Sex disaggregated analysis of risk factors for adverse outcomes in hypertrophic cardiomyopathy

Abstract

Abstract Background Patient sex has been associated with differences in disease penetrance and clinical expression in HCM. We sought to investigate sex-disaggregated differences in risk factors for adverse outcomes in a large international HCM registry. Methods This is a retrospective study of HCM patients from the Sarcomeric Human Cardiomyopathy Registry. Cox proportional hazards models were fit with a sex interaction term to determine significant differences between sexes. Results 6647 (38% women) probands with HCM were included. After a mean follow-up of 6.4 years from first encounter, women had a higher risk of heart failure (HF) composite (HR 1.77; 95% CI 1.56–1.99, p<0.0001), and death (1.22; 1.03–1.45, p=0.02) compared to men. No sex difference existed for ventricular arrhythmia composite (p=0.2) or atrial fibrillation (p=0.6). Sarcomere positive status (Sarc+) and causative variants in MYBPC3 reduced the risk of the HF composite for women, while for men there was no change in risk (P-heterogeneity=0.016 and <0.0001, respectively). Baseline LVEF <35% and larger LA size increased the risk of the HF composite for both sexes but to a greater magnitude in men (P-heterogeneity=0.0003 and 0.04 respectively) (Figure 1). Sarc+ increased the risk of death in men but not women (P-heterogeneity=0.041). Having the HF composite increased the risk of death by 45% in and 240% in men (P-heterogeneity=0.003) (Figure 2). Conclusion There are important sex differences in the risk of heart failure and death in those with HCM, with significant heterogeneity of outcomes based on subgroups defined by genetic and imaging factors. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): The Sarcomeric Human Cardiomyopathy Registry (SHaRe) is supported by an unrestricted research grant from Bristol Myer Squibb, including funds to individual sites for database support.