Associations between female sex, sarcomere variants and clinical outcomes in hypertrophic cardiomyopathy
File(s)HCM in women_revised_clean.docx (88.26 KB)
Accepted version
Author(s)
Type
Journal Article
Abstract
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.
Date Issued
2021-02-01
Online Publication Date
2021-06-07T23:01:52Z
Date Acceptance
2020-11-29
ISSN
2574-8300
Publisher
American Heart Association
Journal / Book Title
Circulation: Genomic and Precision Medicine
Volume
14
Issue
1
Copyright Statement
© 2020 American Heart Association, Inc.
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/33284039
Subjects
cardiomyopathy, hypertrophic
genetics
heart failure
sarcomeres
women
Publication Status
Published
Country
United States
Article Number
ARTN e003062
Date Publish Online
2020-12-07