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Genome-wide association study identifies a susceptibility locus at 21q21 for ventricular fibrillation in acute myocardial infarction.

ABSTRACT: Sudden cardiac death from ventricular fibrillation during acute myocardial infarction is a leading cause of total and cardiovascular mortality. To our knowledge, we here report the first genome-wide association study for this trait, conducted in a set of 972 individuals with a first acute myocardial infarction, 515 of whom had ventricular fibrillation and 457 of whom did not, from the Arrhythmia Genetics in The Netherlands (AGNES) study. The most significant association to ventricular fibrillation was found at 21q21 (rs2824292, odds ratio = 1.78, 95% CI 1.47-2.13, P = 3.3 x 10(-10)). The association of rs2824292 with ventricular fibrillation was replicated in an independent case-control set consisting of 146 out-of-hospital cardiac arrest individuals with myocardial infarction complicated by ventricular fibrillation and 391 individuals who survived a myocardial infarction (controls) (odds ratio = 1.49, 95% CI 1.14-1.95, P = 0.004). The closest gene to this SNP is CXADR, which encodes a viral receptor previously implicated in myocarditis and dilated cardiomyopathy and which has recently been identified as a modulator of cardiac conduction. This locus has not previously been implicated in arrhythmia susceptibility.

SUBMITTER: Bezzina CR

PROVIDER: S-EPMC3966292 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

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Genome-wide association study identifies a susceptibility locus at 21q21 for ventricular fibrillation in acute myocardial infarction.

Bezzina Connie R CR Pazoki Raha R Bardai Abdennasser A Marsman Roos F RF de Jong Jonas S S G JSSG Blom Marieke T MT Scicluna Brendon P BP Jukema J Wouter JW Bindraban Navin R NR Lichtner Peter P Pfeufer Arne A Bishopric Nanette H NH Roden Dan M DM Meitinger Thomas T Chugh Sumeet S SS Myerburg Robert J RJ Jouven Xavier X Kääb Stefan S Dekker Lukas R C LRC Tan Hanno L HL Tanck Michael W T MWT Wilde Arthur A M AAM

Nature genetics 20100711 8

Sudden cardiac death from ventricular fibrillation during acute myocardial infarction is a leading cause of total and cardiovascular mortality. To our knowledge, we here report the first genome-wide association study for this trait, conducted in a set of 972 individuals with a first acute myocardial infarction, 515 of whom had ventricular fibrillation and 457 of whom did not, from the Arrhythmia Genetics in The Netherlands (AGNES) study. The most significant association to ventricular fibrillati ...[more]

PMID: 20622880

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Project description:Patients with acute myocardial infarction (AMI) complicated by acute heart failure or cardiogenic shock have high mortality with conventional management.This study evaluated outcomes of patients with AMI who received durable ventricular assist devices (VAD).Patients in the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) registry who underwent VAD placement in the setting of AMI were included and compared with patients who received VAD for non-AMI indications.VAD were implanted in 502 patients with AMI: 443 left ventricular assist devices; 33 biventricular assist devices; and 26 total artificial hearts. Median age was 58.3 years, and 77.1% were male. At implantation, 66% were INTERMACS profile 1. A higher proportion of AMI than non-AMI patients had pre-operative intra-aortic balloon pumps (57.6% vs. 25.3%; p < 0.01), intubation (58% vs. 8.3%; p < 0.01), extracorporeal membrane oxygenation (17.9% vs. 1.7%, p < 0.01), cardiac arrest (33.5% vs. 3.3%, p < 0.01), and higher-acuity INTERMACS profiles. At 1 month post-VAD, 91.8% of AMI patients were alive with ongoing device support, 7.2% had died on device, and 1% had been transplanted. At 1-year post-VAD, 52% of AMI patients were alive with ongoing device support, 25.7% had been transplanted, 1.6% had left VAD explanted for recovery, and 20.7% had died on device. The AMI group had higher unadjusted early phase hazard (hazard ratio [HR]: 1.24; p = 0.04) and reduced late-phase hazard of death (HR: 0.57; p = 0.04) than the non-AMI group did. After accounting for established risk factors, the AMI group no longer had higher early mortality hazard (HR: 0.89; p = 0.30), but it had lower late mortality hazard (HR: 0.55; p = 0.02).Patients with AMI who receive VAD have outcomes similar to other VAD populations, despite being more critically ill pre-implantation. VAD therapy is an effective strategy for patients with AMI and acute heart failure or shock in whom medical therapy is failing.

Dataset Information

Genome-wide association study identifies a susceptibility locus at 21q21 for ventricular fibrillation in acute myocardial infarction.

Publications

Genome-wide association study identifies a susceptibility locus at 21q21 for ventricular fibrillation in acute myocardial infarction.

Similar Datasets

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