• Dan Hu, Sami Viskin, Antonio Oliva, Tabitha Carrier, Jonathan M Cordeiro, Hector Barajas-Martinez, Yuesheng Wu, Elena Burashnikov, Serge Sicouri, Ramon Brugada, Rafael Rosso, Alejandra Guerchicoff, Guido D Pollevick, and Charles Antzelevitch.
• Masonic Medical Research Laboratory, Utica, New York, USA.
• Heart Rhythm. 2007 Aug 1; 4 (8): 1072-80.

BackgroundVentricular tachycardia (VT) and ventricular fibrillation (VF) complicating Brugada syndrome, a genetic disorder linked to SCN5A mutations, and VF complicating acute myocardial infarction (AMI) both have been linked to phase 2 reentry.ObjectiveGiven the mechanistic similarities in arrhythmogenesis, the purpose of this study was to examine the contribution of SCN5A mutations to VT/VF complicating AMI.MethodsNineteen consecutive patients developing VF during AMI were enrolled in the study. Wild-type (WT) and mutant SCN5A genes were coexpressed with SCN1B in TSA201 cells and studied using whole-cell patch clamp techniques.ResultsAmong the cohort of 19 patients, one missense mutation (G400A) in SCN5A was detected in a conserved region. An H558R polymorphism was detected on the same allele. Unlike the other 18 patients, who each developed 1-2 VF episodes during AMI, 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. Flecainide and adenosine challenge performed to unmask Brugada and long QT syndromes both were negative. Peak G400A and G400A+H558R current were 70.7% and 88.4% less than WT current at -35 mV (P ConclusionWe 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.

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