Genetic marker of torsades de pointes risk following myocardial infarction

Abstract

a L i r i s c e c c c g Q Sudden cardiac death (SCD) secondary to ventricular arrhythmia is a common cause of adult mortality especially in the setting of acute myocardial infarction (MI). Epidemiological evidence supports an important contribution of genetic factors to SCD susceptibility as inferred from the robust nature of family history as an independent risk factor for this deadly event. Ventricular fibrillation dominates s the cause for SCD during the acute phase (minutes to ours) following acute MI. Sudden death risk remains subtantially elevated during the subacute (hours to days) and hronic (days to weeks) phases of the recovery period, but he substrate for this predisposition may be different than hat in the acute phase. Infrequently, subjects in the early post-MI period exhibit vidence of abnormal ventricular repolarization, specifically prolonged QT interval, that predisposes to the polymorhic ventricular tachyarrhythmia, torsades de pointes TdP). Although this phenomenon was originally regarded s a form of acquired long-QT syndrome (LQTS), one might have speculated that this idiosyncratic phenotype occurred in genetically predisposed individuals. In this issue of HeartRhythm, Crotti et al report results f a genetic investigation of infarct-related TdP. In this andidate gene, case-control association study, the investiators studied 13 subjects with prolonged QT intervals and dP occurring 2–11 days following acute MI. The subjects ere screened for genetic variants in 5 genes previously inked with congenital LQTS (KCNQ1, KCNH2, SCN5A, CNE1, and KCNE2). Importantly, none of the cases were xposed to QT-prolonging drugs or arrhythmogenic metaolic conditions (eg, hypokalemia). A control group conisting of 133 acute MI survivors without TdP and matched or ethnicity was also genotyped. The investigators discovered 2 types of genetic predisosition. In 2 of the 13 infarct-related TdP cases (15%), utations in either KCNH2 or SCN5A were identified that egregated with prolonged QT intervals in first-degree rel-