Sex-Specific Differences in Patients with Hypertrophic Cardiomyopathy: A Cohort Study from Vienna

<b>Background</b>: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease and affects male patients more often than women. Prior studies, however, suggested that women are diagnosed later and at advanced stages of the disease, present with more pronounced symptoms, and experience worse outcomes. <b>Objectives</b>: To investigate sex-specific differences in clinical, laboratory, and comprehensive imaging characteristics in a contemporary cohort of HCM patients from a tertiary referral center in Austria. <b>Methods</b>: We retrospectively analyzed 321 HCM patients enrolled in a prospective registry (2018-2024). All patients underwent a comprehensive baseline evaluation, including medical history, laboratory assessment, transthoracic echocardiography, and cardiac magnetic resonance imaging. <b>Results</b>: At diagnosis, women were significantly older (62 vs. 53 years, <i>p</i> < 0.001) and presented with more advanced functional class (NYHA ≥ II: 80% vs. 49%, <i>p</i> < 0.001). Six-minute walking distance was lower and obstructive HCM was more prevalent in women (425 vs. 505 m, <i>p</i> < 0.001, and 55% vs. 32%, <i>p</i> < 0.001, respectively). Echocardiographic assessment revealed higher diastolic filling pressures (E/E' 18 vs. 10, <i>p</i> < 0.001), larger indexed atrial volumes (29.5 vs. 26.6 mL/m², <i>p</i> < 0.001), a higher left ventricular ejection fraction (70% vs. 62%, <i>p</i> < 0.001), and a larger indexed interventricular septal thickness in women (10.2 vs. 9.3 mm/m², <i>p</i> = 0.004). Moreover, serum levels of NT-proBNP were significantly higher in women (760 vs. 338 pg/L, <i>p</i> < 0.001). <b>Conclusions</b>: Female patients with HCM were diagnosed at an older age, presented with more advanced symptoms, had higher rates of obstructive physiology, and a phenotype characterized by diastolic dysfunction and elevated biomarkers, closely resembling heart failure with preserved ejection fraction. Recognizing these sex-specific disparities is crucial in improving diagnostic awareness and individualized therapeutic management.