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

Abstract

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 ×7 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 Ca ²⁺ ( I _Ca ), transient-outward ( I _to ), and the slow delayed-rectifier ( I _Ks ) currents while increasing the Na ⁺ -Ca ²⁺ 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.