TDI combined with pulsed-wave Doppler echocardiography predicted the LVEDP of VSD infants, whereas the plasma BNP value did not have a significant association with the LVEDP.

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Background: The sequelae of Kawasaki disease (KD) vary widely with the greatest risk for future cardiovascular events among those who develop giant coronary artery aneurysms (CAA). We sought to define the molecular signature associated with different outcomes in pediatric and adult KD patients. Methods: Molecular profiling was conducted using mass spectrometry–based shotgun proteomics, transcriptomics, and glycomics methods on 8 pediatric KD patients at the acute, subacute, and convalescent time points. Shotgun proteomics was performed on 9 KD adults with giant CAA and matched healthy controls. Plasma calprotectin was measured by ELISA in 28 pediatric KD patients 1 year post-KD, 70 adult KD patients, and 86 healthy adult volunteers. Results: A characteristic molecular profile was seen in pediatric patients during the acute disease, which resolved at the subacute and convalescent periods in patients with no coronary artery sequelae but persisted in 2 patients who developed giant CAA. We, therefore, investigated persistence of inflammation in KD adults with giant CAA by shotgun proteomics that revealed a signature of active inflammation, immune regulation, and cell trafficking. Correlating results obtained using shotgun proteomics in the pediatric and adult KD cohorts identified elevated calprotectin levels in the plasma of patients with CAA. Investigation of expanded pediatric and adult KD cohorts revealed elevated levels of calprotectin in pediatric patients with giant CAA 1 year post-KD and in adult KD patients who developed giant CAA in childhood. Conclusions: Complex patterns of biomarkers of inflammation and cell trafficking can persist long after the acute phase of KD in patients with giant CAA. Elevated levels of plasma calprotectin months to decades after acute KD and infiltration of cells expressing S100A8 and A9 in vascular tissues suggest ongoing, subclinical inflammation. Calprotectin may serve as a biomarker to inform the management of KD patients following the acute illness.

B-type natriuretic peptide (BNP) reflects volume overload on left ventricle and pulmonary hypertension (PH) in patients with ventricular septal defect (VSD). Pulmonary vascular resistance (PVR) has been reported to correlate positively with BNP in VSD patients with various degrees of PH. We aimed to investigate the relationship between PVR and BNP in VSD patients with severe PH. We examined 24 subjects with VSD concomitant severe PH aged from 2 months to 17 years (median: 4 months). The ratio of pulmonary to systemic pressure (Pp/Ps), the ratio of pulmonary to systemic flow (Qp/Qs), the ratio of pulmonary to systemic resistance (Rp/Rs), and PVR were determined by cardiac catheterization. PVR and Rp/Rs ranged from 1.6 to 15.5 (mean: 5.7 +/- 3.9) Wood unit . m(2) and 0.1 to 0.8 (mean: 0.4 +/- 0.2), respectively. BNP ranged from 5.5 to 69 (mean: 31 +/- 19) pg/ml. Negative correlations were observed between BNP and PVR (r = -0.56, p = 0.004) and BNP and Rp/Rs (r = -0.51, p = 0.01). BNP was significantly lower (<10 pg/ml) in VSD patients with Eisenmenger physiology as compared with the others (p = 0.003). We should draw attention to evaluate BNP values in VSD patients with severe PH.

Background Infliximab, a monoclonal antibody directed against tumor necrosis factor-α, is being evaluated as adjunctive therapy to intravenous immunoglobulin (IVIG) for treatment of young children with acute Kawasaki disease (KD).Objective The aim of this study was to develop a population pharmacokinetic (PopPK) model for infliximab in children with KD and to evaluate the impact of covariates on infliximab disposition. Specifically, we wanted to investigate the effect of body weight and IVIG administration on pharmacokinetic parameters. MethodsIn the current PopPK analysis, 70 subjects with median (interquartile range) age of 2.9 (1.3-4.4) years were included from two randomized controlled trials.Infliximab concentration-time data were best described by a two-compartment model with first-order elimination using NONMEM 7.3. Results KEY POINTS1. KD can cause life-threatening coronary artery aneurysms and is the leading cause of acquired heart disease in children. Infliximab is being evaluated as adjunctive therapy in acute KD because 10-20% of children are resistant to first-line IVIG therapy and this is the first report of a PopPK analysis of infliximab in children with acute KD.2. When assessing the pharmacokinetics of infliximab in children with acute KD and evaluating the impact of covariates on infliximab disposition and dosing, we found that administering infliximab after IVIG, as opposed to before, results in a 50% decrease of V2.3. Our study shows that timing of infliximab relative to IVIG administration affects the disposition of the biologic. As biologics are increasingly used in the treatment of inflammation-mediated diseases, data regarding impact and timing of IVIG administration on disposition of biologics is important.