Abstract 9638: Multimodal Mechanisms for Rapid Conversion of Atrial Fibrillation by Pulmonary Delivery of a Novel Flecainide Formulation

IntroductionFlecainide administered with a handheld nebulizer causes signature increases in PR interval and QRS complex duration with potential to terminate atrial fibrillation (AF) by optimizing dose and speed of drug delivery.HypothesisInhaled flecainide will terminate AF through multimodal actions.MethodsIn 6 anesthetized Yorkshire pigs, intrapericardial injection of acetylcholine followed by burst pacing induced AF reproducibly. A novel solubility-enhancing cyclodextrin formulation (HPßCD) containing 75 mg/ml flecainide (0.5 or 1.0 mg/kg, bolus) was instilled intratracheally at 2 min after AF initiation. Effects on PR interval and atrial depolarization (Pa) duration were studied in 4 additional pigs.ResultsIntratracheal instillation of flecainide HPßCD (0.5 mg/kg or 1.0 mg/kg) accelerated conversion of AF to normal sinus rhythm in a dose-dependent manner. Following placebo instillation, AF spontaneously converted to sinus rhythm at 10.4±0.05 min. The lower dose of flecainide terminated AF at 5.5±0.01 min (mean ± SEM), shortening AF duration by 4.9 min or 48% (*p=0.014), whereas the higher dose terminated AF at 2.9±0.02 min, shortening AF by 7.5 min or 72% (*p=0.008) (Figure). AF dominant frequency (Figure) was reduced from 7.3±0.8 (placebo) to 6.5±1.0 Hz by the lower dose (*p