Non-atrial fibrillation cardiac phenotypes associated with common atrial fibrillation genotypic risk

Background: Atrial fibrillation (AF) genetics studies have focused on a linear genotype- phenotype relationship, i.e. genetic predisposition to the arrhythmia. Genome wide association studies have implicated numerous upstream mechanisms responsible for AF. Objective: We hypothesized that the genetic predisposing factors for AF might be associated with non-AF clinical phenotypes and sought to characterize electrophysiology parameters as a function of AF genetic risk. Methods: . Biosamples were obtained from 405 subjects for classification of carrier status at 12 single nucleotide polymorphisms with a known association to AF allowing calculation of a validated AF genetic risk score. We then analyzed subgroups within the total population; in order to understand the effect on (a) sinus node function and cardiac conduction (b) primary atrial flutter (c) left atrial appendage morphology. Results: We evaluated 405 patients consisting of a range of genetic risk scores from −1.016 to +2.178. Within this, we identified 86 patients without prescribed chronotropic pharmacotherapy with a 24-hour Holter recording to investigate sinus node function; 181 patients with invasive H-V measurement at the time of electrophysiologic study to investigate cardiac conduction; 78 undergoing cavotricuspid isthmus ablation for typical atrial flutter without prior diagnosis of AF; and 284 patients with cardiac imaging of the left atrial appendage. Conclusions: A common AF genetic risk score is associated with a number of non-AF electrophysiologic relevant phenotypes. Sinus node function, AV node physiology, post flutter ablation AF risk, atrial appendage morphology all appear to be associated with the common genetic AF risk.