Prevalence and prognostic significance of adrenergic escape during chronic β-blocker therapy in chronic heart failure
Department of Cardiology, Angiology, Pulmology, University of Heidelberg, 69120 Heidelberg, Germany
* Corresponding author. Tel: +49 6221 563 8895, Fax: +49 622 156 6547, Email: lutz.frankenstein{at}med.uni-heidelberg.de
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Abstract |
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Aims: Like aldosterone escape to ACE-inhibitors, adrenergic escape (AE) to β-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 β-blocker agents and doses.
Methods and results: This was a prospective, observational study of 415 patients with systolic CHF receiving chronic stable β-blocker therapy. AE was defined by norepinephrine levels above the upper limit of normal. Irrespective of the individual β-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 β-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; 
2: 15.60).
Conclusion: We verified the presence of AE in CHF patients on chronic stable β-blocker therapy, irrespective of the individual β-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.
Key Words: Adrenergic escape • β-Blocker • Chronic heart failure • Prognosis
Received March 21, 2008; Revised August 26, 2008; Accepted November 12, 2008