SPC365

Sex-related differences in HCM: cardiogenetics, disease severity and major outcomes

Session: Sessão de Comunicações Orais 11 – Corações espessos e rígidos: amiloidose cardíaca e companhia
Speaker: Margarida Urpina Matias

Congress: CPC 2026
Topic: F. Valvular, Myocardial, Pericardial, Pulmonary, Congenital Heart Disease
Theme: 30. Cardiovascular Disease in Special Populations
Subtheme: 30.2 Cardiovascular Disease in Women
Session Type: Comunicações Orais
FP Number: ---
Authors: Margarida Urpina Matias; Raquel Montalvão; Maria Inês Soares; Rui Gomes; Mariana Ramos; Márcia Presume; Débora Correia; Samuel Azevedo; Carlos Aguiar; Sérgio Maltês; Bruno Rocha

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Arial,sans-serif"><u><span style="font-size:12.0pt"><span style="font-family:&quot;Times New Roman&quot;,serif">Introduction</span></span></u><span style="font-size:12.0pt"><span style="font-family:&quot;Times New Roman&quot;,serif">: Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac disease with heterogeneous clinical expression and outcomes. Sex differences in phenotypic expression and outcomes are well known in several cardiovascular conditions. Emerging data in patients with HCM also suggests important sex differences in clinical presentation, myocardial remodeling, and therapeutic management that may influence patient prognosis.</span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Arial,sans-serif"><u><span style="font-size:12.0pt"><span style="font-family:&quot;Times New Roman&quot;,serif">Purpose</span></span></u><span style="font-size:12.0pt"><span style="font-family:&quot;Times New Roman&quot;,serif">: To characterize sex-related differences in clinical profile, imaging features, genetics, and treatment among patients with HCM followed in a dedicated tertiary center.</span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Arial,sans-serif"><u><span style="font-size:12.0pt"><span style="font-family:&quot;Times New Roman&quot;,serif">Methods</span></span></u><span style="font-size:12.0pt"><span style="font-family:&quot;Times New Roman&quot;,serif">: We conducted a retrospective analysis of patients with a diagnosis of HCM followed at a tertiary care center up until November 2025. Data collected included demographics, NYHA class, imaging parameters, invasive and device-based therapies, treatment, genetic testing, and mortality. Comparisons between male and female patients were performed using chi-square tests for categorical variables and independent t-tests or Mann&ndash;Whitney U tests for continuous variables, as appropriate. Survival analyses were conducted using the Kaplan&ndash;Meier method.</span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Arial,sans-serif"><u><span style="font-size:12.0pt"><span style="font-family:&quot;Times New Roman&quot;,serif">Results</span></span></u><span style="font-size:12.0pt"><span style="font-family:&quot;Times New Roman&quot;,serif">: Overall, 550 patients were included (mean age 62 &plusmn; 12 years; 43% female). Women were first diagnosed at a significantly older age than men (58 vs. 53 years, p = 0.019), exhibited a higher symptomatic burden (NYHA III&ndash;IV: 24% vs. 10%, p = 0.001) and NT-proBNP levels (1487 [512&ndash;3940] pg/mL vs. 571 [200&ndash;1931] pg/mL, p = 0.01). Myosin inhibitor therapy was more frequently prescribed to women (14% vs. 3%, p &lt; 0.001). Imaging assessments revealed similar left ventricular ejection fraction and maximal wall thickness between sexes, but women had a higher prevalence of significant left ventricular outflow tract (LVOT) obstruction (34% vs. 14%, p &lt; 0.001), higher maximal LVOT gradient (65 [45&ndash;100] vs. 51 [20&ndash;89] mmHg, p &lt; 0.001), and elevated E/e&rsquo; ratio (14 &plusmn; 7 vs. 11 &plusmn; 5, p = 0.01). The prevalence of significant late gadolinium enhancement (&gt;15% of myocardial mass) was also higher in women (20% vs. 11%, p = 0.04). Likely pathogenic and pathogenic (LP/P) sarcomeric mutations were identified in approximately one-third of genotyped patients, with no significant sex difference in prevalence. Rates of device implantation, appropriate or inappropriate shocks, heart transplantation and all-cause mortality were similar between men and women.</span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Arial,sans-serif"><u><span style="font-size:12.0pt"><span style="font-family:&quot;Times New Roman&quot;,serif">Conclusion</span></span></u><span style="font-size:12.0pt"><span style="font-family:&quot;Times New Roman&quot;,serif">: In this large cohort of HCM patients, we found that women were often diagnosed later than men despite presenting at baseline with more severe symptoms, higher NT-proBNP levels, worse diastolic function, greater LVOT obstruction, and increased myocardial fibrosis. Our findings emphasize sex-related differences in disease severity at diagnosis and underscore the importance of timely, comprehensive evaluation in women to guide optimal management.</span></span></span></span></p>