A Decade of NT-proBNP in Acute Kawasaki Disease, from Physiological Response to Clinical Relevance

Abstract

Kawasaki disease (KD) is an inflammatory febrile illness of early childhood and the primary cause of acquired heart disease during childhood. Coronary artery aneurysms (CAA) are a serious complication of KD, leading to ischemic heart disease, myocardial infarction, and sudden cardiac death. Timely diagnosis in the first ten days of fever is crucial to reduce the risk of coronary artery complications. Nitrogen-terminal B-type natriuretic peptide (NT-proBNP), originally used for the management of adults with heart disease, was shown to be useful in the diagnosis and management of patients with KD. NT-proBNP is released by cardiomyocytes in response to mechanical factors such as the dilation of cardiac chambers, and to pro-inflammatory cytokines. The utility of NT-proBNP as a biological marker in KD is based on the universal myocardial inflammatory component early in the course of the disease. Patients with KD have higher NT-proBNP at the time of diagnosis than febrile controls, with a pooled sensitivity of 89% (95% confidence interval 78–95), and a specificity of 72% (95% confidence interval 58–82). The positive likelihood ratio is 3.2:1 (95% confidence interval 2.1–4.8). Moreover, patients with resistance to intravenous immunoglobulin treatment and CAA were found to have higher levels of NT-proBNP, suggesting a prognostic role. Nevertheless, the non-specificity of NT-proBNP to KD limits its use as a stand-alone test. In this light, a tentative associative retrospective diagnostic algorithm was highly reliable for including all cases at risk of CAA, which warrants further prospective studies for a better diagnostic index of suspicion and risk stratification of patients.