p value less than 0.2 in univariate analysis were entered into multivariable analysis. A p value less than 0.05 was considered statistically significant. A mixed model, treating patients as a random effect and time and group as fixed effects, was constructed to analyze changes in the number of reversible ischemic segments and left ventricular volume indices according to the groups and time periods. The Scheffé method was used for ad hoc analysis. Results Early Clinical Results Three operative mortalities occurred (3 of 59, 5.1%); 2 deaths resulting from intractable ventricular arrhythmia that developed on the first postoperative day and 1 death resulting from massive pulmonary embolism on the eighth postoperative day. Improved mild degree IMR after OPCAB was observed in all 3 operative mortality patients by intraoperative transesophageal echocardiogram. Postoperative complications included atrial fibril- Table 2. Early Mortality and Morbidities of the Study Patients Variable Total (n 59) RMR Group (n 15) NMR Group (n 41) p Value Early mortality 3 (5.1%) Postoperative complications Atrial fibrillation 22 (38.6%) 5 (33.3%) 16 (39.0%) Acute renal failure 5 (8.5%) 2 (13.3%) 2 (4.9%) Perioperative myocardial infarction 3 (5.1%) 2 (13.3%) 1 (2.4%) Bleeding reoperation 2 (3.4%) 0 (0%) 2 (4.9%) Low cardiac output syndrome 2 (3.4%) 1 (6.7%) 1 (2.4%) Stroke 1 (1.7%) 1 (6.7%) 0 (0%) NMR group less than or equal to mild degree residual ischemic mitral regurgitation; RMR group greater than mild degree ischemic mitral regurgitation.

4 1160 HWANG ET AL Ann Thorac Surg OPCAB IN ACS PATIENTS WITH FUNCTIONAL ISCHEMIC MR 2012;94: Fig 1. Early postoperative changes in mitral regurgitation after isolated off-pump coronary revascularization. lation (n 22, 37.3%), acute renal failure (n 5, 8.5%), and perioperative myocardial infarction (n 3, 5.1%) (Table 2). Postoperative Changes in IMR Early postoperative ( days) transthoracic echocardiography was performed in all survivors (n 56). The IMR degree improved in 80% (45 of 56) of patients and none of the patients had worsened IMR compared with preoperative grading. Fifteen patients had residual IMR graded greater than mild degree (RMR group; mild to moderate in 9 and moderate in 6 patients) and 41 patients had residual IMR graded mild degree or less (NMR group) (Fig 1). There was no correlation between the preoperative grade of IMR and residual IMR (p 0.813). Preoperative regional wall motion abnormalities in the anterior, lateral, and inferior walls also were not associated with residual IMR (p 0.365, 0.751, and 0.736, respectively). Overall completeness of revascularization was not associated with residual IMR. Instead, multivariable analysis revealed that successful revascularization of right coronary artery territory with proven early patency predicted a resolution of IMR early postoperatively (p 0.024) (Table 3). Impact of Residual IMR on Clinical Outcomes There were no differences in postoperative complications between the NMR and RMR groups (Table 2). Among 56 Table 3. Independent Predictors of Residual Mitral Regurgitation Early After Surgery Univariate Multivariable Variables p Value Odds Ratio [95% CI] p Value Age (years) Sex Body mass index (m 2 /kg) Smoking Diabetes mellitus Hypertension [ ] History of stroke [ ] Dyslipidemia [ ] Chronic renal failure Left main disease Three-vessel disease Incomplete revascularization Right coronary territory revascularization [ ] Grade of preoperative mitral regurgitation Left ventricular end-systolic dimension Left ventricular end-diastolic dimension [ ] Left ventricular ejection fraction CI confidence interval.

5 Ann Thorac Surg HWANG ET AL 2012;94: OPCAB IN ACS PATIENTS WITH FUNCTIONAL ISCHEMIC MR 1161 Fig 2. Overall survival rates at 5 and 10 years were 84.6%, and 78.1%, respectively. Logrank test revealed no difference in overall survival between the RMR (greater than mild degree ischemic mitral regurgitation [IMR]) and NMR (less than or equal to mild degree residual IMR) groups (p 0.397). survivors, late death occurred in 7 (12.5%) patients, including 3 cardiac deaths (2 sudden deaths and 1 death associated with congestive heart failure). Overall survival rates at 5 and 10 years were 84.6% and 78.1%, respectively. None of the patients needed subsequent mitral valve surgery during the follow-up period. Four patients underwent reoperation (n 1; due to graft occlusion) or reintervention (n 3; due to graft occlusion in 1 and native disease progression in 2). Four patients needed hospital readmission due to congestive heart failure. Five and 10-year major adverse cardiac event-free survival rates were 75.1% and 68.3%, respectively. There were no differences in overall and major adverse cardiac eventfree survival rates between the 2 groups (p and 0.570, respectively) (Figs 2, 3). Changes in Mitral Regurgitation at One Year Forty-eight patients underwent 1-year follow-up echocardiograms (13 of 15 patients in the RMR group and 35 of 41 patients in the NMR group), and IMR graded greater than mild degree was observed in 5 patients (10.4%) (Fig 4). In the RMR group, residual IMR resolved in 10 of the 13 patients (76.9%). The degree of IMR remained unchanged in the other 3 patients who had mild to moderate IMR early postoperatively. In the NMR group, recurrent IMR graded greater than mild degree occurred in 2 patients (2 of 35, 5.7%). None of the variables, including preoperative risk factors and operative data, were significantly associated with residual IMR at 1 year postoperatively. Early and One-Year Angiographic Patency Early and 1-year postoperative angiographic patency rates were 97.8% (177 of 181) and 97.3% (143 of 147), respectively (Table 4). There were no differences in early and 1-year patency rates between the RMR and NMR groups. All 5 patients who had IMR graded greater than mild degree at 1 year underwent 1-year angiography, and only 1 graft anastomosed to the obtuse marginal artery was occluded in 1 patient. Myocardial SPECT Test Myocardial SPECT tests were performed preoperatively and at 3 months and 1 year postoperatively in 35 (24 in NMR and 11 in RMR groups), 31 (22 in NMR and 9 in RMR groups), and 24 (17 in NMR and 7 in RMR groups) patients, respectively. Preoperative myocardial SPECT test was not performed in patients who experienced recent myocardial infarction ( 2 weeks before surgery) and those who underwent emergent surgery. Preoperative SPECT tests revealed that the number of viable segments were similar between the 2 groups (RMR vs NMR groups; vs segments, p 0.926). However, patients in the RMR group had a larger number of reversible ischemic segments than those in the NMR group (RMR vs NMR groups; vs segments, p 0.009). When analyzing risk factors for residual IMR, a larger number of reversible ischemic myocardial segments was the only significant predictor of residual IMR in the early postoperative period (Table 5). In both groups, the number of reversible ischemic segments decreased significantly at 3 months and 1 year postoperatively (p 0.001), although RMR group patients still had a larger number of reversible ischemic myocardial segments at 1 year postoperatively (RMR vs NMR groups; vs segments, p 0.004). Myocardial SPECT test also revealed that left ventricular ejection fraction and left ventricular end-diastolic and

6 1162 HWANG ET AL Ann Thorac Surg OPCAB IN ACS PATIENTS WITH FUNCTIONAL ISCHEMIC MR 2012;94: Fig 3. Freedom from major adverse cardiac events (MACE) at 5 and 10 years were 75.1% and 68.3%, respectively. Log-rank test demonstrated no difference in MACE-free survival between the RMR (greater than mild degree ischemic mitral regurgitation [IMR]) and NMR (less than or equal to mild degree residual ischemic mitral regurgitation [IMR]) groups (p 0.570). end-systolic volume indices improved significantly postoperatively (p 0.001, in each) with similar trends between the 2 groups (Fig 5). These variables were further improved at 1 year postoperatively. Comment The present study demonstrated 3 main findings. First, most functional IMR associated with ACS, including severe IMR, improved early after isolated OPCAB. Second, residual IMR early postoperatively after OPCAB further improved in 77% of patients 1 year postoperatively and did not affect long-term clinical outcomes. Third, myocardial SPECT test revealed that a larger number of reversible ischemic myocardial segments was observed in patients with residual IMR than in patients without residual IMR, although the number of ischemic reversible segments decreased significantly 1 year after OPCAB. Functional IMR has various pathophysiologic processes, ranging from acute myocardial ischemia to chronic left ventricular remodeling [1, 16]. Most previous studies suggested that IMR greater than moderate degree should be treated at the time of CABG [4 6]. However, we have found no previous studies that have examined patients with acute coronary syndrome after exclusion of patients with chronic IMR, even though Fig 4. Changes in residual mitral regurgitation after isolated off-pump coronary artery bypass grafting after 1 year.

7 Ann Thorac Surg HWANG ET AL 2012;94: OPCAB IN ACS PATIENTS WITH FUNCTIONAL ISCHEMIC MR 1163 Table 4. Early and 1-Year Angiographic Patency Rates Early Total (n 54) RMR Group (n 14) NMR Group (n 40) p Value Left ITA 56/56 (100%) 13/13 (100%) 43/43 (100%) Other arterial grafts 89/91 (97.8%) 20/21 (95.2%) 69/70 (98.6%) Saphenous vein 32/34 (94.1%) 12/13 (92.3%) 20/21 (95.2%) Total 177/181 (97.8%) 45/47 (95.7%) 132/134 (98.5%) year Total (n 43) IMR mild at 1-year (n 5) IMR mild at 1year (n 38) Left ITA 45/46 (97.8%) 5/5 (100%) 40/41 (97.6%) Other arterial grafts 76/78 (97.4%) 6/6 (100%) 70/72 (97.2%) Saphenous vein 22/23 (95.7%) 4/5 (80.0%) 18/18 (100%) Total 143/147 (97.3%) 15/16 (93.8%) 128/131 (97.7%) IMR ischemic mitral regurgitation; ITA internal thoracic artery; NMR group less than or equal to mild degree residual IMR; RMR group greater than mild degree IMR. differences in the pathophysiology of IMR are anticipated in patients with acute myocardial ischemia and those with chronic hypoperfusion. The present study demonstrated that most functional IMR associated with ACS improved early after isolated OPCAB, suggesting that acute pathology could be reversed effectively after myocardial revascularization compared with chronic stable ischemia with ventricular remodeling. Early improvement of IMR was partly associated with right coronary territory revascularization rather than overall completeness of revascularization. This was in agreement with previous studies which demonstrated that posteromedial papillary muscle ischemia and dysfunction, and incomplete revascularization, particularly in the posterior descending coronary artery territory, were related to significant IMR after CABG [2, 17]. Results of OPCAB have demonstrated several advantages by avoiding the potentially detrimental effects of cardiopulmonary bypass and eliminating intraoperative global myocardial ischemia [18]. In addition, it is possible to assess the changes in IMR grade by performing transesophageal echocardiography after completion of each distal anastomosis during OPCAB. In the present study, mitral valve surgery was considered only if the degree of IMR was worsened or remained severe after completion of all anastomoses compared with the baseline grading measured after anesthetic induction. This real-time evaluation of changes in degree of IMR is another advantage of OPCAB. Previous studies demonstrated that residual IMR negatively impacted long-term clinical outcomes [4, 5]. One study showed that progression to significant IMR was common after isolated CABG, and might be related to incomplete revascularization [17]. In contrast, another study demonstrated that IMR improved after isolated CABG in the majority of patients with viable myocardium [6]. The present study demonstrated that residual IMR early after OPCAB improved further in a majority of patients 1 year postoperatively and did not affect long-term clinical outcomes. Myocardial SPECT test revealed that approximately 75% of the myocardial segments were viable in our study population without intergroup difference. However, more reversible ischemic myocardial segments were observed in patients with residual IMR than in those without residual IMR. This could be explained by a previous study which Table 5. Independent Predictors of Early Postoperative Residual Mitral Regurgitation in 35 Patients Who Underwent Myocardial Single-Photon Emission Computed Tomography Univariate Multivariable Variables p Value Odds Ratio [95% CI] p Value Hypertension [ ] History of stroke [ ] Dyslipidemia [ ] Right coronary territory revascularization [ ] LV end-diastolic dimension [ ] Number of reversible ischemic segments [ ] Coronary territory of ischemic area LV ejection fraction on SPECT [ ] LV end-systolic volume index on SPECT LV end-diastolic volume index on SPECT CI confidence interval; LV left ventricular; SPECT single-photon emission computed tomography.

8 1164 HWANG ET AL Ann Thorac Surg OPCAB IN ACS PATIENTS WITH FUNCTIONAL ISCHEMIC MR 2012;94: demonstrated that myocardial perfusion did not improve completely early postoperatively and further improved until 1 year after OPCAB [15]. In the present study, the early postoperative residual IMR resolved in most of the patients, accompanied by a decreased number of reversible ischemic segments at 1 year after OPCAB in both groups. Complete revascularization, if possible, of all diseased segments and resultant improvement in myocardial ischemia might play a role in further improvement of residual IMR. In the present study, however, we did not find any significant correlation between any independent variable such as completeness of revascularization and late improvement of residual IMR at 1 year postoperatively, probably because only a small number of patients had residual IMR at 1 year postoperatively. There are limitations to the present study that must be recognized. First, the present study was not performed in a prospective manner, although all consecutive ACS patients with functional IMR who underwent isolated OPCAB were included. Second, we did not compare these results in patients who underwent on-pump CABG because almost all CABG procedures at our institution were performed using the off-pump technique during the study period. Third, because the number of enrolled patients was relatively small and follow-up echocardiography was not performed in all study patients, the data may be insufficient to reach a definite conclusion. Fig 5. Changes in (A) left ventricular ejection fraction (LVEF) and (B) end-diastolic and (C) end-systolic volume indices (LVEDVI and LVESVI) before surgery (preop), and 3 months and 1 year postoperatively. (The central box represents the values from the lower to upper quartile and the middle line represents the median. A line extends from the minimum to the maximum value). References 1. Levine RA, Schwammenthal E. Ischemic mitral regurgitation on the threshold of a solution; from paradoxes to unifying concepts. Circulation 2005;112: Otsuji Y, Handschumacher MD, Liel-Cohen N, et al. Mechanism of ischemic mitral regurgitation with segmental left ventricular dysfunction: three-dimensional echocardiographic studies in models of acute and chronic progressive regurgitation. J Am Coll Cardiol 2001;37: Persson A, Hartford M, Herlitz J, Karlsson T, Omland T, Caidahl K. Long-term prognostic value of mitral regurgitation in acute coronary syndromes. Heart 2010;96: Schroder JN, Williams ML, Hata JA, et al. Impact of mitral valve regurgitation evaluated by intraoperative transesophageal echocardiography on long-term outcomes after coronary artery bypass grafting. Circulation 2005;112(suppl I):I Mihaljevic T, Lam BK, Rajeswaran J, et al. Impact of mitral valve annuloplasty combined with revascularization in patients with functional ischemic mitral regurgitation. J Am Coll Cardiol 2007;49: Penicka M, Linkova H, Lang O, et al. Predictors of improvement of unrepaired moderate ischemic mitral regurgitation in patients undergoing elective isolated coronary artery bypass graft surgery. Circulation 2009;120: Duarte IG, Shen Y, MacDonald MJ, Jones EL, Craver JM, Guyton RA. Treatment of moderate mitral regurgitation and coronary disease by coronary bypass alone: late results. Ann Thorac Surg 1999;68: Fattouch K, Guccione F, Sampognaro R, et al. POINT: efficacy of adding mitral valve restrictive annuloplasty to coronary artery bypass grafting in patients with moderate ischemic mitral valve regurgitation: a randomized trial. J Thorac Cardiovasc Surg 2009;138: Eagle KA, Guyton RA, Davidoff R, et al. ACC/AHA 2004 guideline update for coronary artery bypass graft surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Com-

9 Ann Thorac Surg HWANG ET AL 2012;94: OPCAB IN ACS PATIENTS WITH FUNCTIONAL ISCHEMIC MR 1165 mittee to Update the 1999 Guidelines for Coronary Artery Bypass Graft Surgery). Circulation 2004;110;e Lam BK, Gillinov AM, Blackstone EH, et al. Importance of moderate ischemic mitral regurgitation. Ann Thorac Surg 2005;79: Aklog L, Filsoufi F, Flores KQ, et al. Dose coronary artery bypass grafting alone correct moderate ischemic mitral regurgitation? Circulation 2001;104(suppl I):I Kim KB, Cho KR, Chang WI, Lim C, Ham BM, Kim YL. Bilateral skeletonized internal thoracic artery graftings in off-pump coronary artery bypass: early result of Y versus in situ grafts. Ann Thorac Surg 2002;74:S Enriquez-Sarano M, Miller FA Jr, Hayes SN, Bailey KR, Tajik AJ, Seward JB. Effective mitral regurgitant orifice area: clinical use and pitfalls of the proximal isovelocity surface area method. J Am Coll Cardiol 1995;25: Zoghbi WA, Enriquez-Sarano M, Foster E, et al. Recommendations for evaluation of the severity of native valvular regurgitation with two dimensional and Doppler echocardiography. J Am Soc Echocardiogr 2003;16: Cho KR, Hwang HY, Kang WJ, Lee DS, Kim K-B. Progressive improvement of myocardial perfusion after off-pump revascularization with bilateral internal thoracic arteries: comparison of early versus 1-year postoperative myocardial singlephoton emission computed tomography. J Thorac Cardiovasc Surg 2007;133: Chan KM, Amirak E, Zakkar M, Flather M, Pepper JR, Punjabi PP. Ischemic mitral regurgitation: in search of the best treatment for a common condition. Prog Cardiovasc Dis 2009;51: Campwala SZ, Bansal RC, Wang N, Razzouk A, Pai RG. Mitral regurgitation progression following isolated coronary artery bypass surgery: frequency, risk factors, and potential prevention strategies. Eur J Cardiothorac Surg 2006;29: Puskas JD, Thourani VH, Marshall JJ, et al. Clinical outcomes, angiographic patency, and resource utilization in 200 consecutive off-pump coronary bypass patients. Ann Thorac Surg 2001;71: DISCUSSION DR JENNIFER SUE LAWTON (St. Louis, MO): About 45% of your patients who had off-pump CABG had moderate or severe MR [mitral regurgitation] at the time of surgery. Could you maybe just tell us a little bit about your preoperative planning in someone with severe MR? How did you decide that it would be safe to do off-pump revascularization rather than having on-pump CABG [coronary artery bypass grafting] with mitral repair? DR HWANG: Our revascularization strategy is trying to perform off-pump revascularization for acute coronary syndrome patients associated with functional ischemic mitral regurgitation, including severe degree. We believe that ACS [acute coronary syndrome] patients have acute pathology for IMR [ischemic mitral regurgitation] and the acute pathology will be reversed effectively after myocardial revascularization compared with chronic stable ischemia with ventricular remodeling. We performed off-pump revascularization using a Y-composite graft based on the in situ left internal thoracic artery in most patients. By performing transesophageal echocardiography, we could observe the improvement of wall motion abnormality and IMR grade after completion of each distal anastomosis during offpump revascularization using a Y-composite graft. DR LAWTON: So you took a good look at the leaflets and made a decision based on whether the valve was structurally normal or not. You performed off-pump CABG if MR was functional even in severe MR cases, right? DR HWANG: After anesthetic induction, mitral leaflet and subvalvular structure, degree of IMR, and eccentricity of regurgitation jet were reevaluated using transesophageal echocardiogram. When the mitral regurgitation was diagnosed as functional IMR, we performed off-pump revascularization. Mitral valve surgery was considered only if the grade of IMR had worsened or remained severe after completion of all anastomoses. DR HAROLD G. ROBERTS (Lauderdale Lakes, FL): Frankly, I will need to digest this data that you presented more carefully before I can really draw conclusions, but one slide that actually jumped out at me led me to a different conclusion than what I believe you had, and that was that you showed that your patients that have significant residual MR had a distinctly poorer long-term survival, and I think this has been documented in many numerous studies, not the least of which is Sarano s data from Mayo. And I wonder, could you tell us what percentage of these patients with the residual MR were present in the whole study, and, number two, on the basis of these results have you altered your policy as far as leaving, say, moderate or worse mitral regurgitation? DR HWANG: May I have my slides again? (Slide) As I presented in this slide, 15 of the 56 patients had residual IMR graded greater than mild; no one had severe degree IMR in the early postoperative period. (Next slide) It looked like that the survival rates were different between the two groups. However, this was due to the small sample size of our patient population; this drop indicated only one event. There was no statistically significant difference and the probability value was (Next slide) Five of 48 patients had residual IMR of mild to moderate or moderate degree at one year postoperatively. DR SIMON MOTEN (Melbourne, Australia): Like Hal, I need a little bit more time to digest some of those numbers, but if I am correct, you said that revascularizing the right coronary artery territory had an odds ratio of.2 and was protective against recurrent mitral regurgitation, but then you went on to say that if you had increased reversible ischemic segments, you were more likely to get recurrent mitral regurgitation. Is there an association between these two points, in that your late ischemic segments are in the right coronary territory or have you differentiated out between right and left territory ischemic segments and maybe there is a correlation with recurrent MR there? DR HWANG: Posteromedial papillary muscle ischemia and dysfunction was suggested to be one of the mechanisms for inducing IMR, and the present study showed that early improvement of IMR was partly associated with right coronary artery territory revascularization. More ischemic reversible myocardial segments in preoperative myocardial SPECT [single-photon emission computed tomography] test were observed in patients with residual IMR than in those without residual IMR, although the number of ischemic reversible segments significantly decreased one year after offpump revascularization in both groups. We evaluated the impact of number of ischemic myocardial segments according to the ischemic coronary artery territories; however, we did not find any significant correlation between number of ischemic myocardial segments according to the ischemic coronary artery territories and residual IMR at one year postoperatively.