Conduction Disturbances in Patients with Atrial Fibrillation

University dissertation from Department of Cardiology, Clinical sciences, Lund University

Abstract: Background: The electrophysiological mechanisms underlying atrial fibrillation (AF) are incompletely understood. Experimental studies have shown that remodelling of the atrial myocardium is linked to the occurrence and perpetuation of AF. Interatrial conduction disturbances and also delayed conduction at the posteroparaseptal region have also been reported as potential arrhythmogenic substrates. However, there is insufficient clinical evidence. Pulmonary vein (PV) potentials are invariably recordable at the PV ostia in patients with AF, and delayed conduction around the PV ostia may play a role in the initiation and maintenance of AF. Objectives: 1) To find clinical evidence for the atrial remodelling in patients with chronic and paroxysmal AF; 2) to delineate the electrophysiological properties of transseptal conduction from the left to the right atrium in patients with paroxysmal AF; 3) to analyze the conduction velocities across the coronary sinus (CS) ostium (cross-CS ostium) and within the coronary sinus (intra-CS) in patients with and without paroxysmal AF; and 4) to investigate the presence and extent of PV potentials in patients without AF. Methods: Study I: To estimate the refractoriness of the atrium during AF, monophasic action potentials (MAPs) were recorded during AF from 1?3 sites in the right atrium in 7 patients with chronic AF (CAF) and in 11 patients with paroxysmal AF (PAF). The fibrillatory (FF) interval between two consecutive upstrokes of the MAP was measured. The mean, median, 15th, 10th, and 5th percentile and the shortest FF intervals were calculated in each patient and used as estimates of the local atrial effective refractory period (AERP) during AF. In 9 patients, AERP was also tested using the extra stimulus technique during sinus rhythm. Study II: To evaluate the left-to-right transseptal conduction, right atrial mapping using the CARTO electroanatomic mapping system was performed at 111 ? 16 sites during pacing from the distal CS in 16 patients with paroxysmal AF. Activation maps of the right atrium were obtained from all patients and the earliest breakthrough site was identified. The conduction times from the pacing site 1) to the earliest activation site of the septum, 2) to CS ostium, 3) to the presumed insertion of Bachmann's bundle, 4) the total septal activation time, and 5) the total right atrial activation time. Study III: To study the conduction delay across the CS ostium, the activation times and spatial distances of cross-CS ostium and intra-CS were measured between 5?11 paired sites, from which the activation velocities of cross-CS ostium and intra-CS were obtained in 13 patients with paroxysmal AF and 10 control patients with AV nodal re-entry tachycardia or ectopic atrial tachycardia, using the CARTO electroanatomic mapping system. Study IV: Circumferential catheter recordings at the PV ostia were obtained from 10 patients with paroxysmal AF and 9 with concealed WPW syndrome without any history of AF. Typical PV potential was defined as either rapid deflections that were separate from local atrial deflection with a time delay in between, or continuous, fractionated potentials that were not separate from the atrial deflection. The existence of PV potentials was verified during sinus rhythm and during atrial pacing at the distal CS for the left PVs or at the right atrial appendage for the right PVs. To quantify the extent to which the PV potentials were recordable, the number of PVs with typical PV potentials for each PV and for each patient was counted. The time interval from the onset to the end of the electrograms recordable at the PV ostium (A-PV interval) was measured, and the maximum and mean of these intervals were obtained. Results: Study I: Thirty-eight MAP recordings were obtained. The shortest FF interval during AF was significantly shorter in patients with chronic AF than in patients with paroxysmal AF (50±13 vs. 72±31 ms, p < 0.05). Similar differences were seen in the mean, median, 15th, 10th and 5th percentile FF interval. The AERP during sinus rhythm was significantly longer than the estimated AERPs (p < 0.05 to p < 0.01). Study II: A single transseptal breakthrough near the CS ostium was observed in all patients. The activation time from the pacing site to the earliest septal activation site was 47?13 ms. The total septal activation time (68±16 ms) was markedly longer than that in patients without AF in a previous observation, but the total RA activation time (118±17 ms) was similar. Study III: During sinus rhythm, the cross-CS ostium activation velocities in the AF group (1.2±0.2 m/s) were significantly slower than those in the control group (2.9±1.6m/s, p < 0.05). During distal CS pacing, the cross-CS ostium activation velocities in the AF group (1.0±0.5 m/s) also appeared slower than those in the control group (1.4±0.2m/s, p = 0.07). However, no difference was found in the intra-CS activation velocities between the two groups (2.8±1.9 m/s vs. 3.2±2.2 m/s and 1.5±0.3 m/s vs. 1.4±0.3 m/s, p > 0.05) during sinus rhythm and distal CS pacing. Study IV: Typical PV potentials were recorded in 31 of 34 PVs (91%) in patients with AF, but in 4 of 36 PVs (11.1%) in patients with concealed WPW syndrome. A simple, narrow potential was recorded in 3/34 PVs (9%) in patients with AF, but in 29/36 (81%) PVs in patients with concealed WPW syndrome. The maximal and mean A-PV intervals were significantly longer in patients with AF (71±24 and 49±13 ms, respectively) than in patients with concealed WPW syndrome (33±14 and 25±6 ms). Conclusions: Electrical remodelling of the atrial myocardium is more marked in patients with chronic AF than in patients with paroxysmal AF. The AERP was significantly shortened during AF as compared to that during sinus rhythm, and the AERP shortening was more marked in patients with chronic AF than in patients with paroxysmal AF. These clinical findings support the connection between the electrical remodelling and the occurrence and/or perpetuation of the AF. The preferential site of transseptal conduction during distal CS pacing is near the CS ostium in patients with paroxysmal AF. This has clinical implications when surgical dissection or catheter ablation is considered to eliminate interatrial connection in patients with AF. Interatrial conduction at the postero-paraseptal region across the CS ostium was significantly slower in patients with paroxysmal AF than in control patients, further supporting the link between interatrial conduction deterioration and paroxysmal AF. In patients with AF, typical PV potentials with marked conduction time delay were almost invariably recordable at the PV ostium; but in patients without any history of AF, merely simple, narrow potentials were found. These findings support the involvement of conduction delay and re-entrant activities around the PV ostia in the genesis and/or perpetuation of AF.