Abstract Background Viral myocarditis presents a significant burden of disease, particularly among children and young adults. However, clinical guidelines and treatment strategies for pediatric patients are derived from those for adult patients due to a lack of pediatric data. Current animal models of viral myocarditis use adult mice, so conclusions from these models cannot necessarily be extrapolated to the pediatric population. We sought to develop a juvenile mouse model of myocarditis to examine differences between these two distinct clinical populations. Methods Male and female BALB/c 3-4-week-old “juvenile” and 8-week-old “adult” mice were infected intraperitoneally with 10 3 PFU of heart-passaged coxsackievirus B3. Sera was used to evaluate testosterone and estradiol levels. Cardiac histological evaluations included overall inflammation, fibrosis, and specific cell-type infiltration. RNA was extracted from cardiac tissue and evaluated for changes in gene expression of cell-type markers, complement components, and NLRP3 inflammasome components. Results Juvenile mice exhibited more severe inflammation than adult mice but no sex differences in overall inflammation. Juvenile mice demonstrated iancreased infiltration of CD11b+ cells, F4/80+ cells, and CD3+ T-cells vs. adults. Inflammasome genes NLRP3 and caspase-1 were significantly increased in juvenile compared with adult myocarditis. Conclusions This paper is the first to describe a juvenile mouse model of coxsackievirus B3 myocarditis and provides a direct comparison to a translational adulat mouse model. Juvenile mice had greater cardiac inflammation than adults. This model replicates clinical populations and provides a valuable tool to study age as a factor in the pathogenesis of myocarditis.

OBJECTIVES:Minimally invasive cardiac output (CO) monitoring technologies lack validation in the adolescent population. We aimed to test the accuracy and precision of the FloTrac arterial pressure cardiac output (APCO) and ClearSight photoplethysmography cardiac output (PPGCO; Edwards Lifesciences, Irvine, CA) technologies in adolescents undergoing elective cardiac catheterization. DESIGN:Prospective, single-arm, nonrandomized, observational study. SETTING:Cardiac catheterization laboratory at three freestanding pediatric hospitals in the United States. PATIENTS:Adolescent patients 12-18 years of age undergoing surveillance cardiac catheterization after heart transplantation. INTERVENTIONS:Swan-Ganz pulmonary artery catheterization with the intermittent thermodilution CO (iCO) technique was used as the gold standard for CO measurements. APCO was measured using an existing femoral arterial sheath, and PPGCO was measured utilizing a volumetric cuff placed on the finger of the upper extremities. Two sets of simultaneous iCO, APCO, and PPGCO measurements were compared. Bias and level of concordance were assessed using Bland-Altman analysis. MEASUREMENTS AND MAIN RESULTS:Out of the 89 subjects enrolled, 73 underwent measurements and provided a total of 60 sets of measurements for each device. The median age was 16 years (interquartile range [IQR], 14-17 yr) with a median body surface area of 1.6 m2 (IQR, 1.5-1.8 m2). The median averaged intermittent cardiac index was 2.7 L/min/m2 (IQR, 2.3-3.1 L/min/m2). FloTrac APCO mean bias was 0.32 L/min/m2 (IQR, 0.20-0.44 L/min/m2) with a precision of 0.70 L/min/m2 (IQR, 0.58-0.82 L/min/m2). ClearSight PPGCO mean bias was 0.28 L/min/m2 (95% CI, 0.16-0.41 L/min/m2) with a precision of 0.71 L/min/m2 (95% CI, 0.59-0.84 L/min/m2). No serious adverse events were reported related to the devices. CONCLUSIONS:The minimally and noninvasive CO measurements with FloTrac and ClearSight APCO show acceptable bias and precision under standardized elective clinical conditions in an adolescent pediatric population, making them useful tools in the routine clinical management of critically ill children.

Coronary allograft vasculopathy (CAV) is a leading cause of allograft failure in pediatric heart transplant recipients. Percutaneous coronary intervention (PCI) is performed to manage atherosclerotic coronary artery disease. However, there is currently limited data regarding use and long-term benefit of PCI due to the diffuse nature of coronary disease in CAV. We sought to evaluate our experience utilizing PCI for CAV. Patients followed at our center who were transplanted as pediatric patients who developed CAV and subsequently underwent PCI were included. Demographic variables were collected, including pre- and post-transplant, pre- and post-PCI, and follow-up data. Categorical variables are presented as N (%) and continuous variables as median (IQR). Kaplan-Meier survival estimates approximated freedom from retransplantation or death. Our cohort had 17 patients who underwent 21 PCI procedures. Of these, 9 (52.9%) were males, 10 (58.8%) were white, and the median age at transplant was 13.6 years [10.4,16.4]. The median age at CAV detection was 16.2 [13.8,19.1] years, and the median time from transplant to first PCI was 7.7 years [5.5,9.2]. Five patients had congenital heart disease, 12 had cardiomyopathy as indication for transplantation. At last follow-up, 4 patients required a repeat PCI, 3 patients underwent retransplant, and 5 patients died. Kaplan-Meier estimates show freedom from death or retransplantation of 88% at 1 years, 64% at 3 years, and 57% at 5 years after initial PCI. In our cohort with advanced CAV, PCI showed favorable immediate outcomes with freedom from death or retransplant in 57% patients at 5 years.

Pre-transplant psychosocial assessment, in conjunction with medical and surgical evaluation, is a critical component of determining pediatric heart transplant candidacy. Psychosocial factors such as family dynamics, health literacy, mental health, financial stability, and adherence potential are often multidimensional and interdependent, making their assessment both vital and complex. However, few standardized tools exist to guide these evaluations in pediatric heart transplant settings, and even fewer have demonstrated empirical validity or predictive value. To address this gap, the Pediatric Psychosocial Assessment Tool (PPAT) was developed to provide a structured, semi-quantitative framework for evaluating psychosocial risk in pediatric transplant candidates. This study presents initial validation data for the PPAT, based on 189 assessments conducted at a large pediatric heart transplant center. The tool evaluates nine psychosocial domains, assigns risk ratings, and yields a total risk score. Confirmatory factor analysis supported the unidimensional structure of the tool, and internal consistency was strong (α = 0.89). Higher PPAT scores were significantly associated with lower odds of being listed for transplant by the center's multidisciplinary medical review board (MRB), even after accounting for clinical factors. Domain-level findings revealed financial and health literacy issues as commonly identified risk areas. The PPAT holds promise as a valid, reliable, and clinically useful instrument for guiding MRB discussions and targeting interventions to support high-risk families. Future directions include expanding implementation to other centers and integrating the PPAT into digital platforms using artificial intelligence and natural language processing to enhance efficiency, consistency, and patient-centered care.

We present a case of infectious endocarditis in the immediate post-transplant period in a 7-year-old child. On postoperative day 6, an elevation in inflammatory markers was detected, and the echocardiogram revealed a pedunculated mass on the mitral valve. The patient underwent surgical resection on postoperative day 14, followed by a 6-week course of antibiotics. The patient demonstrated complete resolution of endocarditis and, at 5-year follow-up, has excellent allograft function without recurrence of endocarditis.

BACKGROUND We report our comprehensive approach to the management of patients with hypo- plastic left heart syndrome (HLHS) and describe our outcomes in 100 consecutive neonates. METHODS We stratified 100 consecutive neonates (January 1, 2015 to September 1, 2023, inclusive) into 3 pathways. Pathway 1: 77 of 100 (77%) were standard risk and underwent an initial Norwood Stage 1. Pathway 2: 10 of 100 (10%) were high-risk with noncardiac risk factors and underwent an initial Hybrid Stage 1. Pathway 3:13 of 100 (13%) were high-risk with cardiac risk factors: 10 underwent an initial Hybrid Stage 1 + Ventricular Assist Device insertion (HYBRID+VAD), and 3 were supported with prostaglandin as a planned bridge to primary cardiac transplantation. RESULTS The overall 1-year mortality for the entire cohort of 100 patients was 9% (9 of 100). Pathway 1: Operative Mortality in Pathway 1 for the initial Norwood Stage 1 was 2.6% (2 of 77). Of the 75 survivors of Norwood Stage 1, 72 underwent successful Glenn, 2 underwent successful biventricular repair, and 1 underwent successful cardiac transplantation. Pathway 2: Operative Mortality in Pathway 2 for the initial Hybrid Stage 1 without VAD was 10% (1 of 10). Of 9 survivors of Hybrid Stage 1, 4 underwent successful cardiac transplantation, 1 died while awaiting cardiac transplantation, 3 underwent Comprehensive Stage 2 (with 1 Operative Mortality after Comprehensive Stage 2), and 1 underwent successful biventricular repair. Pathway 3: Of 10 patients supported with initial HYBRID+VAD in Pathway 3,7 (70%) underwent successful cardiac transplantation and are alive today, and 3 (30%) died on VAD while awaiting transplantation. Median VAD support time was 134 days (range, 56-226 days). Of 3 patients who were bridged to transplant with prostaglandin, 2 underwent successful transplantation and 1 died while awaiting transplantation. CONCLUSIONS A comprehensive approach to the management of patients with HLHS is associated with an Operative Mortality after Norwood of 2.6% (2 of 77) and an overall 1-year mortality of 9% (9 of 100). Ten patients (10%) were stabilized with HYBRID+VAD while awaiting transplantation. VAD facilitates survival on the waiting list during prolonged waiting times. (Ann Thorac Surg 2025;119:169-79) (c) 2024 by The Society of Thoracic Surgeons. Published by Elsevier Inc.

Mitochondrial trifunctional protein deficiency is a long-chain fatty acid disorder that may include manifestations of severe cardiomyopathy and arrhythmias. The pathophysiology for the severe presentation is unclear but is an indicator for worse outcomes. Triheptanoin, a synthetic medium chain triglyceride, has been reported to reverse cardiomyopathy in some individuals, but there is limited literature in severe cases. We describe a neonatal onset of severe disease whose clinical course was not improved despite mechanical support and triheptanoin.

Objective:Pediatric heart transplantation is challenged by limited donor organ availability, prolonged waitlist times, and elevated risks of late acute rejection (LAR) and hospitalization. Current predictive models for post-transplant outcomes lack high accuracy due to reliance on registry data without integrating dynamic clinical and social factors. This study aimed to improve predictive performance and model interpretability by incorporating electronic health records (EHR), social determinants of health (SDoH), and United Network for Organ Sharing (UNOS) data. Materials and Methods:We used EHR and UNOS data from 111 pediatric heart transplant patients (ages 0-18) at the University of Florida Health Shands Children's Hospital to build predictive models for organ rejection at 1-, 3-, and 5-year intervals post-transplant. UNOS data includes pre- and post-transplant health and medical records, encompassing procedures, clinical evaluations, and post-transplant follow-up information, EHR data included evolving clinical parameters (e.g., comorbidities, medication adherence, and laboratory results), while SDoH encompassed socioeconomic status, living conditions, and healthcare access. Feature importance was assessed using Shapley Variable Importance Cloud (ShapleyVIC), which integrates Shapley Additive Explanations (SHAP) to provide robust, interpretable insights across nearly optimal models. Results:Models integrating EHR, SDoH, and UNOS data outperformed those using UNOS data alone, with AUROC of 0.743 (0.607-0.879), 0.798 (0.725-0.871), and 0.760 (0.692-0.828). Key predictors of rejection included severe pre-transplant conditions (e.g., life support, prolonged waitlist times), elevated bilirubin and creatinine levels, and social factors (e.g., transportation barriers, BMI, insurance type). Discussion:Findings reveal the importance of integrating clinical and social data to address multisystem dysfunction, disparities in healthcare access, and adherence challenges. ShapleyVIC enhanced model interpretability, providing actionable insights for improving post-transplant care. Conclusion:Holistic, data-driven approaches that combine EHR, SDoH, and registry data significantly enhance predictive accuracy and interpretability, supporting improved long-term outcomes for pediatric heart transplant patients.

BACKGROUND:Unique challenges exist with providing ventricular assist device (VAD) support to neonates, infants, and children with congenital heart disease (CHD), functionally univentricular circulation, and those weighing <5 kg. We review our experience with all patients ever supported with Berlin Heart at University of Florida and assess risk factors for mortality and outcomes in high-risk subgroups. METHODS:Overall outcomes of 99 patients who underwent 100 separate episodes of support with Berlin Heart were assessed; 47 patients weighed <5 kg. Patients with CHD (n =53) were compared with those with acquired heart disease (n = 45), and patients with functionally univentricular circulation (n = 40) were compared with those with biventricular circulation (n = 59). The primary outcome was mortality. Survival was modeled by the Kaplan-Meier method. Univariable Cox proportional hazard models identified prognostic factors for survival. Kaplan-Meier methods and log-rank tests were used to assess group differences in long-term survival. RESULTS:Risk factors for mortality were CHD (hazard ratio [HR], 2.25; 95% CI, 1.22-4.13; P = .009), liver dysfunction (HR, 3.46; 95% CI, 1.56-7.69; P = .002), and bleeding (HR, 3.91; 95% CI, 1.87-8.18; P = .0002). Biventricular heart (HR, 0.38; 95% CI, 0.18-0.8; P = .01) and biventricular assist device support (HR, 0.35; 95% CI, 0.16-0.76; P = .007) were protective. Overall survival at 1 and 5 years in all 99 patients was 74.5% (95% CI, 66.4%-83.7%) and 69.8% (95% CI, 61.1%-79.7%). Survival at 1 and 5 years in all 47 patients <5 kg was 63.4% (95% CI, 50.9%-78.9%) and 60.9% (95% CI, 48.3%-76.9%). Longitudinal survival is better in acquired heart disease vs CHD (log-rank P = .003) and biventricular vs univentricular patients (log-rank P = .026). CONCLUSIONS:Pulsatile VAD facilitates bridge to transplantation in neonates, infants, and children; however, survival is worse in smaller patients, those with CHD, and those with functionally univentricular circulation. These challenging subgroups represent important opportunities for improvement.

BACKGROUND:High-risk patients with hypoplastic left heart syndrome can be supported with combined Hybrid Stage 1 (arterial duct stenting, bilateral pulmonary artery banding, and atrial septectomy if needed) and ventricular assist device (VAD) insertion (HYBRID+VAD) as a bridge to transplantation. Concerns have been raised about the challenges and complexity of the subsequent cardiac transplantation. The purpose of this analysis was to review the investigators' experience with 7 consecutive infants with functionally univentricular ductal-dependent systemic circulation who underwent cardiac transplantation after HYBRID+VAD. METHODS:Ten consecutive high-risk neonates with functionally univentricular ductal-dependent systemic circulation and major cardiac risk factors were supported with HYRID+VAD, and 7 underwent subsequent cardiac transplantation. The characteristics and outcomes of cardiac transplantation for these 7 patients were reviewed. RESULTS:The median length of VAD support was 154 days (range, 64-226 days). The median age at cardiac transplantation was 177 days (range, 84-250 days). Six of 7 transplants (85.7%) were ABO incompatible. All 7 patients successfully underwent transplantation with aortic arch reconstruction and simple pulmonary artery band removal and dilation. No patients underwent pulmonary artery augmentation at transplantation. Median (range) transplantation times in minutes were as follows: cardiopulmonary bypass time, 169 (139-208); cross-clamp time, 89 (56-116); antegrade cerebral perfusion time, 29 (24-39); and donor ischemic time, 212 (139-236). The minimum temperature was 20.4 °C (range, 19.6-22.8 °C). One patient had posttransplant vocal cord dysfunction and underwent gastrostomy tube insertion. The median posttransplant length of stay was 26 days (range, 8-43 days). No patients have undergone subsequent transcatheter or surgical interventions on their aorta or pulmonary arteries. All 7 patients are currently alive and well, with follow-up after transplantation of 3.9 years (range, 2.2-7.1 years). CONCLUSIONS:Cardiac transplantation after HYBRID+VAD can be performed safely and effectively and results in excellent short-term and midterm outcomes.

Background Pre-transplant psychosocial assessment, in conjunction with medical and surgical evaluation, is a critical component of determining pediatric heart transplant candidacy. Psychosocial factors such as family dynamics, health literacy, mental health, financial stability, and adherence potential are often multidimensional and interdependent, making their assessment both vital and complex. However, few standardized tools exist to guide these evaluations in pediatric heart transplant settings, and even fewer have demonstrated empirical validity or predictive value. To address this gap, the Pediatric Psychosocial Assessment Tool (PPAT) was developed to provide a structured, semi-quantitative framework for evaluating psychosocial risk in pediatric transplant candidates. Methods This study presents initial validation data for the PPAT, based on 189 assessments conducted at a large pediatric heart transplant center. The tool evaluates nine psychosocial domains, assigns risk ratings, and yields a total risk score. Results Confirmatory factor analysis supported the unidimensional structure of the tool, and internal consistency was strong (α = 0.89). Higher PPAT scores were significantly associated with lower odds of being listed for transplant by the center’s multidisciplinary medical review board (MRB), even after accounting for clinical factors. Domain-level findings revealed financial and health literacy issues as commonly identified risk areas. Conclusion The PPAT holds promise as a valid, reliable, and clinically useful instrument for guiding MRB discussions and targeting interventions to support high-risk families. Future directions include expanding implementation to other centers and integrating the PPAT into digital platforms using artificial intelligence and natural language processing to enhance efficiency, consistency, and patient-centered care.

Myocarditis is an inflammatory heart disease that is more prevalent in men. The etiology of myocarditis is often multifactorial with viral infections being a predominant cause of myocarditis. Other etiologies such as autoimmune mediated or secondary to certain medical therapies such as immune checkpoint inhibitors are also seen however less commonly. The wide spectrum of clinical symptoms with which these patients present and the lack of reliable patterns or biomarkers of progression make it difficult to both diagnose and risk-stratify patients. Importantly, this disease is widely prevalent in pediatric populations and is a leading cause of sudden cardiac death in young patients. However, much of the knowledge of pathogenesis and treatment of this disease is extrapolated from adult studies. Current research in myocarditis has increasingly identified the role of hormones and the apparent sex differences seen predominantly in adult patients; however, such data is not well established in pediatric patients. Thus, there is an increased need to evaluate the age and sex-based differences in pediatric patients with myocarditis. Therefore, this review aims to present an overview of our current understanding of pathogenesis, diagnosis, and treatment strategies for myocarditis, with an emphasis on outlining both adult and pediatric studies to emphasize the continued need for research into this disease.

BackgroundWe reviewed our management strategy and outcome data for all 112 patients with congenital heart disease (CHD) who underwent cardiac transplantation at University of Florida from January 2011, to January 2022, and evaluated the impact of a pretransplant ventricular assist device (VAD).MethodsContinuous variables are presented as mean (SD); median [interquartile range] (range); categorical variables are presented as N (%). Univariable associations with long-term survival were assessed with Cox proportional hazards models. The impact of pretransplant VAD on survival was estimated with multivariable models.ResultsPretransplant VAD was present in 24 of 112 patients who underwent cardiac transplantation (21.4%). Patients with a VAD were younger (years): 3.0 (3.8); 1 [0.5,6] (0.1,14) versus 12.9 (14.9); 9 [0.6,19] (0.1,58), P = .008. More patients with a VAD had prior cardiac operations: 24 of 24 (100%) versus 71 of 88 (80.7%), P = .021 and were more likely to receive an ABO-incompatible transplant: 6 of 24 (25%) versus 7 of 88 (8%), P = .032.Univariable associations with long-term mortality include: Number of prior cardiac surgeries-hazard ratio (HR) multiplies by 1.2 for each additional surgery (1.02-1.44), P = .029.Pretransplant renal dysfunction - HR = 2.8 (1.21-6.68), P = .017.Cardiopulmonary bypass (CPB) time at transplant: HR multiplies by 1.1 for each 10 min increase above the minimum CPB time in this series (1.03-1.19), P = .008.In multivariable analysis, pretransplant VAD does not impact survival when controlling for each one of the factors shown in univariable analysis to be associated with long-term survival. Kaplan-Meier five-year survival (95% confidence interval) is 77.4% (68.4%-87.5%) for all patients; 76.5% (66.7%-87.9%) without pretransplant VAD and 84.3% (69.3%-99.9%) with pretransplant VAD (P = .436).ConclusionOur single-institution analysis of 112 patients with CHD undergoing cardiac transplantation over 11.25 years reveals similar survival in patients with (n = 24) and without (n = 88) pretransplant VAD. The presence of a pretransplant VAD is not a risk factor for survival after transplantation in patients with CHD.

Background:Patients with Fontan physiology are predisposed to congestive hepatopathy, progressive liver fibrosis, and end-stage liver disease. Ultrasound-based shear wave elastography (SWE) is a non-invasive tool to diagnose and monitor liver fibrosis. We sought to determine whether the degree of hemodynamic derangement prior to and after the Fontan operation is associated with increased liver stiffness measured by SWE. Methods:A single-center retrospective study of patients with Fontan circulation who underwent ultrasound elastography between 2008 and 2024 was conducted. Liver stiffness was measured by SWE and reported as velocity in m/s. Hemodynamic assessment with cardiac catheterization and echocardiograms were collected before and after the Fontan operation. Data was analyzed as a continuous (linear regression model) and a dichotomous variable (t-test). Results:78 post-Fontan ultrasound elastography studies performed in 56 patients were analyzed. Pre-Fontan hemodynamics included median effective pulmonary flow of 2.45 L/min/m2 [2.21, 3.16] (p = 0.46), ventricular end-diastolic pressure of 10 mmHg [8, 10.5] (p = 0.77), and median Glenn pressure of 12 mmHg [13, 15] (p = 0.83). Post-Fontan median systemic cardiac index was 2.80 L/min/m2 [2.4, 3.34] (p = 0.93), median ventricular end-diastolic pressure of 12 mmHg [13.5, 14] (p = 0.99), median systemic saturation of 93% [87, 96] (p = 0.77), median indexed pulmonary vascular resistance of 1.80 WU·m2 [1.49, 2.37] (p = 0.93), and median Fontan pressure of 18 mmHg [16, 21] (p = 0.86). No correlation was found between SWE and hemodynamics. On echocardiography, no correlation was found between SWE and systemic ventricular systolic function (p = 0.35) or degree of systemic atrioventricular valve regurgitation (p = 0.35). Conclusions:The degree of liver stiffness by SWE in this cohort did not correlate with pre- and post-Fontan hemodynamics on cardiac catheterization, degree of ventricular dysfunction, or severity of atrioventricular valve regurgitation by echocardiography.

Fontan-associated liver disease (FALD) is a common complication after the Fontan procedure. A liver biopsy is the gold standard for assessing liver fibrosis. However, ultrasound (US) elastography has increasingly been used as a non-invasive method to diagnose and monitor liver fibrosis. Nonetheless, a clear correlation of severity of fibrosis between US elastography and liver biopsy in this population has not yet been established. In this single-center retrospective study, we included patients with Fontan physiology who had liver fibrosis evaluation between 2008 and 2022 with both US elastography and liver biopsy. Fibrosis was classified by US elastography and liver biopsy based on the METAVIR scoring system and congestive hepatic fibrosis score, respectively. Overall, 29 patients had both US elastography and liver biopsy with a median age of 17 years (IQR 13–27 years). The median time between Fontan operation and liver biopsy was 14 years (IQR 9–23). Nine patients underwent isolated heart transplantation (31