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Original Investigation
September 6, 2017

Survival and Cardiovascular Outcomes of Patients With Secondary Mitral RegurgitationA Systematic Review and Meta-analysis

Author Affiliations
  • 1Division of Cardiology, Department of Medicine, Baylor University Medical Center, Baylor Heart and Vascular Hospital, Dallas, Texas
  • 2Currently with Division of Cardiology, Department of Medicine, Università Degli Studi di Napoli Federico II, Naples, Italy
  • 3Department of Cardiothoracic Surgery, The Heart Hospital Baylor Plano, Plano, Texas
  • 4Division of Cardiology, Department of Medicine, University of Texas Southwestern Medical Center, Dallas
  • 5Division of Cardiology, Department of Medicine, Università Degli Studi di Napoli Federico II, Naples, Italy
JAMA Cardiol. Published online September 6, 2017. doi:10.1001/jamacardio.2017.2976
Key Points

Question  What is the association between secondary mitral regurgitation and morbidity and mortality of patients with left ventricular dysfunction?

Findings  In this meta-analysis of 53 studies and 45 900 patients, secondary mitral regurgitation in patients with ischemic or idiopathic cardiomyopathies was associated with a significant worsening of survival. Although secondary mitral regurgitation is known to be dynamic and load dependent, it was consistently associated with higher mortality regardless of its severity.

Meaning  Secondary mitral regurgitation may be a strong marker of adverse outcomes in patients with left ventricular dysfunction.


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.