SPC365

Phenotypes and natural history of TNNT2 gene mutation carriers with familial hypertrophic cardiomyopathy: a long follow up study

Session: Comunicações Orais - Sessão 21 - Miocardiopatia hipertrófica
Speaker: Catarina Gregório

Congress: CPC 2023
Topic: F. Valvular, Myocardial, Pericardial, Pulmonary, Congenital Heart Disease
Theme: 17. Myocardial Disease
Subtheme: 17.7 Myocardial Disease - Other
Session Type: Comunicações Orais
FP Number: ---
Authors: Catarina Gregório; Beatriz Garcia; Sofia Morgado; Nuno Cortez Dias; Oana Moldovan; Fausto J. Pinto; Hugo Madeira; Dulce Brito
<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#212121"><span style="background-color:#ffffff"><strong>Background and aim:</strong></span></span></span></span><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#212121"><span style="background-color:#ffffff"> In hypertrophic cardiomyopathy (HCM), variants (Vs) in&nbsp;cardiac troponin T gene </span></span></span></span><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#212121"><span style="background-color:#ffffff"><em>(TNNT2)</em></span></span></span></span><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#212121"><span style="background-color:#ffffff"> have been associated with high risk of sudden cardiac death (SCD) and mild left ventricular hypertrophy (LVH</span></span></span></span><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#212121"><span style="background-color:#ffffff"><em>).&nbsp; </em></span></span></span></span><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#212121"><span style="background-color:#ffffff">We did a retrospective longitudinal observational study of a cohort with HCM and </span></span></span></span><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#212121"><span style="background-color:#ffffff"><em>TNNT2</em></span></span></span></span><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#212121"><span style="background-color:#ffffff"> Vs.</span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#212121"><span style="background-color:#ffffff"><strong>Methods:</strong></span></span></span></span><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#212121"><span style="background-color:#ffffff"> The study group comprised 11 probands with Vs in </span></span></span></span><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#212121"><span style="background-color:#ffffff"><em>TNNT2</em></span></span></span></span><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#212121"><span style="background-color:#ffffff"> gene (G+) and 17 G+ out of 51 relatives. Clinical, ECG and echocardiographic (echo) data, and 5-year estimation risk of SCD applying ESC score, were evaluated at the time of diagnosis (T0) and compared with those at the last follow up (Fup) visit (T1). Lifelong time to disease presentation was estimated by Kaplan-Meier survival analysis method.&nbsp;</span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#212121"><span style="background-color:#ffffff"><strong>Results:</strong></span></span></span></span><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#212121"><span style="background-color:#ffffff"> At T0, from the 28 genetic carriers, 20 had HCM phenotype (G+Ph+), 8 had no LVH (G+/Ph-). Four different Vs were identified by Next Generation Sequencing in the 11 families (F): p.Trp287ter [6F,n=12]; p.Asn271Ile (2F,n=9); p.Arg278Cys (2F,n=5); and p.Lys66Asn (1F,n=2). Two Vs were known as pathogenic/likely pathogenic; 2 are classified as VUS (Vs of unknown significance), but both co-segregated with the disease in the families. During a median Fup of 13(8-19) years(y), penetrance of the 4 Vs was 86%.The 20 G+/Ph+ pts, 9 males, aged 44 (30-59)y, had maximal wall thickness (MWT) of 16.5(14.0-21.0) mm; 6 pts had diffuse LVH and 3 were obstructive</span></span></span></span><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#212121"><span style="background-color:#ffffff"><em>.</em></span></span></span></span><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#212121"><span style="background-color:#ffffff"> Left atrial dimension (LAD) was 37.0(33.4-43.3) mm. Three patients (pts) had normal ECG. Thirteen(65%) pts had an uneventful evolution; 7(35%) needed hospitalization related to HCM, including 2 cases of septal myectomy and 2 that evolved to a dilated phase. No SCD occurred. There were 2 non-cardiac deaths. At T1, MWT was 19.0(14.0-21.0) mm (p=NS vs.T0) but LAD increased significantly [46.3(38.0-52.6) mm, p&lt;0.001]; 2 pts had atrial fibrillation; 4 were obstructive forms.. The median ESC risk score [1.6(1-2.6) at T0)] came to 1.9(1-2.6) and similarly for all the different Vs. Only 4 out the 8 G+/Ph- pts developed LVH but, in the remaining, ECG abnormalities emerged. Groups did not differ in gender, age at diagnosis, and Fup time. All Vs behave similarly regarding echo expression (fig.1).&nbsp;</span></span></span></span></p>

<p><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#212121"><span style="background-color:#ffffff"><strong>Conclusions:</strong></span></span></span></span><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#212121"><span style="background-color:#ffffff">HCM associated with </span></span></span></span><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#212121"><span style="background-color:#ffffff"><em>TNNT2</em></span></span></span></span><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#212121"><span style="background-color:#ffffff"> mutations expressed phenotypically at all ages; ECG abnormalities were frequent even in the absence of LVH;LVH was variable, but mild to moderate in most patients; the natural history associated with these 4 variants in the </span></span></span></span><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#212121"><span style="background-color:#ffffff"><em>TNNT2</em></span></span></span></span><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#212121"><span style="background-color:#ffffff"> gene was benign in most patients. No SCD occurred.</span></span></span></span><span style="font-size:11pt"><span style="font-family:'Quattrocento Sans',sans-serif"><span style="color:#212121"><span style="background-color:#ffffff"> </span></span></span></span></p>