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The cardiac effects of novel coronavirus disease 2019 (COVID-19) infection on the pediatric heart has become an area of particular interest as elevated cardiac enzymes and abnormalities on echocardiogram and electrocardiogram were seen in a portion of children affected by the virus. In this article, we review the cardiac manifestations of acute COVID-19 infection, multisystem inflammatory syndrome in children, and postvaccine myocarditis. The limited research on the effects of COVID-19 on neonates and infants is also reported. KEY POINTS: · Cardiac involvement from MIS-C is much higher than the risk of COVID-19 vaccine-induced myocarditis.. · Neonates and infants have overall been less affected by COVID-19 than adults and older children.. · At this point in time, there is limited research on the cardiac effects of COVID-19 in neonates..

Background and objective: Evidence for the treatment of multisystem inflammatory syndrome in children (MIS-C) is lacking. Anakinra, which targets IL-1-mediated inflammation, is reserved for refractory cases of MIS-C; however, its use in the treatment of MIS-C is not clearly established. Patients and Methods: To examine a role for anakinra in MIS-C, we performed a single center prospective observational cohort study of all MIS-C patients diagnosed at our children’s hospital from May 15 to November 15, 2020. Demographics, clinical features, diagnostic testing, and cardiac function parameters were compared between MIS-C patients treated with intravenous immunoglobulin (IVIG) monotherapy and IVIG with anakinra (IVIG+anakinra). Results: Among 46 patients with confirmed MIS-C, 32 (70%) were in the IVIG+anakinra group, of which 9 of these patients (28%) were also given corticosteroids (CS). No patients were treated with anakinra alone. MIS-C patients in the IVIG+anakinra group were enriched in a CV shock phenotype (p=0.02), and those with CV shock were treated with higher doses of anakinra for a longer duration. Furthermore, MIS-C patients in the IVIG+anakinra group exhibited improvements in fever and cardiac function with and without CS. No significant adverse events were observed, and no differences in IL-1β levels were found among MIS-C patients in the IVIG+anakinra group. Conclusions: Anakinra treatment, which was co-administered with IVIG and primarily in patients with severe MIS-C, was associated with improvements in fever and cardiac function, and demonstrated a favorable side-effect profile. These findings suggest a role for adjunctive anakinra in the treatment of MIS-C.

Kawasaki Disease (KD) is still the most common acquired heart disease in children below the age of five years; it has been well described in the developed world; however, data from the Arab world are limited to case reports or single-center case series. In an effort of optimizing KD research in the Arab world, a group of physicians and researchers established the KD Arab Initiative (Kawarabi) in 2021, and published the first survey, which showed disparities in the availability of intravenous immunoglobulin (IVIG); this had prompted Kawarabi to assess the access to care and therapy of KD patients in Arab countries. A 32 structured questions survey was conducted in thirteen Arab countries and addressed KD patients’ access to healthcare in urban and rural settings. The survey results showed that access to care was uniform across large, mid-size cities and rural areas in 7/13 (54%) countries, while in 6/13 (46%) countries, it was in favor of large and mid-size cities over rural areas. The quality of medical services received by children with KD in large cities was rated as excellent in 6/13 or good in 7/13 countries compared to fair in 4/13 or poor in 4/13 countries in rural areas. Availability of IVIG was limited (23%) in mid-size cities and almost impossible (23%) in rural areas. The KD patients in mid-size cities and rural areas have limited access to standard healthcare in the Arab world. This survey laid the foundation for future Kawarabi endeavors to improve the care of children with KD.

Comparing first and second wave MIS-C cohorts at our quaternary pediatric institution, second wave were older, presented more frequently with shortness of breath, higher maximum troponin and N-terminal BNP, and more frequently required advanced respiratory and inotropic support. Despite increased severity in the second cohort, both cohorts had similar rates of coronary artery abnormalities, systolic dysfunction, and length of stay.

Purpose of review We provide the readers with a review of cardiac complications in children with multi-system inflammatory syndrome in children (MIS-C) and its short-term outcomes. Recent findings Recent reports described the acute cardiac manifestations of MIS-C in children and provided a glimpse of the short-term outcomes. Summary Children with MIS-C have been reported to acutely have variable degrees of cardiac findings including abnormal cardiac enzymes, abnormal electrocardiographs, decreased systolic function, coronary artery abnormalities from coronary dilation to giant aneurysms, mitral valve regurgitation, tricuspid valve regurgitation, aortic valve insufficiency, pericardial effusion, diastolic dysfunction, abnormal cardiac strain, and abnormal cardiac MRI. The majority of these abnormalities resolved during short-term follow-up. Further studies are needed to assess if transient or persistent cardiac complications are associated with long-term adverse cardiac events in children with MIS-C. Supplementary information The online version contains supplementary material available at 10.1007/s40124-021-00258-5.

Multisystem inflammatory syndrome in children (MIS-C) is a new illness that evolved during the COVID-19 pandemic with initial reports of severe disease including use of extracorporeal membrane oxygenation and death. Institutions rapidly assembled task forces to develop treatment algorithms. At the national/international levels, collaboratives and associations assembled consensus writing groups to draft guidelines. These guidelines and algorithms were initially based on expert opinion and small case series. Some groups utilized the Delphi approach, and the resultant guidelines often mimicked those for other conditions that resembled MIS-C, like Kawasaki disease (KD). For instance, intravenous immunoglobulin (IVIG), a known effective treatment in KD, was recommended for MIS-C. Early in the pandemic many favored IVIG over steroids as first line therapy. As evidence evolved so did some guidelines which now endorse the dual use of IVIG plus steroids as first line therapy. In contrast, withholding immunotherapy became an option for some MIS-C patients with mild symptoms. Here, we review guidelines and discuss the evidence informing early recommendations, how this has evolved, the role and limitations of expert opinion and observational data, and the importance of leveraging existing research infrastructures, such as the intensive care unit collaborative (Overcoming COVID-19 surveillance registry), and the International KD Registry. Finally, we discuss strategies to rapidly develop, deploy and adapt clinical trials evaluating the treatment of such rare conditions in children, which may include alternatives to conventional clinical trial design. The emergence of MIS-C during the COVID-19 pandemic has highlighted unmet needs regarding research of a new condition.

OBJECTIVE To describe associations between the Child Opportunity Index (COI) and multisystem inflammatory syndrome of childhood (MIS-C) diagnosis among hospitalized children. METHODS We used a retrospective case control study design to examine children ≤21 years hospitalized at a single, tertiary care children’s hospital between March 2020 and June 2021. Our study population included children diagnosed with MIS-C (n = 111) and a control group of children hospitalized for MIS-C evaluation who had an alternative diagnosis (n = 61). Census tract COI was the exposure variable, determined using the patient’s home address mapped to the census tract. Our outcome measure was MIS-C diagnosis. Odds ratios measured associations between COI and MIS-C diagnosis. RESULTS Our study population included 111 children diagnosed with MIS-C and 61 children evaluated but ruled out for MIS-C. The distribution of census tract overall COI differed significantly between children diagnosed with MIS-C compared with children with an alternate diagnosis (P = .03). Children residing in census tracts with very low to low overall COI (2.82, 95% confidence interval [CI]: 1.29–6.17) and very low to low health/environment COI (4.69, 95% CI 2.21–9.97) had significantly higher odds of being diagnosed with MIS-C compared with children living in moderate and high to very high COI census tracts, respectively. CONCLUSION Census tract child opportunity is associated with MIS-C diagnosis among hospitalized children suggesting an important contribution of place-based determinants in the development of MIS-C.

Overweight/obesity, prevalent cardiovascular risk factors in children, can be associated with increased risk of adverse outcomes in children with heart disease. The American College of Cardiology (ACC) developed quality metrics including a BMI metric related to identifying and counseling overweight and obese children presenting to cardiology clinics. This metric was used for a multicenter collaborative learning Quality improvement (QI) Project through the ACC Quality Network (QNet). Our aim was to increase the percentage of children between ages 3 and 18 years presenting to cardiology clinics at participating centers with BMI > 85th percentile who received appropriate counseling. Participating centers submitted data quarterly to QNet for a sample of patients who received counseling. A Key Driver Diagram was created to help teams drive improvement. Individual centers customized interventions and participated in network-wide educational learning sessions about QI and shared experience. Statistical process control charts were used. From 04/01/2017 to 09/30/2019, 27,511 patient visits were included. Among 32 participating centers, overall counseling rate was 54%. The BMI counseling rate increased from 25% in 2017Q2 to 54% in 2019Q3. There was a wide variation from 10 to 100% in the performance of individual centers. The overall rate of identification and counseling of overweight and obese children presenting to ambulatory cardiology clinics in participating centers is low. There is wide variation in the performance of centers, providing an opportunity for improvement. Using this multicenter learning approach, individual centers have demonstrated improvement. This demonstrates that collaborative learning approaches in QI can increase implementation of the metric.

The globalburdenof paediatric and congenital heart disease (PCHD) is substantial. We propose a novel public health framework with recommendations for developing effective and safe PCHD services in low-income and middle-income countries (LMICs). This framework was created by the Global Initiative for Children’s Surgery Cardiac Surgery working group in collaboration with a group of international rexperts in providing paediatric and congenital cardiac care to patients with CHD and rheumatic heart disease (RHD) in LMICs. Effective and safe PCHD care is inaccessible to many, and there is no consensus on the best approaches to provide meaningful access in resource-limited settings, where it is often needed the most. Considering the high inequity in access to care for CHD and RHD, we aimed to create an actionable framework for health practitioners, policy makers and patients that supports treatment and prevention. It was formulated based on rigorous evaluation of available guidelines and standards of care and builds on a consensus process about the competencies needed at each step of the care continuum. We recommend a tier-based framework for PCHD care integrated within existing health systems. Each level of care is expected to meet minimum benchmarks and ensure high-quality and family centred care. We propose that cardiac surgery capabilities should only be developed at the more advanced levels on hospitals that have an established foundation of cardiology and cardiac surgery services, including screening, diagnostics, inpatient and outpatient care, postoperative care and cardiac catheterisation. This approach requires a quality control system and close collaboration between the different levels of care to facilitate the journey and care of every child with heart disease. This effort was designed to guide readers and leaders in taking action, strengthening capacity, evaluating impact, advancing policy and engaging in partnerships to guide facilities providing PCHD care in LMICs.

The 2019 novel coronavirus disease (COVID-19) pandemic produced an abrupt and near shutdown of nonemergent patient care. Children's National Hospital (CNH) mounted a multidisciplinary, coordinated ambulatory response that included supply chain management, human resources, risk management, infection control, and information technology. To ensure patient access, CNH expanded telemedicine and instituted operational innovations for outpatient procedures. While monthly in-person ambulatory subspecialty visits decreased from 25 889 pre-COVID-19 to 4484 at nadir of the COVID-19 pandemic, telemedicine visits increased from 70 to 13 539. Further studies are needed to assess the impact of innovations in health care delivery and operations that the crisis prompted.

Objective To decrease referrals to cardiology of patients ages 7 to 21 years with low-probability cardiac pathology who presented to primary care with chest pain by 50% within 24 months. Study Design A multidisciplinary team designed and implemented an initiative consisting of 1) a decision support tool (DST), 2) educational sessions, 3) routine feedback to improve use of referral criteria, and 4) patient family education. Four pediatric practices, comprising 34 pediatricians and 7 nurse practitioners, were included in this study. We tracked progress via statistical process control charts. Results A total of 421 patients ages 7 to 21 years presented with chest pain to their pediatrician. The utilization of the DST increased from baseline of 16% to 68%. Concurrently, the percentage of low-probability cardiology referrals in pediatric patients ages 7 to 21 years who presented with chest pain decreased from 17% to 5% after our interventions. At a median follow-up time of 0.9 years (interquartile range, 0.3–1.6 years), no patient had a life-threatening cardiac event. Conclusion Our health care improvement initiative to reduce low-probability cardiology referrals for children presenting to primary care practices with chest pain was feasible, effective, and safe.

In the 2017 American Heart Association (AHA) Kawasaki disease (KD) guidelines, risk levels (RLs) for long-term management are defined by both maximal and current coronary artery (CA) dimensions normalized as z-scores. We sought to determine the degree to which current recommended practice differs from past actual practice, highlighting areas for knowledge translation efforts. The International KD Registry (IKDR) included 1651 patients with CA aneurysms (z-score > 2.5) from 1999 to 2016. Patients were classified by AHA RL using maximum CA z-score (RL 3 = small, RL 4 = medium, RL 5 = large/giant) and subcategorized based on decreases over time. Medical management provided was compared to recommendations. Low-dose acetylsalicylic acid (ASA) use ranged from 86 (RL 3.1) to 95% (RL 5.1) for RLs where use was “indicated.” Dual antiplatelet therapy (ASA + clopidogrel) use ranged from 16% for RL 5.2 to 9% for RL 5.4. Recommended anticoagulation (warfarin or low molecular weight heparin) use was 65% for RL 5.1, while 12% were on triple therapy (anticoagulation + dual antiplatelet). Optional statin use ranged from 2 to 8% depending on RL. Optional beta-blocker use was 2–25% for RL 5, and 0–5% for RLs 3 and 4 where it is not recommended. Generally, past practice was consistent with the latest AHA guidelines, taking into account the flexible wording of recommendations based on the limited evidence, as well as unmeasured patient-specific factors. In addition to strengthening the overall evidence base, knowledge translation efforts may be needed to address variation in thromboprophylaxis management.

Background: Statin use for hypercholesterolemia in children is predominantly reported from short-term clinical trials. In this study, we assess the efficacy and safety of statin treatment in clinical pediatric practice. Methods: Records of all patients who began statin treatment at age 6 months from 5 pediatric lipid clinics were reviewed. Information at baseline and from all clinic evaluations after statin initiation was recorded, including lipid measurements, statin drug/dose, safety measures (anthropometry, hepatic enzymes, creatine kinase levels), and symptoms. Lipid changes on statin therapy were assessed from baseline to 6 ± 3 months and from 6 ± 3 months to last follow-up with a mixed-effects model, using piecewise linear splines to describe temporal changes, controlling for repeated measures, sex, and age. Results: There were 289 patients with median low-density lipoprotein cholesterol (LDL-C) of 5.3 mmol/L (interquartile range [IQR]:4.5–6.5) and mean age of 12.4 ± 2.9 years at statin initiation. Median duration of therapy was 2.7 years (IQR: 1.6–4.5) with 95% on statins at last evaluation. There were significant decreases in total cholesterol, LDL-C, and non–high-density lipoprotein cholesterol (non–HDL-C) from baseline to 6 ± 3 months (P < 0.001) and from 6 ±3 months to last follow-up (P < 0.001). Triglycerides and HDL-C were unchanged but the triglyceride to HDL-C ratio decreased significantly by late follow-up. At final evaluation, median LDL-C had decreased to 3.4 mmol/L (IQR:2.8–4.2). No patient had statins discontinued for safety measures or symptoms. Conclusions: In real-world clinical practice, intermediate-term statin treatment is effective and safe in children and adolescents with severe LDL-C elevation. Résumé: Contexte: Les statines sont fréquemment employées pour traiter l’hypercholestérolémie chez les enfants dans le cadre d’essais cliniques de courte durée. Dans l’étude présentée ici, nous évaluons l’efficacité et l’innocuité de l’emploi de statines dans la pratique clinique en pédiatrie. Méthodologie: Nous avons passé en revue les dossiers de tous les patients de cinq cliniques pédiatriques des lipides qui ont commencé à prendre une statine avant l’âge de 18 ans et qui ont poursuivi le traitement pendant plus de six mois. Les valeurs mesurées au départ et à chacune des évaluations cliniques après l’instauration d’un traitement par une statine ont été consignées, notamment la lipidémie, le type et la dose de la statine prescrite, les paramètres d’évaluation de l’innocuité (anthropométrie, enzymes hépatiques, taux de créatine kinase) et les symptômes. La variation de la lipidémie chez les patients recevant une statine a été évaluée sur deux périodes, soit entre le début du traitement et l’évaluation effectuée à 6 ± 3 mois ainsi qu’entre l’évaluation effectuée à 6 ± 3 mois et la dernière évaluation de suivi, à l’aide d’un modèle à effets mixtes et de splines linéaires par morceaux pour décrire les changements temporels, en contrôlant pour les mesures répétées, le sexe et l’âge. Résultats: L’étude portait sur 289 patients ayant un taux de cholestérol des lipoprotéines de basse densité (C-LDL) médian de 5,3 mmol/l (intervalle interquartile [IIQ] : 4,5 à 6,5) et âgés de 12,4 ± 2,9 ans en moyenne au moment de l’instauration du traitement par une statine. La durée médiane du traitement était de 2,7 ans (IIQ : 1,6 à 4,5), 95 % des sujets étant toujours sous statine à la dernière évaluation. Les taux de cholestérol total, de C-LDL et de cholestérol des lipoprotéines non de haute densité (C-non-HDL) avaient diminué de manière significative entre le début du traitement et l’évaluation à 6 ± 3 mois (p < 0,001) et entre l’évaluation à 6 ± 3 mois et la dernière évaluation de suivi (p < 0,001). Les taux des triglycérides et du C-HDL n’avaient pas bougé, mais le rapport triglycérides/C-HDL avait diminué considérablement vers la fin du suivi. À l’évaluation finale, le taux de C-LDL avait diminué à 3,4 mmol/l (IIQ : 2,8 à 4,2). Aucun patient n’avait abandonné le traitement par une statine en raison de problèmes d’innocuité ou des symptômes. Conclusions: En situation réelle dans la pratique clinique, le traitement à moyen terme par une statine est efficace et sûr chez les enfants et les adolescents présentant une élévation grave du taux de C-LDL.

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 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%). ASA was frequently used among respondents (91%), including anti-inflammatory and/or anti-platelet 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., There is a delayed and often critical presentation of a multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19. Cardiac manifestations can include ventricular dysfunction and/or coronary artery dilation. We surveyed the management approaches of the membership of the International Kawasaki Disease Registry. Management often includes immunomodulatory therapies and thromboprophylaxis with variation in indications across institutions.

Previous reports have identified risk factors associated with development of post-Fontan protein-losing enteropathy. Less is known about the economic impact and resource utilisation required for post-Fontan protein-losing enteropathy in the current era. We conducted a single-centre retrospective study to assess the impact of post-Fontan protein-losing enteropathy on transplant-free survival. We also described resource utilisation and treatment variations among post-Fontan protein-losing enteropathy patients. Children who received care at our centre between 2009 and 2017 after the Fontan surgery were eligible. Initial admissions for the Fontan operative procedure were excluded. Demographics, hospital admissions, resource utilisation, medications and charges were reviewed. Patients were divided into two groups based on the presence of post-Fontan protein-losing enteropathy. Of the 343 patients screened, 147 met the eligibility criteria. Of these, 28 (19%) developed protein-losing enteropathy. After adjusting for follow-up duration, the protein-losing enteropathy group had higher number of encounters (2.15 ± 2.16 versus 1.47 ± 2.56, p 0.002), hospital length of stay (days) (25 ± 51.3 versus 11.4 ± 41.7, p < 0.0001) and total charges (2018US$) (388,489 ± 759,859 versus 202,725 ± 1,076,625, p < 0.0001). Encounters for patients with protein-losing enteropathy utilised more therapies. Among those with protein-losing enteropathy, use of digoxin was associated with slightly decreased odds for mortality and/or transplant (0.95, confidence interval 0.90–0.99, p 0.021). The 10-year transplant-free survival for patients with/without protein-losing enteropathy was 65.7/97.3% (p 0.002), respectively. Post-Fontan protein-losing enteropathy is associated with reduced 10-year transplant-free survival, higher resource utilisation, charges and medication use compared with the non-protein-losing enteropathy group. Practice variation among post-Fontan protein-losing-enteropathy patients is common. Further larger studies are needed to assess the impact of standardisation on the well-being of children with post-Fontan protein-losing enteropathy.

Multisystem inflammatory syndrome in children (MIS-C) is a novel disease that was identified during the COVID-19 pandemic and is characterised by systemic inflammation following SARS-CoV-2 infection. Early detection of MIS-C is a challenge given its clinical similarities to Kawasaki disease and other acute febrile childhood illnesses. We aimed to develop and validate an artificial intelligence algorithm that can distinguish among MIS-C, Kawasaki disease, and other similar febrile illnesses and aid in the diagnosis of patients in the emergency department and acute care setting.In this retrospective model development and validation study, we developed a deep-learning algorithm called KIDMATCH (Kawasaki Disease vs Multisystem Inflammatory Syndrome in Children) using patient age, the five classic clinical Kawasaki disease signs, and 17 laboratory measurements. All features were prospectively collected at the time of initial evaluation from patients diagnosed with Kawasaki disease or other febrile illness between Jan 1, 2009, and Dec 31, 2019, at Rady Children's Hospital in San Diego (CA, USA). For patients with MIS-C, the same data were collected from patients between May 7, 2020, and July 20, 2021, at Rady Children's Hospital, Connecticut Children's Medical Center in Hartford (CT, USA), and Children's Hospital Los Angeles (CA, USA). We trained a two-stage model consisting of feedforward neural networks to distinguish between patients with MIS-C and those without and then those with Kawasaki disease and other febrile illnesses. After internally validating the algorithm using stratified tenfold cross-validation, we incorporated a conformal prediction framework to tag patients with erroneous data or distribution shifts. We finally externally validated KIDMATCH on patients with MIS-C enrolled between April 22, 2020, and July 21, 2021, from Boston Children's Hospital (MA, USA), Children's National Hospital (Washington, DC, USA), and the CHARMS Study Group consortium of 14 US hospitals.1517 patients diagnosed at Rady Children's Hospital between Jan 1, 2009, and June 7, 2021, with MIS-C (n=69), Kawasaki disease (n=775), or other febrile illnesses (n=673) were identified for internal validation, with an additional 16 patients with MIS-C included from Connecticut Children's Medical Center and 50 from Children's Hospital Los Angeles between May 7, 2020, and July 20, 2021. KIDMATCH achieved a median area under the receiver operating characteristic curve during internal validation of 98·8% (IQR 98·0-99·3) in the first stage and 96·0% (95·6-97·2) in the second stage. We externally validated KIDMATCH on 175 patients with MIS-C from Boston Children's Hospital (n=50), Children's National Hospital (n=42), and the CHARMS Study Group consortium of 14 US hospitals (n=83). External validation of KIDMATCH on patients with MIS-C correctly classified 76 of 81 patients (94% accuracy, two rejected by conformal prediction) from 14 hospitals in the CHARMS Study Group consortium, 47 of 49 patients (96% accuracy, one rejected by conformal prediction) from Boston Children's Hospital, and 36 of 40 patients (90% accuracy, two rejected by conformal prediction) from Children's National Hospital.KIDMATCH has the potential to aid front-line clinicians to distinguish between MIS-C, Kawasaki disease, and other similar febrile illnesses to allow prompt treatment and prevent severe complications.US Eunice Kennedy Shriver National Institute of Child Health and Human Development, US National Heart, Lung, and Blood Institute, US Patient-Centered Outcomes Research Institute, US National Library of Medicine, the McCance Foundation, and the Gordon and Marilyn Macklin Foundation.

Studies on Kawasaki disease (KD) in Arab countries are scarce, often providing incomplete data. This along with the benefits of multicenter research collaboratives led to the creation of the KD Arab Initiative [Kawarabi] consortium. An anonymous survey was completed among potential collaborative Arab medical institutions to assess burden of KD in those countries and resources available to physicians. An online 32-item survey was distributed to participating institutions after conducting face validity. One survey per institution was collected. Nineteen physicians from 12 countries completed the survey representing 19 out of 20 institutions (response rate of 95%). Fifteen (79%) institutions referred to the 2017 American Heart Association guidelines when managing a patient with KD. Intravenous immunoglobulin (IVIG) is not readily available at 2 institutions (11%) yet available in the country. In one center (5%), IVIG is imported on-demand. The knowledge and awareness among countries' general population was graded (0 to 10) at median/interquartiles (IQR) 3 (2-5) and at median/IQR 7 (6-8) in the medical community outside their institution. Practice variations in KD management and treatment across Arab countries require solid proactive collaboration. The low awareness and knowledge estimates about KD among the general population contrasted with a high level among the medical community. The Kawarabi collaborative will offer a platform to assess disease burden of KD, among Arab population, decrease practice variation and foster population-based knowledge.

OBJECTIVES: Multisystem inflammatory syndrome in children is a newly defined complication of severe acute respiratory syndrome coronavirus 2 infection that can result in cardiogenic shock in the pediatric population. Early detection of cardiac dysfunction is imperative in directing therapy and identifying patients at highest risk for deterioration. This study compares the strengths of conventional and strain echocardiography in identifying cardiac dysfunction in critically ill children with multisystem inflammatory syndrome in children and their association with ICU therapeutic needs and clinical outcomes. DESIGN: Retrospective, observational cohort study. SETTING: A large, quaternary care PICU. PATIENTS: Sixty-five pediatric patients admitted to the PICU with the diagnosis of multisystem inflammatory syndrome in children from March 2020 to March 2021. INTERVENTIONS: Global longitudinal strain four chamber was measured retrospectively by strain echocardiography and compared with conventional echocardiography. Cardiac dysfunction was defined by left ventricular ejection fraction less than 55% and global longitudinal strain four chamber greater than or equal to -17.2%. Clinical variables examined included cardiac biomarkers, immune therapies, and ICU interventions and outcomes. MEASUREMENTS AND MAIN RESULTS: Twenty-four patients (37%) had abnormal left ventricular ejection fraction and 56 (86%) had abnormal global longitudinal strain four chamber. Between patients with normal and abnormal left ventricular ejection fraction, we failed to identify a difference in cardiac biomarker levels, vasoactive use, respiratory support needs, or ICU length of stay. Global longitudinal strain four chamber was associated with maximum cardiac biomarker levels. Abnormal global longitudinal strain four chamber was associated with greater odds of any vasoactive use (odds ratio, 5.8; 95% CI, 1.3-25.3; z-statistic, 2.3; p = 0.021). The number of days of vasoactive infusion was correlated with global longitudinal strain four chamber (r = 0.400; 95% CI, 2.4-3.9; p < 0.001). Children with abnormal strain had longer ICU length of stay (4.5 d vs 2 d; p = 0.014). CONCLUSIONS: Our findings suggest strain echocardiography can detect abnormalities in cardiac function in multisystem inflammatory syndrome in children patients unrecognized by conventional echocardiography. These abnormalities are associated with increased use of intensive care therapies. Evaluation of these patients with strain echocardiography may better identify those with myocardial dysfunction and need for more intensive therapy.

Although intravenous immunoglobulin (IVIG) is effective therapy for Kawasaki disease, 10-20% of patients have recrudescent fever as a sign of persistent inflammation and require additional treatment. We aimed to compare infliximab with a second infusion of IVIG for treatment of resistant Kawasaki disease.In this multicentre comparative effectiveness trial, patients (aged 4 weeks to 17 years) with IVIG resistant Kawasaki disease and fever at least 36 h after completion of their first IVIG infusion were recruited from 30 hospitals across the USA. Patients were randomly assigned (1:1) to second IVIG (2 g/kg over 8-12 h) or intravenous infliximab (10 mg/kg over 2 h without premedication), by using a randomly permuted block randomisation design with block size of two or four. Patients with fever 24 h to 7 days following completion of first study treatment crossed over to receive the other study treatment. The primary outcome measure was resolution of fever at 24 h after initiation of study treatment with no recurrence of fever attributed to Kawasaki disease within 7 days post-discharge. Secondary outcome measures included duration of fever from enrolment, duration of hospitalisation after randomisation, and changes in markers of inflammation and coronary artery Z score. Efficacy was analysed in participants who received treatment and had available outcome values. Safety was analysed in all randomised patients who did not withdraw consent. This clinical trial is registered with ClinicalTrials.gov, NCT03065244.Between March 1, 2017, and Aug 31, 2020, 105 patients were randomly assigned to treatment and 103 were included in the intention-to-treat population (54 in the infliximab group, 49 in the second IVIG group). Two patients randomised to infliximab did not receive allocated treatment. The primary outcome was met by 40 (77%) of 52 patients in the infliximab group and 25 (51%) of 49 patients in the second IVIG infusion group (odds ratio 0·31, 95% CI 0·13-0·73, p=0·0076). 31 patients with fever beyond 24 h received crossover treatment: nine (17%) in the infliximab group received second IVIG and 22 (45%) in second IVIG group received infliximab (p=0·0024). Three patients randomly assigned to infliximab and two to second IVIG with fever beyond 24h did not receive crossover treatment. Mean fever days from enrolment was 1·5 (SD 1·4) for the infliximab group and 2·5 (2·5) for the second IVIG group (p=0·014). Mean hospital stay was 3·2 days (2·1) for the infliximab group and 4·5 days (2·5) for the second IVIG group (p0·001). There was no difference between treatment groups for markers of inflammation or coronary artery outcome. 24 (44%) of 54 patients in the infliximab group and 33 (67%) of 49 in the second IVIG group had at least one adverse event. A drop in haemoglobin concentration of at least 2g/dL was seen in 19 (33%) of 58 patients who received IVIG as either their first or second study treatment (three of whom required transfusion) and in three (7%) of 43 who received only infliximab (none required transfusion; p=0·0028). Haemolytic anaemia was the only serious adverse events deemed definitely or probably related to study treatment, and was reported in nine (15%) of 58 patients who received IVIG as either their first or second study treatment and none who received infliximab only.Infliximab is a safe, well tolerated, and effective treatment for patients with IVIG resistant Kawasaki disease, and results in shorter duration of fever, reduced need for additional therapy, less severe anaemia, and shorter hospitalisation compared with second IVIG infusion.Patient Centered Outcomes Research Institute.

Background Although intravenous immunoglobulin (IVIG) is effective therapy for Kawasaki disease (KD), the most common cause of acquired heart disease in children, 10–20% of patients are IVIG-resistant and require additional therapy. This group has an increased risk of coronary artery aneurysms (CAA) and there has been no adequately powered, randomized clinical trial in a multi-ethnic population to determine the optimal therapy for IVIG-resistant patients. Objectives The primary outcome is duration of fever in IVIG-resistant patients randomized to treatment with either infliximab or a second IVIG infusion. Secondary outcomes include comparison of inflammatory markers, duration of hospitalization, and coronary artery outcome. An exploratory aim records parent-reported outcomes including signs, symptoms and treatment experience. Methods The KIDCARE trial is a 30-site randomized Phase III comparative effectiveness trial in KD patients with fever ≥36 h after the completion of their first IVIG treatment. Eligible patients will be randomized to receive either a second dose of IVIG (2 g/kg) or infliximab (10 mg/kg). Subjects with persistent or recrudescent fever at 24 h following completion of the first study treatment will cross-over to the other treatment arm. Subjects will exit the study after their first outpatient visit (5–18 days following last study treatment). The parent-reported outcomes, collected daily during hospitalization and at home, will be compared by study arm. Conclusion This trial will contribute to the management of IVIG-resistant patients by establishing the relative efficacy of a second dose of IVIG compared to infliximab and will provide data regarding the patient/parent experience of these treatments.

Background The Pediatric Acute Care Cardiology Collaborative (PAC3 ) was established in 2014 to improve the quality, value, and experience of hospital-based cardiac acute care outside of the intensive care unit. An initial PAC3 project was a comprehensive survey to understand unit structure, practices, and resource utilization across the collaborative. This report aims to describe the previously unknown degree of practice variation across member institutions. Methods A 126-stem question survey was developed with a total of 412 possible response fields across nine domains including demographics, staffing, available resources and therapies, and standard care practices. Five supplemental questions addressed surgical case volume and number of cardiac acute care unit (CACU) admissions. Responses were recorded and stored in Research Electronic Data Capture (REDCap). Results Surveys were completed by 31 out of 34 centers (91%) with minimal incomplete fields. A majority (61%) of centers have a single dedicated CACU, which is contiguous or adjacent to the intensive care unit in 48%. A nurse staffing ratio of 3:1 is most common (71%) and most (84%) centers employed a resource nurse. Centralized wireless rhythm monitoring is used in 84% of centers with 54% staffed continuously. There was significant variation in the use of noninvasive respiratory support, vasoactive infusions, and ventricular assist devices across the collaborative. Approximately half of the surveyed centers had lesion-specific postoperative pathways and approximately two-thirds had protocols for single-ventricle patients. Conclusions The PAC3 hospital survey is the most comprehensive description of systems and care practices unique to CACUs to date. There exists considerable heterogeneity among unit composition and variation in care practices. These variations may allow for identification of best practices and improved quality of care for patients.

To compare clinical and laboratory features of children with Multisystem Inflammatory Syndrome in Children (MIS-C) to those evaluated for MIS-C in the Emergency Department (ED).We conducted a retrospective review of the medical record of encounters with testing for inflammatory markers in an urban, tertiary care Pediatric ED from March 1, 2020 to July 31, 2020. We abstracted demographic information, laboratory values, selected medications and diagnoses. We reviewed the record for clinical presentation for the subset of patients admitted to the hospital for suspected MIS-C. We then used receiver operating curves and logistic regression to evaluate the utility of candidate laboratory values to predict MIS-C status.We identified 32 patients with confirmed MIS-C and 15 admitted and evaluated for MIS-C but without confirmation of SARS CoV-2 infection. We compared these patients to 267 encounters with screening laboratories for MIS-C. Confirmed MIS-C patients had an older median age, higher median fever on presentation and were predominantly of Hispanic and non-Hispanic Black race/ethnicity. All children with MIS-C had a C-reactive protein (CRP)4.5 mg/dL, were more likely to have Brain Natriuretic Peptide400 pg/mL (OR 10.50, 95%CI 4.40-25.04), D-Dimer3 μg/mL (7.51, [3.18-17.73]), and absolute lymphocyte count (ALC)1.5 K/mcL (21.42, [7.19-63.76]). We found CRP4.5 mg/dL and ALC1.5 K/mcL to be 86% sensitive and 91% specific to identify MIS-C among patients screened in our population.We identified that elevated CRP and lymphopenia was 86% sensitive and 91% specific for identification of children with MIS-C.

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 2 conditions.We completed a systematic review of KDSS and performed a meta-analysis comparison between reported KDSS cases and KD controls.A total of 10 case-control series were included in the meta-analysis. Patients with KDSS were older (38.4 ± 30.6 vs 21.9 ± 19.5 months; P0.001) compared with standard KD with equal sex distribution and completeness of clinical diagnostic criteria. KDSS present higher C-reactive protein (59.4 ± 29.2 mg/dL vs 20.8 ± 14.8 mg/dL; P0.001), lower albumin (2.7 ± 0.5 g/dL vs 3.3 ± 0.5 g/dL; P0.01), and lower platelets (255 ± 149 109/L vs 394 ± 132 109/L; P0.001) but only borderline higher white blood cells (P = 0.06). Differences in alanine transaminase, aspartate aminotransferase, and erythrocyte sedimentation rate were nonsignificant. The odds of intravenous immunoglobulin resistance (44.4% vs 9.6%; (P0.001) and the hospital length of stay (10.9 ± 5.8 vs 5.0 ± 3.0 days; P0.001) were higher in KDSS, as were the odds of coronary-artery abnormalities (33.9% vs 8.6%; P0.001).This first meta-analysis on KDSS vs KD represents a basis for future works on KDSS and opens the opportunity for future multicentre 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 and KDSS open new horizons to the understanding of the etiology and pathophysiology related to KDSS.

We performed a retrospective study of cardiology telemedicine visits at a large academic pediatric center between 2016 and 2019 (pre COVID-19). Telemedicine patient visits were matched to data from their previous in-person visits, to evaluate any significant differences in total charge, insurance compensation, patient payment, percent reimbursement and zero reimbursement. Miles were measured between patient's home and the address of previous visit. We found statistically significant differences in mean charges of telemedicine versus in-person visits (2019US$) (172.95 vs 218.27, p=0.0046), patient payment for telemedicine visits versus in-person visits (2019US$) (11.13 vs 62.83, p≤0.001), insurance reimbursement (2019US$) (65.18 vs 110.85, p≤0.001) and insurance reimbursement rate (43% vs 61%, p=0.0029). Rate of zero reimbursement was not different. Mean distance from cardiology clinic was 35 miles. No adverse outcomes were detected. This small retrospective study showed cost reduction and a decrease in travel time for families participating in telemedicine visits. Future work is needed to enhance compensation for telemedicine visits.

Introduction: A novel pediatric disease, MIS-C, has emerged during the COVID -19 pandemic. The majority of cases were reported from European and Northeastern US centers. We present our experience of MIS-C with cardiac findings from a large tertiary pediatric cardiac center. Methods: We conducted a retrospective study of all MIS-C patients evaluated and treated from 03/29/2020 to 6/18/2020 at our center. Demographics, clinical, echo and ECG data were extracted from the echo database and EHR. Abnormal cardiac findings during the acute phase were defined as coronary artery abnormality (CAA), decreased ejection fraction (EF) and rhythm abnormality. CAAs were defined as dilation (z-score of > 2 to ≤ 2.49) or aneurysm (2.5 to < 5) as well as reviewed for qualitative changes. Results: 32 children, 17 (53%) males have been treated for MIS-C. The median (IQR) age was 9 (7 - 13) years. Underlying medical conditions were noted in 9 (28%) patients including 2 with cardiac conditions (one with previous history of atypical Kawasaki Disease (KD) and one with previous history of pericardial effusion s/p pericardial window). Ten (31%) patients had abnormal cardiac findings; 4 had isolated CAA, 3 had combined CAA and low EF and 2 had isolated low EF. One patient had aneurysms in all 3 CA’s, 2 patients had abnormalities in 2 CA’s (LMCA and RCA aneurysms in 1 and LMCA aneurysm and LAD dilation in 1 patient), and 4 patients had single CAA (RCA dilation in 1, LAD aneurysm in 1, and LAD dilation in 2 patients). No patient with CAA had morphologic evidence of saccular or fusiform changes. CAA persisted on subsequent echo in 3 patients and normalized in 3 patients. EF normalized on subsequent echo in 3 patients. One of the patients with isolated low EF was also found to have intermittent high grade atrioventricular (AV) block. The 10 th patient had normal echo but 1st degree AV block, sinus bradycardia, and long QTc. No arrhythmia was noted. No mortality occurred and overall length of stay was 13.6±9 days. Conclusion: Our MIS-C patients had a high rate of cardiac findings in the acute phase which exceeded rates historically observed in the setting of KD. Further long term study is needed to assess if the cardiac abnormalities persist, improve with immune modulation or are associated with major cardiac events.

Objectives:Advanced practice providers (APPs) are being employed at increasing rates in order to meet new in-hospital care demands. Utilising the Paediatric Acute Care Cardiology Collaborative (PAC3) hospital survey, we evaluated variations in staffing models regarding first-line providers and assessed associations with programme volume, acuity of care, and post-operative length of stay (LOS).Study design:The PAC3 hospital survey defined staffing models and resource availability across member institutions. A resource acuity score was derived for each participating acute care cardiology unit. Surgical volume was obtained from The Society of Thoracic Surgeons database. Pearson’s correlation coefficients were used to evaluate the relationship between staffing models and centre volume as well as unit acuity. A previously developed case-mix adjustment model for total post-operative LOS was utilised in a multinomial regression model to evaluate the association of APP patient coverage with observed-to-expected post-operative LOS.Results:Surveys were completed by 31 (91%) PAC3 centres in 2017. Nearly all centres (94%) employ APPs, with a mean of 1.7 (range 0–5) APPs present on weekday rounds. The number of APPs present has a positive correlation with surgical volume (r = 0.49, p < 0.01) and increased acuity (r = 0.39, p = 0.03). In the multivariate model, as coverage by APPs increased from low to moderate or high, there was greater likelihood of having a shorter-than-expected post-operative LOS (p < 0.001).Conclusions:The incorporation of paediatric acute care cardiology APPs is associated with reduced post-operative LOS. Future studies are necessary to understand how APPs impact these patient-specific outcomes.

Overweight/obesity, prevalent cardiovascular risk factors in children, can be associated with increased risk of adverse outcomes in children with heart disease. The American College of Cardiology (ACC) developed quality metrics including a BMI metric related to identifying and counseling overweight and obese children presenting to cardiology clinics. This metric was used for a multicenter collaborative learning Quality improvement (QI) Project through the ACC Quality Network (QNet). Our aim was to increase the percentage of children between ages 3 and 18 years presenting to cardiology clinics at participating centers with BMI 85th percentile who received appropriate counseling. Participating centers submitted data quarterly to QNet for a sample of patients who received counseling. A Key Driver Diagram was created to help teams drive improvement. Individual centers customized interventions and participated in network-wide educational learning sessions about QI and shared experience. Statistical process control charts were used. From 04/01/2017 to 09/30/2019, 27,511 patient visits were included. Among 32 participating centers, overall counseling rate was 54%. The BMI counseling rate increased from 25% in 2017Q2 to 54% in 2019Q3. There was a wide variation from 10 to 100% in the performance of individual centers. The overall rate of identification and counseling of overweight and obese children presenting to ambulatory cardiology clinics in participating centers is low. There is wide variation in the performance of centers, providing an opportunity for improvement. Using this multicenter learning approach, individual centers have demonstrated improvement. This demonstrates that collaborative learning approaches in QI can increase implementation of the metric.

In the 2017 American Heart Association (AHA) Kawasaki disease (KD) guidelines, risk levels (RLs) for long-term management are defined by both maximal and current coronary artery (CA) dimensions normalized as z-scores. We sought to determine the degree to which current recommended practice differs from past actual practice, highlighting areas for knowledge translation efforts. The International KD Registry (IKDR) included 1651 patients with CA aneurysms (z-score 2.5) from 1999 to 2016. Patients were classified by AHA RL using maximum CA z-score (RL 3 = small, RL 4 = medium, RL 5 = large/giant) and subcategorized based on decreases over time. Medical management provided was compared to recommendations. Low-dose acetylsalicylic acid (ASA) use ranged from 86 (RL 3.1) to 95% (RL 5.1) for RLs where use was "indicated." Dual antiplatelet therapy (ASA + clopidogrel) use ranged from 16% for RL 5.2 to 9% for RL 5.4. Recommended anticoagulation (warfarin or low molecular weight heparin) use was 65% for RL 5.1, while 12% were on triple therapy (anticoagulation + dual antiplatelet). Optional statin use ranged from 2 to 8% depending on RL. Optional beta-blocker use was 2-25% for RL 5, and 0-5% for RLs 3 and 4 where it is not recommended. Generally, past practice was consistent with the latest AHA guidelines, taking into account the flexible wording of recommendations based on the limited evidence, as well as unmeasured patient-specific factors. In addition to strengthening the overall evidence base, knowledge translation efforts may be needed to address variation in thromboprophylaxis management.

Since 1967, researches have hunted for an etiology for Kawasaki Disease (KD). Meanwhile, the 2019 Coronavirus Disease (COVID-19) pandemic has produced a strange new illness termed multisystem inflammatory syndrome in children (MIS-C) and raised hopes that a cause for KD may be identified. This current review paper discusses KD and its potential connection to pediatric COVID-19 and MIS-C illness.

The Adult Congenital and Pediatric Cardiology (ACPC) Section of the American College of Cardiology sought to develop quality indicators/metrics for ambulatory pediatric cardiology practice. The objective of this study was to report the creation of metrics for patients with Kawasaki disease. Over a period of 5 months, 12 pediatric cardiologists developed 24 quality metrics based on the most relevant statements, guidelines, and research studies pertaining to Kawasaki disease. Of the 24 metrics, the 8 metrics deemed the most important, feasible, and valid were sent on to the ACPC for consideration. Seven of the 8 metrics were approved using the RAND method by an expert panel. All 7 metrics approved by the ACPC council were accepted by ACPC membership after an “open comments” process. They have been disseminated to the pediatric cardiology community for implementation by the ACPC Quality Network.

Active euthanasia, or mercy killing, describes the act of causing death for beneficent reasons by an active intervention. The Groningen Protocol which includes active euthanasia was introduced in the Netherlands for selected circumstances. In this chapter we discuss all options including euthanasia in the care of children with hypoplastic left heart syndrome. When a newborn child or infant is diagnosed with complex cardiac anatomy that is likely to result in a short and uncomfortable life, physicians and parents are often faced with a daunting dilemma. Should they embark on multiple palliative operations or should they withhold life-sustaining treatment and choose palliative care? This decision is often complicated by its impact on the well-being of parents, siblings, families, and health professionals. Although not currently a possibility in this country, there may be a third option—active euthanasia.

Objective To evaluate practice variation in pharmacologic management in the International Kawasaki Disease Registry (IKDR). Study design Practice variation in intravenous immunoglobulin (IVIG) therapy, anti-inflammatory agents, statins, beta-blockers, antiplatelet therapy, and anticoagulation was described. Results We included 1627 patients from 30 IKDR centers with maximum coronary artery aneurysm (CAA) z scores 2.5-4.99 in 848, 5.0-9.99 in 349, and ≥10.0 (large/giant) in 430 patients. All centers reported IVIG and acetylsalicylic acid (ASA) as primary therapy and use of additional IVIG or steroids as needed. In 23 out of 30 centers, (77%) infliximab was also used; 11 of these 23 centers reported using it in 20% of patients. Nonsteroidal anti-inflammatory agents were used in >10% of patients in only nine centers. Beta-blocker (8.8%, all patients) and abciximab (3.6%, all patients) were mainly prescribed in patients with large/giant CAAs. Statins (2.7%, all patients) were mostly used in one center and only in patients with large/giant CAAs. ASA was the primary antiplatelet modality for 99% of patients, used in all centers. Clopidogrel (18%, all patients) was used in 24 centers, 11 of which used it in >50% of their patients with large/giant CAAs. Conclusions In the IKDR, IVIG and ASA therapy as primary therapy is universal with common use of a second dose of IVIG for persistent fever. There is practice variation among centers for adjunctive therapies and anticoagulation strategies, likely reflecting ongoing knowledge gaps. Randomized controlled trials nested in a high-quality collaborative registry may be an efficient strategy to reduce practice variation.