Kawasaki Disease in the Time of COVID-19 and MIS-C: The International Kawasaki Disease Registry.

BACKGROUND: Patients with multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease (KD) have overlapping clinical features. We compared demographics, clinical presentation, management, and outcomes of patients according to evidence of previous SARS-CoV-2 infection. METHODS: The International Kawasaki Disease Registry (IKDR) enrolled KD and MIS-C patients from sites in North, Central, and South America, Europe, Asia, and the Middle East. Evidence of previous infection was defined as: Positive (household contact or positive polymerase chain reaction [PCR]/serology), Possible (suggestive clinical features of MIS-C and/or KD with negative PCR or serology but not both), Negative (negative PCR and serology and no known exposure), and Unknown (incomplete testing and no known exposure). RESULTS: Of 2345 enrolled patients SARS-CoV-2 status was Positive for 1541 (66%) patients, Possible for 89 (4%), Negative for 404 (17%) and Unknown for 311 (13%). Clinical outcomes varied significantly among the groups, with more patients in the Positive/Possible groups presenting with shock, having admission to intensive care, receiving inotropic support, and having longer hospital stays. Regarding cardiac abnormalities, patients in the Positive/Possible groups had a higher prevalence of left ventricular dysfunction, and patients in the Negative and Unknown groups had more severe coronary artery abnormalities. CONCLUSIONS: There appears to be a spectrum of clinical features from MIS-C to KD with a great deal of heterogeneity, and one primary differentiating factor is evidence for previous acute SARS-CoV-2 infection/exposure. SARS-CoV-2 Positive/Possible patients had more severe presentations and required more intensive management, with a greater likelihood of ventricular dysfunction but less severe coronary artery adverse outcomes, in keeping with MIS-C.

Obesity and Outcomes of Kawasaki Disease and COVID-19-Related Multisystem Inflammatory Syndrome in Children.

Importance: Obesity may affect the clinical course of Kawasaki disease (KD) in children and multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19. Objective: To compare the prevalence of obesity and associations with clinical outcomes in patients with KD or MIS-C. Design, Setting, and Participants: In this cohort study, analysis of International Kawasaki Disease Registry (IKDR) data on contemporaneous patients was conducted between January 1, 2020, and July 31, 2022 (42 sites, 8 countries). Patients with MIS-C (defined by Centers for Disease Control and Prevention criteria) and patients with KD (defined by American Heart Association criteria) were included. Patients with KD who had evidence of a recent COVID-19 infection or missing or unknown COVID-19 status were excluded. Main Outcomes and Measures: Patient demographic characteristics, clinical features, disease course, and outcome variables were collected from the IKDR data set. Using body mass index (BMI)/weight z score percentile equivalents, patient weight was categorized as normal weight (BMI <85th percentile), overweight (BMI ≥85th to <95th percentile), and obese (BMI ≥95th percentile). The association between adiposity category and clinical features and outcomes was determined separately for KD and MIS-C patient groups. Results: Of 1767 children, 338 with KD (median age, 2.5 [IQR, 1.2-5.0] years; 60.4% male) and 1429 with MIS-C (median age, 8.7 [IQR, 5.3-12.4] years; 61.4% male) were contemporaneously included in the study. For patients with MIS-C vs KD, the prevalence of overweight (17.1% vs 11.5%) and obesity (23.7% vs 11.5%) was significantly higher (P < .001), with significantly higher adiposity z scores, even after adjustment for age, sex, and race and ethnicity. For patients with KD, apart from intensive care unit admission rate, adiposity category was not associated with laboratory test features or outcomes. For patients with MIS-C, higher adiposity category was associated with worse laboratory test values and outcomes, including a greater likelihood of shock, intensive care unit admission and inotrope requirement, and increased inflammatory markers, creatinine levels, and alanine aminotransferase levels. Adiposity category was not associated with coronary artery abnormalities for either MIS-C or KD. Conclusions and Relevance: In this international cohort study, obesity was more prevalent for patients with MIS-C vs KD, and associated with more severe presentation, laboratory test features, and outcomes. These findings suggest that obesity as a comorbid factor should be considered at the clinical presentation in children with MIS-C.

Cardiac Biomarkers Aid in Differentiation of Kawasaki Disease from Multisystem Inflammatory Syndrome in Children Associated with COVID-19.

Kawasaki disease (KD) and Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 show clinical overlap and both lack definitive diagnostic testing, making differentiation challenging. We sought to determine how cardiac biomarkers might differentiate KD from MIS-C. The International Kawasaki Disease Registry enrolled contemporaneous KD and MIS-C pediatric patients from 42 sites from January 2020 through June 2022. The study population included 118 KD patients who met American Heart Association KD criteria and compared them to 946 MIS-C patients who met 2020 Centers for Disease Control and Prevention case definition. All included patients had at least one measurement of amino-terminal prohormone brain natriuretic peptide (NTproBNP) or cardiac troponin I (TnI), and echocardiography. Regression analyses were used to determine associations between cardiac biomarker levels, diagnosis, and cardiac involvement. Higher NTproBNP (≥ 1500 ng/L) and TnI (≥ 20 ng/L) at presentation were associated with MIS-C versus KD with specificity of 77 and 89%, respectively. Higher biomarker levels were associated with shock and intensive care unit admission; higher NTproBNP was associated with longer hospital length of stay. Lower left ventricular ejection fraction, more pronounced for MIS-C, was also associated with higher biomarker levels. Coronary artery involvement was not associated with either biomarker. Higher NTproBNP and TnI levels are suggestive of MIS-C versus KD and may be clinically useful in their differentiation. Consideration might be given to their inclusion in the routine evaluation of both conditions.

ehealth technology in cardiac exercise therapeutics for pediatric patients with congenital and acquired heart conditions: a summary of evidence and future directions.

Many children and adolescents with congenital and acquired heart disease (CHD) are physically inactive and participate in an insufficient amount of moderate-to-vigorous intensity exercise. Although physical activity (PA) and exercise interventions are effective at improving short- and long-term physiological and psychosocial outcomes in youth with CHD, several barriers including resource limitations, financial costs, and knowledge inhibit widespread implementation and dissemination of these beneficial programs. New and developing eHealth, mHealth, and remote monitoring technologies offer a potentially transformative and cost-effective solution to increase access to PA and exercise programs for youth with CHD, yet little has been written on this topic. In this review, a cardiac exercise therapeutics (CET) model is presented as a systematic approach to PA and exercise, with assessment and testing guiding three sequential PA and exercise intervention approaches of progressive intensity and resource requirements: (1) PA and exercise promotion within a clinical setting; (2) unsupervised exercise prescription; and (3) medically supervised fitness training intervention (i.e., cardiac rehabilitation). Using the CET model, the goal of this review is to summarize the current evidence describing the application of novel technologies within CET in populations of children and adolescents with CHD and introduce potential future applications of these technologies with an emphasis on improving equity and access to patients in low-resource settings and underserved communities.

Early preclinical experience of a mixed reality ultrasound system with active GUIDance for NEedle-based interventions: The GUIDE study.

Background: Use of ultrasound (US) to facilitate vascular access has increased compared to landmark-based procedures despite ergonomic challenges and need for extrapolation of 2-dimensional images to understand needle position. The MantUS™ system (Sentiar, Inc.,) uses a mixed reality (MxR) interface to display US images and integrate real-time needle tracking. Objective: The purpose of this prospective preclinical study was to evaluate the feasibility and usability of MantUS in a simulated environment. Methods: Participants were recruited from pediatric cardiology and critical care. Access was obtained in 2 vascular access training models: a femoral access model and a head and neck model for a total of 4 vascular access sites under 2 conditions-conventional US and MantUS. Participants were randomized for order of completion. Videos were obtained, and quality of access including time required, repositions, number of attempts, and angle of approach were quantified. Results: Use of MantUS resulted in an overall reduction in number of needle repositions (P = .03) and improvement in quality of access as measured by distance (P <.0001) and angle of elevation (P = .006). These findings were even more evident in the right femoral vein (RFV) access site, which was a simulated anatomic variant with a deeper more oblique vascular course. Use of MantUS resulted in faster time to access (P = .04), fewer number of both access attempts (P = .02), and number of needle repositions (P <.0001) compared to conventional US. Postparticipant survey showed high levels of usability (87%) and a belief that MantUS may decrease adverse outcomes (73%) and failed access attempts (83%). Conclusion: Use of MantUS improved vascular access among all comers, including the quality of access. This improvement was even more notable in the vascular variant (RFV). MantUS readily benefited users by providing improved spatial understanding. Further development of MantUS will focus on improving user interface and experience, with larger clinical usage and in-human studies.

A Single-center Experience Comparing First- Versus Second-generation Insertable Cardiac Monitors in Pediatric Patients.

Insertable cardiac monitors (ICMs) have undergone advancements in size and functionality over the past decade, resulting in the introduction of small, easily insertable devices capable of long-term remote monitoring. We define first-generation ICMs as implantable cardiac monitoring devices that require an incision and surgical creation of a subcutaneous pocket and second-generation ICMs as devices implanted using a custom-made tool for subcutaneous insertion, respectively. The aim of this study was to understand the differences between first- and second-generation pediatric ICM implants, implant indications, and time to diagnosis. We performed a retrospective, single-center chart review of patients who underwent ICM implantation from 2009-2019, spanning a 5-year course of first-generation ICM implantations and 5-year course of second-generation ICM implantations. Demographic data, past medical history, implant indication, and time to diagnosis were obtained. A total of 208 patients were identified over the 10-year time period, including 38 (18%) who underwent implantation with a first-generation device and 170 (82%) who underwent implantation with a second-generation device. Implant indications for first-generation ICMs included syncope (71%), palpitations (16%), inherited arrhythmia syndrome (IAS) management (5%), and premature ventricular contractions/ventricular tachycardia (VT) (8%); implant indications for second-generation ICMs included syncope (48%), palpitations (19%), IAS management (40%), premature ventricular contractions/VT (11%), atrial fibrillation (2%), tachycardia (3%), and heart block (0.5%). The average time to diagnosis was 38 weeks for patients with first-generation devices and 55 weeks for those with second-generation devices. With innovations in ICM technologies, there are expanding indications for ICM implantation in pediatric patients for long-term monitoring, specifically regarding the management of IAS patients.

EKG Abnormalities in a Youth Athlete Following COVID-19: It's Not Always Myocarditis!

COVID-19 associated myocarditis following mild infections is rare while incidental findings may be more common. A young athlete fully recovered from a mild COVID-19 infection presented with inferolateral T-wave inversions and left ventricular hypertrophy on imaging. Exercise testing aided in correctly diagnosing the patient with masked systolic hypertension.

Single-Centre Case Series Assessment of Early Exercise Capacity Data Among Patients Who Received an Alterra Prestent and SAPIEN 3 Valve Placement.

Previous studies have used cardiopulmonary exercise test (CPET) data to objectively assess physiological changes in patients undergoing percutaneous pulmonary valve implantation. A retrospective review was performed to assess pre- and post-CPET data among patients undergoing Alterra Adaptive Prestent and SAPIEN 3 transcatheter heart valve (Alterra) placement. Of the 7 patients eligible for the study, 5 (71%) were male. The mean age was 22 years (range: 12-49 years). CPET data showed significant (P = 0.03) improvement in ventilatory efficiency (VE/VCO2) while only 2 (29%) patients had an improvement of percent predicted peak oxygen consumption (VO2). These findings suggest favourable haemodynamic changes though further investigation is needed.

Des résultats aux épreuves d'effort cardiorespiratoire ont été utilisés lors d'études antérieures pour mesurer de manière objective les changements physiologiques chez les patients ayant subi l'implantation percutanée d'une valvule pulmonaire. Nous présentons une étude rétrospective des résultats à ces épreuves avant et après l'intervention dans des cas d'implantation transcathéther d'une prothèse Alterra Adaptive Prestent et d'une valve cardiaque SAPIEN 3 (Alterra). Parmi les sept patients admissibles à l'étude, cinq (71 %) étaient de sexe masculin. L'âge moyen des sujets était de 22 ans (plage de 12 à 49 ans). Les résultats obtenus à l'épreuve d'effort cardiorespiratoire ont démontré une amélioration significative (P = 0,03) de l'efficacité respiratoire (VE/VCO2), mais seulement deux patients (29 %) ont présenté une amélioration du pourcentage prévu de la consommation maximale d'oxygène (VO2). Bien que ces observations semblent indiquer des changements hémodynamiques favorables, d'autres études sont nécessaires pour élucider la question.

Incorporation of the CardioMEMS™ System During an Exercise Physiology Test in a Pediatric Congenital Heart Disease Patient Contributing to Medical Decision-Making.

Exercise testing among the pediatric congenital heart disease population continues to transform and expand the way patients are evaluated and managed. We describe a case where a stress echocardiogram was performed while successfully collecting data from a previously implanted CardioMEMS™ HF system which helped guide decision-making.

Assessment of Apple Watch Series 6 pulse oximetry and electrocardiograms in a pediatric population.

BACKGROUND: Recent technologic advances have resulted in increased development and utilization of direct-to-consumer cardiac wearable devices with various functionality. This study aimed to assess Apple Watch Series 6 (AW6) pulse oximetry and electrocardiography (ECG) in a cohort of pediatric patients. METHODS: This single-center, prospective study enrolled pediatric patients ≥ 3kg and having an ECG and/or pulse oximetry (SpO2) as part of their planned evaluation. Exclusion criteria: 1) non-English speaking patients and 2) patients in state custody. Simultaneous tracings were obtained for SpO2 and ECG with concurrent standard pulse oximeter and 12-lead ECG. AW6 automated rhythm interpretations were compared to physician over-read and categorized as accurate, accurate with missed findings, inconclusive (automated interpretation: "inconclusive"), or inaccurate. RESULTS: A total of 84 patients were enrolled over a 5-week period. 68 patients (81%) were placed into the SpO2 and ECG arm, with 16 patients (19%) placed into the SpO2 only arm. Pulse oximetry data was successfully collected in 71/84 (85%) patients and ECG data in 61/68 (90%). ΔSpO2 between modalities was 2.0±2.6% (r = 0.76). ΔRR was 43±44msec (r = 0.96), ΔPR 19±23msec (r = 0.79), ΔQRS 12±13msec (r = 0.78), and ΔQT 20±19msec (r = 0.9). The AW6 automated rhythm analysis yielded a 75% specificity and found: 1) 40/61 (65.6%) "accurate", 2) 6/61 (9.8%) "accurate with missed findings", 3) 14/61 (23%) "inconclusive", and 4) 1/61 (1.6%) incorrect. CONCLUSION: The AW6 can accurately measure oxygen saturation when compared to hospital pulse oximeters in pediatric patients and provide good quality single lead ECGs that allow for accurate measurement of RR, PR, QRS, and QT intervals with manual interpretation. The AW6-automated rhythm interpretation algorithm has limitations for smaller pediatric patients and patients with abnormal ECGs.

A unique cardiovascular presentation of pheochromocytoma.

We describe a unique presentation of a pheochromocytoma in a normotensive teenager, who presented with symptoms of headache, neck pain, and palpitations. Holter and event monitor tracings revealed intermittent junctional rhythm causing electromechanical dyssynchrony between atrial and ventricular contraction resulting in reported symptoms. Exercise stress testing helped correlate symptomatic junctional rhythm events to episodic hypertension which led to the eventual diagnosis of pheochromocytoma. The exercise test provided insight into the physiologic coupling that the sympathetic and parasympathetic autonomic nervous systems have on the cardiovascular system during exercise and exaggerated hypertension. The patient was found to have MEN2A and partial adrenalectomy resulted in complete resolution of symptoms and arrhythmia. This unusual presentation illustrates the benefit of a comprehensive clinical evaluation, which led to the eventual diagnosis.

Delayed Development of Coronary Artery Dilitation in Suspected Severe Acute Respiratory Syndrome Coronavirus 2 Multisystem Inflammatory Syndrome: More Research Needed.

Although significant disease burden in the severe acute respiratory syndrome coronavirus 2 pandemic has been relatively uncommon in children, worldwide cases of a postinfectious multisystem inflammatory syndrome in children and possible atypical Kawasaki-like disease attributing to severe acute respiratory syndrome coronavirus 2 infection have arisen. Original thinking for coronavirus disease-19 disease was that an overwhelming proinflammatory response drove disease pathogenesis. Emerging reports suggest that a robust immune suppression may be more relevant and predominant. Recently reported data on children with multisystem inflammatory syndrome in children have demonstrated a heterogeneity of immune phenotypes among these patients, with concern for a strong initial proinflammatory state; however, data are lacking to support this. Likewise, understanding development of certain clinical findings to changes in the immune system is lacking. CASE SUMMARY: We report a 12-year-old multiracial male with negative coronavirus disease-19 nasopharyngeal RNA polymerase chain reaction testing but positive severe acute respiratory syndrome coronavirus 2 serology, subsequent development of vasodilatory shock with myocardial depression, and subsequent delayed development of coronary artery dilatation after resolution of myocardial depression. Unlike previous reported cases of multisystem inflammatory syndrome in children, he exhibited profound lymphopenia without specific inflammatory cytokines elevations, whereas nonspecific markers (ferritin and C-reactive protein) were increased. He subsequently was discharged on day 12 of hospitalization with complete recovery. CONCLUSION: Our representative case of a patient with coronavirus disease-19-associated multisystem inflammatory syndrome in children without robust hyperinflammation and a delayed finding of coronary artery dilatation compared with reported case series highlights the need for further mechanistic understanding of coronavirus disease-19 disease and subsequent multisystem inflammatory syndrome in children or Kawasaki disease development. This report offers a number of disease mechanisms and clinical evolution considerations for further elucidation to guide development of potential therapies.

Institutional experience of healthy pediatric patients presenting with atrial fibrillation who had an electrophysiology study.

INTRODUCTION: Atrial fibrillation (AF) is a very common tachyarrhythmia with increasing prevalence with age, but uncommon in the pediatric population. Understanding that AF increases comorbidities make the need for investigation and potential elimination of alternate etiologies in pediatric AF patients critical. The objective of this study was to review our institutional data and compare our findings with previously documented adult AF risk factors to pediatric patients while also identifying which patients had alternate electrophysiology diagnoses amenable to transcatheter ablation. METHODS: A retrospective chart review was performed identifying AF patients who were less than 21 years old, had no significant congenital cardiovascular anomalies, a documented episode of AF on electrocardiogram and underwent invasive electrophysiology study (EPS). RESULTS: Nineteen patients were identified over a 9-year period of time finding a male predominance (74%), the average age of 14.95 ± 4.17 years, the average weight of 78.5 ± 31.4 kg, and average body mass index of 26.8 ± 6.87 kg/m2 . Preprocedural left atrial volumes made on echocardiograms demonstrated a mean of 33.96 ± 16.35 mL/m2 (Z-scores -0.81 ± 1.50), indicating no dilation. Five of nineteen patients (26%) had additional electrophysiologic diagnoses during EPS, including atrioventricular reentrant tachycardia (n = 2, 10%) and atrioventricular nodal reentrant tachycardia (n = 3, 16%). Four patients underwent successful ablation with no documented or clinical AF recurrence. CONCLUSIONS: Adult risk factors of male predominance and obesity were seen in pediatric AF patients, while left atrial enlargement was not. Twenty-one percent of the pediatric AF patients who had additional electrophysiologic substrates and successful ablations resulted in no further clinical episodes of AF. This suggests that pediatric patients presenting with AF might benefit from an EPS as part of a complete evaluation.

Recanalization of an atretic intramural left main coronary artery after bypass surgery in a pediatric patient with anomalous aortic origin of the left main coronary artery arising from the right sinus of Valsalva.

We report a pediatric patient with nonatherosclerotic chronic total occlusion (CTO) of the left main coronary artery (LMCA) leading to complete LMCA atresia which was successfully recanalized via retrograde techniques through a previous internal mammary bypass graft. After the CTO was treated, the artery was found to be anomalous off the right cusp with an intramural coarse and slit-like orifice. The patient's ischemic symptoms resolved after Percutaneous Coronary Intervention (PCI), and she has continued to do well.