Sex-related differences in exercise performance and outcome of patients with hypertrophic cardiomyopathy

Aims Exercise performance is known to predict outcome in hypertrophic cardiomyopathy (HCM), but whether sex-related differences exist is unresolved. We explored whether functional impairment, assessed by exercise echocardiography, has comparable predictive accuracy in females and males with HCM. Methods We retrospectively evaluated 292 HCM patients (46 +/- 16 years, 72% males), consecutively referred for exercise echocardiography; 242 were followed for 5.9 +/- 4.2 years. Results Peak exercise capacity was 6.5 +/- 1.6 metabolic equivalents (METs). Sixty patients (21%) showed impaired exercise capacity (<= 5 METs). Exercise performance was reduced in females, compared with males (5.6 +/- 1.6 vs 6.9 +/- 1.5 METs, p < 0.001; peak METs <= 5 in 40% vs 13%, p < 0.001), largely driven by a worse performance in women >50 years of age. At multivariable analysis, female sex was independently associated with impaired exercise capacity (odds ratio: 4.67; 95% confidence interval (CI): 1.83-11.90; p = 0.001). During follow-up, 24 patients (10%) met the primary endpoint (a combination of cardiac death, heart failure requiring hospitalization, sustained ventricular tachycardia, appropriate implantable cardioverter defibrillator discharge, resuscitated sudden cardiac death and cardioembolic stroke). Event-free survival was reduced in females (p = 0.035 vs males). Peak METs were inversely related to outcome in males (hazard ratio (HR) per unit increase: 0.57; 95% CI: 0.39-0.84; p = 0.004) but not in females (HR: 1.22; 95% CI: 0.66-2.24; p = 0.53). Conclusions Female patients with HCM showed significant age-related impairment in functional capacity compared with males, particularly evident in post-menopausal age groups. While women were at greater risk of HCM-related complications and death, impaired exercise capacity predicted adverse outcome only in men. These findings suggest the need for sex-specific management strategies in HCM.