SPC365

Beyond the genotype in hypertrophic cardiomyopathy: prevalence, phenotypic expression and disease-related outcomes

Session: Sessão de Posters 18 - Miocardiopatia hipertrófica: genética, fenótipo e desfechos
Speaker: Helena Santos Moreira

Congress: CPC 2026
Topic: F. Valvular, Myocardial, Pericardial, Pulmonary, Congenital Heart Disease
Theme: 17. Myocardial Disease
Subtheme: 17.1 Myocardial Disease – Pathophysiology and Mechanisms
Session Type: Posters Eletrónicos
FP Number: ---
Authors: Helena Santos Moreira; Miguel Rocha; Pedro Mangas Palma; Catarina Marques; Mariana Vasconcelos; Elisabete Martins; Rui André Rodrigues; Ana Lebreiro

<p style="text-align:justify"><span style="font-family:Aptos,sans-serif"><strong><span style="font-family:&quot;Aptos Display&quot;,sans-serif">Background: </span></strong><span style="font-family:&quot;Aptos Display&quot;,sans-serif">Genetic testing plays a pivotal role in hypertrophic cardiomyopathy (HCM) but its real-world clinical impact remains uncertain.</span></span></p>

<p style="text-align:justify"><span style="font-family:Aptos,sans-serif"><strong><span style="font-family:&quot;Aptos Display&quot;,sans-serif">Purpose: </span></strong><span style="font-family:&quot;Aptos Display&quot;,sans-serif">To characterize the genetic profile of a real-world HCM cohort and assess its correlation with phenotypic expression and disease-related outcomes (DRO).</span></span></p>

<p style="text-align:justify"><span style="font-family:Aptos,sans-serif"><strong><span style="font-family:&quot;Aptos Display&quot;,sans-serif">Methods: </span></strong><span style="font-family:&quot;Aptos Display&quot;,sans-serif">Single-centre retrospective study of patients (pts) with confirmed HCM and prior genetic testing. Syndromic or infiltrative phenocopies were excluded. DRO&nbsp;included cardiovascular (CV) mortality, CV hospitalizations/urgent visits, device implantation and/or therapies, arrhythmias (ventricular arrhythmias and atrial fibrillation/flutter) and advanced heart failure. Data were obtained from medical record review.</span></span></p>

<p style="text-align:justify"><span style="font-family:Aptos,sans-serif"><strong><span style="font-family:&quot;Aptos Display&quot;,sans-serif">Results: </span></strong><span style="font-family:&quot;Aptos Display&quot;,sans-serif">101 pts were included, 55 male (54.5%), mean age 60&plusmn;18 years. 29.7% had no identifiable genetic variants (n=30), 43.6% (n=44) carried pathogenic/likely pathogenic (P/LP) variants and 26.7% (n=27) had variants of uncertain significance (VUS). Among genotype-positive (GP) pts, sarcomere variants predominated (n=38, 86.4%), mostly involving &beta;-myosin heavy chain &nbsp;- MYH7 (n=16, 36%) and cardiac myosin-binding protein C gene - MYBPC3 (n=8, 18.2%) genes.</span></span></p>

<p style="text-align:justify"><span style="font-family:Aptos,sans-serif"><span style="font-family:&quot;Aptos Display&quot;,sans-serif">Although diagnosis was more common&nbsp;through routine/familial screening (58.4%), genotype-negative (GN) pts were diagnosed significantly later&nbsp;(52&plusmn;18 vs 40&plusmn;21 years; p&lt;0.001) and&nbsp; due to symptoms (p=0.006). GP pts had more family history of HCM (47.8% vs 17.5%; p&lt;0.001) but&nbsp;without differences in sudden death history.&nbsp;</span></span></p>

<p style="text-align:justify"><span style="font-family:Aptos,sans-serif"><span style="font-family:&quot;Aptos Display&quot;,sans-serif">GN pts had a higher rates of arterial hypertension (51.9%, p&lt;0.001), dyslipidemia (63%, p&lt;0.001) and diabetes (22.2%, p=.019).</span></span></p>

<p style="text-align:justify"><span style="font-family:Aptos,sans-serif"><span style="font-family:&quot;Aptos Display&quot;,sans-serif">Asymmetric septal morphology was predominant (n=77, 76.2%), with similar maximal wall thickness (19 &plusmn; 4 mm; <em>p</em>=0.89). GN pts exhibited more left ventricle outflow tract obstruction (LVOTO) (n=16, 28.1% in GN vs n=5, 11.6% in GP, p=0.046) and systolic anterior motion of the mitral valve/subvalvular apparatus (n=17, 29.8% in GN vs n=6, 14% in GP, p&lt;0.050).&nbsp; LV ejection fraction (65 &plusmn; 5%; p=0.99) and&nbsp;diastolic parameters were similar.&nbsp;</span></span></p>

<p style="text-align:justify"><span style="font-family:Aptos,sans-serif"><span style="font-family:&quot;Aptos Display&quot;,sans-serif">Cardiac MRI showed a higher proportion of late gadolinium enhancement (LGE) &gt;15% in GP pts (n= 23, 53.3% in GP vs n=14, 24.6% in GN, p=0.016) and broader intramyocardial LGE beyond septal segments (n=19, 54.3% in GP vs n=10, 20.8%&nbsp; in GN, p=0.017).&nbsp;&nbsp;</span></span></p>

<p style="text-align:justify"><span style="font-family:Aptos,sans-serif"><span style="font-family:&quot;Aptos Display&quot;,sans-serif">Biomarkers, namely NTpBNP&nbsp;(p=0.64) and hs-Troponin I (p=0.44), were comparable.</span></span></p>

<p style="text-align:justify"><span style="font-family:Aptos,sans-serif"><span style="font-family:&quot;Aptos Display&quot;,sans-serif">After a median follow-up of 6 (IQR 9) years, no significant differences were observed in the composite endpoint of DRO&nbsp;(log-rank p=0.179) &ndash; figure 1.</span></span></p>

<p style="text-align:justify"><span style="font-family:Aptos,sans-serif"><strong><span style="font-family:&quot;Aptos Display&quot;,sans-serif">Conclusions:</span></strong><span style="font-family:&quot;Aptos Display&quot;,sans-serif"> &nbsp;In our real-world cohort, GP pts exhibited greater myocardial fibrosis, while GN pts showed a higher burden of later diagnosis and obstructive physiology. Despite these genotype&ndash;phenotype differences, DRO were similar, underscoring the limitations of current risk models and the need for deeper understanding and integration of genetic testing in HCM. </span></span></p>