Dissociation between ionic remodeling and ability to sustain atrial fibrillation during recovery from experimental congestive heart failure

Background - Congestive heart failure (CHF) downregulates atrial transient outward (I-to), slow delayed rectifier (I-Ks), and L-type Ca2+ (I-Ca,I- L) currents and upregulates Na+-Ca2+ exchange current (I-NCX) ( ionic remodeling) and causes atrial fibrosis ( structural remodeling). The relative importance of ionic versus structural remodeling in CHF-related atrial fibrillation (AF) is controversial. Methods and Results - We measured hemodynamic and echocardiographic parameters, mean duration of burst pacing induced AF (DAF), and atrial-myocyte ionic currents in dogs with CHF induced by 2-week ventricular tachypacing (240 bpm), CHF dogs allowed to recover without pacing for 4 weeks (REC), and unpaced controls. Left ventricular ejection fraction averaged 58.6 +/- 1.2% (control), 36.2 +/- 2.3% (CHF, P < 0.01), and 57.9 +/- 1.6% (REC), indicating full hemodynamic recovery. Similarly, left atrial pressures were 2.2 +/- 0.3 (control), 13.1 +/- 1.5 (CHF), and 2.4 +/- 0.4 (REC) mm Hg. CHF reduced I-to density by approximate to 65% ( P < 0.01), decreased I-Ca,I-L density by approximate to 50% ( P < 0.01), and diminished I-Ks density by approximate to 40% ( P < 0.01) while increasing I-NCX density by approximate to 110% ( P < 0.05). In REC, all ionic current densities returned to control values. DAF increased in CHF (1132 +/- 207 versus 14.3 +/- 8.8 seconds, control) and remained increased with REC (1014 +/- 252 seconds). Atrial fibrous tissue content also increased in CHF (2.1 +/- 0.2% for control versus 10.2 +/- 0.7% for CHF, P < 0.01), with no recovery observed in REC (9.4 +/- 0.8%, P < 0.01 versus control, P = NS versus CHF). Conclusions - With reversal of CHF, there is complete recovery of ionic remodeling, but the prolonged-AF substrate and structural remodeling remain. This suggests that structural, not ionic, remodeling is the primary contributor to AF maintenance in experimental CHF.