Antiadrenergic effect of chronic amiodarone therapy in human heart failure

OBJECTIVES The aim of the present study was to evaluate the influence of amiodarone on neurochemical parameters of sympathetic nervous activity in patients with congestive heart failure. BACKGROUND Unlike most antiarrhythmic agents, amiodarone has been shown to exert a ben eficial effect on survival in some studies of patients with congestive hear t failure. The pharmacology of this agent is complex, and as such, the mode of its action is unclear in humans. Some experimental studies suggest that amiodarone exerts a sympatholytic effect. METHODS To evaluate the effect of amiodarone on sympathetic nervous activity, we me asured the total systemic and cardiac norepinephrine (NE) spillover rate by isotope dilution in 58 patients with severe heart failure (left ventricula r ejection fraction 20 +/- 1%), 22 of whom were receiving chronic amiodaron e treatment Release rates for dihydroxyphenylalanine (DOPA, a precursor of NE), and endogenous and radiolabeled dihydroxyphenylglycol (DHPG and H-3-DH PG, intraneuronal metabolites of NE and H-3-NE, respectively) were also det ermined to assess sympathetic neuronal integrity. RESULTS Amiodarone-treated patients had significantly lower cardiac spillover rates for NE (42%, p = 0.001), DOPA (74%, p < 0.001), DHPG (44%, p < 0.01) and H -3 DHPG (51%, p < 0.01) than those patients not treated with amiodarone Hem odynamic assessment of amiodarone-treated patients revealed higher cardiac out-put (4.4 +/- 0.2 vs. 3.7 +/- 0.2 liters/min, p < 0.01), and slightly lo wer pulmonary capillary wedge pressure (18 +/- 2 vs. 22 +/- 1, p = NS) than in untreated patients. After correction for the potential confounding effe ct of hemodynamic differences, amiodarone-treated patients continued to dem onstrate significantly lower spillover rates of NE, DOPA and DHPG from the heart. CONCLUSIONS These data indicate that amiodarone may exert beneficial effects on the fai ling human heart and this action appears to be relatively cardioselective a through a sympatholytic process, and this action appears to be relatively cardiovascular. (C) 1999 by the American College of Cardiology.