Heart failure
Usefulness of Intermediate Amino-Terminal Pro-Brain Natriuretic Peptide Concentrations for Diagnosis and Prognosis of Acute Heart Failure

https://doi.org/10.1016/j.amjcard.2006.02.043Get rights and content

Age-stratified cutpoints for aminoterminal pro-brain natriuretic peptide (NT–pro-BNP) concentrations are diagnostic in 83% of all subjects with acute dyspnea. This study analyzed subjects with NT–pro-BNP concentrations between the “rule-out” and “rule-in” cutpoints, the so-called natriuretic peptide gray zone. NT–pro-BNP concentrations, clinical characteristics, and 60-day mortality were studied in 1,256 acutely dyspneic patients from an international multicenter study. Of all subjects, 215 had gray-zone NT–pro-BNP concentrations, 116 of whom (54%) were diagnosed with heart failure (HF). Among these subjects, patients with HF were more likely to be older, to have a history of HF, to be in atrial fibrillation, and to have elevated troponin T concentrations compared with those without HF. In multivariate analysis, the use of loop diuretics on presentation (odds ratio [OR] 3.99, 95% confidence interval [CI] 1.58 to 10.1, p = 0.003), paroxysmal nocturnal dyspnea (OR 4.50, 95% CI 1.31 to 15.4, p = 0.02), jugular venous distention (OR 3.05, 95% CI = 1.06 to 8.79, p = 0.04), and the absence of cough (OR 0.18, 95% CI 0.06 to 0.52, p = 0.001) were associated with a diagnosis of acute HF in gray-zone patients. Subjects with HF and diagnostically elevated NT–pro-BNP concentrations had the highest mortality rates, subjects without HF and NT–pro-BNP concentrations <300 ng/L had the lowest mortality rates, and subjects with gray-zone NT–pro-BNP had intermediate outcomes, irrespective of their final diagnoses. Adding specific clinical information to NT–pro-BNP improves diagnostic accuracy in subjects with intermediate NT–pro-BNP concentrations. Mortality rates in subjects with intermediate NT–pro-BNP concentrations are lower than in those with NT–pro-BNP concentrations diagnostic for HF but are higher than in subjects with NT–pro-BNP concentrations less than the gray zone.

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    Furthermore, increased levels of NT-proBNP correlate with reduced left ventricular ejection fraction and abnormal ventricular systolic function [5,6]. While circulating levels of BNP have been used to monitor cardiac function [7–9], its bio-inert product, NT-proBNP, has a longer biological half-life and can be used to more accurately separate patients with normal and impaired systolic function, as compared to BNP measurements alone [9–13]. A study investigating methods for the quantification of BNP and NT-proBNP revealed much greater variability (coefficient of variation of >30) for detection of BNP, as compared to NT-proBNP [7].

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    In 2 studies with ARNI, NT-proBNP levels were reduced (12,14), with the reduction in 1 study being associated with improved clinical outcomes (12). A substantial evidence base exists that supports the use of natriuretic peptide biomarkers to assist in the diagnosis or exclusion of HF as a cause of symptoms (e.g., dyspnea, weight gain) in the setting of chronic ambulatory HF (15–21) or in the setting of acute care with decompensated HF (22–30), especially when the cause of dyspnea is unclear. The role of natriuretic peptide biomarkers in population screening to detect incident HF is emerging (31–37).

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The International Collaborative of NT-proBNP Study was partially sponsored by unrestricted grants from Roche Diagnostics, Basel, Switzerland.

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