Author + information
- Received February 25, 2008
- Revision received July 7, 2008
- Accepted July 8, 2008
- Published online October 7, 2008.
- Sanjiv M. Narayan, MD, FACC⁎,⁎ (, )
- Dhruv Kazi, MD⁎,
- David E. Krummen, MD⁎ and
- Wouter-Jan Rappel, PhD†
- ↵⁎Reprint requests and correspondence:
Dr. Sanjiv M. Narayan, Cardiology/111A, 3350 La Jolla Village Drive, San Diego, California 92161
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.
- atrial fibrillation
- action potential duration
- conduction velocity
- electrical restitution
- monophasic action potentials
- electrical remodeling
Supported by grants to Dr. Narayan from the National Institutes of Health (HL70529, HL83359) and the Doris Duke Charitable Foundation, and to Dr. Krummen by an American College of Cardiology–Merck Fellowship. Francis Marchlinksi, MD, served as Guest Editor for this article.
- Received February 25, 2008.
- Revision received July 7, 2008.
- Accepted July 8, 2008.
- American College of Cardiology Foundation