IMPORTANCE OF REFRACTORINESS HETEROGENEITY IN THE ENHANCED VULNERABILITY TO ATRIAL-FIBRILLATION INDUCTION CAUSED BY TACHYCARDIA-INDUCED ATRIAL ELECTRICAL REMODELING

Background-Rapid atrial activation causes electrical remodeling that p romotes the occurrence and the maintenance of atrial fibrillation (AF) . Although remodeling has been shown to alter electrophysiological var iables, the spatial uniformity of these changes is unknown. Methods an d Results-Dogs subjected to rapid atrial pacing (400 bpm) for 24 hours (n=12) were compared with sham-operated dogs (instrumented but: not p aced, n=12). Epicardial mapping (240 bipolar electrodes) and extrastim ulation at a large number of sites (mean+/-SEM, 66+/-4 per dog) were u sed to evaluate atrial activation and the heterogeneity of the effecti ve refractory period (ERP), respectively. Rapid pacing increased both the percentage of sires at which AF could be induced by single prematu re stimuli (from 2.6+/-0.9% to 11.8+/-2.8%, P=0.007) and AF duration ( from 39+/-28 to 146+/-49 seconds, P=0.03). Atrial tachycardia decrease d atrial ERP (from 120+/-4 to 103+/-2 ms, P=0.003), increased the coef ficient of variation of ERP (from 14.9+/-0.9% to 20.7+/-0.9%, P<0.0001 ), and accelerated conduction velocity (from 91+/-2 to 108+/-3 cm/s, P =0.0004), with no change in the wavelength. The increase in ERP hetero geneity was due both to interregional differences in the extent of ERP remodeling and to increased intersite variability within regions. Ste pwise multilinear regression indicated that ERP heterogeneity was an i ndependent determinant of the inducibility (P<0.0001) and duration (P< 0.0001) of AF, whereas ERP per se and wavelength were not significant determinants. Combined mapping of AF induction and atrial ERP showed t hat premature extrastimuli induced AF at sites with short ERP by causi ng local conduction slowing and/or block in adjacent zones with longer ERP values. Conclusions-Atrial tachycardia causes nonuniform remodeli ng of atrial refractoriness that plays an important role in increasing atrial vulnerability to AF induction and the duration of induced AF.