Abstract 2197: A Genotype Dependent Intermediate ECG Phenotype in Patients with Persistent Lone Atrial Fibrillation
Introduction: Atrial fibrillation (AF) is heterogeneous at the clinical and molecular levels. Association studies have reported that common single nucleotide polymorphisms (SNPs) in KCNE1 and SCN5A may predispose to AF. In this study, we tested the hypothesis that specific AF-associated genotypes confer variation on the appearance of AF assessed by analysis of fibrillatory rate of the atria.
Methods: Twenty-six unrelated patients (21 male, mean age 55 ± 12 years) with persistent lone AF (median AF duration 5 weeks) not taking class I or III antiarrhythmic drugs were studied. Atrial fibrillatory rate was obtained by spatiotemporal QRST cancellation and time-frequency analysis of the index surface ECG. Genotypes at the AF-associated loci in KCNE1 (G38S) and SCN5A (H558R) were determined by direct DNA sequencing.
Results: The atrial fibrillatory rate was 418±50 fibrillations per minute (fpm, range 336–521) in the study cohort. Carriers of the 38GG KCNE1 genotype (n=13) had significantly lower fibrillatory rates (392±36 vs 443±49 fpm, p=.006) compared to those with GS or SS genotype (n=13). Importantly 8 patients (30%) with fibrillatory rates > 450 fpm, all had either the GS or SS genotype. In contrast, there was no significant difference in the fibrillatory rate between the SCN5A H558R genotypes (409±52 [558HH] vs 432±44 [HR/RR] fpm, n=16 p=0.249). There were no significant associations between fibrillatory rate and clinical (age, gender, AF duration, drug treatment) or echocardiographic (left atrial diameter, LVEF) variables. In multivariate analysis, KCNE1 (G38S) was the only independent predictor of fibrillatory rate (R=.528, B=45.091, p=.006).
Conclusion: Atrial fibrillatory rate obtained from the surface ECG is at least in part determined by KCNE1 (G38S) genotype, suggesting this variant exerts functional effects on atrial electrophysiology. This intermediate phenotype may be useful for identifying subsets of patients for variability in AF susceptibility or response to therapies.