Structural and Functional Remodeling and Long‐Term Outcomes in Women With Hypertrophic Cardiomyopathy

BACKGROUND: Sex-related differences in hypertrophic cardiomyopathy (HCM) are increasingly recognized, yet women remain underrepresented in most cohorts. This study aimed to characterize sex-specific differences in clinical features, myocardial mechanics, and long-term outcomes, with a focus on distinctive characteristics in women with HCM. METHODS: We studied 501 patients with HCM who underwent comprehensive clinical and echocardiographic evaluation between August 2010 and July 2017; 181 (36%) were women. Survival and event-free outcomes were assessed during a median follow-up of 6.23 years (range: 2.8-9.25 years) using Kaplan-Meier analysis and the log-rank test. RESULTS: At baseline, women were more likely to have familial HCM and were less symptomatic (NYHA class, p < 0.01) but had higher heart rate (p < 0.001), smaller LV end-diastolic and end-systolic diameters, and lower LV mass index (LVMI) than men. Women demonstrated higher E/E' ratio (p < 0.03), increased pulmonary artery systolic pressure (p < 0.03), reduced global longitudinal strain (GLS) (-10.6 ± 4.7 vs. -12.0 ± 5.1, p < 0.003), and lower early diastolic strain rate (SRe, P < 0.0001). Hospitalizations for heart failure, arrhythmias, or stroke were more frequent in women (34.4% vs. 24.4%, p < 0.03). Kaplan-Meier analysis showed a nonsignificant trend toward poorer survival in women. Cox regression analysis identified age as an independent predictor of hospitalization, while LV end-diastolic diameter, S' velocity, independently predicted mortality. CONCLUSIONS: Women with HCM exhibit distinct structural and mechanical features, including smaller ventricular size, lower LV mass, higher filling pressures, and impaired myocardial deformation. These differences are associated with increased morbidity and support the need for sex-specific diagnostic thresholds and individualized management strategies. KEY FINDINGS: In this cohort of 501 patients with HCM, women exhibited smaller ventricles, higher filling pressures, and more impaired myocardial deformation despite fewer symptoms. These sex-specific structural and functional differences were associated with increased hospitalizations and highlight the need for tailored diagnostic thresholds and management strategies in women.