Let's get physical: Aerobic capacity, muscle strength, and muscle endurance after pediatric heart transplantation.

BACKGROUND: Pediatric heart (HTx) and kidney transplant (KTx) recipients may have lower physical fitness than healthy children. This study sought to quantify fitness levels in transplant recipients, investigate associations to clinical factors and quality of life, and identify whether a quick, simple wall-sit test is feasible as a surrogate for overall fitness for longitudinal assessment. METHODS: Aerobic capacity (6-min walk test, 6MWT), normalized muscle strength, muscle endurance, physical activity questionnaire (PAQ), and quality of life (PedsQL™) were prospectively assessed in transplanted children and matched healthy controls. RESULTS: Twenty-two HTx were compared to 20 controls and 6 KTx. 6MWT %predicted was shorter in HTx (87.2 [69.9-118.6] %) than controls (99.9 [80.4-120] %), but similar to KTx (90.3 [78.6-115] %). Muscle strength was lower in HTx deltoids (6.15 [4.35-11.3] kg/m2) and KTx quadriceps (9.27 [8.65-19.1] kg/m2) versus controls. Similarly, muscle endurance was lower in HTx push-ups (28.6 [0-250] %predicted), KTx push-ups (8.35 [0-150] %predicted), HTx curl-ups (115 [0-450] %predicted), and KTx wall-sit time (18.5 [10.0-54.0] s) than controls. In contrast to HTx with only 9%, all KTx were receiving steroid therapy. The wall-sit test significantly correlated with other fitness parameters (normalized quadriceps strength R = .31, #push-ups R = .39, and #curl-ups R = .43) and PedsQL™ (R = .36). CONCLUSIONS: Compared to controls, pediatric HTx and KTx have similarly lower aerobic capacity, but different deficits in muscle strength, likely related to steroid therapy in KTx. The convenient wall-sit test correlates with fitness and reported quality of life, and thus could be a useful easy routine for longitudinal assessment.

Myocarditis and Pericarditis Following mRNA COVID-19 Vaccination: 2024 Status and Management Update.

In 2021, the Canadian Journal of Cardiology published a "Practical Clinical Practice Update" to address emerging concerns about myocarditis and pericarditis following mRNA COVID-19 vaccines.1 Since publication, researchers have underscored the importance of standardizing diagnostic criteria and evaluation of incident cases. In this brief review, we summarize new evidence about the epidemiology and outcomes of patients with mRNA COVID-19 post-vaccine myocarditis and pericarditis. We also provide consensus guidance for evaluation, management, and follow-up. Finally, we identify persistent knowledge gaps that inform the National Active Surveillance Study of Myocarditis and/or Pericarditis following mRNA COVID-19 Vaccination (MYCOVACC) and areas for future research.

Unique Aspects of Hypertrophic Cardiomyopathy in Children.

Hypertrophic cardiomyopathy (HCM) is a primary heart muscle disease characterized by left ventricular hypertrophy that can be asymptomatic or with presentations that vary from left ventricular outflow tract obstruction, heart failure from diastolic dysfunction, arrhythmias, and/or sudden cardiac death. Children younger than 1 year of age tend to have worse outcomes and often have HCM secondary to inborn errors of metabolism or syndromes such as RASopathies. For children who survive or are diagnosed after 1 year of age, HCM outcomes are often favourable and similar to those seen in adults. This is because of sudden cardiac death risk stratification and medical and surgical innovations. Genetic testing and timely cardiac screening are paving the way for disease-modifying treatment as gene-specific therapies are being developed.

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.

Assessing Donor-Recipient Size Mismatch in Pediatric Heart Transplantation: Lessons Learned From Over 7,500 Transplants.

BACKGROUND: To date, no studies have identified an optimal metric to match donor-recipient (D-R) pairs in pediatric heart transplantation (HT). OBJECTIVES: This study sought to identify size mismatch metrics that predicted graft survival post-HT. METHODS: D-R pairs undergoing HT in Pediatric Heart Transplant Society database from 1993 to 2021 were included. Effects of size mismatch by height, weight, body mass index, body surface area, predicted heart mass, and total cardiac volume (TCV) on 1- and 5-year graft survival and morbidity outcomes (rejection and cardiac allograft vasculopathy) were evaluated. Cox models with stepwise selection identified size metrics that independently predicted graft survival. RESULTS: Of 7,715 D-R pairs, 36.0% were well matched (D-R ratio: -20% to +20%) by weight, 39.0% by predicted heart mass, 50.0% by body surface area, 57.0% by body mass index, 71.0% by height, and 93.0% by TCV. Of all size metrics, only D-R mismatch by height and TCV predicted graft survival at 1 and 5 years. Effects of D-R size mismatch on graft survival were nonlinear. At both 1 and 5 years post-HT, D-R undersizing and oversizing by height led to increased graft loss, with graft loss observed more frequently with undersizing. Moderately undersized donors by height (D-R ratio: <-30%) frequently experienced rejection post-HT (P < 0.001). Assessing D-R size matching by TCV, minimal donor undersizing was protective, while oversizing up to 25% was not associated with increased graft loss. CONCLUSIONS: In pediatric HT, D-R appear most optimally matched using TCV. Only D-R size mismatch by TCV and height independently predicts graft survival. Standardizing size matching across centers may reduce donor discard.

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.

Uncertain benefit of statins in pediatric heart transplant recipients: A PHTS analysis.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is a leading cause of graft failure in pediatric heart transplant recipients (HTRs). Early statin use has been shown to reduce CAV incidence and all-cause mortality in adult HTRs. We sought to evaluate the contemporary prevalence and trends of statin use in pediatric HTRs and the association between statin use with CAV development and graft failure. METHODS: Patients aged <17 years at the time of primary heart transplant who survived to ≥3 years without CAV were identified from the Pediatric Heart Transplant Society database (2001-2018). Statin use in the first 3 years posttransplant was defined as consecutive, intermediate, or absent. Kaplan-Meier survival, multivariable modeling, and propensity score-matched analyses evaluated associations between statin use and CAV incidence and graft survival, with subanalyses performed on subjects aged ≥10 years at transplant. RESULTS: Among 3,485 (of which 1,086 aged ≥10 years) HTRs, 584 (17%) received consecutive statin therapy, 647 (19%) received intermediate use, and 2,254 (65%) received no statin therapy. Statin use varied widely between sites, with increasing use in the ≥10-year-old cohort over time. By multivariate analysis, statin use was not associated with graft loss. Consecutive statin use was also not associated with graft survival or freedom from CAV development when compared to absent statin use in unmatched or propensity-matched analyses. CONCLUSIONS: While statins remain commonly utilized in pediatric HTRs, early consecutive statin therapy did not decrease CAV incidence or graft loss. The differing effects of statins on CAV development and progression in pediatric vs adult HTRs suggest differing risk and mediating factors and require further study.

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.

Evaluating a Telemedicine Video Game-Linked High-Intensity Interval Training Exercise Programme in Paediatric Heart Transplant Recipients.

Paediatric heart transplant recipients (HTRs) have reduced exercise capacity, physical activity (PA), health-related quality of life (HRQoL), and self-efficacy towards PA. Exercise interventions have demonstrated improvements in exercise capacity and functional status in adult HTRs, with a specific emerging interest in the role of high-intensity interval training (HIIT). Studies of exercise interventions in paediatric HTRs have been limited and nonrandomized to date. HIIT has not yet been evaluated in paediatric HTRs. We thus seek to evaluate the safety and feasibility of a randomized crossover trial of a 12-week, home-based, video game-linked HIIT intervention using a cycle ergometer with telemedicine and remote physiological monitoring capabilities (MedBIKE) in paediatric HTRs. The secondary objective is to evaluate the impact of the intervention on (1) exercise capacity, (2) PA, (3) HRQoL and self-efficacy towards PA, and (4) sustained changes in secondary outcomes at 6 and 12 months after intervention. After a baseline assessment of the secondary outcomes, participants will be randomized to receive the MedBIKE intervention (12 weeks, 36 sessions) or usual care. After the intervention and a repeated assessment, all participants will cross over. Follow-up assessments will be administered at 6 and 12 months after the MedBIKE intervention. We anticipate that the MedBIKE intervention will be feasible and safely yield sustained improvements in exercise capacity, PA, HRQoL, and self-efficacy towards PA in paediatric HTRs. This study will serve as the foundation for a larger, multicentre randomized crossover trial and will help inform exercise rehabilitation programmes for paediatric HTRs.

La tolérance à l'effort, le niveau d'activité physique (AP), le score de la qualité de vie liée à la santé (QVLS) ainsi que l'auto-efficacité à la pratique d'une AP se trouvent diminués chez les patients pédiatriques ayant reçu une transplantation cardiaque. Il a été montré que les exercices physiques permettent d'améliorer la tolérance à l'effort ainsi que le statut fonctionnel chez les patients adultes ayant reçu une transplantation cardiaque. D'ailleurs, le rôle de l'entraînement par intervalles de haute intensité (EIHI) suscite depuis peu un nouvel intérêt à cet égard. Les études réalisées à ce jour sur les programmes d'activité physique chez les patients pédiatriques ayant reçu une transplantation cardiaque sont toutefois peu nombreuses et ne reposent pas sur une répartition aléatoire. De plus, l'EIHI n'a pas encore été évalué chez ce groupe de patients. La présente étude a donc pour objectif d'évaluer la faisabilité et l'innocuité d'un essai clinique croisé à répartition aléatoire d'une durée de 12 semaines chez des patients pédiatriques ayant reçu une transplantation cardiaque. Le programme d'activité physique prendra la forme d'un EIHI à la maison au moyen d'un jeu vidéo et d'une bicyclette ergométrique permettant une assistance et une surveillance des données physiologiques à distance (MedBIKE). Les objectifs secondaires de l'étude consistent à évaluer les effets du programme sur : 1) la tolérance à l'effort; 2) le niveau d'AP; 3) la QVLS ainsi que l'auto-efficacité à la pratique d'une AP; et 4) le maintien des améliorations relatives aux critères d'évaluation se-condaires à 6 et 12 mois. Après une évaluation initiale des critères d'évaluation secondaires, les participants seront répartis aléatoirement dans le groupe suivant le programme à l'aide du vélo MedBIKE (36 séances réparties sur 12 semaines) ou dans le groupe recevant le traitement usuel. Tous les participants changeront ensuite de groupe, et une nouvelle évaluation des critères d'évaluation se-condaires sera effectuée. Les évaluations de suivi auront lieu 6 et 12 mois après la fin du programme. On s'attend à ce que ce dernier soit sûr, facile à suivre et accompagné d'améliorations soutenues de la tolérance à l'effort, du niveau d'AP, de la QVLS et de l'auto-efficacité à la pratique d'une AP chez les patients pédiatriques ayant reçu une transplantation cardiaque. Cette étude servira de modèle à un essai clinique croisé, multicentrique, à répartition aléatoire de plus grande envergure. Elle permettra aussi de générer des renseignements utiles pour les programmes de réadaptation destinés aux patients pédiatriques ayant reçu une transplantation cardiaque.

Incidental Normocalcemic Primary Hyperparathyroidism Presenting With Symptomatic Hypophosphatemia: A Case Report.

Normocalcemic primary hyperparathyroidism (NHPT) is a newly defined variant of primary hyperparathyroidism (PHPT). It's defined by consistently normal total and ionised calcium levels with elevated parathyroid hormone in the absence of secondary causes of hyperparathyroidism in at least three consecutive times over a period of three to six months. Consensus whether the same criteria used to recommend surgery in PHPT should be used to recommend surgery in NHPT is still lacking. Even though PHPT is known to cause hypophosphatemia, serum phosphate is not relevant when diagnosing it or NHPT. No current guideline include any phosphate cutoff level to guide management or indicate surgery in PHPT or NHPT patients. Herein, we present a rare case of incidental NHPT presenting with symptomatic hypophosphatemia and managed surgically.

DNA major versus minor groove occupancy of monomeric and dimeric crystal violet derivatives. Toward structural correlations.

Six monomeric (1a-1f) and five dimeric (2a-2e) derivatives of the triphenylmethane dye crystal violet (CV) have been prepared. Evaluation of the binding of these compounds to CT DNA by competitive fluorescent intercalator displacement (FID) assays, viscosity experiments, and UV and CD spectroscopy suggest that monomeric derivative 1a and dimeric derivative 2d likely associate with the major groove of DNA, while dimeric derivatives 2a and 2e likely associate with the minor groove of DNA. Additional evidence for the groove occupancy assignments of these derivatives was obtained from ITC experiments and from differential inhibition of DNA cleavage by the major groove binding restriction enzyme BamHI, as revealed by agarose gel electrophoresis. The data indicate that major groove ligands may be optimally constructed from dye units containing a sterically bulky 3,5-dimethyl-N,N-dimethylaniline group; furthermore, the groove-selectivity of olefin-tethered dimer 2d suggests that stereoelectronic interactions (n â†’ π*) between the ligand and DNA are also an important design consideration in the crafting of major-groove binding ligands.

Participant Perceptions of Augmented Reality Simulation for Cardiac Anesthesiology Training: A Prospective, Mixed-Methods Study.

Background: Simulations are a critical component of anesthesia education, and ways to broaden their delivery and accessibility should be studied. The primary aim was to characterize anesthesiology resident, fellow, and faculty experience with augmented reality (AR) simulations. The secondary aim was to explore the feasibility of quantifying performance using integrated eye-tracking technology. Methods: This was a prospective, mixed-methods study using qualitative thematic analysis of user feedback and quantitative analysis of gaze patterns. The study was conducted at a large academic medical center in Northern California. Participants included 7 anesthesiology residents, 6 cardiac anesthesiology fellows, and 5 cardiac anesthesiology attendings. Each subject participated in an AR simulation involving resuscitation of a patient with pericardial tamponade. Postsimulation interviews elicited user feedback, and eye-tracking data were analyzed for gaze duration and latency. Results: Thematic analysis revealed 5 domains of user experience: global assessment, spectrum of immersion, comparative assessment, operational potential, and human-technology interface. Participants reported a positive learning experience and cited AR technology's portability, flexibility, and cost-efficiency as qualities that may expand access to simulation training. Exploratory analyses of gaze patterns suggested that trainees had increased gaze duration of vital signs and gaze latency of malignant arrythmias compared with attendings. Limitations of the study include lack of a control group and underpowered statistical analyses of gaze data. Conclusions: This study suggests positive user perception of AR as a novel modality for medical simulation training. AR technology may increase exposure to simulation education and offer eye-tracking analyses of learner performance.

Evaluating the prevalence of lipid assessments in children in Alberta, Canada.

BACKGROUND: Familial hypercholesterolemia is a common, inherited, life-threatening and treatable condition that is characterized by marked elevations of low-density lipoprotein cholesterol (LDL-C), resulting in a high risk of cardiovascular disease, but treatment starting in childhood dramatically reduces this risk. We sought to evaluate the prevalence of pediatric lipid assessments among children in Alberta. METHODS: We reviewed laboratory and administrative data from Alberta Health between Apr. 1, 2012, and Dec. 31, 2021. We evaluated 2 pediatric cohorts (children aged 2-10 yr and children aged 9-17 yr) to allow for longitudinal assessments throughout the pediatric period. We also reviewed annual frequencies of lipid assessment for all children between 2013 and 2021. RESULTS: Pediatric lipid assessments were performed for 1972 (4.3%) of 46 170 children aged 2-10 years and for 8158 (19.9%) of 40 926 children aged 9-17 years. Female children (aged 2-10 yr) and those living in rural communities were significantly less likely to have a lipid assessment, compared with male children and those in nonrural communities. Among those with lipid assessments, 23 (1.2%) and 86 (1.1%) children aged 2-10 years and 9-17 years, respectively, had an LDL-C level suggestive of probable familial hypercholesterolemia (≥ 4.0 mmol/L). Statin therapy was prescribed in 16 children during the study period. The frequency of lipid assessments was relatively stable, with the exception of a decrease in 2020. INTERPRETATION: Rates of pediatric lipid assessment in Alberta are suboptimal. These findings highlight the need to increase awareness of the benefits of early diagnosis and treatment of familial hypercholesterolemia with regard to long-term health and identify and overcome barriers to diagnosis and treatment.

Exploring the Promise of Telemedicine Exercise Interventions in Children and Adolescents With Congenital Heart Disease.

Youth with congenital heart disease (CHD) have reduced exercise capacity via various physical and psychosocial mechanisms. In addition to limited physiologic exercise capacity, these patients experience lower levels of physical activity, physical activity self-efficacy, health-related quality of life, and endothelial function. The study of exercise interventions and cardiac rehabilitation programs in pediatric CHD populations remains limited, particularly home-based interventions that incorporate real-time physiologic monitoring. Home-based interventions provide improved access and convenience to patients. This is principally important for patients from geographically disperse regions who receive their care at centralized subspecialty centres, as is the case for Canadian pediatric cardiac care. These programs, however, have traditionally not permitted the supervision of safety, technique, and adherence that are afforded by hospital/facility-based programs. As such, telemedicine is an important evolving area that combines the benefits of traditional home and facility-based cardiac rehabilitation. An additional key area lacking study surrounds the types of exercise interventions in youth with CHD. To date, interventions have often centred around moderate-intensity continuous exercise. High-intensity interval training might offer superior cardiorespiratory advantages but remains understudied in the CHD population. In this review, we highlight the existing evidence basis for exercise interventions in youth with CHD, explore the promise of incorporating telemedicine home-based solutions, and highlight key knowledge gaps. To address identified knowledge gaps, we are undertaking a 12-week randomized crossover trial of a home-based telemedicine high-intensity interval training intervention in youth with repaired moderate-severe CHD using a video game-linked cycle ergometer (known as the MedBIKE; https://spaces.facsci.ualberta.ca/ahci/projects/medical-projects/remote-rehab-bike-projects).

Toward a Roadmap for Best Practices in Pediatric Preventive Cardiology: A Science Advisory From the American Heart Association.

Cardiovascular disease risk factors are highly prevalent among youth in the United States and Canada. Pediatric preventive cardiology programs have independently developed and proliferated to address cardiovascular risk factors in youth, but there is a general lack of clarity on best practices to optimize and sustain desired outcomes. We conducted surveys of pediatric cardiology division directors and pediatric preventive cardiology clinicians across the United States and Canada to describe the current landscape and perspectives on future directions for the field. We summarize the data and conclude with a call to action for various audiences who seek to improve cardiovascular health in youth, reduce the burden of premature cardiovascular disease, and increase healthy longevity. We call on heart centers, hospitals, payers, and policymakers to invest resources in the important work of pediatric preventive cardiology programs. We urge professional societies to advocate for pediatric preventive cardiology and provide opportunities for training and cross-pollination across programs. We encourage researchers to close evidence gaps. Last, we invite pediatric preventive cardiology clinicians to collaborate and innovate to advance the practice of pediatric preventive cardiology.

Prospective examination of HLA sensitization after VAD implantation in children and adults.

BACKGROUND: Ventricular assist devices (VADs) have improved survival to heart transplantation (HTx). However, VADs have been associated with development of antibodies against human leukocyte antigen (HLA-Ab) which may limit the donor pool and decrease survival post-HTx. Since HLA-Ab development after VAD insertion is poorly understood, the purpose of this prospective single-center study was to quantify the incidence of and evaluate risk factors for HLA-Ab development across the age spectrum following VAD implantation. METHODS: Adult and pediatric patients undergoing VAD placement as bridge to transplant or transplant candidacy between 5/2016 and 7/2020 were enrolled. HLA-Ab were assessed pre-VAD and at 1-, 3-, and 12-months post-implant. Factors associated with HLA-Ab development post-VAD implant were explored using univariate and multivariate logistic regression. RESULTS: 15/41 (37%) adults and 7/17 (41%) children developed new HLA-Ab post-VAD. The majority of patients (19/22) developed HLA-Ab within two months of implant. New class I HLA-Ab were more common (87% adult, 86% pediatric). Prior pregnancy was strongly associated with HLA-Ab development in adults post-VAD (HR 16.7, 95% CI 1.8-158, p = 0.01). Of the patients who developed new HLA-Ab post-VAD, in 45% (10/22) the HLA-Ab resolved while in 55% (12/22) the HLA-Ab persisted. CONCLUSION: More than one-third of adult and pediatric VAD patients developed new HLA-Ab early after VAD implant with the majority having class I antibodies. Prior pregnancy was strongly associated with post-VAD HLA-Ab development. Further studies are needed to predict regression or persistence of HLA-Ab developed post-VAD, to understand modulation of individuals' immune responses to sensitizing events, and to determine whether transiently detected HLA-Ab post-VAD recur and have long-term clinical impact post-heart transplantation.

COVID-19 Positive Versus Negative Complete Kawasaki Disease: A Study from the International Kawasaki Disease Registry.

To determine clinical differences for children with complete Kawasaki disease (KD) with and without evidence of preceding SARS-CoV-2 infection. From January 2020, contemporaneous patients with complete KD criteria were classified as either SARS-CoV-2 positive (KDCOVID+; confirmed household exposure, positive PCR and/or serology) or SARS-CoV-2 negative (KDCOVID-; negative testing and no exposure) and compared. Of 744 patients in the International Kawasaki Disease Registry, 52 were KDCOVID- and 61 were KDCOVID+. KDCOVID+ patients were older (median 5.5 vs. 3.7 years; p < 0.001), and all additionally met diagnostic criteria for multisystem inflammatory syndrome in children (MIS-C). They were more likely to have abdominal pain (60% vs. 35%; p = 0.008) and headache (38% vs. 10%; p < 0.001) and had significantly higher CRP, troponin, and BUN/creatinine, and lower hemoglobin, platelets, and lymphocytes. KDCOVID+ patients were more likely to have shock (41% vs. 6%; p < 0.001), ICU admission (62% vs. 10%; p < 0.001), lower left ventricular ejection fraction (mean lowest LVEF 53% vs. 60%; p < 0.001), and to have received inotropic support (60% vs. 10%; p < 0.001). Both groups received IVIG (2 doses in 22% vs. 18%; p = 0.63), but KDCOVID+ were more likely to have received steroids (85% vs. 35%; p < 0.001) and anakinra (60% vs. 10%; p = 0.002). KDCOVID- patients were more likely to have medium/large coronary artery aneurysms (CAA, 12% vs. 0%; p = 0.01). KDCOVID+ patients differ from KDCOVID-, have more severe disease, and greater evidence of myocardial involvement and cardiovascular dysfunction rather than CAA. These patients may be a distinct KD phenotype in the presence of a prevalent specific trigger.

Successful ABO incompatible heart transplantation after desensitization therapy in an older child.

BACKGROUND: ABO-incompatible heart transplantation (HTx) has become a standard procedure for children below 2 years of age due to an immunologically immature immune system and associated low isohemagglutinin titers. METHODS: We report a case of an ABO-incompatible HTx (recipient blood group O, donor blood group A) at the age of 5 years and 11 months with a fully matured immune system and previously high isohemagglutinin titers that diminished as a result of human leucocyte antigen (HLA) desensitization therapy with rituximab and immunoglobulins. RESULTS: The anti-A titer at the time of HTx was 1:16 with post-transplant isoagglutinin titers never exceeding 1:4 without any signs of rejection with now 3 years of post-HTx follow-up. CONCLUSIONS: ABO isohemagglutinin titers should be routinely assessed in children undergoing desensitization therapy since ABOi transplantation can be considered in selected cases to expand the donor pool with the option of crossing the ABO barrier to find a better-matched allograft.