Abstract 1922: NOS1AP is Associated With Arrhythmias in a Heart Failure Population With Severe LV Dysfunction
Background: Arrhythmias and sudden cardiac death (SCD) remain a major cause of mortality in patients with heart failure (HF). QT interval prolongation is a risk factor for SCD, and variants in the nitric oxide synthase 1 adaptor protein (NOS1AP) have been associated with QT prolongation and in patients without systolic heart failure. The role of NOS1AP in HF patients is unknown.
Methods: The Genetic Risk Assessment of Defibrillator Events (GRADE) study enrolled the prospectively followed subjects with an EF ≤ 0.30 and implantable cardiac defibrillators (ICD) for up to 5 years. Subjects were genotyped for the NOS1AP variant rs 10494366 T>G (G allele previously associated with QTc prolongation) by RT-PCR; freedom from appropriate shocks and survival were compared by genotype using ANOVA, SPSS and Kaplan-Meier analysis.
Results: Median follow-up on 808 subjects (81% male, 84% white, 73% ischemic, age 63±12 years, EF 0.21±0.06, NYHA class 2.2±0.6, 14.9% LBBB) was 23.8 ± 15.5 months. QTc was not related to appropriate shocks. The G allele frequency was 35% in whites (287 TT, 312 TG, 81 GG) and 65% in blacks (12 TT, 66 TG, 50 GG). Genotype was not associated QTc intervals (ms; 467±62 GG, 473±55 GT, 470±54 TT; p=0.820). GG homozygotes had more appropriate shocks than T-allele carriers (1 yr: 16±3% vs. 8±1%; 2 yr: 25±5% vs. 15±2%; p=0.018) but no difference in mortality (Figure⇓).
Conclusions: NOS1AP is associated with ventricular arrhythmias in cardiomyopathy patients, despite the absence of a detectable change in QTc. Variants in genes associated with cardiac repolarization may help to predict the risk of SCD in HF patients.