First-of-its-kind findings from two independent studies have identified a gene associated with sudden cardiac death.
Results of the studies were presented by Heiner Wieneke (Contilia Heart and Vessel Centre, St Marien-Hospital Mülheim, Germany) at the European Society of Cardiology Congress (ESC; 28 August – 2 September, London, UK).
The studies evaluated genetic markers to determine which gene abnormalities may be associated with ventricular tachyarrhythmias that can lead to sudden cardiac death.
The DISCOVERY (Diagnostic data influence on disease management and relation of genetic polymorphisms to ventricular tachyarrhythmia in ICD patients) study, which was sponsored by Medtronic, identified a gene associated with sudden cardiac death in patients with implantable cardioverter defibrillators (ICDs). A second study, Oregon SUDS (Oregon sudden unexpected death study), supported by the National Heart, Lung and Blood Institute (NHLBI) and the American Heart Association, confirmed this finding in the general population.
The DISCOVERY trial, conducted in 91 European centres between April 2007 and June 2011, used ICDs to monitor patients for abnormal heart rhythms and then identified the gene associated with a 50% relative risk increase in these life-threatening heart rhythms. These results were confirmed by Oregon SUDS, which is a community-based study conducted by the Arrhythmia Research Laboratory at the Cedars-Sinai Heart Institute, Los Angeles, USA. Oregon SUDS analysed causes of sudden cardiac death.
“This is the first time a gene has been identified using ICD monitoring and then confirmed to be associated with sudden cardiac death in the general population,” said Wieneke, principal investigator of the DISCOVERY trial. “These findings are a first step to learning more about how to determine better ways to prevent and treat this condition.”
“This research is vital to helping us better understand why some patients are at higher risk of sudden cardiac death, one of the leading causes of death globally,” said Sumeet Chugh, associate director of the Cedars Sinai Heart Institute and lead investigator for Oregon SUDS. “These findings put us one step closer to understanding the complexities of sudden cardiac death and may, someday, help us identify which patients are at risk.”
The two-part presentation started with the DISCOVERY trial, a prospective, multicentre study of 1,145 patients that investigated the association of single nucleotide polymorphisms (SNPs, a genetic variation) with the occurrence of ventricular arrhythmias in patients receiving ICDs for primary prevention of sudden cardiac death. Data showed that the gene GNAS holds two SNPs (c.2273C>T and c.393C>T) that were associated with an increased risk for ventricular tachyarrhythmias as identified by the ICDs.
In the second part of the analysis, the database of blood samples collected from 1,335 patients in the Oregon-SUDS trial was reviewed for the presence of SNPs identified in the DISCOVERY trial. During the validation phase, c.393C>T was found to be associated with an increased risk for SCD in a general population under both additive (odds ratio [OR] =1.2 [1.0-1.4], p=0.039) and recessive (OR=1.5 [1.1-2.1], p=0.01) genetic models. The study confirmed that this SNP was associated with a 50% increased risk of sudden cardiac death.