SCN5A Genetic Polymorphisms Associated With Increased Defibrillator Shocks in Brugada Syndrome

Abstract

Background: Brugada syndrome (BrS) is an inherited primary arrhythmia disorder leading to sudden cardiac arrest. SCN5A, encoding the α-subunit of the cardiac sodium channel (Nav1.5), is the most common pathogenic gene of BrS. An implantable cardioverter defibrillator (ICD) is the standard treatment for secondary prevention. This study aimed to evaluate association of the SCN5A variant with this cardiac conduction disturbance and appropriate ICD shock therapy in Thai symptomatic BrS patients with ICD implants.

Methods and results: Symptomatic BrS patients diagnosed at university hospital were enrolled from 2008 to 2011. The primary outcome of the study was an appropriate ICD shock defined as having non-pacing-associated ICD shock after the occurrence of ventricular tachycardia or ventricular fibrillation. Associations between SCN5A polymorphisms, cardiac conduction disturbance, and potential confounding factors associated with appropriate ICD shock therapy were analyzed. All 40 symptomatic BrS patients (median age, 43 years) with ICD implantations were followed for 24 months. There were 16 patients (40%) who had the appropriate ICD shock therapy after ICD treatment. An independent factor associated with appropriate ICD shock therapy was SCN5A-R1193Q with an adjusted hazard ratio of 10.550 (95% CI, 1.631-68.232).

Conclusions: SCN5A-R1193Q is associated with cardiac conduction disturbances. It may be a genetic marker associated with ventricular arrhythmia leading to appropriate ICD shock therapy in symptomatic BrS patients with ICD treatment. Because of the small sample size of study population and the appropriate ICD shock outcome, further large studies are needed to confirm the results of this study.

Keywords: Brugada syndrome; SCN5A R1193Q; appropriate implantable cardioverter defibrillator shock therapy; genetics; implantable cardioverter defibrillator.

Figure 1

ECGs of an SCN5A‐R1193Q carrier who had recurrent ventricular fibrillation (VF) with appropriate implantable cardioverter defibrillator (ICD) treatment. A, ECG shows widening of QRS duration (152 ms) and prolongation of PR interval (200 ms). B, ICD record with appropriate VF detection. C, Successful ICD shock from VF.

Figure 2

Kaplan–Meier survival curve of symptomatic Brugada Syndrome patients treated with an implantable cardioverter defibrillator (ICD) showed probabilities of ICD shock free and time to the first ICD shock categorized by presence of R1193Q polymorphism.