Associations Between Female Sex, Sarcomere Variants and Clinical Outcomes in Hypertrophic Cardiomyopathy. Circulation. Genomic and precision medicine Lakdawala, N. K., Olivotto, I., Day, S. M., Han, L., Ashley, E. A., Michels, M., Ingles, J., Semsarian, C., Jacoby, D., Jefferies, J. L., Colan, S. D., Pereira, A. C., Rossano, J. W., Wittekind, S., Ware, J. S., Saberi, S., Helms, A. S., Cirino, A. L., Leinwand, L. A., Seidman, C. E., Ho, C. Y. 2020


Background - The impact of sex on phenotypic expression in hypertrophic cardiomyopathy (HCM) has not been well characterized in genotyped cohorts. Methods - Retrospective cohort study from an international registry of patients receiving care at experienced HCM centers. Sex-based differences in baseline characteristics and clinical outcomes were assessed. Results - Of 5,873 patients (3,788 genotyped), 2,226 (37.9%) were women. At baseline, women were older (49.0±19.9 vs. 42.9±18.4 years, p<0.001) and more likely to have pathogenic/likely-pathogenic sarcomeric variants (SARC+; 51% vs 43%, p<0.001) despite equivalent utilization of genetic testing. Age at diagnosis varied by sex and genotype despite similar distribution of causal genes. Women were 3.6 to 7.1 years older at diagnosis (p<0.02) except for patients with MYH7 variants where age at diagnosis was comparable for women and men (n=492; 34.8±19.2 vs 33.3±16.8 years, p=0.39). Over 7.7 median years of follow up, NYHA III-IV heart failure (HF) was more common in women (HR 1.87, CI 1.48-2.36, p<0.001), after controlling for their higher burden of symptoms and outflow tract obstruction at baseline, reduced ejection fraction, SARC+, age and hypertension. All-cause mortality was increased in women (HR 1.50, CI 1.13-1.99, p<0.01), but neither ICD utilization nor ventricular arrhythmia varied by sex. Conclusions - In HCM, women are older at diagnosis, partly modified by genetic substrate. Regardless of genotype, women were at higher risk of mortality and developing severe HF symptoms. This points to a sex-effect on long-term myocardial performance in HCM, which should be investigated further.

View details for DOI 10.1161/CIRCGEN.120.003062

View details for PubMedID 33284039