Sex Differences in Prognosis of Patients With Genetic Dilated Cardiomyopathy
Year: 2025
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Dilated cardiomyopathy (DCM) is a genetically heterogeneous disease, presenting diverse clinical phenotypes and outcomes based on the underlying gene affected. The influence of sex on the gene-specific long-term prognosis of patients with genetic DCM remains unclear. This study aims to determine the effect of sex on the long-term prognosis per underlying genogroup. METHODS: A retrospective cohort study was conducted using data from 4 international referral centers. Baseline and longitudinal clinical data of patients with DCM, with a median follow-up of 6.7 years (interquartile range, 3.5–11.9 years), were collected. The study included men and women with DCM who had undergone genetic testing. Patients were categorized into 7 genotype groups: cytoskeletal/Z-disk, desmosomal, nuclear envelope, motor sarcomeric, TTN , other genetic, and genotype negative. The main outcomes measured were left ventricular reverse remodeling, mortality, heart failure hospitalization, heart transplantation, and malignant ventricular arrhythmias. RESULTS: Among 1716 patients, 1130 (66%) were men and 510 (30%) had a (likely) pathogenic variant. Ventricular remodeling was gene-dependent in women, with TTN patients exhibiting the highest rate ( P =0.003) and desmosomal patients the lowest ( P =0.04) compared with the genotype-negative group. After a median follow-up of 6.7 years, 334 men (29%) and 140 women (24%) reached the primary end point. Men with a (likely) pathogenic variant had the poorest prognosis, showing a higher rate of major adverse events (adjusted hazard ratio, 1.48 [95% CI, 1.12–1.95]; P =0.02) and malignant ventricular arrhythmias (adjusted hazard ratio, 1.83 [95% CI, 1.16–2.88]; P =0.009) compared with genotype-negative women. Prognosis varied by gene in men (log-rank P <0.0001) but not in women (log-rank P =0.1). The cytoskeletal/Z-disk, desmosomal, and nuclear envelope groups had the worst prognosis in men. CONCLUSIONS: The genetic architecture and sex are critical predictors of left ventricular reverse remodeling and long-term prognosis in DCM. These factors should be integrated into individualized risk prediction models to enhance clinical outcomes in patients with DCM.
Source: Circulation Heart Failure
Authors: Sophie L.V.M. Stroeks, Marco Merlo, Nerea Mora-Ayestaran, Max Jason, Upasana Tayal, Ping Wang, Antonio Cannatà, Maurits A. Sikking, Matteo Dal Ferro, Belen Peiro, Myrthe Willemars, Debby M.E.I. Hellebrekers, Rick E.W. van Leeuwen, Martina Setti, Esther Gonzalez-Lopez, Ingrid P.C. Krapels, Carola Pio Loco Detto Gava, Arthur van den Wijngaard, Michiel T.H.M. Henkens, Manuela Iseppi, Anne G. Raafs, Martijn F. Hoes, Vanessa P.M. van Empel, Elizabeth A.V. Jones, Miranda Nabben, Matthew Taylor, Han G. Brunner, Juan Pablo Ochoa, Fernando Dominguez, Neal K. Lakdawala, Gianfranco Sinagra, Pablo Garcia-Pavia, Luisa Mestroni, Stephane R.B. Heymans, Job A.J. Verdonschot
Institutions: Maastricht University Medical Centre, Maastricht University, ERN GUARD-Heart, KU Leuven, Azienda Sanitaria Universitaria Integrata di Trieste, Centro de Investigación en Red en Enfermedades Cardiovasculares, Hospital Universitario Puerta de Hierro Majadahonda, University of Colorado Anschutz, Guy's and St Thomas' NHS Foundation Trust, Imperial College London, King's College London, British Heart Foundation, King's College Hospital, University of Verona, Netherlands Heart Institute, Radboud University Nijmegen, Radboud University Medical Center, Spanish National Centre for Cardiovascular Research, Brigham and Women's Hospital, Harvard University
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4414452029