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Eur J Cardiothorac Surg 2007;31:267-275. doi:10.1016/j.ejcts.2006.11.014
Copyright © 2007, European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved


Review

Meta-analysis of clinical outcomes following surgical mitral valve repair or replacement

Jeffrey Shuhaibera,*, Robert J. Andersonb

a Loyola University Stritch School of Medicine, Department of Thoracic and Cardiovascular Surgery, Maywood, IL 60153, United States
b Division of Epidemiology and Biostatistics, University of Illinois at Chicago, Chicago, IL 60612, United States

Received 13 March 2006; received in revised form 31 October 2006; accepted 14 November 2006.

* Corresponding author. Address: 42 Hamdenway Papworth Everard, Cambridge CB3 8UG, United Kingdom. Tel.: +1 312 404 8710; fax: +1 708 327 2503. (Email: jeffrey01{at}mac.com).


    Abstract
 Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Limitations of meta-analysis
 6. Conclusion
 Appendix A
 Pubmed/Medline
 Embase
 References
 
Although the use of mitral valve surgery has been successful at alleviating mitral valve disease, published studies on either replacement or repair have yielded mixed clinical outcomes regarding differences between repair and replacement. Meta-analysis of various outcomes from 29 published studies was conducted. Studies were separated into four groups by etiology of disease: ischemic; degenerative/myxomatous; rheumatic and mixed. The summary odds ratio for early mortality, comparing replacement to repair, was 2.24 (1.78–2.80), while the summary total survival hazard ratio was 1.58 (1.41–1.78), replacement compared to repair, indicating worse outcomes among those undergoing mitral valve replacement. The risk of thromboembolism was lower in the repair group (summary hazard ratio = 1.86, replacement vs. repair), while there was no statistical difference in time to re-operation between the two treatment groups (hazard ratio = 0.88 [95% confidence interval: 0.48, 1.62]). Analysis stratified by etiologic classification was able to detect strong evidence of differences in 30-day and total survival outcomes favoring repair for three disease groups (rheumatic, mixed and degenerative). Surgery for ischemic mitral valve had lower 30-day mortality for repair than replacement, but no statistically significant difference in the overall survival was detected. The reported information in the published studies used in the current work lacks sufficient detail to allow summary determination of outcomes by mitral valve repair techniques and by type of mitral valve replacement.

Key Words: Mitral valve repair • Mitral valve replacement • Meta-analysis


    1. Introduction
 Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Limitations of meta-analysis
 6. Conclusion
 Appendix A
 Pubmed/Medline
 Embase
 References
 
Repair and replacement of the mitral valve are two independent therapeutic techniques for treating mitral valve disease. The surgical community has become more aware of the known merits of mitral valve repair compared to replacement. Repair is associated with a lower rate of re-operation, thromboembolism and valve infection than mitral valve replacement [1]. Despite these perceived benefits, the results of such outcomes among studies that simultaneously compared the two treatment modalities have not been totally consistent. We believe that a meta-analysis comparing the two techniques, mitral valve replacement versus mitral valve repair, is timely and important, to provide stronger summary information and future directions.

Differences in understanding, surgical and institutional experience still remain key determining factors for selection of surgical therapy in a non-controlled setting. Nonetheless, there has been a significant shift towards repair in the surgical management of mitral valve regurgitation towards the end of the last century. Those who advocate repair understand that left ventricular function is better after repair than after replacement [1,2]; furthermore, repair may offer a lower risk for embolism. However, it has been reported that repair of moderate ischemic mitral valve increases the probability of the patient spending more time on cardiopulmonary bypass, with its associated potential risks [3]. In addition, the application of existing repair techniques requires acquisition of ‘years of experience’ and mental cognition of the valve's morphology. These two requirements for achieving successful repair make valve replacement an attractive and technically simpler alternative in certain circumstances. More recently, late survival outcome for ischemic mitral valve disease has been shown to be indifferent to repair versus replacement [4,5].

In this study, meta-analysis was used to summarize information from 29 studies using approximately 10,000 subjects, in an attempt to achieve a clearer understanding of the comparison of some outcome measures for these two methods of treatment of mitral valve disease.


    2. Methods
 Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Limitations of meta-analysis
 6. Conclusion
 Appendix A
 Pubmed/Medline
 Embase
 References
 
A literature search using various bibliographic tools at University of Illinois at Chicago library was performed. All publications were identified through Pubmed and Embase for all English-only journals published during the period between 1960 and September 2005. The search strategies employed a number of free-text keywords as well as controlled vocabulary terms, including (but not limited to) the following concepts: mitral valve disease; mitral valve; mitral valve repair; mitral valve replacement (see Appendix A for actual search strategies). We also conducted further searches of article bibliographies to ensure that no studies were missed. The selected studies to be analyzed provided the data used in the current analysis.

The requirements study inclusion in this analysis were: (1) the type of patients included could be appropriately categorized into one of the five broad etiologic categories, and (2) survival information (total survival; time to development of thromboembolism, and to re-operation) and occurrence rates (early mortality) had to be provided in sufficient detail to allow extraction of hazard ratios and odds ratios, respectively, comparing the repair and replacement treatment methods. The authors (JS and RA) each reviewed each study and determined if each study had adequate representation of survival to allow for calculation of hazard or odds ratios for the four outcomes used in this study. When several articles reported on the same patient material, only the most recent article was included. Due to the small number of studies providing suitable comparison information, separate analyses for the separate etiologic groups were not possible for either the thromboembolism or the re-operation outcomes. Similarly, lack of sufficient data detail did not allow for comparison among types of mitral valve replacement (biological vs. mechanical), nor among various repair techniques.

2.1 Statistical analysis
Summary hazard ratios (HR) (for total survival, re-operation, and thromboembolism) and the summary odds ratio (OR) for 30-day survival were obtained as weighted averages of the measures from the individual studies, with inverse variances used as weights in the usual manner [8]. When only the graphed survival curves and the baseline sample sizes in the comparison groups were provided, the method of Parmer et al. [6] was used to determine the desired hazard ratio estimate and its variance. When this estimation method was required, the implementation by Sydes was used (Matthew Sydes (Cancer Division) in collaboration with the Meta-analysis Group of the MRC Clinical Trials Unit, London, Personal Communication). The method of Williamson et al. [7] was used to obtain the hazard ratio estimates and variances if the number of persons at risk at each of several time points for the graphed curves was available. Estimated ratios and their variances were used to construct summary 95% confidence intervals for the parameters of interest for individual studies as well as for the summary measures. Comprehensive Meta-Analysis, Version 2 (Borenstein and Rothstein) [8] was used to compute these results, and to generate Forrest plots for displaying the results. The mixed model method was used to account for the random variability between studies. Heterogeneity of the hazard ratios or odds ratios among the included studies was assessed by Cochran's Q statistic, as implemented by Borenstein et al. [8]


    3. Results
 Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Limitations of meta-analysis
 6. Conclusion
 Appendix A
 Pubmed/Medline
 Embase
 References
 
The systematic literature search provided a total of 55 publications to be evaluated. After reviewing the papers, 26 studies were excluded as being unusable for the analysis because of the following reasons: one-group designs, or comparisons within only one of the two treatments of interest; no survival data comparing repair and replacement; apparent subset of cases from later (included) publication; secondary surgery only. A total of 21 [9–30] papers were used in the meta-analysis of total survival comparing repair and replacement, and 28 [9–37] papers were used in the meta-analysis for 30-day survival. Both of these outcomes were analyzed with adjustment for etiology of mitral valve disease.

3.1 Results of the combined studies
The average age in most of the studies was between 50 and 70 years (Table 1 ). Reported studies using younger subjects used (a) a young adult group [36]; (b) a group from South Africa with mean age in the middle twenties [28]; (c) a group of middle-aged patients from Canada [29]. Most of the studies had a preponderance of male patients (see Table 1), except the studies reported by Lee et al. [11] and Yau et al. [29].


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Table 1. Demographic information on included studies
 
When available, prevalence of risk factors of interest are given in Table 2 separately for each study. These risk factors were: New York Heart Association (NYHA) class III or IV, prior history of hypertension, diabetes, atrial fibrillation, and previous cardiac operation.


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Table 2. Risk factors of patients undergoing mitral valve versus replacement
 
Table 3 shows the summary hazard ratios for the 21 studies used to analyze total survival. These results are displayed graphically in the Forrest plot of Fig. 1 . We note that the summary hazard ratio is 1.58 [95% CI = (1.41, 1.78)], indicating that the replacement group has a 58% increased risk of dying compared to the repair group. The heterogeneity test was not significant (p > 0.20) for each of the four etiology groups tested, as well as for all of the included studies, suggesting that there was no clear evidence of a major discrepancy among the hazard ratios for the studies analyzed.


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Table 3. Meta-analysis results for total survival outcome, comparing repair to replacement, using mixed model, adjusting for etiology
 

Figure 1
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Fig. 1. Comparison of total survival experience in the mitral valve repair and replacement groups obtained from included papers, including summary measures computed overall and by etiologic group using meta-analysis methods.

 
3.2 Results of early mortality
Several papers included in the current meta-analysis were not precisely consistent in their definition of early mortality. For the purpose of the current analysis, outcomes labeled ‘early mortality’ (n = 3), ‘hospital label’ (n = 15), ‘operative mortality’ (n = 6), and ‘30-day mortality’ (n = 2) were combined under the ‘early mortality’ label. We note here that eight of these papers [30–37] were not included in the analysis for total mortality because they lacked information to allow estimation of the hazard ratios, although they did provide information regarding the early mortality endpoint.

When analyzing the 28 studies that provided information on early mortality (Table 4 , Fig. 2 ), there was stronger evidence favoring repair to replacement. The odds of early mortality for replacement were more than twice that for repair [Table 4: OR = 2.24, 95% CI = (1.78, 2.80)]. The benefit of repair rather than replacement was detected in all but for surgery on chordae tendineae sub-group. The heterogeneity test was consistently non-significant (p ≥ 0.30), again suggesting that there was no evidence to indicate that there were important differences among the odds ratios of the analyzed studies.


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Table 4. Meta-analysis results for early mortality outcome, comparing repair to replacement, using mixed model, adjusting for etiology
 

Figure 2
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Fig. 2. Comparison of 30-day survival experience in the mitral valve repair and replacement groups obtained from included papers, including summary measures computed overall and by etiologic group using meta-analysis methods.

 
3.3 Results for re-operation and postoperative thromboembolism
Out of the articles reviewed, only six articles provided information to allow determination of the re-operative hazard ratio for mitral valve replacement relative to repair.

Although the summary hazard ratio of 0.88 suggests that the re-operation rate after replacement may be lower than that following repair, this result was not statistically significant [Fig. 3 : HR = 0.88, 95% CI = (0.48, 1.62)]. The several reasons for re-operation included technical mistakes and valve-related causes (e.g. infection, progression of disease, and thrombosis). From all of the reviewed articles, five reported information for determining the hazard ratio for development of thromboembolism. Summarizing those studies, the hazard for developing post-operative thromboembolism was nearly twice as high for replacement as for repair [Fig. 4 : HR = 1.86, 95% CI = (1.24, 2.81)]. The reasons provided by the authors for thromboembolism were several, including sub-therapeutic anti-coagulation and pro-thrombotic tendencies for bioprosthetic valves.


Figure 3
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Fig. 3. Comparison of re-operation experience in the mitral valve repair and replacement groups obtained from included papers, including summary measures computed overall using meta-analysis methods.

 

Figure 4
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Fig. 4. Comparison of post-operative thromboembolism experience in the mitral valve repair and replacement groups obtained from included papers, including summary measures computed overall and by etiologic group using meta-analysis methods.

 

    4. Discussion
 Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Limitations of meta-analysis
 6. Conclusion
 Appendix A
 Pubmed/Medline
 Embase
 References
 
The current meta-analysis is an attempt to pool basic available information on the outcome experience of the two treatment methods for mitral valve disease, specifically defined as mitral valve repair or mitral valve replacement. Information comparing the two treatments for the specific outcomes of survival, thromboembolism and re-operation was possible. All of the studies included in the present analysis used the repair techniques described by Carpentier [38]. Reported surgical repair procedures differed in some details, according to method of annuloplasty (suture vs. ring), type of ring annuloplasty (flexible or rigid), and chordal modification (transposition, shortening and replacement). The variations were designed to improve the efficacy and minimize valvular incompetence. While the selection of a surgical procedure (repair vs. replacement) is a binary decision, the decision process terminates in the operating room, and at times can be a multifactorial process influenced by surgeon, patient and institution.

The exact natural history of mitral valve regurgitation remains a work-in-progress. Nonetheless, it has been defined by structural context of the valve, etiology of the valvular disease, left ventricular function, age of patients as well as possibly other co-morbidities. Differential patient recruitment and analysis of this risk-mix has hindered widespread interpretation of survival outcome to the surgical community, and hence limiting the provision of possible benefits to patients. In addition, there has been an important evolution in the techniques used for valve repair over time, as has there been an evolution in valve prosthesis generation and design, however, foundation principles of repair used by the authors were always adopted. Nonetheless, these changes could have an affect on long-term results and re-operation rates.

In this study we attempted to determine summaries of the outcomes comparing mitral valve disease repair and replacement for well-defined etiologies of mitral valve disease, using publications which provided comparisons between these two treatment modalities.

4.1 Rheumatic disease of the mitral valve
This meta-analysis showed consistent findings favoring a lower early mortality for the repair group, with the one exception reported by Gometza [37]. This study included a cohort of patients with active rheumatic mitral valve disease [29]. While Antunes [28] and Gometza et al. [37] stated that most re-operations for residual or recurrent mitral valve regurgitation occurred in the first 6 months, Yau et al. [29] reported that most of the re-operations occurred after 72 months. Despite the 10-year difference in the length of follow-up and different geographical location for patient sampling between the Yau et al. and the Antunes studies, a higher re-operative rate for rheumatic heart disease following repair was observed due to active progression of disease in this article.

It is known that repair of rheumatic mitral regurgitation cannot be consistent. If there is significant calcification, fibrosis of the subvalvular apparatus mitral valve replacement has a higher freedom from re-operation than repair or commissurotomy. From the meta-analysis in this study, repair was associated with higher re-operation especially when there was risk for disease progression. The effect of further studies comparing the two techniques in the context of modern antibiotic therapy and prophylaxis will provide more evidence to this statistical summary in the near future.

4.2 Ischemic mitral disease
Ischemic mitral valve disease is mainly a ventricular disease [39]. Current understanding of the mechanism of functional ischemic mitral disease suggests that left ventricular dysfunction alters both annulus and subvalvular apparatus geometry. Annular dilation and lateral displacement of the subvalvular apparatus is common. As the ventricle fails, the progressive dilation of the left ventricle gives rise to regurgitation. Alterations include myocardial thinning and dilation with loss of the aortic-mitral angle. This cascade of events alters the stresses on the valve, leading to long-term valve changes.

Ischemic mitral regurgitation confers a definite risk for higher mortality especially in the context of congestive heart failure determined by poor ventricular function. Certain series reporting on the surgical treatment of ischemic mitral valve disease had a worse long-term survival (43% ± 13%) compared to the structural subset (76% ± 13%) at 5 years [15,40] while others did not detect any major difference [16].

The four reports of treatment outcomes for patients with ischemic valve disease [14–17] individually failed to confirm a significant difference in total survival for repair compared to replacement. However, the current meta-analysis (Table 4) demonstrated that repair of ischemic mitral valve had a lower overall 30-day mortality (OR = 2.01). This suggests that if repair is possible, a trend towards superior peri-operative survival outcomes can be achieved with valve repair as compared to valve replacement.

An attempt to determine the role of repair in ischemic disease may be better explained by more thorough review of the article by Gillinov et al. [41]. The reader should be aware that closer matching between repair and replacement was made through the use of propensity scores. In this study, repair was preferable to replacement for most low risk patient subgroup, but not for high-risk patients. However, given that this type of analysis was not available in the other comparison papers, it was not possible to incorporate the survival statistics from Gillinov et al. in our intended meta-analysis. Furthermore, the literature awaits further comparison studies over a long-term period to determine the roles of repair and replacement on ventricular function and recurrent mitral regurgitation following mitral valve surgery.

Our meta-analysis suggests that when successful repair of the mitral valve is not feasible, mitral valve replacement is the next best choice available to the surgeon. Yet despite the known merits of preserving the subvalvular apparatus [41], a weakness in reporting this information for purposes of meta-analysis still exists.

4.3 Degenerative and myxomatous mitral valve disease
Meta-analysis of the included studies demonstrated superior early and total survival with repair compared to replacement of the mitral valve. The data did not provide sufficient information to carry out a subgroup analysis of bileaflet mitral valve repair compared to monoleaflet repair. And among the included articles equivalent success of posterior repair and bileaflet repair was not observed. Moreover similar finding were not found to be the case for anterior mitral valve disease [13]. The biology and geometry of such subtypes are different from those with only posterior leaflet prolapse. Anterior leaflet degeneration alone, or such degeneration in combination with posterior leaflet, was an independent risk factor for valve-related complications [13]. Lee et al. [11] stated that the main reason for valve replacement rather than repair was major anterior leaflet pathology, as anterior leaflet repair was more difficult. Additionally, patients who had anterior leaflet prolapse had lower survivals and higher re-operative incidence with repair than replacement [10,12].

Ischemic mitral regurgitation must be distinguished from organic mitral valve disease with co-existing coronary artery disease; the latter carries a favorable prognosis. And when degenerative and ischemic heart disease coexisted, Gillinov et al. determined that the type of surgical procedure used did not influence outcome in patients with severe heart failure (EF < 30%) [10]. It was apparent that older patients with preoperative atrial fibrillation and renal dysfunction did worse with replacement after statistical risk adjustment [10]. However, we could not subject our findings to different pathophysiological subgroup analysis—an inherent weakness in consistent reporting this disease subgroup.

We await comparison data over a long calendar period in degenerative mitral valve disease using contemporary methods of diagnosis of ventricular and coronary disease. This will help in determination of best surgical therapy. Until then, the meta-analysis should demonstrate that repair overall remains superior to replacement for all comers of degenerative subgroup.

4.4 Mixed etiology
Survival outcome analysis in this subgroup was based on the aggregation of ‘mixed’ etiologies as documented from the respective available studies. Each of these studies classified the etiology as a mixture of two or more diseases of the mitral valve. Given that we had information from enough patients, we were interested to formulate and systematically analyze this subgroup. Of all the etiologies incorporated into this subgroup, the bulk of the pathology was either degenerative or ischemic mitral valve disease.

The natural history of patients with ischemic mitral regurgitation alone is considerably different from that of patients with concomitant degenerative mitral valve and ischemic heart disease. The poor prognosis with ischemic mitral regurgitation can skew the survival outcome of this mixed category. But what is known is that as people age, the morphology of the degenerating valve changes (e.g., calcification) including left ventricular remodeling, and coronary artery disease development.

Mitral valve repair rather than replacement exhibited a survival advantage in this etiologic group. Among several investigators, mitral valve replacement was found to be a risk factor for late death [26]. While two studies showed that repair was associated with reduced hospital mortality [19,21], that conclusion was not supported in other studies [18,20,23,24,26,36].

4.5 Thromboembolic and re-operative rate following repair compared to replacement
Among the papers citing time to re-operation, we noted that the confidence intervals from all four of the cited studies traversed the ratio of 1, and so are unable to conclude that the hazard ratio detects a statistically significant benefit for either treatment.

However, the post-operative risk of thromboembolism was statistically different for repairs compared to replacements (95% CI: 1.24, 2.81). Only one study [25] demonstrated lower risk of developing thromboembolism among the repair group as compared to the replacement. These findings, however, await adequately powered studies comparing current generation mitral valve replacement designs to repair in the context of therapeutic anti-coagulation tests and other anti-arrhythmia treatment modalities. This will help to provide future directions and stronger conclusions.


    5. Limitations of meta-analysis
 Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Limitations of meta-analysis
 6. Conclusion
 Appendix A
 Pubmed/Medline
 Embase
 References
 
The meta-analysis analyzed over a very long time frame consists of several series of operative techniques that have been a work in progress since 1960. The current work is a meta-analysis of observational studies, not randomized treatment assignment trials. Hence we do not have the information which would allow us to quantify how much of the treatment effect is due to actual treatment differences, and how much is due to selective treatment assignment based on characteristics of individual patients. The surgical spectrum extends from simple techniques, e.g., Kay annuloplasty to complex Carpentier's techniques and chordal replacement. This also holds true for differences in preserving the subvalvular apparatus during mitral valve replacement over the last 30 years. While some data were available for some risk factors in some papers, the reporting of this available information was inconsistent to allow for their consideration as moderators/covariates in a meta-regression analysis. The published data do not allow discrimination by type of repair, and so no independent data for annuloplasty, chordal substitution or adjustment, leaflet surgery alone could be isolated and scrutinized. Finally, the recruited published series did not provide adequate information to consistently determine the benefits and disadvantages of biological versus mechanical mitral valve replacement for different disease subgroups.


    6. Conclusion
 Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Limitations of meta-analysis
 6. Conclusion
 Appendix A
 Pubmed/Medline
 Embase
 References
 
The systematic meta-analyses reported in this study indicate some strong support for repair relative to replacement surgery in patients with non-ischemic mitral valve disease. For ischemic mitral repair, there was a trend toward a lower 30-day mortality that did not achieve statistical significance. No difference in total mortality was observed between repair and replacement of ischemic mitral valve long term. Repair does appear to have a lower risk of development of thromboembolism. However, treatment-related differences in the risk of re-operation remain uncertain and await further longitudinal comparison research studies or trials.

Because the etiology of mitral valve disease is the predominant predictor of the outcome of treatment, documentation of the etiologic categories and modality of surgical therapy should be more comprehensive and detailed to attempt to reduce the current limitations in future publications.


    Appendix A
 Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Limitations of meta-analysis
 6. Conclusion
 Appendix A
 Pubmed/Medline
 Embase
 References
 


    Pubmed/Medline
 Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Limitations of meta-analysis
 6. Conclusion
 Appendix A
 Pubmed/Medline
 Embase
 References
 
#1
Search ‘mitral valve repair’

#2
Search ‘ mitral valve replacement’

#3
Search #1 AND #2

#4
Search #1 AND #2, Field: All Fields, Limits: English

#5
Search #4 AND (human[mh] OR premedline[sb] OR publisher[sb]), Limits: English

#6
Search #5 NOT (letter[pt] OR news[pt] OR comment[pt] OR editiorial[pt] OR case report[mh]), Limits: English

#7
Search #6 AND (randomized controlled trial[pt] OR controlled clinical trial[pt] OR randomized controlled trials[mh] OR random allocation[mh] OR double-blind method[mh] OR single-blind method[mh] OR clinical trial[pt] OR clinical trials[mh] OR (‘clinical trial’[tw] OR ((singl*[tw] OR doubl*[tw] OR trebl*[tw] OR tripl*[tw]) AND (mask*[tw] OR blind*[tw])) OR ‘latin square’[tw] OR placebos[mh] OR placebo*[tw] OR random*[tw] OR research design[mh:noexp] OR comparative study[mh] OR evaluation studies[mh] OR follow-up studies[mh] OR prospective studies[mh] OR cross-over studies[mh] OR control*[tw] OR prospective*[tw] OR volunteer*[tw] OR sham OR meta-analysis[mh] OR meta-analysis[pt] OR ‘meta-analysis’[tw] OR outcomes research[mh] OR multicenter study[pt]), Limits: English

#8
Search #6 NOT #7, Limits: English

#9
Search cox jl [au], Limits: English

#10
Search cox jl [au] AND maze, Limits: English


    Embase
 Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Limitations of meta-analysis
 6. Conclusion
 Appendix A
 Pubmed/Medline
 Embase
 References
 
S1
Mitral valve disease

S2
Heart Mitral Valve /De from 73

S3
Mitral valve ! /DE FROM 155

S4
S1 OR S2 OR S3

S5
S4 AND Mitral valve repair AND mitral valve replacement


    References
 Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Limitations of meta-analysis
 6. Conclusion
 Appendix A
 Pubmed/Medline
 Embase
 References
 

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