Frequency Dependent Effects of Class I Antiarrhythmic Agents Studied in Patients with Implanted Pacemakers

Use and frequency dependency are common properties of Class I antiarrhythmic agents, which block cardiac sodium channels in vitro. The purpose of this study was to examine the rate dependent effects of Class I agents on ventricular conduction in humans in a crossover fashion. Twelve patients with implanted pacemakers who required antiarrhythmic therapy were studied. Four Class I agents were administered as follows: lidocaine, 1 mg/kg bolus followed by 4 mg/min infusion; disopyramide, 1 mg/kg bolus followed by 0.02 mg/kg per hour; aprindine, 1 mg/kg bolus followed by 4 mg/min infusion; and flecainide, 100 mg/day orally for 1 week. Trains of ventricular test stimuli between 70-180 ppm were applied during stable VVI pacing at 60 ppm. QRS duration was determined using signal-averaged as well as standard ECGs. Lidocaine produced significant QRS prolongation at rates > 110 ppm (3.0% +/- 1.4% at 120 ppm, P < 0.05; 7.2% +/- 1.8% at 180 ppm, P < 0.01). Aprindine, disopyramide, and flecainide produced significant QRS prolongation at rates as low as 70 ppm and in a frequency dependent manner: 12.7% +/- 1.5%, 9.6% +/- 1.6%, and 13.3% +/- 2.8% at 70 ppm, respectively, (P < 0.01); 21.6% +/- 0.6%, 14.7% +/- 2.4%, and 29.9% +/- 4.2% at 180 ppm, respectively, (P < 0.01). Time constants of the single exponential development of QRS prolongation when the pacing rate was abruptly increased to 150 ppm were 0.09 +/- 0.02 sec for lidocaine, 5.1 +/- 1.2 sec for aprindine, 8.1 +/- 1.7 sec for disopyramide, and 11.9 +/- 1.4 sec for flecainide.(ABSTRACT TRUNCATED AT 250 WORDS)