Abstract 2682: CAPON Alleles Predict Firings of ICDs Implanted for Primary Prevention of Sudden Cardiac Death
Background: Sudden cardiac death (SCD) remains the leading cause of death in individuals with ischemic and non-ischemic cardiomyopathies. Despite the risk-reduction of death offered by implantable cardioverter defibrillators (ICD), only a small proportion of patients of individuals with an ICD require defibrillation for ventricular arrhythmias (VT). To evaluate the genetic, structural and electrophysiological risk factors associated with SCD, we have established a registry of patients with cardiomyopathies referred for ICD implantation for primary prevention of SCD.
Methods and Results: A total of 465 (age 61 ± 12 years, 79% male, 28% African American) patients have been enrolled, 73% are former or current smokers, 49% hypertensive, 27% diabetic, and 65% had an ischemic cardiomyopathy. NYHA Class I, II, and III HF symptoms are present in 21%, 28%, and 51%, respectively, mean LVEF was 22 ± 10%. Monomorphic VT could be induced in 32% percent of the patients on programmed electrical stimulation at the time of ICD implantation. Approximately 90% of patients were treated with ACE inhibitors and beta blockers, ~70% with aspirin and statins. Over an average follow up of 1.5 ± 1 years, 16 patients died and 3 underwent cardiac transplantation. Thirty-one patients experienced ICD shocks of which, 16 were for VT/VF (annualized firing rate of 4.5%). We have previously shown that a common variant of the nNOS regulator CAPON, is highly associated with prolonged QT interval. Genotyping and haplotype analysis of CAPON revealed that the allele associated with prolonged QT interval was associated with the rate of appropriate ICD intervention in Caucasians (HR 8.3, 95% CI 1.1 - 65.4) adjusting for age and gender. Too few events were recorded in African Americans for analysis.
Conclusions: In patients with an ICD for primary prevention of SCD the presence of the minor allele of CAPON is associated with an increase in the rate of appropriate ICD therapy. The annualized appropriate ICD firing rate is less than that of previous studies. This registry will be an important resource for identifying the most suitable candidates for ICD implantation.