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Mitral valve surgery and coronary artery bypass grafting for moderate-to-severe ischemic mitral regurgitation: Meta-analysis of clinical and echocardiographic outcomes

Open ArchivePublished:March 21, 2017DOI:https://doi.org/10.1016/j.jtcvs.2017.03.039

      Abstract

      Objective

      This meta-analysis was conducted to compare clinical and echocardiographic outcomes following isolated coronary artery bypass grafting (CABG) versus CABG and mitral valve (MV) surgery in patients with moderate-to-severe ischemic mitral regurgitation (IMR).

      Methods

      Seven databases were systematically searched to identify relevant studies. For eligibility, studies were required to report on the primary endpoint of perioperative or late mortality. Data were analyzed according to predefined clinical endpoints.

      Results

      Four randomized controlled trials (RCTs) (n = 505) and 15 observational studies (OS) (n = 3785) met the criteria for inclusion. Compared with isolated CABG, concomitant CABG and MV surgery was not associated with increased perioperative mortality (RCTs: relative risk [RR] 0.89, 95% confidence interval [CI], 0.26-3.02; OS: RR 1.40, 95% CI, 0.88-2.23). CABG and MV surgery was associated with significantly lower incidence of moderate-to-severe MR at follow-up (RCTs: RR 0.16, 95% CI, 0.04-0.75; OS: RR 0.20, 95% CI, 0.09-0.48). Late mortality was similar between the surgical approaches in RCTs (hazard ratio [HR] 1.20, 95% CI, 0.57-2.53) and OS (HR 0.99, 95% CI, 0.81-1.21). There were no significant differences in echocardiographic outcomes. These results remained consistent in subgroup analyses restricted to patients with strictly moderate IMR.

      Conclusions

      In patients with moderate-to-severe IMR, the addition of MV surgery to CABG was not associated with increased perioperative mortality. Although concomitant MV surgery reduced recurrence of moderate-to-severe MR at follow-up, this was not associated with a reduction in late mortality. Larger trials with longer follow-up duration are required to further assess long-term survival and freedom from reintervention.

      Key Words

      Abbreviations and Acronyms:

      CABG (coronary artery bypass grafting), CI (confidence interval), CPB (cardiopulmonary bypass), HR (hazard ratio), IMR (ischemic mitral regurgitation), LVEF (left ventricular ejection fraction), LVESVI (left ventricular end-systolic volume index), MD (mean difference), MV (mitral valve), NYHA (New York Heart Association), RCT (randomized controlled trial), RR (relative risk)
      Figure thumbnail fx1
      Forest plot for late mortality following CABG versus CABG and mitral valve surgery.
      In patients with moderate-to-severe ischemic mitral regurgitation, there was no difference in perioperative or late mortality following isolated CABG versus CABG and mitral valve surgery.
      In patients with moderate-to-severe ischemic mitral regurgitation, the addition of mitral valve (MV) surgery to coronary artery bypass grafting was not associated with increased perioperative mortality. Concomitant MV surgery reduced recurrence of moderate-to-severe mitral regurgitation at follow-up, but this was not associated with a reduction in late mortality.
      See Editorial Commentary page 137.
      Ischemic mitral regurgitation (IMR) is common after myocardial infarction, occurring in up to 50% of patients.
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      In IMR, valvular insufficiency is predominantly due to the adverse left ventricular remodeling and annular dilatation that occurs following myocardial injury, resulting in tethered mitral leaflets with poor coaptation.
      Isolated coronary artery bypass grafting (CABG) is well-established as the standard treatment for trivial-to-mild IMR.
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      • et al.
      2015 American Association for Thoracic Surgery (AATS) Consensus Guidelines: Ischemic mitral valve regurgitation.
      However, the optimal management of moderate-to-severe IMR remains controversial.
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      Revascularization alone may sufficiently restore left ventricular function and dimensions, thereby addressing regurgitation without the potentially increased perioperative risk associated with concomitant mitral valve (MV) surgery.
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      • Wann S.
      Low-dose do- butamine stress echocardiography to predict reversibility of mitral regurgitation with CABG.
      However, it remains unclear whether isolated CABG can achieve similar midterm survival outcomes in patients with moderate-to-severe IMR.
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      • Chen R.H.
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      • et al.
      Does coronary artery bypass grafting alone correct moderate ischemic mitral regurgitation?.
      The aim of the present meta-analysis was to compare clinical and echocardiographic outcomes following isolated CABG and CABG and MV surgery in patients with at least moderate IMR.

      Methods

      Search Strategy and Study Selection

      Electronic searches were performed using Ovid Medline, Embase, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register, Database of Abstracts of Reviews of Effects, and ACP Journal Club from their dates of inception to February 2016. The search terms “mitral” AND (“ischemic” OR “ischaemic”) AND (“repair” OR “annuloplasty” OR “replacement”) AND (“mortality” OR “death” OR “survival”) were entered as keywords and MeSH terms. This was supplemented by hand searching the reference lists of key reviews and all potentially relevant studies.
      Two reviewers (A.S. and D.D.) independently screened the title and abstract of records identified in the search. Full-text publications were subsequently reviewed separately if either reviewer considered the manuscript as being potentially eligible. Disagreements regarding final study inclusion were resolved by discussion and consensus.

      Eligibility Criteria

      Eligible studies were those reporting perioperative mortality or late survival following isolated CABG and CABG and MV surgery in patients with at least moderate IMR. Studies were excluded if they included patients with trivial-to-mild IMR without subgroup analysis by IMR severity. Studies with fewer than 10 patients in either the isolated CABG or CABG and MV surgery arm were also excluded.
      All publications were limited to those involving human subjects and written in English. Abstracts, conference presentations, editorials, and expert opinions were excluded. Review articles were omitted because of potential publication bias and duplication of results. When institutions published duplicate studies with accumulating numbers of patients or increased lengths of follow-up, only the most complete reports were included for quantitative assessment.

      Data Extraction

      All data were independently extracted from text, tables, and figures by 2 investigators (A.S. and D.D.). The final results were reviewed by the senior reviewer (C.C.). The predetermined primary endpoints were perioperative mortality and late survival. Perioperative mortality was defined as death within 30 days after surgery or during the same hospitalization. Secondary outcomes included perioperative morbidity, recurrence of moderate-to-severe MR (grade ≥2) at latest follow-up, aortic cross-clamp and cardiopulmonary bypass (CPB) durations, New York Heart Association (NYHA) functional status, and echocardiographic measurements.

      Statistical Analysis

      Baseline characteristics and operative details were presented as raw values (%), mean ± standard deviation or median (interquartile range [IQR]) unless otherwise indicated. The relative risk (RR), mean difference (MD), or hazard ratio (HR) were used as the summary statistics, and reported with 95% confidence intervals (CIs). When available, adjusted ratios were used from individual studies. Otherwise, unadjusted ratios were computed from the exposure distribution given in the articles. For survival analysis, HRs and associated variance were obtained or calculated from each study by using techniques described by Parmar et al
      • Parmar M.K.B.
      • Torri V.
      • Stewart L.
      Extracting summary statistics to perform meta- analyses of the published literature for survival endpoints.
      and Tierney et al.
      • Tierney J.F.
      • Stewart L.A.
      • Ghersi D.
      • Burdett S.
      • Sydes M.R.
      Practical methods for incorporating summary time-to-event data into meta-analysis.
      When direct calculations were not possible due to a lack of presented data, HRs were estimated using Kaplan-Meier graphs. For analysis of continuous data, data presented as median and IQR were converted to mean and standard deviation using the method of Wan et al.
      • Wan X.
      • Wang W.
      • Liu J.
      • Tong T.
      Estimating the sample mean and standard devi- ation from the sample size, median, range and/or interquartile range.
      Meta-analyses were performed by using random-effects models to take into account the anticipated clinical and methodological diversity between studies. The I2 statistic was used to estimate the percentage of total variation across studies due to heterogeneity rather than chance, with values exceeding 50% indicative of considerable heterogeneity. Mixed-effects meta-regression models were formed by using follow-up duration as a continuous moderator to assess its impact on the incidence of survival and residual MR.
      Subgroup analysis was performed by study design to take into account the different levels of evidence provided by observational studies and randomized trials. Sensitivity analysis was performed by IMR severity to specifically assess the impact of concomitant MV surgery in patients with moderate IMR. Publication bias was assessed by using funnel plots comparing log odds ratios with their standard error. The Egger linear regression method and Begg rank correlation test were used to detect funnel plot asymmetry.
      • Begg C.B.
      • Mazumdar M.
      Operating characteristics of a rank correlation test for publication bias.
      • Egger M.
      • Smith G.D.
      • Schneider M.
      • Minder C.
      Bias in meta-analysis detected by a simple, graphical test.
      The Trim-and-Fill method was used to explore the impact of studies potentially missing due to publication bias.
      • Duval S.
      • Tweedie R.
      Trim and fill: a simple funnel-plot–based method of testing and adjusting for publication bias in meta-analysis.
      Statistical analysis was conducted with Review Manager Version 5.1.2 (Cochrane Collaboration, Software Update, Oxford, United Kingdom) and publication bias assessed by using Comprehensive Meta-Analysis v2.2 (Biostat Inc, Englewood, NJ). All P values were 2 sided, and values < .05 were considered statistically significant.

      Results

      A total of 1125 unique records were identified through the database and bibliographic searches. Of these, 1091 were excluded on the basis of title and abstract content. After screening the full text of the remaining 34 articles, 20 studies met the criteria for inclusion.
      • Bouchard D.
      • Jensen H.
      • Carrier M.
      • Dermers P.
      • Pellerin M.
      • Perrault L.P.
      • et al.
      Effect of systematic downsizing rigid ring annuloplasty in patients with moderate ischemic mitral regurgitation.
      • Smith P.K.
      • Puskas J.D.
      • Ascheim D.D.
      • Voisine P.
      • Gelijns A.C.
      • Moskowitz A.J.
      • et al.
      Surgical treatment of moderate ischemic mitral regurgitation.
      • Chan K.M.J.
      • Punjabi P.P.
      • Flather M.
      • Wage R.
      • Symmonds K.
      • Roussin I.
      • et al.
      Coronary artery bypass surgery with or without mitral valve annuloplasty in moderate functional ischemic mitral regurgitation final results of the Randomized Ischemic Mitral Evaluation (RIME) trial.
      • Fattouch K.
      • Guccione F.
      • Sampognaro R.
      • Panzarella G.
      • Corrado E.
      • Navarra E.
      • 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.
      • Castleberry A.W.
      • Williams J.B.
      • Daneshmand M.A.
      • Honeycutt E.
      • Shaw L.K.
      • Samad Z.
      • et al.
      Surgical revascularization is associated with maximal survival in patients with ischemic mitral regurgitation: a 20-year experience.
      • Sá M.P.
      • Soares E.F.
      • Santos C.A.
      • Figueiredo O.J.
      • Lima R.O.
      • Escobar R.R.
      • et al.
      Mitral valve replacement combined with coronary artery bypass graft surgery in patients with moderate-to-severe ischemic mitral regurgitation.
      • Deja M.A.
      • Grayburn P.A.
      • Sun B.
      • Rao V.
      • She L.
      • Kreica M.
      • et al.
      Influence of mitral regurgitation repair on survival in the surgical treatment for ischemic heart failure trial.
      • Jeong D.S.
      • Lee H.Y.
      • Kim W.S.
      • Sung K.
      • Park P.W.
      • Lee Y.T.
      Off pump coronary artery bypass versus mitral annuloplasty in moderate ischemic mitral regurgitation.
      • Silberman S.
      • Eldar O.
      • Oren A.
      • Tauber R.
      • Fink D.
      • Klutstein M.W.
      • et al.
      Surgery for ischemic mitral regurgitation: should the valve be repaired.
      • de Waroux J.B.
      • Pouleur A.-C.
      • Vancraeynest D.
      • Pasquet A.
      • Gerber B.L.
      • El Khoury G.
      • et al.
      Early hazards of mitral ring annuloplasty in patients with moderate to severe ischemic mitral regurgitation undergoing coronary revascularization: the importance of preoperative myocardial viability.
      • Goland S.
      • Czer L.S.C.
      • Siegel R.J.
      • DeRobertis M.A.
      • Mirocha J.
      • et al.
      Outcomes in patients with moderate ischemic mitral regurgitation.
      • Mihaljevic T.
      • Lam B.-K.
      • Rajeswaran J.
      • Takagaki M.
      • Lauer M.S.
      • Gillinov A.M.
      • et al.
      Impact of mitral valve annuloplasty combined with revascularization in patients with functional ischemic mitral regurgitation.
      • Bonacchi M.
      • Prifti E.
      • Maiani M.
      • Frati G.
      • Nathan N.S.
      • Leacche M.
      Mitral valve surgery simultaneous to coronary revascularization in patients with end-stage ischemic cardiomyopathy.
      • Buja P.
      • Tarantini G.
      • Del Bianco F.
      • Razzolini R.
      • Bilato C.
      • Ramondo A.
      • et al.
      Moderate-to-severe ischemic mitral regurgitation and multivessel coronary artery disease: impact of different treatment on survival and rehospitalization.
      • Kang D.-H.
      • Kim M.-J.
      • Kang S.-J.
      • Song J.M.
      • Song H.
      • Hong M.K.
      • et al.
      Mitral valve repair versus revascularization alone in the treatment of ischemic mitral regurgitation.
      • Kim Y.-H.
      • Czer L.S.C.
      • Soukiasian H.J.
      • De Robertis M.
      • Magliato K.E.
      • Blanche C.
      • et al.
      Ischemic mitral regurgitation: revascularization alone versus revascularization and mitral valve repair.
      • Wong D.R.
      • Agnihotri A.K.
      • Hung J.W.
      • Vlahakes G.J.
      • Akins C.W.
      • Hilgenberg A.D.
      • et al.
      Long-term survival after surgical revascularization for moderate ischemic mitral regurgitation.
      • Diodato M.D.
      • Moon M.R.
      • Pasque M.K.
      • Barner H.B.
      • Moazami N.
      • Lawton J.S.
      • et al.
      Repair of ischemic mitral regurgitation does not increase mortality or improve long-term survival in patients undergoing coronary artery revascularization: a propensity analysis.
      • Trichon B.H.
      • Glower D.D.
      • Shaw L.K.
      • Cabell C.H.
      • Anstrom K.J.
      • Felker G.M.
      • et al.
      Survival after coronary revascularization, with and without mitral valve surgery, in patients with ischemic mitral regurgitation.
      • Harris K.M.
      • Sundt T.M.
      • Aeppli D.
      • Sharma R.
      • Barzilai B.
      Can late survival of patients with moderate ischemic mitral regurgitation be impacted by intervention on the valve?.
      The study selection process is summarized in Figure 1.
      Figure thumbnail gr1
      Figure 1PRISMA flow chart for literature search and study selection.
      Of the included studies, 4 were randomized controlled trials (RCTs) and the remainder were observational studies. These included data on a total of 4290 patients, including 3038 who underwent isolated CABG and 1252 patients who underwent combined CABG and MV surgery. For patients who underwent MV surgery, all patients included in the RCTs, and most patients included in the observational studies, underwent mitral valve repair. The mean or median follow-up duration ranged from 12 to 87 months. A full summary of study characteristics is presented in Table 1. Baseline demographic and clinical characteristics of study participants are summarized in Table 2.
      Table 1Summary of studies comparing isolated coronary artery bypass graft surgery versus concomitant mitral repair for ischemic mitral regurgitation
      StudyStudy designNo. of patientsType of mitral surgeryFollow-up, moMean MR gradePreoperative MR grade inclusion criteria
      CABGCABG + MVSCABGCABG + MVS
      Bouchard 2014RCT1615MVr (100%)12M2 (all patients)2+ (Moderate Only)
      Smith 2014RCT151150MVr (100%)12M2 (all patients)2+ (Moderate Only)
      Chan 2012RCT3833MVr (100%)12M2 (all patients)2+ (Moderate Only)
      Fattouch 2009RCT5448MVr (100%)32 ± 182 (all patients)2+ (Moderate Only)
      Castleberry 2014OS1651243MVR or MVr (% NR)64.4M2.25
      P < .05.
      3.46
      P < .05.
      ≥ 2+ (Moderate to Severe)
      Sa 2013OS2616MVR (100%)NRNRNRNS (Moderate to Severe)
      Deja 2012OS4249MVr (98%); MVR (2%)56MNRNRNS (Moderate to Severe)
      Jeong 2012OS7763MVr (100%)44 ± 34.5NRNR3+ (Moderate Only)
      Silberman 2011OS10887MVr (100%)87 ± 503.1 ± 0.3
      P < .05.
      3.8 ± 0.4
      P < .05.
      ≥ 3+ (Moderate to Severe)
      de Waroux 2009OS4234MVr (100%)51 ± 442.2 ± 0.42.4 ± 0.5≥ 3+ (Moderate to Severe)
      Goland 2009OS5528MVr (100%)61.2 ± 43.23 (all patients)3+ (Moderate Only)
      Mihaljevic 2007OS5454MVr (100%)48M3.243.19≥ 3+ (Moderate to Severe)
      Bonacchi 2006OS3640MVr (100%)32.4 ± 112.5 ± 0.5
      P < .05.
      3.3 ± 0.6
      P < .05.
      ≥ 2+ (Moderate to Severe)
      Buja 2006OS5039MVR (56%); MVr (44%)34.9 [5.3-104]NRNR≥ 3+ (Moderate to Severe)
      Kang 2006OS5750MVr (100%)41 ± 27 (CABG)

      37 ± 22 (MVr + CABG)
      2.5 ± 0.52.8 ± 0.42+/3+ (Moderate to Severe)
      Kim 2005OS168187MVr (100%)NR2.63
      P < .05.
      3.81
      P < .05.
      ≥ 3+ (Moderate to Severe)
      Wong 2005OS22031MVr (100%)51.6m2.3 ± 0.7
      P < .05.
      3.1 ± 0.3
      P < .05.
      3+ (Moderate Only)
      Diodato 2004OS5151MVr (100%)39 ± 25 (CABG)

      37 ± 25 (MVr + CABG)
      NRNR≥ 2+ (Moderate to Severe)
      Harris 2002OS14234MVr (85%); MVR (15%)61.2 ± 3.6 (CABG)

      56.4 ± 7.2 (MVS + CABG)
      2.1 ± 0.3
      P < .05.
      2.6 ± 0.5
      P < .05.
      2+/3+ (Moderate Only)
      Data presented as n (%), mean ± standard deviation, or median [interquartile range], unless stated otherwise. CABG, Coronary artery bypass graft; MVS, mitral valve surgery; MR, mitral regurgitation; RCT, randomized controlled trial; MVr, mitral valve repair; OS, observational study; MVR, mitral valve replacement; NR, not reported; NS, not specified; M, median; m, mean.
      P < .05.
      Table 2Baseline characteristics of participants in studies comparing isolated coronary artery bypass graft surgery versus concomitant mitral repair for ischemic mitral regurgitation
      StudyAgeMale (%)HTN (%)Diabetes (%)AF (%)Prior MI (%)LVEF %
      CABGCABG + MVrCABGCABG + MVrCABGCABG + MVrCABGCABG + MVrCABGCABG + MVrCABGCABG + MVrCABGCABG + MVr
      Bouchard 201465 ± 1269 ± 78875567350271320756041.5 ± 17.445.7 ± 11.4
      Smith 201465.2 ± 11.364.3 ± 9.66671NRNR445123
      P < .05.
      13
      P < .05.
      646941.2 ± 11.639.3 ± 10.9
      Chan 201270.4 ± 7.970.9 ± 10.5747459503835106727440.3 ± 16.140.0 ± 17.3
      Fattouch 200966 ± 764 ± 9656343545958NRNR10010043 ± 942 ± 10
      Castleberry 201466 (58-73)
      P < .05.
      66 (58-74)
      P < .05.
      655469613635NRNRNRNR48 (35 -60)
      P < .05.
      45 (31-60)
      P < .05.
      Sa 2013NRNR545685944225NRNR465047 ± 345 ± 5
      Deja 201264 (56-70)60 (54-68)8890505955
      P < .05.
      27
      P < .05.
      NRNR748230 (25-35)
      P < .05.
      22 (19-28)
      P < .05.
      Jeong 201265.4 ± 9.163.9 ± 9.16983695946494
      P < .05.
      18
      P < .05.
      10010041.5 ± 12.338.3 ± 12.0
      Silberman 201168 ± 9
      P < .05.
      63 ± 10
      P < .05.
      707864614453127NRNRNRNR
      de Waroux 200961.4 ± 10.164.0 ± 8.4797629242441NRNRNRNR34.4 ± 10.133.0 ± 12.5
      Goland 200969 ± 1168 ± 9648065613629NRNR446139 ± 1137 ± 11
      Mihaljevic 200766 ± 9.266 ± 9.6596970714232008983NRNR
      Bonacchi 200664.5 ± 664.6 ± 6705753633841NRNRNRNR27 ± 527.6 ± 5
      Buja 200675 ± 7.472 ± 9.16462727442413831888538 ± 13
      P < .05.
      50 ± 14
      P < .05.
      Kang 200663 ± 961 ± 106874NRNR5652012NRNR36 ± 936 ± 11
      Kim 200571 ± 1172 ± 9677164624040NRNR48
      P < .05.
      63
      P < .05.
      43 ± 15
      P < .05.
      38 ± 14
      P < .05.
      Wong 2005NRNRNRNRNRNRNRNRNRNRNRNR42.2 ± 15.339.0 ± 13.6
      Diodato 200469 ± 11
      P < .05.
      65 ± 10
      P < .05.
      51476982NRNRNRNR677831 ± 1135 ± 12
      Harris 200268.8 ± 9.865.6 ± 10.8544476684650NRNR807638.7 ± 12.638.0 ± 13.8
      HTN, Hypertension; AF, atrial fibrillation; MI, myocardial infarction; LVEF, left ventricular ejection fraction; CABG, coronary artery bypass graft; MVr, mitral valve repair. NR, not reported.
      P < .05.

      Intraoperative Outcomes

      In 4 RCTs and 11 observational studies including a total of 1963 patients, CABG and MV surgery was associated with significantly longer CPB (MD 48.12; 95% CI, 38.05-58.15; P < .001; Figure 2, A) and aortic cross-clamp (MD 39.13; 95% CI, 32.39-45.86; P < .001; Figure 2, B) durations. These results were consistent in subgroup analyses by study design.
      Figure thumbnail gr2
      Figure 2Forest plot displaying the mean difference (MD) in aortic cross-clamp (2A) and cardiopulmonary bypass (CPB) durations (2B) for isolated coronary artery bypass graft (CABG) surgery versus CABG and mitral valve (MV) surgery. The MD in each study corresponds to the middle of the squares, the horizontal lines show the 95% confidence intervals (CIs), and the pooled MD is represented by the middle of the solid diamond. A test of heterogeneity between studies is given below the summary statistics. SD, Standard deviation; RCT, randomized controlled trial.

      Perioperative Mortality

      In 3 RCTs including a total of 474 patients, concomitant MV surgery was not associated with significantly increased perioperative mortality compared with CABG alone (RR 0.89; 95% CI, 0.26-3.02; P = .85; I2 = 0%; Figure 3, A). Likewise, in 14 observational studies including a total of 1975 patients, perioperative mortality was not significantly increased with the addition of concomitant MV surgery (RR 1.40; 95% CI, 0.88-2.23; P = .16; I2 = 35%; Figure 3, B).
      Figure thumbnail gr3
      Figure 3Forest plot displaying relative risk (RR) for perioperative mortality following isolated coronary artery bypass graft (CABG) surgery versus CABG and mitral valve (MV) surgery in randomized controlled trials (3A) and observational studies (3B). The RR of individual studies correspond to the middle of the squares, the horizontal lines show the 95% confidence intervals (CIs), and the pooled RR is represented by the middle of the solid diamond. A test of heterogeneity between studies is given below the summary statistics. RCT, Randomized controlled trial.

      Perioperative Morbidity

      In 3 RCTs including a total of 203 patients, CABG and MV surgery was not associated with significantly increased risk of stroke (RR 1.65; 95% CI, 0.27-10.22; P = .53; I2 = 0%).
      • Smith P.K.
      • Puskas J.D.
      • Ascheim D.D.
      • Voisine P.
      • Gelijns A.C.
      • Moskowitz A.J.
      • et al.
      Surgical treatment of moderate ischemic mitral regurgitation.
      • Chan K.M.J.
      • Punjabi P.P.
      • Flather M.
      • Wage R.
      • Symmonds K.
      • Roussin I.
      • et al.
      Coronary artery bypass surgery with or without mitral valve annuloplasty in moderate functional ischemic mitral regurgitation final results of the Randomized Ischemic Mitral Evaluation (RIME) trial.
      • Fattouch K.
      • Guccione F.
      • Sampognaro R.
      • Panzarella G.
      • Corrado E.
      • Navarra E.
      • 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.
      Likewise, in 2 observational studies including a total of 182 patients, the risk of stroke was not significantly increased with concomitant MV surgery (RR 0.90; 95% CI, 0.23-3.53; P = .70; I2 = 0%).
      • Sá M.P.
      • Soares E.F.
      • Santos C.A.
      • Figueiredo O.J.
      • Lima R.O.
      • Escobar R.R.
      • et al.
      Mitral valve replacement combined with coronary artery bypass graft surgery in patients with moderate-to-severe ischemic mitral regurgitation.
      • Jeong D.S.
      • Lee H.Y.
      • Kim W.S.
      • Sung K.
      • Park P.W.
      • Lee Y.T.
      Off pump coronary artery bypass versus mitral annuloplasty in moderate ischemic mitral regurgitation.
      In 2 RCTs including a total of 173 patients, the incidence of acute renal failure was not significantly increased with the addition of MV surgery (RR 1.38; 95% CI, 0.44-4.31; P = .58; I2 = 0%).
      • Chan K.M.J.
      • Punjabi P.P.
      • Flather M.
      • Wage R.
      • Symmonds K.
      • Roussin I.
      • et al.
      Coronary artery bypass surgery with or without mitral valve annuloplasty in moderate functional ischemic mitral regurgitation final results of the Randomized Ischemic Mitral Evaluation (RIME) trial.
      • Fattouch K.
      • Guccione F.
      • Sampognaro R.
      • Panzarella G.
      • Corrado E.
      • Navarra E.
      • 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.
      Similarly, in 3 observational studies including a total of 433 patients, there was no significant difference in acute renal failure between the 2 groups (RR 1.08; 95% CI, 0.28-4.19; P = .91; I2 = 79%).
      • Sá M.P.
      • Soares E.F.
      • Santos C.A.
      • Figueiredo O.J.
      • Lima R.O.
      • Escobar R.R.
      • et al.
      Mitral valve replacement combined with coronary artery bypass graft surgery in patients with moderate-to-severe ischemic mitral regurgitation.
      • Jeong D.S.
      • Lee H.Y.
      • Kim W.S.
      • Sung K.
      • Park P.W.
      • Lee Y.T.
      Off pump coronary artery bypass versus mitral annuloplasty in moderate ischemic mitral regurgitation.
      • Wong D.R.
      • Agnihotri A.K.
      • Hung J.W.
      • Vlahakes G.J.
      • Akins C.W.
      • Hilgenberg A.D.
      • et al.
      Long-term survival after surgical revascularization for moderate ischemic mitral regurgitation.
      Meta-analyses could not be performed for other morbidity endpoints due to the lack of outcome reporting across studies.

      Survival

      In 3 RCTs involving a total of 462 patients, there was no difference in survival at follow-up between patients who underwent isolated CABG and those who underwent CABG and MV surgery (HR 1.20; 95% CI, 0.57-2.53; P = .62; I2 = 0%; Figure 4, A). Similarly, in 14 observational studies involving a total of 3828 patients, the 2 surgical cohorts had similar survival at the time of latest follow-up (HR 0.99; 95% CI, 0.81-1.21; P = .92; I2 = 47%; Figure 4, B). Aggregated survival was calculated by using either Kaplan-Meier curves assuming constant censoring
      • Fattouch K.
      • Guccione F.
      • Sampognaro R.
      • Panzarella G.
      • Corrado E.
      • Navarra E.
      • 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.
      • Buja P.
      • Tarantini G.
      • Del Bianco F.
      • Razzolini R.
      • Bilato C.
      • Ramondo A.
      • et al.
      Moderate-to-severe ischemic mitral regurgitation and multivessel coronary artery disease: impact of different treatment on survival and rehospitalization.
      or with censoring information,
      • Castleberry A.W.
      • Williams J.B.
      • Daneshmand M.A.
      • Honeycutt E.
      • Shaw L.K.
      • Samad Z.
      • et al.
      Surgical revascularization is associated with maximal survival in patients with ischemic mitral regurgitation: a 20-year experience.
      • Silberman S.
      • Eldar O.
      • Oren A.
      • Tauber R.
      • Fink D.
      • Klutstein M.W.
      • et al.
      Surgery for ischemic mitral regurgitation: should the valve be repaired.
      • de Waroux J.B.
      • Pouleur A.-C.
      • Vancraeynest D.
      • Pasquet A.
      • Gerber B.L.
      • El Khoury G.
      • et al.
      Early hazards of mitral ring annuloplasty in patients with moderate to severe ischemic mitral regurgitation undergoing coronary revascularization: the importance of preoperative myocardial viability.
      • Goland S.
      • Czer L.S.C.
      • Siegel R.J.
      • DeRobertis M.A.
      • Mirocha J.
      • et al.
      Outcomes in patients with moderate ischemic mitral regurgitation.
      • Bonacchi M.
      • Prifti E.
      • Maiani M.
      • Frati G.
      • Nathan N.S.
      • Leacche M.
      Mitral valve surgery simultaneous to coronary revascularization in patients with end-stage ischemic cardiomyopathy.
      • Harris K.M.
      • Sundt T.M.
      • Aeppli D.
      • Sharma R.
      • Barzilai B.
      Can late survival of patients with moderate ischemic mitral regurgitation be impacted by intervention on the valve?.
      events and P value,
      • Chan K.M.J.
      • Punjabi P.P.
      • Flather M.
      • Wage R.
      • Symmonds K.
      • Roussin I.
      • et al.
      Coronary artery bypass surgery with or without mitral valve annuloplasty in moderate functional ischemic mitral regurgitation final results of the Randomized Ischemic Mitral Evaluation (RIME) trial.
      • Jeong D.S.
      • Lee H.Y.
      • Kim W.S.
      • Sung K.
      • Park P.W.
      • Lee Y.T.
      Off pump coronary artery bypass versus mitral annuloplasty in moderate ischemic mitral regurgitation.
      • Mihaljevic T.
      • Lam B.-K.
      • Rajeswaran J.
      • Takagaki M.
      • Lauer M.S.
      • Gillinov A.M.
      • et al.
      Impact of mitral valve annuloplasty combined with revascularization in patients with functional ischemic mitral regurgitation.
      • Kang D.-H.
      • Kim M.-J.
      • Kang S.-J.
      • Song J.M.
      • Song H.
      • Hong M.K.
      • et al.
      Mitral valve repair versus revascularization alone in the treatment of ischemic mitral regurgitation.
      • Kim Y.-H.
      • Czer L.S.C.
      • Soukiasian H.J.
      • De Robertis M.
      • Magliato K.E.
      • Blanche C.
      • et al.
      Ischemic mitral regurgitation: revascularization alone versus revascularization and mitral valve repair.
      adjusted HR,
      • Deja M.A.
      • Grayburn P.A.
      • Sun B.
      • Rao V.
      • She L.
      • Kreica M.
      • et al.
      Influence of mitral regurgitation repair on survival in the surgical treatment for ischemic heart failure trial.
      or unadjusted HR,
      • Smith P.K.
      • Puskas J.D.
      • Ascheim D.D.
      • Voisine P.
      • Gelijns A.C.
      • Moskowitz A.J.
      • et al.
      Surgical treatment of moderate ischemic mitral regurgitation.
      • Wong D.R.
      • Agnihotri A.K.
      • Hung J.W.
      • Vlahakes G.J.
      • Akins C.W.
      • Hilgenberg A.D.
      • et al.
      Long-term survival after surgical revascularization for moderate ischemic mitral regurgitation.
      as per methods described by Tierney and colleagues.
      • Tierney J.F.
      • Stewart L.A.
      • Ghersi D.
      • Burdett S.
      • Sydes M.R.
      Practical methods for incorporating summary time-to-event data into meta-analysis.
      Figure thumbnail gr4
      Figure 4Forest plot displaying hazard ratio (HR) for late mortality following isolated coronary artery bypass graft (CABG) surgery versus CABG and mitral valve (MV) surgery in randomized controlled trials (4A) and observational studies (4B). The HR of individual studies correspond to the middle of the squares, the horizontal lines show the 95% confidence intervals (CIs), and the pooled HR is represented by the middle of the solid diamond. A test of heterogeneity between studies is given below the summary statistics. RCT, Randomized controlled trial; SE, standard error.

      Recurrence of Moderate-to-Severe Mitral Regurgitation

      In 4 RCTs including a total of 459 patients, CABG and MV surgery was associated with significantly lower incidence of moderate-to-severe (grade ≥ 2) regurgitation at latest follow-up (RR 0.16; 95% CI, 0.04-0.75; P = .02; I2 = 68%; Figure 5, A). This result was also demonstrated in an analysis of 4 observational studies including a total of 312 patients (RR 0.25; 95% CI, 0.12-0.50; P < .001; I2 = 21%; Figure 5, B).
      Figure thumbnail gr5
      Figure 5Forest plot displaying relative risk (RR) for recurrence of moderate-to-severe mitral regurgitation following isolated coronary artery bypass graft (CABG) surgery versus CABG and mitral valve (MV) surgery in randomized controlled trials (5A) and observational studies (5B). The RR of individual studies corresponds to the middle of the squares, the horizontal lines show the 95% confidence intervals (CIs), and the pooled RR is represented by the middle of the solid diamond. A test of heterogeneity between studies is given below the summary statistics. RCT, Randomized controlled trial.

      Echocardiographic Outcomes

      Due to limited data from observational studies, meta-analyses of echocardiographic outcomes were limited to RCTs. In 3 RCTs including 402 patients, CABG and MV surgery was not associated with significantly greater increase in left ventricular ejection fraction (LVEF) at follow-up (MD 0.19; 95% CI, −3.26 to 3.65; P = .91).
      • Bouchard D.
      • Jensen H.
      • Carrier M.
      • Dermers P.
      • Pellerin M.
      • Perrault L.P.
      • et al.
      Effect of systematic downsizing rigid ring annuloplasty in patients with moderate ischemic mitral regurgitation.
      • Smith P.K.
      • Puskas J.D.
      • Ascheim D.D.
      • Voisine P.
      • Gelijns A.C.
      • Moskowitz A.J.
      • et al.
      Surgical treatment of moderate ischemic mitral regurgitation.
      • Fattouch K.
      • Guccione F.
      • Sampognaro R.
      • Panzarella G.
      • Corrado E.
      • Navarra E.
      • 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.
      In 2 RCTs including 339 patients, the decrease in left ventricular end-systolic volume index (LVESVI) was not significantly greater following CABG and MV surgery (weighted mean difference [WMD] −3.59; 95% CI, −17.98 to 10.81; P = .63).
      • Smith P.K.
      • Puskas J.D.
      • Ascheim D.D.
      • Voisine P.
      • Gelijns A.C.
      • Moskowitz A.J.
      • et al.
      Surgical treatment of moderate ischemic mitral regurgitation.
      • Chan K.M.J.
      • Punjabi P.P.
      • Flather M.
      • Wage R.
      • Symmonds K.
      • Roussin I.
      • et al.
      Coronary artery bypass surgery with or without mitral valve annuloplasty in moderate functional ischemic mitral regurgitation final results of the Randomized Ischemic Mitral Evaluation (RIME) trial.
      In 2 RCTs including 88 patients, the decrease in residual regurgitant volume was not significantly different between patients who underwent CABG and MV surgery and those who underwent isolated CABG (WMD −4.78; 95% CI, −26.61 to 17.06; P = .67; I2 = 94%).
      • Bouchard D.
      • Jensen H.
      • Carrier M.
      • Dermers P.
      • Pellerin M.
      • Perrault L.P.
      • et al.
      Effect of systematic downsizing rigid ring annuloplasty in patients with moderate ischemic mitral regurgitation.
      • Chan K.M.J.
      • Punjabi P.P.
      • Flather M.
      • Wage R.
      • Symmonds K.
      • Roussin I.
      • et al.
      Coronary artery bypass surgery with or without mitral valve annuloplasty in moderate functional ischemic mitral regurgitation final results of the Randomized Ischemic Mitral Evaluation (RIME) trial.

      NYHA Functional Status

      In 3 RCTs including a total of 330 patients, the proportion of patients in NYHA class III/IV at follow-up were similar following isolated CABG or CABG and MV surgery (RR 0.67; 95% CI, 0.25-1.82; P = .43; I2 = 18%).
      • Bouchard D.
      • Jensen H.
      • Carrier M.
      • Dermers P.
      • Pellerin M.
      • Perrault L.P.
      • et al.
      Effect of systematic downsizing rigid ring annuloplasty in patients with moderate ischemic mitral regurgitation.
      • Smith P.K.
      • Puskas J.D.
      • Ascheim D.D.
      • Voisine P.
      • Gelijns A.C.
      • Moskowitz A.J.
      • et al.
      Surgical treatment of moderate ischemic mitral regurgitation.
      • Chan K.M.J.
      • Punjabi P.P.
      • Flather M.
      • Wage R.
      • Symmonds K.
      • Roussin I.
      • et al.
      Coronary artery bypass surgery with or without mitral valve annuloplasty in moderate functional ischemic mitral regurgitation final results of the Randomized Ischemic Mitral Evaluation (RIME) trial.
      This result was also demonstrated in an analysis of 4 observational studies including a total of 292 patients (RR 1.23; 95% CI, 0.78-1.93; P = .37; I2 = 5%).
      • Mihaljevic T.
      • Lam B.-K.
      • Rajeswaran J.
      • Takagaki M.
      • Lauer M.S.
      • Gillinov A.M.
      • et al.
      Impact of mitral valve annuloplasty combined with revascularization in patients with functional ischemic mitral regurgitation.
      • Bonacchi M.
      • Prifti E.
      • Maiani M.
      • Frati G.
      • Nathan N.S.
      • Leacche M.
      Mitral valve surgery simultaneous to coronary revascularization in patients with end-stage ischemic cardiomyopathy.
      • Trichon B.H.
      • Glower D.D.
      • Shaw L.K.
      • Cabell C.H.
      • Anstrom K.J.
      • Felker G.M.
      • et al.
      Survival after coronary revascularization, with and without mitral valve surgery, in patients with ischemic mitral regurgitation.
      • Despotis G.J.
      • Filos K.S.
      • Zoys T.N.
      • Hogue Jr., C.W.
      • Spitznagel E.
      • Lappas D.G.
      Factors associated with excessive postoperative blood loss and hemostatic transfusion requirements: a multivariate analysis in cardiac surgical patients.

      Subgroup Analysis: Moderate MR

      Subgroup analysis was conducted to assess studies in which all patients had only moderate IMR. This included 4 RCTs and 4 observational studies, reporting on a total of 1155 patients.
      • Bouchard D.
      • Jensen H.
      • Carrier M.
      • Dermers P.
      • Pellerin M.
      • Perrault L.P.
      • et al.
      Effect of systematic downsizing rigid ring annuloplasty in patients with moderate ischemic mitral regurgitation.
      • Smith P.K.
      • Puskas J.D.
      • Ascheim D.D.
      • Voisine P.
      • Gelijns A.C.
      • Moskowitz A.J.
      • et al.
      Surgical treatment of moderate ischemic mitral regurgitation.
      • Chan K.M.J.
      • Punjabi P.P.
      • Flather M.
      • Wage R.
      • Symmonds K.
      • Roussin I.
      • et al.
      Coronary artery bypass surgery with or without mitral valve annuloplasty in moderate functional ischemic mitral regurgitation final results of the Randomized Ischemic Mitral Evaluation (RIME) trial.
      • Fattouch K.
      • Guccione F.
      • Sampognaro R.
      • Panzarella G.
      • Corrado E.
      • Navarra E.
      • 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.
      • Jeong D.S.
      • Lee H.Y.
      • Kim W.S.
      • Sung K.
      • Park P.W.
      • Lee Y.T.
      Off pump coronary artery bypass versus mitral annuloplasty in moderate ischemic mitral regurgitation.
      • Goland S.
      • Czer L.S.C.
      • Siegel R.J.
      • DeRobertis M.A.
      • Mirocha J.
      • et al.
      Outcomes in patients with moderate ischemic mitral regurgitation.
      • Wong D.R.
      • Agnihotri A.K.
      • Hung J.W.
      • Vlahakes G.J.
      • Akins C.W.
      • Hilgenberg A.D.
      • et al.
      Long-term survival after surgical revascularization for moderate ischemic mitral regurgitation.
      • Harris K.M.
      • Sundt T.M.
      • Aeppli D.
      • Sharma R.
      • Barzilai B.
      Can late survival of patients with moderate ischemic mitral regurgitation be impacted by intervention on the valve?.
      Within this group, combined CABG and MV surgery was found to be associated with significantly increased perioperative mortality in observational studies (RR 1.81; 95% CI, 1.03-3.15; P = .02; I2 = 0%) but not within RCTs (RR 0.89; 95% CI, 0.26-3.02; P = .85; I2 = 0%). Patients who underwent combined CABG and MV surgery still had significantly reduced recurrence of MR at latest follow-up in both RCTs (RR 0.16; 95% CI, 0.04-0.75; P < .001; I2 = 68%) and observational studies (RR 0.26; 95% CI, 0.11-0.65; P = .004; I2 = 38%). There remained no difference between the surgical approaches with regard to long-term survival (HR 1.09; 95% CI, 0.84-1.42; P = .53; I2 = 0%) or NYHA functional status (RR 1.16; 95% CI, 0.61-2.21; P = .65; I2 = 37%).

      Meta-Regression Analyses

      Meta-regression analyses demonstrated that duration of follow-up was not a significant moderator for long-term survival (P = .60) and residual MR (P = .20). Meta-regression analyses could not be performed for other endpoints due to the paucity of studies.

      Publication Bias

      Neither the Begg rank correlation test (P = .51) nor Egger linear regression method (P = .40) suggested publication bias was a significant factor when perioperative mortality was selected as an endpoint. Likewise, publication bias was not found to significantly influence results for late mortality (Begg rank correlation test, P = .97; Egger linear regression method, P = .51).

      Discussion

      Despite the prevalence of IMR in patients referred for surgical revascularization and its association with poorer clinical outcomes, the optimal management of moderate-to-severe IMR remains unclear.
      • Grigioni F.
      • Enriquez-Sarano M.
      • Zehr K.J.
      • Bailey K.R.
      • Tajik A.J.
      Ischemic mitral regurgitation long-term outcome and prognostic implications with quantitative Doppler assessment.
      The present meta-analysis assessed the safety and efficacy of isolated CABG versus combined CABG and MV surgery in patients with moderate-to-severe IMR. Concomitant MV surgery was not associated with an increase in perioperative mortality. However, the addition of MV surgery to CABG resulted in significantly reduced recurrence of moderate-to-severe MR at latest follow-up. There was no significant difference in late mortality or NYHA functional status between patients who underwent isolated CABG or those who underwent CABG and MV surgery. These findings were replicated in subgroup analysis conducted to assess the impact of concomitant MV surgery in patients with strictly moderate IMR.
      CPB and aortic cross-clamp durations were found to be significantly higher in patients undergoing CABG + MV surgery. This is an intuitive finding given the increased complexity of a combined procedure. Longer CPB and aortic cross-clamp durations have been linked with a number of complications, including microemboli, increased transfusion requirements, coagulation defects, and immunosuppression.
      • Despotis G.J.
      • Filos K.S.
      • Zoys T.N.
      • Hogue Jr., C.W.
      • Spitznagel E.
      • Lappas D.G.
      Factors associated with excessive postoperative blood loss and hemostatic transfusion requirements: a multivariate analysis in cardiac surgical patients.
      • Sablotzki A.
      • Welters I.
      • Lehmann N.
      • Menges T.
      • G€orlach G.
      • Dehne M.
      • et al.
      Plasma levels of immunoinhibitory cytokines interleukin-10 and transforming growth factor-b in patients undergoing coronary artery bypass grafting.
      • Taylor K.M.
      Brain damage during cardiopulmonary bypass.
      In the present meta-analysis, increased operative durations did not translate to an increase in adverse perioperative events. However, it must be emphasized that the present study was unable to assess key perioperative morbidity outcomes, such as major bleeding, reoperation, myocardial infarction, and wound infection. In particular, there were a very limited number of studies assessing neurological events and the event rate may have been too low to enable sufficiently powered analysis. Indeed, in 2 of the included RCTs, the point estimate for stroke suggested a possible trend toward increased risk following combined CABG + MV surgery.
      • Smith P.K.
      • Puskas J.D.
      • Ascheim D.D.
      • Voisine P.
      • Gelijns A.C.
      • Moskowitz A.J.
      • et al.
      Surgical treatment of moderate ischemic mitral regurgitation.
      • Chan K.M.J.
      • Punjabi P.P.
      • Flather M.
      • Wage R.
      • Symmonds K.
      • Roussin I.
      • et al.
      Coronary artery bypass surgery with or without mitral valve annuloplasty in moderate functional ischemic mitral regurgitation final results of the Randomized Ischemic Mitral Evaluation (RIME) trial.
      As such, given the paucity of endpoints reported in current studies, it is not possible to exclude an increased risk of perioperative morbidity with the addition of concomitant MV surgery.
      Key findings from the present study demonstrated that the proportion of patients with residual MR of at least moderate severity was significantly lower following concomitant mitral intervention. However, this was not associated with any significant advantage with regard to survival or functional status at the time of latest follow-up. This represents an unexpected finding given the association previously demonstrated between persistent MR and increased mortality.
      • Di Salvo T.G.
      • Acker M.A.
      • Dec G.W.
      • Byrne J.G.
      Mitral valve surgery in advanced heart failure.
      It is possible the limited sample size and follow-up durations of the included studies, particularly the RCTs, may not have provided sufficient time or statistical power to highlight the clinical benefit of reduced residual MR. Alternatively, surgical revascularization alone may have sufficiently improved adverse left ventricular remodeling and contractility so as to mitigate the adverse impact of residual MR.
      • Penicka M.
      • Linkova H.
      • Lang O.
      • Fojt R.
      • Kocka V.
      • Vanderheyden M.
      • et al.
      Predictors of improvement of unrepaired moderate ischemic mitral regurgitation in patients undergoing elective isolated coronary artery bypass graft surgery.
      • Roshanali F.
      • Mandegar M.H.
      • Yousefnia M.A.
      • Alaeddini F.
      • Wann S.
      Low-dose do- butamine stress echocardiography to predict reversibility of mitral regurgitation with CABG.
      The latter suggestion was supported by our meta-analysis of echocardiographic outcomes, which demonstrated similar pooled LVEF and LVESVI in patients who underwent either isolated CABG or CABG and MV surgery. Nonetheless, larger randomized trials with longer follow-up durations are required to clarify this discrepancy between echocardiographic and clinical outcomes.
      The present meta-analysis highlighted the considerable variability that exists with regard to the definition of “moderate” IMR. Although the American Society of Echocardiography and American Heart Association/American College of Cardiology have proposed standardized guidelines for the determination of MR grade,
      • Bonow R.O.
      • Carabello B.A.
      • Chatterjee K.
      • de Leon A.C.
      • Faxon D.P.
      • Freed M.D.
      • et al.
      2008 focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to revise the 1998 guidelines for the management of patients with valvular heart disease) Endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons.
      • Zoghbi W.A.
      • Enriquez-Sarano M.
      • Foster E.
      • Grayburn P.A.
      • Kraft C.D.
      • Levine R.A.
      • et al.
      Recommendations for evaluation of the severity of native valvular regurgitation with two-dimensional and Doppler echocardiography.
      these were only adopted by several studies.
      • Smith P.K.
      • Puskas J.D.
      • Ascheim D.D.
      • Voisine P.
      • Gelijns A.C.
      • Moskowitz A.J.
      • et al.
      Surgical treatment of moderate ischemic mitral regurgitation.
      • Chan K.M.J.
      • Punjabi P.P.
      • Flather M.
      • Wage R.
      • Symmonds K.
      • Roussin I.
      • et al.
      Coronary artery bypass surgery with or without mitral valve annuloplasty in moderate functional ischemic mitral regurgitation final results of the Randomized Ischemic Mitral Evaluation (RIME) trial.
      Most included studies graded MR severity according to local institutional criteria, using a wide range of cutoffs for jet regurgitant area, vena contracta diameter, and/or proximal isovelocity surface area. This likely contributed to the considerable heterogeneity present in several of our analyses. To standardize comparative data across institutions, it is imperative that future studies use well-defined echocardiographic grading criteria according to established guidelines.
      Results of the present meta-analysis were limited by several restraints, and should be interpreted with caution. First, there were only 4 RCTs, and observational studies provided a significant proportion of clinical data. As observational studies did not use propensity-score matching or report adjusted estimates, it was not possible to account for potential baseline differences between the 2 surgical arms. In recognition of this limitation, we performed subgroup analyses by study design. Second, due to the lack of reporting, it was not possible to assess quality-of-life scores or measures of resource utilization and cost-effectiveness, such as length of intensive care unit stay, despite these being increasingly key considerations in clinical practice. Third, follow-up periods and endpoint definitions differed between institutions, and some studies may have underestimated adverse events due to incomplete follow-up. Although meta-regression analyses did not demonstrate significant interaction between follow-up duration and survival or residual MR, there was not enough data to perform meta-regression for other outcomes such as NYHA functional class. Last, due to the lack of available data, residual MR was assessed using a binary approach rather than through a longitudinal, competing risks method.
      In conclusion, available data in the current literature demonstrated that MV surgery in addition to CABG was not associated with increased perioperative mortality in patients with moderate-to-severe IMR. Compared with isolated CABG, concomitant MV surgery was associated with reduced recurrence of moderate-to-severe MR at follow-up. However, there was no significant difference between the 2 treatment approaches with regard to late mortality or NYHA functional status. Larger trials with longer follow-up duration are required to further assess overall survival and freedom from reintervention, as well as the impact of both surgical approaches on quality of life and health care costs.

      Conflict of Interest Statement

      Authors have nothing to disclose with regard to commercial support.

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