D-SOTALOL DECREASES DEFIBRILLATION ENERGY-REQUIREMENTS IN HUMANS - A NOVEL INDICATION FOR DRUG-THERAPY

Introduction: We assessed the effect of d-sotalol on defibrillation vo ltage and energy requirements in patients undergoing automatic defibri llator implantation, Drugs that primarily prolong cardiac refractorine ss generally decrease the energy requirements for defibrillation in an imal models, Despite the widespread use of antiarrhythmic drugs in pat ients with implanted cardioverter defibrillators, the effect of such d rugs on defibrillation energy requirements in humans has not been well studied, Sotalol (in the d,l racemic form) is an antiarrhythmic with beta-blocking and cardiac refractoriness prolonging effects, The d-iso mer of sotalol is largely devoid of beta-blocking effects; both forms decrease defibrillation energy requirements in animals, We hypothesize d that d-sotalol would decrease defibrillation voltage and energy requ irements in humans. Methods and Results: Fifteen patients undergoing i mplanted cardioverter defibrillator implantation were studied before a nd 20 minutes after d-sotalol infusion (2 mg/kg IV in 15 min, followed by 1 mg/kg per hour). The estimated energy (E(50)) and voltage (V-50) for 50% success in defibrillation (estimated from two successive defi brillation ''threshold'' measurements), ventricular effective refracto ry period, monophasic action potential duration, and mean cycle length of ventricular fibrillation were measured, along with heart rate, blo od pressure, and plasma concentration of d-sotalol, There was a signif icant decrease in defibrillation energy (E(50) = 12.4 +/- 5.0 J before and 8.4 +/- 4.0 J after d-sotalol, P < 0.003) and voltage (V-50 = 440 +/- 77 V before and 354 +/- 93 V after d-sotalol, P < 0.001). Consist ent with the Class III effect of d-sotalol, ventricular effective refr actory period increased from 284 +/- 21 to 330 +/- 24 msec (P < 0.001) , and action potential duration was prolonged from 296 +/- 28 to 340 /- 22 msec (P < 0.001), Following d-sotalol, there was a tendency for induced tachyarrhythmia to self-terminate (23/102 episodes before vs 7 4/150 after sotalol, P < 0.001), and ventricular fibrillation cycle le ngth was increased from 216 +/- 20 msec before to 274 +/- 23 msec (P < 0.001) after d-sotalol, despite the persistence of a rapid, disorgani zed rhythm of the surface EGG. No patient suffered adverse effects. Co nclusions: d-Sotalol lowers defibrillation energy by a mean 32% +/- 27 % at concentrations producing a 16% +/- 7% increase in ventricular eff ective refractory period. Along with its other antiarrhythmic effects, d-sotalol may increase the safety margin for defibrillation or allow lower programmed energies in patients with implanted defibrillators.