Clinical outcomes of surgery of mitral valve regurgitation and coronary artery bypass grafting

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1 doi: /icvts Interactive CardioVascular and Thoracic Surgery 5 (2006) Institutional report - Cardiac general Clinical outcomes of surgery of mitral valve regurgitation and coronary artery bypass grafting Srikrishna Sirivella*, Isaac Gielchinsky Newark Beth Israel Medical Center, Department of Cardiovascular and Thoracic Surgery, Newark University of Medicine & Dentistry of New Jersey, Newark, NJ 07112, USA Received 12 January 2006; received in revised form 13 April 2006; accepted 18 April 2006 Abstract The impact of etiology of associated mitral valve regurgitation and a valve procedure on operative and long-term outcomes after coronary bypass grafting surgery is yet to be clearly defined. Results of combined coronary artery bypass grafting and valve procedures for mitral valve regurgitation were retrospectively analyzed in 468 patients. The regurgitation was of ischemic in 45%, degenerative in 55% and 78% valve repairs, 22% valve replacements were performed. Severe coronary artery disease, acute myocardial infarction, low ejection fraction, ischemic mitral regurgitation, advanced heart failure symptoms, failure to use internal mammary artery, valve replacement surgery, and emergency operations are predictors of operative mortality. The 5-year survivals for propensity-matched patients of ischemic and degenerative disease were similar (66%), but 67% vs. 83%, respectively, for unmatched patients. Low ejection fraction (-35%), advanced age ()67 years), valve replacement surgery, residual mitral regurgitation, and severe coronary artery disease were predictors of poor longterm survival. Left ventricular remodeling processes, optimal valve procedure without residual mitral regurgitation and left ventricular function are important determinants of long-term outcome than the etiology of valve regurgitation Published by European Association for Cardio-Thoracic Surgery. All rights reserved. Keywords: Coronary artery bypass grafts (CABG); Ischemic mitral regurgitation; Mitral valve repair; Mitral valve replacement; Outcomes 1. Introduction The coexistence of mitral valve regurgitation (MR) in patients undergoing myocardial revascularization procedures is often associated with poor operative and long-term outcomes w1,2x. The influence of etiology of valve regurgitation and additional valve procedure on outcomes after coronary bypass surgery (CABG) is not yet clearly defined. We conducted this study in a group of patients with ischemic and degenerative disease, who underwent coronary artery bypass grafting surgery (CABG) and valve operations for MR to identify the predictors of operative mortality and long-term outcomes. We studied the effect of etiology of MR and type of a valve procedure on early and long-term survivals, functional outcomes and recurrence in valve regurgitation. 2. Patients and methods At Newark Beth Israel Medical Center, from July 1985 through June 2002, a total of 1687 mitral valve procedures were performed. This study consisted of 468 patients with MR who underwent a valve procedures and simultaneous *Corresponding author: 28 Cathedral Gardens Road, BRS Hospitals, Nungambakkam, Madras , India. Tel.: q ; fax: q address: s_sirivella475@yahoo.com (S. Sirivella). CABG. MR was due to degenerative disease in 55% (253) and ischemic in 45% (215) of patients. We have excluded patients having combined major cardiac operations, mitral valve procedures for infracted and ruptured papillary muscle subsequent to an acute myocardial infarction, calcific mitral valve disease (rheumatic origin) and regurgitation associated with extensive leaflet calcification andyor calcified annulus. The study was divided into two time periods (i.e. July 1985 through June 1992, and July 1992 through June 2002), and the outcomes were analyzed. After hospital discharge, the patients follow up had ranged from 3 months to 246 months. Median follow-up was 9.2 years and 20% of patients were followed up for 16 years or more Patient demographics and characteristics These were classified based on etiology of MR (i.e. ischemic or degenerative disease) and operative technique utilized in correction of regurgitation (i.e. valve repair versus prosthetic valve replacement) (Table 1). Equal percentage (22%) of both ischemic and degenerative diseases had valve replacements. The ischemic MR and valve replacement groups had increased incidence of diabetes, threevessel coronary disease, acute myocardial infarction, emergency operations, low probability of use of internal mammary graft, and longer cardiopulmonary bypass time as compared to degenerative and valve repair groups.

2 S. Sirivella, I. Gielchinsky / Interactive CardioVascular and Thoracic Surgery 5 (2006) Table 1 Patient / characteristics Patient variable Degenerative Ischemic P-value Valve P-valueq (ns253) (ns215) Replacement Repair ns103 ns365 Age )67 years 75% 55% % 66% 0.8 Sex ratio MyF NYHA Class IIIyIV 65% 85% % 76% CCS Class III & IV 32% 65% % 44% 0.34 Hypertension 70% 76% % 72% 0.15 Diabetes mellitus 12% 24% % 17% 0.03 Renal dysfunction* 7% 13% % 13% Acute MI 2% 24% % 12% Ejection fraction -35% 10% 43% % 28% vessel CAD 36% 82% % 54% Emergency operatons 3% 16% % 4% Valve replacement 22% 22% 0.99 Cross-clamp time 74"32 min 76"29 min "27 min 78"32 min CPB time 114"46 min 122"43 min q47 min 115"43 min 0.01 Number of grafts 2.26" " "1 2.3"1 0.9 LIMA 78% 52% % 76% Ischemic mitral 46% 46% 0.54 CCS s Canadian Cardiovascular Society; CPB s cardiopulmonary bypass; EF s ejection fraction; LIMA s left internal mammary artery; NYHA s New York Heart Association; MI s myocardial infarction; *serum creatinine )2.5 mgydl or a need for a dialysis. P-value s ischemic versus degenerative disease, P-valueq svalve replacement versus valve repair Operative technique The etiology of MR was determined by the patient s clinical history, echocardiographic findings and surgeon s observation at operating table. The diagnosis of MR was established after agreement of findings by two expert echocardiographers. Histological examination of resected leaflet tissue confirmed the diagnosis Ischemic mitral valve disease All patients had one or more prior myocardial infarctions (mostly inferior) with associated regional wall motion abnormalities w3x. The regurgitant jet is central with normal valve leaflets, chordae and papillary muscles. The leaflets failed to coapt or showed restricted mobility of valve leaflets (Carpentier type IIIb). Seventy-eight percent valve repairs and 22% valve replacements were done. Repair techniques were annuloplasty alone in 88% (posterior ring 72%, commissural 22%, and full ring 6%) and combination of annuloplasty with leaflet and chordal procedures in 12% due to mixed disease. In none of the patients undersized mitral rings were used. Repair was complex if leaflet procedures were combined with annuloplasty. Valve replacement was done for annular enlargement either without or with papillary muscle dysfunction (40%) Degenerative mitral valve disease The regurgitant jet was non-central or peripheral and the leaflets were floppy and thickened, with elongated or ruptured chordae-tendinae. In some patients with annular dilatation but without discernable leaflet prolapse, thick billowing of valve leaflets was noted. Valve repairs were done in 78% (197) of cases. Repairs were leaflet plication or quadrangular resection of posterior leaflet supple- Table 2 Post-operative complications Outcomes Degenerative Ischemic P-value Valve P-valueq (ns253) (ns215) Repair Replacement (ns365) (ns103) Inotropes )2 days 14% 43% % 39% IABP 2% 26% % 22% 0.05 Ventilator )24 h 13% 28% % 26% Atrial arrhythmias 47% 34% % 24% Ventricular tachycardia 7% 5% % 13% 0.01 Pneumonia 5% 14% % 14% Reoperationybleeding 4% 5% % 6% Sternal infection 1% 2% % 2% Renal failure 1% 2% % 4% Stroke 0% 3% % 2% Length of stayydays 9* (6 15) 10* (6 19) * (6 16) 11* (6 20) 0.5 ICU stayydays 2* (1 4) 4*(2 6) * (2 7) 3* (2 7) 0.4 Operative mortality 3.6% 14% % 14.5% IABP s intraaortic balloon pump; ICU s intensive care unit. P-value s ischemic versus degenerative disease, P-valueq svalve replacement versus valve repair. *() Median with range.

3 394 S. Sirivella, I. Gielchinsky / Interactive CardioVascular and Thoracic Surgery 5 (2006) Table 3 Risk predictors of operative mortality (univariate analysis) Variable Mortality (%) OR P-value Age )67 years Age -67 years 6.6 Femaley Male 6.8 Unstable angina No unstable angina 6 Diabetes mellitus No diabetes 8.5 Renal failure No renal failure 6 Acute MI No acute MI 6 Three-vessel CAD Two or 1-vessel CAD 2 EF -35% EF )35% 6 RV dysfunction Mildyno RV dysfunction 2 NYHA IIIyIV NYHA IyII 0.8 LIMA No LIMA 15 Emergencyyvs Elective 7 Crossclamp time ()90 min) (-90 min) 7 Ischemic disease Degenerative 3.6 Valve replacementy Valve repair 6.5 Simple repairy Complex repair 11 Operations patient survival was estimated by the Kaplan Meier technique, with log-rank tests to compare stratified groups. The important influencing variables or risks were analyzed by univariate and multivariate Cox proportional hazard models and expressed as risk ratios with 95% confidence intervals. Propensity scoring was done to match patients with degenerative and ischemic regurgitation to assess the long-term survival. Seventy variables were used in a logistic regression model (saturated) for analysis by the propensity score, which matched 117 patients of each group Operative mortality and morbidity Death occurred in 39 patients (within 30 days of operation or during the same hospitalization) with a mortality rate of 8.3%. Mortality during the years 1985 to 1992 was 12% compared to 5% during the years 1992 to The earlier period was characterized by more emergency operations (13 vs. 5.5%), less valve repairs (71 vs. 84%), and less frequent use of IMA graft (49 vs. 80%). The operation rate early after myocardial infarction was similar in both periods (12 vs. 12.5%). CAD s coronary artery disease; EF s ejection fraction; LIMA s left internal mammary artery; MI s myocardial infarction; NYHA s New York Heart Association. ORsodds ratio. mented by an annuloplasty (60%), leaflet transposition (11%), commissural leaflet resection 6%, bileaflets repairs (31%), chordal procedures (13%) and annuloplasty alone (9%). The repair was simple (in 136 patients), if it involves annuloplasty with or without leaflet resection or plication, and complex for chordal, anterior leaflet, and bileaflet repairs (61 patients). Valve replacements were done in 22% (56) of cases, mostly for bileaflet prolapse (67%), and chordal rupture (55%). Overall valve repair was performed in 78% (365) and prosthetic mitral valve replacement in 22% (103) of cases. Attempts were made to preserve the posterior (58%), anterior (6%) and both leaflets (2%) during valve replacements w4x. Associated preoperative tricuspid regurgitation of 2q or more was repaired Statistical analysis All statistical analysis was performed using SAS software (SAS Institute, Cary, North Carolina). Univariate analyses included two-tailed Wilcoxon rank sum or t-tests for continuous variables and x or Fisher s exact tests for discrete 2 variables. A P-value )0.05 was considered not statistically significant. NYHA functional class IIIyIV symptoms and Fig. 1. A. Overall survival (Kaplan Meier) of patients undergoing mitral valve repair or replacement plus coronary bypass graft (CABG). B. Overall CHF free survival of patients undergoing mitral valve repair or replacement and CABG.

4 S. Sirivella, I. Gielchinsky / Interactive CardioVascular and Thoracic Surgery 5 (2006) The operative mortality for ischemic disease was 14% as compared to 3.6% for degenerative disease. The mortality for prosthetic valve replacement was higher as compared to valve repair (14.5 vs. 6.5%, PF0.05). The major operative morbidity rates were higher in the ischemic group and valve replacement was associated with more complications than valve repair (Table 2). The risk predictors of operative mortality by univariate analysis are shown in Table Long-term results The overall survival at 5 and 10 years was 73% (95% confidence interval (CI): 65% to 76%) and 52% (95% CI: 42% to 56%), respectively (Fig. 1A), but CHF-free survival rates were 63% (95% CI: 54% to 66%) at 5 years, 39% (95% CI: 26% to 42%) at 10 years (Fig. 1B). The 5- and 10-year survivals for early ( ) vs. recent study ( ) were 67% and 44% vs. 72% and 48% (Ps0.06) respectively. The patients )67 years had poor survivals as compared to age -67 years (62% vs. 78% at 5 years, 54% vs. 37% at 10 years, PF0.0001). Operations in the presence of acute MI had no influence on long-term survival (60%, 42% vs. 69%, 45% (no MI) at 5 and 10 years, respectively, Ps0.09). Poor survivals were associated with preoperative NYHA class III & IV symptoms, diminished left ventricular function (EF -0.35), three-vessel coronary artery disease, right ventricular dysfunction, and a valve replacement surgery (Fig. 2). Survivals were poor for ischemic MR as compared to degenerative MR (i.e. 67% {95% CI 62% to 74%} vs. 83% {95% CI 71% to 86%} at 5 years, 47% {95% CI 43% to 55%} vs. 62% {95% CI 54% to 72%} at 10 years (Fig. 3A), but were similar for propensity-matched patients (117 each) of both groups (65% vs. 66% at 5 years and 46% vs. 48% at 10 years, Ps0.23 (Fig. 3B). The risk predictors for survival on univariate and multivariate analyses are shown in Table 4. The important independent predictors of poor long-term survival were residual mitral valve regurgitation (grade II or more) at hospital discharge, three-vessel coronary artery disease, reduced ventricular function, valve replacement surgery, but not the etiology of valve regurgitation Recurrent CHF The cumulative risk of developing CHF was 22% (95% CI: 18% to 32%) at 5 years, 46% (95% CI: 38% to 58%) at 10 years. Residual MR? grade II was associated with Fig. 2. Overall survival (Kaplan Meier) of patients shown in percentages on Y-axis, patients at risk were shown on X-axis at indicated time periods. A. Survival stratified by preoperative NYHA functional class (I & II and III & IV). B. Survival stratified by preoperative left ventricular ejection fraction (EF). C. Survival stratified by extent of coronary artery disease. D. Survival stratified by valve repair versus valve replacement. E. Survival stratified by preoperative right ventricular function. Fig. 3. A. Unmatched overall survival of patients with degenerative and Ischemic mitral regurgitation (MR) and CABG. B. Overall survival of propensity matched patients (117 each) with degenerative and ischemic disease.

5 396 S. Sirivella, I. Gielchinsky / Interactive CardioVascular and Thoracic Surgery 5 (2006) Table 4 Predictors for long-term survival (univariate and multivariate analyses) Risk variable Univariate Multivariate Multivariate P-value Risk ratio (CI) P-value Age )67 yearsy ( ) Age -67 years EF -35%y ( ) EF )35% Acute MI 0.09 No acute MI Three-vessel CAD ( ) Oney2-vessel CAD MR? grade II ( ) No MR NYHA IIIyIV ( ) NYHA IyII RV dysfunction ( ) 0.09 No RV dysfunction Ischemic ( ) 0.21 Degenerative LIMA ( ) 0.46 No LIMA left ventricular remodeling, which occurs after myocardial infarction, may continue several months and may impact long-term outcomes in both types of regurgitation w6,8x. Residual MR after a valve procedure influences the recurrent CHF, functional outcomes and long-term survival in both degenerative and ischemic MR. The volume burden imposed by residual MR (grade II or more) impairs ventricular remodeling processes and progresses to recurrent congestive heart failure w9,10x. MR detected in the postoperative period is managed by optimizing the preload and after-load with beta blockers, angiotensin converting enzyme inhibitors and inotropes, if a faulty valve repair technique was ruled out w6,11x. Insertion of a prosthetic valve is mandatory if doubt exists about the adequacy of mitral valve repair. Poor long-term results observed in this study for residual MR dictates a rationale for a valve repair if the regurgitation jet is of moderate in patients undergoing concomitant CABG. Several important studies have demonstrated that MR which persists long-term in patients with significant coronary artery disease results in poor survival w11,12x. Despite controversy on the choice of an optimal corrective technique for ischemic MR, mitral valve repair in good-risk Replacementy ( ) Repair Operations CAD s coronary artery disease; CI s confidence interval; EF s ejection fraction; LIMA s left internal mammary artery; MR s mitral regurgitation; NYHA s New York Heart Association. increased incidence of CHF (Fig. 4A) and decreased survivals (Fig. 4B). The independent risk predictors for CHF on long follow-up were residual MR? grade II at hospital discharge, ejection fraction -35% (Ps0.002), preoperative NYHA class IIIyIV symptoms (Ps0.014), and significant right ventricular dysfunction (Ps0.02) Freedom from re-operation Freedom from operation at 5 and 10 years was 95% (95% CI: 87% to 98%), and 87% (95% CI: 72% to 94%) after valve repair and 89% (95% CI: 75 99%) and 78% (95% CI: 57% to 100%) after a valve replacement. The overall failure rates for simple vs. complex valve repairs were similar (5 vs. 6%), but complex valve repair in ischemic MR had resulted in a failure in 60% (12 of 20 patients), and 25% (5 patients) required valve placement. 3. Discussion The determinants of operative risk and poor long-term survival noted in this study for surgery of MR and associated CABG is consistent with several others w3,5,6x. Ischemic etiology of mitral valve regurgitation, however, was not found to be an independent predictor of long-term survival. The equally poor long-term outcomes associated for matched patients of both degenerative and ischemic disease may imply that in the presence of ongoing ischemia Fig. 4. A. The incidence of postoperative CHF. Patients were stratified by the presence or absence of residual MR? Grade II at hospital discharge. B. Overall survival of patients stratified by the presence or absence of residual MR? Grade II at discharge. CHFscongestive heart failure; NYHAsNew York Heart Association.

6 S. Sirivella, I. Gielchinsky / Interactive CardioVascular and Thoracic Surgery 5 (2006) patients was associated with lower operative mortality and better survival than with prosthetic valve replacement, though this advantage in survival was not seen in poor-risk patients w1,13x. The extent of left and right ventricular dysfunction, severity of the coronary artery disease and optimal corrective technique in ischemic MR are paramount. Due to increased failure of complex valve repairs in ischemic MR, a prosthetic valve replacement may be warranted at an initial operation, but under-sizing of mitral annuloplasty ring may improve results of valve repair. References w1x Gillinov AM, Wierup PN, Blackstone EH, Bishay ES, Cosgrove DM, White J, Lytle BW, McCarthy PM. Is repair preferable to replacement for ischemic mitral regurgitation? J Thorac CardioVasc Surg 2001;122: w2x Wong DR, Agnihotri AK, Hung JW, Vlahakes GJ, Akins CW, Hilgenberg AD, Madsen JC, MacGillivray TE, Picard MH, Torchiana DF. Long-term survival after surgical revascularization for moderate ischemic mitral regurgitation. Ann Thorac Surg 2005;80: w3x Akins CW, Hilgenberg AD, Buckley MJ, Vlahakes GJ, Torchiana DF, Daggett WM, Austen WG. Mitral valve replacement versus reconstruction for degenerative or ischemic mitral regurgitation. Ann Thorac Surg 1994;58: w4x DeAnda Jr A, Komeda M, Nikolic SD, Daughters GT, Ingels NB, Miller DC. Left ventricular function, twist, and tecoil after mitral valve replacement. Circulation 1995;92: w5x Harris KM, Sundt TM, Aeppli D, Sharma R, Barzilai B. Can late survival of patients with moderate ischemic mitral regurgitation be impacted by intervention on the valve? Ann Thorac Surg 2002;74: w6x 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: w7x St John-Sutton MG, Sharpe N. Left ventricular remodeling after myocardial infarction; pathophysiology and therapy. Circulation 2000;101: w8x Levine RA, Schumenthal E. Ischemic regurgitation on the threshold of a solution: from paradoxes to unifying concepts. Circulation Aug 2005; 112: w9x Ling LH, Enriquez-Sarano M, Seward JB, Orszulak TA, Schaff HV, Bailey KR, Tajik AJ, Frye RL. Early surgery in patients with mitral regurgitation due to flail leaflets: a long-term outcome study. Circulation 1997;96: w10x Kuwaki K, Kiyofumi M, Tsukamoto M, Abe T. Early and late results of mitral valve repair for mitral valve regurgitation. J Cardiovasc Surg 2000;41: w11x Aklog L, Filsoufi F, Flores KQ, Chen RH, Cohn LH, Nathan NS, Byrne JG, Adams DH. Does coronary artery bypass grafting alone correct moderate ischemic mitral regurgitation? Circulation 2001;104: w12x Lamas GA, Mitchell GF, Flaker GC, Smith Jr SC, Gersh BJ, Basta L, Moyé L, Braunwald E, Pfeffer MA. Clinical significance of mitral regurgitation after myocardial infarction. Circulation 1997;96: w13x Grossi EA, Goldberg JD, LaPietra A, Ye X, Zakow P, Sussman M, Delianides J, Culliford AT, Esposito RA, Ribakove GH, Galloway AC, Colvin SB. Ischemic mitral valve reconstruction and replacement: comparison of long-term survival and complications. J Thorac CardioVasc Surg 2001;122: