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CLINICAL RESEARCH: HEART RHYTHM DISORDER

Repolarization and Activation Restitution Near Human Pulmonary Veins and Atrial Fibrillation Initiation

A Mechanism for the Initiation of Atrial Fibrillation by Premature Beats

Sanjiv M. Narayan, MD, FACC^_*,_*, Dhruv Kazi, MD^_*, David E. Krummen, MD^_* and Wouter-Jan Rappel, PhD

^_* University of California and Veterans Affairs Medical Center, San Diego, California
Department of Physics and Center for Theoretical Biology, University of California, San Diego, California

Manuscript received February 25, 2008; revised manuscript received July 7, 2008, accepted July 8, 2008.

^_* Reprint requests and correspondence: Dr. Sanjiv M. Narayan, Cardiology/111A, 3350 La Jolla Village Drive, San Diego, California 92161 (Email: snarayan{at}ucsd.edu).

Objectives: The authors sought to study mechanisms to explain why single premature atrial complexes (PACs) from the pulmonary veins (PVs) may initiate human atrial fibrillation (AF).

Background: Theoretically, single PACs may initiate AF if the rate response of action potential duration (APD) restitution has a slope >1. However, human left atrial APD restitution and its relationship to AF have not been studied. We hypothesized that an APD restitution slope >1 near PVs explains the initiation of clinical AF.

Methods: We studied 27 patients with paroxysmal and persistent (n = 13) AF. We advanced monophasic action potential catheters transseptally to superior PVs. Restitution was plotted as APD of progressively early PACs against their diastolic interval (DI) from prior beats. Activation time restitution was measured using the time from the pacing artifact to each PAC.

Results: Compared with paroxysmal AF, patients with persistent AF had shorter left atrial APD and effective refractory period (p = 0.01). In paroxysmal AF, maximum left atrial APD restitution slope was 1.5 ± 0.4; and 12 of 13 patients had slope >1 (p < 0.001). In persistent AF, PACs encountered prolonged activation for a wider range of beats than in paroxysmal AF (p = 0.01), which prolonged DI and flattened APD restitution (slope 0.7 ± 0.2; p < 0.001); no patient had APD restitution slope >1. A single PAC produced AF in 5 patients; in all, an APD restitution slope >1 caused extreme APD oscillations after the PAC, then AF.

Conclusions: In patients with paroxysmal AF, maximum APD restitution slope >1 near the PVs enables single PACs to initiate AF. However, patients with persistent AF show marked dynamic activation delay near PVs that flattens APD restitution. Studies should determine how regional APD and conduction dynamics contribute to the substrates of persistent AF.

Key Words: atrial fibrillation • human • action potential duration • conduction velocity • electrical restitution • monophasic action potentials • electrical remodeling • alternans

Abbreviations and Acronyms   AF = atrial fibrillation   AP = action potential   APD = action potential duration   AT = activation time   DI = diastolic interval   ERP = effective refractory period   FRP = functional refractory period   LA = left atrium/atrial   MAP = monophasic action potential   PAC = premature atrial complex   PV = pulmonary vein

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