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(Circulation. 2006;114:2434-2442.)
© 2006 American Heart Association, Inc.

Arrhythmia/Electrophysiology

Activation of Inward Rectifier Potassium Channels Accelerates Atrial Fibrillation in Humans

Evidence for a Reentrant Mechanism

Felipe Atienza, MD, PhD; Jesús Almendral, MD, PhD; Javier Moreno, MD; Ravi Vaidyanathan, MS; Arkazdi Talkachou, MS; Jérôme Kalifa, MD; Angel Arenal, MD; Julian P. Villacastín, MD, PhD; Esteban G. Torrecilla, MD, PhD; Ana Sánchez, MD; Robert Ploutz-Snyder, PhD; José Jalife, MD; Omer Berenfeld, PhD

From Hospital General Universitario Gregorio Marañón (F.A., J.A., J.M., A.A., J.P.V., E.T., A.S.) and Hospital Clínico San Carlos (J.M., J.P.V.), Madrid, Spain, and Institute for Cardiovascular Research, SUNY Upstate Medical University, Syracuse, NY (R.V., A.T., J.K., R.P.-S., J.J., O.B.).

Correspondence to José Jalife, MD, Institute for Cardiovascular Research, SUNY Upstate Medical University, 766 Irving Ave, Syracuse, NY 13210. E-mail jalifej{at}upstate.edu

Received August 31, 2005; de novo received April 17, 2006; revision received September 19, 2006; accepted September 25, 2006.

Background— It is unclear whether atrial fibrillation (AF) drivers in humans are focal or reentrant. To test the hypothesis that functional reentry is involved in human AF maintenance, we determined the effects of adenosine infusion on local dominant frequency (DF) at different atrial sites. By increasing inward rectifier potassium channel conductance, adenosine would increase DF of reentrant drivers but decrease it in the case of a focal mechanism.

Methods and Results— Thirty-three patients were studied during AF (21 paroxysmal, 12 persistent) using recordings from each pulmonary vein–left atrial junction (PV-LAJ), high right atrium, and coronary sinus. DFs were determined during baseline and peak adenosine effect. In paroxysmal AF, adenosine increased maximal DF at each region compared with baseline (PV-LAJ, 8.03±2.2 versus 5.7±0.8; high right atrium, 7±2.2 versus 5.4±0.7; coronary sinus, 6.6±1.1 versus 5.3±0.7 Hz; P=0.001) and increased the left-to-right DF gradient (P=0.007). In contrast, in persistent AF, adenosine increased DF only in the high right atrium (8.33±1.1 versus 6.8±1.2 Hz; P=0.004). In 4 paroxysmal AF patients, real-time DF mapping of the left atrium identified the highest DF sites near the PV-LAJ, where adenosine induced an increase in DF (6.7±0.29 versus 4.96±0.26 Hz; P=0.008). Finally, simulations demonstrate that the frequency of reentrant drivers accelerates proportionally to the adenosine-modulated inward rectifier potassium current.

Conclusions— Adenosine accelerates drivers and increases frequency differently in paroxysmal compared with persistent human AF. The results strongly suggest that AF is maintained by reentrant sources, most likely located at the PV-LAJ in paroxysmal AF, whereas non-PV locations are more likely in persistent AF.

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