Intravenous dofetilide terminated atrial fibrillation in 100% of dogs with congestive heart failure compared to only 20% of dogs with rapid atrial pacing (P<0.01).
Does dofetilide terminate and prevent atrial fibrillation differently in dog models of rapid atrial pacing versus congestive heart failure?
Dofetilide is highly effective at terminating and preventing AF in a canine model of heart failure (macroreentry) but largely ineffective in a rapid atrial pacing model (multiple-wave front reentry).
Absolute Event Rate: 100% vs 20%
p-value: p=<0.01
BACKGROUND: Rapid atrial pacing (RAP) and congestive heart failure (CHF) produce different experimental substrates for atrial fibrillation (AF). We tested the hypothesis that AF maintained by different substrates responds differently to antiarrhythmic-drug therapy. METHODS AND RESULTS: The class III antiarrhythmic agent dofetilide was given intravenously at doses of 10 (D10) and 80 (D80) microg/kg to dogs with AF induced either (1) after 7 days of RAP at 400 bpm or (2) in the presence of CHF induced by rapid ventricular pacing. Dofetilide terminated AF in all CHF dogs, but D10 failed to terminate AF in any RAP dog, and D80 terminated AF in only 1 of 5 RAP dogs (20%) (P<0.01 for efficacy in CHF versus RAP dogs). Dofetilide was highly effective in preventing AF induction by atrial burst pacing in dogs with CHF but was totally ineffective in dogs with RAP. Dofetilide increased atrial effective refractory period and AF cycle length to a greater extent in CHF dogs. Epicardial mapping with 248 bipolar electrodes showed that CHF-related AF was often due to macroreentry, with dofetilide terminating AF by causing block in reentry circuits. RAP-related AF was due to multiple-wave front reentry, with dofetilide slowing reentry and decreasing the number of simultaneous waves, but not sufficiently to stop AF. CONCLUSIONS: The mechanism underlying AF importantly influences dofetilide efficacy. The dependence of drug efficacy in AF on the underlying mechanism has potentially significant implications for antiarrhythmic drug use and development and may explain the well-known therapeutic resistance of longer-duration AF.
Li et al. (Tue,) conducted a other in Atrial fibrillation. Dofetilide vs. Rapid atrial pacing (RAP) model vs Congestive heart failure (CHF) model was evaluated on Termination of atrial fibrillation (p=<0.01). Intravenous dofetilide terminated atrial fibrillation in 100% of dogs with congestive heart failure compared to only 20% of dogs with rapid atrial pacing (P<0.01).