Abstract
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.