Development Of Coronary Artery Aneurysms Research Articles

Long-term cardiovascular inflammation and fibrosis in a murine model of vasculitis induced by Lactobacillus casei cell wall extract.

Kawasaki disease (KD), an acute febrile illness and systemic vasculitis, is the leading cause of acquired heart disease in children in industrialized countries. KD leads to the development of coronary artery aneurysms (CAA) in affected children, which may persist for months and even years after the acute phase of the disease. There is an unmet need to characterize the immune and pathological mechanisms of the long-term complications of KD. We examined cardiovascular complications in the Lactobacillus casei cell wall extract (LCWE) mouse model of KD-like vasculitis over 4 months. The long-term immune, pathological, and functional changes occurring in cardiovascular lesions were characterized by histological examination, flow cytometric analysis, immunofluorescent staining of cardiovascular tissues, and transthoracic echocardiogram. CAA and abdominal aorta dilations were detected up to 16 weeks following LCWE injection and initiation of acute vasculitis. We observed alterations in the composition of circulating immune cell profiles, such as increased monocyte frequencies in the acute phase of the disease and higher counts of neutrophils. We determined a positive correlation between circulating neutrophil and inflammatory monocyte counts and the severity of cardiovascular lesions early after LCWE injection. LCWE-induced KD-like vasculitis was associated with myocarditis and myocardial dysfunction, characterized by diminished ejection fraction and left ventricular remodeling, which worsened over time. We observed extensive fibrosis within the inflamed cardiac tissue early in the disease and myocardial fibrosis in later stages. Our findings indicate that increased circulating neutrophil counts in the acute phase are a reliable predictor of cardiovascular inflammation severity in LCWE-injected mice. Furthermore, long-term cardiac complications stemming from inflammatory cell infiltrations in the aortic root and coronary arteries, myocardial dysfunction, and myocardial fibrosis persist over long periods and are still detected up to 16 weeks after LCWE injection.

Susceptibility of TSPAN5 polymorphisms to Kawasaki disease and immunoglobulin therapy resistance in southern Chinese children

Kawasaki disease (KD) is a condition characterized by acute multi-system vasculitis and high fever in infants and children. Intravenous immunoglobulin (IVIG) is the established therapeutic approach of KD,foralleviating inflammation and mitigate the risk of arterial wall dilation and the development of coronary artery aneurysms (CAA). But almost 20% of the patients developed resistance to IVIG and displayed persistent fever after standard primary treatment. TSPAN5, belonging to the Tetraspanin family, has been demonstrated to modulate innate immunity in a range of human diseases. It accomplishes this by engaging with integrins and actively participating in the process of infection recognition. However, its relevance to susceptibility and IVIG therapy response of KD was unexposed. In the present study, our Integrative analysis of KD transcriptomic data and GTEx data revealed that the eQTL rs12504972 might modify the downregulation of TSPAN5 in KD patients. Moreover, our findings suggest a potential association between TSPAN5/rs12504972 and an elevated susceptibility as well as IVIG resistance among patients with Kawasaki disease in southern China. The results provided a new insight that TSPAN5 triggered KD susceptibility and resistance of IVIG therapy on the genomic level.

Sex-Specific Susceptibility Loci Associated With Coronary Artery Aneurysms in Patients With Kawasaki Disease.

Kawasaki disease (KD) is an acute vasculitis that primarily affects children under age 5 years. Approximately 20-25% of untreated children with KD and 3-5% of those treated with intravenous immunoglobulin therapy develop coronary artery aneurysms (CAAs). The prevalence of CAAs is much higher in male than in female patients with KD, but the underlying factors contributing to susceptibility to CAAs in patients with KD remain unclear. This study aimed to identify sex-specific susceptibility loci associated with CAAs in KD patients. A sex-stratified genome-wide association study (GWAS) was performed using previously obtained GWAS data from 296 KD patients and a new replication study in an independent set of 976 KD patients by comparing KD patients without CAA (controls) and KD patients with aneurysms (internal diameter ≥5 mm) (cases). Six male-specific susceptibility loci, PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ (odds ratios [ORs], 2.25-9.98; p=0.00204-1.96×10-6), and 2 female-specific susceptibility loci, SMAD3 (OR, 4.59; p=0.00016) and IL1RAPL1 (OR, 4.35; p=0.00026), were significantly associated with CAAs in patients with KD. In addition, the numbers of CAA risk alleles additively contributed to the development of CAAs in patients with KD. A sex-stratified GWAS identified 6 male-specific (PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ) and 2 female-specific (SMAD3 and IL1RAPL1) CAA susceptibility loci in patients with KD.

Elevation of IL-17 Cytokines Distinguishes Kawasaki Disease From Other Pediatric Inflammatory Disorders.

Kawasaki disease (KD) is a systemic vasculitis of young children that can lead to development of coronary artery aneurysms. We aimed to identify diagnostic markers to distinguish KD from other pediatric inflammatory diseases. We used the proximity extension assay to profile proinflammatory mediators in plasma samples from healthy pediatric controls (n=30), febrile controls (n=26), and patients with KD (n=23), multisystem inflammatory syndrome in children (MIS-C; n=25), macrophage activation syndrome (n=13), systemic and nonsystemic juvenile idiopathic arthritis (n=14 and n=10, respectively), and juvenile dermatomyositis (n=9). We validated the key findings using serum samples from additional patients with KD (n=37) and febrile controls (n=28). High-fidelity proteomic profiling revealed distinct patterns of cytokine and chemokine expression across pediatric inflammatory diseases. Although KD and MIS-C exhibited many similarities, KD differed from MIS-C and other febrile diseases in that most patients exhibited elevation in one or more members of the interleukin-17 (IL-17) cytokine family, IL-17A, IL-17C, and IL-17F. IL-17A was particularly sensitive and specific, discriminating KD from febrile controls with an area under the receiver operator characteristic curve of 0.95 (95% confidence interval 0.89-1.00) in the derivation set and 0.91 (0.85-0.98) in the validation set. Elevation of all three IL-17-family cytokines was observed in over 50% of KD patients, including 19 of 20 with coronary artery aneurysms, but was rare in all other comparator groups. Elevation of IL-17 family cytokines is a hallmark of KD and may help distinguish KD from its clinical mimics.

Study of the relationship between occurrence of Kawasaki disease and air pollution in Chengdu by parametric and semi-parametric models.

Kawasaki disease (KD) is a pediatric vasculitis of unknown etiology which is mainly associated with the development of coronary artery aneurysms. The etiology of KD seems to be multifactorial, but there is rare research on the association between KD and potential environmental risk factors. So, we would like to examine the correlation between KD and potential environmental risk factors in West China. We included KD patients in Chengdu from 2015 to 2021 and analyzed the correlation between air pollution indexes and climate condition indexes. The autocorrelation of the data was eliminated by first-order difference, the risk factors were screened by stepwise regression with AIC criterion, and the multiple regression model was established. Random forest and Winsorize were used to test the robustness of the screening results, and it was found that particulate matter with a diameter less than or equal to 2.5 μm (PM2.5) had a significant positive effect on the incidence of KD. In addition, several variables were positively correlated with KD incidence, but not statistically significant. The GAM model was used to explore the nonlinear correlation between PM2.5 and KD incidence. The results showed that PM2.5 concentration was positively correlated with KD incidence, and the effects varied among different concentration levels of PM2.5. Fisher's exact test was used to explore the influence of PM2.5 on the incidence of coronary tumors. It is found that PM2.5 may be a risk factor for it. This study suggested that exposure to high concentrations of PM2.5 may significantly increase the risk of KD. The evidence for the association between other environmental factors and KD incidence, as well as the association between PM2.5 and coronary tumors, was limited and needed further verification.

Predictive factors of medium-giant coronary artery aneurysms in Kawasaki disease

BackgroundWe aimed to examine predictive measures for medium and giant coronary artery aneurysms (CAA) in Kawasaki disease (KD) patients.MethodsPatients who were diagnosed with KD from 2015 to 2021 were retrospectively reviewed. The clinical and laboratory data were compared between medium-giant group and non-medium-giant group.ResultsA total of 1331 KD patients were investigated, of whom 63 patients (4.7%) developed medium-giant CAA including 27 patients (2%) with giant CAA. Sex, age, fever duration, intravenous immunoglobulin (IVIG) resistance, platelet count, and albumin level independently predicted medium or giant CAA by multivariate logistic regression analysis. Male, age, duration of fever, IVIG resistance, platelet count, hemoglobin, and erythrocyte sedimentation rate were independent predictors for giant CAA. The two new scoring systems using these factors in identifying patients with medium-giant CAA and giant CAA had respectively sensitivities of 86.89% and 92.59%, and specificities of 81.65% and 87.93%. Validation in 2021 dataset (193 KD patients) showed comparable sensitivity and specificity to development dataset.ConclusionsMale, age, fever duration, IVIG resistance, platelet count, albumin, hemoglobin, and erythrocyte sedimentation rate might be significant predictors of medium and giant CAA. The sensitivity and specificity in our risk prediction model were higher than in previous research.ImpactThis is the first study to search for risk factors and establish a prediction model for the development of medium-giant CAA in the Chinese population using z-scores and absolute inner diameter values based on large sample sizes.The sensitivity and specificity in our model were higher than in previous studies.Our research could help clinicians better predict medium-giant CAA and choose more appropriate treatment.

Retrospective analysis of children diagnosed with Kawasaki disease.

The aim of our study was to evaluate the long-term impacts of Kawasaki disease on our patients regarding coronary involvement demographic characteristics, treatment regimens, and clinical course. Our study included 104 patients diagnosed and hospitalized with Kawasaki disease in our center, from January 2004 to January 2019. In our study, patients were divided into three groups according to coronary artery involvement. Patients in group 1 had no echocardiographic findings, while the ones in group 2 had coronary artery dilatation and ones in group 3 had coronary artery aneurysm (CAA). Among 104 patients, the median age was 9.15 (3.0-22.0) years, and 61 of the patients were male while 43 of the patients were female. With a wide range of 1.50-16.50 years of follow-up time, the median diagnosis age of our patients was 31 months (3.0-164.0). Fever duration (median day 10 (5-21), p = 0.025) was statistically significantly higher in group 3. Blood C-reactive protein (CRP) levels, white blood cell (WBC) counts, and neutrophil counts were significantly higher in group 3. There was a statistically significant difference between patients in group 3 and group 2 in which the lowest strain deformation values were in the patients of group 3. In contrast to group 1, the time for initiation of IVIG therapy is significantly prolonged both in group 2 (median: 9.5 days, p = 0.028) and group 3 (median: 10 days, p = 0.036). In our study, serum CRP levels, WBC count, and neutrophil count were higher in patients with coronary artery abnormalities, in agreement with the previous studies. In the light of our results, we consider that the most important determining factor for the development of coronary artery aneurysm is the time of intravenous immunoglobulin (IVIG) administration.

Risk Factors for Coronary Artery Aneurysm in a Chinese Pediatric Population with Kawasaki Disease at Low Risk of Intravenous Immunoglobulin Resistance: A Retrospective Cohort Study

Introduction: Multiple scoring systems for predicting intravenous immunoglobulin (IVIG) resistance have been developed. Although low-scoring patients with Kawasaki disease (KD) have a favorable prognosis, many develop coronary artery aneurysms (CAAs). Herein, we determined the risk factors for CAA development among patients with KD with low risk of IVIG resistance. Methods: We compared 14 scoring systems for predicting IVIG resistance among patients with KD hospitalized from 2003 to 2022. Patients were risk stratified using an optimal scoring system. Association between baseline characteristics and CAA development was assessed within the low-risk group. Results: Overall, 664 pediatric patients with KD were included; 108 (16.3%) had IVIG resistance, and the Liping scoring system had the highest area under the curve (0.714). According to this system, 444 (66.9%) patients with KD were classified as having low risk of developing IVIG resistance (<5 points). CAA development was significantly associated with male sex (odds ratio [OR], 1.946; 95% CI: 1.015–3.730), age <6 months at fever onset (OR, 3.142; 95% CI: 1.028–9.608), and a baseline maximum Z score of ≥2.72 (OR, 3.451; 95% CI: 2.582–4.612). CAA incidence increased with the number of risk factors, and comparisons with a Kobayashi score of <5 points among patients with KD revealed similar results. Conclusions: Predicting the response to IVIG might help further reduce CAA development in patients with KD.

Complete and incomplete Kawasaki disease: Clinical differences and coronary artery outcome from a national prospective surveillance study in Switzerland.

The aim of this national prospective surveillance study was to compare the clinical presentation, laboratory findings, treatment, and coronary artery outcome in patients with incomplete and complete Kawasaki disease (KD). Between March 2013 and February 2019, children with a diagnosis of complete and incomplete KD were reported by the Swiss Paediatric Surveillance Unit and prospectively enrolled. Clinical data, laboratory values, treatment, and echocardiographic features were collected at diagnosis and 1 year of follow-up. Data were compared between children with complete or incomplete KD. A total of 351 questionnaires were registered from children with a diagnosis of KD. Of them, 219 (62.4%) children had complete KD, and 132 (37.6%) children had incomplete KD. Children with incomplete KD were younger and had a longer-lasting fever; however, there were no differences in the level of C-reactive protein. All but four children received intravenous immunoglobulin treatment, whereas 14% of children were treated with corticosteroids. Children with incomplete KD were more often treated with corticosteroids than children with incomplete KD (p = 0.01). At diagnosis, 39 (11.1%) patients had only coronary artery dilation and 57 (16.2%) had at least one coronary artery aneurysm. There were no differences in coronary artery involvement between the two groups. At follow-up, 273 of 294 (92.8%) patients had no coronary artery involvement, with no difference between the two groups (p = 0.609). The overall incidence of coronary artery aneurysms at diagnosis was 16.2%. At follow-up, most coronary artery aneurysms had regressed, and coronary artery aneurysms were present in only 5.8% of the patients. Coronary artery aneurysms were slightly more frequent in patients with incomplete KD at follow-up (p = 0.039) but not at diagnosis (p = 0.208). Although the clinical presentation in children with incomplete and complete KD differs, the absence of coronary artery involvement does not. The use of corticosteroids appears to be preventive against the development of coronary artery aneurysms in these patients. However, the results of this study suggest a lower rate of coronary artery aneurysm regression in patients with incomplete KD. Further studies on a larger scale are needed to assess the risk of non-regression of coronary artery aneurysms in this particular group of patients.

Cardiovascular Complications in Patients with Kawasaki Disease in a Tertiary Care Hospital in West Bengal, Eastern IndiaA Prospective Clinical Study

ABSTRACT Introduction: Kawasaki Disease (KD) is an acute self-limiting systemic vasculitis involving medium and small-sized arteries. It may soon replace rheumatic fever to become the most common cause of acquired heart disease in Indian children. Coronary Artery Aneurysm (CAA) which can develop in 15-25% of untreated children remains the most dreaded complication of KD. Predicting the risk of CAA and taking timely measures can help in reducing the fatality of the condition. Aim: To study the spectrum of cardiovascular complications in patients with KD and also to assess associated risk factors for developing CAA in the patients under study. Materials and Methods: This prospective clinical study was carried out in the Paediatric Medicine Ward, Burdwan Medical College and Hospital, West Bengal, Eastern India, from 1st January, 2020 to 31st May, 2021. Total 52 children diagnosed with KD, aged between one month to 12 years, were included and followed-up for six months. Data regarding demographic variables, duration of fever, Intravenous Immunoglobulin (IVIG) resistance, hepatomegaly, neutrophilia, thrombocytopenia, haematocrit, Erythrocyte Sedimentation Rate (ESR), C-Reactive Protein (CRP), hepatic transaminases (alanine transaminase, aspartate amino-transferase), hyponatremia, hypoalbuminemia, and N-terminal-brain natriuretic peptide (NT-proBNP) were collected. Univariate and multivariate regression analyses were done using these variables for assessment of risk factors. Results: In the present study, out of 52 children, 28 (53.85%) were males and 24 (46.15%) were females with mean age of 3.74±2.55 years. Cardiovascular complications were observed in 27 (51.92%) patients, of whom 19 (35.54%) had CAA. Duration of fever ≥10 days, IVIG resistance, thrombocytopenia, low hematocrit, Alanine Transaminase (ALT) ≥100 U/L, hypoalbuminemia, and raised NT-proBNP were proven to be significant risk factors for development of CAA on univariate analysis. Thrombocytopenia and raised NT-proBNP came across as significant on binary logistic regression analysis. Conclusion: In this study, one or more types of cardiovascular abnormalities were present in 51.92% cases. Seven risk factors were identified to be significant in development of CAA on univariate analysis and among them two were proven significant in binary logistic regression.

Risk factors and coronary artery outcomes of coronary artery aneurysms differing in size and emergence time in children with Kawasaki disease.

Coronary artery aneurysm (CAA) is a serious cardiac complication arising from Kawasaki disease (KD) and is becoming the leading cause of acquired heart disease in children. The aim of this study was to determine the potential risk factors associated with coronary artery aneurysms (CAAs), which differ in size and emergence time, and track its regression within 3 years of onset. The laboratory data, clinical features, and coronary artery outcomes of patients, who were diagnosed with KD and received treatment from January 2003 to January 2019 were retrospectively analyzed. A total of 484 pediatric patients with KD were examined during the study period. Among them, 130 (26.9%) presented with CAA, including mid- to large-sized CAA in 38 patients (7.9%) and de novo CAA after intravenous immunoglobulin (IVIG) treatment in 22 patients (4.5%). Albumin-to-globin (A/G) ratio was significantly negatively associated with the absolute internal diameter of coronary artery at 1 month of onset and may be used as a predictor of mid- to large-sized CAA development in patients with KD. The area under the receiver operating characteristic curve was 0.637 (95% confidence interval: 0.551–0.724), and a cutoff of 1.32 yielded a sensitivity and specificity of 79 and 49%, respectively, for predicting mid- to large-sized CAA development. De novo CAA after IVIG may lead to an increased risk of developing progressive CAA [13 (59.1%) of 22 vs. 31 (28.7%) of 108; P = 0.006] and had significantly greater changes in both the magnitude of CAA dimension variation and maximum z-score of the coronary arteries at 2 and 4 weeks and then 3 months after onset (P < 0.001). Kaplan–Meier survival analysis revealed that the estimated median time of aneurysm persistence was significantly higher in the progressive CAA group than in the non-progressive CAA group (25 vs. 4 months, P < 0.001), as well as among the three groups of patients (giant CAA > medium-sized CAA > small-sized CAA, P < 0.001). Children with KD who had low A/G ratio were more likely to develop mid- to large-sized CAA. Nevertheless, de novo CAA after IVIG treatment may increase the risk of more severe arterial damage and development of progressive coronary artery damage; and both mid- to large-sized and de novo CAA could dramatically prolong coronary artery normalization time. Thus, aggressive risk modifications should be employed, and close monitoring with frequent echocardiography is needed for this vulnerable patient population.

A Rare Presentation of Coronary Aneurysm following Bare-metal Stent

We present a case of post-percutaneous transluminal coronary angioplasty with a bare-metal stent to the right coronary artery (RCA). He presented with acute ST-elevation inferior wall myocardial infarction. Coronary angiography showed an aneurysm of proximal RCA extending from the proximal end of the stent to the distal end. There was a 90% discrete lesion beyond the stent with TIMI III flow. The development of coronary artery aneurysms (CAAs) was reported even before the era of stents. CAA can develop after plain balloon angioplasty, after directional coronary atherectomy, and after bare-metal and drug-eluting stents also but not after coronary angiography. Kachru et al. reported an incidence of 0.2% (4 of 2408) per DES without routine angiographic follow-up and Rha et al. reported an incidence of 1.7% (five out of 296) per patient at 6-month routine angiographic follow-up. CAA is an uncommon and often accidental finding, we report a case of CAA which presented as acute myocardial infarction mimicking stent thrombosis.

Risk scores for Kawasaki disease, a management tool developed by the KAWA-RACE cohort.

Asian scores developed to predict unresponsiveness to intravenous immunoglobulin (IVIG) or development of coronary artery aneurysms (CAA) in patients with Kawasaki disease (KD) are not appropriate in Western populations. The purpose of this study is to develop 2 scores, to predict unresponsiveness to IVIG and development of CAA, appropriate for Spanish population. Data of 625 Spanish children with KD collected retrospectively (2011-2016) were used to identify variables to develop the 2 scores of interest: unresponsiveness to IVIG and development of CAA. A statistical model selected best variables to create the scores, and scores were validated with data from 98 patients collected prospectively. From 625 patients of the retrospective cohort, final analysis was performed in 439 subjects: 37 developed CAA, and 212 were unresponsive to IVIG. For the score to predict CAA, a cutoff ≥ 8 was considered for high risk, considering a score system with a different weight for each of the eight variables. External validation showed a sensitivity of 22% and a specificity of 75%. The score to predict unresponsiveness to IVIG established a cutoff ≥ 8 for high risk, considering a score system with a different weight for each of the nine variables. External validation showed a sensitivity of 78% and a specificity of 50%. Two risk scores for KD were developed from Spanish population, to predict development of CAA and unresponsiveness to IVIG; validation in other cohorts could help to implement these tools in the management of KD in other Western populations.

Comparison of post-covid-19 multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease

Post-covid-19 multisystem inflammatory syndrome in children (MIS-C) is a novel, life-threatening hyperinflammatory condition that develops in children a few weeks after infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Its clinical features and laboratory characteristics are similar to those of Kawasaki disease (KD), KD shock syndrome, and toxic shock syndrome that present diagnostic and therapeutic challenges to the physician. However, this new disorder has some distinct clinical features and laboratory characteristics. MIS-C presents with a greater variety of signs and symptoms and is more often characterized by gastrointestinal and neurologic symptoms. MIS-C more typically presents with ventricular dysfunction and shock (more than 50% in MIS-C versus 5–10% in KD). The development of coronary artery aneurysms in both disorders may increase diagnostic uncertainty. Children with MIS-C have lower absolute lymphocyte and platelet counts, higher ferritin and D-dimer levels, and a higher likelihood of having elevated troponin or ProBNP levels. This review will compare and contrast MIS-C and KD in terms of clinical symptoms, blood markers, cardiac manifestations, diagnostic criteria, and treatment.

Risk Factors for Resistance to Intravenous Immunoglobulin Treatment and Coronary Artery Abnormalities in a Chinese Pediatric Population With Kawasaki Disease: A Retrospective Cohort Study.

BackgroundThe factors predicting high-risk Kawasaki disease (KD) remain unclear. Therefore, we aimed to determine the risk factors for resistance to intravenous immunoglobulin (IVIG) treatment and coronary artery aneurysm (CAA) development in a Chinese pediatric population with high-risk KD.MethodsWe compared the performances of 11 scoring systems that have been reported to predict IVIG resistance among patients with KD hospitalized from January 2013 through August 2021. Patients were risk-stratified based on the optimal scoring system. The association of baseline characteristics with IVIG treatment resistance and CAA development was investigated within the high-risk group of KD.ResultsIn total, 346 pediatric patients with KD were included, of whom 63 (18.2%) presented with IVIG resistance. The Kobayashi score and five Chinese scoring system scores (Tang et al., Yang et al., Lan et al., Liping et al., and Wu et al.) were significantly higher in the IVIG non-responsive KD group than in the IVIG responsive KD group, and the results of the receiver operating characteristic (ROC) curves analysis were observed to be highest in the Xie Liping scoring system for IVIG resistance (area under the curve, 0.650). Especially, 87 (25.1%) patients comprised the high-risk KD group based on this optimal scoring system (≥5 points). IVIG resistance was significantly associated with the total bilirubin-to-albumin ratio (B/A ratio) [odds ratio, 7.427; 95% confidence interval (CI): 1.022–53.951]. The area under the ROC was 0.703 (95% CI: 0.586–0.821), and the cutoff point was 0.383, which indicated a sensitivity and specificity for predicting treatment resistance of 58% and 80%, respectively. The serum albumin level (odds ratio, 1.401; 95% CI: 1.049–1.869) and Z score of the left main coronary artery (odds ratio, 9.023; 95% CI: 1.070–76.112) were independent predictors of CAA development.ConclusionsIn the Chinese pediatric population with KD, the Xie Liping scoring system is the most appropriate method for identifying high-risk patients, and IVIG resistance could be predicted based on the B/A ratio. Serum albumin level and Z score of the left main coronary artery at baseline were warning indicators for CAA development. More intensified or adjunctive therapies and close follow-up should be considered for high-risk patients with these risk factors.

Association of Models of Care for Kawasaki Disease With Utilization and Cardiac Outcomes.

Describe the prevalence of different care models for children with Kawasaki disease (KD) and evaluate utilization and cardiac outcomes by care model. Multicenter, retrospective cohort study of children aged 0 to 18 hospitalized with KD in US children's hospitals from 2017 to 2018. We classified hospital model of care via survey: hospitalist primary service with as-needed consultation (Model 1), hospitalist primary service with automatic consultation (Model 2), or subspecialist primary service (Model 3). Additional data sources included administrative data from the Pediatric Health Information System database supplemented by a 6-site chart review. Utilization outcomes included laboratory, medication and imaging usage, length of stay, and readmission rates. We measured the frequency of coronary artery aneurysms (CAAs) in the full cohort and new CAAs within 12 weeks in the 6-site chart review subset. We included 2080 children from 44 children's hospitals; 21 hospitals (48%) identified as Model 1, 19 (43%) as Model 2, and 4 (9%) as Model 3. Model 1 institutions obtained more laboratory tests and had lower overall costs (P < .001), whereas echocardiogram (P < .001) and immune modulator use (P < .001) were more frequent in Model 3. Secondary outcomes, including length of stay, readmission rates, emergency department revisits, CAA frequency, receipt of anticoagulation, and postdischarge CAA development, did not differ among models. Modest cost and utilization differences exist among different models of care for KD without significant differences in outcomes. Further research is needed to investigate primary service and consultation practices for KD to optimize health care value and outcomes.

Treatment and Coronary Artery Aneurysm Formation in Kawasaki Disease: A Per-Day Risk Analysis

To assess whether 'treatment day' is a significant predicting factor in Kawasaki disease and imposes a risk for coronary artery aneurysms (CAAs) in a per-day analysis. CAA formation can be reduced from 25% to 10% when treated with intravenous immunoglobulin (IVIG). Patient data from (n=1016) a single center were collected for an observational cohort study. After exclusions, we retrospectively analyzed 776 patients in total. A multivariate analysis was performed with treatment day as a continuous variable (n=691). Patients were categorized as no enlargement, small CAA, medium CAA, and giant CAA. Late treatment per-day was a significant predicting factor for the development of larger CAAs. ORs for medium and giant CAAs per delayed day were 1.1 (95% CI 1.1-1.2) P<.05 and 1.2 (95% CI 1.1-1.2) P<.05, respectively. We showed that every day of delay in treatment of patients with Kawasaki disease inherently carries a risk of medium and giant aneurysm formation. There was no cut-off point for treatment day that could mark a safe zone.

Identifying children with Kawasaki disease at high risk for coronary aneurysms

Kawasaki disease, a childhood vasculitis manifested by symptoms of high fever, mucocutaneous inflammation, and unilateral cervical adenopathy, can cause lasting damage to the coronary arteries, and more rarely, other medium-sized muscular arteries. Most children respond well to prompt treatment with high-dose intravenous immunoglobulin (IVIG). However, coronary artery aneurysms, defined by internal lumen diameter at least 2.5 SDs above the population mean for body surface area (Z≥2.5), occur in ∼25% of affected children and are the principal cause of long-term morbidity and mortality in Kawasaki disease. Several risk scores have attempted to predict which children are likely to develop coronary aneurysms. In previous studies in North America, baseline risk factors for coronary artery aneurysms on echocardiography performed 2-8 weeks after Kawasaki disease onset have included higher coronary artery dimensions on baseline echocardiography, IVIG resistance (the persistence or recrudescence of fever after a single dose of IVIG), young age (<12 months or <6 months depending upon the risk score), Asian race, and late diagnosis and treatment with IVIG. Japanese risk scores based upon clinical and laboratory variables have been highly accurate in predicting IVIG resistance, one of the strongest risk factors for coronary artery aneurysms. In Japanese children predicted to have high risk of IVIG resistance, primary adjunctive therapy with corticosteroids or cyclosporine has been shown in randomized clinical trials to reduce the incidence of coronary artery aneurysms. However, Japanese children predicted to be at low risk for aneurysms on the basis of laboratory measures may still develop coronary abnormalities. Understanding the risk factors for aneurysm development thus requires further refinement. In this volume of The Journal, Iio et al analyze independent risk factors for development of coronary artery aneurysms in 1632 Japanese children with Kawasaki disease who were predicted to be at low risk for resistance to primary IVIG treatment. In this low-risk group, 5.5% of patients developed any coronary artery aneurysms and 1%, medium or large coronary aneurysms. In multivariable analysis, baseline coronary artery Z score >2.5, age <12 months at fever onset, and IVIG resistance were independent risk factors for diagnosis of coronary artery aneurysms on echocardiography one month after disease onset. Among these risk factors, coronary artery Z score ≥2.5 was most strongly associated with aneurysm development. Taken together with previous literature, these data suggest that enlarged coronary Z scores measured on baseline echocardiography can be used to select children at high risk for subsequent coronary artery aneurysms and thus who may benefit from adjunctive therapy. The study of Iio et al adds weight to the concept that a high-risk cohort for randomized clinical trials of primary adjunctive therapy in Kawasaki disease may be most simply selected through findings on baseline echocardiography. The ability to select such a high-risk cohort is critical to the design of trials to answer remaining questions in Kawasaki disease therapy: In children of all races and ethnicities, who should receive treatment with adjunctive therapies? How do antiinflammatory therapies compare with each other, and what is the cost/benefit ratio for these therapies? Article page 158 Risk Factors of Coronary Artery Aneurysms in Kawasaki Disease with a Low Risk of Intravenous Immunoglobulin Resistance: An Analysis of Post RAISEThe Journal of PediatricsVol. 240PreviewTo detect risk factors of coronary artery aneurysm (CAA) development in patients with Kawasaki disease determined to have a low risk for resistance to primary intravenous immunoglobulin (IVIG) treatment based on the Kobayashi score. Full-Text PDF

P078 Multi-system inflammatory syndrome associated with SARS-CoV-2 in children: clinical and therapeutic characteristics

BackgroundThe COVID-19 pandemic was associated with the emergence of a new disease resembling the Kawasaki disease (kDa). That was primarily reported in children of western countries strongly affected by SARS-CoV-2. This syndrome was called Pediatric Multi-System Inflammatory Syndrome (PIMS or MIS-C), and has affected thousands of children, adolescents and young adults throughout the world since the alert launched by the National Health Service of the United Kingdom at the end of April 2020. This work is a literature review of data focusing on the clinical and prognostic characteristics of the MIS-C, the links between Covid-19 and MIS-C, and current therapeutic recommendations.Material and methodsWe carried out research of the studies recently published in the electronic bibliographic databases (Google Scholar, PubMed, Science direct, EmConsults, Research Gate, Medline, Cochrane, Trip).Results25 studies were selected, involving 3015 MIS-C patients from different countries (France, United Kingdom, Italy, Germany, Spain, Brazil, Mexico, Chile, United States, India, Pakistan, Iran). Fever and gastrointestinal disorders were the most frequent clinical manifestations, followed by cardiovascular and respiratory symptom. Biological markers of inflammation and SARS-CoV-2 serology were assessed in all studies. Characteristics similar to Kawasaki disease, and toxic shock syndrome were reported in all studies. Complications such as coronary artery aneurysm; cardiac insufficiency, renal insufficiency, respiratory distress were noted as well as a significant rate of admission to intensive care units. Finally, the mortality rate was low in the majority of studies. The treatment adopted in the majority of the studies was an association of intravenous immunoglobulins and corticosteroids.ConclusionAlthough the fact that the exact pathogenesis of MIS-C remains unknown, post-infectious immune deregulation induced by the SARS-CoV-2 virus appears to be the trigger of MIS-C. MIS- C has been described as a new and serious disease entity with multi-organ involvement and a wide range of signs ranging from fever and gastrointestinal symptoms to myocardial damage, shock, and the development of coronary artery aneurysms.KeywordsCOVID-19, Multi-System Inflammatory Syndrome (MIS-C), Kawasaki Disease (kDa), Child

Risk Factors of Coronary Artery Aneurysms in Kawasaki Disease with a Low Risk of Intravenous Immunoglobulin Resistance: An Analysis of Post RAISE

To detect risk factors of coronary artery aneurysm (CAA) development in patients with Kawasaki disease determined to have a low risk for resistance to primary intravenous immunoglobulin (IVIG) treatment based on the Kobayashi score. This study included 1757 predicted IVIG responders from Prospective Observational study on STRAtified treatment with Immunoglobulin plus Steroid Efficacy for Kawasaki disease (Post RAISE), a large-scale, multicenter, prospective cohort study of Kawasaki disease in Japan. Predicted IVIG responders were defined as patients with Kawasaki disease with a Kobayashi score of <5, a predictive scoring system for IVIG resistance created in Japan. The primary outcome was CAA development at 1month after disease onset. CAA was defined as a Z score of ≥2.5. Multivariable logistic regression was used to identify the independent risk factors of CAA. The variables for inclusion were identified based on univariate analysis results and previously reported risk factors of CAA. Among 1632 patients who had complete coronary outcome data, CAA developed in 90 patients (5.5%) at 1month after disease onset. Multivariable analysis found that a baseline maximum Z score of >2.5, age of <12months at fever onset, and nonresponsiveness to IVIG were significant, independent risk factors of CAA development at 1month after disease onset. Among the risk factors, a baseline maximum Z score of >2.5 was most strongly associated with CAA development (OR, 7.1; 95% CI, 4.1-12.2; P≤.001). Predicted IVIG responders with CAA risk factors identified in this study may be candidates for futureclinical trials of intensified primary IVIG treatment with prednisolone, cyclosporine or infliximab.