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(Circulation. 2004;110:1520-1526.)
© 2004 American Heart Association, Inc.

Arrhythmia/Electrophysiology

Atrial Ionic Remodeling Induced by Atrial Tachycardia in the Presence of Congestive Heart Failure

Tae-Joon Cha, MD; Joachim R. Ehrlich, MD; Liming Zhang, MSc; Stanley Nattel, MD

From the Department of Medicine, Montreal Heart Institute and University of Montreal, Montreal, Quebec, Canada.

Correspondence to Stanley Nattel, 5000 Belanger St E, Montreal, Quebec, H1T 1C8, Canada. E-mail stanley.nattel{at}icm-mhi.org

Received December 1, 2003; de novo received March 22, 2004; accepted April 26, 2004.

Background— Atrial fibrillation (AF) and congestive heart failure (CHF) produce discrete forms of atrial ionic remodeling. The in vivo effects of atrial tachycardia (AT) remodeling are altered by CHF. This study evaluated underlying mechanisms at the level of ionic remodeling.

Methods and Results— We studied 4 groups of dogs: (1) unpaced controls (CTLs); (2) CHF caused by 2-week ventricular tachypacing (VTP, 240 bpm); (3) AT (400 bpm x7 days); and (4) CHF+AT (2-week VTP with AT for the last 7 days). CHF and CHF+AT groups equally increased left atrial pressure. AF duration was increased in all paced groups. Effective refractory period (ERP) was decreased by 42% in AT versus CTL but by only 24% in AT+CHF versus CHF. CHF reduced L-type Ca²⁺ (I_Ca), transient-outward (I_to), and the slow delayed-rectifier (I_Ks) currents while increasing the Na⁺-Ca²⁺ exchanger (I_NCX) and not affecting the inward-rectifier (I_K1) current. AT reduced I_to and I_Ca while increasing I_K1 and leaving I_Ks unaltered. The addition of AT to CHF failed to alter I_to, I_Ks, or I_NCX beyond the effect of CHF alone, decreased I_Ca slightly compared with CHF alone, but had smaller effects on I_Ca and I_K1 compared with AT alone. Thus, CHF+AT, as would occur in a CHF patient who develops AF, produced an ionic remodeling pattern different from that of CHF or AT alone and from what would have been predicted from additive effects of CHF and AT.

Conclusions— The presence of CHF alters AT-induced ionic remodeling. Thus, the ionic remodeling caused by cardiac arrhythmias in the presence of cardiac pathology is not necessarily predictable from the effects of either alone, with important potential implications for understanding the pathophysiology of arrhythmias in the diseased heart.

Key Words: heart failure • ion channels • atrium • fibrillation

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