Gender-related differences in hypertrophic cardiomyopathy: from clinical presentation to outcomes
A Martins, M Amado, J Pereira, A Vazao, C Esteves, C Ruivo, C Domingues, D DuraoAbstract
Introduction
Hypertrophic cardiomyopathy (HCM) is a heritable heart disease characterized by substantial phenotypic heterogeneity. Although most diagnosed patients are male, women tend to present with a more severe disease phenotype and worse clinical outcomes.
Objectives
To assess gender-related differences in clinical characteristics at presentation, including imaging and laboratory parameters, as well as clinical outcomes in patients with HCM followed at a Cardiomyopathy Clinic in a regional hospital in Portugal.
Methods
Retrospective single-center cohort study of adult patients diagnosed with HCM between 2018 and 2024 with ≥6 months of follow-up. Patients with uncontrolled hypertension or significant valvular disease were excluded. Baseline clinical, imaging, and laboratory data were collected, and the occurrence of events during follow-up was assessed (Table 1). Follow-up events included new-onset atrioventricular (AV) or interventricular (IV) conduction disturbances, new-onset atrial fibrillation (AF), and extended major adverse cardiovascular events (MACE), defined as cardiovascular mortality, myocardial infarction, stroke, or heart failure hospitalizations. Female patients (Group 1) were compared with male patients (Group 2).
Results
A total of 165 patients were included, of whom 59 (36%) were female. Median age was 63 years (IQR 18), and median follow-up was 45 months (IQR 41). Female patients more frequently exhibited obstructive HCM (53 vs. 30%, p=0.005) and had higher E/e’ ratio (15.7 vs. 11.4, p<0.001), relative wall thickness (RWT) (0.66 vs. 0.58, p=0.023), and NT-proBNP levels [1250.0 (IQR 2538.0) vs. 555.5 (IQR 658.0) pg/ml, p<0.001]. Conversely, male patients showed higher left ventricular mass index (165.1 vs. 136.2 g/m², p=0.046) and right ventricular global longitudinal strain (-19.7 vs. -20.5%, p=0.035). Regarding ECG findings, male patients more frequently exhibited AV/IV conduction disturbances at baseline, including a higher prevalence of first-degree AV block (16 vs. 5%, p=0.046), right bundle branch block (12 vs. 2%, p=0.004), and bifascicular block (10 vs. 2%, p=0.014). During follow-up, new-onset AF occurred more frequently in female patients (17 vs. 6%, p=0.019), with no other significant gender-related differences. ROC analysis identified optimal cut-off values for continuous variables, and only those with AUC >0.650 were included in the multivariate analysis. After multivariate logistic regression, obstructive HCM and NT-proBNP ≥881 pg/ml (sensitivity 57%, specificity 70%) remained independently associated with female sex (Table 1B).
Conclusions
In this cohort, pronounced gender-related differences were observed in HCM patients. Female patients presented with a more advanced clinical profile and were more likely to develop new-onset AF during follow-up.Table 1For image description, please refer to the figure legend and surrounding text.