Cardiac Biomarkers Aid in Differentiation of Kawasaki Disease from Multisystem Inflammatory Syndrome in Children Associated with COVID-19

Abstract

Kawasaki disease (KD) and Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 show clinical overlap and both lack definitive diagnostic testing, making differentiation challenging. We sought to determine how cardiac biomarkers might differentiate KD from MIS-C. The International Kawasaki Disease Registry enrolled contemporaneous KD and MIS-C pediatric patients from 42 sites from January 2020 through June 2022. The study population included 118 KD patients who met American Heart Association KD criteria and compared them to 946 MIS-C patients who met 2020 Centers for Disease Control and Prevention case definition. All included patients had at least one measurement of amino-terminal prohormone brain natriuretic peptide (NTproBNP) or cardiac troponin I (TnI), and echocardiography. Regression analyses were used to determine associations between cardiac biomarker levels, diagnosis, and cardiac involvement. Higher NTproBNP (≥ 1500 ng/L) and TnI (≥ 20 ng/L) at presentation were associated with MIS-C versus KD with specificity of 77 and 89%, respectively. Higher biomarker levels were associated with shock and intensive care unit admission; higher NTproBNP was associated with longer hospital length of stay. Lower left ventricular ejection fraction, more pronounced for MIS-C, was also associated with higher biomarker levels. Coronary artery involvement was not associated with either biomarker. Higher NTproBNP and TnI levels are suggestive of MIS-C versus KD and may be clinically useful in their differentiation. Consideration might be given to their inclusion in the routine evaluation of both conditions.

Keywords: Amino-terminal prohormone brain natriuretic peptide (NTproBNP); Cardiac biomarkers; Kawasaki disease (KD); Multisystem Inflammatory Syndrome in Children (MIS-C); Troponin I (TnI).

Figure 1

Inclusion and Exclusion Criteria AHA: American Heart Association, CDC: Centers for Disease Control and Prevention, KD: Kawasaki disease, MIS-C: Multisystem Inflammatory Syndrome in Children, NTproBNP: amino-terminal prohormone brain natriuretic peptide

Figure 2

Number of KD Clinical Criteria Present for KD Versus MIS-C Patients KD: Kawasaki disease, MIS-C: Multisystem Inflammatory Syndrome in Children

Figure 3

Distribution of Cardiac Biomarkers by Diagnosis: A) log(NTproBNP) and B) log(TnI) at Presentation Box encloses the 25^th to 75^th percentiles with the line indicating the median and diamond the mean. Whiskers range from the maximum to minimum value within the fence, with circles indicating outliers. log(NTproBNP): logarithmic transformation of amino-terminal prohormone brain natriuretic peptide, log(troponin I): logarithmic transformation of troponin I, MIS-C: Multisystem Inflammatory Syndrome in Children

Figure 4

Receiver Operating Characteristic Curves Predicting MIS-C (vs KD) for A) NTpro BNP and B) TnI at Presentation KD: Kawasaki Disease, MIS-C: Multisystem Inflammatory Syndrome in Children, NTproBNP: amino-terminal prohormone brain natriuretic peptide, ROC: receiver operating characteristic, TnI: troponin I