Functional characterization of atrial electrograms in sinus rhythm delineates sites of parasympathetic innervation in patients with paroxysmal atrial fibrillation

Objectives This study sought to characterize left atrial (LA) sinus rhythm electrogram (EGM) patterns and their relationship to parasympathetic responses during atrial fibrillation (AF) ablation. Background The mechanistic basis of fractionated LA EGMs in patients with paroxysmal AF is not well understood. Methods We analyzed 1,662 LA ablation sites from 30 patients who underwent catheter ablation for paroxysmal AF. Preablation EGM characteristics (number of deflections, amplitude, and duration) were measured in sinus rhythm. Parasympathetic responses during radiofrequency application (increase of atrial-His interval by 10 ms or decrease of sinus rate by >= 20%) were assessed at all sites. We also prospectively studied the effect of adenosine, a pharmacological agent mimicking acetylcholine signaling in myocytes, on LA EGMs. Finally, we performed mathematical simulations of atrial tissue to delineate possible mechanisms of fractionated EGMs in sinus rhythm. Results A specific pattern of pre-ablation sinus rhythm EGM (deflections >= 4, amplitude >= 0.7 mV, and duration >= 40 ms) was strongly associated with parasympathetic responses (sensitivity 72%, specificity 91%). The sites associated with these responses were found to be located mainly in the posterior wall of the LA. Adenosine administration and mathematical simulation of the effect of acetylcholine were able to reproduce a similar EGM pattern. Conclusions Parasympathetic activation during AF ablation is associated with the presence of pre-ablation high-amplitude fractionated EGMs in sinus rhythm. Local acetylcholine release could potentially explain this phenomenon.