SPC365

The phenotypic expression of hypertrophic cardiomyopathy – insights from a population with pathogenic mutations in the MYBPC3 gene

Session: Sessão de Posters 45 - Miocardiopatia hipertrófica
Speaker: Ana Beatriz Garcia

Congress: CPC 2024
Topic: F. Valvular, Myocardial, Pericardial, Pulmonary, Congenital Heart Disease
Theme: 17. Myocardial Disease
Subtheme: 17.4 Myocardial Disease – Treatment
Session Type: Cartazes
FP Number: ---
Authors: Ana Beatriz Garcia; Catarina Gregório; Catarina Simões de Oliveira; Ana Margarida Martins; Oana Moldovan; Daniel Caldeira; Hugo Madeira; Fausto J. Pinto; Dulce Brito

<p style="text-align:justify"><span style="font-family:Calibri"><span style="font-size:11,0000pt"><span style="font-family:'Calibri Light'">Introduction:&nbsp;</span></span></span><span style="font-family:Calibri"><span style="font-size:11,0000pt"><span style="font-family:'Calibri Light'">Sarcomeric hypertrophic cardiomyopathy (HCM) is a heterogeneous genetic disorder that leads to left ventricular hypertrophy and fibrosis. Myosin-binding protein C (</span></span><em><span style="font-size:11,0000pt"><span style="font-family:'Calibri Light'"><em>MYBPC3</em></span></span></em><span style="font-size:11,0000pt"><span style="font-family:'Calibri Light'">) is the most frequently mutated gene. The disease &nbsp;has a complex genetic and phenotypic expression, posing challenges in the clinical evaluation and counselling of affected individuals. </span></span></span></p>

<p style="text-align:justify"><span style="font-family:Calibri"><span style="font-size:11,0000pt"><span style="font-family:'Calibri Light'">Purpose:&nbsp;</span></span></span><span style="font-family:Calibri"><span style="font-size:11,0000pt"><span style="font-family:'Calibri Light'">To analyse the HCM phenotype and the evolutive profile in </span></span><em><span style="font-size:11,0000pt"><span style="font-family:'Calibri Light'"><em>MYBPC3</em></span></span></em><span style="font-size:11,0000pt"><span style="font-family:'Calibri Light'">-HCM families.</span></span></span></p>

<p style="text-align:justify"><span style="font-family:Calibri"><span style="font-size:11,0000pt"><span style="font-family:'Calibri Light'">Methods:&nbsp;</span></span></span><span style="font-family:Calibri"><span style="font-size:11,0000pt"><span style="font-family:'Calibri Light'">A prospective analysis of </span></span><em><span style="font-size:11,0000pt"><span style="font-family:'Calibri Light'"><em>MYBPC3</em></span></span></em><span style="font-size:11,0000pt"><span style="font-family:'Calibri Light'">-HCM family members followed in a tertiary centre was performed, considering those who have a </span></span><em><span style="font-size:11,0000pt"><span style="font-family:'Calibri Light'"><em>MYBPC3</em></span></span></em><span style="font-size:11,0000pt"><span style="font-family:'Calibri Light'">&nbsp;mutation classified as pathogenic or likely pathogenic (P/LP) according to ClinVar. Data on clinical evaluation, laboratory values, results on electrocardiography (ECG) and echocardiogram (Echo) were recorded.</span></span></span></p>

<p style="text-align:justify"><span style="font-family:Calibri"><span style="font-size:11,0000pt"><span style="font-family:'Calibri Light'">Results:&nbsp;</span></span></span><span style="font-family:Calibri"><span style="font-size:11,0000pt"><span style="font-family:'Calibri Light'">Twenty-four HCM probands (unrelated families) were included, totalling 123 studied individuals (99 relatives); 29 out of 123 were mutation carriers only (no phenotype) and 47/123 had phenotypic expression (defined by a wall thickness &ge; 15mm or &ge; 13 mm in relatives). Twelve different P/LP mutations were identified. On average, 5 relatives were studied per family (varying from 1 to 17), making possible the identification of 3 additional individuals at risk (mutation carrier only or already with the HCM phenotype) for each studied proband, with the inherent clinical implications and possibility of focused counselling.&nbsp;</span></span></span><span style="font-family:Calibri"><span style="font-size:11,0000pt"><span style="font-family:'Calibri Light'">During a mean follow-up (FUP) time of 10 years, only 2 out of 29 carriers developed the disease. Considering the 47 patients with phenotypic expression, 53% were male and the diagnosis was done at a mean age of 45 &plusmn;16 years. &nbsp;The diagnosis was primarily prompted by family screening (74%), with a minority of patients diagnosed due to symptoms (15%, mainly fatigue), ECG abnormalities (9%), and echocardiographic features (2%). Most patients were in NYHA functional class I at the initial evaluation. The mean maximum NT-proBNP value was 630 pg/mL. ECG analysis during FUP revealed an evolution toward the presence of abnormal repolarization (p=0.001) and the appearance of necrosis-like patterns. Mean left ventricular ejection fraction (LVEF) was about 60%. Four patients (11%) developed heart failure (HF) with reduced LVEF. The mean maximum wall thickness was 18 mm at initial evaluation and 19 mm at FUP. Lef ventricular outflow tract (LVOT) obstruction was identified in 19 % of affected patients at diagnosis, with a mean gradient at rest and with Valsalva manoeuvre of 64 and 139 mmHg, respectively. At FUP, only 4% had obstructive-HCM. Septal myectomy was performed in 6% of patients and 26% received an ICD. </span></span></span></p>

<p style="text-align:justify"><span style="font-family:Calibri"><span style="font-size:11,0000pt"><span style="font-family:'Calibri Light'">Conclusion:&nbsp;</span></span></span><span style="font-family:Calibri"><span style="font-size:11,0000pt"><span style="font-family:'Calibri Light'">This analysis gathers information about patients with 12 different pathogenic variants in the </span></span><em><span style="font-size:11,0000pt"><span style="font-family:'Calibri Light'"><em>MYBPC3</em></span></span></em><span style="font-size:11,0000pt"><span style="font-family:'Calibri Light'">&nbsp;gene, contributing to a better understanding of the natural history of the disease.</span></span></span></p>

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