SCN5A Mutations in Brugada Syndrome
What is the prognostic significance of the SCN5A mutation in patients with Brugada syndrome (BS)?
Among 415 patients (mean age 46 years) with BS enrolled in a registry, 60 patients (13.3%) had an SCN5A mutation and the other 355 patients were genotype-negative. Clinical and electrocardiographic characteristics were compared between the two groups, as were cardiac events (first appropriate implantable cardioverter-defibrillator shock, aborted cardiac arrest [ACA], sudden cardiac death) during a mean follow-up of 72 months.
Genotype-positive patients had a first episode of syncope at a younger age (mean age 34 vs. 42 years). There was not a significant difference between the two groups in the prevalence of a type I Brugada pattern or in the inducibility of ventricular tachycardia/fibrillation. The cardiac event rate was 2.5%/year overall and was significantly higher in the genotype-positive patients than in the genotype-negative patients. Among 228 patients who were asymptomatic at the time of enrollment, the cardiac event rate during follow-up was 0.9%/year, with no significant difference between the genotype-positive and genotype-negative patients. By multivariate analysis, genotype-positivity and a history of ACA were the only significant predictors of cardiac events.
BS patients who have an SCN5A mutation experience syncope at a younger age and have a higher risk of cardiac events during follow-up.
In the BS, SCN5A mutations cause a reduction in the inward sodium current and are associated with an acceleration in myocyte apoptosis. This results in conduction abnormalities and fibrosis that increase the risk of a malignant ventricular arrhythmia, perhaps explaining why genotype-positivity was associated with a higher rate of cardiac events in this study.
Keywords: Apoptosis, Arrhythmias, Cardiac, Brugada Syndrome, Death, Sudden, Cardiac, Defibrillators, Implantable, Genetic Association Studies, Genotype, Heart Conduction System, Mutation, Syncope, Tachycardia, Ventricular, Ventricular Fibrillation
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