Chronic effects of amiodarone in patients with refractory ventricular tachycardia

We examined the chronic electrophysiologic, systemic, and pharmacologic effects of chronic oral amiodarone therapy in 24 patients with refractory ventricular tachycardia and organic heart disease. Chronic amiodarone therapy resulted in significant increases in R-R interval (from 798 +/- 182 msec to 912 +/- 100 msec; P less than 0.01), P-R interval (from 205 +/- 66 msec to 221 +/- 87 msec; P less than 0.02), QRS duration (from 103 +/- 24 msec to 115 +/- 28 msec; P less than 0.001), and Q-Tc interval (from 413 +/- 48 msec to 470 +/- 46 msec; P less than 0.001). Significant increases were also noted in P-A interval (from 36 +/- 14 msec to 45 +/- 13 msec; P less than 0.05), A-H interval (from 119 +/- 61 msec to 141 +/- 87 msec; P less than 0.02), and H-V interval (from 52 +/- 12 msec to 64 +/- 11 msec; P less than 0.001). Electrophysiologic parameters showing changes included corrected sinus node recovery time (from 271 +/- 140 msec to 425 +/- 122 msec; P less than 0.01), the effective refractory period of the atrium (from 263 +/- 32 msec to 321 +/- 47 msec; P less than 0.01), the effective refractory period of the atrioventricular node (from 348 +/- 109 msec to 478 +/- 157 msec; P less than 0.001), the effective refractory period of the ventricle (from 253 +/- 21 msec to 291 +/- 28 msec; P less than 0.001), the atrial pacing cycle length producing A-V nodal Wenckebach (from 436 +/- 109 msec to 531 +/- 95 msec; P less than 0.001), and the functional refractory period of the A-V node (from 422 +/- 68 msec to 499 +/- 95 msec; P less than 0.001). Programmed electrical stimulation performed after 21-88 (mean 31) days of treatment was highly predictive of long-term results if suppression of arrhythmia induction was demonstrated (12 patients) or if the spontaneous arrhythmia was reinduced (5 patients). Induction of morphologically new ventricular tachyarrhythmias was frequent (42%) but had a low spontaneous recurrence rate (10%) during follow-up. Systemic parameters on chronic amiodarone therapy showed significant increases in total T4 and reverse T3, with no change in pulmonary function tests or left ventricular ejection fraction. Serum amiodarone levels at chronic electrophysiologic study ranged from 0.44-4.10 (mean 1.3) micrograms/ml. Long-term follow-up (2.5 to 20 months) demonstrated a marked improvement in clinical symptoms and mortality, but a significant recurrence rate of a well-tolerated slower arrhythmia persisted. Adverse effects on chronic amiodarone therapy were frequent (10 patients) and often disabling but required drug discontinuation in only 1 patient.