Prognostic Implications of Mitral Regurgitation Across Hypertrophic Cardiomyopathy Subtypes: A Report From REVEAL-HCM Study

BACKGROUND: Mitral regurgitation (MR) is a frequent comorbidity in patients with hypertrophic cardiomyopathy (HCM), which includes distinct subtypes with various characteristics. However, data on the long-term prognostic impact of MR and its progression or regression over time remain limited, particularly across individual HCM subtypes. METHODS: Patients with HCM were retrospectively included from a Japanese multicenter registry and compared by MR severity (moderate or greater versus mild or less) within each subtype: hypertrophic obstructive cardiomyopathy (HOCM), end-stage HCM (ES-HCM), and other HCM (including nonobstructive, midventricular obstruction, and apical HCM). RESULTS: Among 3602 patients (HOCM: n=837; ES-HCM: n=275; other HCM: n=2490), the prevalence of moderate or greater MR was highest in HOCM (36.3%), followed by ES-HCM (21.5%) and other HCM (8.5%). During a median follow-up of 5.3 (interquartile range, 2.1–9.3) years, the cumulative 5-year incidence of all-cause death or heart failure hospitalization was not significantly different between the moderate or greater MR and mild or less MR groups in HOCM (14.6% versus 12.4%; P =0.35) or ES-HCM (60.7% versus 54.7%; P =0.84). After adjustment for clinical covariates, no significant association was observed in either subtype (HOCM: hazard ratio, 1.13 [95% CI, 0.79–1.60], P =0.51; ES-HCM: hazard ratio, 0.84 [95% CI, 0.55–1.28], P =0.42). In contrast, in other HCM, moderate or greater MR was significantly associated with the higher 5-year cumulative incidence of all-cause death or heart failure hospitalization (34.2% versus 13.9%, P <0.001), which remained significant after adjustment, with a significant interaction (hazard ratio, 1.45 [95% CI, 1.09–1.91], P =0.01; P interaction =0.02). MR severity improved over time in HOCM, showed no clear change in ES-HCM, and worsened in other HCM ( P <0.001, 0.46, and <0.001, respectively; P interaction <0.001). CONCLUSIONS: In patients with HCM, moderate or greater MR was not associated with worse outcomes in HOCM or ES-HCM, but had significant prognostic implications in other HCM subtypes, suggesting the need for HCM subtype-specific MR management.