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

Abstract

Background-The effect of ␤-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 Ͻ40%) 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 (PϽ0.01 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 1 ⁄2␣) of BNP was prolonged by metoprolol (5.6Ϯ0.45 to 11Ϯ1.3 versus 5.7Ϯ0.8 to 6.6Ϯ1.3 minutes in control subjects; Pϭ0.019). 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 ␤-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.

Atrial remodelling in heart failure: recent developments and relevance for heart failure with preserved ejection fraction

“…Increased BNP clearance by adipose tissue (in HFpEF) and decreased BNP production due to ‘cardiac cachexia’ have been proposed as mechanisms,62 but an impaired production or secretion in the atrial (or ventricular) myocardium in HFpEF remains to be explored 63. Beta‐blockade with metoprolol increases plasma BNP levels in HFrEF 64. BNP given subcutaneously can improve the haemodynamic response to acute volume load in patients with HFpEF,65 corroborating a relative deficit of natriuretic peptides.…”

Assessing the benefits of natriuretic peptides-guided therapy in chronic heart failure

“…Most published data, i.e. 19 publications [8,9,18,[24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] are from these cardiologists. The number of treated patients in these centers outweighs that of patients treated elsewhere and the results from the 'specialized' and 'normal' centers are different and sometimes opposed.…”

“…The response to the beta-blocker metoprolol is complex, sometimes with a rise of BNP levels in the first 2-3 months followed by a fall [26]. Treatment with the direct renin inhibitor aliskiren was also found to reduce NT-proBNP levels [28] but this fall was not associated with reduced clinical events [50].…”

Prognostic value of sequential measurements of amino‐terminal prohormone of B‐type natriuretic peptide in ambulatory heart failure patients

“…Longer time intervals might delay recognition of treatment failure and thereby also delay appropriate measures to rescue the patient (for example evaluation for transplantation). With shorter time intervals, beta-blocker therapy which transiently increases natriuretic peptides 6 weeks after initiation [22], might impair the prognostic accuracy of repetitive measurements of natriuretic peptides at significantly shorter time intervals than three months.…”