Sex Differences in Characteristics and Outcomes Among Patients With Hypertrophic Cardiomyopathy: Insights From the REVEAL-HCM Study

J Am Heart Assoc. 2026 Jul 7;15(13):e046708. doi: 10.1161/JAHA.125.046708. Epub 2026 Jun 23.

Abstract

Background: Female sex has been associated with poor prognosis in hypertrophic cardiomyopathy (HCM), but the factors contributing to this disparity remain insufficiently defined. We aimed to clarify sex differences in clinical characteristics and factors associated with cardiovascular death in Japan.

Methods: This multicenter, retrospective observational study of HCM was conducted between January 1, 2006, and December 31, 2018 (REVEAL-HCM study [Multicenter Registry to Evaluate Risk Factors for Disease Progression, Sudden Cardiac Death and Adverse Clinical Outcomes in Japanese Patients With Hypertrophic Cardiomyopathy]; UMIN000046932). Patients aged ≥16 years with HCM were enrolled. Baseline characteristics and clinical outcomes including cardiovascular death were assessed. Univariable and multivariable Cox proportional hazards models were used to identify factors associated with cardiovascular death.

Results: Of 3247 patients (median age, 67 years; 43% women), women were older and more symptomatic at presentation (52% New York Heart Association class II-IV versus 35% in men). Cardiovascular death was more common in women (hazard ratio [HR], 1.37 [95% CI, 1.02-1.82]; P=0.03). In multivariable analysis, older age (per 1-year increase; HR, 1.04 [95% CI, 1.02-1.06]), advanced New York Heart Association class (HR, 1.99 [95% CI, 1.40-2.82]), history of atrial fibrillation (HR, 1.55 [95% CI, 1.10-2.18]), greater maximal wall thickness indexed to body surface area (per 1-mm/m2 increase; HR, 1.12 [95% CI, 1.06-1.20]), and apical HCM (HR, 0.53 [95% CI, 0.32-0.88]) were independently associated with cardiovascular death, attenuating the HR for female sex.

Conclusions: Sex differences in clinical characteristics and outcomes were observed. The excess cardiovascular death in women with HCM was largely explained by older age, more advanced symptoms, greater indexed wall thickness, and sex-specific differences in both the prevalence and prognostic impact of apical HCM.

Keywords: hypertrophic cardiomyopathy; outcomes; sex difference.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Cardiomyopathy, Hypertrophic* / diagnosis
  • Cardiomyopathy, Hypertrophic* / epidemiology
  • Cardiomyopathy, Hypertrophic* / mortality
  • Death, Sudden, Cardiac* / epidemiology
  • Death, Sudden, Cardiac* / etiology
  • Disease Progression
  • Female
  • Humans
  • Japan / epidemiology
  • Male
  • Middle Aged
  • Prognosis
  • Registries
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Sex Factors