Prevalence and prognostic significance of adrenergic escape during chronic beta-blocker therapy in chronic heart failure.
OBJECTIVE
Like aldosterone escape to ACE-inhibitors, adrenergic escape (AE) to beta-blockers appears conceivable in chronic heart failure (CHF), as generalized systemic neurohumoral activation has been described as the pathophysiological basis of this syndrome. The aim of this study was to examine the prevalence and prognostic value of AE with respect to different beta-blocker agents and doses.


RESULTS
This was a prospective, observational study of 415 patients with systolic CHF receiving chronic stable beta-blocker therapy. AE was defined by norepinephrine levels above the upper limit of normal. Irrespective of the individual beta-blocker agents used and the dose equivalent taken, the prevalence of AE was 31-39%. Norepinephrine levels neither correlated with heart rate (r=0.02; 95% CI: -0.08-0.11; P=0.74) nor were they related to underlying rhythm (P=0.09) or the individual beta-blocker agent used (P=0.87). The presence of AE was a strong and independent indicator of mortality (adjusted HR: 1.915; 95% CI: 1.387-2.645; chi2: 15.60).


CONCLUSIONS
We verified the presence of AE in CHF patients on chronic stable beta-blocker therapy, irrespective of the individual beta-blocker agent and the dose equivalent. As AE might indicate therapeutic failure, the determination of AE could help to identify those patients with CHF that might benefit from more aggressive treatment modalities. Heart rate, however, is not a surrogate for adrenergic escape.
Frankenstein
Lutz
L
Department of Cardiology, Angiology, Pulmology, University of Heidelberg, 69120 Heidelberg, Germany. lutz.frankenstein@med.uni-heidelberg.de
Zugck
Christian
C
Schellberg
Dieter
D
Nelles
Manfred
M
Froehlich
Hanna
H
Katus
Hugo
H
Remppis
Andrew
A
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000368:Aged; D000369:Aged, 80 and over; D002908:Chronic Disease; D004837:Epinephrine / Q000097:blood; D005260:Female; D054143:Heart Failure, Systolic / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D006339:Heart Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009638:Norepinephrine / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D011379:Prognosis; D015996:Survival Rate
D000319:Adrenergic beta-Antagonists; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D009638:Norepinephrine; D004837:Epinephrine