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(Circulation. 2007;115:2094-2102.)
© 2007 American Heart Association, Inc.

Arrhythmia/Electrophysiology

Mechanism Underlying Initiation of Paroxysmal Atrial Flutter/Atrial Fibrillation by Ectopic Foci

A Simulation Study

Yunfan Gong, PhD; Fagen Xie, PhD; Kenneth M. Stein, MD; Alan Garfinkel, PhD; Calin A. Culianu, MS; Bruce B. Lerman, MD; David J. Christini, PhD

From the Department of Medicine, Division of Cardiology, Weill Medical College of Cornell University, New York, NY (Y.G., K.M.S., C.A.C., B.B.L., D.J.C.); Department of Physiology and Biophysics, Weill Graduate School of Medical Sciences of Cornell University, New York, NY (D.J.C.); and Department of Medicine, Division of Cardiology, University of California, Los Angeles (F.X., A.G.).

Correspondence to Yunfan Gong, PhD, or David J. Christini, PhD, Department of Medicine, Division of Cardiology, Weill Medical College of Cornell University, 520 E 70th St, Box 161, New York, NY 10021. E-mail yfgong{at}hotmail.com or dchristi@med.cornell.edu

Received February 9, 2006; accepted February 16, 2007.

Background— The mechanisms underlying paroxysmal atrial flutter/atrial fibrillation initiation by ectopic foci from various locations are unclear.

Methods and Results— We used parallel computational techniques to study an anatomically accurate 3-dimensional atrial structure incorporating a detailed ionic-current model of an atrial myocyte. At the single-cell level, upregulation of the L-type Ca²⁺ current I_Ca,L steepened restitution curves of action potential duration and conduction velocity compared with the control. Spontaneous firings of ectopic foci, coupled with sinus activity, produced dynamic spatial dispersions of repolarization, including discordant alternans, which caused conduction block and reentry only for the elevated I_Ca,L case. For each foci location, a vulnerable window for atrial flutter/atrial fibrillation induction was identified as a function of the coupling interval and focus cycle length. For ectopic foci in the pulmonary veins and left atrium, the site of conduction block and reentry gradually shifted, as a function of coupling interval, from the right atrium to the interatrial area and finally to the left atrium. The size of the vulnerable window was largest for pulmonary vein foci, becoming markedly smaller for right atrial foci, especially those near the sinoatrial node.

Conclusions— These findings suggest that a mechanism of dynamically induced repolarization dispersion, especially discordant alternans, underlies the induction of atrial flutter/atrial fibrillation by atrial ectopic foci. The sites and likelihood of reentry induction varied according to ectopic focus location and timing, with the largest vulnerable window corresponding to the pulmonary vein region.

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