SPC365

Clinical profile and outcomes of patients with Hypertrophic Cardiomyopathy associated with mutations in the MYH7 gene: a long longitudinal follow up study

Session: Sessão de Posters 45 - Miocardiopatia hipertrófica
Speaker: Catarina Gregório

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: Catarina Gregório; Ana Beatriz Garcia; Daniel Cazeiro; Marta Vilela; Oana Moldovan; Hugo Madeira; Fausto Pinto; Dulce Brito

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="font-size:11.0pt"><strong>Introduction: </strong>Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disease and is characterized by increased LV wall thickness with no other identified cause. Variants in <em>MYH7</em> gene are one of the most common underlying defects associated with HCM.</span></span></span></p>

<p><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="font-size:11.0pt"><strong>Aim:</strong> To describe the clinical characteristics and outcomes of patients (pts) with HCM associated with pathogenic or likely pathogenic (P/LP) variants in the <em>MYH7</em> gene, followed over a long period of time.</span></span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="font-size:11.0pt"><strong>Methods: </strong>Single center retrospective longitudinal study. Clinical, ECG and echocardiographic data from 29 unrelated HCM probands and their relatives with P/LP variants in<em> </em>the<em> MYH7</em> gene (G+) were evaluated at the time of diagnosis and at the last FUP visit. </span></span></span></p>

<p><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="font-size:11.0pt"><strong>Results: </strong>A total of 115 pts were included and studied (29 unrelated probands and 86 relatives). There were 75 genetic carriers (G+); at diagnosis, 51 (68%) had HCM phenotype (G+Ph+) and 24 (32%) had no ventricular hypertrophy (G+Ph-). Sixteen different variants were identified by Next Generation Sequencing but only 12 were classified as P/LP.</span></span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="font-size:11.0pt">The most frequent P/LP variants were: p.Ile263Thr </span><span style="font-size:11.0pt">[</span><span style="font-size:11.0pt">4Families (F), n=28</span><span style="font-size:11.0pt">]</span><span style="font-size:11.0pt">, p.Ala797Thr (4F, n=8), p.Glu1356Lys (3F, n=8), and p.Arg663His (1F, n=7). One family express a co-dominance of two variants in the <em>MYH7 </em>gene (p.Arg633His) and <em>MYBPC3</em> gene (p.Glu619Lys), however the <em>MYH7</em> variant was considered as the main responsible for the disease expression. The population G+ was evaluated during a FUP of 14.3&plusmn;2 years (0.2-46.8) years; globally the penetrance of all P/LP variants was 67%. Ten (34.5%) out of 29 families had a known history of premature sudden cardiac death (SCD).</span></span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="font-size:11.0pt">The 51 G+/Ph+ pts, 24 male, 40&plusmn;2.6 years at diagnosis, maximal wall thickness (MWT) was 18.6&plusmn;0.84 mm, left atrial dimension (LAD) was 43.6&plusmn;0.9 mm and 12 (23.5%) had left ventricular tract obstruction (LVOTO) at rest. </span></span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="font-size:11.0pt">During a median follow-up of 8.5 (0.2-46.8) years, 6 (12%) pts had a hospital admission due to HF and 14 (27%) pts worsened at least one NYHA functional class. One patient progressed to a burn-out phase, 6 pts developed LVOTO, and 3 pts had</span><span style="font-size:11.0pt"> a septal reduction procedure. Fifteen pts died during FUP, but no SCD occurred; however 9 (17%) pts received an ICD for primary prevention. At FUP, the MWT increased to 20.6&plusmn; 0.8 (p=NS), and LAD increased significantly to 47.9&plusmn;10.4 mm (p=0.01). </span></span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="font-size:11.0pt">Only 1 out the 24 G+/Ph- pts at diagnosis, developed phenotype during a FUP of 6.2&plusmn;1.6 years (mild LV hypertrophy of 14 mm) and no events occurred in any of the 24 pts. </span></span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="font-size:11.0pt">Comparing pts affected by the 4 most commons identified mutations, no differences were observed regarding HF admissions and survival during FUP (p=0.09).</span></span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="font-size:11.0pt"><strong>Conclusions:</strong> The majority of pts with <em>MYH7</em>-related HCM present with a benign phenotype over a long FUP period. However the risk of SCD exist in about 30% of pts demanding the need for preventive ICD implantation and in addition worsening HF affects more than 25% of the pts during their lifetime.</span></span></span></p>