New heart attack study findings reported from D. Hu and co-authors
2007 OCT 29 -- "' Ventricular 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. OBJECTIVE Given the mechanistic similarities in arrhythmogenesis, the purpose of this study was to examine the contribution of SCN5A mutations to VT/VF complicating AMI," investigators in the United States report. "Nineteen 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 Among 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 changesand 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 <= .001). G400A current decay was accelerated and steady-state inactivation was shifted -6.39 mV (V-1/2 = -98.9 +/- 0.1 mV vs -92.5 +/- 0.1 mV, P<= .001). No mutations were detected in KCNH2, KCNQ1, KCNE1, or KCNE2 in the G400A patient. We describe the first sodium channel mutation to be associated with the development of an arrhythmic storm during acute ischemia," wrote D. Hu and colleagues. The researchers concluded: "These findings suggest that a loss of function in SCN5A may predispose to ischemia-induced arrhythmic storm." Hu and colleagues published their study in Heart Rhythm (Novel mutation in the SCN5A gene associated with arrhythmic storm development during acute myocardial infarction. Heart Rhythm, 2007;4(8):1072-1080). For additional information, contact C. Antzelevitch, Masonic Med Research Laboratory, 2150 Bleecker St., New York City, NY 13501, USA. The publisher of the journal Heart Rhythm can be contacted at: Elsevier Science Inc., 360 Park Avenue South, New York, NY 10010-1710, USA. Keywords: United States, New York, Biotechnology, Brugada Syndrome, Cardiology, Gene Therapy, Genetics, Genomics, Heart Attack, Myocardial Infarction, Tachycardia, Ventricular Tachycardia. This article was prepared by Cardiovascular Week editors from staff and other reports. Copyright 2007, Cardiovascular Week via NewsRx.com.
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