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.