DUGi

Sex differences in dilated cardiomyopathy: A comparative analysis of cardiac remodeling, clinical outcomes, and genetic risk stratification by sex in dilated cardiomyopathy

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INTRODUCTION Dilated cardiomyopathy is a heterogeneous disease characterized by left ventricular dilation and systolic dysfunction not explained by abnormal loading conditions or coronary artery disease. Emerging evidence suggests sex-related differences in clinical presentation and prognosis, although comparative data remain limited. This study aims to compare clinical, functional, and prognostic characteristics between men and women with dilated cardiomyopathy to support future research and more personalized management. METHODS This observational, retrospective, cohort study included 266 patients with DCM, aged between 18 and 87 years, from the GENCARDIO RESEARCH project, followed at Hospital Josep Trueta (Girona, Spain). Sex-related differences in cardiac remodeling and clinical outcomes were assessed using logistic regression and Cox proportional hazards models, with Kaplan–Meier curves for event timing. The Madrid DCM Genotype Score was evaluated using regression models, ROC curve analysis, and complemented by diagnostic yield analyses, to assess its predictive performance and sex-specific effects. RESULTS DCM was more prevalent in men (69%) than in women (31%). Men showed a lower likelihood of LVEF recovery (adjusted OR 0.43, 95% CI 0.24–0.77; p = 0.004) and a trend toward higher incidence and earlier onset of malignant ventricular arrhythmias (adjusted HR 2.74, 95% CI 0.95–7.91; p = 0.063), while women exhibited more favorable LV systolic recovery. No significant sex-related differences were observed in genetic status, advanced heart failure, stroke, mortality or recovery of LV dilation. Overall Madrid DCM Genotype Score values were comparable between sexes (median score 36.83 in men vs. 31.84 in women), but the score showed higher discrimination in men (AUC 0.775 vs. 0.687), reflecting higher score values among genetically positive male patients (p = 0.037). CONCLUSIONS Sex-based analysis of our DCM cohort showed differences in disease expression, with men representing almost 70% of the cohort and exhibiting a more severe clinical profile. The Madrid DCM Score showed better ability to identify genetically positive cases in males. These sex-related differences may open the door to a more refined risk stratification and personalized management

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