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

Abstract Background Hypertrophic cardiomyopathy (HCM) is often a genetic condition that involves abnormal thickening of the heart wall, and is categorised into obstructive and non-obstructive subtypes. Although established HCM treatment guidelines do not differ based on sex, evidence is emerging to support the existence of sex-based differences in clinical presentation, disease progression and patient outcomes. Physiological differences between males and females may contribute to different clinical dispositions not taken into account in clinical care pathways and treatment guidelines. Purpose A targeted literature review (TLR) and meta-analysis, alongside a retrospective cohort study (conducted using primary data from University Hospital Coventry, UK) was undertaken, to investigate the prevalence of sex-based differences in clinical presentation, diagnosis, and patient outcomes between males and females diagnosed with obstructive and non-obstructive HCM. Methods The TLR searched MEDLINE and Web of Science, was supplemented by targeted web searching, and aimed to capture sex-disaggregated echocardiographic (ECG) and cardiac magnetic resonance imaging (MRI) values, genetic mutation effects, biomarker levels, and outcomes related to HCM. The cohort study was conducted utilising patient records from all patients diagnosed with HCM between January 2007 and January 2025. Demographics, diagnostic data, and patient outcomes were sex-disaggregated, and the prognostic significance of diagnostic parameters at a differential threshold for adults diagnosed with HCM were explored. Results The TLR found that females were associated with a higher age at HCM diagnosis, exhibited significantly lower septal and left ventricular wall thickness, as well as left ventricular mass (LVM). Meta-analysis demonstrated that males exhibit lower NT-proBNP levels, and females exhibit significantly higher rates of pathogenic mutations relating to HCM, correlating with differences in clinical presentation. Among 207 HCM patients in the primary cohort study, 38% were female; non-obstructive HCM was more common (61%) than oHCM (39%). Females had a higher mean age at HCM diagnosis (59.4±20.5 vs 53.5±16.1, respectively; p=0.026), with no significant differences in ethnicity, HCM subtype, and social deprivation score at baseline. Maximal wall thickness was significantly higher in males versus females (21.7±6.8 vs 18.2±2.9, respectively; p=0.007). Females had a higher rate of septal reduction therapy (44.1% vs 19.6%, respectively; p=0.018) and mortality (20.5% vs 9.3%, respectively; p=0.022; 28 deaths at the end of follow up). Conclusion The findings of the primary cohort study support existing evidence from the TLR indicating that females are diagnosed later, and experience worse symptoms and outcomes. Further research should highlight the implications of accounting for these differences in clinical practice, and updating of current clinical guidelines to note these sex-specific disparities.