Spontaneous pulmonary vein firing in man: Relationship to tachycardia-pause early afterdepolarizations and triggered arrhythmia in canine pulmonary veins in vitro

Introduction: Rapid firing originating within pulmonary veins (PVs) initiates atrial fibrillation (AF). The following studies were performed to evaluate spontaneous PV firing in patients with AF to distinguish focal versus reentrant mechanisms. Methods: Intracardiac recordings were obtained in 18 patients demonstrating paroxysmal AF. Microelectrode (ME) recordings were obtained from superfused canine PV sleeves (N = 48). Results: Spontaneous PV firing (566 +/- 16 bpm; 127 +/- 6 ms cycle length) giving rise to AF (52 episodes) was observed. Tachycardia-pause initiation was present in 132 of 200 episodes of rapid PV firing and 34 of 52 AF episodes. The pause cycle length preceding PV firing was 1,039 +/- 86 ms following tachycardia (420 +/- 40 ms cycle length). The remaining episodes were initiated following a 702 +/- 32 ms pause during sinus rhythm (588 +/- 63 ms). Spontaneous firing recorded with a multipolar mapping catheter did not detect electrical activity bridging the diastolic interval between the initial ectopic and preceding post-pause sinus beat. Tachycardia-pause initiated PV firing (138 +/- 7 ms coupling interval) in patients correlated with tachycardia-pause enhanced isometric force, early afterdepolarization (EAD) amplitude, and triggered firing within canine PVs. Rapid firing (1,172 +/- 134 bpm; 51 +/- 8 ms cycle length) following an abbreviated coupling interval (69 +/- 12 ms) was initiated in 13 of 18 canine PVs following tachycardia-pause pacing during norepinephrine + acetylcholine superfusion. Stimulation selectively activating local autonomic nerve terminals facilitated tachycardia-pause triggered firing in canine PVs (5 of 15 vs 0 of 15; P < 0.05). Conclusions: The studies demonstrate (1) tachycardia-pause initiation of rapid, short-coupled PV firing in AF patients and (2) tachycardia-pause facilitation of isometric force, EAD formation, and autonomic-dependent triggered firing within canine PVs, suggestive of a common arrhythmia mechanism.