Electrophysiological Abnormalities Occur Prior to the Development of Clinical Episodes of Atrial Fibrillation: Observations from Human Epicardial Mapping

Background: Atrial fibrillation (AF) is characterized by irregular atrial activation maintained by an arrhythmogenic substrate. We addressed the hypothesis that the substrate of human AF includes changes in atrial conduction properties. Methods: Patients in sinus rhythm (SR) and permanent AF undergoing cardiac surgery underwent right atrial epicardial mapping. AF was induced by burst pacing in patients in SR and was defined as sustained at >30 seconds. Epicardial maps were analyzed to determine conduction properties, AF activation patterns, and refractoriness. Patients in SR underwent postoperative Holter monitoring. Results: Thirty‐seven subjects were recruited. (27 in SR and 10 in permanent AF). Sustained AF was induced in 17 patients in SR. Only patients with sustained AF developed any episodes of postoperative AF (P < 0.05), indicating the preexistence of an arrhythmogenic substrate, which was characterized by prolonged unipolar electrograms (37.0 ± 9.4 ms vs 27.5 ± 6.4 ms, P = 0.03), particularly in the region of the crista terminalis (41.2 ms ± 12.1 vs 26.7 ms ± 5.8, P = 0.004) compared with the nonsustaining group. However, these differences in electrogram characteristics were not associated with changes in wavefront propagation velocity (WPV) during SR or pacing. Activation mapping of acutely induced AF was compared with permanent AF and although there were shorter mean fibrillation intervals in permanent AF (171 ± 16 ms vs 229 ± 51 ms, P < 0.001), there was no difference in fibrillatory activation pattern (complexity scores: 2.21 ± 0.52 vs 2.02 ± 0.61) or WPV (46.9 ± 15.4 cm/s vs 53.5 ± 17.6 cm/s, P = 0.37). Fibrillatory activation pattern was associated with both WPV (P = 0.03) and wavelength (P = 0.03) in both pacing‐induced and permanent AF. Conclusions: Patients in SR capable of sustaining pacing‐induced AF have differences in electrogram duration, which are apparent before clinical episodes of AF. Although patients with permanent AF had shortening of refractoriness, there was no evidence of further changes in fibrillatory activation pattern or macroscopic wavefront propagation velocity in permanent AF. These results imply that changes occur before the onset of AF and indicate the presence of a substrate capable of maintaining AF with only alterations in refractoriness required for the development of permanent AF.