LAUSR

BACKGROUND The negative inotropic effect of Class IC antiarrhythmic drugs limits their use for acute cardioversion of atrial fibrillation (AF). OBJECTIVE In an intact porcine model, we examined effects of pulmonary and intravenous (IV) administration of flecainide on left ventricular (LV) contractility and QRS complex width at doses that are effective in converting new-onset AF to sinus rhythm. METHODS Flecainide (1.5 mg/kg bolus) was delivered by intratracheal administration and compared to 2.0 mg/kg 10-min IV administration (ESC guideline) and to 0.5 and 1.0 mg/kg 2-min IV doses in 40 closed-chest, anesthetized Yorkshire pigs. Catheters were fluoroscopically positioned in the LV to monitor QRS complex width and contractility and at the bifurcation of the main bronchi to deliver intratracheal flecainide. RESULTS Peak flecainide plasma concentrations (Cmax) were similar but the 30-min AUC of plasma levels was 1.4- to 2.9-fold greater for 2.0 mg/kg 10-min IV infusion than for the lower, more rapidly delivered intratracheal and IV doses. The AUC for LV contractility, i.e., negative inotropic burden, was 2.2- to 3.6-fold greater for 2.0 mg/kg 10-min IV dose than for the lower, more rapidly delivered doses. QRS complex widening by flecainide was highly correlated with the decrease in LV contractility (r2=0.890, p<0.0001, for all IV doses; r2=0.812, p=0.014, for intratracheal flecainide). CONCLUSIONS QRS complex widening in response to flecainide is strongly correlated with the decrease in LV contractility. Rapid pulmonary or IV flecainide delivery reduces the negative inotropic burden while quickly achieving Cmax levels associated with conversion of AF.