Key result
Male sex is linked to ~2-fold higher risk of major arrhythmic events in LMNA cardiomyopathy.
Why the study?
Whether the higher prevalence of DCM in males reflects biological differences or under-diagnosis in females remains uncertain, and the long-term prognosis of DCM in females is less clear.
Does sex influence the risk of major arrhythmic and heart failure events in patients with genetic dilated cardiomyopathy?
Meta-Analysis (n=3,192)
Does sex influence the risk of major arrhythmic and heart failure events in patients with genetic dilated cardiomyopathy?
Absolute Event Rate: 34% vs 17%
p-value: p=0.01
Sex and genotype significantly influence clinical outcomes in genetic dilated cardiomyopathy, highlighting the need for sex-specific risk stratification models.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“This research highlights the importance of considering women-specific risk factors in understanding who is at risk of developing DCM. We need to be vigilant for the development of DCM in women with a history of hypertensive disorders of pregnancy.”
Supports sex-specific arrhythmic risk stratification in LMNA cardiomyopathy; extends evidence for genotype-sex interactions across genetic DCM.
Dilated cardiomyopathy (DCM), affecting 1 in 250 people, is a leading global cause of heart failure and the most common indication for heart transplantation. Evidence suggests DCM is more prevalent in males, but whether this reflects biological differences or under-diagnosis in females remains uncertain. This review explores the impact of sex on DCM, examining differences in epidemiology, etiology, clinical presentation, treatment response, and outcomes. Females 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 females 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, RBM20, DSP, and PLN carriers faced the highest arrhythmic risk, with TTNtv carriers the lowest. PLN and LMNA carriers had the highest heart failure risk in both sexes, while female BAG3, RBM20, and TTN carriers had lower heart failure rates 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 (ICDs), may under-treat females due 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 females 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.
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Stroeks et al. (2025) conducted a meta-analysis in Genetic Dilated Cardiomyopathy (n=3,192). Male sex vs. Female sex was evaluated on Major arrhythmic events (sudden cardiac death and malignant ventricular arrhythmias) in LMNA variant carriers (p=0.01). Male patients with dilated cardiomyopathy and LMNA variants had a significantly higher pooled proportion of major arrhythmic events compared to female carriers (34% vs 17%, p=0.01).
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