Sex differences in dilated cardiomyopathy: evidence gaps and future directions
File(s)
Accepted version
Author(s)
Stroeks, Sophie LVM
Oko-Osi, Shanelle
Arasu, Arianna
Hirst, Jane E
Tayal, Upasana Paz
Type
Journal Article
Abstract
Dilated cardiomyopathy (DCM), which affects 1 in 250 people, is a leading global cause of heart failure and the most common indication for heart transplantation. Evidence suggests that DCM is more prevalent in men, but whether this reflects biological differences or underdiagnosis in women remains uncertain. This review explores the impact of sex on DCM, examining differences in epidemiology, etiology, clinical presentation, treatment response, and outcomes. Women often present with less severe cardiac phenotypes, including lower levels of fibrosis and better left ventricular function, yet the long-term prognosis of DCM in women is less clear. Through a systematic review and meta-analysis, we found that male DCM patients with variants in PLN, DSP, and LMNA had higher arrhythmic event rates compared with TTNtv and BAG3 carriers. In female patients with DCM, those with RBM20, DSP, and PLN variants faced the highest arrhythmic risk, and TTNtv carriers the lowest. PLN and LMNA variants had the highest heart failure risk in both sexes, whereas BAG3, RBM20, and TTN variants had lower heart failure rates in female compared with male carriers. These findings highlight the influence of sex and genotype on clinical outcomes. Current risk-stratification tools, such as those used for implantable cardioverter-defibrillators, may undertreat women owing to reliance on sex-neutral thresholds. We highlight the role of genetic, environmental, and reproductive factors in shaping these disparities, including the influence of pregnancy, pregnancy complications, and menopause. This review identifies key gaps in knowledge and calls for expanded representation of women in DCM studies and the development of sex-specific risk models. Addressing these gaps is essential to improving outcomes and advancing equitable personalized care for all DCM patients.
Date Issued
2026-02-17
Date Acceptance
2025-09-05
Citation
JACC, 2026, 87 (6), pp.723-735
ISSN
0735-1097
Publisher
Elsevier BV
Start Page
723
End Page
735
Journal / Book Title
JACC
Volume
87
Issue
6
Copyright Statement
© 2025 by the American College of Cardiology Foundation. Published by Elsevier. This is the author’s accepted manuscript made available under a CC-BY licence in accordance with Imperial’s Research Publications Open Access policy (www.imperial.ac.uk/oa-policy)
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/41295940
PII: S0735-1097(25)09811-0
Subjects
DCM
female
heart
male
sex-specific
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2025-11-26