Prognostic significance of functional mitral regurgitation in heart failure patients undergoing cardiac resynchronization therapy

Introduction Functional mitral regurgitation (FMR) is common in heart failure (HF) patients undergoing cardiac resynchronization therapy (CRT). Although CRT can improve FMR, the long-term evolution and prognostic significance of FMR post-CRT remain unclear. Purpose This study aims to evaluate the prevalence, evolution, and prognostic impact of FMR in HF patients undergoing CRT. Methods We conducted a single-center retrospective study of consecutive patients who underwent CRT implantation between January 2017 and April 2024. Echocardiographic assessments were performed at baseline and 6-12 months post-CRT. FMR severity was classified as mild, moderate or severe, according to quantitative and qualitative methods, and FMR improvement was defined as a reduction of ≥1 grade in MR class. Patients with a ≥15% reduction in left ventricle end-systolic volume (LVESV) or a ≥10% increase in left ventricle ejection fraction (LVEF) were considered responders to CRT. The primary endpoint was major adverse cardiac events (MACE), including cardiovascular mortality or HF hospitalization. Results A total of 206 patients (median age 74 [IQR 66-79] years, 68.4% male, 67.5% non-ischemic etiology, 88.7% NYHA class II-III) were evaluated. At baseline, FMR was present in 152 patients (55,3% mild, 34,2% moderate, 10,5% severe), with a total of 68 patients having significant FMR (moderate or severe). Significant FMR was more common in older patients (74.0 vs 71.5 years, p=0.012) and women (54.9% vs 36.0%, p=0.024). At 1-year follow-up, FMR improved in 59.6% of patients with significant FMR. As expected, these patients exhibited better CRT response (90.3% vs 60.0%, p=0.015), lower LVESV (65 [43-96] ml vs 128 [101-169] ml, p<0.001) and lower proBNP levels (567 [277-1692] pg/mL vs 4071 [1203-9351] pg/mL, p<0.001). During a mean follow-up of 35±24 months, 18 (8.7%) patients died from cardiovascular causes and 44 (21.4%) experienced MACE. Persistent significant FMR post-CRT was associated with an increased risk of MACE, after adjusting for CRT response (HR: 4.369, 95% CI 1.425–13.398, p=0.010). Conclusion In this study, 59.6% of patients experienced FMR improvement, which correlated with better therapeutic response and prognosis. In contrast, persistent significant FMR post-CRT was associated with a higher incidence of MACE, regardless of CRT responsiveness. These findings highlight the need for closer follow-up and the importance of considering valvular interventions in patients with persistent FMR post-CRT.