Kawasaki Disease Shock Syndrome vs Classical Kawasaki Disease: A Meta-analysis and Comparison With SARS-CoV-2 Multisystem Inflammatory Syndrome.

BACKGROUND: The emergence of increasing reports worldwide of a severe inflammatory process and shock in pediatric patients resembling Kawasaki disease (KD) and more specifically Kawasaki disease shock syndrome (KDSS), prompted us to explore KDSS in a preamble of a systematic comparison between the two conditions. METHODS: We completed a systematic review of KDSS and performed a meta-analysis comparison between reported KDSS cases and KD controls. RESULTS: A total of ten case-control series were included in the meta-analysis. KDSS patients were older (38.4 ± 30.6 vs. 21.9±19.5 months; P<0.001) compared to standard KD with equal sex distribution and completeness of clinical diagnostic criteria. KDSS present higher CRP (59.4±29.2 mg/dL vs. 20.8±14.8 mg/dL; p<0.001), lower albumin (2.7±0.5 g/dL vs. 3.3±0.5 g/dL; p<0.01), and lower platelets (255±149 109/L vs. 394±132 109/L; p<0.001) but only borderline higher WBC's (p=0.06). Differences in ALT, AST and ESR were non-significant. The odds of IVIG resistance (44.4% vs. 9.6%; (p<0.001) and the hospital length of stay (10.9±5.8 vs. 5.0±3.0 days; p<0.001) were higher in KDSS as were the odds of coronary artery abnormalities (33.9% vs. 8.6%; p<0.001). CONCLUSION: This first meta-analysis on KDSS versus KD represents a basis for future works on KDSS and opens the opportunity for future multicenter studies in the search of causal relationships between presenting elements and the eventual complications of KDSS. The similarities between SARS-CoV-2 multisystem inflammatory syndrome in children (MIS-C) and KDSS open new horizons to the understanding of the etiology and pathophysiology related to KDSS

Medium-Term Complications Associated With Coronary Artery Aneurysms After Kawasaki Disease: A Study From the International Kawasaki Disease Registry.

Background Coronary artery aneurysms (CAAs) may occur after Kawasaki disease (KD) and lead to important morbidity and mortality. As CAA in patients with KD are rare and heterogeneous lesions, prognostication and risk stratification are difficult. We sought to derive the cumulative risk and associated factors for cardiovascular complications in patients with CAAs after KD. Methods and Results A 34-institution international registry of 1651 patients with KD who had CAAs (maximum CA

Kawasaki syndrome: an intriguing disease with numerous unsolved dilemmas

More than 40 years have passed since Kawasaki syndrome (KS) was first described. Yet KS still remains an enigmatic illness which damages the coronary arteries in a quarter of untreated patients and is the most common cause of childhood-acquired heart disease in developed countries. Many gaps exist in our knowledge of the etiology and pathogenesis of KS, making improvements in therapy difficult. In addition, many KS features and issues still demand further efforts to achieve a much better understanding of the disease. Some of these problem areas include coronary artery injuries in children not fulfilling the classic diagnostic criteria, genetic predisposition to KS, unpredictable ineffectiveness of current therapy in some cases, vascular dysfunction in patients not showing echocardiographic evidence of coronary artery abnormalities in the acute phase of KS, and risk of potential premature atherosclerosis. Also, the lack of specific laboratory tests for early identification of the atypical and incomplete cases, especially in infants, is one of the main obstacles to beginning treatment early and thereby decreasing the incidence of cardiovascular involvement. Transthoracic echocardiography remains the gold-standard for evaluation of coronary arteries in the acute phase and follow-up. In KS patients with severe vascular complications, more costly and potentially invasive investigations such as coronary CT angiography and MRI may be necessary. As children with KS with or without heart involvement become adolescents and adults, the recognition and treatment of the potential long term sequelae become crucial, requiring that rheumatologists, infectious disease specialists, and cardiologists cooperate to develop specific guidelines for a proper evaluation and management of these patients. More education is needed for physicians and other professionals about how to recognize the long-term impact of systemic problems related to KS

Management of Multisystem Inflammatory Syndrome in Children Associated With COVID-19: A Survey From the International Kawasaki Disease Registry

Background: Since April 2020, there have been numerous reports of children presenting with systemic inflammation, often in critical condition, and with evidence of recent infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This condition, since defined as the multisystem inflammatory syndrome in children (MIS-C), is assumed to be a delayed immune response to coronavirus disease 2019 (COVID-19), and there are frequently cardiac manifestations of ventricular dysfunction and/or coronary artery dilation. Methods: We surveyed the inpatient MIS-C management approaches of the members of the International Kawasaki Disease Registry across 38 institutions and 11 countries. Results: Among the respondents, 56% reported using immunomodulatory treatment for all MIS-C patients, regardless of presentation. Every respondent reported use of intravenous immunoglobulin (IVIG), including 53% administering IVIG in all patients. Steroids were most often used for patients with severe clinical presentation or lack of response to IVIG, and only a minority used steroids in all patients (14%). Acetylsalicylic acid was frequently used among respondents (91%), including anti-inflammatory and/or antiplatelet dosing. Respondents reported use of prophylactic anticoagulation, especially in patients at higher risk for venous thromboembolism, and therapeutic anticoagulation, particularly for patients with giant coronary artery aneurysms. Conclusions: There is variation in management of MIS-C patients, with suboptimal evidence to assess superiority of the various treatments; evidence-based gaps in knowledge should be addressed through worldwide collaboration to optimize treatment strategies

The landscape of cardiovascular care in pediatric cancer patients and survivors: a survey by the ACC Pediatric Cardio-Oncology Work Group

Abstract Objective To enhance the understanding of cardiovascular care delivery in childhood cancer patients and survivors. Study design A 20-question survey was created by the Pediatric Cardio-oncology Work Group of the American College of Cardiology (ACC) Cardio-oncology Section to assess the care, management, and surveillance tools utilized to manage pediatric/young adult cardio-oncology patients. The survey distribution was a collaborative effort between Cardio-oncology Section and membership of the Adult Congenital and Pediatric Cardiology Section (ACPC) of the ACC. Results Sixty-five individuals, all self-identified as physicians, responded to the survey. Most respondents (n = 58,89%) indicated childhood cancer patients are regularly screened prior to and during cancer therapy at their centers, predominantly by electrocardiogram (75%), standard echocardiogram (58%) and advanced echocardiogram (50%) (i.e. strain, stress echo). Evaluation by a cardiologist prior to/during therapy was reported by only 8(12%) respondents, as compared to post-therapy which was reported by 28 (43%, p < 0.01). The most common indications for referral to cardiology at pediatric centers were abnormal test results (n = 31,48%) and history of chemotherapy exposure (n = 27,42%). Of note, during post-treatment counseling, common cardiovascular risk-factors like blood pressure (31,48%), lipid control (22,34%), obesity & smoking (30,46%) and diet/exercise/weight loss (30,46%) were addressed by fewer respondents than was LV function (72%). Conclusions The survey data demonstrates that pediatric cancer patients are being screened by EKG and/or imaging prior to/during therapy at most centers. Our data, however, highlight the potential for greater involvement of a cardiovascular specialist for pre-treatment evaluation process, and for more systematic cardiac risk factor counseling in posttreatment cancer survivors

Medium-Term Complications Associated With Coronary Artery Aneurysms After Kawasaki Disease: A Study From the International Kawasaki Disease Registry.

Background Coronary artery aneurysms (CAAs) may occur after Kawasaki disease (KD) and lead to important morbidity and mortality. As CAA in patients with KD are rare and heterogeneous lesions, prognostication and risk stratification are difficult. We sought to derive the cumulative risk and associated factors for cardiovascular complications in patients with CAAs after KD. Methods and Results A 34-institution international registry of 1651 patients with KD who had CAAs (maximum CAA Z score ≥2.5) was used. Time-to-event analyses were performed using the Kaplan-Meier method and Cox proportional hazard models for risk factor analysis. In patients with CAA Z scores ≥10, the cumulative incidence of luminal narrowing (&gt;50% of lumen diameter), coronary artery thrombosis, and composite major adverse cardiovascular complications at 10&nbsp;years was 20±3%, 18±2%, and 14±2%, respectively. No complications were observed in patients with a CAA Z score &lt;10. Higher CAA Z score and a greater number of coronary artery branches affected were associated with increased risk of all types of complications. At 10&nbsp;years, normalization of luminal diameter was noted in 99±4% of patients with small (2.5≤Z&lt;5.0), 92±1% with medium (5.0≤Z&lt;10), and 57±3% with large CAAs (Z≥10). CAAs in the left anterior descending and circumflex coronary artery branches were more likely to normalize. Risk factor analysis of coronary artery branch level outcomes was performed with a total of 893 affected branches with Z score ≥10 in 440 patients. In multivariable regression models, hazards of luminal narrowing and thrombosis were higher for patients with CAAs of the right coronary artery and left anterior descending branches, those with CAAs that had complex architecture (other than isolated aneurysms), and those with CAAs with Z scores ≥20. Conclusions For patients with CAA after KD, medium-term risk of complications is confined to those with maximum CAA Z scores ≥10. Further risk stratification and close follow-up, including advanced imaging, in patients with large CAAs is warranted

Multisystem Inflammatory Syndrome in Children: Survey of Protocols for Early Hospital Evaluation and Management.

ObjectiveTo describe the similarities and differences in the evaluation and treatment of multisystem inflammatory syndrome in children (MIS-C) at hospitals in the US.Study designWe conducted a cross-sectional survey from June 16 to July 16, 2020, of US children's hospitals regarding protocols for management of patients with MIS-C. Elements included characteristics of the hospital, clinical definition of MIS-C, evaluation, treatment, and follow-up. We summarized key findings and compared results from centers in which &gt;5 patients had been treated vs those in which ≤5 patients had been treated.ResultsIn all, 40 centers of varying size and experience with MIS-C participated in this protocol survey. Overall, 21 of 40 centers required only 1&nbsp;day of fever for MIS-C to be considered. In the evaluation of patients, there was often a tiered approach. Intravenous immunoglobulin was the most widely recommended medication to treat MIS-C (98% of centers). Corticosteroids were listed in 93% of protocols primarily for moderate or severe cases. Aspirin was commonly recommended for mild cases, whereas heparin or low molecular weight heparin were to be used primarily in severe cases. In severe cases, anakinra and vasopressors frequently were recommended; 39 of 40 centers recommended follow-up with cardiology. There were similar findings between centers in which &gt;5 patients vs ≤5 patients had been managed. Supplemental materials containing hospital protocols are provided.ConclusionsThere are many similarities yet key differences between hospital protocols for MIS-C. These findings can help healthcare providers learn from others regarding options for managing MIS-C