Amiodarone reduces the prevalence of T wave alternans in a population with ventricular tachyarrhythmias.

INTRODUCTION: Testing for the presence of microvolt T wave alternans (TWA) is useful for arrhythmic risk stratification. Whether antiarrhythmic pharmacotherapy affects the presence of TWA is unknown. We tested whether patients with known ventricular tachyarrhythmias who were receiving amiodarone were less likely to manifest TWA as compared with those not receiving amiodarone. METHODS AND RESULTS: Forty-four patients with a history of ventricular tachyarrhythmias and an implantable cardioverter defibrillator (ICD) implanted at least 1 month earlier underwent TWA testing. In this group, 14 patients were receiving amiodarone and 30 were not. Indeterminate test results occurred in 13 patients without a significant difference in those receiving or not receiving amiodarone. In the 31 patients with determinate TWA testing, a positive test was less likely in those receiving amiodarone (1 of 9 [11%]) as compared with those not receiving amiodarone (14 of 22 [64%]; P = 0.04). During a follow-up period averaging 0.9 +/- 0.2 years, the presence of TWA (P = 0.04) and decreased left ventricular ejection fraction (P = 0.05) predicted appropriate ICD therapy for ventricular tachyarrhythmias. CONCLUSION: The prevalence of TWA was decreased in a chronic ventricular tachyarrhythmic population receiving amiodarone as compared with a population not receiving amiodarone.

Short-term rapid ventricular pacing prolongs ventricular refractoriness in patients.

BACKGROUND: Traditional concepts suggest that ventricular refractoriness should gradually shorten during rapid pacing and gradually return to baseline after termination of pacing. Animal data, however, have shown that under certain circumstances sustained rapid ventricular rates can prolong refractoriness and action potential duration and, thereby, promote ventricular arrhythmias. METHODS AND RESULTS: In humans we evaluated the effect of rapid pacing (cycle length 400 msec for 30 min from either the right ventricular apex [RVA, 13 patients] or high right atrium [HRA, 11 patients]) on the ventricular effective refractory period (VERP) as measured from the RVA, using the extrastimulus method (drive train 500 msec). A control group of seven patients had serial measurements of VERPs in the absence of pacing. For a given patient, all VERPs were measured at constant stimulus output (twice diastolic threshold) from the same ventricular site and at the same drive train cycle length. VERPs obtained immediately following rapid pacing did not differ from those at baseline (P = 0.46); however, VERPs obtained 15 minutes post pacing were prolonged compared with baseline VERPs (231 +/- 20 msec vs 246 +/- 23 msec, P < 0.0026). Pacing site has no impact on VERP prolongation. There was no effect of time on VERP in the absence of pacing. CONCLUSION: In contrast to traditional concepts of refractoriness, after the termination of sustained rapid ventricular rates, VERP prolonged. This phenomenon could help explain the observation of torsades de pointes in some patients after atrioventricular junction ablation or the administration of a Class IA antiarrhythmic agent to convert atrial fibrillation with rapid ventricular response to sinus rhythm.

Aminopyrine infusion breath test for the determination of changes in P450 metabolism in vivo.

1. An osmotic mini-pump was used to maintain a constant infusion of radiolabelled [N-dimethyl-14C] aminopyrine into a rat. After implanting the mini-pump, 14CO2 expiration rate was constant within 12 h, and this rate was maintained for 192 h. 2. Treatment with 2-diethylaminoethyl-2,2-diphenylvalerate HCl (SKF 525-A) or cimetidine, inhibitors of P450-dependent metabolism, resulted in both dose- and time-dependent inhibition of the expiration of 14CO2.