Sex differences in presentation, diagnostics, and outcomes across cardiomyopathies: insights from a prospective cohort.
C Nordberg Backelin, E Bobbio, E Bollano, A Rawshani, M Wideqvist, M Bjorkenstam, M Fu, B Andersson, S Romeo, N Bergh, C LjungmanAbstract
Introduction
Sex-related differences in cardiomyopathy (CMP) may influence clinical presentation, diagnostic strategies, access to advanced heart failure therapies and outcome. However, women remain underrepresented in CMP research and contemporary sex-specific patterns are inadequately understood.
Aim
To investigate sex differences in distribution, clinical presentation, comorbidities, diagnostic evaluation, advanced therapies and outcomes across CMPs. Further to explore sex-specific predictors of outcomes.
Methods
This study is a prospective cohort study including patients ≥18 years with suspected CMPs at a Swedish tertiary center. CMP diagnoses followed ESC criteria, categorized as Arrhythmogenic Right Heart cardiomyopathy (ARVC), Dilated Cardiomyopathy (DCM), Hypertrophic Cardiomyopathy (HCM), myocarditis (including sarcoidosis and giant cell myocarditis), Restrictive Cardiomyopathy (RCM), or other CMPs. The primary outcome was a composite of mechanical circulatory support (MCS), heart transplantation (HTx), and mortality until March 2025. Crude event rates were calculated per 10 000 person-years with 95% confidence intervals. Time-to-event outcomes were assessed using age-adjusted Cox regression, with proportional hazards checked and Kaplan–Meier curves for cumulative incidence. Key predictors were identified using gradient boosting machine (GBM)–based survival models with XGBoost, with variable importance assessed via Shapley values.
Results
In all, 641 patients (mean age 54.4±16.5 years; 72% men) were included. At inclusion, women had lower diastolic blood pressure and BMI (p<0.03) and more frequently endocrine comorbidities (p<0.001), although overall differences were small (table 1). DCM was most prevalent in both sexes, while HCM was more frequent in women and RCM in men (p<0.01). The following sex-related differences in clinical presentation were observed: women presented more often with fatigue and dyspnea in DCM and HCM, respectively, while men more frequently had ventricular arrhythmias, irrespective of diagnoses (p<0.01). Women were more often evaluated with genetic diagnostics (p<0.05) however, no differences were observed in other diagnostic assessments. Men and women received comparable therapies in all CMP groups. No sex difference was found in the primary outcome. GBM analyses identified time from symptom onset to inclusion, NT-proBNP, and LVEF as the strongest predictors of outcome in both sexes (Figure 1).
Conclusion
Despite differences in presentation and CMP distribution, women and men underwent comparable diagnostic evaluation and therapy, with no differences in the primary outcome. Machine-learning analyses also identify largely shared predictors of outcome in both sexes, highlighting equitable care and prognosis.For image description, please refer to the figure legend and surrounding text.For image description, please refer to the figure legend and surrounding text.