Elsevier

American Heart Journal

Volume 150, Issue 3, September 2005, Pages 471-477
American Heart Journal

Clinical Investigation
Congestive Heart Failure
Effect of nesiritide in combination with standard therapy on serum concentrations of natriuretic peptides in patients admitted for decompensated congestive heart failure

https://doi.org/10.1016/j.ahj.2004.11.021Get rights and content

Objective

The objective of this study is to determine the effect of nesiritide (human recombinant BNP [hBNP]) in combination with standard therapy on the concentrations of B-type natriuretic peptide (BNP) and N-terminal probrain natriuretic peptide (NT-proBNP).

Background

B-type natriuretic peptide is synthesized in cardiac ventricles as a prohormone (108 amino acids) and when released into peripheral circulation is cleaved into the active hormone BNP (amino acids 77-108) and an inactive amino terminal fragment NT-proBNP (amino acids 1-76).

Methods

Three groups of patients with acutely decompensated congestive heart failure (CHF) received nesiritide for 24, 36, or 48 hours (n = 5, 7, and 7, respectively) in addition to standard therapy. Serial blood samples were collected. B-type natriuretic peptide and NT-proBNP were measured.

Results

To correct for positive skew, natriuretic peptide concentrations were log transformed. The mean baseline (prenesiritide), 6-, 12-, and 24-hour infusion, and 6-, 12-, and 24-hour postinfusion concentrations of BNP were 1000, 2300, 2200, 1700, 580, 640, and 740 pg/mL, respectively (n = 19). The 6- and 12-hour postinfusion concentrations of BNP were significantly lower (<0.05) than baseline. The mean baseline, 60-, 120-, and 24-hour infusion, and 6-, 12-, and 24-hour postinfusion concentrations of NT-proBNP were 6600, 6500, 5800, 4300, 4100, 4300, and 5100 pg/mL, respectively (n = 19). From the time point 24 hours after initiation of therapy through 12 hours postinfusion, the mean NT-proBNP concentration was significantly (<0.05) lower than baseline.

Conclusion

Nesiritide, in combination with standard therapy, significantly lowered the endogenous concentrations of natriuretic peptides during infusion and after dosing was completed.

Section snippets

Patients

This prospective study was carried out at the San Diego Veterans Affairs Healthcare System between July 2001 and June 2002. Patients requiring hospitalization and intravenous therapy for decompensated CHF were considered for inclusion if they had dyspnea at rest or with minimal activity, clinical evidence of heart failure as the primary etiology of dyspnea, and a BNP level >100 pg/mL. Nineteen men between the ages of 42 and 80 were included in this study. The UCSD Institutional Review Board

Results

Patient characteristics are shown in Table I. The mean age of the patients was 65 years (range 42-80 years) with a preponderance of ischemic cardiomyopathy as the etiology of CHF. Seventy-four percent of the patients were white and the average ejection fraction was 35%. Forty-two percent of the subjects had CHF for 1 to 5 years before therapy. Ninety percent of the patients had jugular venous distension, 79% had rales, and 79% had edema.

All but one subject completed the nesiritide infusion

Discussion

B-type natriuretic peptide has been called the “emergency” cardiac hormone, synthesized in a futile attempt to stave off the large surges by the vasoconstrictor and salt-retaining hormones released during decompensation.17 Nesiritide is metabolized and eliminated via the same pathways as endogenous BNP. These pathways include binding to natriuretic peptide clearance receptors present throughout the vasculature, followed by endocytosis and intracellular lysosomal hydrolysis, proteolytic

References (21)

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