Prognosis of combined moderate mitral and aortic regurgitation and isolated severe aortic regurgitation

Introduction There is limited evidence to guide the management of patients with combined moderate valvular regurgitant lesions. The prognostic significance of moderate mitral regurgitation (MR) and aortic regurgitation (AR) remains poorly defined. Purpose This study aimed to evaluate long-term mortality in patients with combined moderate MR and AR compared with patients with severe AR and no significant MR. Methods This retrospective observational cohort study included patients evaluated at Sheba Medical Center between 2009 and 2025. Patients with native valves and combined moderate MR and AR, as well as patients with severe AR without significant MR, were identified. Patients with prosthetic valves were excluded. The primary outcome was all-cause mortality. Survival was assessed using Kaplan-Meier analysis and Cox proportional hazards models. Multivariable models were adjusted for age, sex, and left ventricular ejection fraction (LVEF), with a fully adjusted model additionally including systolic pulmonary artery pressure (SPAP) and left atrial diameter. Results The study population comprised 780 patients: 230 with combined moderate MR and AR and 550 with severe AR. Overall, 71% were men. Median age was 63 years (IQR 47 to 75), and median LVEF was 55% (IQR 45 to 60). Compared with patients with severe AR, those with combined disease were older, more frequently female with a higher incidence of risk factors. Moreover, lower LVEF, larger left atrial diameter, and higher SPAP were noted in the mixed-disease population (p<0.001 for all; Table 1). During a median with more follow-up of 5 years, 252 deaths occurred (32%). Mortality was markedly higher in patients with combined moderate MR and AR compared with severe AR (57% vs. 26%, p<0.001; Figure 1). In Cox analysis, combined moderate MR and AR was associated with increased mortality in the unadjusted model and remained independently associated with mortality after adjustment for age and sex (HR 1.6, 95% CI 1.2 to 2.1), after additional adjustment for LVEF (HR 1.5, 95% CI 1.1 to 2.2), and in the fully adjusted model including SPAP and left atrial diameter (HR 1.5, 95% CI 1.1 to 2.1). Findings were consistent across all models (p<0.05 for all). Conclusion Combined moderate MR and AR is associated with significantly increased mortality compared with isolated severe AR. These findings highlight the adverse prognostic impact of dual moderate regurgitant lesions and suggest that patients with combined moderate regurgitation may benefit from closer surveillance and earlier therapeutic consideration.