- Research article
- Open Access
- Open Peer Review
Repair or replace ischemic mitral regurgitation during coronary artery bypass grafting? A meta-analysis
https://doi.org/10.1186/s13019-016-0536-6
© The Author(s). 2016
- Received: 14 April 2016
- Accepted: 24 August 2016
- Published: 1 September 2016
Abstract
Background
No agreement has been reached for the best surgical treatment for patients with chronic ischemic mitral regurgitation (IMR) undergoing coronary artery bypass grafting (CABG). Our objective was to meta-analyze the clinical outcomes of repair and replacement.
Methods
A computerized search was performed using Pubmed, Embase, Ovid medline and Cochrane Library. The search terms “ischemic or ischaemic” and “mitral valve” and “repair or replacement or annuloplasty” and “coronary artery bypass grafting” were entered as MeSH terms and keywords. The primary outcomes were operative mortality and late mortality. Secondary outcomes were 2+ or greater recurrence of mitral regurgitation and reoperation rate.
Results
Eleven studies were eligible for the final meta-analysis. These studies included a total of 1750 patients, 60.4 % of whom received mitral valve repair. All patients underwent concomitant coronary artery bypass graft. No differences were found in operative mortality (summary odds ratio [OR] 0.65; 95 % confidence interval [CI] 0.43-1.00; p = 0.05), late mortality (summary hazard ratio [HR] 0.87; 95 % confidence interval [CI] 0.67-1.14; p = 0.31) and reoperation (summary odds ratio [OR] 1.47; 95 % confidence interval [CI] 0.90-2.38; p = 0.12). Regurgitation recurrence was lower in the replacement group (summary odds ratio [OR] 5.41; 95 % confidence interval [CI] 3.12-9.38; p < 0.001).
Conclusion
In patients with chronic ischemic mitral regurgitation during CABG, mitral valve replacement is associated with lower recurrence of regurgitation. No differences were found regarding survival and reoperation rates.
Keywords
- Ischemic mitral regurgitation
- Mitral valve repair
- Mitral valve replacement
- Coronary artery bypass grafting
- Meta-analysis
Background
Chronic ischemic mitral regurgitation (IMR) is a frequent and important complication after myocardial infarction. Its pathophysiologic mechanisms account for remodeling of segmental/global left ventricle (LV) inducing papillary muscle displacement and leaflet tethering [1]. The presence of IMR is independently associated with mortality and morbidity after myocardial infarction [2].
Given the severity of IMR, surgery performed for IMR ranges from coronary artery bypass grafting (CABG) alone to both CABG and mitral valve surgery [3, 4]. Two randomized trials indicated that repair was associated with a reduced prevalence of mitral regurgitation but did not show a clinically meaningful advantage of adding mitral valve repair to CABG [5, 6]. In addition, when compared with replacement, previous meta-analyses concluded that repair is associated with lower operative mortality but higher recurrence of regurgitation in patients with ischemic mitral regurgitation, with or without CABG [7, 8]. For patients with chronic IMR undergoing combined CABG, the best surgical treatment is still controversial. Some studies support replacement [9, 10], others support repair [11, 12], and others showed similar survival for the two procedures [13]. Current guidelines recommend mitral valve surgery for severe IMR, but do not demonstrate a specific type of procedure [14, 15]. Numerous non-randomized studies have been published comparing the clinical outcomes between MVP + CABG and MVR + CABG for IMR. However, there is still no systematic and quantitative assessment of accumulated literature on this topic. Meta-analysis is a powerful tool to provide meaningful comparison of short and long-term outcomes of these procedures. The present meta-analysis aimed to assess the clinical outcomes of patients who underwent mitral valve surgery and CABG for chronic IMR.
Methods
Search strategy
This meta-analysis was conducted according to the recommendations of the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) [16]. A computerized search was performed using Pubmed, Embase, Ovid medline and Cochrane Library from their dates of inception to December 2015 without language restriction. The search terms “ischemic or ischaemic” and “mitral valve” and “repair or replacement or annuloplasty” and “coronary artery bypass grafting” were entered as MeSH terms and keywords. The language of publication was restricted to English. We also reviewed the full text and references lists of all relevant review articles in detail. YW and XS independently undertook the literature search, screening of titles and abstracts. Any disagreement was resolved by consensus.
Study selection
Articles were included if there is a direct comparison of repair versus replacement and all patients with IMR had CABG. The exclusion criteria were applied to select the final articles for the meta-analysis: (1) ischemic etiology in only a subset of the patients with outcomes not specifically provided (2) nonischemic dilated cardiomyopathy (3) beating heart procedures (4) concomitant surgical ventricular restoration (5) preoperative hemodynamic instability (6) lack of annuloplasty in > 20 % of the patients in the repair group (7) acute IMR.
Data extraction and quality assessment
All data were extracted independently by 2 investigators (Y.W., X.S.) according to the prespecified selection criteria, with disagreement resolved by consensus among all authors. The following data from each study were extracted: the last name of the first author, year of publication, study population, patients’ age and gender, comorbidities, cardiac function, severity of mitral regurgitation at baseline and follow-up period. Any disagreement was resolved by consensus.
Based on the extracted data, the quality of the included studies was evaluated using the nine-item Newcastle-Ottawa Quality scale [17], a widely used tool for the quality assessment of non-randomized trials. The high-quality study was defined as a study with ≥6 scores.
Statistical analysis
The primary end points were operative mortality and late mortality (considered to be year after operation). Operative mortality was defined as death within 30 days after operation or in-hospital death. Secondary end points were MR recurrence 2+ or greater and reoperation at follow-up. The meta-analysis was performed using Review Manager (Revman, version 5.3 for windows, Oxford, England, Cochrane Collaboration) and Stata (version 11.0; StataCorp, College Station, TX). Hazard ratio (HR) with a 95 % confidence intervals (CIs), directly extracted from these included studies or indirectly calculated using the method of Tierney and colleagues [18] to assess the efficacy of the surgical intervention in each study. A summary of odds ratio (OR) and their corresponding 95 % CI were computed for each dichotomous outcome using either fixed-effects models or, in the presence of substantial heterogeneity (I2 > 50 %), random-effects models [19]. Statistical heterogeneity across studies was examined with Cochran’s Q test as well as the I2 statistics. Studies with an I2 statistics of <25 % were considered to have low heterogeneity, those with an I2 statistics of 25–50 % were considered to have moderate heterogeneity, and those with an I2 statistics of >50 % were considered to have a high degree of heterogeneity [20]. If there was high heterogeneity, the possible clinical and methodological factors for this were further explored. Potential sources of heterogeneity were investigated using sensitivity analyses and each study involved in the meta-analysis was excluded each time to reflect the influence of the individual data set on the pooled RRs.
Publication bias was assessed using the Egger regression asymmetry test [21] and Begg adjusted rank correlation test [22]; a P value of less than 0.05 was considered representative of statistically significant publication bias. Meta-analysis results are displayed in forest plots. A p value < 0.05 was considered statistically significant.
Results
Search results and study quality
Flow chart of study selection
Key Features of Included Studies
Study | Subjects | Mean Age | Male (%) | HTN (%) | Diabetes (%) | AF (%) | NYHA III-IV (%) | Mean LVEF (%) | MR grade | Follow-up period | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
MVP + CABG | MVR + CABG | MVP + CABG | MVR + CABG | MVP + CABG | MVR + CABG | MVP + CABG | MVR + CABG | MVP + CABG | MVR + CABG | MVP + CABG | MVR + CABG | MVP + CABG | MVR + CABG | MVP + CABG | MVR + CABG | MVP + CABG | MVR + CABG | ||
Lorusso et al. | 244 | 244 | 66 | 66 | 73 | 69 | 41 | 41 | 36 | 35 | 12 | 13 | NR | NR | 35 | 35 | 2.8 ± 0.5 | 2.8 ± 0.5 | 46.5bmo |
Lio et al. | 98 | 28 | 65 | 70d | 74 | 61 | 81 | 89 | 35 | 32 | NR | NR | 61 | 71 | 32 | 34 | NR | NR | 45bmo |
Ljubacev et al. | 34 | 41 | NR | NR | NR | NR | 85 | 80 | 32 | 56d | 26 | 17 | NR | NR | NR | NR | NR | NR | In-hospital |
Roshanali et al. | 26 | 31 | 57 | 57 | 83 | 77 | NR | NR | NR | NR | NR | NR | NR | NR | 38 | 40 | 3.6 ± 0.5 | 3.5 ± 0.5 | 40.2a mo |
Maltais et al. | 302 | 85 | 70 | 70 | 68 | 63 | 71 | 68 | 34 | 26 | NR | NR | 85 | 91 | 34 | 34 | NR | NR | 4.2ayrs |
Qiu et al. | 112 | 106 | 71 | 72 | 64 | 56 | 72 | 75 | 30 | 32 | 28 | 26 | 53 | 49 | 35 | 35 | NR | NR | 48.1amo |
Micovic et al. | 86 | 52 | 61b | 62b | 72 | 73 | 74 | 65 | 21 | 15 | 27 | 29 | 64 | 50 | 29 | 36 | 2.7 ± 0.6 | 2.5 ± 0.7 | 32a mo |
Bonacchi et al. | 36 | 18 | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | 27 | 27 | NR | NR | 32a mo |
Silberman et al. | 38 | 14 | 62 | 67d | 74 | 93 | 50 | 57 | 45 | 57 | NR | NR | 49cd | 32cd | <25 % | NR | NR | 38amo | |
Mantovani et al. | 61 | 41 | 68 | 68 | 67 | 54 | 54 | 51 | 26 | 15 | NR | NR | NR | NR | 45 | 45 | 3.1 ± 0.8 | 3.3 ± 0.7 | 36.8a mo |
Reece et al. | 54 | 56 | 67 | 69 | 41d | 68d | NR | NR | 22 | 21 | NR | NR | NR | NR | 44 | 40 | NR | NR | In-hospital |
Operative characteristics
CPB time (min) | ACC time (min) | MVR prosthesis type | Subvalvular apparatus preservation | MVP partial/suture annuloplasty (%) | MVP ring annuloplasty (%) | MVP undersizing | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
MVP | MVR | MVP | MVR | Mechanical % | Bioprothesis % | Anterior + Posterior (%) | Posterior (%) | None (%) | ||||
Lorusso et al. [9] | 145 | 145 | 94 | 94 | 47 | 53 | 48 | 24 | 43 | 0 | 100 | 27 (26 mm) 52 (28 mm) 13 (30 mm) 6 (32 mm) 1 (34 mm) 1 (36 mm) |
Lio et al. [10] | 156 | 180 | 107 | 132 | 36 | 64 | 100 | 0 | 0 | 0 | 100 | 37 % open ring 63 % closed ring 37 % rigid ring 63 % semi-rigid ring |
Ljubacev et al. [24] | 145 | 152 | 96 | 99 | NR | NR | NR | NR | NR | NR | NR | NR |
Roshanali et al. [28] | NR | NR | NR | NR | 100 | 0 | 100 | 0 | 0 | NR | NR | NR |
Maltais et al. [13] | NR | NR | NR | NR | 46 | 54 | NR | NR | NR | 8 | 92 | 42 (24–28 mm) 36 (30–34 mm) |
Qiu et al. [26] | 136 | 129 | 105 | 98 | 38 | 62 | 11 | 89 | 0 | 0 | 100 | 30 mm |
Micovic et al. [11] | NR | NR | NR | NR | 100 | 0 | 0 | 100 | 0 | 5 | 95 | Median 28 mm (range, 26–34 mm) |
Bonacchi et al. [12] | NR | NR | NR | NR | NR | NR | 0 | 100 | 0 | 17 | 83 | NR |
Silberman et al. [23] | 154 | 184 | 99 | 111 | 100 | 0 | NR | NR | NR | 0 | 100 | 26 ± 1.2 mm |
Mantovani et al. [25] | 179 | 173 | 131 | 122 | 76 | 24 | 0 | 100 | 0 | 0 | 100 | Moderate |
Reece et al. [27] | 112 | 132 | 152 | 171 | NR | NR | NR | NR | NR | 0 | 100 | 28 mm males 26 mm females |
Study quality assessment using the Newcastle-Ottawa Scale for nonrandomized studies
Selection | Outcome | ||||||||
---|---|---|---|---|---|---|---|---|---|
First author, year of publication (reference) | Representativeness of exposed cohort | Selection of nonexposed cohort | Ascertainment of exposure | Outcome of interest absent at start of study | Comparability (Based on design and analysis) | Assessment of outcome | Follow-up long enough for outcomes to occur | Adequacy of follow-up | Total score |
Lorusso et al. | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 7 |
Lio et al. | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 8 |
Ljubacev et al. | 1 | 1 | 1 | 1 | 0 | 1 | 0 | 1 | 6 |
Roshanali et al. | 1 | 1 | 1 | 1 | 2 | 1 | 1 | 1 | 9 |
Maltais et al. | 1 | 1 | 1 | 1 | 2 | 1 | 1 | 1 | 9 |
Qiu et al. | 1 | 1 | 1 | 1 | 2 | 1 | 1 | 1 | 9 |
Micovic et al. | 1 | 1 | 1 | 1 | 2 | 1 | 1 | 1 | 9 |
Bonacchi et al. | 1 | 1 | 1 | 1 | 2 | 1 | 1 | 1 | 9 |
Silberman et al. | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 8 |
Mantovani et al. | 1 | 1 | 1 | 1 | 2 | 1 | 1 | 1 | 9 |
Reece et al. | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 7 |
Peri-operative mortality
Mitral valve repair versus mitral valve replacement on peri-operative mortality
Late mortality
Mitral valve repair versus mitral valve replacement on late mortality
Mitral valve reoperation
Mitral valve repair versus mitral valve replacement on reoperation
Recurrence of MR
Mitral valve repair versus mitral valve replacement on recurrence of mitral valve regurgitation
Discussion
In our meta-analysis of eleven studies, which included patients undergoing repair or replacement electively with CABG surgery, no differences were found regarding peri-operative mortality and long-term survival. Mitral valve replacement was associated with lower incidence of mitral regurgitation in patients with IMR during CABG. The Society of Thoracic Surgeons reports MVP + CABG group had approximately 5 % (4.8 % in-hospital mortality and 5.3 % operative mortality) nationwide mortality rates in contrast with 8 % (7.8 % in-hospital mortality and 8.5 % operative mortality) for MVR + CABG group [29].
Moderate and severe recurrent MR after a restrictive annuloplasty ring, occurred early and affected a substantial proportion of patients by 2 years [30]. In the present study, the main disadvantage of MVP + CABG group is recurrence of MR compared to MVR + CABG group. Although MR recurrence was common, mitral valve reoperation was not. Similar reoperation rate was found between both groups, which suggested that not all patients with MR recurrence 2+ or greater needed reoperation. There were several possible explanations. IMR after annuloplasty might be considered inconsequential compared with the underlying myocardial disease, or surgeons might be hesitant to perform a second or third cardiac operation in these elderly, high-risk patients [31]. Many patients with recurrent MR were just too sick or too old or both to even consider reoperating on them.
A case-matched study found that replacement was associated with lower incidence of valve-related complications than was repair and both mitral valve procedures showed no significant difference in LV function at follow-up [32]. However, replacement had greater thromboembolic and ischemic stroke rates than repair despite anticoagulant therapy [33]. Although mitral valve replacement can sufficiently correct regurgitation, the structural integrity of the mitral valve is usually compromised after replacement, leading to a continuous damage on the left ventricular tethered loop, which results in adverse effects on left ventricular contraction and poor prognosis [8]. Therefore, individualized consideration should be given to the two surgical procedures.
To date, there have been no RCTs that compared the clinical outcomes of the two surgical management particularly in patients with chronic IMR during CABG. To our knowledge, our report is the first meta-analysis comparing short-term and long-term outcomes of two mitral valve procedures specifically on patients with chronic IMR undergoing concomitant CABG. We selected studies for this meta-analysis with rigorous inclusion and exclusion criteria. All the patients in the studies underwent concomitant CABG, which ensures homogeneity of IMR patients and facilitates comparisons between trials. In addition, patients with acute IMR due to ruptured papillary muscles were excluded in our study, thus the outcomes of this meta-analysis not only truly reflect the surgical intervention of chronic IMR but also avoid biasing the results toward worsening the replacement group. By excluding articles that had > 20 % lack of annuloplasty ring, we have made the comparison between the two mitral valves surgeries more powerful. Therefore, the results of our study truly reflect the surgical management of patients with IMR simultaneous to CABG.
Limitations
Our meta-analysis has several limitations. Firstly, this study was based on observational, retrospective studies with inherent bias of such study designs. The publications included in this meta-analysis were relatively small and nonrandomized studies. Secondly, changes in NYHA class, LVEF and left ventricular reversal remodeling were too scarcely reported in the included studies to enable meta-analysis. Eight out of eleven studies included in our meta-analysis reported data on the subvalvular apparatus preservation in mitral valve replacement yet with lack of uniform preservation of both the anterior and posterior leaflets. The other three studies had no description regarding subvalvular apparatus preservation. Thirdly, potential confounding factors such as preoperative risk evaluation (STS score i.e.), mitral valve more suitable for repair, age, cause of mitral regurgitation (ischemia, fibrosis, ventricular remodeling), EF and complexity of revascularization were not considered or adjusted in some of the studies included in our meta-analysis. Therefore, the superiority of repair over replacement may be affected by this and other factors that are not possible to be revealed with meta-analysis of observational trials. Well-designed RCTs are required to further verify the conclusion. Another limitation of our report is the fact that follow-up periods were heterogeneous between some studies with different use of mean and median durations of follow-up. Therefore, subgroup analysis could not be performed statistically.
Conclusions
In patients with chronic ischemic mitral regurgitation during CABG, mitral valve replacement is associated with lower recurrence of regurgitation. No differences were found regarding survival and reoperation rates.
Declarations
Acknowledgements
None.
Funding
None.
Availability of data and material
Not applicable.
Authors’ contributions
YW and XS independently undertook the literature search, screening of titles and abstracts. YW, MW and YC performed the statistics. YW and QZ wrote the paper. All authors read and approved the final manuscript.
Competing interests
The authors declare that they have no competing interests.
Consent for publication
Not applicable.
Ethics approval and consent to participate
Not applicable.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Authors’ Affiliations
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