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Secondary mitral regurgitation may not cause death on its own per se, but it is nevertheless a beacon of left ventricular (LV) dysfunction, researchers said.

In a meta-analysis of 53 studies with 45,900 patients included, -- even mild cases -- whether studies categorized it on a present-or-absent basis (RR 1.79, 95% CI 1.47-2.18) or had it graded by severity (RR 1.96, 95% CI 1.67-2.31), according to Paul Grayburn, MD, of Baylor University Medical Center in Dallas, and colleagues.

Reporting online in JAMA Cardiology, the authors said these factors are also correlated with secondary mitral regurgitation:

• Heart failure hospitalization (RR 2.26, 95% CI 1.92-2.67)
• Cardiac mortality (RR 2.62, 95% CI 1.87-3.69)
• Combined death, heart failure hospitalization, and cardiac transplant (RR 1.63, 95% CI 1.33-1.99)

"To our knowledge, this study is the first meta-analysis to date to demonstrate that secondary mitral regurgitation, even when mild, correlates with adverse outcomes in patients with ischemic or idiopathic cardiomyopathies," Grayburn's group commented.

"In studies with a higher prevalence of New York Heart Association class III or IV heart failure symptoms and in studies with longer follow-up, the relationship between secondary mitral regurgitation and all-cause mortality was attenuated," the authors admitted. "A potential explanation is that, in highly symptomatic patients, heart failure or worsened LV systolic and diastolic function may dominate the prognosis relative to mitral regurgitation severity."

"This is a critical point because, by definition, secondary mitral regurgitation is a consequence of LV dysfunction. Therefore, secondary mitral regurgitation may be a surrogate for more extensive LV dysfunction or heart failure symptoms rather than causal."

The investigators found that increasing severity of secondary mitral regurgitation -- a result of underlying LV dysfunction and/or mitral annular dilation disrupting otherwise normal mitral valve leaflets -- corresponded with a drop in LV ejection fraction.

Grayburn's meta-analysis supports "the concept that secondary mitral regurgitation identifies higher-risk patients with ischemic or dilated cardiomyopathy," agreed JAMA Cardiology editors Robert O. Bonow, MD, MS, of Northwestern University Feinberg School of Medicine in Chicago, and Patrick T. O'Gara, MD, of Boston's Brigham and Women's Hospital.

Yet, "whether secondary MR is merely a marker of severity of LV dysfunction or actually contributes to declining LV function in some patients -- and is thus a target for therapy -- remains uncertain," they said in their .

"We know that guideline-directed medical therapy is associated with improved survival rates among patients with LV dysfunction, and the associated reverse remodeling reduces the severity of secondary mitral regurgitation. This supports current recommendations that the principal management of secondary mitral regurgitation is to first treat the underlying LV dysfunction with guideline-directed medical therapy including, in appropriate patients, cardiac resynchronization therapy."

More research is needed to determine how surgical or transcatheter procedures compare against guideline-directed medical therapy alone for improving outcomes, Bonow and O'Gara concluded.

The present study included individuals who were followed for 40.8 months on average. Those with secondary mitral regurgitation were diagnosed via left ventriculography or echocardiography.

That valve disease was detected with either of two modalities, and graded in a variety of ways across studies, was a major limitation. In addition, most studies lacked information on LV volumes, sphericity, and regional wall motion.

"Current guidelines recommend integration of multiple qualitative and quantitative parameters to determine severity as opposed to simple eyeballing of mitral regurgitation jet size. However, this recommendation is seldom followed in practice and was not specified in the Methods section of most of the studies included in this meta-analysis, which could explain the high disparity in the results," Grayburn and colleagues added.