RyR2 common gene variant G1886S and the risk of ventricular arrhythmias in ICD patients with heart failure.

BACKGROUND: Cardiac ryanodine receptor 2 (RyR2) is critical to the electrical homeostasis of cardiomyocytes. Its gene variant rs3766871 entails channel destabilization and enhanced intracellular Ca2+ oscillation, thus promoting cardiac arrhythmias. We investigated whether the RyR2 rs3766871 variant is associated with aborted SCD or ICD therapy for VT/VF in heart failure (HF) patients implanted with a cardioverter defibrillator (ICD). METHODS AND RESULTS: 183 HF patients with primary or secondary prevention ICD were divided in two groups. A VT/VF group was composed by secondary prevention patients and primary prevention patients with appropriate ICD intervention for VT/VF. An ICD control group was composed by primary prevention patients free from any appropriate ICD intervention after 43±25 months follow-up. Study subjects were genotyped with respect to the rs3766871 RyR2 gene variant. Hazard ratios (HR) were derived from Cox proportional-hazards regression analysis. 56 patients constituted the VT/VF group and 127 patients the ICD control group. Male sex (HR: 3.02; 95% CI:0.99-9.18; p = 0.05), atrial fibrillation (AF; HR: 2.33; 95% CI:0.89-6.10; p = 0.08) and underuse of beta-blockers (HR:2.08; 95%CI:0.84-5.15; p = 0.11) were associated with the VT/VF phenotype. Prevalence of the rs3766871 minor allele was 2.8% in ICD control patients and 8.0% in the VT/VF group (p = 0.02). After adjustment for age, sex, AF and use of beta-blockers, the rs3766871 minor allele was associated with increased risk of VT/VF (HR: 3.49; 95% CI:1.14-10.62; p = 0.02). CONCLUSIONS: Our study identifies a significant role of RyR2 rs3766871 minor allele for increased susceptibility to VT/VF in a population of ICD patients with HF. This article is protected by copyright. All rights reserved