Importance and Interpretation of Intermediate (Gray Zone) Amino-Terminal Pro–B-Type Natriuretic Peptide Concentrations

Amino-terminal pro–B-type natriuretic peptide (NT-proBNP) values between the cut point of 300 ng/L for “ruling out” acute heart failure (HF) and the consensus-recommended age-adjusted cut points for “ruling in” acute HF are referred to as intermediate or gray zone values, which may be seen in approximately 20% of patients with dyspnea in the emergency department. Knowledge of the differential diagnosis of the causes of a gray zone NT-proBNP finding is useful to ascertain the correct diagnosis. Possible causes include cardiac ischemia, atrial fibrillation, and infectious/inflammatory pulmonary diseases. Importantly, a gray zone NT-proBNP result is not associated with a benign prognosis. Regardless of the cause, it should not be ignored because it is a “negative” result. Patients with a gray zone NT-proBNP value are at higher risk for hazard compared with those with a negative NT-proBNP result.