SPC365

Brugada syndrome: characterization of a Portuguese Brugada syndrome cohort

Session: Posters (Sessão 2 - Écran 2) - Arritmias 2 - Arritmias Ventriculares 1
Speaker: Ana Margarida Martins

Congress: CPC 2022
Topic: C. Arrhythmias and Device Therapy
Theme: 08. Ventricular Arrhythmias and Sudden Cardiac Death (SCD)
Subtheme: 08.3 Ventricular Arrhythmias and SCD - Diagnostic Methods
Session Type: Pósters Electrónicos
FP Number: ---
Authors: Margarida Martins; Joana Brito; Pedro Silvério António; Sara Couto Pereira; Pedro Alves da Silva; Beatriz Valente Silva; Ana Beatriz Garcia; Catarina Simões de Oliveira; Catarina Gregório; Afonso Nunes Ferreira; Gustavo Lima da Silva; Luís Carpinteiro; Nuno Cortez-Dias; Fausto j. Pinto; João de Sousa

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><strong><span style="color:black">Introduction</span></strong><span style="color:black">: Brugada syndrome (BrS) is an inherited cardiac arrhythmic disorder <span style="background-color:white">that can lead to sudden cardiac death. Although </span>SCN5A was the first pathogenic associated gene, other potential genes have been described. The relationship between SCN5A, spontaneous type 1 pattern and the predisposition to ventricular arrhythmias is not totally understood.</span></span></span></span><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><span style="color:#000000">&nbsp;</span></span></span></p>

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><strong><span style="color:black">Purpose: </span></strong><span style="color:black">To characterize mutations in a Portuguese cohort with BrS and to explore the genotype-phenotype association in terms of electrocardiographic pattern and arrhythmic risk.</span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><strong><span style="color:black">Methods: </span></strong><span style="color:black">Prospective single-center study of patients (pts) with BrS. Genetic test included SCN5A direct sequencing from 2003 a broad panel of 120 genes associated with cardiomyopathies and arrhythmic disorders from 2018. Genetic test results were classified according to pathogenicity: mutations of unknown significance (MUS), mutations potentially pathogenic (MPP) and known pathogenic mutations (KPM). Kaplan-Meyer survival analysis was used to explore the association between genetic test results and the risk of arrhythmic events during follow-up.</span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><strong><span style="color:black">Results</span></strong><span style="color:black">: A total of 94 pts [46&plusmn;12years, 67% male, 64.9% with type 1 spontaneous pattern, 35.1% with type 1 induced pattern] were submitted to genetic testing. No relevant mutations were identified in 68 pts (72%) and suspicious or pathogenic mutations were recognized in 26 (28%). The most frequent mutations occurred in SCN5A (N=20, 76.9%), and included 8 KPM: 4 in exon 23 (3 of them had the same mutation, c.4018G&gt;A), 2 in exon 26 (c.4534C&gt;T), 1 in exon 28 and 1 in exon 16. All MPP in SCN5A occurred either in exon 23 or 28. Considering MUS, 7 different mutations were described in 6 different exons (8, 15, 18, 23, 25 and two in 28). Additionally, in 6 pts (6,4%) presented MUS in other genes: SCN10A (N=2), ANK2 (N=2), SFM13A, CAV2 (associated with long QT), CACNA1D and PXDNL.&nbsp;</span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">We found no differences in the prevalence of spontaneous type 1 pattern considering gene mutation or mutation pathogenicity. A non-significant trend to higher arrhythmic risk was observed in pts presenting genetic mutations (either KPM, MPP or MUS), Long-Rank: 1.743, p=0.187 &ndash; Figure 1.</span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><strong><span style="color:black">Conclusion</span></strong><span style="color:black">:&nbsp;</span></span></span></span><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">Gene mutations are identified in a minority of BrS pts, mostly at SCN5A gene. No association was noticed between genetic test results and the ECG pattern. However, pts with identified mutation presented a tendency to higher arrhythmic risk. At present time, genetic tests in BrS are only relevant for familial screening, but long-term collection of data is crucial to elucidate the genotype-phenotype relation and arrhythmic risk.</span></span></span></span></p>

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