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RyR2 Common Gene Variant G1886S and the Risk of Ventricular Arrhythmias in ICD Patients with Heart Failure
Author(s) -
FRANCIA PIETRO,
ADDUCI CARMEN,
SEMPRINI LORENZO,
STANZIONE ROSITA,
SERDOZ ANDREA,
CAPRINOZZI MASSIMO,
SANTINI DARIA,
COTUGNO MARIA,
PALANO FRANCESCA,
MUSUMECI MARIA BEATRICE,
RUBATTU SPERANZA,
VOLPE MASSIMO
Publication year - 2015
Publication title -
journal of cardiovascular electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.193
H-Index - 138
eISSN - 1540-8167
pISSN - 1045-3873
DOI - 10.1111/jce.12658
Subject(s) - medicine , cardiology , ryanodine receptor 2 , ventricular fibrillation , implantable cardioverter defibrillator , heart failure , ventricular tachycardia , sudden cardiac death , atrial fibrillation , hazard ratio , ryanodine receptor , confidence interval , receptor
RyR2 G1886S Gene Variant and VT/VF in HF Background Cardiac ryanodine receptor 2 (RyR2) is critical to the electrical homeostasis of cardiomyocytes. Its gene variant rs3766871 entails channel destabilization and enhanced intracellular Ca 2+ oscillation, thus promoting cardiac arrhythmias. We investigated whether the RyR2 rs3766871 variant is associated with aborted sudden cardiac death or ICD therapy for ventricular tachycardia (VT)/fibrillation (VF) in heart failure (HF) patients implanted with a cardioverter defibrillator (ICD). Methods and Results A total of 183 HF patients with primary or secondary prevention ICD were divided in 2 groups. A VT/VF group was composed of secondary prevention patients and primary prevention patients with appropriate ICD intervention for VT/VF. An ICD control group was composed of 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 (HRs) were derived from Cox proportional‐hazards regression analysis. In all, 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 β‐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 β‐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.