Effects of amiodarone on tumor necrosis factor-α levels in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy

Abstract

Tumor necrosis factor-α (TNF-α) has been implicated in the pathogenesis of congestive heart failure and may be associated with an increase in mortality. A recent in vitro study showed that amiodarone decreases TNF-α production by human blood mononuclear cells in response to lipopolysaccharide. However, no previous clinical studies have determined the effect of chronic amiodarone therapy on TNF-α levels. Thus, the purpose of this study was to determine whether amiodarone affects TNF-α levels in patients with ischemic and nonischemic cardiomyopathy. TNF-α levels were analyzed by an enzyme-linked immunoassay using plasma samples at baseline, 1, and 2 years of follow-up in New York Heart Association class III patients (n = 40 in each of the placebo and amiodarone groups, mean ejection fraction 0.25 ± 0.09) who were randomized in the Congestive Heart Failure-Survival Trial of Antiarrhythmic Therapy, a multicenter, double-blind, placebo-controlled study in which the effect of amiodarone on survival was investigated. TNF-α levels were elevated in both groups of patients at baseline, 6.6 ± 3.1 and 7.7 ± 5.3 pg/ml in the amiodarone and placebo groups, respectively (p = 0.3). There were no significant differences in demographic or clinical variables between the 2 groups. Amiodarone treatment was associated with a significant increase in TNF-α levels in patients with ischemic cardiomyopathy, 12.7 ± 12.5 and 6.8 ± 3.7 pg/ml in the amiodarone and placebo groups, respectively (p = 0.03) at 1 year. No change in TNF-α levels was observed in patients with nonischemic cardiomyopathy. In contrast to the in vitro data, amiodarone treatment is associated with an increase in TNF-α levels in patients with ischemic cardiomyopathy. This increase is not associated with an adverse effect on survival.