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(Circulation. 2006;113:977-985.)
© 2006 American Heart Association, Inc.

Heart Failure

Introduction of Metoprolol Increases Plasma B-Type Cardiac Natriuretic Peptides in Mild, Stable Heart Failure

Mark E. Davis, MBChB; A. Mark Richards, MD; M. Gary Nicholls, MD; Timothy G. Yandle, PhD; Christopher M. Frampton, PhD; Richard W. Troughton, MD

From the Christchurch Cardioendocrine Research Group, Christchurch School of Medicine and Health Sciences, Christchurch, New Zealand.

Correspondence to Dr Mark E. Davis, Department of Medicine, Christchurch School of Medicine and Health Sciences, PO Box 4345, Christchurch, New Zealand. E-mail mark.davis{at}chmeds.ac.nz

Received June 13, 2005; revision received November 13, 2005; accepted December 16, 2005.

Background— The effect of ß-blockade on the cardiac natriuretic peptides is poorly understood but could contribute to their beneficial treatment effect and may be relevant to clinical use of plasma brain natriuretic peptide (BNP)/N-terminal pro brain natriuretic peptide (NTproBNP) measurements in risk stratification and in titration of anti–heart failure therapy.

Methods and Results— Sixteen men with mild, stable heart failure (NYHA class II to III; left ventricular ejection fraction <40%) underwent serial blood sampling for plasma natriuretic peptide levels and received infusions of atrial natriuretic peptide (ANP) and BNP before and 6 weeks after the introduction and uptitration of metoprolol or 6 weeks unchanged therapy in a randomized, parallel-group design. Plasma natriuretic peptides (BNP, NTproBNP, ANP, and NTproANP) were increased by metoprolol (P<0.01 for all). The natriuretic responses to ANP and BNP infusions were sustained with the introduction of metoprolol despite reduced renal perfusion pressure. The levels of the noninfused natriuretic peptide were increased by both ANP and BNP infusions, and this effect was enhanced by metoprolol. The early plasma half-life (t) of BNP was prolonged by metoprolol (5.6±0.45 to 11±1.3 versus 5.7±0.8 to 6.6±1.3 minutes in control subjects; P=0.019).

Conclusions— Plasma cardiac natriuretic peptide levels increase significantly with the introduction of metoprolol in heart failure as a result of effects on secretion and clearance. Natriuretic responses to NP infusions are sustained with ß-blockade despite reduced renal perfusion pressure. Clinicians should be aware that the introduction of metoprolol causes a rise in plasma BNP/NTproBNP that is unrelated to deterioration in clinical status and must be considered when measurements are undertaken for risk stratification or titration of treatment.

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