Prognostic impact of mild aortic regurgitation in moderate aortic stenosis: a mixed valve disease phenotype

Introduction Moderate aortic stenosis (MAS) is traditionally considered clinically stable and managed conservatively. However, many patients present concomitant mild aortic regurgitation, resulting in mixed aortic valve disease. Its impact on outcomes and progression in MAS is not well established and is not incorporated into current risk stratification. Purpose To evaluate the prognostic impact of concomitant mild aortic regurgitation in patients with echocardiographically defined MAS. Methods This retrospective study included asymptomatic adults with isolated MAS or MAS with mild aortic regurgitation and preserved ejection fraction (>50%). Patients with cardiomyopathies or moderate-to-severe valvular disease were excluded. The endpoint was time to first occurrence of heart failure hospitalization, valvular intervention (balloon valvuloplasty, surgical replacement, or transcatheter implantation), or death. Cox models adjusted for sex, age, hypertension, diabetes, prior atrial fibrillation, chronic kidney disease, and peak aortic valve gradient (continuous variables) assessed independent associations. Proportional hazards were verified. Results A total of 663 patients were included; median follow-up was 4.2 years. Median age was 80 years (IQR 75–85), and 46% were male (Table 1). During follow-up, 277 patients (42%) reached the endpoint: 66 (10%) heart failure hospitalizations, 108 (16%) valvular interventions, and 103 (16%) deaths. Median event-free survival was 5 years (95% CI 4.7–5.4), corresponding to an incidence rate of 13 events per 100 patient-years. Among patients with events, 53% progressed to severe AS and 19% developed moderate aortic regurgitation. Mixed aortic valve disease was associated with worse outcomes than isolated MAS (unadjusted HR 1.38, 95% CI 1.07–1.77, p=0.013; adjusted HR 1.31, 95% CI 1.02–1.69; p=0.036; Figure 1). Conclusion In MAS, concomitant mild aortic regurgitation independently identifies higher risk of progression, intervention, or death. Mixed moderate aortic valve disease represents a distinct adverse phenotype that may improve risk stratification and follow-up.