SCN5A Mutation associated with acute myocardial infarction
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- 作者：Antonio Oliva ; Dan Hu ; Sami Viskin ; Tabitha Carrier ; Jonathan M. Cordeiro ; Hector Barajas-Martinez ; Yusheng Wu ; Elena Burashnikov ; Ramon Brugada ; Rafael Rosso ; Alex ; ra Guerchicoff ; Guido Pollevick ; Vincenzo L. Pascali ; Charlie Antzelevitch
- 关键词：Ventricular tachycardia ; Fibrillation ; Arrhythmia ; Ischemia ; Sudden cardiac death
- 刊名：Legal Medicine
- 出版年：2009
- 出版时间：April 2009
- 年：2009
- 卷：11
- 期：Supplement 1
- 页码：S206-S209
- 全文大小：239 K
文摘
Ventricular tachycardia and fibrillation (VT/VF) complicating Brugada syndrome, a genetic disorder linked to SCN5A mutations, and VF complicating acute myocardial infarction (AMI) have both been linked to phase 2 reentry. Because of these mechanistic similarities in arrhythmogenesis, we examined the contribution of SCN5A mutations to VT/VF complicating AMI. Nineteen consecutive patients developing VF during AMI were enrolled. Wild-type (WT) and mutant SCN5A genes were co-expressed with SCN1B in TSA201 cells and studied using whole-cell patch-clamp techniques. One missense mutation (G400A) in SCN5A was detected in a conserved region among the cohort of 19 patients. A H558R polymorphism was detected on the same allele. Unlike the other 18 patients who each developed 1-2 VF episodes during acute MI, the mutation carrier developed six episodes of VT/VF within the first 12 hours. All VT/VF episodes were associated with ST segment changes and were initiated by short-coupled extrasystoles. We describe the first sodium channel mutation to be associated with the development of an arrhythmic storm during acute ischemia. These findings suggest that a loss of function in SCN5A may predispose to ischemia induced arrhythmic storm. These results could be very useful for forensic implications regarding genetic screening in relatives.