Partial reversal of cachexia by β-adrenergic receptor blocker therapy in patients with chronic heart failure

Background: Cachexia is a common problem in chronic heart failure (CHF) that may be partly mediated by activation of the sympathetic nervous system. The effects of beta-adrenergic receptor blocker (BB) therapy on body weight in cachectic and noncachectic subjects with CHF has not been previously reported. Methods and results: Body weight and plasma norepinephrine, leptin, and insulin levels were measured in 27 subjects with CHF before and after 6 months of beta-adrenergic receptor blockade with carvedilol or long-acting metoprolol. Before BB therapy, baseline weight, plasma leptin, and plasma insulin levels did not differ between cachectic and noncachectic subjects. Baseline plasma norepinephrine levels were increased in cachectic subjects when compared with noncachectic subjects (930 +/- 248 pg/mL versus 503 +/- 109 pg/mL, P = .063). After 6 months of BB therapy, subjects with baseline cachexia demonstrated significantly greater weight gain (+5.2 +/- 9.6 versus +0.8 +/- 5.0 kg, P = .027), greater increase in plasma leptin levels (+3.7 +/- 3.9 versus +1.2 +/- 4.3 ng/mL, P = .030), and greater decrease in plasma norepinephrine levels (-374 +/- 261 versus -41 +/- 122 pg/mL, P = .012) when compared with noncachectic subjects. Conclusions: Six months of BB therapy with carvedilol or long-acting metoprolol is associated with differential effects on body weight and hormonal levels in cachectic and noncachectic subjects with CHF. Further work is needed to determine the role the sympathetic nervous system in the pathogenesis of cachexia in patients with CHF.