Effect of acute amiodarone loading on energy requirements for biphasic ventricular defibrillation

D the frequent use of amiodarone, questions about the effect of this drug on the defibrillation threshold (DFT) have not been fully answered. Previous clinical investigations have shown this drug to increase the DFT when using monophasic shocks,1–3 whereas other studies showed no effect.4 Implantable cardioverter-defibrillators (ICDs) now use biphasic waveforms because they are more effective in terminating ventricular fibrillation. Several recent uncontrolled studies comparing biphasic DFTs in populations of patients on and off amiodarone suggested no difference in the DFT between the 2 groups.5,6 Pelosi et al7 recently reported an increase in the biphasic DFT with chronic amiodarone use, measured on average 2 to 3 months after drug initiation, but provided no data regarding acute effects of the drug. We examined the immediate effects of in-hospital oral amiodarone loading on the biphasic DFT. • • • This study compared the DFTs of 18 patients (16 men and 2 women, mean age 63 6 10 years) at the time of initial implantation and after receiving an in-hospital load of oral amiodarone for clinically indicated reasons. The initial indication for ICD implantation was ventricular tachycardia in 17 patients and resuscitated cardiac death in 1 patient. Ten patients had underlying coronary artery disease, and 8 had dilated cardiomyopathy. Left ventricular function was severely depressed (,30%) in 15 patients; in 3 other patients it was moderately depressed (30% to 39%), mildly depressed (40% to 49%), and preserved (.50%). The implanted ICD models included the 7223Cx (n 5 7) and 7227Cx (n 5 6) manufactured by Medtronic, Inc. (Minneapolis, Minnesota), and the 1763 (n 5 1), 1782 (n 5 2), 1790 (n 5 1), and 1831 (n 5 1) manufactured by Guidant Corp. (St. Paul, Minnesota). All patients had DFTs determined at the time of device implant using a sequential “change in delivered energy” protocol from an initial delivered energy of 15 J with decrements or increments of 5 J. Ventricular fibrillation was induced using a T-wave shock. The lowest energy required for cardioversion was considered the DFT.8 No patient was receiving antiarrhythmic drugs other than b blockers (10 patients) at the time of initial device implant. The indication for amiodarone was recurrent ventricular tachycardia in 12 patients and atrial fibrillation in 6. The drug was loaded orally in the hospital for a total dose of 8 to 12 g over 6 to 10 days, followed by maintenance doses. Follow-up DFT determination was performed after the oral load using the same protocol used at device implant. The Student’s t test for paired data was used to compare the DFTs from implant and after amiodarone loading. Data are expressed as mean 6 SD. A p value ,0.05 was considered statistically significant. The time between initial DFT determination and the DFT after amiodarone loading ranged from 1 to 32 months. The average time between studies was 226 6 248 days, with a median time of 146 days. In the overall group, the DFT increased significantly after amiodarone loading, from 10.5 6 4.7 to 15.2 6 7.8 J (p ,0.0015). In the subgroup of patients in whom the time between initial DFT determination and initiation of amiodarone was ,6 months (12 of the 18 patients), the DFT also increased from 10.8 6 5.3 to 16.1 6 8.6 J (p 5 0.005). The mean changes in DFT are shown in Figure 1. After loading, 11 of 18 patients had an increase in the DFT, 6 had no change, and 1 patient had a decrease from 10 to 5 J. In 1 patient, termination of amiodarone was required because the DFT after drug loading was unacceptably high (25 J). Individual changes in the DFT are displayed in Figure 2. • • • The main finding of our study was the demonstration of higher DFTs using biphasic energy waveforms after in-hospital oral amiodarone loading over several days. To our knowledge, this is the first time that the effect of short-term amiodarone oral loading on the biphasic DFT has been examined in humans. Although the results observed in our study could be attributed to other long-term physiologic differences (such as changes in ventricular size and ventricular function), we doubt this to be the case. Three of 6 patients who began therapy with amiodarone within 1 month of the initial device implantation had an increase in the DFT after drug loading, including 1 patient whose DFT was raised enough to render an inadequate safety margin. The difference in DFT was also significant in the group of patients in whom amiodarone was started within 6 months of implant. Although the increase in defibrillation energy requirements was statistically significant, it was not universal. One third of patients studied had no change in the DFT after drug initiation, and 1 patient had a From the Department of Internal Medicine (Cardiology, Clinical Cardiac Electrophysiology), The University of Texas Southwestern Medical Center; and The Dallas Veterans Affairs Medical Center, Dallas, Texas. Dr. Joglar’s address is: Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Room CS7.102, 5323 Harry Hines Boulevard, Dallas, Texas 753909047. E-mail: jajogl@parknet.pmh.org. Manuscript received September 14, 2000; revised manuscript received and accepted March 27, 2001.