Pre-treatment with dofetilide improves ablation outcome
NEW YORK, NY. Pulmonary vein isolation (PVI) on its own is not very effective in eliminating persistent and permanent atrial fibrillation. In order to achieve a reasonable rate of success it is necessary to create additional linear lesions in the left atrium as well as targeting sites demonstrating complex fractionated electrograms. This is time-consuming and often leads to post-ablation atrial tachycardias, especially left atrial flutter. Electrophysiologists at the St. Luke's and Roosevelt hospitals now report that pre-ablation treatment with the antiarrhythmic dofetilide (Tikosyn) markedly improves PVI success rate in persistent afibbers.

Their clinical trial involved 71 consecutive patients with persistent AF who had been in continuous afib for a median of 6 months (at least 7 days but no longer than 1 year). The average age of the patients was 59 years, 73% were male, and the average time since diagnosis was 5 years. The outcome of the PVI procedure was compared to that in a group of 35 paroxysmal afibbers.

After achieving a documented INR of 2.0 or greater for at least 3 weeks, patients in the persistent AF group were treated with a minimum of 6 doses of dofetilide over a 3-day period while being monitored in hospital. If normal sinus rhythm (NSR) had not been restored after the last dose electrical cardioversion was performed. Dofetilide treatment was maintained until the PVI and for 1 to 3 months post-ablation. There was no interruption of dofetilide therapy for the PVI procedure. During the time leading up to the ablation 79% of the patients transferred to paroxysmal AF, 18% had complete suppression of any type of AF, and the remaining 3% (2 patients) remained in persistent AF.

After an average wait time of 85 days all patients underwent a standard anatomically-guided PVI with complete electrical isolation of the pulmonary veins as the end point. Fifteen percent underwent an early repeat procedure prompted by recurrent AF. Six months following the procedure 76% of the group were free of AF without the use of antiarrhythmics. This success rate declined to 70% at 12 months. The 35 patients in the paroxysmal group underwent identical PVIs with an average success rate of 80% at 6 months and 75% at 12 months with a 14% repeat rate. The success rate at 6 months was substantially better (92%) among persistent afibbers whose afib was completely suppressed by the pre-ablation dofetilide treatment than among those who converted to paroxysmal AF (75%). Neither of the 2 patients who remained in persistent AF after dofetilide therapy were in NSR at 6 months post-ablation.

Neither age, gender, hypertension, left atrial size, dofetilide dose, duration of persistent AF, time since diagnosis, nor clinical response to dofetilide predicted outcome of the ablation. The only significant variable doing so was the decrease in P-wave duration observed on the electrocardiogram (ECG) prior to initial cardioversion vs that noted just prior to ablation. In patients having a successful PVI P-wave duration decreased by 15% (from 137 ms to 116.7 ms), while it only decreased by 6% (from 132.9 ms to 124.7 ms) in those whose ablation was unsuccessful. There was no significant change in P-wave duration over the 3-month pre-ablation period in the paroxysmal control group.

The researchers suggest that the decrease in P-wave duration associated with dofetilide treatment is an indication that the treatment resulted in reverse electrical remodeling of the left atrium, thus substantially increasing the chance of a successful PVI outcome. They conclude that pre-ablation dofetilide therapy may be a viable alternative to more extensive lesion creation following a standard PVI.

Khan, A, et al. Pulmonary vein isolation alone in patients with persistent atrial fibrillation: an ablation strategy facilitated by antiarrhythmic drug induced reverse remodeling. Journal of Cardiovascular Electrophysiology, August 31, 2010 [Epub ahead of print]

Editor's comment: The observation that pre-ablation dofetilide therapy increases the chance of a successful outcome of PVIs in the case of persistent AF is clearly of great importance and, if confirmed in larger trials, could herald a novel way of effectively dealing with persistent AF.