Background: Biological sex has a diverse impact on the cardiovascular system. Its influence on dilated cardiomyopathy (DCM) remains unresolved.
Objective: To investigate sex-specific differences in DCM presentation, natural history, and prognostic factors.
Methods We conducted a prospective observational cohort study of DCM patients, assessing baseline characteristics, CMR-imaging, biomarkers and genotype. The composite outcome was cardiovascular mortality or major heart-failure (HF) events.
Results: Overall, 206 females and 398 males with DCM were followed for a median of 3.9 years. At baseline female patients had higher left ventricular ejection fraction (LVEF), smaller left ventricular volumes, less prevalent mid-wall myocardial fibrosis (23% vs 42%) and lower high sensitivity cardiac troponin (hs-cTnI) than males (all p<0.05), with no difference in time from diagnosis, age at enrollment, NT-proBNP levels, pathogenic DCM genetic variants, myocardial fibrosis extent or medications used for HF.
Despite a more favourable profile, the risk of the primary outcome at 2 years was higher in females than males (8.6% vs 4.4%, adjusted hazard ratio 3.14, 95% CI 1.55 to 6.35, p=0.001). Between 2-5 years, the effect of sex as a prognostic modifier attenuated. Age, mid-wall myocardial fibrosis, LVEF, left atrial volume, NT-proBNP, hs-cTnI, left bundle branch block and NYHA class were not sex specific prognostic factors.
Conclusions: We identify a novel paradox in prognosis for females with DCM. Female DCM patients have a paradoxical early increase in major HF events despite less prevalent myocardial fibrosis and a milder phenotype at presentation. Future studies should interrogate the mechanistic basis for these sex differences.