NT-proBNP in the Emergency Department

Study Questions:

What is the diagnostic performance of N-terminal pro–B-type natriuretic peptide (NT-proBNP) for acute heart failure in the emergency department (ED)?


The authors conducted a prospective, multicenter trial in the United States and Canada enrolling subjects who presented to an ED with dyspnea. The objective of the study was to validate the use of NT-proBNP cutoffs to aid in the diagnosis or exclusion of HF. The primary endpoints of the study were the positive predictive value (PPV) of age-specific rule-in cutoffs of 450, 900, and 1,800 pg/ml for ages <50, 50-75, and >75 years, respectively for acute HF, and the negative predictive value (NPV) of the rule-out, age-independent cutoff of 300 pg/ml. Receiver-operating characteristic (ROC) curves were constructed relative to the gold-standard diagnosis, and multivariable logistic regression analyses were used to evaluate the significance of age-adjusted NT-proBNP values.


A total of 1,758 subjects were enrolled. Of these, 297 were excluded, leaving 1,461 for the final analysis. In this population, 277 (19%) were diagnosed with acute HF and 1,184 (81%) as not having HF. Mean age was 56.4 ± 14.7 years, 49.1% were female, and 36.6% were black. The median NT-proBNP in patients with acute HF was 2,844 pg/ml, interquartile range (IQR) 1,247-5,976 pg/ml, compared to patients without HF, whose median NT-proBNP was 98 pg/ml, IQR 35-369 pg/ml (p < 0.001). For the diagnosis of acute HF, NT-proBNP had an area under the curve (AUC) of 0.97 (95% confidence interval [CI], 0.94-0.99) for patients <50 years old (n = 462); AUC 0.89 (95% CI, 0.87-0.92) for patients 50-75 years old (n = 833); and, AUC 0.84 (95% CI, 0.78-0.90) for patients >75 years old (n = 166). For the age-dependent cutoffs, NT-proBNP had a positive predictive value (PPV) of 53.6% and sensitivity of 85.7% (age <50 years); PPV 58.4% and sensitivity 79.3% (age 50-75 years), and PPV 62.0% and sensitivity 75.9% (age >75 years). In multivariable logistic regression, an elevated age-adjusted NT-proBNP had the highest odds ratio for HF of all variables retained (including prior HF, interstitial edema on chest radiography, rales on examination, and peripheral edema). The age-independent cutoff of NT-proBNP <300 pg/ml had a NPV of 98% and specificity of 71.7%.


Age-stratified rule-in NT-proBNP levels and age-independent rule-out NT-proBNP levels perform well in aiding in the diagnosis and exclusion of HF in an ED patient population.


For patients presenting to the ED with dyspnea, making the diagnosis of acute HF can be challenging. The present study (ICON-RELOADED) demonstrates that age-stratified NT-proBNP rule-in cutoff values and an age-independent rule-out cutoff value perform well in a multicenter cohort of contemporary ED patients. Future studies should evaluate the generalizability of these cutoff values to patients in other care settings and to patients with other symptoms of acute HF.

Clinical Topics: Anticoagulation Management, Geriatric Cardiology, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Nuclear Imaging

Keywords: Biological Markers, Dyspnea, Edema, Emergency Service, Hospital, Geriatrics, Heart Failure, Natriuretic Peptide, Brain, Peptide Fragments, Radiography, Respiratory Sounds

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