Secondary Mitral Regurgitation Trajectories and Prognosis With Intensification of Guideline-Directed Medical Therapy in Heart Failure

Background Secondary mitral regurgitation (SMR) frequently accompanies heart failure with reduced ejection fraction (HFrEF) and may regress with guideline-directed medical therapy (GDMT). However, real-world data on SMR trajectories and prognostic implications remain scarce. Objectives The purpose of this study was to characterize 12-month trajectories of SMR under optimized GDMT in ambulatory patients with HFrEF and to evaluate the long-term prognostic impact. Methods The authors prospectively studied 2,254 ambulatory HFrEF patients who underwent baseline and 12-month transthoracic echocardiography (TTE), excluding those with mitral valve interventions. The primary endpoint was all-cause mortality, and the secondary endpoint was a composite of all-cause mortality or heart failure hospitalization (HFH) over a median follow-up period of 4.5 years after the 12-month TTE. Results At baseline, 67.6% of patients had none or mild (nonsignificant) SMR, 25.2% had moderate SMR, and 7.3% had severe SMR. After 12 months of optimized GDMT, the distribution shifted ( P < 0.001): 79.5%, 16.5%, and 4.2% had nonsignificant, moderate, and severe SMR, respectively. Among the 731 patients with significant SMR (moderate/severe) at baseline, 57.5% improved to nonsignificant SMR. Improvement from significant to nonsignificant SMR within 12 months was associated with a favorable long-term prognosis, comparable to patients who consistently had nonsignificant SMR. Conversely, patients with persistent significant SMR had a higher risk of all-cause mortality (HR: 1.60; 95% CI: 1.36-1.89; P < 0.001) and the composite outcome of mortality or HFH (HR: 1.59; 95% CI: 1.36-1.85; P < 0.001). Conclusions In this real-world HFrEF cohort, optimizing GDMT use led to SMR improvement in over half of patients with moderate or severe SMR. Nevertheless, both persistent moderate and severe SMR were associated with poor outcomes, underscoring the known benefit of mitral intervention in severe SMR and its potential in moderate SMR.