Sex differences in the clinical presentation and natural history of dilated cardiomyopathy

Owen, R. et al. (2024) Sex differences in the clinical presentation and natural history of dilated cardiomyopathy. JACC: Heart Failure, 12(2), pp. 352-363. (doi: 10.1016/j.jchf.2023.10.009) (PMID:38032570) (PMCID:PMC10857810)

Abstract

Background Biological sex has a diverse impact on the cardiovascular system. Its influence on dilated cardiomyopathy (DCM) remains unresolved. Objectives This study aims 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, cardiac magnetic resonance 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, smaller left ventricular volumes, less prevalent mid-wall myocardial fibrosis (23% vs 42%), and lower high-sensitivity cardiac troponin I than males (all P < 0.05) with no difference in time from diagnosis, age at enrollment, N-terminal pro-B-type natriuretic peptide levels, pathogenic DCM genetic variants, myocardial fibrosis extent, or medications used for HF. Despite a more favorable profile, the risk of the primary outcome at 2 years was higher in females than males (8.6% vs 4.4%, adjusted HR: 3.14; 95% CI: 1.55-6.35; P = 0.001). Between 2 and 5 years, the effect of sex as a prognostic modifier attenuated. Age, mid-wall myocardial fibrosis, left ventricular ejection fraction, left atrial volume, N-terminal pro-B-type natriuretic peptide, high-sensitivity cardiac troponin I, left bundle branch block, and NYHA functional 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.

• Item Type: Articles
• Additional Information: This work was supported by the UK Medical Research Council (MR/W023830/1), the National Heart Lung Institute Research Foundation, Royston Centre for Cardiomyopathy Research, NIHR Biomedical Research Unit Royal Brompton Hospital, NIHR Imperial College Biomedical Research Centre, British Heart Foundation (RE/ 18/4/34215; SP/10/10/28431; SP/17/11/32885; BH FS/ICRF/21/26019), Wellcome Trust (107469/Z/15/Z), Rosetrees Trust, Sir Jules Thorn Charitable Trust [21JTA], and Alexander Jansons Myocarditis UK. Dr Januzzi has been supported in part by the Hutter Family Professorship. Dr van Spall has been funded by the Canadian Institutes of Health Research and Heart and Stroke Foundation of Canada.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McMurray, Professor John
• Authors: Owen, R., Buchan, R., Frenneaux, M., Jarman, J. W.E., Baruah, R., Lota, A. S., Halliday, B. P., Roberts, A. M., Izgi, C., Van Spall, H. G.C., Michos, E. D., McMurray, J. J.V., Januzzi, J. L., Pennell, D. J., Cook, S. A., Ware, J. S., Barton, P. J., Gregson, J., Prasad, S. K., and Tayal, U.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: JACC: Heart Failure
• Publisher: Elsevier
• ISSN: 2213-1779
• ISSN (Online): 2213-1787
• Published Online: 29 November 2023
• Copyright Holders: CROWN COPYRIGHT © 2023
• First Published: First published in JACC: Heart Failure 12(2): 352-363
• Publisher Policy: Reproduced under a Creative Commons licence