Sex differences in cardiomyopathies: Presentation, diagnostic evaluation, and outcomes in a prospective cohort

Sex-related differences in cardiomyopathy (CMP) may influence clinical presentation, diagnostic evaluation, access to advanced therapies and outcomes. Despite this, women remain substantially underrepresented in CMP research.

To examine sex differences in distribution, clinical presentation, comorbidities, diagnostic evaluation, advanced therapies and outcomes across CMPs. Further to identify sex-specific predictors of prognosis.

Adults (≥18 years) with suspected CMPs were prospectively enrolled and diagnosed with arrhythmogenic right heart cardiomyopathy (ARVC), dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), myocarditis, restrictive cardiomyopathy (RCM), or other CMPs. The primary composite outcome included mechanical circulatory support (MCS), heart transplantation (HTx), or death. Age-adjusted Cox regression, and machine-learning survival models identified key outcome predictors.

Among 641 patients (mean age 54.4 ± 16.5 years; 72% men) women had lower diastolic blood pressure, lower body mass index and more often endocrine comorbidities (p < 0.008). Women more often presented with fatigue and men with ventricular arrhythmias (p < 0.013). DCM was the most common CMP in both sexes, while HCM was more frequent in women and RCM in men (p < 0.009). Women more often underwent genetic evaluation but no other statistically significant differences in diagnostic assessments were observed. Use of device therapies and outcome did not differ significantly by sex. Gradient-boosted machine analyses identified NTproBNP, right atrial mean pressure and disease duration as the strongest predictors of outcome in both sexes.

Despite differences in phenotype and presentation no significant differences in outcomes were observed between sexes, indicating that disease severity, not sex, drives prognosis.