Outcome of Functional Mitral Regurgitation Associated with Heart Failure with Mildly Reduced or Preserved Ejection Fraction.

While functional mitral regurgitation (FMR) is frequently observed in patients with heart failure (HF), its underlying mechanisms and clinical significance may differ among various HF subgroups. Data regarding the clinical significance of FMR in heart failure with mildly reduced ejection fraction (HFmrEF) and heart failure with preserved ejection fraction (HFpEF) are limited. We tried to investigate the predominant mechanisms of FMR in HFmrEF and HFpEF and evaluate the impact of FMR on long-term outcomes in these two groups. From 2013 to 2022, 407 consecutive patients with HFmrEF or HFpEF with moderate-to-severe FMR were evaluated prospectively. FMR was classified as either ventricular functional mitral regurgitation (VFMR) or atrial functional mitral regurgitation (AFMR). The primary endpoint was a composite of cardiovascular mortality or hospitalization due to HF, and secondary endpoints included significant MR progression and mitral valve intervention. VFMR was predominant in patients with HFmrEF (87.8%), while AFMR was more common in patients with HFpEF (83.3%, P < 0.001). The incidence of the primary endpoint was similar between the two groups (29.5% for HFmrEF vs. 30.3% for HFpEF, P = 0.865). However, MR progression (35.9% vs 21.2%, P = 0.002) and mitral valve interventions (17.5% vs. 5.1%, P < 0.001) were more common in HFpEF. MR progression was independently associated with the primary endpoint in both HFmrEF (HR: 3.014, 95% CI: 1.586-5.727; P = 0.001) and HFpEF (HR: 1.737, 95% CI: 1.055-2.860; P = 0.030). Among patients with HFmrEF or HFpEF with moderate-to-severe FMR, VFMR and AFMR were the dominant mechanisms of FMR in HFmrEF and HFpEF, respectively. Progression of MR was associated with cardiovascular events in both groups. A comprehensive understanding of the distinct mechanisms of FMR in these HF subgroups may guide tailored therapeutic strategies for managing FMR.