Repetitive 4-Week Periods of Atrial Electrical Remodeling Promote Stability of Atrial Fibrillation

BACKGROUND: Episodes of atrial fibrillation (AF) are known to cause both a rapid reduction in atrial refractoriness (atrial electrical remodeling) and a more delayed increase in AF stability thought to be due to a so-called "second factor." The aim of this study was to quantify the effects and time course of such a factor on AF stability in the chronic goat model. METHODS AND RESULTS: AF was maintained in 6 goats by burst atrial pacing for 3 consecutive 4-week periods separated a mean of 6+/-2.1 days of sinus rhythm. Six days of sinus rhythm was just sufficient for refractoriness changes to reverse fully in all goats. Atrial effective refractory period, AF inducibility, and duration of individual episodes of AF were assessed at regular intervals. There was a progressive reduction from month 1 to 2 to 3 in the mean duration of burst pacing required to induce individual episodes of AF of 60 seconds (178+/-251, 110+/-102, and 21+/-30 hours), 1 hour (229+/-224, 136+/-104, and 68+/-51 hours), and 24 hours (277+/-218, 192+/-190, and 102+/-75 hours; P<0.03). The frequency with which AF was induced during extrastimulus pacing increased progressively from 16.7% in month 1 to 31.7% in month 2 and 46.9% in month 3 (P<0.001). CONCLUSIONS: Sequential 4-week periods of atrial fibrillation result in a progressive increase in AF stability independent of baseline atrial refractory period. This finding suggests the presence of a second factor in the self-perpetuation of AF with a time course comparable to that of AF-induced ultrastructural changes in the atria.