Factors associated with excess female mortality in obstructive hypertrophic cardiomyopathy

Abstract

Background: Several studies have reported excess female mortality in patients with hypertrophic cardiomyopathy, but the cause is unknown. Aims: To compare risk-factors for disease-related death in both sexes in a geographical cohort of patients with obstructive hypertrophic cardiomyopathy (oHCM). Methods and results: Data-bases in all ten hospitals within West Götaland Region yielded 250 oHCM-patients (123 females, 127 males). Mean follow-up was 18.1 y. Risk-factors for disease-related death were evaluated by Cox-hazard regression and Kaplan-Meier survival-curves, with sex-comparisons of distribution of risk-factors and therapy in total and age-matched (n = 166) groups. At diagnosis females were older, median 62 y vs. 51 y, (P < 0.001), but not different in outflow-gradients and median NYHA-class. However, septal hypertrophy was more advanced: 10.6 [IQR = 3.2] vs. 9.6 [2.5] mm/m2 BSA; P = 0.002. Females had higher disease-related mortality than males (P = <0.001), with annual mortality 2.9% vs. 1.5% in age-matched groups (P = 0.010 log-rank). For each risk-category identified (NYHA-class ≥ III, outflow-gradient ≥50 mmHg), a higher proportion of females died (P = 0.0004; P = 0.001). Calcium-blocker therapy was a risk-factor (P = 0.005) and was used more frequently in females (P = 0.034). A beta-blocker dose above cohort-median reduced risk for disease-related death in both males (HR = 0.32; P = 0.0040) and in females (HR = 0.49; P = 0.020). Excess female deaths occurred in chronic heart-failure (P = 0.001) and acute myocardial infarctions (P = 0.015). Fewer females received beta-blocker therapy after diagnosis (64% vs. 78%, P = 0.018), in a smaller dose (P = 0.007), and less frequently combined with disopyramide (7% vs. 16%, P = 0.048). Conclusion: Addressing sex-disparities in the timing of diagnosis and pharmacological therapy has the potential to improve the care of females with oHCM.