A gray zone assigned to inconclusive results of quantitative diagnostic tests: Application to the use of brain natriuretic peptide for diagnosis of heart failure in acute dyspneic patients

Background: Most quantitative diagnostic tests do not perfectly differentiate between persons with and without a given disease. We present a simple method to construct a 3-zone partition for quantitative tests results, including positive and negative zones and a gray zone between, and we describe its use in the diagnosis of heart failure by brain natriuretic peptide (BNP) measurement in acute dyspneic patients. Methods: We conducted a prospective cohort study of 699 consecutive patients with acute dyspnea who were treated at the emergency department of 3 participating hospitals. Heart failure (acute or decompensated) was assessed independently at discharge by cardiologists blind to the results of BNP measurements. Results: The discriminatory performance of BNP was insufficient to provide a single cutoff value that could be used to correctly diagnose heart failure in clinical practice. Also, the discriminatory performance differed between patients with and without a history of chronic heart failure. The gray zone of inconclusive results was 167-472 ng/L for those without and 0-334 ng/L for those with such a history. Diagnosis of the current episode of heart failure by BNP results and history of heart failure was not enhanced by data from any other sources, including electrocardiography. Conclusions: The gray zone approach applied to the diagnosis of heart failure by BNP might allow sensible cutoff values to be determined for clinical practice according to relevant subgroups of patients. The gray zone approach might be usefully applied to many other quantitative tests and clinical diagnostic or screening problems. (c) 2006 American Association for Clinical Chemistry.