Key result
Residual moderate SMR after GDMT is linked to ~69% higher death or HF hospitalization.
Why the study?
While severe secondary mitral regurgitation (SMR) worsens outcomes in heart failure, the prognostic significance of moderate SMR after optimization of guideline-directed medical therapy (GDMT) remained uncertain.
Does residual moderate secondary mitral regurgitation after 12 months of optimized guideline-directed medical therapy increase the risk of all-cause death or first heart failure hospitalization compared to no/mild secondary mitral regurgitation in ambulatory heart failure patients?
Cohort (n=2,468)
Does residual moderate secondary mitral regurgitation after 12 months of optimized guideline-directed medical therapy increase the risk of all-cause death or first heart failure hospitalization compared to no/mild secondary mitral regurgitation in ambulatory heart failure patients?
In ambulatory heart failure patients receiving optimized guideline-directed medical therapy, residual moderate secondary mitral regurgitation at 12 months is independently associated with increased mortality and heart failure hospitalization, carrying a prognostic impact comparable to severe secondary mitral regurgitation.
Residual moderate SMR after GDMT may refine risk stratification in ambulatory HF; leaves open whether targeted reduction improves outcomes.
Background Secondary mitral regurgitation (SMR) frequently develops due to left ventricular remodeling in patients with heart failure with reduced ejection fraction (HFrEF). While severe SMR worsens outcomes in HF, the prognostic significance of moderate SMR after optimization of guideline-directed medical therapy (GDMT) remains uncertain. Methods We analyzed 2,468 ambulatory HF patients who underwent paired transthoracic echocardiography at baseline and after 12 months of optimized GDMT. Mean baseline LVEF was 36.1% ± 13.6%. SMR severity at 12 months was classified as none/mild, moderate, or severe. The primary endpoint was the composite of all-cause death or first heart failure hospitalization (HFH). Secondary endpoints included all-cause mortality and recurrent HFHs. Median follow-up after the 12-month echocardiogram was 6.9 years. Results At 12 months of optimized GDMT, 80.5% of patients had no/mild SMR, 15.6% had moderate SMR, and 3.9% had severe SMR. Compared with no/mild SMR, both moderate and severe SMR at 12 months were independently associated with a higher risk of the primary composite endpoint (moderate: hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.47–1.95; severe: HR 1.81, 95% CI 1.44–2.29). Moderate SMR was also associated with increased all-cause mortality (HR 1.54, 95% CI 1.32–1.79) and recurrent HFHs (incidence rate ratio [IRR] 2.17, 95% CI 1.81–2.60). Among patients with moderate SMR at 12 months, outcomes did not differ according to baseline SMR severity. Conclusions In this large-scale study, in a predominantly HFrEF population receiving contemporary GDMT, residual moderate SMR at 12 months was common and was independently associated with mortality and HFH, with a prognostic impact comparable to severe SMR.
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Molina et al. (2026) conducted a cohort in Heart failure with secondary mitral regurgitation (n=2,468). Moderate secondary mitral regurgitation at 12 months vs. No/mild secondary mitral regurgitation at 12 months was evaluated on Composite of all-cause death or first heart failure hospitalization (HR 1.69, 95% CI 1.47-1.95). Residual moderate secondary mitral regurgitation after 12 months of GDMT was independently associated with higher risk of all-cause death or HF hospitalization vs no/mild SMR (HR 1.69, 95% CI 1.47–1.95).
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