Survival and Cardiovascular Outcomes of Patients With Secondary Mitral Regurgitation: A Systematic Review and Meta-analysis

Abstract

Importance: The outcomes of patients with left ventricular (LV) dysfunction and secondary mitral regurgitation (SMR) are still controversial.

Objective: To clarify the role of SMR in the outcomes of patients with ischemic or idiopathic cardiomyopathies.

Data sources: MEDLINE, ISI Web of Science, and Scopus databases were searched for studies published up to March 2017.

Study selection: Studies reporting data on outcomes in patients with SMR were included. Duplicate publication data, studies lacking data on SMR grade and its correlation with outcomes, mixed data on SMR and primary mitral regurgitation, studies not clearly reporting the outcome of interest, and studies with fewer than 100 patients were excluded. Of the initial 3820 articles identified, 1.4% were finally included.

Data extraction and synthesis: The study met PRISMA requirements. Two of us independently screened articles for fulfillment of inclusion criteria.

Main outcomes and measures: The primary outcome, set after data collection, was the incidence of all-cause mortality in patients with and without SMR. Secondary outcomes included hospitalization for heart failure (HF), cardiac mortality, and a composite end point of death, HF hospitalization, and cardiac transplant.

Results: Fifty-three studies and 45 900 patients were included in the meta-analysis. The mean (SD) length of follow-up was 40.8 (22.2) months. In 26 of 36 studies reporting LV function by SMR grade, increasing SMR severity was associated with worse LV function. When SMR was categorized as present or absent, all-cause mortality was significantly higher in the patients with SMR (17 studies, 26 359 patients; risk ratio [RR],1.79; 95% CI, 1.47-2.18; P < .001, I2 = 85%); when SMR was qualitatively graded, the incidence of all-cause mortality was significantly increased in patients having any degree of SMR compared with patients not having SMR (21 studies, 21 081 patients; RR, 1.96; 95% CI, 1.67-2.31; P < .001, I2 = 74%). Finally, when SMR was quantitatively graded, it remained associated with an increased all-cause mortality rate (9 studies, 3649 patients; RR, 1.97; 95% CI, 1.71-2.27; P < .001, I2 = 0%). Moreover, SMR was associated with an increased risk of hospitalization for HF (16 studies, 10 171 patients; RR, 2.26; 95% CI, 1.92-2.67; P < .001, I2 = 41%), cardiac mortality (12 studies, 11 896 patients; RR, 2.62; 95% CI, 1.87-3.69; P < .001, I2 = 74%), and death, HF, and transplant (11 studies, 8256 patients; RR, 1.63; 95% CI, 1.33-1.99; P < .001, I2 = 78%).

Conclusions and relevance: To our knowledge, this study is the first meta-analysis to date to demonstrate that SMR, even when mild, correlates with adverse outcomes in patients with ischemic or idiopathic cardiomyopathies. Because SMR is an intrinsic consequence of LV dysfunction, causality between SMR and mortality should not be implied.

Figure 1.. Meta-analysis Flowchart

Figure 2.. Relationship Between Left Ventricular Ejection Fraction (LVEF) and Secondary Mitral Regurgitation (SMR) Grade

The variation in LVEF is shown according to different grades of SMR. The solid line represents averaged LVEF values for the 36 studies reporting the data; dotted lines represent the 95% CIs.

Figure 3.. Influence of Secondary Mitral Regurgitation (SMR) on All-Cause Mortality in Studies Defining SMR as Present or Absent

Shown are random-effects risk ratios and 95% CIs for all-cause mortality according to the SMR detection method used. NA indicates not applicable.

Figure 4.. Influence of Secondary Mitral Regurgitation (SMR) on All-Cause Mortality in Studies Grading SMR Qualitatively

Shown are random-effects risk ratios and 95% CIs for all-cause mortality according to SMR grade. NA indicates not applicable.

Figure 5.. Influence of Secondary Mitral Regurgitation (SMR) on All-Cause Mortality in Studies Grading SMR Quantitatively

Shown are random-effects risk ratios and 95% CIs for all-cause mortality according to SMR grading. The cutoff for EROA is 0.2 cm², and the cutoff for regurgitant volume is 30 mL. EROA indicates effective regurgitant orifice area; NA, not applicable; VCW, vena contracta width.