OBJECTIVES: We undertook this study to determine whether human atrial fibrillation (AF) relates to steeply sloped action potential duration restitution (APDR) kinetics and whether the spatial nonuniformity of APDR promotes persistence of AF. BACKGROUND: A steeply sloped APDR curve is known to be an important determinant of the induction of more complex action potential duration (APD) dynamics and fibrillation. METHODS: Patients with chronic atrial fibrillation (CAF) (n = 18), paroxysmal atrial fibrillation (PAF) (n = 14) and normal control subjects (n = 9) were studied. The monophasic action potential duration at 90% repolarization (APD90) and the effective refractory period (ERP) were measured at six sites in the right atrium. After AF was electrically converted, APDR was assessed by delivering a single extrastimulus after a train of stimuli at a cycle length of 600 ms (S1S2) at six different sites of the right atrium, as well as rapid pacing at cycle lengths that induced APD alternans. RESULTS: The APD90 and ERP in patients with CAF were shorter than those in patients with PAF and control subjects (p < 0.05); however, the dispersions of APD90 and ERP in each group were similar. The maximal slopes of APDR by S1S2 and rapid pacing in patients with CAF (1.2 ± 0.4 and 1.7 ± 0.2) and PAF (1.1 ± 0.4 and 1.3 ± 0.4) were higher than those in control subjects (0.5 ± 0.3 and 0.8 ± 0.2, respectively; p < 0.01). The maximal slope obtained by S1S2 did not differ from that obtained by rapid pacing in any group. The inter-regional difference of the maximal slope in patients with CAF (1.6 ± 0.4, p < 0.05) was greater than that in patients with PAF (1.2 ± 0.3, p = NS vs. control) and control subjects (0.4 ± 0.2). CONCLUSIONS: Atrial fibrillation was related to steeply sloped (>1) APDR kinetics. The spatial dispersion of APDR in patients with chronic AF was greater than that of patients with paroxysmal AF and control subjects, indicating that the heterogeneity of APDR of the atrium plays an important role in the persistence ot AF.
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