Autonomic dysfunction in patients with mild heart failure and coronary artery disease and the effects of add-on beta-blockade.
OBJECTIVE
Autonomic impairment is related to the incidence of sudden death in chronic 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 beta-blockade.


RESULTS
Measures of autonomic function (plasma norepinephrine, heart rate [HR] variability, autonomic function testing), and exercise capacity, were compared between 24 patients with mild CHF, and 24 healthy controls. In this mechanistic study, we assessed the effect of 26 weeks metoprolol treatment in a double-blind, randomized, placebo-controlled design. All patients received metoprolol sustained release (200 mg; n=12) or placebo (n=12). Assessments were made at baseline and after 10 and 26 weeks' treatment. At baseline, norepinephrine levels were elevated, while HR variability parameters were decreased in patients vs. controls (both P<0.05). Autonomic function testing showed only small differences, although significant alterations were observed with deep breathing and head up tilting (both P<0.05). After 26 weeks', metoprolol did not affect exercise capacity or norepinephrine concentrations. In contrast, HR variability was markedly improved in metoprolol-treated patients vs. placebo-treated patients (P<0.05). In particular, a shift toward normal in the sympathovagal balance was observed (P<0.05). Autonomic function testing showed only small, and generally non-significant trends after metoprolol.


CONCLUSIONS
Marked autonomic abnormalities are already present in mild CHF, which may be (partially) reversed by metoprolol. These observations support the reported reduction of sudden death by beta-blockade in patients with CHF.
Tjeerdsma
G
G
Department of Cardiology/Thoraxcenter, University Hospital Groningen, P.O. Box 30 001, 9700 RB, Groningen, The Netherlands.
Szabó
B M
BM
van Wijk
L M
LM
Brouwer
J
J
Tio
R A
RA
Crijns
H J
HJ
van Veldhuisen
D J
DJ
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D000704:Analysis of Variance; D001341:Autonomic Nervous System / Q000187:drug effects* / Q000503:physiopathology*; D016022:Case-Control Studies; D002908:Chronic Disease; D003327:Coronary Disease / Q000188:drug therapy* / Q000503:physiopathology*; D004311:Double-Blind Method; D005080:Exercise Test; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000627:therapeutic use*; D009203:Myocardial Infarction / Q000503:physiopathology*; D009638:Norepinephrine / Q000097:blood
D000319:Adrenergic beta-Antagonists; D008790:Metoprolol; D009638:Norepinephrine