Cardiac Electrophysiology
The known relationship between common allele risk scores and AF suggests a fundamental change in electrophysiologic substrate. This study finds an association between sinus node function and AF risk ,though the mechanism is unclear. Large longitudinal studies have noted that those with a higher resting heart have increased risk of incident AF14, 15, consistent with our findings here. Changes in resting heart rate as well as heart rate variability suggest the mechanism may lie within the autonomic nervous system. The associations between common genetic risk for AF and both SDNN and RMSDD infer a consistent relationship possibly mediated through higher vagal tone. Similarly, large longitudinal studies suggest extremes of RMSDD and lower SDNN are independently associated with incident AF14 16. In addition, studies have shown that SDNN typically decreases immediately prior to a paroxysm of AF17. These findings suggest that the genetic loci associated with AF mediate at least part of their effects through sinus node and cardiac autonomic function.
While infrahisian conduction (HV and QRS) does not appear to be associated with common genetic risk for AF there does appear to be an association between dual AVN physiology and the risk score we have deployed. An association of AF genetic risk with dual AV node physiology suggests a potential link through AV node reentrant tachycardia (AVNRT), but it is unclear if this represents a functional or structural change in the AV node. Little is known of the genetics of AVNRT but a fundamental relationship between the substrate for AVNRT and that for AF is supported by an unexpectedly high incidence of new-onset AF in AVNRT patients following ablation 18. Mechanisms of atrioventricular development have previously been implicated in the predisposition to AF with Wolff-Parkinson-White (WPW) syndrome patients also prone to paroxysmal AF at a young age19. Anatomic distribution of Cx43 in defined AV nodal structures has supported an anatomic basis for dual AV nodal physiology and aberrant Cx43 expression has been directly implicated in rare subsets of AF, as well as in the ongoing remodeling of atrial substrate after onset of the arrhythmia20, 21.