Sex-disaggregated data in hypertrophic cardiomyopathy: a targeted literature review, meta-analysis and primary cohort study

OBJECTIVE: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy characterised by pathological left ventricular hypertrophy and categorised into obstructive and non-obstructive subtypes. While its autosomal dominant inheritance pattern would suggest similar prevalence, emerging evidence suggests sex-based physiological differences in presentation, progression and outcomes. We sought to better understand these differences in the literature and among our own cohort of patients with HCM. METHODS: A targeted literature review (TLR) of MEDLINE and Web of Science, and subsequent meta-analysis of NT-proBNP captured sex-disaggregated echocardiographic and cardiac MRI values, genetic mutation effects, biomarker levels and outcomes. A retrospective study of patients diagnosed with HCM at University Hospitals Coventry and Warwickshire NHS Trust, UK between January 2007 and January 2025 examined sex-based differences in presentation, diagnosis and outcomes in HCM. RESULTS: The TLR found that females were older at diagnosis and had significantly lower septal and left ventricular wall thickness and left ventricular mass. The meta-analysis showed males had lower NT-proBNP levels than females, potentially reflecting sex-based differences in cardiovascular stress. In our cohort (n=207) comprising 78 (38%) females, age at diagnosis was higher (59.4±20.5 vs 53.5±16.1 years; p=0.026) among females than males, with no significant baseline differences in ethnicity, HCM subtype or social deprivation. Maximal wall thickness was higher in males (21.7±6.8 vs 18.2±2.9 mm; p=0.007). Females had higher rates of septal reduction therapy (44.1% vs 19.6%; p=0.018). Mortality was higher among females (20.5% vs 9.3%; p=0.022; 28 deaths at end of follow-up) though adjusted analyses did not reach significance (HR 2.09, 95% CI 0.998, 4.45; p=0.057). CONCLUSIONS: The findings from our cohort support the results of the TLR that females tend to be diagnosed with HCM later than males and experience worse symptoms and outcomes. Further research should clarify the implications of sex-based disparities.