Short-Term and Long-Term Survival After Revascularization with or without Mitral Valve Surgery of Patients with Ischemic Mitral Valve Regurgitation: A Meta-Analysis

Background

With the current understanding of the mechanism of coronary artery disease, acute ST segment elevation myocardial infarction, non-ST segment elevation myocardial infarction, and unstable angina can be classified as acute coronary syndrome (ACS). Acute myocardial infarction (AMI) is one of the most common cardiovascular diseases, having the highest morbidity and mortality in the world [1–3]. In the year 2010, more than 6 million patients were hospitalized for treatment of AMI in the United States [4]. Owing to China’s aging population, the incidence rate of this disease has increased drastically. According to official estimates, more than 16 million people annually will succumb to AMI by 2020. Moreover, this number is estimated to rise to 23 million annually by 2030 [5]. Patients suffer AMI due to myocardial necrosis, an ischemic injury that leads to the deformation of mitral annulus. Consequently, the function of papillary muscles becomes impaired. In some cases, the papillary muscles may even rupture. All these adverse events lead to ischemic mitral valve regurgitation (MVR). Ischemic MVR persists in 20% to 30% of patients, even after an AMI [6]. The effects of mild ischemic MVR include left ventricular remodeling and left ventricular enlargement. In severe cases, it can lead to left ventricular dysfunction and left ventricular failure, which is a life-threatening condition. When ischemic MVR is severe, the survival rate is just 1 year in more than 60% cases [7].

Coronary artery bypass grafting (CABG) and mitral valve repair or replacement (MVRR) surgery are carried out on patients who develop significant ischemic MVR after myocardial infarction. These surgical treatments can remove coronary artery blockages and MVR simultaneously, helping restore normal left ventricle geometry. According to current guidelines, surgical intervention is the conventional method for treating ischemic MVR with an ejection fraction (EF) of 30% or greater (class I recommendation); a class II b recommendation is when the EF is 30% or less [8]. However, several studies have reported that the survival rate is not significantly different when patients with ischemic MVR are treated with MVRR and CABG [9–14]. In other words, medical researchers are still dubious that MVRR surgery is suitable for treating patients who develop ischemic MVR after myocardial infarction. In this study, we pooled results of recent studies and performed a meta-analysis to investigate the efficacy and patient prognosis of CABG combined with or without MVRR.

Material and Methods

DATA SOURCE:

A comprehensive search was performed in OvidSP, PubMed, Cochrane Library, and Embase to access medical literature from January 1986 to March 2015. We identified and reviewed all the studies that described the trials comparing the efficacy of only CABG with the combined treatment of CABG and MVRR, which were used to treat patients with moderate to severe ischemic MVR (>2+ grade) after ACS. We reviewed both retrospective observational and prospective randomized studies. In PubMed, search terms were presented in text string format as follows: ischemic mitral valve regurgitation or ischemic mitral valve insufficiency) and (mitral valve repair or mitral valve annuloplasty or mitral valve replacement) and (coronary bypass grafting or surgical revascularization) and (acute myocardial infarction or acute coronary syndrome or ACS).

We performed the meta-analysis to compare the differences in the short-term (mean hospital mortality rate) and long-term survival rates of patients treated with CABG only and those treated with both CABG and MVRR. Secondary outcomes were compared with the preoperative and postoperative degree of MVR, left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), and New York Heart Association (NYHA) class.

EXCLUSION CRITERIA:

The criteria for excluding the articles were as follows: (1) no direct comparison between only CABG and the combined technique of CABG and MVRR; (2) etiologies for MVR were myxomatous, rheumatic, infectious, congenital, or degenerative; (3) mitral valve regurgitation was accompanied by mitral valve prolapse, tendon rupture, or papillary muscle rupture; (4) no survival curves or hazard ratios; (5) articles were not written in English.

DATA QUALITY EVALUATION:

The quality of each included study was evaluated by 2 researchers who cross-checked the extracted data from the selected case control study or randomized controlled trials. If they had differences of opinion, then they sought the opinion of a third researcher.

STATISTICAL ANALYSIS:

Baseline characteristics were described using proportions of discrete variables, while medians and standard deviation were calculated for continuous variables. To compare discrete variables of different groups, the Pearson χ² test was performed. To compare continuous variables of different groups, the Kruskal-Wallis test was conducted. In each individual study, the odds ratio was calculated for short-term survival, while hazard ratios were calculated for determining long-term survival. In each study, the survival curves compared the efficacy of only CABG with the combined technique of CABG and MVRR. These survival curves were checked and evaluated for time intervals of 2, 3, or 6 months depending on their mean follow-up years.

The heterogeneity of patients and treatment procedures were incorporated in the random-effects model, including the study of statistical data and the 95% confidence intervals (CIs). The heterogeneity of patients was examined using Cochran’s Q test and the I2 statistic. The degree of heterogeneity was divided into 3 grades: low (<25%), moderate (25%–75%), and high (>75%) [15]. All the values were considered to be statistically significant when P<0.05. Funnel plots were examined to evaluate potential publication bias. The results of the meta-analysis were represented in forest plots. Publication bias was depicted in funnel plots. Meta-analysis was conducted using Review Manager, version 5.3 (The Cochrane Collaboration, Update Software, Oxford).

Results

DEMOGRAPHIC CHARACTERISTICS:

A total of 3120 patients were included in all the studies that met our inclusion criteria. Among them, 2545 (82%) patients were treated with only CABG, while 575 (18%) patients underwent both CABG and MVRR. Table 1 presents the basic clinical characteristics of patients included in the analysis. The average age of the study population was 67 years; the patients were in the age group of 61 to 70 years. The mean percentage of male patients was 61%. In the analyzed studies, the proportion of male patients varied from 26% to 81%. An average of 35% patients also had diabetes. The study presented by Kang [4] had no published data on the number of patients with hypertension. However, in other studies more than half of the included patients also suffered from hypertension. The mean number of graft vessels was 3.3. An average of 65% patients had a history of myocardial infarction.

Preoperative and postoperative conditions are presented in Table 2. The degree of MVR was more than 2+ in all the patients that were included preoperatively. After performing revascularization surgery, the degree of residual MVR in patients treated with only CABG was less than 1+, but the degree of MVR was lower in patients treated with both CABG and MVRR (0.9±0.6 vs. 0.6±0.6). Nevertheless, there was no significant difference between the 2 groups [11]. CABG combined with MVRR was better than only CABG in reducing the mean LVESV and NYHA classes [11,17], but only 1 study indicated that there were significant differences between the 2 surgical procedures [17]. In the improvement of the mean LVEF, the results of the 2 surgical procedures were similar [11], except for 1 study showing no improvement in CABG combined with MVRR [18].

SHORT-TERM SURVIVAL:

Short-term survival was defined as patients who died within 30 days despite being admitted in a hospital. In 3 studies, a total of 320 patients had hospital mortality [11,17,18]. The total hospital mortality rate in patients treated with both CABG and MVRR techniques was 4.8% (5/104), which was higher than the 2.8% hospital mortality rate of patients treated with only CABG (6/216). However, there was no significant difference in the hospital mortality rates of these patients (P=0.358). Odds ratio (OR) range varied from 1.00 (no favoring) [17] to 8.47 (favoring CABG only) [11]. We also assessed the heterogeneity of patients included in the studies (chi2=1.24, P=0.54, and I2=0%). This indicates that the heterogeneity was null. The pooled OR was 2.54 (95% CI, 0.65–9.95; P=0.18) (Figure 2), indicating that the hospital mortality in patients treated with both CABG and MVRR techniques was similar to that witnessed in patients treated with only CABG. Through the short-term funnel plots, we deduced that there was no publication bias in the included studies (Figure 3).

LONG-TERM SURVIVAL:

Three studies provided important information of survival curves [9,11,16]. The shortest observation period of these studies was approximately 5 years [9], while the longest observation period was over 10 years [16]. Because these studies were not randomized controlled trials, the chosen survival curves were adjusted before analyzing. The study hazard ratios varied from 1.22 [9] to 5.16 [11] (Figure 4). While assessing potential heterogeneity, (Chi2=2.55 and P=0.28) we found that there was no significant heterogeneity in patients included in various studies. Furthermore, I2=21%, so the variability between these studies was due to low heterogeneity. In summary, the hazard ratio was 1.34 (95% CI 1.15–1.58), P=0.003. The pooled study population showed that compared to the CABG group, long-term survival was more pronounced in the group treated with both CABG and MVRR techniques. Moreover, there was no publication bias in the included articles (Figure 5).

Discussion

LIMITATIONS:

There are several limitations to our study. The search method was very limited and failed to include all the published literature, including published papers of organizations and conferences. We only reviewed manuscripts that were published in English, so papers published in other languages were not included. Therefore, we may have missed out some important findings of research studies published in other languages.

The keyword search included ischemic mitral valve regurgitation, functional mitral valve regurgitation, ischemic mitral valve insufficiency and mitral valve repair, mitral valve annuloplasty, mitral valve replacement or MVS, and coronary bypass grafting or surgical revascularization. Although these keywords were consistent with other studies [36–38], we also included acute myocardial infarction or acute coronary syndrome. Therefore, our selected literature may not be same as the meta-analysis of 2009 [13]. Thus, different studies were included and reviewed in our meta-analysis.

Most of the studies that we reviewed were not randomized controlled trials. Most patients with serious MVR were treated with both CABG and MVRR techniques, so there could be bias in selected population.

Myocardial viability also plays an important role in the surgical management of ischemic MVR. After performing the CABG technique, the dysfunctional yet viable myocardium undergoes significant recovery. This improves the functionality of ischemic MVR. We did not perform routine tests to determine the myocardial viability of patients. In the near future, studies must try to determine the relationship between viability and ischemic MVR.

Conclusions

The patients with ACS complicated with ischemic MVR can achieve reduced mitral regurgitation and improved left ventricular function through either only CABG or both CABG and MVRR surgery. There is still no evidence that the long-term survival rate of CABG combined with MVRR is superior to that of only CABG, while the hospital mortality and secondary outcomes were similar in both. We expect that the new technology of mitral valve surgery can bring about some changes. The optimal surgery plan still needs to be adjusted according to the individual situation of the patient.