Brain natriuretic peptide and n-terminal brain natriuretic peptide in the diagnosis of heart failure in patients with acute shortness of breath

C-terminal brain (B-type) natriuretic peptide (BNP)-32 is a widely used clinical biomarker for the diagnosis, prognosis, and treatment of heart failure (HF). The 32-aa peptide is synthesized primarily in the atrial and ventricular myocardium and constitutes the mature biologically active form of immature BNP (pro-BNP). There has been mounting evidence that suggests BNP circulates in different structural forms that impact HF diagnosis and in vivo activity. Herein, we have developed and used an immunoaffinity purification assay to isolate endogenous BNP-32 from New York Heart Association class IV patient plasma for subsequent analysis by nano-liquid chromatography (LC) electrospray ionization Fourier transform ion cyclotron resonance (FT-ICR) MS. We have introduced stable isotope-labeled BNP-32 to the assayed plasma to enable quantification of endogenous levels of BNP-32. Unlike the chemically nonspecific point-of-care tests (POCTs) and RIAs used worldwide to quantify BNP-32 from plasma, FT-ICR-MS (unprecedented mass measurement accuracy) coupled with LC (retention time) affords extraordinary molecular specificity, and when combined with the use of internal standards is able to confidently identify and quantify BNP-32. The significance of this work is despite exceedingly high circulating levels of BNP-32 in the New York Heart Association class IV patients as determined by POCTs (>290 fmol/ml) nano-LC-electrospray ionization-FT-ICR-MS data did not reveal any endogenous BNP-32. These results provide molecularly specific evidence for the absence of circulating BNP-32 in advanced-stage HF patients and suggest the existence of altered forms of BNP that are contributing to the POCT values.

https://www.pnas.org/content/pnas/102/48/17442.full.pdf

Quantitative mass spectral evidence for the absence of circulating brain natriuretic peptide (BNP-32) in severe human heart failure

Objective: To determine normal values of plasma B type natriuretic peptide from infancy to adolescence using a commercially available rapid assay. Setting: Tertiary referral centre. Design: The study was cross sectional. Plasma BNP concentration was measured in 195 healthy infants, children, and adolescents from birth to 17.6 years using the triage BNP assay (a fluorescence immunoassay). Results: During the first week of life, the mean (SD) plasma concentration of BNP in newborn infants decreased significantly from 231.6 (197.5) to 48.4 (49.1) pg/ml (p = 0.001). In all subjects older than two weeks plasma BNP concentration was less than 32.7 pg/ml. There was no significant difference in mean plasma BNP measured in boys and girls younger than 10 years (8.3 (6.9) v 8.5 (7.5) pg/ml). In contrast, plasma concentration of BNP in girls aged 10 years or older was significantly higher than in boys of the same age group (12.1 (9.6) v 5.1 (3.5) pg/ml, p Conclusions: Plasma BNP concentrations in newborn infants are relatively high, vary greatly, and decrease rapidly during the first week of life. In children older than 2 weeks, the mean plasma concentration of BNP is lower than in adults. There is a sex related difference in the second decade of life, with higher BNP concentrations in girls. BNP concentrations in girls are related to pubertal stage.

/pdf/normal-values-of-b-type-natriuretic-peptide-in-infants-4ns0iw803n.pdf

Normal values of B type natriuretic peptide in infants, children, and adolescents

Beneficial neurohormonal profile of spironolactone in severe congestive heart failure: results from the RALES neurohormonal substudy.

Brain natriuretic peptide predicts right heart failure in patients with acute pulmonary embolism.

Congestive heart failure (CHF) is among the most frequently encountered cardiac diagnoses, with an estimated prevalence of 1% (1). Plasma concentrations of B-type natriuretic peptide (BNP) and its precursor, N-terminal pro-BNP (NT pro-BNP), are increased in patients with CHF and have been shown to accurately predict clinical severity and left ventricular ejection fraction (LVEF) as well as morbidity and mortality in those patients (2)(3). A major limitation in the routine determination of natriuretic peptides is the time-consuming nature of analytical techniques, e.g., extraction procedures, long incubation times, or radioactive labeling (4)(5)(6)(7)(8). A rapid bedside test for determination of BNP was introduced recently (Triage BNP; Biosite Diagnostics, San Diego, CA). We evaluated the assay and compared it, in samples from patients with suspected CHF, with other assay systems for determination of either BNP (Shionoria BNP; CIS Diagnostics) or NT pro-BNP (Roche Diagnostics, Tutzing, Germany).

The Triage BNP test is an immunofluorometric assay for quantitative determination of BNP in EDTA-anticoagulated whole blood or plasma (9)(10). A murine recombinant polyclonal antibody is bound to the fluorescent label, and a murine monoclonal antibody against the disulfide bond-mediated ring structure of BNP 32 is bound to the solid phase.

Briefly, after the addition of 250 μL of EDTA-anticoagulated whole blood, the plasma is separated and allowed to react with fluorescent antibody conjugates within a reaction chamber. After an incubation period, complexes of the analyte and fluorescent antibody conjugates are captured on a detection lane. The concentration of BNP in the specimen is proportional to the fluorescence bound to the detection lane, which is determined quantitatively by a handheld fluorescence instrument (Triage Meter) as described in detail elsewhere (11 …

Evaluation of a new, rapid bedside test for quantitative determination of B-type natriuretic peptide.

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Evaluation of a new, rapid bedside test for quantitative determination of B-type natriuretic peptide.