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Background: Patients with Kawasaki disease (KD) with coronary artery involvement require long-term cardiac care. Although respective evidence-based recommendations are missing, cardiac catheterization is still considered the gold standard for diagnosing detailed coronary pathology. Therefore, to better understand coronary artery pathology development, we conducted a survey to document and evaluate cardiac catheterization data in a European population., Methods and Results: We retrospectively analyzed cardiac catheterization data from KD children from the year 2010 until April 2023. This registry covers basic acute-phase clinical data, and more importantly, detailed information on morphology, distribution, and the development of coronary artery pathologies. A total of 164 mainly White patients (65% boys) were included. A relevant number of patients had no coronary artery aneurysm (CAA) at the cardiac catheterization, indicating that distal CAAs were almost exclusively detected alongside proximal CAAs. Patients with multiple CAAs revealed a significant positive correlation between the number of CAAs and their dimensions in diameter and in length. Location of the CAA within the coronary artery, age at onset of KD, or natal sex did not significantly influence CAA diameters, but CAAs were longer in older children and in boys., Conclusions: That distal CAAs were only present together with proximal ones will hopefully reduce diagnostic CCs in patients with KD without echocardiographically detected proximal CAAs. Furthermore, this study gives valuable insights into dimensional specifics of CAAs in patients with KD. As an ongoing registry, future analyses will further explore long-term outcomes and performed treatments, helping to refine clinical long-term strategies for patients with KD., Registration: URL: https://drks.de/; Unique Identifier: DRKS00031022.

Objectives: To determine the long-term outcomes among a cohort of patients with Kawasaki disease (KD) and a history of giant coronary artery aneurysms (CAAs) at a single US center., Study Design: Medical records for all patients with KD and giant CAAs at a pediatric academic institution were reviewed. Primary outcomes included major adverse cardiovascular events (MACE) and normalization of CA luminal diameter, using Kaplan-Meier analyses., Results: There were 60 patients with KD and giant CAAs identified between 1989 and 2023. The majority of patients were male (71.7%) with a median age at diagnosis of 0.9 years (range, 0.2-13.3 years). Patients were followed for a median of 11 years, up to 34.5 years. MACE occurred in 13 patients (21.7%) at a median of 1.4 years (range, 0.04-22.6 years) after KD diagnosis. The 10-, 20-, and 30-year MACE-free rates were 75%, 75%, and 60%. Patients with maximal CA z scores of ≥20 or bilateral CAA were more likely to have MACE. During follow-up, 26.7% of CAA regressed to a normal luminal diameter at a median of 3.6 years (range, 0.6-12.0 years). The 10-, 20- and 30-year likelihood of CA regression to normal luminal diameter was 36%, 46%, and 46%., Conclusions: Over 30 years, MACE occurred in nearly 22% of patients, more often in those with bilateral CAA or CA z scores of ≥20. Despite regression to a normal luminal diameter in >25% of CAAs, patients with a history of KD-associated giant CAA require ongoing surveillance for cardiac complications, even years after the initial disease., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Coronary artery dissection is managed primarily conservatively with serial imaging or percutaneous coronary intervention (PCI). Exposure to contrast in either modality could potentially result in acute tubular necrosis (ATN). However, no data compares ATN incidence in these management strategies. This study compares the incidence of ATN and associated mortality of PCI and conservative management of coronary artery dissection., Methods: A retrospective analysis was performed using data from the National Inpatient Sample database, including patients with coronary artery dissection between 2016 through 2020. We analyzed the incidence of ATN and associated mortality of PCI and conservative management of coronary artery dissection., Results: We found that the odds of developing ATN were 22% lower in patients managed with PCI than those managed conservatively. There was no difference in the in-hospital mortality or hospital length of stay between the two groups but the mortality rate in patients with ATN was double that of those who did not develop ATN in both PCI and conservatively managed groups., Conclusions: The higher incidents of ATN in patients with coronary dissection being managed with conservative measures compared to PCI suggest that the use of CTA may be harmful. Additionally, persons who developed ATN may have higher mortality. Therefore, more studies in the management of coronary artery dissection need to be done which would allow further steps to be taken to reduce this harm., Competing Interests: Declaration of competing interest No disclosures/conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Although Kawasaki disease (KD) is commonly regarded as a single disease entity, clinical subgroups have recently been described. We aimed to validate previous research on clinical subgroups and establish a KD subgroup differentiation model specific to China., Methods: We analysed clinical data of 1682 patients diagnosed with KD at the Kunming Children's Hospital from December 2014 to December 2022. We performed principal component analysis and hierarchical clustering on 13 continuous variables. Then, we grouped the patients based on the optimal number of clusters and analysed the clinical characteristics of each subgroup., Results: We ultimately identified three subgroups. In cluster 1, younger patients predominantly exhibited the highest risk of coronary artery aneurysm and the lowest rate of intravenous immunoglobulin resistance. Cluster 2 was characterised by high inflammatory markers and a lowered risk of coronary artery aneurysm. Cluster 3 was characterised by liver involvement, with significant elevations in liver enzymes, gamma-glutamyl transferase and total bilirubin. We found a positive correlation between the ratio of the rising trend and intravenous immunoglobulin resistance. Cluster 1 and cluster 3 shared similarities with the previously identified younger age subgroup and liver subgroup, respectively, whereas cluster 2 was unique to our study., Conclusions: Our study preliminarily validated a previous KD subgroup study and established a KD subgroup model in China., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To describe the clinical presentation, management, and outcomes of Kawasaki disease (KD) in Latin America and to evaluate early prognostic indicators of coronary artery aneurysm (CAA)., Study Design: An observational KD registry-based study was conducted in 64 participating pediatric centers across 19 Latin American countries retrospectively between January 1, 2009, and December 31, 2013, and prospectively from June 1, 2014, to May 31, 2017. Demographic and initial clinical and laboratory data were collected. Logistic regression incorporating clinical factors and maximum coronary artery z-score at initial presentation (between 10 days before and 5 days after intravenous immunoglobulin [IVIG]) was used to develop a prognostic model for CAA during follow-up (>5 days after IVIG)., Results: Of 1853 patients with KD, delayed admission (>10 days after fever onset) occurred in 16%, 25% had incomplete KD, and 11% were resistant to IVIG. Among 671 subjects with reported coronary artery z-score during follow-up (median: 79 days; IQR: 36, 186), 21% had CAA, including 4% with giant aneurysms. A simple prognostic model utilizing only a maximum coronary artery z-score ≥2.5 at initial presentation was optimal to predict CAA during follow-up (area under the curve: 0.84; 95% CI: 0.80, 0.88)., Conclusion: From our Latin American population, coronary artery z-score ≥2.5 at initial presentation was the most important prognostic factor preceding CAA during follow-up. These results highlight the importance of early echocardiography during the initial presentation of KD., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Coronary artery aneurysms (CAA) are uncommon, often incidental findings in patients with acute coronary syndrome (ACS) that represent a management challenge due to as there is a paucity of literature in this area., Methods: We analyzed the National Inpatient Sample database from 2016 to 2020 by including all patients with the admission diagnosis of the ACS who underwent percutaneous coronary intervention (PCI). We sought to evaluate the association of CAA with other relevant systemic conditions and determine the impact of CAA on in-hospital outcomes., Results: Among 1,733,655 hospital admission with ACS who underwent PCI, 2675 had CAA. There was a 2-fold increase in odds of CAA if the patient had coronary artery dissection (OR 2.05 95%CI 1.12-3.75, p = 0.020) or extracoronary aneurysm (OR 2.47 95%CI 1.46-4.16, p = 0.001) and a 3-fold increase in odds if they had a systematic inflammatory disorder (OR 3.24 95%CI 2.08-5.07, p < 0.001). CAA was not associated with increased odds of mortality (OR 1.22 95%CI 0.76-1.95, p = 0.42), bleeding (OR 1.29 95%CI 0.86-1.95, p = 0.22), acute stroke (OR 0.91 95%CI 0.40-2.07, p = 0.83), major adverse cardiac and cerebrovascular events (OR 1.08 95%CI 0.72-1.61, p = 0.71) or cardiac complications (OR 0.85 95%CI 0.49-1.47, p = 0.55). However, it was significantly associated with increased odds of vascular complications (OR 2.17 95%CI 1.47-3.19, p < 0.001)., Conclusions: For patients with ACS who undergo PCI, the presence of CAA is associated with greater odds of vascular complications but after adjustments there was no difference in mortality or other complications. In this population, CAA is more prevalent in patients with coronary dissection, extracoronary aneurysms and systemic inflammatory disorders., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier Inc.)

Coronary artery ectasia (CAE) is defined as local or generalized aneurysmal dilatation of the coronary arteries. CAE likely represents an exaggerated form of excessive vascular wall remodeling in different clinical settings such as atherosclerosis, vasculitides, connective tissue disorders, hereditary collagen defects, bacterial infections, and congenital malformations. In the present case-control study, we investigated whether the incidental finding of CAE in patients who undergo coronary angiography is associated with presence of autoimmune reactivity. From 2019 to 2022, we identified all consecutive patients with CAE (n = 319) on elective or emergency coronary angiography (n = 7,458). We furthermore included 90 patients with nonectatic coronary arteries as a control group. Antinuclear antibody (ANA) titer was measured in both groups using the indirect immunofluorescence method from peripheral blood samples. The prevalence of CAE in our study cohort was 4.3%. Among patients with CAE (n = 319), presence of positive Antinuclear antibody (ANA) titer was identified in 128 patients (40%). Only 18 patients (20%) from the control group had positive ANA titer. There was a statistically significant greater percentage of patients with positive ANA titer among patients with CAE than among controls (chi-square = 12.39; p <0.001), with an odds ratio of 2.68. Among patients with CAE, there is an increased prevalence of positive ANA titer, suggesting an underlying autoimmune disease. Screening for autoimmune reactivity could be a reasonable diagnostic strategy in patients who undergo coronary angiography with an incidental finding of coronary ectasia because the number needed to screen for positive ANA titer in this subgroup of patients is only 5., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Coronary artery aneurysms (CAA) are infrequent findings among patients undergoing coronary angiography and may be associated with systemic diseases., Methods: We analyzed the National Inpatient Sample database from 2016 to 2020 by including all patients with the admission diagnosis of the chronic coronary syndrome (CCS). We sought to determine the impact of CAA on in-hospital outcomes encompassing all-cause death, bleeding, cardiovascular complications, and stroke. Secondly, we examined the association of CAA with other relevant systemic conditions., Results: The presence of CAA was associated with a 3-fold increase in the odds of cardiovascular complications (OR 3.1, 95 % CI 2.9-3.8), however, it was associated with reduced odds of stroke (OR 0.7, 95 % CI 0.6-0.9). There was no significant impact on all-cause death and overall bleeding complications, although there appeared to be a reduction in the odds of gastrointestinal (GI) bleeding associated with CAA (OR 0.6, 95 % CI 0.4-0.8). Patients with CAA vs. those without CAA had a significantly greater prevalence of extracoronary arterial aneurysms (7.9 % vs. 1.4 %), systemic inflammatory disorders (6.5 % vs. 1.1 %), connective tissue disease (1.6 % vs. 0.6 %), coronary artery dissection (1.3 % vs. 0.1 %), bicuspid aortic valve (0.8 % vs. 0.2 %), and extracoronary arterial dissection (0.3 % vs. 0.1 %). In the multivariable regression, systemic inflammatory disorders, extracoronary aneurysms, coronary artery dissection, and connective tissue diseases were independent predictors of CAA., Conclusions: CAA in patients with CCS is associated with greater odds of cardiovascular complications during hospitalization. These patients also had a substantially greater prevalence of extracardiac vascular and systemic abnormalities., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier Inc.)

Background: 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., Methods: 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)., Results: 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)., Discussion: 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.

Introduction: Kawasaki disease (KD) patients with a high risk of coronary artery aneurysm (CAA) development are well characterized and targeted for intensified primary intravenous immunoglobulin (IVIG) treatment. However, the characteristics of KD patients with a low CAA risk are less well-known., Methods: The present study was a secondary analysis of Prospective Observational study on STRAtified treatment with Immunoglobulin plus Steroid Efficacy for Kawasaki disease (Post RAISE), a multicenter, prospective cohort study of KD patients in Japan. The target of the analysis was patients with a Kobayashi score <5 who were predicted to respond to IVIG. The incidence of CAA during the acute phase, the primary outcome, was assessed based on all echocardiographic evaluations performed between week 1 (days 5-9) and month 1 (days 20-50) after the start of primary treatment. Multivariable logistic regression was used to identify the independent risk factors of CAA during the acute phase, based on which a decision tree was created to identify a subpopulation of patients with KD with a low CAA risk., Results: Multivariate analysis found that a baseline maximum Z score >2.5, age <12 months at fever onset, nonresponsiveness to IVIG, low neutrophils, high platelets and high C-reactive protein were independent predictors of CAA during the acute phase. The decision tree created by using these risk factors identified 679 KD patients who had a low incidence of CAA during the acute phase (4.1%) and no medium or large CAA., Conclusions: The present study identified a KD subpopulation with a low CAA risk comprising around a quarter of the entire Post RAISE cohort., Competing Interests: M.M. received an honorarium from the Japan Blood Products Organization, Teijin Pharma Ltd., and Nihon Pharmaceutical Co, Ltd. outside the submitted work. Y.M. received a Health Science and Labor Research Grant and grants from the Tokyo Metropolitan Government Hospitals, the Japan Agency for Medical Research and Development, the Center for Clinical Trials of the Japan Medical Association, the Japan Science and Technology Agency, the New Energy and Industrial Technology Development Organization, and the Japan Society for the Promotion of Science outside the submitted work. None of these entities were involved in this study in any manner. The other authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Kawasaki Disease (KD) is the leading cause of acquired heart disease in children in developed countries with a variable incidence worldwide. Previous studies reported an unexpectedly high incidence of KD in the Canadian Atlantic Provinces. The goals of our study were to validate this finding in the province of Nova Scotia and to carefully review patients' characteristics and disease outcomes., Methods: This was a retrospective review of all children < 16 years old from Nova Scotia diagnosed with KD between 2007-2018. Cases were identified using a combination of administrative and clinical databases. Clinical information was collected retrospectively by health record review using a standardized form., Results: Between 2007-2018, 220 patients were diagnosed with KD; 61.4% and 23.2% met the criteria for complete and incomplete disease, respectively. The annual incidence was 29.6 per 100,000 children < 5 years. The male to female ratio was 1.3:1 and the median age was 3.6 years. All patients diagnosed with KD in the acute phase received intravenous immunoglobulin (IVIG); 23 (12%) were refractory to the first dose. Coronary artery aneurysms were found in 13 (6%) patients and one patient died with multiple giant aneurysms., Conclusion: We have confirmed an incidence of KD in our population which is higher than that reported in Europe and other regions of North America despite our small Asian population. The comprehensive method to capture patients may have contributed to the detection of the higher incidence. The role of local environmental and genetic factors also deserves further study. Increased attention to regional differences in the epidemiology of KD may improve our understanding of this important childhood vasculitis., (© 2023. The Author(s).)

The long-term prognosis of patients with Kawasaki disease (KD) complicated by coronary artery aneurysms (CAA) is still unclear. The present, multicenter registry study aimed to study the factors associated with coronary events (CE) and determine an appropriate management method for patients with KD complicated with CAA. Patients with KD with onset after 2015 and with a medium-sized or large CAA having an actual diameter ≥ 4 mm or a Z-score ≥ 5.0 at 30 days and later after KD onset were included in the annual survey. The primary endpoint was the time-dependent incidence of CE. Associated factors were also examined. In total, 179 patients from 53 centers were enrolled and followed up for a median of 501 days. The median age at KD onset was 2.2 years, 137 patients were male (77%), 47 had incomplete KD (26%), and 36 had large CAA (20%). CE occurred in 13 patients (7%; 95% confidence interval: 4-12%); eight (62%) experienced CE within 1 year, and all the patients experienced a CE within 2 years. All but one patient received antiplatelet drugs and warfarin. Patients with a large CAA had significantly more CAA (2.8 vs. 1.7, p < 0.001), more cases of warfarin use (86% vs. 43%, p < 0.001), and were more likely to have CE (28% vs. 2%, p < 0.001) than those with a medium-sized CAA. On univariate Cox regression analysis, the factors significantly associated with CE were large CAA (hazard ratio (HR): 17.0), three or more CAA (HR: 23.3), and beaded CAA (HR: 15.9). Multivariable Cox regression analysis revealed that the only associated factor was a large CAA., Conclusion: Patients with a large CAA were more likely to have a CE within 2 years. Antithrombotic therapy with warfarin did not eliminate the CE risk, and better therapies are desirable., What Is Known: • Coronary artery aneurysms are a serious complication of Kawasaki disease, and coronary events are sometimes fatal. • In previous, retrospective studies in Japan, large aneurysms, male sex, and refractoriness to initial immunoglobulin therapy were considered risk factors for coronary events., What Is New: • Of 179 patients with a medium sized or large aneurysm, 13 (7%) experienced coronary events, all of which occurred within 2 years of onset. Factors significantly associated with coronary events were large aneurysms, three or more aneurysms, and beaded aneurysms., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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 (&lt;5 points). CAA development was significantly associated with male sex (odds ratio [OR], 1.946; 95% CI: 1.015-3.730), age &lt;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 &lt;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., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Objective: Coronary thrombosis is a common cardiovascular complication of Kawasaki disease (KD), which seriously affects the long-term therapeutic effect of KD. The purpose was to determine the incidence and timing of coronary thrombosis and to identify risk factors for coronary thrombosis in KD with giant coronary artery aneurysm (GCAA)., Methods and Results: A total of 94 consecutive KD patients with GCAA from Children's Hospital Affiliated to Chongqing Medical University were enrolled retrospectively. The cumulative incidence of coronary thrombosis in KD patients with GCAA was 59 % (n = 54). Coronary thrombosis mainly occurred in the acute phase (n = 41/54, 76 %), with a median time of 16 days after onset. Cox regression analysis was used to identify risk factors for coronary thrombosis. Cox regression analysis indicated that male (hazard ratios, 1.87; 95 % CI, 1.01-3.44; P = 0.43), left anterior descending artery (LAD) involvement (hazard ratios, 3.75; 95 % CI, 1.85-7.39; P < 0.001), coronary absolute diameter ≥ 8 mm (hazard ratios, 2.93; 95 % CI, 1.36-6.29; P = 0.006) constituted a higher risk of coronary thrombosis after adjusting for confounders. Kaplan-Meier method showed the cumulative incidence for coronary thrombosis in KD patients with GCAA was 79 %, 92 %, and 88 % in male, LAD involvement, coronary absolute diameter > 8 mm, respectively., Conclusions: Male, LAD involvement, and coronary absolute diameter ≥ 8 mm were associated with a high incidence of coronary thrombosis. Based on the analysis of the incidence, time and risk factors of coronary thrombosis in different periods, this study may provide an essential reference for thromboprophylaxis management of KD with GCAA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction/objectives: 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., Method: 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., Results: 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%., Conclusions: 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., (© 2022. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Background: Kawasaki disease (KD) disproportionately affects children of Asian descent. San Diego is home to a large Vietnamese population but no previous study has addressed the outcome of KD in this group., Methods: We performed a retrospective review of Vietnamese patients seen at Rady Children's Hospital San Diego from 2001 to 2019. Non-Vietnamese Asian and non-Asian KD patients were matched (2:1) based on date of onset and age with Vietnamese patients. Demographic, clinical, and echocardiographic data were compared. Interviews with cardiologists at the Children's Hospital 1 in Ho Chi Minh City, Vietnam, explored local practices in the diagnosis and management of KD patients. KD publications in Vietnamese were translated and summarized., Results: Of 978 KD patients for whom both parents had the same ethnicity, 20 were Vietnamese (2.1%), 168 (17%) were non-Vietnamese Asian, and 789 (81%) were non-Asian. Vietnamese and non-Vietnamese Asians had an earlier median day of diagnosis at day 6 (interquartile range [IQR] 5-6) and 5.5 (IQR 4-6.75), respectively, compared with non-Asians (day 7, IQR 5-8.75, P = 0.02). Prominent cervical lymphadenopathy at diagnosis was more common in both Vietnamese and non-Vietnamese Asians (20% and 40%, respectively) compared with non-Asians (12.5%, P = 0.01). Importantly, Vietnamese KD patients had a higher rate of coronary artery aneurysms (60% vs. 27.5%) compared to non-Asians (P = 0.024). Vietnamese literature review and structured interviews suggested a high incidence and severity of KD in Vietnamese children., Conclusions: Physicians should be aware that Vietnamese children may be disproportionately affected by KD and have worse coronary artery outcomes., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Kawasaki disease (KD) is most common among East Asian children. There is a lack of data from Middle Eastern countries. We conducted a retrospective study of 27 paediatric patients with KD in Dubai, United Arab Emirates, 2012-2020. The majority of the patients were male, Asian, aged 1-5 years and presented with typical (complete) KD. Timely high-dose intravenous immunoglobulins were administered to 18 patients. Twelve patients did not develop any cardiac complications, 12 had a coronary artery aneurysm and 2 patients developed serious cardiac complications . No patient experienced non-cardiac complications or died. Paediatric patients with KD in Dubai were similar to those from other countries., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The literature on prevalence and outcomes of coronary artery aneurysm (CAA) in the United States (US) is limited., Objective: To study the prevalence, outcomes, and trends of CAA., Methods: Data from the national readmissions database (NRD) sample that constitutes 49.1% of the stratified sample of all hospitals in the US were analyzed for CAA among coronary angiography (CA) related hospitalizations for the years 2012-2018., Results: A total of 6,843,910 index CA related hospitalizations were recorded for the years 2012-2018 in the NRD (Mean age 64.37 ± 13.30 years' 38.6% females). Of these 9671 (0.141%) were CAA, 5092 (52.7%) without-ACS and 4579 (47.3%) with ACS [NSTEMI occurred in 2907(63.5%) and STEMI in 1672(36.5%)]. In-hospital mortality among CAA was comparable to those without-CAA on angiography (n-209,2.17% vs n = 175,120,2.56%;p = 0.08). CAA patients who presented with ACS vs those without ACS had higher mortality (n = 150,3.28%vsn = 60,1.16%;p < 0.001) cardiogenic shock 6.9%vs2%, ventricular arrythmias 9.2%vs5.2%, coronary dissection 58%vs42.7%, and need for mechanical circulatory support 7%vs2.7% respectively. Percutaneous coronary intervention (PCI) was performed among 45.2% patients; however, on coarsened exact matching of baseline characteristics, PCI had no association with mortality, patients (OR 1.22, 95%CI0.69-2.16, p = 0.49). The prevalence of CAA on CA trend towards increased mortality with ACS increased over the years 2012-2018 (linear p-trend <0.05). The 30-day readmissions rate were 13.8% (non-CAA) vs 4.6% (CAA) p = 0.001 predominantly cardiovascular causes (50.9%vs70.7%) and PCI on readmission (7.06%vs17.5%)., Conclusion: CAA is an uncommon anomaly noted on coronary angiography. The higher mortality in patients with ACS and increasing trend of CAA-ACS warrants more research., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: Kawasaki syndrome (KS) is a systemic vasculitis of unknown etiology that affects medium and small blood vessels. The aim of our study is to analyze coronary artery lesions in children with KS and their risk factors., Material and Methods: All children under the age of 15 years-old presenting KS and admitted in the pediatric department of three university hospital (Sahloul hospital, and Farhat Hached hospital of Sousse, Ibn El Jazzar hospital of Kairoun) from January 2000 to December 2018 were included., Results: Sixty-five patients were included in our study. The mean age at diagnosis was of 29.9 months [2-120 months] and the sex ratio was of 1.7. Echocardiography was performed in all patients. It showed coronary dilation in 37% of patients with coronary artery diameter of 4.2 mm on average [3.2-7mm]. The coronary aneurysm was small in 19 cases and medium in 5 cases. No giant aneurysm has been identified. In univariate analysis, the predictors of coronary artery lesions were male sex, atypical form, fever duration more than 10 days, hepatic cytolysis, thrombocytosis and anemia. In multivariate analysis, only the last four parameters were the predictive factors of the coronary artery involvement., Conclusion: Several risk factors can be used to determine which children are predisposed to develop coronary dilations. In case of patient with risk factors, intravenous immunoglobulins should be initiated early to avoid these serious complications., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Background: Accumulating evidence suggests that several microRNA (miRNA) polymorphisms are closely associated with disease susceptibility or progression, such as in Kawasaki disease (KD). Our previous studies revealed the association of miR-149 rs2292832 T>C and miR-196a2 rs11614913 C>T polymorphisms with KD susceptibility. The present study further focused on the relationship between three miRNA polymorphisms (miR-149 rs2292832 T>C, miR-196a2 rs11614913 C>T and miR-499a rs3746444 A>G) and the risk of coronary artery aneurysm (CAA) in southern Chinese KD patients., Methods: We evaluated 318 KD patients with CAAs and 784 patients without CAAs. TaqMan assays were used to estimate genotyping and analyze the relationship between miRNA polymorphisms (miR-149 rs2292832 T>C, miR-196a2 rs11614913 C>T and miR-499a rs3746444 A>G) and risk associations of CAA by odds ratios (ORs) and 95% confidence intervals (CIs)., Results: We found that the miR-149 rs2292832 TC/CC genotype increased the CAA risk (adjusted OR = 1.53, 95% CI = 1.15-2.03, p = 0.003 for TC, adjusted OR = 1.63, 95% CI = 1.08-2.47, p = 0.021 for CC), whereas the miR-499a rs3746444 AG genotype decreased the CAA risk in KD patients (adjusted OR = 0.33, 95% CI = 0.25-0.45 p ≤ 0.001). Moreover, patients carrying two or three of these single nucleotide polymorphism (SNP) genotypes (rs2292832 TC/CC and rs11614913 TT and rs3746444 AA) had a higher risk for CAA than those who harbored only zero or one of these SNP genotypes., Conclusions: Our results demonstrated that the miR-149 rs2292832 T>C polymorphism increased the risk of CAA in KD patients and that the miR-499a rs3746444 A>G polymorphism decreased the risk of CAA in KD patients. Further studies with larger sample sizes and different centers are needed to confirm the findings of the present study., (© 2021 The Authors. The Journal of Gene Medicine published by John Wiley & Sons Ltd.)

This study aimed to explore the incidence and clinical characteristics of multiple complications in children with Kawasaki disease (KD). All patients were diagnosed in our hospital between January 2016 and December 2020. A total of 640 cases were included, 43 patients had coronary artery aneurysm, 51 patients had coronary artery dilation, and 546 patients had no coronary artery damage. The patients were divided into three subgroups based on age: < 1 year old, 1-5 years old, and > 5 years old. The multiple complications of all the KD children and the correlation between extracardiac complications and cardiovascular complications were analyzed. Among the 640 KD children, most were 1-5 years old (415/640, 64.8%). Children < 1 year old (31.6%) and > 5 years old (28.3%) were more likely to have cardiovascular complications. The incidence of respiratory complications was highest in 1-5 year olds (57.1%). Involvement of the digestive and the hematological systems gradually decreased with age, whereas involvement of the nervous system, the urinary system, and the joints gradually increased with age. The incidence of cardiovascular injury with extracardiac complications (22.3%) was higher than that without extracardiac complications (16.3%), although the difference was not statistically significant (p > 0.05).Conclusions: KD can be complicated by multiple-organ injury but there was no significant relationship between the occurrence of extracardiac complications and cardiovascular complications. What is Known: • Cardiovascular disease is generally believed to be the most common and serious complication of Kawasaki disease (KD). • Over recent years, we have found that extracardiovascular complications of KD are more common than generally supposed and, because they have some effect on prognosis, we believe that more attention should be paid to these complications. What is New: • There was no significant relationship between the occurrence of extracardiac complications and cardiovascular complications., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aims: Kawasaki disease (KD) is an acute systemic vasculitis with possible long-term impact of general cardio-vascular health. An endothelial glycocalyx disorder during the disease's acute phase might predispose to long-term vascular anomalies leading to endothelial dysfunction and atherosclerosis. To investigate any association between increased cardiovascular risk and endothelial glycocalyx, we assessed circulating glycocalyx components in patients with a KD history, and analysed their association with acute-phase clinical features and more importantly, with patients' current cardiovascular risk factors., Methods: This prospective observational cohort study included 51 subjects: 31 patients with a history of KD, and 20 healthy subjects matched for age and sex. We analysed serum syndecan-1 and hyaluronan via ELISA. We assessed features reported during the acute phase of KD such as blood counts, C-reactive protein (CRP) levels and coronary artery aneurysms (CAA), and their current blood pressure and lipid markers in relation to measured glycocalyx components., Results: Our multivariate analysis revealed that hyaluronan and syndecan-1 levels were not associated with KD. However, the latter exhibited a significant association with acute-phase blood count alterations in patients with KD. Furthermore, significant interactions of hyaluronan and syndecan-1 with certain cardiovascular risk factors like blood lipids and blood pressure were only present in KD patients., Conclusion: Vasculitis during KD's acute phase might predispose to a long-term endothelial glycocalyx alteration, influenced by other factors having a vascular impact such as blood pressure and circulating lipids., Clinical Trial Registration: German Clinical Trials Register on 25th February 2016, DRKS00010071 https://www.drks.de/drks&#95;web/., (Copyright © 2021. Published by Elsevier Inc.)

Background: Coronary artery aneurysms after drug eluting stents are rare. We present a case series of type II coronary aneurysms after implantation of Everolimus eluting stents including patients developing giant aneurysms with a toxic course., Case Presentation: Over a span of 3.5 years at our center 2572 patients were implanted Everolimus eluting stents out of which 4 patients developed coronary type II aneurysms an incidence of 0.00156 whereas 5838 patients were implanted Sirolimus eluting 2nd generation stents out of which 2 patients developed similar aneurysms with an incidence of 0.00034. The slight increase in incidence in Everolimus stents does not reach statistical significance (p = 0.054) and is limited by single centre non randomized study. We also propose a hypothesis that the slight increase in the incidence maybe due to allergy to Methacrylate present in Everolimus eluting Xience stent's primer which is absent in other Sirolimus eluting stents used at our center but that needs to be further investigated. We also found some patients who developed giant aneurysms including Left main aneurysms. In our series operative repair of these patients had better outcomes than covered stent deployment but larger trials maybe needed to confirm the same., Conclusions: Coronary artery aneurysms after stent implantation are rare but occasionally giant aneurysms are formed with a toxic course. The incidence and morphology of aneurysms after Everolimus and Sirolimus eluting stent deployment do not differ much., (© 2022. The Author(s).)

A retrospective study that compared children younger than 6 months versus older children of a Spanish cohort of patients diagnosed with Kawasaki disease between 2011 and 2016 (Kawa-Race study). From the 598 patients recruited, 42 patients were younger than 6 months (7%) and presented more frequently with an incomplete diagnosis of Kawasaki disease (52.4 vs 27.9%, p = 0.001). Cardiac abnormalities detected by echocardiography were more common in younger patients (52.4 vs 30%, p = 0.002). These younger patients presented with a higher proportion of coronary aneurysms as well (19 vs 8.6%, p < 0.001). Shock at diagnosis (9.5 vs 1.9%, p = 0.016) and admission to intensive care units (17.7 vs 4.1%, p = 0.003) were more frequent in patients younger than 6 months. There were no statistically significant differences in relation to infections, non-response to IVIG, or mid- or long-term outcomes.Conclusion: Data of the Spanish cohort are consistent with other American and Asian studies, although Spanish children younger than 6 months had a lower rate of non-response to IVIG and better clinical outcomes. A high index of suspicion should be considered for this population due to a higher risk of coronary abnormalities, presentation of shock, and admission to the intensive care unit. What is Known: •Children below 6 months of age with Kawasaki disease (KD) have different features compared to older. •Younger patients usually have an incomplete form of KD and coronary artery abnormalities. What is New: •Younger than 6 months with KD presented with shock and required admission to PICU more frequently compared to older. •Infections play a similar role in KD despite the age of the patients., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Kawasaki disease (KD) is a common form of vasculitis in children that can be complicated by coronary artery aneurysms (CAAs). Data of long-term outcomes and major adverse cardiac events (MACE) in children with CAAs following KD in developing country are limited. Our aims were to determine the rates of MACE and identify risk factors associated with MACE in children with KD and CAAs in Thailand. We performed a retrospective analysis of data from 170 children diagnosed with KD and CAAs in two tertiary hospitals between 1994 and 2019. During a median (range) follow-up of 5.4 years (22 days to 23 years), 19 patients (11.2%) experienced MACE, that included 12 coronary artery bypass grafting, 2 percutaneous coronary intervention and 5 children with evidence of myocardial ischemia and coronary occlusion. Coronary interventions were performed at a median time of 4 years (0.01 to 9.5 years) after KD diagnosis. Forty-nine patients (28.8%) had giant CAAs. No MACE was reported in children with small CAAs. Independent risks of MACE were from the absence of intravenous immunoglobulin treatment (HR 7.22; 95% CI 2.21 to 23.59; p = 0.001), the presence of giant aneurysms (HR 13.59; 95% CI 2.43 to 76.09; p = 0.003), and CAAs that involved bilateral branches of coronary arteries (HR 6.19; 95% CI 1.24 to 30.92; p = 0.026). Among children with giant CAAs, the intervention-free rate was 93.8%, 78.7% and 52.2%, at 1, 5 and 10 years, respectively. Of note, 81% of the small CAAs regressed to a normal size, and for medium CAAs, 50% regressed to normal size. Overall, ~10% of children with CAAs following KD experienced MACE in this cohort. Timely IVIG treatment in children with KD following symptom onset will reduce the risk of MACE. Cautious surveillance to identify cardiac complications should be recommended for children once medium or giant CAAs develop. Trial registration: TCTR20190125004., Competing Interests: The authors have declared that no competing interest exist.

Background: Kawasaki disease (KD), an acute, generalized vasculitis, is associated with an increased risk of coronary heart disease and is the most common cause of acquired heart disease in childhood. The incidence of KD is increasing worldwide., Aims: Our study aims to analyze KD's clinical course in children and to evaluate risk factors for persistent changes in coronary vessels after 6-8 weeks of treatment., Methods: The retrospective analysis included patients with KD hospitalized in a single tertiary carehospital. The diagnosis, as well as treatment, were based on the current worldwide treatment standards. The clinical course, selected laboratory parameters, the treatment effect, and following cardiac complications were analyzed in different age groups., Results: In the years 2006-2019, 140 patients aged from two months to 16 years: 52 girls and 88 boys, were diagnosed with KD. Coronary artery aneurysms (CAA) at weeks 6-8 of disease were found in 16% of patients. Boys and infants were more likely to develop aneurysms at weeks 6-8 of the disease (P = 0.045; P = 0.03; respectively). The CAA frequency was related to the atypical course (P = 0.02), late diagnosis (P = 0.04), presence of changes in the coronary arteries at the time of diag nosis (P<0.001), immunoglobulin resistance (P = 0.002), a lower hemoglobin concentraction (P<0.001), and a higher platelet count (P = 0.02). There were 28% of patients resistant to first-line time treatment. In this group, we found CAA in 31% of children., Conclusions: We found that late diagnosis, low hemoglobin level, high platelet count, CAA presence at diagnosis, atypical course of KD, and resistance to intravenous immunoglobulins are predictors of CAA after 6-8 weeks in KD patients.

Objective: 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., Study Design: 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 1 month 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., Results: Among 1632 patients who had complete coronary outcome data, CAA developed in 90 patients (5.5%) at 1 month after disease onset. Multivariable analysis found that a baseline maximum Z score of >2.5, age of <12 months at fever onset, and nonresponsiveness to IVIG were significant, independent risk factors of CAA development at 1 month 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)., Conclusions: Predicted IVIG responders with CAA risk factors identified in this study may be candidates for future clinical trials of intensified primary IVIG treatment with prednisolone, cyclosporine or infliximab., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Data on the delayed diagnosis of (KD) is limited. This study aimed to determine the prevalence and trend of delayed diagnosis over time and identify the associated risk factors in Malaysia., Methods: This retrospective, observational, population-based study involved all children with KD registered in Johor Kawasaki Clinical Registry over 10 years (January 2010 and December 2019). The prevalence of delayed diagnosis and its trend over time was calculated. Multivariable binary logistic regression was used to identify the independent risk factors for delayed diagnosis., Results: There were 556 cases of KD, with 28% having incomplete criteria, 11% atypical presentation, while 10% developed a coronary aneurysm. The overall prevalence of delayed diagnosis was 9.9% (95% confidence interval (CI): 7.6-12.7%). There was a statistically significant decrease in delayed diagnosis over time (P = 0.008), with the latest rate of 4.6%. The majority of delayed diagnoses were due to failure to diagnose the disease during the initial consultation. Independent risk factors for delayed diagnosis were children older than 1 year, diagnosis before 2015, atypical presentation, and incomplete KD, with adjusted odds ratios (ORs) of 2.7, 2.3, 4.3, and 3.6, respectively. Compared to early diagnosis of KD, delayed diagnosis was significantly associated with coronary aneurysms (27.3% vs. 8.2%, P < 0.001, OR 4.2, [95% CI: 2.1-8.3])., Conclusions: One-tenth of cases of KD were diagnosed late, but it has improved over time. Children > 1 year, presenting with atypical presentation, and incomplete criteria are associated with late diagnosis., (© 2022 Japan Pediatric Society.)

Coronary artery ectasia (CAE) is described in 5% of patients undergoing coronary angiography. Previous studies have shown controversial results regarding the prognostic impact of CAE. The prevalence and prognostic value of CAE in patients with acute myocardial infarction (AMI) remain unknown. In 4788 patients presenting with AMI referred for coronary angiography the presence of CAE (defined as dilation of a coronary segment with a diameter ≥1.5 times of the adjacent normal segment) was confirmed in 174 (3.6%) patients (age 62 ± 12 years; 81% male), and was present in the culprit vessel in 79.9%. Multivessel CAE was frequent (67%). CAE patients were more frequently male, had high thrombus burden and were treated more often with thrombectomy and less often was stent implantation. Markis I was the most frequent angiographic phenotype (43%). During a median follow-up of 4 years (1-7), 1243 patients (26%) experienced a major adverse cardiovascular event (MACE): 282 (6%) died from a cardiac cause, 358 (8%) had a myocardial infarction, 945 (20%) underwent coronary revascularization and 58 (1%) presented with a stroke. Patients with CAE showed higher rates of MACE as compared to those without CAE (36.8% versus 25.6%; p <0.001). On multivariable analysis, CAE was associated with MACE (HR 1.597; 95% CI 1.238-2.060; p <0.001) after adjusting for risk factors, type of AMI and number of narrowed coronary arteries. In conclusion, the prevalence of CAE in patients presenting with AMI is relatively low but was independently associated with an increased risk of MACE at follow-up., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Data on Kawasaki disease from tropical countries are scarce. Hence, this population-based study aims to determine the epidemiology, clinical characteristics, and outcome of Kawasaki disease in children enrolled in the Kawasaki disease registry between 2006 and 2019 in Southern Malaysia. Diagnosis of Kawasaki disease was made using standard criteria. Primary outcome measure was a coronary artery aneurysm. Multivariable logistic regression was used to analyze the associated risk factors for coronary artery aneurysm. There were 661 Kawasaki disease, with 27% incomplete and 11% atypical presentations. Male-to-female ratio was 2:1, and median age of diagnosis was 1.4 years (interquartile range 9 to 32 months). Incidence in children of less than 5 years was 14.8 (95% confidence interval [CI]: 13.6 to 16.0) per 100,000 population, higher in males (19/100,000) and Chinese (22/100,000), with a gradual increase from 5.7/100,000 in 2006 to 19.6/100,000 in 2019, p < 0.001. Incidence in children between 5 and 9 years old was 1.3 (95% CI: 0.9 to 1.6) per 100,000 population and remained stable over time. There was a seasonal pattern with peak incidence during the rainy season. Out of 625 intravenous immunoglobulins (IVIG)-treated Kawasaki disease, 7.4% were resistant, and 9% had coronary artery aneurysms. Atypical presentation, male sex, late diagnosis, and IVIG resistance were independent risk factors for coronary artery aneurysms.Conclusions: Despite the tropical climate, Kawasaki disease epidemiology is similar to non-tropic regions with seasonal patterns and a rising incidence. Atypical presentation, male sex, late diagnosis, and IVIG resistance were significantly associated with coronary artery aneurysms. What is Known: • Kawasaki disease predominantly occurs in males, children less than 5 years old, and the Asian population. • Male sex, late diagnosis, incomplete Kawasaki disease, and IVIG resistance were associated with coronary artery aneurysms. What is New: • In multi-ethnic Asian countries such as Malaysia, ethnic Chinese have a higher prevalence of Kawasaki disease compared to other ethnicities. • Kawasaki disease with atypical presentation can occur in both complete and incomplete Kawasaki disease and is significantly associated with a coronary artery aneurysm., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The diagnosis of coronary artery abnormalities (CAA), including dilation and aneurysm, in patients with Kawasaki disease is paramount to treatment planning. CAA are defined using various standards, which makes diagnosis difficult. The aims of this study were to determine the variability of CAA prevalence according to existing guidelines and Z score formulas and to examine the discrepancies in widely used Z score formulas., Methods: Using data from a Korean national survey on Kawasaki disease, 6,889 patients were included and analyzed. The overall prevalence of CAA and the prevalence for subgroups were compared on the basis of aneurysm severity, age, and body surface area. Finally, discrepancies among five Z score formulas were evaluated by comparing two of the formulas in pairs., Results: According to the Japanese criteria, the prevalence of CAA was 18%. According to the American Heart Association criteria, the prevalence of dilation or aneurysm was about 21% to 42%, and that of aneurysm of the left anterior descending artery or right coronary artery was about 8% to 27%. The prevalence of CAA and that of left anterior descending or right coronary artery aneurysm was significantly different, with discrepancies between the Japanese and AHA Z score criteria, as well as among the five Z score formulas. Additionally, misclassification of aneurysm severity was observed for each criterion or Z score formula. There was significant variation among calculated Z scores. The more extreme the Z score values, the more discrepancy was observed., Conclusions: Different guidelines and Z score formulas yield significantly different prevalence rates and classifications of CAA. In addition, more discrepancies were observed with higher Z score values. As CAA or aneurysm severity could be changed by guidelines or Z score formulas, they should be chosen carefully, and when a particular formula is chosen, consistency is needed., (Copyright © 2021 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Objective: Kawasaki disease (KD) is a vasculitis of unknown aetiology with a high risk of coronary aneurysms if untreated. Timely treatment with intravenous immunoglobulin decreases the risk for coronary artery aneurysms (CAA). In this study, we set out to elucidate the factors associated with the risk of developing CAA., Methods: Records of all KD-diagnosed children in Skåne between 2004 and 2014 were collected and clinical and demographic data were compiled. KD is defined according to the revised American Heart Association diagnostic criteria and classified as either complete KD (cKD) or incomplete KD (iKD)., Results: KD was diagnosed in 77 children and CAA was found in 31% (n = 24). Children with CAA were younger compared with children without (median; 20 vs 34 months) and intravenous immunoglobulin treatment within 10 days was less likely to be received (75% vs 91%). In children presenting with iKD, 47% developed CAA compared with 21% in cKD patients. Using multivariate analysis, an association between the risk of CAA with low age in children with iKD was observed., Conclusion: The risk of CAA development is disturbingly high in young children with iKD. This highlights the importance of rapid intense treatment and vigilance in infants, who are the most difficult to diagnose, in order to reduce the frequency of CAA., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Competing Interests: Competing interests: None declared.

Objective: To explore the trends in diagnosis of Kawasaki disease (KD) and determine the characteristics for patients outside the usual age range of 6 months to 4 years., Method: A retrospective review of patients with KD identified in four epidemiological surveys spanning 20 years (1998-2017) in Shanghai was performed., Results: A total of 8416 patients were included. All in all, 223 (2.6%) were aged 0 to 2 months, 639 (7.6%) were 3 to 5 months, 6556 (77.9%) were 6 months to 4 years, 915 (10.9%) were 5 to 9 years, and 83 (1.0%) were ≥ 10 years. The use of intravenous immunoglobulin increased in all extreme age groups, and delayed treatment rates decreased in all patients except in those aged 0 to 2 months and ≥ 10 years. The number of patients outside the usual age increased over time, but the proportion of these patients did not change significantly. They had more incomplete KD and coronary artery aneurysms (CAA), while those aged 0 to 2 months and ≥ 10 years had more delayed diagnoses in their respective age groups. The incidence of CAA was similar in younger and older children, but the former group had more cases of incomplete KD and abnormal laboratory parameters, while the latter group had longer duration of fever and was more difficult to diagnose promptly., Conclusions: The proportion of KD outside the usual age range did not increase over time. Older and younger children have different clinical and laboratory characteristics. Key Points • The number of patients outside the usual age increased over time, but the proportion of these patients did not increase. • Patients aged 0 to 2 months and ≥ 10 years had more delayed diagnoses in their respective age groups. • Younger children had more cases of incomplete KD and abnormal laboratory parameters, while older children had longer duration of fever and were more difficult to diagnose promptly.

A giant coronary artery (CA) aneurysm is a potentially fatal cardiac complication resulting from Kawasaki disease (KD). We aimed to identify epidemiologic characteristics and potential risk factors associated with giant CA aneurysms identified after acute KD. We analyzed 90,252 patients diagnosed with KD from 2011 to 2018, using data obtained in nationwide KD surveys conducted in Japan. Multivariable logistic regression analyses were performed to evaluate potential risk factors associated with subsequent giant CA aneurysm complications (defined as lumen size ≥ 8 mm), adjusting for all potential factors. Giant CA aneurysms were identified in 144 patients (0.16%) after acute KD. The annual prevalence ranged from 0.07 to 0.20% during the study period. In the multivariate analyses, male sex (adjusted odds ratio 2.09 [95% confidence interval 1.41-3.11], recurrent KD (1.90 [1.09-3.33]), IVIG administration at 1-4 days of illness (1.49 [1.04-2.15]) and ≥ 8 days after KD onset (2.52 [1.38-4.60]; reference, 5-7 days), detection of CA dilatations and aneurysms at initial echocardiography (4.17 [1.85-5.41] and 46.5 [28.8-74.8], respectively), and resistance to IVIG treatment (6.09 [4.23-8.75]) were significantly associated with giant CA aneurysm complications identified after acute KD. The annual prevalence of giant CA aneurysms identified after acute KD did not increase during the study period. Patients with larger CA abnormalities detected at initial echocardiography were independently associated with progression to giant CA aneurysm complications after acute KD regardless of the number of days from onset at treatment initiation.

Objectives: Kawasaki disease (KD) is the most frequent cause of acquired heart disease in children in high-income countries because of coronary artery involvement. Risk factors for coronary lesions can vary in consideration of different genetic background and environmental factors., Methods: Multicenter retrospective and prospective study including 372 consecutive children (58% boys; mean age 34.3 ± 30.3 months, Caucasian 85%) was diagnosed with KD. We divided the cohort into 2 groups according to the presence of coronary anomalies (CAA) and aneurysms. We compared the groups and studied the risk factors for CAA and for aneurysms, the most severe lesions., Results: Children with CAA were 91/372 (24.46%, aneurysms 20/372, 5.37%). Children with CAA were more likely to have a longer duration of fever (p < 0.001), later day of treatment (p < 0.001), to be IVIG non-responders and late treated (p < 0.001), while age, clinical presentation, and seasonality were not different. They also had significantly higher WBC and neutrophils, lower lymphocytes, Hb and Na during the acute stage, and slower resolution of inflammation. Age, IVIG unresponsiveness, and presence of non-coronary cardiac findings were independent risk factors for CAA and for aneurysms, while neutrophils just for CAA. Age under 6 months was a risk factor for the aneurysm. Aneurysms occurred more frequently in the first quartile of the age of KD onset (under 14 months)., Conclusion: Very young children with non-coronary cardiac findings are at increased risk for a more severe form of KD with aneurysms. These children could benefit from adjunctive therapy beside IVIG, especially if they have higher markers of inflammation, particularly neutrophils. Key points • Risk factors for coronary lesions can vary in consideration of different genetic background and environmental factors. • Risk factors for coronary involvement have been extensively studied in the Asian population, and others have been validated in cohorts with mixed ethnicities. • In our predominantly Caucasian population, non-coronary cardiac findings, age younger than 6 months, and IVIG unresponsiveness are independent risk factors for a more severe form of KD with aneurysms.

Coronary artery aneurysms (CAAs) are infrequent but not rare. Because of the lack of supportive data and a substantial knowledge gap in this field, clinicians are in a dilemma how to manage patients with coronary artery aneurysms. Most often, CAAs are discovered incidentally, while symptomatic patients present with diverse complications of unstable angina, myocardial infarction, arrhythmias, or sudden cardiac death. Therapeutical approaches consist of surgical procedure, percutaneous coronary intervention (PCI), and medical management. Because of the scarcity of randomized trials or large-scale data on symptomatic and asymptomatic patients with coronary artery aneurysms, the management of these patients poses considerable challenges for the cardiologists. This review summarizes the current literature, a proposed algorithm for the management of CAAs is highlighted in the text. In view of the majority of current proposal information based on small series of case reports or observational studies, an individualized therapeutic regimen should be on the basis of the location, expansion by time, morphology, complications, and etiologies of the coronary artery aneurysms, the clinical presentations, and the patient's characteristics., (Copyright © 2020 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.)

Background: This study aimed to investigate recent epidemiologic features of Kawasaki disease (KD) in South Korea., Methods: The ninth triennial nationwide questionnaire survey collected data on the demographic findings, symptoms and signs, treatment patterns and coronary artery complications of acute-phase KD occurred in 2015-2017 from 98 hospitals with pediatric residency programs and 108 community hospitals without residency programs., Results: We received data from 93 of the 98 hospitals (response rate: 94.9%) with residency programs and 75 of the 108 community-based children's hospitals (response rate: 69.4%) without residency programs. In the 3-year survey period, a total of 15,378 (5449 in 2015, 5171 in 2016 and 4758 in 2017) cases of KD were reported. The mean age at diagnosis was 33.0 ± 24.8 months (range: 0-205 months), and the male-to-female ratio was 1.41:1. The overall KD incidence was 196.9 (202.2 in 2015, 197.1 in 2016 and 191.0 in 2017) per 100,000 younger than 5 years population. Recurrent cases were 4.85%. KD occurred more frequently during winter (December-January) and late spring (May-June). Intravenous immunoglobulin (IVIG) was administered to 95% of the patients; nonresponder rate for the first IVIG was 14.8%. Coronary artery aneurysms and giant coronary artery aneurysms (internal diameter >8 mm) occurred in 1.7% and 19 patients, respectively. Two patients died due to multiorgan failure and hepatic encephalopathy., Conclusion: Peak incidence of KD in South Korea was 202.2 per 100,000 younger than 5 years population (2015), and the incidence of giant coronary artery aneurysm decreased to 0.09% (2017).

Kawasaki disease is an acute febrile illness and systemic vasculitis of unknown aetiology that predominantly afflicts young children, causes coronary artery aneurysms and can result in long-term cardiovascular sequelae. Kawasaki disease is the leading cause of acquired heart disease among children in the USA. Coronary artery aneurysms develop in some untreated children with Kawasaki disease, leading to ischaemic heart disease and myocardial infarction. Although intravenous immunoglobulin (IVIG) treatment reduces the risk of development of coronary artery aneurysms, some children have IVIG-resistant Kawasaki disease and are at increased risk of developing coronary artery damage. In addition, the lack of specific diagnostic tests and biomarkers for Kawasaki disease make early diagnosis and treatment challenging. The use of experimental mouse models of Kawasaki disease vasculitis has considerably improved our understanding of the pathology of the disease and helped characterize the cellular and molecular immune mechanisms contributing to cardiovascular complications, in turn leading to the development of innovative therapeutic approaches. Here, we outline the pathophysiology of Kawasaki disease and summarize and discuss the progress gained from experimental mouse models and their potential therapeutic translation to human disease.

Background: Coronary artery ectasia is a relatively common entity characterized by inappropriate dilatation of the coronary vasculature. In some cases of acute coronary syndrome without obstructive coronary lesions, coronary ectasia is the sole cause. The exact mechanism of its development is unknown but evidence suggests a combination of genetic predisposition, common risk factors for coronary artery disease, and abnormal vessel wall metabolism. As there are few data regarding the pattern of coronary risk factors in patients with coronary ectasia, the objective of the study was to determine the frequency and distribution of coronary risk factors in patients with acute coronary syndrome solely due to coronary ectasia., Methods: The study included 155 patients over a period of 6 months, with coronary angiographic evidence of coronary ectasia as the sole cause of acute coronary syndrome. There were 79 (51%) men and 76 (49%) women with a mean age 51.92 ± 7.83 years; 73 (47.10%) were aged 20-50 years and 82 (52.90%) were 51-80 years of age. The frequencies of coronary risk factors were stratified according to sex and the two age groups., Results: Seventy-one patients (45.80%) had diabetes mellitus, 83 (53.54%) had hypertension, 55 (35.48%) were smokers, 46 (29.68%) had dyslipidemia, and 47 (30.3%) were obese., Conclusion: Hypertension is the leading coronary risk factors in patients with acute coronary syndrome solely due to coronary ectasia, followed by diabetes mellitus and smoking.

Background: Kawasaki disease (KD) is the leading cause of acquired heart disease in children, and is steadily increasing in prevalence in East Asia. KD is often complicated by coronary artery damage, including dilatation and/or aneurysms. Aspirin is used with intravenous immunoglobulin (IVIG) to prevent coronary artery abnormalities in KD. However, the role and optimal dose of aspirin remain controversial. Identifying the dose of aspirin in the acute phase will facilitate development of a more appropriate treatment strategy in improving the outcome of KD., Methods: A total of 2369 patients with KD were retrospectively analyzed and divided into three groups according to the aspirin dose: 510 in group 1 (20-29 mg/kg/day), 1487 in group 2 (30-39 mg/kg/day), and 372 in group 3 (40-50 mg/kg/day). The differences in laboratory data, rate of IVIG resistance and coronary artery damage were compared among the groups., Results: There was no difference in the incidence of coronary artery aneurysms (CAAs) in group 1 compared with groups 2 and 3 (2 weeks of illness: 2.94% vs. 1.90% vs. 3.36%; 3-4 weeks of illness: 1.94% vs. 2.32% vs. 2.65%). The risk for developing CAA was not reduced at 2 weeks of illness onset in groups 2 and 3 compared with group 1 (adjusted OR = 1.05, 95% confidence interval: 0.34-3.18; aOR = 1.81, 95% CI: 0.42-7.83). Furthermore, the risk for developing CAA was not reduced at 3-4 weeks of illness onset in groups 2 and 3 (aOR = 2.63, 95% CI: 0.61-11.28; aOR = 0.52, 95% CI: 0.03-9.54). There was no significant difference in the rate of IVIG resistance among the groups. Platelet levels after IVIG treatment in group 1 were significantly lower than those in groups 2 and 3 (522.29 × 10 9 /L, 544.69 × 10 9 /L, and 557.77 × 10 9 /L, p = 0.013). C reactive protein of the 30-40 mg/kg*day group was slightly higher than the other two groups. (7.76, 8.00, and 7.01 mg/L, p = 0.028)., Conclusions: Aspirin at the dose of 20-29 mg/kg/day dose not increase the risk of coronary artery damage and IVIG resistance compared with the dose of 30-50 mg/kg/day. This low dose may have a lower risk for a potential effect on liver function.

Background: Kawasaki disease (KD) is characterized as a self-limited systemic vasculitis. C1q/tumor necrosis factor-related protein-1 (CTRP1) had been associated with the occurrence of vasculitis in KD. Methylation at the promoter region of certain genes was reported to be involved in the development process of KD. This study aims to investigate the methylation levels of CTRP1 in KD, as well as, its potential to predict coronary artery aneurysms (CAAs)., Methods: 31 patients with KD and 14 healthy controls (HCs) were recruited into this study. The KD group was further divided into KD with CAA (KD-CAAs) group and KD without NCAAs (KD-NCAAs) group. Methylation levels of CpG sites were determined by MethylTarget sequencing, a method that uses multiple targeted CpG methylation analysis., Results: The methylation levels of CTRP1 promoter region in the KD group were lower than that in the HC group at all predicted CpG sites, especially at sites 34, 51, 69, 79, 176 and 206. Compared with KD-CAAs group, the methylation levels of almost every CpG sites of CTRP1 were increased in the KD-NCAAs group, with site 69 and 154 found to be strongly related to the occurrence of CAAs., Conclusions: The difference in methylation levels of CTRP1 promoter may be involved in the development process of KD, and may be a potential predictive marker for the occurrence of CAAs., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest and no authors' financial ties to products in the study., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Kawasaki disease (KD) is an acute, self-limited vasculitis. Coronary artery aneurysm (CAA) serves as a major contributor to the long-term prognosis of KD. In addition, acute KD usually also leads to several kinds of noncoronary cardiac abnormalities (NCA) involving the pericardium, myocardium and endocardium., Materials and Methods: A total of 142 Chinese children with KD were recruited from July 2015 to April 2018. Blood samples were collected at 24 hours pre-intravenous immunoglobulin (IVIG) therapy. Several inflammatory mediators and biomarkers for acute myocardial infarction were detected. Echocardiography and electrocardiography (ECG) were performed., Results: Plasma white blood cell counts (WBC) were significantly increased in patients with IVIG-nonresponsive KD when compared with their IVIG-responsive counterparts. A total of 106 children (74.65%) suffered from NCA, including 8 patients (5.63%) with pericardial effusion, 23 patients (16.20%) with acute myocarditis, 101 patients (71.13%) with valvular regurgitation and 8 patients (5.63%) with abnormal ECG. No significant differences were observed in the distribution of clinical classification and the response to IVIG therapy regardless of NCA exhibited or not., Conclusions: Noncoronary cardiac abnormalities is almost universal in acute KD and mainly manifests as valvular regurgitation. However, it has no influence on clinical classification and the response to IVIG therapy., (© 2020 Stichting European Society for Clinical Investigation Journal Foundation.)

Background: Coronary Aneurysms are a focal dilatation of an artery segment >1.5-fold the normal size of adjacent segments. Although some series have suggested a prevalence of 0.3-12%, data are lacking. In addition, they are not mentioned in practice guidelines. Our aim was investigate its prevalence, management and long-term outcomes., Methods and Results: The coronary artery aneurysm registry (CAAR) involved 32 hospitals across 9 countries in America and Europe. We reviewed 436,467 consecutive angiograms performed over the period 2004-2016. Finally, 1565 patients were recruited. Aneurysm global prevalence was 0.35%. Most patients were male (78.5%) with a mean age of 65 years and frequent cardiovascular risk factors. The main indication for angiogram was an acute coronary syndrome, 966 cases. The number of aneurisms was ≤2 per patient in 95.8% of the cases, mostly saccular, most frequently found in the left anterior descending and with numbers proportional with coronary stenosis. Aortopathies were related with more aneurysms too. Most patients received any revascularization procedure (69%), commonly percutaneous (53%). After a median follow-up of 37.2 months, 485 suffered a combined event (MACE) and 240 died. Without major differences comparing CABG vs PCI, MACE and death were more frequent in patients who received bare metal stents., Conclusions: Coronary artery aneurysms are not uncommon. Usually, they are associated with coronary stenosis and high cardiovascular risk. Antiplatelet therapy seems reasonable and a percutaneous approach is safe and effective., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Coronary aneurysms are classically defined as a segment of the artery in which dilation exceeds the diameter of an adjacent portion (considered as a reference point) by more than 1.5times. In rare instances, coronary artery aneurysms are large enough to be called giant coronary artery aneurysms, which have been reported as occurring with an incidence of 0.02%. However, there is no clear consensus on how giant coronary artery aneurysms should be defined, and their aetiology is not entirely clear; many causes have been suggested, with atherosclerosis being the most common among adults, accounting for up to 50% of cases, and paediatric diseases, such as Kawasaki disease and Takayasu arteritis, being the other main aetiology. Although giant coronary artery aneurysms are often incidental findings, many complications, such as local thrombosis, distal embolization, rupture and vasospasm, associated with ischaemia, heart failure and arrhythmias, have been reported. The optimal medical, interventional or surgical management, still needs to be clarified. This literature review aims to summarize current knowledge on giant coronary artery aneurysms., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Background: Mycotic coronary aneurysms (MCA) are rare but often lead to significant morbidity and mortality. Evidence on the topic is limited to case reports and small case series. A systematic review was performed to improve understanding of this challenging diagnosis. A case report prompting this review is also included., Methods: Relevant articles were identified by searching databases Medline and Google Scholar for terms 'mycotic coronary aneurysm'. Manual searching from article references identified further case reports., Results: Ninety-seven (97) published cases of MCA were identified between 1812 and 2017; 80 cases since the introduction of percutaneous coronary intervention (PCI) with stents in 1986. The most common associations were PCI (40.0%) and infective endocarditis (IE) (40.0%). Complications including aneurysm rupture (28.9%), pericardial effusion (37.3%) and myocardial infarction (39.8%) were frequent. Short-term mortality was high at 42.6%. The most common treatment was surgical resection of the aneurysm with bypass grafting., Conclusions: We present a case and the largest systematic review to date of this rare diagnosis, identifying 97 published case reports. Clinical scenarios in which to consider MCA include febrile illness after recent PCI, febrile illness (particularly infective endocarditis) with evidence of coronary ischaemia, and purulent pericarditis. Given the high rate of complications and mortality, immediate surgical referral is recommended., (Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.)

Background: Coronary artery aneurysms (CAAs) are a well-known complication of Kawasaki disease (KD), but there are no data on incidence or outcomes of systemic artery aneurysms (SAAs) in the current era., Methods: From April 1, 2016, to March 31, 2019, we screened for SAAs in 162 patients with KD at risk for SAAs with magnetic resonance angiography or peripheral angiography and analyzed incidence and early outcomes of SAAs., Results: Twenty-three patients had SAAs, demonstrating an incidence of 14.2% (23 of 162) in patients who were screened at 1 month after onset. The proportion of patients with SAAs was estimated to be 2% (23 of 1148) of all patients with KD. The median age at onset of KD with SAAs was 5 months. All patients with SAAs had CAAs, with z scores >8. Of patients with giant CAAs, 38.6% (17 of 44) had SAAs. A total of 129 SAAs occurred in 17 different named arteries. The most common sites for SAAs were the axillary (18.6%), common iliac (12.4%), and brachial (11.6%) arteries. During a median follow-up time of 6 months, 92.9% (79 of 85) of SAAs had some degree of regression, with 80% (68 of 85) of SAAs returning to normal. The overall regression rate was higher for medium to large SAAs than for medium to giant CAAs., Conclusions: Although the incidence of SAAs may not be as dramatically reduced as we expected compared with previous data, SAAs have a high regression rate during short-term follow-up., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2019 by the American Academy of Pediatrics.)

Objective: Based on 2017 guidelines, participation in competitive sports with prior history of Kawasaki Disease (KD) requires those with coronary artery aneurysms (CAA) z score ≥ 5 to undergo evaluation for evidence of inducible ischemia or arrhythmias. The use of exercise stress testing (EST) to evaluate arrhythmias among KD patients has never been reported. This retrospective single-center case series study sought to describe the presence of inducible arrhythmias during EST in KD patients with or without CAA., Methods: Single-center retrospective review of medical records of patients diagnosed with KD between 1989-2015 at Texas Children's Hospital, Houston, Texas who underwent EST were included., Results: Among 1007 patients diagnosed with KD, 95 (9%) underwent 165 ESTs at a median time of 9.6 years (IQR 5.8-11.3 years) from diagnosis. Of these 95 patients, 37 had normal coronaries, 21 dilated (z score 2 to <2.5), 10 small (5 >z ≥2.5), 12 medium (10>z ≥ 5 absolute dimension <8 mm), 10 large (z ≥10 or absolute dimension ≥8 mm), 5 severe (myocardial infarct or bypass graft). Supraventricular tachycardia was not seen. Ventricular arrhythmias during EST were uncommon and seen only among patients with CAA z ≥5. Ventricular tachycardia occurred in a single patient with a large CAA, known VT and ICD. High-grade ventricular ectopy was seen in one patient who had severe CAA and underwent bypass grafting., Conclusions: Arrhythmias on EST were noted only among patients with CAA z ≥5. The current guidelines are a reasonable approach to increasing healthy activity among KD patients. Clarification regarding which inducible arrhythmias meet criteria for activity restriction may be helpful to guide sport participation., (© 2019 Wiley Periodicals, Inc.)