Autonomic dysfunction in patients with mild heart failure and coronary artery disease and the effects of add-on beta-blockade

Aim: Autonomic impairment is related to the incidence of sudden death in ch ronic heart failure (CHF). Our objective was to study autonomic profiles in patients with mild CHF due to coronary artery disease, and to investigate the value of add-on P-blockade. Methods and results: Measures of autonomic function (plasma norepinephrine, heart rate [HR] variability, autonomic fun ction testing), and exercise capacity, were compared between 24 patients wi th mild CHF, and 24 healthy controls. In this mechanistic study, we assesse d the effect of 26 weeks metoprolol treatment in a double-blind, randomized , placebo-controlled design. All patients received metoprolol sustained rel ease (200 mg; n = 12) or placebo (n = 12). Assessments were made at baselin e and after 10 and 26 weeks' treatment. At baseline, norepinephrine levels were elevated, while HR variability parameters were decreased in patients v s. controls (both P < 0.05). Autonomic function testing showed only small d ifferences, although significant alterations were observed with deep breath ing and head up tilting, (both P < 0.05). After 26 weeks', metoprolol did n ot affect exercise capacity or norepinephrine concentrations. In contrast, HR variability was markedly improved in metoprolol-treated patients vs. pla cebo-treated patients (P < 0.05). In particular, a shift toward normal in t he sympathovagal balance was observed (P<0.05). Autonomic function testing showed only small, and generally non-significant trends after metoprolol. C onclusions: Marked autonomic abnormalities are already present in mild CHF, which may be (partially) reversed by metoprolol. These observations suppor t the reported reduction of sudden death by P-blockade in patients with CHF . (C) 2001 European Society of Cardiology. All rights reserved.