SPC365

Clinical outcomes in a population with Hypertrophic Cardiomyopathy and MYBPC3 gene disease: the short version of a long history.

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:10,0000pt"><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'">Hypertrophic cardiomyopathy (HCM) is an autosomal-dominant disease with variable genotypic and phenotypic expressions. </span></span><span style="font-size:11,0000pt"><span style="background-color:#ffffff"><span style="font-family:'Calibri Light'"><span style="color:#212121">Mutations in cardiac myosin binding protein C (encoded by </span></span></span></span><em><span style="font-size:11,0000pt"><span style="background-color:#ffffff"><span style="font-family:'Calibri Light'"><span style="color:#212121"><em>MYBPC3 </em></span></span></span></span></em><span style="font-size:11,0000pt"><span style="background-color:#ffffff"><span style="font-family:'Calibri Light'"><span style="color:#212121">gene) are the most common cause of HCM.</span></span></span></span><span style="font-size:11,0000pt"><span style="font-family:'Calibri Light'"><span style="color:#000000">&nbsp;Mutations in this gene are described as associated with a later onset of disease and a more benign prognosis.</span></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'"><span style="color:#000000">To evaluate prevalence of events in patients with sarcomeric HCM and pathogenic or likely pathogenic(P/LP) variants in the </span></span></span><em><span style="font-size:11,0000pt"><span style="font-family:'Calibri Light'"><span style="color:#000000"><em>MYBPC3</em></span></span></span></em><span style="font-size:11,0000pt"><span style="font-family:'Calibri Light'"><span style="color:#000000">&nbsp;gene.</span></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'"><span style="color:#000000">Methods:&nbsp;</span></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 patients (probands and affected relatives) followed in a tertiary centre was performed, considering only 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'">mutation classified as P/LP according to ClinVar. Data on clinical characteristics and events during the follow up were recorded. Descriptive and inferential statistics were performed.&nbsp;</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'"><span style="color:#000000">Results:&nbsp;</span></span></span></span><span style="font-family:Calibri"><span style="font-size:11,0000pt"><span style="font-family:'Calibri Light'"><span style="color:#000000">We included in this study 47 HCM patients from 24</span></span></span><em><span style="font-size:11,0000pt"><span style="font-family:'Calibri Light'"><span style="color:#000000"><em>&nbsp;MYBPC3</em></span></span></span></em><span style="font-size:11,0000pt"><span style="font-family:'Calibri Light'"><span style="color:#000000">-HCM unrelated families (53% male; mean age 45&plusmn;16 years), followed for a mean time of 12&plusmn;12 years. &nbsp;Twelve different P/LP variants were identified. Nineteen percent of patients had resting obstructive HCM at the initial evaluation, with a significant clinical and haemodynamic improvement during follow up to 4% (p=0.033), achieved through medical and septal reduction therapy (septal myectomy was performed in 6% of patients). Six (25%) families reported a history of sudden cardiac death (SCD). Twenty-six percent of patients received an implantable cardioverter-defibrillator (ICD), with 42% for primary prevention and 58% for secondary prevention.&nbsp;</span></span></span></span><span style="font-family:Calibri"><span style="font-size:11,0000pt"><span style="font-family:'Calibri Light'"><span style="color:#000000">Atrial fibrillation (AF) was documented in 36% of patients and was diagnosed at a mean age of 61 &plusmn; 14 years. Two patients with AF had a stroke, and no cerebrovascular events were identified in patients without AF. Nine percent developed heart failure (HF) with reduced left ventricular ejection fraction (LVEF), and among them, 2 had HF-related hospital admissions. Two patients with preserved LVEF also had HF hospital admissions. Six percent were admitted to the hospital with an initial diagnosis of acute coronary syndrome, but none had obstructive coronary disease. The mean maximum NT pro-BNP value in affected patients was 630 pg/mL.&nbsp;</span></span></span></span><span style="font-family:Calibri"><span style="font-size:11,0000pt"><span style="font-family:'Calibri Light'"><span style="color:#000000">Eight patients died, half having cardiovascular-related causes (2 had SCD). The composite outcome of AF, and/or stroke, hemodynamically significant ventricular arrhythmias, or HF hospital admission, occurred in 47% of patients (Figure 1). The NT pro-BNP plasma value during follow up was associated with the occurrence of this outcome (p=0.006).</span></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'"><span style="color:#000000">Conclusion:&nbsp;</span></span></span></span><span style="font-family:Calibri"><span style="font-size:11,0000pt"><span style="font-family:'Calibri Light'"><span style="color:#000000">We studied a cohort of patients with 12 MYBPC3 pathogenic variants, providing information about the clinical evolution and outcomes of these patients. Despite the relatively benign phenotype described, there are significant morbid events reflected in this population that need clinical and prognostic consideration and specific management.</span></span></span></span></p>