Elsevier

Heart Failure Clinics

Volume 5, Issue 4, October 2009, Pages 501-514
Heart Failure Clinics

Natriuretic Peptides in the Diagnosis and Management of Chronic Heart Failure

https://doi.org/10.1016/j.hfc.2009.04.002Get rights and content

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B-type natriuretic peptide: a cardiac hormone activated in heart failure

Within the heart, the BNP gene (NPPB) produces a 134–amino acid pre-proBNP precursor peptide, which after removal of a 26–amino acid signal peptide, results in the 108–amino acid prohormone, proBNP (Fig. 1). Subsequently, the enzyme corin cleaves ProBNP into the biologically active mature 32–amino acid, BNP (BNP 1–32), containing the critical 17–amino acid disulfide ring. A second cleavage product is the linear 76–amino acid N-terminal peptide, NTproBNP 1–76. All studies suggest that mature BNP

Diagnostic and prognostic significance of B-type natriuretic peptide

Given its association with cardiac load, it is not surprising that BNP has been found to convey diagnostic and prognostic information in acute HF and in other settings. Of note, BNP levels are affected not only by cardiac overload but also by factors such as age, sex, renal function, obesity, and genetic factors.16, 17, 18, 19, 20, 21 In the setting of acute HF, the contribution of these factors is small compared with the impact of cardiac overload so that even single, unadjusted BNP values can

Changes of B-type natriuretic peptide over time

If cardiac overload negatively impacts prognosis and if BNP reflects cardiac overload, then reductions in BNP would be expected to indicate an improved prognosis. If this were so, BNP could be used to help assess the efficacy of a therapeutic intervention in normal clinical practice and in clinical trials. Elevated levels could indicate impending clinical deterioration not yet apparent from symptoms and signs and trigger an earlier intervention, which could result in improved outcomes. With

B-type natriuretic peptide–guided therapy

As discussed earlier, higher BNP levels are related to cardiac overload and have been associated with worse outcomes. This association provides the rationale for the hypothesis that intensifying treatment so as to reduce BNP levels below a certain threshold could improve outcomes. Important study characteristics to consider are the treatment goal (ie, target BNP value) and the treatment algorithm to be followed. Some of the study characteristics discussed in the following paragraphs are shown

What Exactly Are We Measuring?

As mentioned previously, most current assay systems use antibodies directed against epitopes of BNP 1–32 or NTproBNP. This approach can have only limited specificity, and indeed, several conventional assays also detect circulating proBNP.5, 6 Because proBNP has reduced biologic activity compared with BNP 1–32, nonspecific assays may not accurately reflect biologic activity.5, 6 Recently, a proBNP assay was developed that uses an antibody directed against the hinge region of proBNP so that

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    This research was supported by PO1 HL76611 and RO1 HL36634 (JCB), and by T32 HL07111 (GB). JCB also has research support from BioRad.

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