natriuretic-peptide--brain and Mucocutaneous-Lymph-Node-Syndrome

Cervical lymphadenitis (CL) cannot be easily distinguished from Kawasaki disease (KD). We therefore explored whether brain natriuretic peptide (BNP) levels are useful in this context.. We retrospectively analyzed 14 children with CL and 177 children with KD. Patients with KD were divided into three groups according to their clinical symptoms at hospitalization - 97 patients had typical KD, 35 had node-first KD (NFKD), and 45 had KD without lymphadenopathy. We reviewed data on clinical and laboratory parameters, including serum BNP levels, at hospitalization together with factors that might distinguish KD from CL.. Patients with CL were older than those with KD. Serum BNP levels were higher in all the KD groups than in the CL group. Multivariate logistic regression analyses indicated that higher BNP levels were associated with NFKD (odds ratio: 1.12, 95% confidence interval: 1.01-1.25). The receiver operating characteristic curve yielded a BNP cutoff of 18.3 pg/mL, with a sensitivity of 0.680, a specificity of 0.857, and an area under the curve of 0.806 (95% confidence interval: 0.665-0.947).. Serum BNP levels can be used to distinguish KD from CL, especially in patients with NFKD.

Topics: Biomarkers; Child; Humans; Lymphadenitis; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments; Retrospective Studies; ROC Curve

This study aimed to investigate the diagnostic accuracy of circulating N-terminal pro-brain natriuretic peptide (NT-proBNP) for Kawasaki disease (KD).. We searched the PubMed, Web of Science and EMBASE databases to identify the eligible studies investigating the diagnostic accuracy of NT-proBNP for KD. The revised tool for the quality assessment of diagnostic accuracy studies (QUADAS-2) was used to evaluate the eligible studies' quality. A meta-analysis was performed with the bivariate model and summary receiver operating characteristic (sROC) curve. We also performed subgroup, publication bias and sensitivity analyses.. We included 12 studies with 2173 KDs and 1909 control. The pooled sensitivity and specificity of eligible studies were 0.80 (95%CI: 0.72-0.86) and 0.81 (95%CI: 0.73-0.88), respectively. The area under sROC curve was 0.88 (95%CI: 0.84-0.90). Patient selection bias and partial verification bias were the major design weakness of the eligible studies. Sensitivity analysis revealed that the results of this meta-analysis were robust. Subgroup analysis revealed that study design, NT-proBNP assay and participants' body temperature were not the source of heterogeneity across all eligible studies. No publication bias was observed.. NT-proBNP has moderate diagnostic accuracy for KD. It cannot be used for ruling in or ruling out KD when used alone.

Topics: Biomarkers; Humans; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments; ROC Curve; Sensitivity and Specificity

Can laboratory tests that are routinely used in adult patients also be used in pediatric patients? Does the current literature support the routine use of troponin, brain natriuretic peptide, D-dimer, and lactate in children? Adult problems such as acute coronary syndrome and pulmonary embolism are rare in pediatrics, and there is a paucity of literature on how blood tests commonly used to help diagnose these conditions in adults play a role in the diagnosis and management of children. This article presents the literature about 4 common blood tests and examines the clinical applications of each.

Topics: Asthma; Biomarkers; Child; Fibrin Fibrinogen Degradation Products; Heart Diseases; Humans; Infections; Intussusception; Lactic Acid; Mitochondrial Diseases; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Prognosis; Pulmonary Embolism; Respiratory Distress Syndrome; Sepsis; Troponin; Wounds and Injuries

Coronary artery lesion (CAL) caused by Kawasaki disease (KD) is currently the most common acquired heart disease in children in many countries. Nevertheless, there is no single useful marker existing for predicting CAL of KD. Recently, many reports have noted that N-terminal pro-brain natriuretic peptide (NT-proBNP) can be utilized as a biomarker to predict CAL. Thus, we perform a meta-analysis to ascertain the diagnostic value of NT-proBNP in detecting CAL of KD in the acute phase. PubMed, the Cochrane Central Register of Controlled Trials, EMBASE, and China National Knowledge Infrastructure were searched to detect relevant publications. Finally, eight eligible studies were included. The overall diagnostic sensitivity and specificity were 0.84 (95% confidence interval [CI]: 0.78-0.89) and 0.71 (95% CI: 0.68-0.75), respectively. The area under the summary receiver operating characteristic curves value (SROC) curve was 0.8582 ± 0.0531. Moreover, the overall sensitivity and specificity across five studies adopted the threshold of approximately 900 ng/L were 0.82 (95% CI: 0.73-0.89) and 0.72 (95% CI: 0.68-0.76), respectively. SROC was 0.8868 ± 0.0486. This meta-analysis would be the first one to describe the role of NT-proBNP in detecting CAL of KD. We register this study with PROSPERO (CRD42019130083).

Topics: Biomarkers; China; Coronary Artery Disease; Coronary Vessels; Diagnostic Tests, Routine; Humans; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments; ROC Curve; Sensitivity and Specificity

Kawasaki disease (KD) is a systemic childhood vasculitis with peculiar tropism for the heart. Coronary artery aneurysms are the primary cause of morbidity and mortality in these patients. The timely administration of gammaglobulin decreases the risk for development of coronary artery aneurysms, highlighting the importance of early KD recognition. However, the most significant dilemma in the management of KD is the diagnosis itself. In this article, we review the recent literature focusing on the diagnostic utility of N-terminal probrain natriuretic peptide as a biomarker for diagnosis of KD. The main conclusion is that N-terminal probrain natriuretic peptide is an useful biomarker for KD diagnostic that represents a valuable addition to the current diagnostic workup of patients with suspected KD, increasing the diagnostic accuracy.

Topics: Biomarkers; Diagnostic Tests, Routine; Humans; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis

Some studies have estimated the diagnostic value of N-terminal pro-brain natriuretic peptide (NTproBNP) for Kawasaki Disease (KD), but the results are not always consistent. The aim of this study was to ascertain the diagnostic value of NT-proBNP for KD.. EMBSAE and PubMed were searched up to June 30, 2015, to identify eligible studies that evaluated the diagnostic value of NT-proBNP for KD. The quality of the eligible studies was evaluated using the revised Quality Assessment for Studies of Diagnostic Accuracy (QUADAS-2) tools. The overall diagnostic value of NT-proBNP for KD was pooled in a bivariate model.. Finally, 7 studies were included for systematic review and meta-analysis. The overall diagnostic sensitivity and specificity were 0.84 (95% CI: 0.78 - 0.89) and 0.79 (95% CI: 0.74 - 0.84), respectively. The area under the summary receiver operating characteristic (sROC) curve (AUC) was 0.87 (95% CI: 0.84 - 0.90). The overall sensitivity and specificity across five studies adopted the threshold of approximately 200 ng/L were 0.85 (95% CI: 0.78 - 0.90) and 0.76 (95% CI: 0.69 - 0.82), respectively. The major design weaknesses of the eligible studies were twogate design and threshold not pre-specified.. We concluded that available studies suggest that NT-proBNP is a useful biomarker for KD. In addition, further well-designed studies are needed to rigorously evaluate the value of NT-proBNP in KD diagnosis.

Topics: Biomarkers; Humans; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments; Sensitivity and Specificity

Kawasaki disease (KD) is a major cause of acquired heart disease among children and increases the risk of myocardial infarction. While the biochemical basis of the disease is unclear, the evidence suggests interplay between a microbial infection and a genetic predisposition in the development of the disease. Diagnosis of KD based on clinical observation is not completely reliable and is problematic due to the time-sensitive nature of the disease. Hence, identification of inflammatory, proteomic, and genetic biomarkers may assist in earlier and more effective diagnosis and treatment. This review of observational studies and clinical trials analyzes biomarkers in recent research that may be used to establish a gold standard test for KD diagnosis. 65 articles in the literature are assessed to investigate these new biomarkers in addition to biomarkers presently in use. ESR≥40mm/h, leukocyte count ≥16∗10(9)/L and increased WBC count are together suggestive of the presence of KD. Among proteomic biomarkers, elevated NT-proBNP and differing levels of several other proteomic biomarkers such as iNOS in monocytes and neutrophils have been observed in KD patients. Genetic polymorphisms of six HLA class I genes have also been linked with the disease, alongside MICA alleles A4 and A5.1. The results suggest that NT-proBNP is currently a very promising biomarker for future investigation; further research is warranted to allow for accurate and early detection of the disease using this biomarker.

Topics: Biomarkers; Genetic Predisposition to Disease; Humans; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Observational Studies as Topic; Peptide Fragments; Proteomics

To examine the diagnostic value of serum B-type natriuretic peptide (BNP) in acute Kawasaki disease (KD).. Systematic review and meta-analysis.. A systematic literature search strategy was designed and carried out using MEDLINE, EMBASE and the Cochrane Library from inception to December 2013. We also performed manual screening of the bibliographies of primary studies and review articles, and contacted authors for additional data.. We included all BNP and NT-pro (N-terminal prohormone) BNP assay studies that compared paediatric patients with KD to patients with febrile illness unrelated to KD. We excluded case reports, case series, review articles, editorials, congress abstracts, clinical guidelines and all studies that compared healthy controls.. The performance characteristics of BNP were summarised using forest plots, hierarchical summary receiver operating characteristic (ROC) curves and bivariate random effects models.. We found six eligible studies including 279 cases of patients with KD and 203 febrile controls. Six studies examined NT-proBNP and one examined BNP. In general, NT-proBNP is a specific and moderately sensitive test for identifying KD. The pooled sensitivity was 0.89 (95% CI 0.78 to 0.95) and the pooled specificity was 0.72 (95% CI 0.58 to 0.82). The area under the summary ROC curve was 0.87 (95% CI 0.83 to 0.89). The positive likelihood ratio (LR+ 3.20, 95% CI 2.10 to 4.80) was sufficiently high to be qualified as a rule-in diagnostic tool in the context of high pre-test probability and compatible clinical symptoms. A high degree of heterogeneity was found using the Cochran Q statistic.. Current evidence suggests that NT-proBNP may be used as a diagnostic tool for KD. NT-proBNP has high diagnostic value for identifying KD in patients with protracted undifferentiated febrile illness. Prospective large cohort studies are needed to help determine best cut-off values and further clarify the role of NT-proBNP in the diagnosis process of KD.

Topics: Acute Disease; Biomarkers; Humans; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Prospective Studies; ROC Curve; Sensitivity and Specificity

Topics: Biomarkers; Child; Child, Preschool; Critical Illness; Early Diagnosis; Heart Failure; Humans; Infant; Intensive Care Units; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Pulmonary Heart Disease; Risk Assessment; Sepsis; Ventricular Dysfunction, Left

Brain natriuretic peptide (BNP) and N-terminal brain natriuretic peptide (NT-proBNP) are important biomarkers for pediatric cardiovascular diseases. Peptide levels are associated with age and gender. Current studies have shown that BNP and NT-proBNP are valuable in the diagnosis of heart failure, with a high specificity and sensitivity. They also contribute to differentiating heart failure from acute respiratory distress induced by simple pulmonary factors. In addition, BNP and NT-proBNP are useful in the evaluation of disease severity and treatment guidance in children with pulmonary hypertension, cardiomyopathy and Kawasaki disease. Current limitations include the relatively small sample size of the study, the detection method and a range of normal values that are not completely uniform.

Topics: Cardiomyopathies; Cardiovascular Diseases; Child; Dyspnea; Familial Primary Pulmonary Hypertension; Heart Failure; Humans; Hypertension, Pulmonary; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments

Biochemical markers are available to detect cardiac involvement in many pediatric disease states and should be considered.. Analyses of three markers are readily available in clinical laboratories for improved diagnosis.. Increased workload of the heart has been associated with the release of biochemical markers (natriuretic peptides and cardiac enzymes) that indicate that a new genetic program has been activated and maladaptation is occurring in the atria, ventricles, or both. This review summarizes those that have been identified in fetal and pediatric practice. The expression of such markers is traced from early embryonic development to fetal life, to the neonate, to childhood, and then to adult life.

Topics: Adolescent; Adult; Atrial Natriuretic Factor; Biomarkers; Child; Graft Rejection; Heart Diseases; Humans; Infant; Infant, Newborn; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Renal Insufficiency; Sepsis; Troponin T

Serum N-terminal pro-brain natriuretic peptide (NT-proBNP) tends to rise in acute phase Kawasaki disease (KD), but the cause of NT-proBNP elevation has not been clarified. In a previous study, cardiac function evaluated on 2-D echocardiography (2D-E) such as ejection fraction was normal, but this does not reflect subtle changes in cardiac dysfunction, and hence the association between cardiac function and NT-proBNP elevation is still controversial. The aim of this study was therefore to elucidate the influence of cardiac function on NT-proBNP elevation, by evaluating cardiac function via strain on 3-D speckle tracking imaging (3D-STI), in acute and subacute KD patients. Given that cytokines are also thought to induce NT-proBNP in acute phase KD, serum cytokines and cytokine receptors were measured at the same time.. Laboratory data and echocardiography in 52 KD patients in the acute and subacute phases were reviewed.. Median NT-proBNP was significantly elevated in the acute phase compared with the subacute phase (356.5 pg/mL; IQR, 145-904 pg/mL vs 103.5 pg/mL; IQR, 59-150 pg/mL, P < 0.01). All cytokines were also significantly elevated in the acute phase compared with the subacute phase. Tumor necrosis factor (TNF)-α, soluble TNF receptor (sTNFR)1, and sTNFR2 concentration were all significantly higher in the acute phase. Indices of cardiac function were not significant different between phases. NT-proBNP in the acute and subacute phases correlated with sTNFR1 (r = 0.63/0.43, P < 0.01), sTNFR2 (r = 0.50/0.31, P < 0.05), and interleukin-6 (r = 0.58/0.43, P < 0.01). NT-proBNP did not correlate with global longitudinal strain (GLS) on 3D-STI.. Although no correlation was seen between NT-proBNP and GLS on 3D-STI, correlations between NT-proBNP and cytokines were clear. NT-proBNP might be a marker of inflammation in KD, but is not a marker of cardiac function.

Topics: Acute Disease; Biomarkers; Child; Child, Preschool; Cytokines; Echocardiography; Female; Heart; Humans; Imaging, Three-Dimensional; Infant; Male; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments

The relationship between left ventricular (LV) function and longitudinal or radial contraction has not yet been elucidated in acute Kawasaki disease (KD), especially before and after treatment with intravenous immunoglobulin (IVIG).. We studied 28 KD patients without coronary aneurysms (average age, 3.2 years). The LV end-diastolic volume (LVEDV), end-systolic volume (LVESV), stroke volume (LVSV), and ejection fraction (LVEF) were assessed on 3-D echocardiography before IVIG, after IVIG, and in the convalescent phase. LV fractional shortening (LVFS) and the mitral annular plane systolic excursion (MAPSE) z-score were measured as surrogates for radial and longitudinal LV wall motions, respectively. Serum brain natriuretic peptide (BNP) was also assessed as a heart failure indicator in acute KD patients.. In all KD patients, LVEDV decreased in the acute phase with preservation of LVESV. Both LVSV and MAPSE z-score were lowest before IVIG and increased after IVIG. MAPSE z-score was highly correlated with LVEF before and after IVIG treatment. Although there was a good correlation between logBNP and LVEF before IVIG, it was lost after IVIG.. LVEDV decreased longitudinally during the acute phase of KD with preservation of LVESV, reducing both LVSV and LVEF. Serum BNP is a useful marker for evaluating LV function only prior to IVIG treatment.

Topics: Acute Disease; Biomarkers; Child; Child, Preschool; Echocardiography, Three-Dimensional; Female; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Infant; Male; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Prospective Studies; Treatment Outcome; Ventricular Dysfunction, Left

To determine whether the serum N-terminal pro-brain natriuretic peptide (NT-proBNP) can be a useful marker not only to identify the patients with Kawasaki disease (KD) who are at a higher risk of developing coronary artery lesions (CAL), and predict resistance to intravenous immunoglobulin (IVIG).. We enrolled 80 patients with the acute phase of KD at a single center. The demographic, clinical, and laboratory data were prospectively collected.. Nineteen of the 80 patients developed CAL, despite IVIG administration. They had a significantly higher serum NT-proBNP level in comparison with the patients without CAL. The NT-proBNP cut-off value of 1300 pg/mL yielded a sensitivity of 95% and a specificity of 85% for predicting CAL. However, 17 of the 80 patients were IVIG non-responders. They also had a significantly higher serum NT-proBNP level in comparison with the IVIG responders. The NT-proBNP cut-off value of 800 pg/mL yielded a sensitivity of 71% and a specificity of 62% for predicting IVIG non-responders.. The serum NT-proBNP level is increased in children with KD with CAL and IVIG resistance. It may be useful to predict CAL and IVIG resistance in KD.

Topics: Biomarkers; Child; Child, Preschool; Coronary Artery Disease; Drug Resistance; Female; Humans; Immunoglobulins, Intravenous; Infant; Male; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Risk Factors; Sensitivity and Specificity

Coronary arteritis rather than myocardial involvement is typically emphasized in Kawasaki disease (KD). Moreover, the criteria and the usual biological markers oversee the importance of cardiac-specific markers in diagnosing this disease. We sought to study the clinical usefulness of measuring B-type natriuretic peptide (BNP) and its N-terminal moiety (NT-proBNP) at the onset of KD. Our objective was to evaluate blood concentrations of BNP and NT-proBNP during the acute and subacute phases of KD. We conducted a prospective study comparing newly diagnosed KD patients to non-KD febrile controls. Blood specimens were collected at presentation, 6-12 h after intravenous immunoglobulin (IVIG) therapy, 1-2 weeks later, and 2-3 months later, or only upon reenrollment for controls. Forty-there KD and 19 control patients were enrolled consecutively. The mean age was 47.1 +/- 34.3 and 62.2 +/- 44.9 months, respectively (p = NS). Pre-IVIG NT-proBNP levels were significantly higher in KD patients than in controls (923.6 +/- 1361.7 vs. 186.2 +/- 198.0 ng/L; p < 0.001), with no statistical difference for BNP (141.9 +/- 227.5 vs. 59.9 +/- 72.4 ng/L; p = 0.112). In conclusion, our data indicate that NT-proBNP is a better marker of myocardial involvement in acute KD than BNP, particularly in cases with incomplete diagnostic criteria, and suggest that it may be a valid adjunctive diagnostic method to support the diagnosis of KD.

Topics: Acute Disease; Biomarkers; Child, Preschool; Disease Progression; Double-Blind Method; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Male; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Protein Precursors

Multisystem inflammatory syndrome in children (MIS-C) after COVID-19 shares clinical similarities to Kawasaki disease (KD). We sought to determine whether cardiac biomarker levels differentiate MIS-C from KD and their association with cardiac involvement.. Subjects included 38 MIS-C patients with confirmed prior COVID-19 and 32 prepandemic and 38 contemporaneous KD patients with no evidence of COVID-19. Patient, clinical, echocardiographic, electrocardiographic, and laboratory data timed within 72 hours of cardiac biomarker assessment were abstracted. Groups were compared, and regression analyses were used to determine associations between biomarker levels, diagnosis and cardiac involvement, adjusting for clinical factors.. MIS-C patients had fewer KD clinical features, with more frequent shock, intensive care unit admission, inotrope requirement, and ventricular dysfunction, with no difference regarding coronary artery involvement. Multivariable regression analysis showed that both higher N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin I (TnI) were associated with MIS-C vs KD, after adjusting for significant covariates. Receiver operating characteristic curves for diagnosis showed that any detectable TnI greater than 10 ng/L was predictive of MIS-C vs KD with 91% sensitivity and 76% specificity. NT-proBNP > 2000 ng/L predicted MIS-C vs KD with 82% sensitivity and 82% specificity. Higher TnI but not NT-proBNP was associated with lower LV ejection fraction. Neither biomarker was associated with coronary artery involvement.. Positive TnI and higher NT-proBNP may differentiate MIS-C from KD, which may become more relevant as evidence of prior COVID-19 becomes more challenging to determine. Cardiac biomarkers may have limited associations with cardiac involvement in this setting.

Topics: Biomarkers; Child; COVID-19; Echocardiography; Humans; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments

N-terminal pro-brain natriuretic peptide (NT-proBNP) has been studied as a diagnostic screening tool for Kawasaki disease (KD). However, brain natriuretic peptide (BNP) has been less studied while has less variability among age groups. We aimed to find out if BNP can be used as a diagnostic screening tool for KD in Korea. This was a retrospective cohort study performed in a single pediatric emergency department. Patients younger than 19 years of age who presented with fever and underwent BNP examination for suspected KD was included. The primary outcome was the diagnostic performance of BNP for KD, and the secondary outcome was the diagnostic performance of BNP for coronary artery aneurysm (CAA). We also derived a scoring system for predicting KD and CAA. Of the 778 patients who were finally included, 400 were not diagnosed with KD and 378 were diagnosed with KD. The odds ratio of BNP at the cutoff of 30 pg/mL for KD was 7.80 (95% CI, 5.67-10.73) in the univariate analysis and 3.62 (95% CI, 2.33-5.88) in the multivariable analysis. The odds ratio of BNP at the cutoff of 270 pg/mL for CAA was 3.67 (95% CI, 2.18-6.19) in the univariate analysis and 2.37 (95% CI, 1.16-8.74) in the multivariable analysis. The AUC of KD and CAA were 0.884 and 0.726, respectively, which was the highest AUCs among all variables. Additionally, we proposed a scoring system for KD and CAA. It is important to clinically suspect KD and CAA in children with high BNP levels.

Topics: Biomarkers; Child; Coronary Aneurysm; Fever; Humans; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments; Retrospective Studies

To compare the values of N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) in acute phase of Kawasaki disease (KD), sepsis and other acute febrile illnesses.. We conducted a cross-sectional study on 40 KD patients and 40 age- and sex-matched controls with sepsis and other febrile illnesses between January, 2019 and June, 2020. Complete blood count, C-reactive protein (CRP), liver and renal function tests, serum electrolytes, chest X-ray, NT-proBNP level, Bactec blood culture, urine microscopy and culture along with detailed physical examination was done for all cases and control.. Mean (SD) values of NT-proBNP levels in acute KD was higher than sepsis/other febrile illnesses (914.9 vs 219 pg/mL; P=0.001). Also, the number of KD patients whose NT-proBNP was elevated were significantly higher compared to controls (70% vs 32.5%; P<0.001).. NT-proBNP may be useful as a biomarker in the diagnosis of acute phase KD.

Topics: Biomarkers; Cross-Sectional Studies; Humans; Microscopy; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments; Sepsis; Urinalysis

Post-COVID multisystem hyperinflammatory syndrome in children (MISC) has clinical and laboratory similarities with Kawasaki disease (KD). Inflammatory markers like C-reactive protein (CRP), interleukin 6 (IL6) as well as N-terminal probrain natriuretic peptide (NT-proBNP) are elevated in both. This study attempts a comparative analysis of the 3 markers in an attempt at early differentiation for planning appropriate management.. This analytical study conducted at the Institute of Child Health, Kolkata, India compared the levels of the above 3 markers at admission between 72 patients with KD, 30% of whom had coronary artery lesions (CALs) collected over a period of 18 months (Jan 2017-June 2018), with 71 MISC patients over a period of 6 months (July 2020-December 2020). The non-parametric Mann-Whitney U test was used to test for similarity in distributions of the samples of CRP, NT-proBNP and IL6 in KD and MISC patients using correction factor for similar ranks. The 3 parameters were compared using receiver operating characteristic (ROC) curve analysis.. Mean IL6 value in KD was 83.22 pg/mL and in MISC 199.91 pg/mL, which was not found to be statistically significant (P = .322 > .05).However mean NT-proBNP (914.91 pg/mL) with CRP level (96.32 mg/L) in KD was significantly lower (P < .05 for both cases) than that in MISC (9141.16 pg/mL and 145.66 mg/L respectively). ROC analysis showed NT-proBNP has the best sensitivity and specificity in predicting MISC.. NT-proBNP and CRP are significantly higher among MISC patients; ROC analysis shows levels >935.7 pg/mL and >99.55 mg/L respectively might act as a guide to differentiate between them.

Topics: Biomarkers; C-Reactive Protein; Child; Child, Preschool; COVID-19; Humans; India; Infant; Interleukin-6; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments; ROC Curve; SARS-CoV-2; Systemic Inflammatory Response Syndrome

To determine the frequency of coronary artery lesion (CAL) in children with Kawasaki disease (KD) and to analyse the related risk factors of CAL and the predictive value of risk factors for CAL.. A descriptive study.. Department of Pediatrics, People's Hospital of Linquan County, Anhui Province, China, from January 2019 to January 2022.. Clinical data of 71 children with KD were retrospectively analysed, including 31 in the CAL group and 40 in the non-CAL group. The age, gender, days of fever, blood routine, plasma N-terminal B-type natriuretic peptide (NT-proBNP), and Kobayashi score were registered as independent variables of all the children, and the presence or absence of CAL was used as the dependent variable. All the independent variables were subjected to univariate analysis between the groups, and those with significance in univariate analysis were further subjected to unconditional binary logistic regression analysis. A receiver operating curve (ROC) was drawn to analyse the predictive power and optimal cut-off value of related risk factors for CAL.. On univariate analysis, age, NT-proBNP and Kobayashi's score were closely related to CAL (all p<0.05). Multivariate analysis showed that NT-proBNP and Kobayashi scores were independent risk factors for CAL in children with KD. ROC curve analysis showed that the area under the curve (AUC) of NT-proBNP and Kobayashi scores were 0.771 and 0.732, respectively, at optimal critical values of 543.12 ng/L and 7.50 points, respectively.. The frequency of CAL in children with KD is high. NT-proBNP and Kobayashi scores are independent risk factors for the occurrence of CAL in children with KD, and they have good predictive performance for the diagnosis of CAL.. Kawasaki disease, Children, Coronary artery lesion, Risk factors, Kobayashi score, NT-pro BNP.

Topics: Biomarkers; Child; Coronary Artery Disease; Coronary Vessels; Humans; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments; Retrospective Studies; Risk Factors; ROC Curve

The relationship between serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and the clinical features of patients with Kawasaki disease (KD) has been the subject of research. Recent studies have revealed that serum NT-proBNP levels vary with age. We therefore aimed to determine the utility of age-stratified cut-off values for NT-proBNP in predicting coronary artery lesions (CALs) in patients with KD.. We retrospectively assessed the electronic medical records of patients who were hospitalized for KD or incomplete KD between January 1, 2015, and August 31, 2019. The patients were divided into high and normal NT-proBNP groups using age-stratified cut-off based on serum NT-proBNP levels measured immediately before KD treatment initiation.. The study comprised 242 cases, including 71 and 171 cases in high and normal NT-proBNP groups, respectively. Thirty-seven of them (15.3%) were resistant to treatment; 15 (6.2%) had CALs, with a higher incidence in the high NT-proBNP group than in the normal NT-proBNP group. On multivariate logistic regression analysis, high serum NT-proBNP levels were significantly correlated to CALs (OR, 9.76; 95% CI, 2.64-36.2). On logistic regression analysis to compare the predictive accuracy of the age-stratified and fixed cut-off for CALs, the age-stratified cut-off values showed a larger area under the receiver operating characteristic curve than fixed cut-off value.. Based on age-stratified cut-off values for serum NT-proBNP, high NT-proBNP levels at the time of diagnosis were significantly associated with CALs in patients with KD. Higher predictive accuracy for CALs of the age-stratified cut-off values was also suggested.

Topics: Biomarkers; Humans; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments; Retrospective Studies; ROC Curve

Topics: Abdominal Pain; Acute Kidney Injury; Adolescent; Adult; Asthenia; Chest Pain; Conjunctivitis; Coronary Angiography; Coronary Care Units; COVID-19; Diarrhea; Dyspnea; Electrocardiography; Exanthema; Extracorporeal Membrane Oxygenation; Female; Fever; France; Headache; Humans; Hypotension; Intensive Care Units; Magnetic Resonance Imaging; Male; Mucocutaneous Lymph Node Syndrome; Myocarditis; Natriuretic Peptide, Brain; Peptide Fragments; Respiration, Artificial; SARS-CoV-2; Stroke Volume; Systemic Inflammatory Response Syndrome; Tachycardia; Troponin; Ventricular Dysfunction, Left; Young Adult

Kawasaki disease (KD) is a febrile disease of childhood characterized by systemic vasculitis that can lead to coronary artery lesions (CAL). This was a prospective cohort study to determine the levels of the pentraxin 3 (PTX3), soluble CD24-Subtype (Presepsin) and N-terminal pro-brain natriuretic peptide (NT-pro BNP) in consecutive KD patients. From January 2013 to March 2015, all patients with KD admitted to Aichi Medical University Hospital who provided consent had their plasma saved before IVIG administration. In total, 97 cases were registered. 22 cases of incomplete KD were excluded from the outcome analysis. The total 75 cases were used for statistical analyses. A PTX3 threshold of >7.92 ng/ml provided a specificity of 88.5 %, a sensitivity of 94.4 %, and a likelihood ratio as high as 15.92 for the diagnosis of KD compared with febrile non-KD controls. Although an echocardiographic diagnosis of CAL in the early course of the disease was confirmed in 24 cases, it was not in the remaining 51 cases. Neither NT-proBNP nor Presepsin had statistical significance for the prediction of the echocardiographic CAL diagnosis. Only PTX3 was significantly predictive of the echocardiographic CAL diagnosis (p=0.01). The PTX3 level was significantly higher in the intravenous immunoglobulin (IVIG) non-responders (45.9±7.45) than in the IVIG responders (17.0 ± 1.46 ng/ml) (p< 0.001). The PTX3 level also correlated with the number of IVIG treatment courses needed to resolve fever (R² =0.64). Persistent CAL (pCAL) formation was observed in three cases; one of aneurysm only and two aneurysms with dilatations. The patients with pCAL had significantly higher PTX3 levels (85 ± 8.4 ng/ml) than patients without pCAL (22 ± 2.2 ng/ml) (p< 0.0001). In terms of pCAL prediction, the area under the curve (AUC) of receiver operating characteristic ROC curve of PTX3 was 0.99, and it was significantly greater than that of Presepsin (0.67) or NT-proBNP (0.75). PTX3 is a soluble pattern recognition molecule that acts as a main component of the innate immune system. These data suggest that PTX3 can be utilized as a definitive biomarker for the prediction of IVIG resistance and subsequent CAL formation in patients with KD.

Topics: Biomarkers; C-Reactive Protein; Case-Control Studies; Child; Child, Preschool; Coronary Aneurysm; Echocardiography; Female; Humans; Immunoglobulins, Intravenous; Infant; Lipopolysaccharide Receptors; Male; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Reproducibility of Results; Serum Amyloid P-Component; Treatment Outcome; Up-Regulation

To determine the expression levels and clinical significance of serum N-terminal pro-brain natriuretic peptide (NT-proBNP), hydrogen sulfide (H₂S) and interleukin-6 (IL-6) in children with Kawasaki disease (KD).. Descriptive comparative study.. Department of Pediatric Medicine, Baoding Children's Hospital, from July 2017 to July 2018.. Ninety-five KD children were chosen as the case group, and were classified into CAL group (23 patients) and NCAL group (72 patients, according to the presence of a coronary artery lesion (CAL). Forty-six non-KD children with an upper respiratory infection in the same time period were chosen as the control group. Electrochemiluminescence method was used to detect serum NT-proBNP levels. The spectrophotometer method was used to test H2S levels, and an enzyme-linked immunosorbent assay was used to test serum IL-6 levels and to analyse the correlation.. In the acute phase and recovery phase, serum NT-proBNP and IL-6 levels were higher in the case group than the control group, while H2S levels were lower than those in the control group (p<0.001). In both the acute and recovery phases, serum NT-proBNP and IL-6 levels were higher in the CAL group than in the NCAL group, while H2S levels were lower than those in the NCAL group (p<0.001).. NT-proBNP and IL-6 levels rise and the H2S level decreases in the blood of KD children, indicating that these indicators may participate in the pathogenesis of KD and that their levels are related to CAL occurrence and the vascular inflammatory response.

Topics: Biomarkers; Case-Control Studies; Child; Child, Preschool; Coronary Artery Disease; Female; Humans; Hydrogen Sulfide; Interleukin-6; Male; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments; Spectrophotometry

The N-terminal proBNP (NT-proBNP), produced by cardiomyocytes, has several reported utilities and associations in acute Kawasaki disease (KD). The objective of this study is to examine the relationship between serum values of NT-proBNP at time of KD diagnosis with cardiac systolic, diastolic function and electrocardiographic changes, at onset of the disease and during the first year of follow-up. KD was diagnosed in 127 children between March 2007 and July 2014, mean diagnostic age 3.5 ± 2.9 years. Coronary artery maximum z score was 2.6 ± 2.8 (range - 0.6 to + 18.9), with giant aneurysm in 5/122 (4.1%). Age-adjusted NT-proBNP was 2.6 ± 1.6 z score, 78/122 (63.9%) > 2.0. There was a crescendo correlation between onset NT-proBNP z score and C-Reactive protein (CRP) serum levels (slope + 0.49, p < 0.001). There was a crescendo correlation between NT-proBNP z score and indexed left ventricular (LV) mass (slope + 1.86, p = 0.02), LV diastolic function parameter E/e' ratio (slope + 0.31, p = 0.04) and a decrescendo correlation with age-adjusted LV shortening fraction (SF) (- 0.63, p = 0.02). Lower SF z score, higher left ventricular mass index and E/e' ratio were associated with higher NT-proBNP z score, but without correlation with CRP levels. Within 2-3 months from the onset of the disease, there was a resolution of the systolic dysfunction. Electrocardiographic parameter changes were associated with decreased LV shortening fraction but not with NT-proBNP. KD patients with elevated NT-proBNP at onset have sub-clinical myocardial involvement and might benefit from follow-up and continued evaluation, even in the absence of coronary artery involvement.

Topics: Biomarkers; Child; Child, Preschool; Echocardiography; Female; Humans; Infant; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments; Ventricular Dysfunction, Left

BACKGROUNDPediatric SARS-CoV-2 infection can be complicated by a dangerous hyperinflammatory condition termed multisystem inflammatory syndrome in children (MIS-C). The clinical and immunologic spectrum of MIS-C and its relationship to other inflammatory conditions of childhood have not been studied in detail.METHODSWe retrospectively studied confirmed cases of MIS-C at our institution from March to June 2020. The clinical characteristics, laboratory studies, and treatment response were collected. Data were compared with historic cohorts of Kawasaki disease (KD) and macrophage activation syndrome (MAS).RESULTSTwenty-eight patients fulfilled the case definition of MIS-C. Median age at presentation was 9 years (range: 1 month to 17 years); 50% of patients had preexisting conditions. All patients had laboratory confirmation of SARS-CoV-2 infection. Seventeen patients (61%) required intensive care, including 7 patients (25%) who required inotrope support. Seven patients (25%) met criteria for complete or incomplete KD, and coronary abnormalities were found in 6 cases. Lymphopenia, thrombocytopenia, and elevation in inflammatory markers, D-dimer, B-type natriuretic peptide, IL-6, and IL-10 levels were common but not ubiquitous. Cytopenias distinguished MIS-C from KD and the degree of hyperferritinemia and pattern of cytokine production differed between MIS-C and MAS. Immunomodulatory therapy given to patients with MIS-C included intravenous immune globulin (IVIG) (71%), corticosteroids (61%), and anakinra (18%). Clinical and laboratory improvement were observed in all cases, including 6 cases that did not require immunomodulatory therapy. No mortality was recorded in this cohort.CONCLUSIONMIS-C encompasses a broad phenotypic spectrum with clinical and laboratory features distinct from KD and MAS.FUNDINGThis work was supported by the National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases; the National Institute of Allergy and Infectious Diseases; Rheumatology Research Foundation Investigator Awards and Medical Education Award; Boston Children's Hospital Faculty Career Development Awards; the McCance Family Foundation; and the Samara Jan Turkel Center.

Topics: Adolescent; Adrenal Cortex Hormones; Betacoronavirus; Biomarkers; Child; Child, Preschool; COVID-19; Female; Fibrin Fibrinogen Degradation Products; Humans; Immunoglobulins, Intravenous; Immunomodulation; Infant; Interleukin 1 Receptor Antagonist Protein; Interleukin-10; Interleukin-6; Macrophage Activation Syndrome; Male; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Retrospective Studies; SARS-CoV-2; Systemic Inflammatory Response Syndrome

This case aims to remind all providers to scrutinise for atypical presentations of multisystem inflammatory syndrome in children (MIS-C) which may mimic a more routine diagnosis. In the absence of mucocutaneous symptoms, the diagnosis of MIS-C can be missed. Given the potential for rapid deterioration of patients with MIS-C, early treatment and inpatient interventions are necessary.

Topics: Abdominal Pain; Adenosine Monophosphate; Alanine; C-Reactive Protein; Child; COVID-19; COVID-19 Drug Treatment; COVID-19 Nucleic Acid Testing; COVID-19 Serological Testing; Diagnosis, Differential; Fever; Humans; Interleukin 1 Receptor Antagonist Protein; Intubation, Intratracheal; Male; Mucocutaneous Lymph Node Syndrome; Myocarditis; Nasopharynx; Natriuretic Peptide, Brain; SARS-CoV-2; Systemic Inflammatory Response Syndrome; Tachycardia; Treatment Outcome

Topics: Betacoronavirus; Biomarkers; Child; Coronavirus Infections; COVID-19; Heart Diseases; Heart Failure; Humans; Infant, Newborn; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Neoplasms; Pandemics; Peptide Fragments; Pneumonia, Viral; Renal Insufficiency, Chronic; SARS-CoV-2; Troponin I; Troponin T; Virus Diseases

The purpose of this study was to detect the expression levels of plasma microRNA-21 (miRNA-21) and NT-proBNP (N-terminal prohormone of brain natriuretic peptide) in children with Kawasaki disease (KD), as well as their clinical significance.. Children with KD (n=100) who were treated in our hospital from June 2017 to May 2019 were included. In the same period, non-KD children with febrile diseases were included as controls. Plasma levels of miRNA-21 and NT-proBNP were detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and electrochemiluminescence, respectively. Then, the relationship between miRNA-21 and NT-proBNP in children with KD was analyzed by Pearson's correlation test. Potential factors influencing KD were analyzed by Multivariate logistic regression test. Finally, receiver operating characteristic (ROC) curves were depicted to assess the diagnostic potentials of miRNA-21 and NT-proBNP in KD.. The results showed that miRNA-21 and NT-proBNP levels were higher in children with KD. Plasma level of miRNA-21 was positively correlated with NT-proBNP level in children with KD. Besides, both miRNA-21 and NT-proBNP were risk factors influencing the onset of KD. According to ROC curves, the sensitivity and specificity of miRNA-21 in diagnosing KD was 83% and 89%, respectively (AUC=0.9212, 95% CI: 0.8809-0.9614, cut-off value=1.985). NT-proBNP also displayed diagnostic potential in KD (AUC=0.9788, 95% CI: 0.9630-0.9946, cut-off value=265.6, sensitivity=88%, specificity=95%).. MiRNA-21 and NT-proBNP are upregulated in plasma of children with KD. They are positively correlated with each other and serve as risk factors for KD. Both of them can be utilized as indicators of auxiliary diagnosis in KD.

Topics: Biomarkers; Child; Child, Preschool; Female; Humans; Infant; Male; MicroRNAs; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain

The prediction of resistance to intravenous immunoglobulins (IVIG) is currently still one of the main research areas in Kawasaki disease (KD). Several studies have reported on the use of N-terminal pro-brain natriuretic peptide (NT-ProBNP) to this end. However, considering the age-dependency of NT-ProBNP levels, age- specific NT-ProBNP cutoff levels to predict IVIG resistance in KD might be more precise and should be evaluated.. A prospective cohort study with standardized data collection involving 393 KD patients aged 1 month to 125 months was conducted between June 2015 and April 2018. The demographic characteristics, clinical manifestations and laboratory data were compared between the patients responding to initial intravenous immunoglobulin (IVIG-response group) and those who did not (IVIG-resistance group). We further distinguished four subgroups according to patients' age (< 1 year, 1-2 years, 2-6 years, > 6 years). The cutoff values of NT-ProBNP for the prediction of IVIG resistance overall and in the subgroups were obtained using receiver operating characteristic (ROC) analysis.. In all KD patients, the level of NT-ProBNP was significantly higher in the IVIG-resistance compared to the IVIG-response group (P = 0.006). This findings was similar in the subgroups except for patients older than six years. The best cutoff values of NT-ProBNP to predict IVIG resistance were 3755 pg/ml for all KD patients, 3710 pg/ml, 2800 pg/ml, 2480 pg/ml for those aged 2-6 years, 1-2 years and < 1 year, respectively. The corresponding sensitivities were 44.0, 52.2, 50.0 and 75.0%, while the specifities were 84.1, 86.3, 77.9 and 71.8%, respectively.. NT-proBNP is a complementary laboratory marker for the prediction of IVIG resistance in KD patients, particularly for those younger than one year. Applying age-specific cutoff values is more precise than one value for all ages.

Topics: Age Factors; Child; Child, Preschool; Female; Humans; Immunoglobulins, Intravenous; Infant; Infant, Newborn; Male; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Treatment Failure

Topics: Biomarkers; Humans; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain

Topics: Humans; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments

Coronary artery dilatation (CAD) is a great concern with Kawasaki disease (KD). This study aimed to investigate the relationship between serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and CAD in patients with the hyperacute phase (≤4 days of fever) of KD.. Serum NT-proBNP levels were compared between patients with and those without CAD, who underwent transthoracic echocardiography (TTE) within 24 h of the hyperacute phase of KD in the pediatric emergency department (PED). Electronic medical records of patients aged 1 month to 15 years who visited the PED were retrospectively assessed from January 2010 to December 31, 2014.. One hundred nine patients were enrolled in the study. Twenty-three of those patients had CAD within 24 h of TTE. Median serum NT-proBNP levels were significantly higher in patients with CAD (824.1 pg/ml; interquartile range [IQR], 515.4-1570.0184.8-767.8 pg/ml) than in patients without CAD (396.4 pg/ml; IQR, 184.8-767.8 pg/ml) (p ≤ 0.001). The cutoff value of serum NT-proBNP, which predicted CAD during the hyperacute phase of KD, was 515.4 pg/ml, which yielded sensitivity of 78.26% and specificity of 61.63%. The area under the curve for NT-proBNP for predicting CAD during hyperacute KD was 0.749 (95% CI, 0.642-0.856).. Serum NT-proBNP might be an additional laboratory marker for detecting early CAD during the hyperacute phase of KD in the PED.

Topics: Adolescent; Adult; Biomarkers; Coronary Vessels; Echocardiography; Female; Humans; Logistic Models; Male; Middle Aged; Mucocutaneous Lymph Node Syndrome; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Retrospective Studies; ROC Curve; Sensitivity and Specificity; Vasodilation; Young Adult

Kawasaki disease (KD) vasculitis is an acute febrile illness of childhood characterized by systemic vasculitis of unknown origin, and is the most common cause of acquired heart disease among children in the United States. While  histological evidence of myocarditis can be found in all patients with acute KD, only a minority of patients are clinically symptomatic and a subset demonstrate echocardiographic evidence of impaired myocardial function, as well as increased left ventricular mass, presumed to be due to myocardial edema and inflammation. Up to a third of KD patients fail to respond to first-line therapy with intravenous immunoglobulin (IVIG), and the use of interleukin (IL)-1 receptor antagonist (IL-1Ra, anakinra) is currently being investigated as an alternative therapeutic approach to treat IVIG-resistant patients. In this study, we sought to investigate the effect of IL-1Ra on myocardial dysfunction and its relation to myocarditis development during KD vasculitis. We used the Lactobacillus casei cell-wall extract (LCWE)-induced murine model of KD vasculitis and investigated the effect of IL-1Ra pretreatment on myocardial dysfunction during KD vasculitis by performing histological, magnetic resonance imaging (MRI) and echocardiographic evaluations. IL-1Ra pretreatment significantly reduced KD-induced myocardial inflammation and N-terminal pro B-type natriuretic peptide (NT-proBNP) release. Both MRI and echocardiographic studies on LCWE-injected KD mice demonstrated that IL-1Ra pretreatment results in an improved ejection fraction and a normalized left ventricular function. These findings further support the potential beneficial effects of IL-1Ra therapy in preventing the cardiovascular complications in acute KD patients, including the myocarditis and myocardial dysfunction associated with acute KD.

Topics: Animals; Cardiomyopathies; Disease Models, Animal; Immunoglobulins, Intravenous; Inflammation; Interleukin 1 Receptor Antagonist Protein; Lacticaseibacillus casei; Male; Mice; Mice, Inbred C57BL; Mucocutaneous Lymph Node Syndrome; Myocarditis; Natriuretic Peptide, Brain; Receptors, Interleukin-1; Vasculitis

To examine clinical characteristics of Kawasaki disease (KD) in infants younger than 3 months of age and to develop a method for detecting KD in febrile infants.. In a case-control study, we retrospectively collected clinical and laboratory data from 24 KD infants younger than 3 months of age out of 410 KD patients. We then compared younger infants with both older patients and febrile infants with respiratory syncytial virus (RSV) infection and urinary tract infections (UTI).. The frequency of incomplete KD was higher in the younger group than in the control group (79% vs. 36%, P < 0.0001). Furthermore, before treatment, the incidence of coronary artery lesions (CAL) was significantly higher in the younger group (29% vs. 3.9%, P = 0.0001), resulting in a higher incidence of coronary artery sequelae (21% vs. 3.4%, P = 0.0023). Our results revealed that the serum N-terminal prohormone of brain natriuretic peptide (NT-proBNP) level of KD patients was higher than that of RSV and UTI patients (3110 ± 2076 vs. 698 ± 436, P = 0.0001; and 971 ± 589 pg/mL, P = 0.0002, respectively). Thus, NT-proBNP might be suitable as a diagnostic marker of KD in young infants (P = 0.0005, criterion values: 1555 pg/mL [sensitivity: 80%, specificity: 85%]).. Kawasaki disease infants younger than 3 months of age appear to be at higher risk for incomplete KD and early-onset CAL prior to the appearance of coronary artery sequelae. We suggest performing an echocardiogram and evaluating NT-proBNP in young infants with fever that has lasted longer than 2 days, regardless of the presence or absence of manifestations associated with KD.

Topics: Age Factors; Biomarkers; Coronary Artery Disease; Echocardiography; Fever; Humans; Incidence; Infant; Japan; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Retrospective Studies; Risk Factors; Time Factors; Up-Regulation

To assess the predictors for intravenous immunoglobulin (IVIG) resistance and coronary artery lesions (CALs) in Kawasaki disease (KD).. A total of 560 KD patients were reviewed retrospectively, including 410 complete KD (cKD) and 150 incomplete KD (iKD) patients. The laboratory data were compared between the IVIG-resistant and IVIG-responsive groups, as well as between the coronary artery lesions (CALs+) and without coronary artery lesions (CALs-) groups.. In the cKD patients, C-reactive protein (CRP) levels had a sensitivity of 65.52% and a specificity of 62.7% for predicting IVIG-resistance at a cutoff point of >100 mg/L. When albumin <32 g/L, the sensitivity and specificity for predicting IVIG-resistance were 72 and 83.19%, respectively. N-terminal pro-brain natriuretic peptide (NT-proBNP) levels had a sensitivity of 73.91% and a specificity of 76.43% for predicting IVIG-resistance at a cutoff point of >1300 pg/ml. Interleukin-6 levels had a sensitivity of 76.19% and a specificity of 61.59% at a cutoff value of >45 pg/ml. Erythrocyte sedimentation rate (ESR) levels had a sensitivity of 53.26% and a specificity of 64.14% for predicting CALs at a cutoff point of >75 mm/h. In the iKD patients, the sensitivity and specificity for predicting IVIG-resistance were 80 and 54.1% when hemoglobin <110 g/L. When proportion of neutrophils >70%, the sensitivity and specificity for predicting IVIG-resistance were 68 and 66.94%, respectively. ESR levels had a sensitivity of 70.83% and a specificity of 65.81% for predicting IVIG-resistance at a cutoff point of >80 mm/h. NT-proBNP levels had a sensitivity of 78.57% and a specificity of 56.67% for predicting IVIG-resistance at a cutoff point of >360 pg/ml. Interleukin-6 levels had a sensitivity of 70.59% and a specificity of 66.28% at a cutoff value of >25 pg/ml. Interleukin-10 levels had a sensitivity of 64.71% and a specificity of 74.42% for predicting IVIG-resistance at a cutoff value of >8 pg/ml. ESR levels had a sensitivity of 61.82% and a specificity of 65.12% for predicting CALs at a cutoff point of >75 mm/h.. The white blood cell count, proportion of neutrophils, hemoglobin, CRP, ESR, albumin, NT-proBNP, interleukin-6 and 10 may be effective predictors for IVIG resistance and CALs in KD patients.

Topics: Blood Sedimentation; C-Reactive Protein; Child, Preschool; Coronary Artery Disease; Drug Resistance; Female; Hemoglobins; Humans; Immunoglobulins, Intravenous; Infant; Interleukin-6; Leukocyte Count; Male; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments; Regression Analysis; Retrospective Studies; Risk Factors; Serum Albumin

We previously reported the clinical usefulness of the mitral annular plane systolic excursion (MAPSE) to evaluate the left ventricular (LV) function in patients with Kawasaki disease (KD) in the acute-phase. However, the feasibility of the MAPSE z-score has not been evaluated in patients with acute KD. We prospectively studied 60 KD patients without coronary aneurysms. The MAPSE z-scores were calculated using our standard MAPSE data. Brain natriuretic peptide (BNP) was measured as a parameter of LV function. In total, 281 healthy age- and body size-matched subjects were chosen as the control group. The MAPSE z-score decreased in the acute-phase (median value, -1.4) and increased in the convalescent phase (median value, 0.18; P < 0.0001). However, there was no significant difference in the MAPSE z-score between patients in the convalescent phase and the control patients (0.18 vs. 0.02, P = 0.199). Multivariate regression analysis revealed that BNP was an independent predictor of the MAPSE z-score (β = 0.40, P < 0.005). According to the receiver operating characteristic (ROC) analysis, the optimal cutoff value for the MAPSE z-score to judge LV dysfunction was -0.9. The MAPSE z-score is a useful index to evaluate LV function, and the cutoff value of -0.9 can be an indicator to judge LV dysfunction in the patients with acute-phase KD.

Topics: Acute Disease; Child; Child, Preschool; Echocardiography; Feasibility Studies; Female; Health Status Indicators; Humans; Infant; Male; Mitral Valve; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Predictive Value of Tests; Prospective Studies; Systole; Ventricular Dysfunction, Left; Ventricular Function, Left

Coronary artery involvement remains the most important complication with Kawasaki disease (KD). Additional myocardial injury can be caused by inflammatory response and ischemic event. However, the long-term outcome of myocardial function has not been fully known in KD. The purpose of this study is to evaluate myocardial function in school-aged children who had the past history of KD. Sixty-seven children in the second grade of elementary schools, who had the past history of KD, were included. Echocardiographic measurements of each coronary artery and myocardial function were obtained as the long-term follow-up data, and compared with the baseline data at the time of initial presentation of KD. The mean age of the subjects was 8.6 ± 2.4 years, and 4.3 ± 3.4 years have passed since the diagnosis of KD. Among the echocardiographic data, interventricular septum thickness at end-diastole (IVSd), LV internal diameters at end-systole (LVIDs), maximal velocity of late diastolic filling across mitral valve (mitral A) flow, maximal velocity of early diastolic filling across mitral valve (mitral E)/A ratio, mitral inflow E wave to peak early diastolic tissue velocity (E/E') ratio showed significant differences between the baseline and follow-up measurements. Coronary Z-score of left main artery (LMA), left anterior descending (LAD), and right coronary artery (RCA) showed no significant difference. The school-aged children with the past history of KD may have diastolic dysfunction. Therefore, appropriate assessment of myocardial function would be recommended during the follow-up period in children with KD.

Topics: Child; Child, Preschool; Coronary Vessels; Echocardiography; Female; Heart Ventricles; Humans; Male; Mitral Valve; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Stroke Volume

N-terminal prohormone of brain natriuretic peptide (NT-proBNP) was recently reported as a biomarker for diagnosing Kawasaki disease (KD). The basal NT-proBNP level, however, gradually decreases with age. We investigated the usefulness of an age-stratified cutoff value of NT-proBNP for diagnosing KD. All the patients enrolled in this study visited Chonnam National University Hospital between December 2007 and March 2016. The KD groups consisted of 214 patients with complete KD and 129 patients with incomplete KD. The control group included 62 children with simple febrile illness but without heart disease. Laboratory data including NT-proBNP level were evaluated. Each group was divided into subgroups according to patient age (<6 months, 6-12 months, 12-24 months, and >24 months), and different cutoff values of NT-proBNP were calculated. The cutoff values of NT-proBNP used to diagnose total KD and incomplete KD were 762 and 762 pg/mL (<6 months), 310 and 310 pg/mL (6-12 months), 326 and 326 pg/mL (12-24 months), and 208 and 137 pg/mL (>24 months), respectively. In conclusion, age-stratified NT-proBNP is a useful biomarker for the differential diagnosis of KD in patients with a simple febrile illness.

Topics: Age Factors; Biomarkers; Case-Control Studies; Child, Preschool; Female; Humans; Infant; Male; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Sensitivity and Specificity

Diagnosis of Kawasaki disease (KD) can be challenging in the absence of a confirmatory test or pathognomonic finding, especially when clinical criteria are incomplete. We recently proposed serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) as an adjunctive diagnostic test.. We retrospectively tested a new algorithm to help KD diagnosis based on NT-proBNP, coronary artery dilation (CAD) at onset, and abnormal serum albumin or C-reactive protein (CRP). The goal was to assess the performance of the algorithm and compare its performance with that of the 2004 American Heart Association (AHA)/American Academy of Pediatrics (AAP) algorithm.. The algorithm was tested on 124 KD patients with NT-proBNP measured on admission at the present institutions between 2007 and 2013. Age at diagnosis was 3.4 ± 3.0 years, with a median of five diagnostic criteria; and 55 of the 124 patients (44%) had incomplete KD. CA complications occurred in 64 (52%), with aneurysm in 14 (11%). Using this algorithm, 120/124 (97%) were to be treated, based on high NT-proBNP alone for 79 (64%); on onset CAD for 14 (11%); and on high CRP or low albumin for 27 (22%). Using the AHA/AAP algorithm, 22/47 (47%) of the eligible patients with incomplete KD would not have been referred for treatment, compared with 3/55 (5%) with the NT-proBNP algorithm (P < 0.001).. This NT-proBNP-based algorithm is efficient to identify and treat patients with KD, including those with incomplete KD. This study paves the way for a prospective validation trial of the algorithm.

Topics: Adolescent; Algorithms; American Heart Association; Biomarkers; Child; Child, Preschool; Clinical Decision-Making; Decision Support Techniques; Female; Humans; Infant; Infant, Newborn; Male; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments; Retrospective Studies; United States

The diagnosis of Kawasaki disease (KD), a common pediatric vasculitis, is based solely on clinical criteria. There is a need for a robust laboratory marker that can help differentiate KD from other acute, febrile, childhood illnesses and also to predict cardiac involvement. We conducted a cross-sectional study of 25 consecutive patients admitted with diagnosis of KD from January 2013 to April 2014 and compared them with age- and sex-matched febrile controls. We studied the serum pro-brain natriuretic peptide (ProBNP) [ProBNP and N-terminal pro-B-type natriuretic peptide (NT-ProBNP) levels], a marker of myocardial dysfunction, in children with KD in acute and convalescent phases of disease. These levels were also estimated in febrile controls for comparison. The ProBNP (ProBNP and NT-ProBNP) levels were much higher in the acute phase of the KD patients compared to levels in the convalescent phase of KD (p = 0.000014). Similarly, the levels in the acute phase were higher when compared to the age- and sex-matched febrile controls (p = 0.000126). The receiver operating curve (ROC) analysis for the ProBNP levels in the acute phase of KD yielded an area under the curve of 0.954 ± 0.034 (p < 0.000, 95 % CI 0.886-1.0). Based on ROC analysis, a cutoff of 1025 pg/mL for ProBNP levels in the acute phase of KD had 88 % sensitivity and 96 % specificity for the diagnosis of KD. A lower cut-off of 514 pg/mL yielded a 100 % sensitivity and 80 % specificity for the diagnosis of KD. The ProBNP levels were higher in those with coronary artery abnormalities (CAA) compared to those without CAA in both acute (p = 0.013) and convalescent (p = 0.045) phases. ProBNP levels may be used as a surrogate marker for the differentiation of KD from other febrile, infectious illnesses and may also predict the involvement of coronary arteries.

Topics: Area Under Curve; Biomarkers; Case-Control Studies; Child; Child, Preschool; Coronary Artery Disease; Cross-Sectional Studies; Diagnosis, Differential; Female; Humans; India; Infant; Male; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; ROC Curve; Up-Regulation

The aim of this study was to investigate the clinical significance and factors that affect N-terminal pro-brain natriuretic peptide (NT-proBNP) elevation in the acute phase of Kawasaki disease (KD) despite the absence of apparent cardiac complications.. The laboratory and echocardiography results of 44 KD patients in the acute and subacute phases were reviewed.. With preserved cardiac function, median NT-proBNP was significantly elevated in the acute phase compared with the subacute phase (343 pg/mL, IQR, 162-1182 pg/mL vs 98 pg/mL, IQR, 61-205 pg/mL, respectively; P < 0.0001). The respective levels of tumor necrosis factor (TNF)-α, soluble TNF receptor (sTNFR)1, and sTNFR2 were also significantly elevated in the acute phase compared with the subacute phase: TNF-α, 3.3 pg/mL (IQR, 2.6-4.8 pg/mL) versus 2.4 pg/mL (IQR 1.9-4.0 pg/mL; P < 0.01), sTNFR1, 2741 pg/mL (IQR, 2080-3183 pg/mL) versus 976 pg/mL (IQR, 814-1247 pg/mL; P < 0.0001), sTNFR2, 5644 pg/mL (IQR, 4693-7520 pg/mL) versus 3169 pg/mL (IQR, 2132-3878 pg/mL; P < 0.0001). Log-transformed NT-proBNP was correlated with TNF-α (r = 0.29, P = 0.056), sTNFR1 (r = 0.60, P < 0.0001), and sTNFR2 (r = 0.65, P < 0.0001). TNF-α was correlated with sTNFR1 (r = 0.35, P = 0.02) and sTNFR2 (r = 0.51, P < 0.001).. Tumor necrosis factor-α may cause NT-proBNP elevation in the acute phase of KD, and NT-proBNP level may be an indicator of TNF-α activity.

Topics: Acute Disease; Biomarkers; Child, Preschool; Disease Progression; Echocardiography; Female; Follow-Up Studies; Humans; Male; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Tumor Necrosis Factor-alpha

The purpose of this study was to determine whether the serum N-terminal pro-brain natriuretic peptide (NT-proBNP) level could be a useful marker for Kawasaki disease in the pediatric emergency department (PED) and in the presence of fever duration of 4 days or less (hyper-acute phase of Kawasaki disease). Medical records of patients who were 1 month to 15 years old of age and presented at the PED with suspected Kawasaki disease from January 1, 2010, to December 31, 2014, were collected retrospectively. Two hundred thirty-nine patients with a history of fever for 4 days or less were diagnosed with Kawasaki disease, as well as 111 patients with other febrile diseases, and were enrolled. The NT-proBNP level was significantly higher in patients with Kawasaki disease (Kawasaki disease vs. other febrile disease group, 444.8 (189.7-951.5) vs. 153.4 (68.9-287.6) pg/mL; p < 0.001), and a cutoff value of 244.7 pg/mL yielded a sensitivity and specificity of 68.6 and 70.3 %, respectively. The area under the curve of the NT-proBNP for predicting Kawasaki disease was 0.763 (95 % CI 0.712-0.814).. NT-proBNP might be an adjunctive laboratory marker for hyper-acute phase of Kawasaki disease in the PED. What is Known: • N-terminal pro-brain natriuretic peptide level has been reported as a useful marker for diagnosis in patients with the acute phase of Kawasaki disease. • But, in the cases of less than 5 days of fever, the appropriate level of NT-proBNP for differentiating Kawasaki disease in PED has not been yet evaluated. What is New: • NT-proBNP might be an adjunctive laboratory marker for hyper-acute phase of Kawasaki disease.

Topics: Acute Disease; Biomarkers; Child; Child, Preschool; Diagnosis, Differential; Female; Fever; Humans; Infant; Male; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments; Retrospective Studies; ROC Curve; Sensitivity and Specificity

Topics: Biomarkers; Child; Follow-Up Studies; Humans; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies

We have lately documented the importance of N-terminal pro-brain natriuretic peptide in aiding the diagnosis of Kawasaki disease.. We sought to investigate the potential value of N-terminal pro-brain natriuretic peptide pertaining to the prediction of coronary artery dilatation (Z-score>2.5) and/or of resistance to intravenous immunoglobulin therapy. We hypothesised that increased serum N-terminal pro-brain natriuretic peptide level correlates with increased coronary artery dilatation and/or resistance to intravenous immunoglobulin.. We carried out a prospective study involving newly diagnosed patients treated with 2 g/kg intravenous immunoglobulin within 5-10 days of onset of fever. Echocardiography was performed in all patients at onset, then weekly for 3 weeks, then at month 2, and month 3. Coronary arteries were measured at each visit, and coronary artery Z-score was calculated. All the patients had N-terminal pro-brain natriuretic peptide serum level measured at onset, and the Z-score calculated.. There were 109 patients enrolled at 6.58±2.82 days of fever, age 3.79±2.92 years. High N-terminal pro-brain natriuretic peptide level was associated with coronary artery dilatation at onset in 22.2 versus 5.6% for normal N-terminal pro-brain natriuretic peptide levels (odds ratio 4.8 [95% confidence interval 1.05-22.4]; p=0.031). This was predictive of cumulative coronary artery dilatation for the first 3 months (p=0.04-0.02), but not during convalescence at 2-3 months (odds ratio 1.28 [95% confidence interval 0.23-7.3]; p=non-significant). Elevated N-terminal pro-brain natriuretic peptide levels did not predict intravenous immunoglobulin resistance, 15.3 versus 13.5% (p=1).. Elevated N-terminal pro-brain natriuretic peptide level correlates with acute coronary artery dilatation in treated Kawasaki disease, but not with intravenous immunoglobulin resistance.

Topics: Acute Coronary Syndrome; Biomarkers; Child; Child, Preschool; Coronary Vessels; Echocardiography; Female; Humans; Immunoglobulins, Intravenous; Infant; Male; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Prospective Studies

It is well known that brain natriuretic peptide (BNP) is elevated in the acute phase of Kawasaki disease (KD). We hypothesized that mitral annular plane systolic excursion (MAPSE) could identify LV dysfunction in the acute phase of KD. Fifty patients with KD were enrolled in this study. BNP sampling and an echocardiographic study were performed just before and after intravenous immunoglobulin administration. MAPSE was measured in M-mode in the apical four-chamber view. The %MAPSE was calculated as the MAPSE measured in the acute phase divided by that measured in the convalescent phase. We compared the acute and the convalescent phases of KD. The values of the MAPSE were significantly reduced (45 out of 50 patients) during the acute phase and immediately recovered in the convalescent phase (10.0 ± 1.9 vs. 12.7 ± 1.9 mm, P < 0.0001). Of the parameters tested, %MAPSE was the only echocardiographic parameter that was associated with Log-BNP. Additionally, %MAPSE had a significant negative correlation with Log-BNP (r = -0.45, P < 0.0039). Longitudinal LV contraction is impaired in the acute phase of KD, but it immediately recovers in the convalescent phase. Measuring the longitudinal LV contractility should be essential for evaluating LV function in the acute phase of KD, and MAPSE is useful for this evaluation.

Topics: Acute Disease; Child; Child, Preschool; Echocardiography; Female; Humans; Infant; Infant, Newborn; Male; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Systole; Ventricular Dysfunction, Left; Ventricular Function, Left

Kawasaki disease (KD) is the primary cause of heart disease among children, but because its clinical symptoms are nonspecific, it is difficult to diagnose. The purpose of this study was to evaluate laboratory indices for possible use in the early diagnosis of KD and to determine which indices are predictive of a response to intravenous immunoglobulin (IVIG) and can be used to monitor the effects of treatment.. Three hundred thirty KD patients, 330 age-matched children with KD-like febrile disease, and 330 age-matched healthy children (controls) were enrolled in this prospective study. Levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and cytokines were determined in all study subjects.. In the derivation cohort, 181 patients in the KD group were compared with 181 patients in the KD-like febrile group. The following indices were found to be useful in the diagnosis of KD: NT-proBNP (area under the curve [AUC] 0.923), ESR (AUC 0.909), CRP (AUC 0.834), and interleukin-6 (IL-6; AUC 0.678). The diagnostic efficiency of each index demonstrated in the derivation cohort was repeated in the 149 KD patients in the validation cohort. There were significant differences in NT-proBNP levels between IVIG-responsive KD patients (n = 270) and IVIG-nonresponsive KD patients (n = 60), with higher NT-proBNP levels in IVIG-nonresponsive KD patients. The NT-proBNP level can effectively distinguish IVIG-responsive KD patients from IVIG-nonresponsive patients, and its AUC was 0.73. There were also significant differences in the NT-proBNP levels before and after treatment, with a significant decline after treatment.. Serum levels of NT-proBNP can be used in the diagnosis of KD, the prediction of a patient's sensitivity to IVIG treatment, and the monitoring of the effects of IVIG treatment, but more attention must be paid to the scope of its application.

Topics: Adolescent; Biomarkers; Blood Sedimentation; C-Reactive Protein; Case-Control Studies; Child; Child, Preschool; Cytokines; Diagnostic Tests, Routine; Female; Humans; Immunoglobulins, Intravenous; Infant; Infant, Newborn; Male; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Reproducibility of Results; Sensitivity and Specificity

To explore the correlation of heart rate variability (HRV) indices with cardiac troponin I (cTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in children with Kawasaki disease (KD) and their prognostic value.. A total of 130 children with KD were assigned into coronary artery lesion (CAL) group (n=47) and non-coronary artery lesion (NCAL) group (n=83). Meanwhile, 110 healthy children and 29 children in the recovery stage of non-cardiovascular diseases were selected as control and non-KD groups, respectively. Patients in the four groups received 24-hour HRV monitoring. Levels of serum cTnI and NT-proBNP were measured in the KD and the non-KD group.. Compared with the controls of the same sex and age, the KD patients had significantly reduced standard deviation of all normal sinus RR intervals (SDNN), mean of SDNN (SDNN index), percentage of successive normal sinus RR intervals>50 ms (pNN50), very low frequency (VLF), low frequency (LF), and high frequency (HF) but a significantly increased LF/HF ratio (P<0.05). The HRV indices including SDNN, standard deviation of all mean 5-minute RR intervals (SDANN), SDNN index, root mean squared successive difference, pNN50, VLF, LF, and HF in the CAL group all significantly decreased compared with those in the control and non-KD groups, while the LF/HF ratio was higher in the CAL group than in the control group (P<0.05). The serum levels of cTnI and NT-proBNP in the CAL and NCAL groups were significantly higher than those in the non-KD group (P<0.05). In children with KD, serum cTnI level was negatively correlated with SDNN and HF but positively correlated with the LF/HF ratio (P<0.05); serum NT-proBNP level was negatively correlated with SDNN, SDANN, and HF (P<0.05).. HRV indices have certain clinical significance in assessing CAL of children with KD.

Topics: Child; Child, Preschool; Coronary Vessels; Female; Heart Rate; Humans; Infant; Male; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments; Troponin I

Topics: Biomarkers; Communicable Diseases; Female; Humans; Interleukin-17; Male; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments

To explore the diagnostic value of blood N-terminal pro-brain natriuretic peptide (NT-proBNP) and interleukin-17(IL-17) for incomplete Kawasaki disease.. Patients with Kawasaki disease, Incomplete Kawasaki disease and unclear infectious fever were included in this retrospective study. Their clinical features, and laboratory test results of blood NT-proBNP and IL-17 were collected and compared.. 766 patients with complete clinical information were recruited, consisting of 291 cases of Kawasaki disease, 74 cases of incomplete Kawasaki disease, and 401 cases of unclear infectious diseases. When the consistency with indicator 2 and 3 in Kawasaki disease diagnosis criteria was assessed with blood IL-17 ?11.55 pg/mL and blood NT-proBNP ? 225.5 pg/dL as the criteria, the sensitivity and specificity for distinguishing incomplete Kawasaki disease and infectious diseases reached 86.5% and 94.8%, respectively. When we chose the consistency with indicator 1 and 2 in Kawasaki disease diagnosis criteria, the appearance of decrustation and/or the BCG erythema, blood IL-17 ?11.55 pg/mL and blood NT-Pro BNP ?225.5 pg/dL as the criteria, the sensitivity and specificity for distinguishing incomplete Kawasaki disease and infectious diseases was 43.2% and 100%, respectively.. Blood NT-proBNP and IL-17 are useful laboratory indicators for distinguishing incomplete Kawasaki disease and infectious diseases at the early stage.

Topics: Biomarkers; Child, Preschool; Communicable Diseases; Female; Humans; Infant; Interleukin-17; Male; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments; Retrospective Studies; ROC Curve; Sensitivity and Specificity

To detect plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) in acute Kawasaki disease (KD) and analyze the relationship between NT-proBNP and other bio-markers in order to evaluate if NT-proBNP could be as a useful diagnostic marker to predict the risk of coronary arterial lesions in acute KD.. Totally 106 patients with KD were recruited from January 2012 to April 2014 at Department of Pediatrics of Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology,64 were boys and 42 were girls, their age ranged from 2 months to 8 years and 4 months. Of the 106 cases, 48 had typical KD(TKD) and 58 incomplete KD(IKD). They were divided into two groups according to echocardiography results: coronary arterial lesions (KD-CAL, n = 33) and non coronary arterial lesions (KD-nCAL, n = 73). Forty children whose age and gender matched with respiratory tract infection were selected as control group, 22 were boys and 18 were girls, age range from 7 months to 7 years and 11 months. Plasma NT-proBNP levels were measured by using the enzyme-linked fluorescence analysis (ELFA) at the day of admission, meanwhile blood routine tests, liver function tests, determination of C-reactive protein (CEP), erythrocyte sedimentation rate (ESR), electrolytes were performed in these patients. Pearson's correlation analysis was used to evaluate the association. The ROC curve analysis was done to identify the threshold of coronary 'arterial lesions.. The levels of NT-proBNP were (1 037 271) ng/L in TKD group and (1,325 ± 264) ng/L in IKD group. The levels of NT-proBNP in control group was (125 ± 22) ng/L. Both the levels of NT-proBNP in TKD and IKD group were significantly higher than that of control group (t = 3.360, 3.590; P < 0.05). The level of NT-proBNP in KD-CAL group was (2,775 ± 842) ng/L and that of KD-nCAL group was (830 ± 145) ng/L, NT-proBNP levels of KD-nCAL group was significantly higher than that of control group (t = 3.660, P = 0.007) ; moreover the level of NT-proBNP of KD-CAL group was also significantly higher than that of KD-nCAL group ( t = 3.860, P = 0.005). The levels of total white blood cell count, neutrophil percentage, platelet count, CRP and ESR of KD-CAL group were significantly higher than those of the control group, however there was no significant difference between KD-CAL group and KD-nCAL group. The levels of albumin and Na of KD-nCAL group were significantly lower than those of the control group. Plasma NT-proBNP level in KD group was positively correlated with white blood cell count, neutrophil percentage, and CRP (r = 0.239, P = 0.025; r = 0.359, P = 0.001; r = 0.474, P = 0.001), there was a negative correlation between albumin and Na (r = -0.303, P = 0.015; r = -0.338, P = 0.002). When the level of NT-proBNP was higher than 950 ng/L, the sensitivity for diagnosis of coronary arterial lesions in the KD was 88.1% and the specificity was 89.0%.. The plasma NT-proBNP can be used as a useful parameter in early diagnosis of KD. Plasma NT-proBNP could be used to predict the risk of coronary arterial lesions in KD.

Topics: Biomarkers; Blood Sedimentation; C-Reactive Protein; Case-Control Studies; Child; Child, Preschool; Coronary Vessels; Female; Humans; Infant; Male; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; ROC Curve; Sensitivity and Specificity

Serum N-terminal pro-brain natriuretic peptide (NTproBNP) is often elevated in patients with acute Kawasaki disease (KD), but the NTproBNP level in normal children is higher than in adults. Thus, characterization of the normal levels and cut-off values of NTproBNP according to age is warranted for proper diagnosis of acute KD in children.. Six hundred and fifty-five patients aged 1 month-15 years (median, 2.9 years) were included. Patients were admitted to the NTT East Japan Sapporo Hospital between October 2007 and October 2011. Serum NTproBNP level was examined in 149 patients with KD (median, 2.1 years) and 506 control patients with acute infectious disease (median, 3.2 years). In the control group, a Z-score curve of NTproBNP was generated for each age group using least mean square-based methods. The Z-score distribution of KD patients was then compared with that of the control group. The specificity and sensitivity of NTproBNP for diagnosing acute KD were 97.8% and 47.0%, respectively, at Z-score >2.0. Additionally, simple cut-offs every 100 pg/ml according to age were established for more convenient use at the bedside.. The Z-score curve for NTproBNP in children was characterized. A Z-score >2.0 or the cut-off for children may be used to diagnose acute KD.

Topics: Acute Disease; Adolescent; Adult; Age Factors; Child; Child, Preschool; Female; Humans; Infant; Male; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments; Retrospective Studies

Intravenous immunoglobulin (IVIG) administered in the acute stage of Kawasaki disease (KD) is the standard therapy. Few reports describe nonresponders to initial treatment with IVIG in KD, which remains the most consistent risk factor for coronary artery lesions (CALs). This study aimed to investigate whether the serum level of N-terminal pro-brain natriuretic peptide (NT-proBNP) can be a predictive indicator for identifying patients with KD at higher risk of IVIG treatment failure. In this study, 135 patients with a diagnosis of KD admitted for IVIG treatment were retrospectively enrolled for analysis. Of these 135 patients, 22 were nonresponders who received additional rescue therapy because they had an elevated body temperature 36 h after completion of initial IVIG treatment. The NT-proBNP concentration was significantly higher in the nonresponder group (2,465.36 ± 3,293.24 pg/mL) than in the responder group (942.38 ± 1,293.48 pg/mL) (p < 0.05). The optimal sensitivity and specificity cutoff point for predicted nonresponders was 1,093.00 pg/mL or higher. The sensitivity and specificity for prediction of IVIG response were respectively 70.0 and 76.5 %. The findings show that NT-proBNP is a helpful marker in determining patients at risk for not responding to initial IVIG treatment. The authors suggest that patients with an NT-proBNP level of 1,093.00 pg/dL or higher are likely to fail initial IVIG and may require further rescue therapy.

Topics: Biomarkers; Child, Preschool; Female; Follow-Up Studies; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Male; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Retrospective Studies; Risk Factors; Treatment Failure

Endomycocardial biopsies have demonstrated that subclinical myocarditis is a universal feature of acute Kawasaki disease (KD).. We investigated biochemical evidence of myocardial strain, oxidative stress, and cardiomyocyte injury in 55 acute KD subjects (30 with paired convalescent samples), 54 febrile control (FC), and 50 healthy control (HC) children by measuring concentrations of cardiovascular biomarkers.. Levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and soluble ST2 (sST2) were elevated in acute vs. convalescent KD, FC, and HC (p≤0.002), while γ-glutamyl transferase and alanine amino transferase as measures of oxidative stress were increased in acute vs. FC (p≤0.0002). Cardiac troponin I (cTnI) levels, using a highly sensitive assay, were elevated in 30% and 40% of paired acute and convalescent KD subjects, respectively, and normalized within two years of disease onset. NT-proBNP and sST2 negatively correlated with deceleration time, but only NT-proBNP correlated with MV E:A ratio and internal diameter of the coronary arteries (RCA/LAD Zworst).. NT-proBNP and sST2 were elevated in acute KD subjects and correlated with impaired myocardial relaxation. These findings, combined with elevated levels of cTnI, suggest that both cardiomyocyte stress and cell death are associated with myocardial inflammation in acute KD.

Topics: Acute Disease; Adolescent; Biomarkers; Child; Child, Preschool; Female; Humans; Infant; Male; Mucocutaneous Lymph Node Syndrome; Myocarditis; Natriuretic Peptide, Brain; Peptide Fragments; Troponin I

Kawasaki disease (KD), an acute febrile vasculitis, is the most common cause of acquired heart disease in infants and young children. However, the diagnosis of infantile KD can be difficult or delayed due to vague clinical manifestations. This current study aimed to assess the clinical characteristics and cardiac complications of infantile KD. The study retrospectively reviewed the data of 242 patients with KD. The clinical, laboratory, and echocardiographic data between infants and older children were analyzed. The patients were divided into two groups: infants 12 months old or younger and children older than 12 months. The rate of incomplete KD was much more frequent in infants. During all phases, prohormone brain natriuretic peptide (Pro-BNP) levels were higher in infants, as was thrombocytosis. The coronary artery z-score was higher in infants at all phases of KD. On tissue Doppler imaging, the E/E' ratio (ratio of transmitral Doppler early filling velocity to tissue Doppler early diastolic mitral annular velocity) was higher at the septal and lateral annulus in infants. Infant patients with KD are at increased risk for the development of coronary abnormalities and diastolic dysfunction. Higher levels of Pro-BNP and thrombocytosis with diastolic echo parameters of a higher E/E' ratio can help to identify incomplete KD in infants.

Topics: C-Reactive Protein; Child, Preschool; Coronary Angiography; Echocardiography, Doppler; Female; Follow-Up Studies; Heart Diseases; Heart Ventricles; Humans; Incidence; Infant; Male; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Protein Precursors; Republic of Korea; Retrospective Studies; Risk Factors; Ventricular Function, Left

This study was undertaken to identify factors correlating with plasma levels of B-type natriuretic peptide (BNP) and its N-terminal portion (NTpro BNP) in the acute phase of Kawasaki disease (KD).. This study included 91 patients with KD treated at a hospital affiliated to Hamamatsu University School of Medicine between October 2003 and June 2011. We quantified BNP and NT-pro BNP in the acute phase. The BNP level was expressed as the NT-pro BNP level using the formula NT-pro BNP=9.080×BNP(0.923). We sought relationships between NT-pro BNP values and different clinical and laboratory data in the acute phase of KD.. Of the 91 patients, 14 failed to respond to the initial intravenous immunoglobulins therapy. NTpro BNP levels were significantly higher in these nonresponders than in the responders (1689.3±1168.8 pg/ dL vs. 844.4±1276.3 pg/dL, P<0.001). Seventeen patients developed coronary artery lesions, but this was not associated with NT-proBNP levels. NT-pro BNP was positively correlated with CRP (r=0.421, P<0.001) and negatively correlated with the hematocrit (r=-0.206, P=0.050), Na value (r=-0.214, P=0.041) and albumin level (r=-0.345, P<0.001). Stepwise multiple linear regression analysis with NT-pro BNP as a dependent variable revealed significant correlations with CRP and albumin (beta=0.345, P=0.001; beta=-0.225, P=0.027).. A high level of NT-pro BNP in acute phase KD is associated with systemic inflammatory responses and increased vascular permeability. The NT-pro BNP level is a useful marker to identify potential non-responders to IVIG among KD patients.

Topics: Acute Disease; Child; Child, Preschool; Female; Humans; Infant; Male; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments

The aim of the present study was to investigate the diagnostic value of the N-terminal B-type natriuretic peptide (NT-proBNP) in acute Kawasaki disease (KD) given that the clinical criteria and the current basic laboratory tests lack the necessary specificity for accurate diagnosis.. Basic biological tests and serum NT-proBNP levels obtained from acute KD patients were compared to that of febrile controls. NT-proBNP was considered abnormal based on the following definitions: above a cut-off determined on receiver operator characteristic (ROC) analysis, above the upper limit for age, or above 2 SD calculated from healthy children. Analyses were also performed for KD cases with complete or incomplete criteria combined and separately.. There were 81 patients and 49 controls aged 3.60 ± 2.77 versus 4.25 ± 3.88 years (P= 0.69). ROC analysis yielded significant area under the curve for NT-proBNP. The sensitivity, specificity, positive and negative predictive values were 70.4-88.9%, 69.4-91.8%, 82.8-93.4%, and 65.2-79.1%. The odds ratios based on NT-proBNP definitions varied between 18.13 (95% confidence interval [CI]: 7.21-45.57), 20.82 (95%CI: 8.18-53.0), and 26.71 (95%CI: 8.64-82.57; P < 0.001). Results were reproducible for cases with complete or incomplete criteria separately.. NT-proBNP is a reliable marker for the diagnosis of KD. Prospective clinical studies with emphasis on NT-proBNP in a diagnostic algorithm are needed.

Topics: Biomarkers; Child; Child, Preschool; Female; Humans; Infant; Male; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prospective Studies; ROC Curve; Sensitivity and Specificity

The pathogenesis of hyponatremia in acute Kawasaki disease (KD) remains unclear. A recent case report of KD complicated by syndrome of inappropriate anti-diuretic hormone (SIADH) led us to determine the prevalence of SIADH in acute KD patients.. Subjects were 39 Japanese KD patients (2-84 months of age, 25 males and 14 females) treated with intravenous immunoglobulin (IVIG), 2 g/kg/day and oral aspirin. SIADH was defined when hyponatremic patients (serum sodium concentration <135 mEq/L) had decreased serum osmolality <280 mOsm/kg H(2) O, elevated urine sodium concentration >20 mEq/L and elevated urine osmolality >100 mOsm/kg H(2) O without dysfunctions of renal, thyroid or adrenal gland. We also studied the relation between clinical course of SIADH and the amount of infused fluid during IVIG.. Before IVIG, 27 patients (69%) had hyponatremia and 11 (28% of total; 41% of hyponatremic patients) had SIADH while after IVIG, 13 (33%) hyponatremia and four (10%; 31% of hyponatremic patients) SIADH. Among 11 patients with SIADH before IVIG, SIADH improved in 10 after IVIG, but hyponatremia persisted in five. Significant correlation was observed between serum sodium concentration after IVIG and infusion amount in SIADH patients (r=-0.64, P= 0.03), but not in non-SIADH patients.. This is the first report to show that SIADH is common as a cause of hyponatremia in acute KD and hence careful management of water and sodium is warranted.

Topics: Blood Urea Nitrogen; Child, Preschool; Female; Humans; Hyponatremia; Inappropriate ADH Syndrome; Infant; Japan; Male; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Prevalence; Retrospective Studies; Sodium

Kawasaki disease, a systemic vasculitis of unknown etiology, develops frequently in infants and demonstrates a variety of clinical symptoms during the disease course. The most important complication, coronary artery lesions, is found in 15-25% of untreated patients. Meanwhile, acute myocarditis, another complication that can occur during the acute phase of severe systemic vasculitis, has been found in more than 50% of affected individuals when asymptomatic cases are included. However, cases that require treatment are rare as reported by Yoshikawa et al. (Circ J 70:202-205, 2006). As for neural complications, aseptic meningitis is well known, but it is extremely rare for these patients to develop encephalitis or encephalopathy as reported by Imai et al. (Jpn Soc Emerg Pediatr 8:50-55, 2009). Recently reported magnetic resonance images (MRIs) have shown reversible lesions in the median splenium of patients complicated with encephalitis or encephalopathy. Reversible lesions have also been observed after the administration of an antiepileptic agent, drastic weight loss, and development of metabolic abnormalities as reported by Massimo et al. (Neuroradiology 49:541-544, 2007) and Tada et al. (Neurology 63:1854-1858, 2004). Aggressive therapy for such lesions is not considered necessary because most disappear without neurologic aftereffects. However, the clinical significance and pathogenesis of the condition remain largely unknown. We present the first known report of a Kawasaki disease case complicated with acute myocarditis and mild encephalitis/encephalopathy with a reversible splenial lesion (MERS). These findings may be valuable for the diagnosis and treatment of affected patients.

Topics: Acute Disease; Adolescent; C-Reactive Protein; Coronary Aneurysm; Corpus Callosum; Diffusion Magnetic Resonance Imaging; Echocardiography; Encephalitis; Female; Follow-Up Studies; gamma-Globulins; Humans; Mucocutaneous Lymph Node Syndrome; Myocarditis; Natriuretic Peptide, Brain; Peptide Fragments; Tomography, X-Ray Computed

The aim of this study was to identify possible factors associated with type-B natriuretic peptide (BNP) production in the acute phase of Kawasaki disease (KD).. Subjects were 54 patients with KD (KD group [KDG]) and 18 age-matched controls (control group [CG]). We evaluated left ventricular function using multi-modal echocardiography and determined blood chemistry including BNP, white blood cell count, C-reactive protein (CRP), and interleukin (IL)-6 in the KDG. We compared echocardiographic parameters between the KDG and the CG and determined the correlation between log (BNP) and echocardiographic parameters, white blood cell count, CRP, and IL-6 in the KDG.. The KDG showed high BNP (169.6 ± 529.6 pg/ml) despite preserved left ventricular function indicated by no significant difference in left ventricular ejection fraction (72.2 ± 9.2 vs 71.2 ± 7.8 %), z-score of left ventricular diastolic dimension (0.8 ± 1.3 vs 0.9 ± 0.8 SD), and Tei index (0.29 ± 0.09 vs 0.30 ± 0.06) between the KDG and the CG. However, left ventricular ejection fraction (r =-0.44, P= .001) and left ventricular end-diastolic dimension (r = 0.30, P < .05) significantly correlated with log (BNP). On the other hand, the KDG showed high CRP (89.7 ± 55.6 mg/l) and high IL-6 (242.2 ± 243.5 pg/ml), and CRP (r = 0.60, P < 0.0001) and IL-6 (r = 0.78, P < 0.0001) significantly correlated with log (BNP). Multiple stepwise regression analysis identified IL-6 (r = 0.77, P < 0.0001) most significantly correlated with log (BNP).. In acute KD, BNP significantly increases, despite well-preserved global left ventricular function, and inflammation might be associated with this increased BNP.

Topics: Acute Disease; Child, Preschool; Echocardiography; Female; Humans; Interleukin-6; Male; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Stroke Volume; Ventricular Function, Left

Kawasaki disease (KD) is an acute systemic vasculitis associated with the development of coronary arterial lesions (CALs) occurring in 3-5% of children treated by intravenous immune globulin (IVIG). However, a considerable number of patients who are not responding to IVIG are at much higher risk. Although studies have explored potential biomarkers to predict patients with KD who are at risk of CAL, no useful single marker exists. We hypothesized that the serum concentrations of the N-terminal moiety of brain natriuretic peptide (NT-proBNP) can be useful to predict CAL. Forty-three children with KD (29 males and 14 females) were enrolled in this study. Despite IVIG, 6 of the 43 patients developed CAL. There were, however, no significant differences in variables between children with CAL and those without CAL: These include age, gender, day of the illness, leukocyte count, and the serum levels of sodium, C-reactive protein, and albumin. The serum NT-proBNP level was significantly higher in children with CAL than those without CAL (2,611 ± 1,699 vs. 1,073 ± 1,427 pg/ml; P = 0.03): the cutoff value of 1,000 pg/ml to predict CAL produced a specificity of 0.68, sensitivity of 0.83, and an odds ratio as high as 10.4. In conclusion, NT-proBNP is increased in KD patients who are developing CAL, and patients with an elevated serum NT-proBNP >1,000 pg/ml have a risk of CAL ~10 times higher than that of patients with a modest increase.

Topics: Biomarkers; Child; Child, Preschool; Coronary Artery Disease; Female; Humans; Infant; Male; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments; Risk Assessment; ROC Curve

The diagnosis of Kawasaki disease (KD) is based on clinical data and non-pathognomonic symptoms. As no specific diagnostic test for KD exists, BNP or NT-pro-BNP might be of importance in identifying KD. We compared serum hs-CRP and NT-pro-BNP level in the acute phase of 59 KD patients and evaluated the diagnostic performance of these laboratory markers in KD to estimate the cut-off level for differentiating KD from other febrile illnesses as age-matched controls.. The study groups consisted of 59 KD patients in the disease group and 45 other patients with febrile illnesses as age-matched controls. NT-pro-BNP was measured using Elecsys proBNP (Roche Diagnostics, Mannheim, Germany), and hs-CRP was tested with CardioPhase hs-CRP (Siemens Healthcare Diagnostics, Marburg, Germany).. NT-pro-BNP levels were significantly higher in the KD patients than in the controls (P < 0.001). In the ROC curve analysis, the sensitivity was 66.10%, and the specificity was 77.08% at 235.2 pg/mL. hs-CRP levels tended to be higher in KD patients compared to controls.. This study indicates that NT-pro-BNP might be a more useful laboratory marker as an adjuvant diagnostic tool for KD than hs-CRP. Especially in a patient with incomplete clinical features of KD, the diagnosis and the start of treatment were delayed to confirm a fever persisting for at least 5 days. Therefore, we expect that NT-pro- BNP would be especially useful for KD patients with these atypical clinical presentations.

Topics: Biomarkers; C-Reactive Protein; Child; Child, Preschool; Female; Humans; Infant; Male; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments; ROC Curve

To study serum levels of brain natriuretic peptide (BNP) in children with Kawasaki disease (KD) and the correlation between BNP levels and the heart function.. Forty-three children with KD and thirty healthy children were enrolled. Serum levels of BNP were measured using ELISA. KD children received an echocardiographic examination, including measurements of left ventricular ejection fraction (LVEF), left ventricular shorten fraction (LVSF), cardiac index (CI) and left ventricular inflow velocity through the mitral annulus.. Mean serum level of BNP at the acute stage in children with KD was significantly higher than that at the recovery stage as well as the control group (p<0.01). The LVEF, LVSF and CI levels at the acute stage were significantly lower than those at the recovery stage in children with KD (p<0.05). The linear regression analysis showed that the BNP level was negatively correlated with the levels of LVEF, LVSF and CI (r=-0.63, -0.52, -0.53, p<0.05).. The serum BNP levels increase significantly in KD children at the acute stage, and are negatively correlated with the levels of LVEF, LVSF and CI. Measurement of serum BNP level is useful for the early diagnosis of KD.

Topics: Child; Child, Preschool; Female; Heart; Humans; Infant; Male; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain

The clinical manifestations and risk factors for developing coronary artery abnormalities (CAA) in Kawasaki disease (KD) might differ depending on age.. From January 2001 to July 2007, 161 patients with an age younger than 1 year (younger group) and 60 patients with an age older than 5 years (older group) were diagnosed with KD at the Korea University Medical Center. Their medical records were reviewed retrospectively and the two groups were compared in terms of a number of variables commonly associated with the development of CAA, including clinical manifestations and laboratory findings.. While the overall incidence of KD-associated CAA in our hospital was 6.7%, CAA developed in 20 (12.4%) of the younger group and ten (16.7%) of the older group, respectively. The CAA (+) cases of the younger group had a longer duration of total fever (9.1 +/- 3.3 vs 6.3 +/- 1.9 days, p = 0.002) and showed fewer diagnostic symptoms (3.0 +/- 1.2 vs 4.3 +/- 1.1, p < 0.001) than the CAA (-) cases. The CAA (+) cases of the older group had a longer duration of total fever (14.1 +/- 10.4 vs 6.5 +/- 1.9 days, p = 0.045), especially with respect to post-intravenous gamma globulin (IVGG) fever (7.9 +/- 9.6 vs 1.1 +/- 0.8 days, p = 0.052), and had higher total white blood cell counts, erythrocyte sedimentation rates, C-reactive protein levels, total bilirubin levels, and Harada scores and lower serum albumin and sodium levels than the CAA (-) cases. Multivariable logistic regression analysis revealed that the factors that were associated significantly with the development of CAA were the number of total symptoms (OR = 0.494, 95% confidence interval (CI) = 0.281-0.871, p = 0.015) in the younger group and the duration of post-IVGG fever (OR = 1.958, 95% CI = 1.098-3.492, p = 0.023) and the Harada score (OR = 3.455, 95% CI = 1.012-11.796, p = 0.048) in the older group.. Incomplete clinical manifestations in the younger group and IVGG nonresponsiveness in the older group are associated with the development of KD-associated CAA. These age-specific characteristics could aid the customization of the diagnostic and therapeutic strategies of KD, thereby helping to improve the outcome of this disease.

Topics: Age Distribution; Age Factors; Algorithms; Biomarkers; Blood Sedimentation; C-Reactive Protein; Child, Preschool; Coronary Aneurysm; Coronary Disease; Diagnosis, Differential; Electrocardiography; Female; gamma-Globulins; Humans; Immunologic Factors; Incidence; Infant; Injections, Intravenous; Male; Mucocutaneous Lymph Node Syndrome; Natriuretic Agents; Natriuretic Peptide, Brain; Predictive Value of Tests; Republic of Korea; Retrospective Studies; Risk Factors; Severity of Illness Index; Treatment Failure; Treatment Outcome

Serum concentrations of brain natriuretic peptide and its amino-terminal cleavage pro-fragment, NT-proBNP, have never been reported in refractory Kawasaki disease. Changes in NT-proBNP levels after infliximab treatment in an infant with severe cardiovascular complications are reported here. The regular evaluation of this cardiac biomarker after infliximab treatment may have clinical relevance in patients with refractory Kawasaki disease and severe heart involvement.

Topics: Biomarkers; Disease Progression; Follow-Up Studies; Heart Failure; Humans; Infant; Male; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments; Protein Precursors

Topics: Acute Disease; Convalescence; Coronary Aneurysm; Echocardiography, Doppler; Female; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Infant; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Plasma Exchange

Topics: Adrenergic beta-Antagonists; Carbazoles; Carvedilol; Coronary Aneurysm; Coronary Angiography; Coronary Artery Bypass; Coronary Stenosis; Heart Failure; Humans; Infant; Male; Mucocutaneous Lymph Node Syndrome; Myocardial Infarction; Natriuretic Peptide, Brain; Propanolamines; Stroke Volume; Ventricular Pressure

The aims of this study were to evaluate myocardial mechanics using pulsed tissue Doppler imaging (TDI), and to determine the relationship between abnormal myocardial performance and plasma brain natriuretic peptide (BNP) levels and oxidative stress in acute Kawasaki disease (KD).. Consecutive TDI parameters, including peak systolic velocity (Sw) and early (Ew) and late diastolic excursion of the mitral annuli were obtained in 42 patients with KD (mean age: 2.4+/-0.4 years) in weeks 1, 2, and 3, and during convalescence. Plasma BNP level and urinary 8-isoprostane were also examined during the acute phase. These data were then compared with TDI profiles from 62 healthy children, plasma BNP levels in 38 controls with other febrile illnesses, and urinary 8-isoprostane levels in 13 healthy children. Ew in week 1 was significantly lower than in controls, subsequently normalizing in the convalescent stage. Plasma BNP level in acute KD patients was significantly higher (65+/-9 pg/ml) than in controls (13+/-2 pg/ml). Urinary 8-isoprostane level in acute KD patients was significantly higher as compared with control (596 +/-37 vs 379+/-26 pg/ml Cr, p<0.05). There was a significant negative correlation between week 1 Sw and plasma BNP level (r=-0.55, p=0.0001). Change in Sw velocity in the BNP >/=51 group was significantly greater than in the BNP <51 group. There was a significant negative correlation between week 1 Sw and urinary 8-isoprostane level (r=-0.48, p=0.001).. Latent abnormal tissue Doppler profiles, possibly reflecting long-axis systolic and diastolic dysfunction have been noted in KD patients. Abnormal myocardial mechanics may contribute to the increased plasma BNP level and enhanced oxidative stress may contribute to cardiac dysfunction in KD.

Topics: Acute Disease; Blood Flow Velocity; Case-Control Studies; Child, Preschool; Dinoprost; Echocardiography, Doppler; Female; Heart Diseases; Humans; Infant; Male; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Oxidative Stress; Systole

The increase in B-natiuretic peptide (BNP) is well correlated with cardiovascular symptoms in adults. Its use in children is recent and only partially evaluated. The authors undertook a prospective study of BNP concentrations and its kinetics in 54 children with an average age of 15 months (5 days to 11 years) admitted as paediatric emergencies. The symptoms were dyspnoea (60%), shock (15%), suspicion of Kawasaki disease (15%) and other (10%). Twenty children had BNP levels of more than 100 pg/ml related to decompensation of known congenital heart disease in 7 patients (average BNP 462 +/- 323 pg/ml), due to neonatal coarctation in 2 patients (BNP > 3000 pg/ml), due to cardiomyopathy in 6 patients (BNP= 2576 +/- 1215 pg/ml), due to an arrhythmia in 1 patient (BNP= 3754 pg/ml) and to Kawasaki disease in 4 patients (BNP= 521 +/- 448 pg/ml). Thirty-four children had BNP values of less than 100 pg/ml; 29 had no cardiac disease and 5 had known congenital heart disease with other symptoms. Measuring BNP is quick and economical and is a valuable aid in the diagnosis of cardiac dysfunction in symptomatic children in the emergency room. High BNP values seem to be correlated with the severity of the cardiac disease. Low BNP values seem to have a good negative predictive value in children without underlying cardiac disease. The interpretation of intermediary values, especially when there is previous cardiac disease, is more difficult in view of the absence of known threshold values for different haemodynamic situations. Further studies are required to determine the value of this test for the follow-up and setting up of prognostic values in children with congenital heart disease.

Topics: Aortic Coarctation; Arrhythmias, Cardiac; Biomarkers; Cardiac Output, Low; Cardiomyopathies; Child; Child, Preschool; Dyspnea; Emergency Service, Hospital; Heart Defects, Congenital; Humans; Infant; Infant, Newborn; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Predictive Value of Tests; Prospective Studies; Shock

Topics: Atrial Natriuretic Factor; Biomarkers; Child; Heart Failure; Humans; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments; Reference Values; Severity of Illness Index

Brain natriuretic peptide (BNP) is a cardiac hormone and its plasma level increases in congestive heart failure and myocarditis. An increased level of serum BNP has been reported in children in the acute stage of Kawasaki disease (KD). But the mechanism of increased level of BNP in children with KD has not been elucidated and the change in BNP in children with KD in China has not been reported. The aim of this study was to investigate the change in plasma N-terminal pro-brain natriuretic peptide (NT-pro BNP) in children with KD, examine the value of NT-pro BNP in the diagnosis of KD and explore the mechanism of the change in plasma NT-pro BNP in children with KD.. Thirteen patients, aged from 4 months to 56 months, with KD were enrolled and nine patients with acute upper respiratory infection were used as controls. Blood sample was obtained to measure plasma NT-pro BNP concentrations in the acute (n = 13) and convalescent (n = 8) phases of KD and in the acute phase of the control patients. Plasma NT-pro BNP was measured using enzyme immunoassay. Other laboratory data including complete blood cell count, C-reactive protein, etc, were also measured in acute phase in both groups. The serum cardiac troponin I was also detected in acute phase of children with KD. All patients with KD had complete echocardiographic study, including measurement of left ventricular end diastolic diameter (LVDd), left ventricular ejection fraction (LVEF) and left ventricular inflow velocity through the mitral annulus (including E-velocity and A-velocity). Two dimensional echocardiography was performed to check for coronary lesions of patients with KD. The correlation between plasma NT-pro BNP and the above parameters was analyzed.. The mean plasma NT-pro BNP concentration in patients with KD in the acute phase was (691 +/- 86) ng/L, and it was (47 +/- 10) ng/L in patients of control group. The plasma NT-pro BNP in patients with KD in the acute phase was significantly higher than that of the control group (P < 0.001). In 8 cases of KD, the plasma NT-pro BNP concentrations were measured both in the acute and convalescent phase. The mean plasma NT-pro BNP concentration in the acute phase of KD was (636 +/- 89) ng/L and it was (164 +/- 35) ng/L in the convalescent phase. The level of plasma NT-pro BNP decreased significantly in the convalescent phase (P < 0.01). Through linear regression analysis, there was no significant correlation between the plasma concentrations of NT-pro BNP in acute phase of KD and LVEF, LVDd and E/A ratio, respectively. But the NT-pro BNP level correlated positively with C-reactive protein and white blood cells counts (r = 0.615, P < 0.05 and r = 0.547, P < 0.05), respectively. NT-pro BNP level correlated positively with serum cTnI, a sensitive biologic marker of cardiac injury (r = 0.611, P < 0.05).. The plasma NT-pro BNP concentration increased in the acute phase and decreased significantly in the convalescent phase of KD. The plasma NT-pro BNP might be one of the useful biological markers of KD, and the mechanism of change in plasma NT-pro BNP in KD might be associated with cardiac injury and inflammatory factors.

Topics: Biomarkers; Case-Control Studies; Child, Preschool; Echocardiography; Humans; Infant; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments

So as to determine the value of brain natriuretic peptide in the plasma as a biochemical marker for myocarditis of Kawasaki disease, we studied 69 patients. The blood samples, electrocardiograms and cross-sectional echocardiograms were obtained before the commencement of treatment and in the convalescent phase.. The mean concentration of brain natriuretic peptide in the plasma was 73.2 +/- 107.7 (mean +/- SD) pg/ml in the acute phase, and 7.9 +/- 7.5 pg/ml in the convalescent phase. We checked the electrocardiograms to find abnormal Q waves, elevation or depression of the ST segments, change in the pattern of the QRS complexes, and flattening or inversion of the T wave, all believed to be markers of myocarditis in Kawasaki disease. Those in whom the concentrations were greater than 50 pg/ml in the acute phase showed abnormal electrocardiograms more frequently than did those in whom the values were less than 50 pg/ml (21/29 vs 3/40, p < 0.0001 odds ratio 32.4). Amplitudes of the T wave in standard limb leads were measured both in the acute and convalescent phases, and the differences calculated. We regarded the sum total of these differences as representing "flattening T wave", and we named this variable as the total suppressed T wave voltage. We examined the correlation between the variable and the levels of brain natriuretic peptide in the plasma during the acute phase, demonstrating a significant correlation (r = 0.500, p < 0.0001). We conclude, therefore, that the concentration of brain natriuretic peptide measured in the plasma can be a useful biochemical marker for the myocarditis of Kawasaki disease. When the titer is over 50 pg/ml, the patient probably has an abnormal electrocardiogram and is most likely to have myocarditis.

Topics: Biomarkers; Chi-Square Distribution; Child; Child, Preschool; Cohort Studies; Echocardiography; Electrocardiography; Female; Humans; Infant; Male; Mucocutaneous Lymph Node Syndrome; Myocarditis; Natriuretic Peptide, Brain; Probability; Prognosis; Retrospective Studies; Sensitivity and Specificity; Severity of Illness Index

Brain natriuretic peptide (BNP) is a cardiac hormone and plasma levels of it increase in patients with congestive heart failure and in those with acute myocardial infarction. Kawasaki disease (KD) is a well-known generalized vasculitis and the most prominent features of this disease are the cardiovascular manifestations, which involve the pericardium, myocardium, endocardium and coronary arteries. It was hypothesized that the plasma concentrations of BNP in patients with KD might be increased and that plasma BNP might be a useful biological marker of cardiovascular manifestations in patients with KD.. Blood was obtained to measure and compare plasma BNP concentrations in the acute (n = 32) and convalescent (n = 35) phases of KD and in the acute phase of the patients with viral infection (n = 26), which included adenovirus, influenza, measles and herpes group virus infection. In patients with KD, two-dimensional echocardiography was performed to check for pericardial effusion and coronary arterial lesions and to measure the dimensions of the left ventricle at diastole and the shortening fraction of the left ventricle (LVSF).. The mean plasma BNP concentration in patients with KD in the acute phase was 55.0 +/- 39.5 pg/mL, but was 6.8 +/- 7.3 pg/mL in patients with viral infection. The plasma BNP concentration in patients with KD in the acute phase was significantly higher than in patients with viral infection (P < 0.0001). In 31 cases of KD, the plasma BNP concentrations were measured both in the acute and convalescent phases. The mean plasma BNP concentration in the acute phase of KD was 55.3 +/- 40.1 pg/mL and in the convalescent phase was 5.9 +/- 5.7 pg/mL. The level of plasma BNP decreased significantly in the convalescent phase (P < 0.0001). The mean BNP level in patients with KD with pericardial effusion (n = 8) in the acute phase was 80.3 +/- 43.4 pg/mL and that in patients without pericardial effusion (n = 24) was 46.5 +/- 35.1 pg/mL. The BNP level in patients with pericardial effusion was significantly higher than that of patients without pericardial effusion (P < 0.05). There was no significant correlation between the plasma concentrations of BNP in the acute phase of KD and LVSF (r = -0.161, P = 0.39, n = 31).. It was shown that the plasma BNP concentration increased in the acute phase of KD and decreased to within normal range in the convalescent phase. Further examinations are needed to clarify the mechanism by which the elevated levels of plasma BNP occur in the acute phase of KD. However, plasma BNP might be a useful biological marker of the cardiovascular manifestations in patients with KD.

Topics: Acute Disease; Biomarkers; Chi-Square Distribution; Child; Child, Preschool; Female; Humans; Infant; Male; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Time Factors; Virus Diseases