The microRNA-200 family plays a key role in inflammatory and vascular processes, making it a relevant target for Kawasaki disease, a vasculitis with coronary complications. This study aimed to evaluate the diagnostic potential of urinary exosomal microRNA-200 family members in Kawasaki disease patients.

Urine samples from 15 Kawasaki disease patients and 15 healthy controls underwent total exosome isolation and high-throughput sequencing. Differential expression of microRNA-200 family members was validated using quantitative real-time polymerase chain reaction. Diagnostic potential was assessed via receiver operating characteristic analysis, and correlations with clinical parameters were evaluated using Spearman correlation.

High-throughput sequencing identified upregulation of microRNA-429, microRNA-200b-3p/5p, microRNA-141-3p, microRNA-200a-3p/5p, and microRNA-200c-3p in Kawasaki disease patients. We confirmed significant upregulation of microRNA-200a-3p/5p, microRNA-200b-3p/5p, and microRNA-429, with receiver operating characteristic analysis showing high diagnostic potential for these microRNAs (area under the curves of 0.844, 0.791, 0.942, 0.842, and 0.898, respectively) and a combined analysis yielding a perfect area under the curve of 1.000. MicroRNA-141 and microRNA-200c-3p/5p, however, showed no significant diagnostic value. MicroRNA-200a-3p and microRNA-200a-5p were positively correlated with white blood cells, platelet counts, and C-reactive protein, while microRNA-200b-3p and microRNA-429 were positively correlated with white blood cells, platelet counts, erythrocyte sedimentation rate, and C-reactive protein. microRNA-200b-5p showed moderate correlations with platelet counts and erythrocyte sedimentation rate.

Urinary exosomal microRNA-200 family members, especially microRNA-200a-3p/5p, microRNA-200b-3p/5p, and microRNA-429, demonstrate strong diagnostic potential for Kawasaki disease, correlating with key inflammatory markers. MicroRNA-141 and microRNA-200c did not demonstrate significant diagnostic utility.

Giant coronary artery aneurysms and myocardial fibrosis after Kawasaki disease may lead to devastating cardiovascular outcomes. We characterised the vascular and myocardial outcomes in five selected Kawasaki disease patients with a history of giant coronary artery aneurysms that completely regressed.

Five patients were selected who had giant coronary artery aneurysm in early childhood that regressed when studied 12–33 years after Kawasaki disease onset. Coronary arteries were imaged by coronary CT angiography, and coronary artery calcium volume scores were determined. We used endocardial strain measurements from CT imaging to assess myocardial regional wall function. Calprotectin and galectin-3 (gal-3) as biomarkers of inflammation and myocardial fibrosis were measured by enzyme-linked immunosorbent assay.

The five selected patients with regressed giant coronary artery aneurysms had calcium scores of zero, normal levels of calprotectin and gal-3, and normal appearance of the coronary arteries by coronary computed tomography angiography. CT strain demonstrated normal peak systolic and diastolic strain patterns in four of five patients. In one patient with a myocardial infarction at the time of Kawasaki disease diagnosis at the age of 10 months, CT strain showed altered global longitudinal strain, reduced segmental peak strain, and reduced diastolic relaxation patterns in multiple left ventricle segments.

These patients illustrate that regression of giant aneurysms after Kawasaki disease is possible with no detectable calcium, normal biomarkers of inflammation and fibrosis, and normal myocardial function. Individuals with regressed giant coronary artery aneurysm still require longitudinal surveillance to assess the durability of this favourable outcome.

Giant coronary artery aneurysms are rare but potentially fatal complications of Kawasaki disease. The lack of evidence-based recommendations on their management and treatment cause guidelines and practices to differ. We aimed to assess these variations.

An anonymous online survey regarding surveillance, imaging, pharmacological management, and interventional practices was distributed among 134 physicians attending to Kawasaki disease patients worldwide. A p-value of <0.05 was deemed significant.

The majority (60%) of respondents were general paediatric cardiologists, and 29% interventional specialists. The average years in practice was 15 ± 9.6. Physicians from Asia had the most experience with giant coronary artery aneurysms. American practitioners preferred combining anticoagulants with aspirin. Beta-blockers and statins were more likely used in teenagers versus younger children. Cardiac catheterisation was most (52%) chosen for coronary surveillance in patients with echocardiogram anomalies, followed by Coronary CT-angiography. The indications for coronary intervention were split among respondents, regardless of geographic region or experience. The preferred treatment of coronary stenosis was percutaneous intervention (69%) versus bypass surgery. For thrombosis, thrombolytics (50%) were preferred over percutaneous (39%) and surgical (11%) interventions. Most (92%) preferred intervening in young children in a paediatric facility but were split between a paediatric and adult facility for older children. Most chose combined management by adult and paediatric specialists for either age-scenarios (70, 82%).

As identified by our study, the lack of large studies and evidence-based recommendations cause uncertainty and ambivalence towards certain treatments. International collaborative efforts are needed to provide more robust evidence in the management of these patients.

Coronary artery lesions are the most severe complications of Kawasaki disease. Despite recent advances, evidence of the association between risk factors and coronary artery lesion is lacking. In this study, we demonstrated the potential clinical indicators that could assist to evaluate the prevalence of coronary artery lesion among paediatric patients with Kawasaki disease.

We retrospectively enrolled 260 paediatric patients with Kawasaki disease. Patients with coronary dilation, coronary aneurysm, and intimal thickening of coronary arteries were included in this study. Medical records of each patient were collected. Logistic regression analysis was performed to explore risk factors and the occurrence of coronary artery lesion in patients with Kawasaki disease.

Respectively, 64 (24.6%), 39 (15%), and 56 patients (21.5%) of the participants had coronary dilation, coronary aneurysm, and intimal thickening of coronary arteries. Univariate analysis revealed that age, gender, duration of fever, time of initial use of intravenous immunoglobulin, erythrocyte sedimentation rate, white blood cell counts, time of platelet increase, the maximum value of platelet, albumin, and immunoglobulin G level was associated with coronary artery lesion. In multivariable logistic analysis, those younger and mainly males were associated with all three outcomes of coronary artery lesion, lower serum albumin levels, and later initial use of intravenous immunoglobulin were linked to a higher risk of coronary dilation and coronary aneurysm.

The potential risk factors that could be used to estimate the occurrence of coronary artery lesion in Kawasaki disease patients are young age, male, lower serum albumin lever, and later initial use of intravenous immunoglobulin. However, long-term follow-up and multi-centre studies are required to verify our findings in the future.

Adult Kawasaki patients may require intervention for occlusive coronary artery disease. Some adverse effects of first-generation drug-eluting stent implantation with sirolimus have been reported in this population.

A total of nine lesions in eight (seven males, one female) patients who underwent stent implantations in this population between 2000 and 2021 were reviewed.

The age at stent implantation ranged from 31 to 47 years, with a median of 37 years. There were six lesions treated by primary percutaneous transluminal coronary interventions, and three by elective procedures. A coronary aneurysm was found in two lesions, and coronary artery calcification was found in all culprit lesions. The numbers of everolimus-eluting stents, sirolimus-eluting stents and bare metal stents were six, two, and one, respectively. As anti- thrombotic therapy, aspirin, clopidogrel, and prasugrel were given to four, three, and one, respectively. Warfarin was given to five patients. The follow-up ranged from 2 to 12 years, with a median of 4 years. Follow-up angiograms were performed for eight lesions, at 2 to 38 months, with a median of 11 months. The patency of the target vessel was confirmed in all eight vessels. Slight malapposition, and peri-stent contrast staining were found in two lesions each.

Acute coronary syndrome due to coronary artery lesions caused by Kawasaki disease occurred, even in lesions without any apparent coronary artery aneurysms. In our study, we show safe and efficacious placement of second-generation stent without adverse effects during the short-term follow-up, but long-term follow-up is needed to determine the efficacy and complication.

Kawasaki disease is an acute febrile disease causing systemic vasculitis that is common in infants and young children. This study was conducted to explore the relationships of the rs1412125, and rs2249825 single nucleotide polymorphisms of the high mobility group box 1 gene to Kawasaki disease and its complication of coronary artery injury.

In total, 200 children with Kawasaki disease (49 with coronary artery injury) and 200 healthy controls were enrolled in this study. Polymerase chain reaction was used to amplify the target gene, and direct sequencing was performed to determine distributions at the rs1412125 T/C and rs2249825 C/G loci in the HMGB1 gene. The chi-squared test was used to compare data between groups. Linkage disequilibrium coefficients and single nucleotide polymorphism haplotype analysis were conducted, and a false-positive report probability analysis was used to assess significant associations. Expression quantitative trait loci analysis was performed to determine if single nucleotide polymorphisms affected mRNA levels via the GTEx portal.

Significant differences in the genotype TT, TC, and CC distributions (χ2 = 7.918, P = 0.019) and allele T and C frequencies (χ2 = 6.125, P = 0.013) of rs1412125 T/C locus were found between the Kawasaki disease and healthy control groups. The genotype CC was associated with a greater Kawasaki disease risk [odds ratio = 3.205, 95% confidence interval = 1.352–7.595, χ2 = 7.560, P = 0.006]. C allele carriers had a higher Kawasaki disease risk than did T allele carriers (odds ratio = 1.469, 95% confidence interval = 1.083–1.993, χ2 = 6.125, P = 0.013). The rs1412125 genotype T/C distribution (χ2 = 10.906, P = 0.004) and allele frequencies (χ2 = 8.813, P = 0.003) differed significantly between patients with and without coronary artery injury. In the dominant model, the coronary artery injury risk was 3.006 times greater for patients with the TT genotype than for those with the other genotypes (odds ratio = 3.006, 95% confidence interval = 1.540–5.867, χ2 = 10.875, P = 0.001). No significant difference in the rs2249825 genotype C/G distribution or allele frequencies was found between the Kawasaki disease and control groups, or between the coronary artery injury and without coronary artery injury groups.

The rs1412125 polymorphism of the HMGB1 gene is associated with Kawasaki disease and its coronary artery injury complication. The CC genotype may be a risk factor for Kawasaki disease onset, and the TT genotype may be a risk factor for coronary artery injury in Kawasaki disease.

I encountered three adult patients with major coronary artery occlusion after Kawasaki disease in childhood, who had developed again acute coronary syndrome of adults in the peripheral branches, such as the 4th segments, the atrioventricular node artery, and the posterior descending artery, of the right coronary artery.

I reviewed their clinical course and coronary angiograms.

Their age at onset of acute coronary syndrome ranged from 29 to 33 years. The male patient with a previous anteroseptal myocardial infarction in children had a symptomatic occlusion of the branch of the 4th posterior descending artery at 32 years of age. Acute coronary syndrome occurred in the area of 4th atrioventricular node artery in two female patients. The collateral arteries from the circumflex artery to the 4th atrioventricular node arteries were not clearly injected. It was suspected that they had developed bilateral giant aneurysms after acute Kawasaki disease. Two patients had an acute myocardial infarction due to thrombotic occlusion in a giant aneurysm of the right coronary artery or the left anterior descending artery, and one patient had an asymptomatic coronary occlusion of the right coronary artery and left anterior descending artery in children.

Occlusion of peripheral coronary arteries in adulthood can occur in patients with multi-vessel disease caused by Kawasaki disease. Recurrent events of acute coronary syndrome can occur in adults, although its prevalence may be low. Careful follow-up in adults is also needed in this population.

Children who develop coronary artery aneurysms after Kawasaki disease are at risk for cardiovascular morbidity, requiring health care transition and lifelong follow-up with an adult specialist. Follow-up losses after health care transition have been reported but without outcome and patient experience evaluation.

The Theoretical Domains Framework underpinned our aim to explore the required self-care behaviours and experiences of young adults’ post-health care transition.

A qualitative description approach was used for virtual, 1:1 interviews with 11 participants, recruited after health care transition from a regional cardiac centre in Ontario. Directed content analysis was employed.

Health, psychosocial, and lifestyle challenges were compounded by a sense of loss. Six themes emerged within the Theoretical Domains Framework categories. Participants offered novel health care transition programme recommendations.

The realities of health care transition involve multiple, overlapping stressors for young adults with Kawasaki disease and coronary artery aneurysms. Our findings will inform a renewed health care transition programme and will include outcome evaluation.

Coronary artery aneurysms have been considered the most serious complication of Kawasaki disease. However, some coronary artery aneurysms do regress. Therefore, the ability to predict the expected time of coronary artery aneurysm regression is critical. Herein, we have created a nomogram prediction system to determine the early regression (<1 month) among patients with small to medium coronary artery aneurysms.

Seventy-six Kawasaki disease patients identified with coronary artery aneurysms during the acute or subacute phase were included. All the patients who met inclusion criteria demonstrated regression of coronary artery aneurysms within the first-year post Kawasaki disease diagnosis. The clinical and laboratory parameters were compared between the groups of coronary artery aneurysms regression duration within and beyond 1 month. Multivariate logistic regression analysis was used to identify the independent parameters for early regression based on the results from the univariable analysis. Then nomogram prediction systems were established with associated receiver operating characteristic curves.

Among the 76 included patients, 40 cases recovered within 1 month. Haemoglobin, globulin, activated partial thromboplastin time, the number of lesions, location of the aneurysm, and coronary artery aneurysm size were identified as independent factors for early regression of coronary artery aneurysms in Kawasaki disease patients. The predictive nomogram models revealed a high efficacy in predicting early regression of coronary artery aneurysms.

The size of coronary artery aneurysms, the number of lesions, and the location of aneurysms presented better predictive value for predicting coronary artery aneurysms regression. The nomogram system created from the identified risk factors successfully predicted early coronary artery aneurysm regression.

Kawasaki disease is a vasculitis that can lead to cardiac complications, including coronary artery disease and cardiogenic shock. Various scoring systems have been developed to determine those that will be refractory to routine intravenous immunoglobulin therapy or develop coronary artery disease. The objective of this study was to determine if the neutrophil–lymphocyte ratio could predict refractory disease and coronary artery lesions in patients with Kawasaki disease.

A systematic review of the literature was performed to identify manuscripts describing comparisons of neutrophil–lymphocyte ratio between those who had refractory disease and those who did not, and between those who developed coronary artery lesions and those who did not. Mean difference was compared between groups. Areas under the curve were utilised to determine the pooled area under the curve.

12 studies with 5593 patients were included in the final analyses of neutrophil–lymphocyte ratio for the prediction of refractory disease. Neutrophil–lymphocyte ratio before therapy was higher in refractory disease with a mean difference of 2.55 (p < 0.01) and pooled area under the curve of 0.724. Neutrophil–lymphocyte ratio after therapy was higher in refractory disease with a mean difference of 1.42 (p < 0.01) and pooled area under the curve for of 0.803. Five studies with 1690 patients were included in the final analyses of neutrophil–lymphocyte ratio for the prediction of coronary artery lesions. Neutrophil–lymphocyte ratio before therapy was higher in coronary artery lesions with a mean difference of 0.65 (p < 0.01).

The use of neutrophil–lymphocyte ratio may help physicians in the identification of patients at risk of refractory disease and coronary artery lesions in patients with Kawasaki disease.

Endothelial dysfunction is a marked feature of Kawasaki disease during convalescence, but its pathogenesis is currently unclear. Circulating microRNAs (miRNAs) are associated with the progression of Kawasaki disease. However, the role and mechanism of circulating miRNAs in endothelial dysfunction are largely unknown. Kawasaki disease patients were found to have a unique circulating miRNA profile, including upregulation of miRNA-210-3p, miR-184 and miR-19a-3p, compared to non-Kawasaki disease febrile controls. This study aimed to investigate the effects of these three miRNAs on endothelial function.

Overexpression of miRNAs in human umbilical vein endothelial cells was done by transfection of miRNA mimics. The tube formation assay was used to evaluate the function of human umbilical vein endothelial cells. The potential binding sites of miRNAs on 3’untranslated regions were predicted by using TargetScan database and validated by dual luciferase reporter assay. The protein expression of AGO2, PTEN and VEGF in human umbilical vein endothelial cells was detected by Western blot. Overexpression of AGO2 in human umbilical vein endothelial cells was done by transfection of AGO2 expression plasmids.

Overexpression of miRNA-184 and miRNA-19a-3p, but not miR-210-3p, impaired the function of human umbilical vein endothelial cells. Mechanistically, miR-184 and miR-19a-3p could target the 3’untranslated regions of AGO2 mRNA to downregulate its expression and subsequently impede the AGO2/PTEN/VEGF axis. To be noted, the rescue of the expression of AGO2 remarkably recovered the function that was impaired by overexpression of miRNA-184 and miRNA-19a-3p.

This study suggested that miR-184 and miR-19a-3p could target AGO2/PTEN/VEGF axis to induce endothelial dysfunction in Kawasaki disease.

Long-term physiological dysfunction in coronary/systemic vasculature may persist in individuals with Kawasaki disease even in the absence of coronary artery abnormalities. We perform a systematic review and meta-analyses of studies assessing long-term vascular function in Kawasaki disease.

PubMed, Embase, and Web of Science databases were searched for relevant literature published till May 2021. Patients with Kawasaki disease were included as cases and healthy age/sex-matched individuals as controls. Newcastle Ottawa Scale was used to assess the study quality. Outcome measures were differences in markers of vascular function 1 year after diagnosis of Kawasaki disease. Data were analysed using Review Manager software. Comprehensive meta-analysis software was used for meta-regression. To assess the certainty of evidence, GRADE Profiler software was utilised.

Of 2280 citations, 49 case-control studies (comprising 2714 cases and 2118 controls) were included for data synthesis. Decreased flow-mediated dilatation [3.83, 95%CI 0.94–6.72] and increased pulse-wave velocity [39.34 cm/sec, 95%CI 20.86–57.83], arterial stiffness [0.35, 95%CI 0.11–0.59], and common carotid artery intima-media thickness were noted in patients with Kawasaki disease. No significant difference was observed for nitroglycerine-mediated dilatation and endothelial peripheral artery tonometry (endo-PAT). Significant inter-study heterogeneity was observed for flow-mediated dilatation, arterial stiffness, carotid artery intima-media thickness, and endo-PAT. The GRADE evidence was of ‘very low quality’ for all outcome measures except ‘moderate quality’ for pulse-wave velocity.

Evidence suggests the presence of long-term endothelial dysfunction in patients with Kawasaki disease even in the absence of coronary artery abnormalities. Avoidance of development of other cardiovascular risk factors seems prudent in patients with Kawasaki disease.

Multi-system inflammatory syndrome in children and Kawasaki disease have overlapping clinical features but comparative echocardiographic studies are lacking.

We reviewed echocardiography findings of all multi-system inflammatory syndrome cases between 1st April and 31st July, 2020 and typical Kawasaki disease patients with coronary arteries abnormalities consecutively followed between 1st October, 2016 and June 30th, 2019.

We included 40 multi-system inflammatory syndrome children (25 males, 62.5%) and 45 Kawasaki disease patients (31 males, 68.9%) at a mean age of 6.4 years old and 8 years old, respectively. Four out of 40 multi-system inflammatory syndrome children had coronary arteries abnormalities. Left ventricle ejection fraction was normal in both groups. Global longitudinal strain was normal although Kawasaki disease group had significantly lower values (–20.0 versus –21.7%; p = 0.02). Basal segments were the most affected in Kawasaki disease patients with significant differences in the basal anterior, anterolateral, and anteroseptal strain: –18.2 versus –23.0% (p = 0.002), –16.7 versus –22.0% (p < 0.001), –16.7 versus –19.5% (p = 0.034), respectively. The basal anterolateral and anteroseptal segments in Kawasaki disease patients were the only ones with an absolute reduction of longitudinal strain (–16.7% both) consistent with the greater left main coronary involvement in this cohort.

Our findings are consistent with the transient cardiac involvement in multi-system inflammatory syndrome, as opposed to the subtle and chronic myocardial involvement in Kawasaki disease children with coronary arteries abnormalities. We speculate that the mechanism of cardiac impairment in the few multi-system inflammatory syndrome children with reduced global longitudinal strain is not related to coronary arteries abnormalities.

We describe a cohort of children referred with multisystem inflammatory syndrome in children associated with severe acute respiratory syndrome coronavirus 2 and compare this cohort with a 2019 cohort of children with Kawasaki disease.

We conducted a retrospective cohort study of 2019 and 2020 referrals to the inflammatory cardiology service at Great Ormond Street Hospital for Children. We compared cardiac and inflammatory parameters of a sub-section of the 2020 cohort who presented with reduced left ventricular ejection fraction with the remainder of the cohort.

Referrals significantly increased between February and June 2020 compared to 2019 (19.8/30 days versus 3.9/30 days). Frequency of coronary artery aneurysms (11/79 (13.9%) versus 7/47 (14.9%)) or severe coronary artery aneurysms (6/79 (7.6%) versus 3/47 (6.4%)) was similar between 2020 and 2019, respectively. The 2020 cohort was older (median age 9.07 years versus 2.38 years), more likely to be of Black, Asian, or other minority ethnic group (60/76 (78.9%) versus 25/42 (59.5%)), and more likely to require inotropic support (22 (27.5%) versus 0 (0%)). Even children with significantly reduced left ventricular ejection fraction demonstrated complete recovery of cardiac function within 10 days (mean 5.25 days ± 2.7).

We observed complete recovery of myocardial dysfunction and an overall low rate of permanent coronary sequelae, indicating that the majority of children with multisystem inflammatory syndrome in children are unlikely to encounter long-term cardiac morbidity. Although the frequency of myocardial dysfunction and inotropic support requirement is not consistent with a diagnosis of Kawasaki disease, the frequency of coronary artery abnormalities and severe coronary artery abnormalities suggests a degree of phenotypic overlap.