Faculty Bibliography

ABO-incompatible (ABOi) heart transplantation, first performed in infants by West and colleagues in 1996, transformed pediatric heart allocation by challenging longstanding immunologic constraints. Early success of this approach leveraged the developmental immaturity of the neonatal immune system and has since shown comparable short- and long-term outcomes to ABO-compatible (ABOc) transplantation. Over three decades, increasing clinical experience and policy evolution, including broader ABOi eligibility criteria and relaxed titer thresholds, have expanded access to donor hearts and reduced waitlist mortality, particularly among blood group ABO-O candidates. Despite these advances, marked variability persists among centers in the measurement, interpretation, and reporting of ABO antibody titers, directly influencing candidate selection, perioperative management, and post-transplant surveillance. Most assays rely on manual hemagglutination techniques that are subject to significant inter-laboratory and intra-laboratory variability. Emerging single-antigen bead-based methods utilizing the Luminex™ platform may provide an opportunity for standardized, semi-quantitative assessment of graft-relevant anti-A and -B antibody levels. Perioperative strategies are individualized according to ABO antibody titer, with intraoperative plasma exchange or immunoadsorption typically employed when titers exceed a center-specific level. Standard immunosuppression regimens are generally sufficient, with anti-B cell therapies (e.g., rituximab) reserved for elevated or rebound titers. Long-term outcomes remain excellent, with most patients not producing donor-specific ABO antibodies after ABOi transplant. Most centers perform surveillance biopsies only when rising titers, an uncommon occurrence, are accompanied by graft dysfunction or biopsy-proven antibody-mediated rejection, managed with combinations of plasmapheresis, IVIG, and anti-B cell therapies as indicated. Future multicenter collaborations incorporating standardized reporting and longitudinal follow-up will be critical to optimize candidate selection, refine management algorithms, and further improve utilization and outcomes of ABOi heart transplantation.

Cirrhotic cardiomyopathy is a complication of cirrhosis resulting in cardiac dysfunction. It remains poorly characterized in children. The aim of this study was to assess relationship of pre-liver transplant (LT) conventional and novel parameters of biventricular function with post-LT clinical course. This is a retrospective study of pre-LT echocardiograms performed on patients < 18 years of age with cirrhosis at a single center, who received a LT. Demographic, clinical, and echocardiographic data were collected. Speckle tracking echocardiography (STE) analysis was performed by a single observer using TomTec system. Descriptive data were expressed as mean (SD) and number (%). The relationship between clinical data and echocardiographic variables were assessed using Spearman correlation coefficient. Significance was set at < 0.05. Thirty-five patients (median age 6.5; IQR 14.2 years) underwent LT between 2010 and 2020. Pre-LT diagnosis was biliary atresia in 14 (40%) patients and 7 (20%) patients were listed as status 1A/1B. Their median natural pediatric/model end-stage liver disease score was 13 (IQR 9). Their pre-LT echocardiogram showed normal left ventricular systolic (LV) function by ejection fraction and strain parameters. Right ventricular (RV) function was abnormal in 74% of patients as measured by RV GLS (23 ± 3%). There was correlation between echocardiographic parameters with pre-transplant clinical disease and post-operative LT course (length of stay and duration of mechanical ventilation). Children undergoing liver transplant have RV dysfunction as evidenced by abnormal RV GLS on STE. There is echocardiographic parameter correlation between clinical liver disease and post-LT clinical course. This evidence highlights the importance of using novel technology like STE in assessment of children undergoing evaluation for liver transplant.

BACKGROUND:The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) began in 2018 as a collaborative learning health system committed to improving outcomes in pediatric heart failure, including children and adults with congenital heart disease, supported with ventricular assist devices (VADs). This report describes patient and device characteristics, and outcomes through 1-year post-implant. METHODS:The ACTION VAD registry report was created from data submitted to the ACTION learning network from April 2018 to June 2023. It includes 1,430 devices implanted in 1,220 pediatric patients (≤18) from 57 sites across North America. RESULTS:Males comprised 55% of the registry patients. The median age was 3.7 years with a median implant weight of 13.6 kg; 36% of the cohort was <10 kg. Nearly 40% of patients had a primary diagnosis of congenital heart disease (CHD). Patients with CHD represented 26% of VAD implants in 2018 which increased to 42% in 2023 (p=0.03). At implant, 25% of patients were supported with extracorporeal membrane oxygenation (ECMO), 4.9% with dialysis, and 54% were mechanically ventilated. Paracorporeal pulsatile pumps comprised 40.2% of implants, followed in incidence by paracorporeal continuous flow (28.5%), and implantable continuous flow (24.1%). The number of patients in the VAD Registry patients increased from 102 in 2018 to 256 in 2022, partly reflecting increased center participation in ACTION. Overall survival on support at 1 year was 79.2%, and the incidence of stroke was 13.7%. Infants demonstrated the poorest outcomes, with a 1-year survival of 72.9% and a higher incidence of stroke (20.8%). CONCLUSION/CONCLUSIONS:The 5-year ACTION VAD experience highlights the growing collaboration in the pediatric VAD community and changes in clinical practice. More work is needed to improve survival and limit adverse outcomes, especially in younger patients.

The authors recognize the limitations of our study, most of which are due to being a single-center study and the small sample size of our cohort. We tried to keep our population as homogeneous as possible and included patients only with cirrhosis. Imaging modalities like cardiac MRI, 3D echocardiography, and tissue Doppler imaging as well as exercise testing often give us significantly more information about cardiac function but come with their inherent limitations of requiring general anesthesia, limited availability, and age-dependent variability. We agree with both reviewers that our study lacks the longitudinal aspect which would allow us to study the reversibility of findings post-liver transplantation. However, the purpose of our study was to correlate the pre-transplantation echocardiographic findings as a risk stratification method for post-transplantation clinical measures like duration of mechanical ventilation and length of hospital stay. We believe that the results of our study can serve as a basis for further prospective studies in the evaluation of patients prior to liver transplantation as well as demonstrating reversal of findings in long-term post-transplant period.

The use of genetic testing has enhanced the diagnostic accuracy of heritable genetic cardiomyopathies. However, it remains unclear how genetic information is interpreted and incorporated into clinical practice for children with cardiomyopathy. The primary aim of this study was to understand how clinical practice differs regarding sequence variant classifications amongst pediatric cardiologists who treat children with cardiomyopathy. A secondary aim was to understand the availability of genetic testing and counseling resources across participating pediatric cardiomyopathy programs. An electronic survey was distributed to pediatric heart failure, cardiomyopathy, or heart transplantation physicians between August and September 2022. A total of 106 individual providers from 68 unique centers responded to the survey. Resources for genetic testing and genetic counseling vary among large pediatric cardiomyopathy programs. A minority of centers reported having a geneticist (N = 16, 23.5%) or a genetic counselor (N = 21, 31%) on faculty within the division of pediatric cardiology. A total of 9 centers reported having both (13%). Few centers (N = 13, 19%) have a formal process in place to re-engage patients who were previously discharged from cardiology follow-up if variant reclassification would alter clinical management. Clinical practice patterns were uniform in response to pathogenic or likely pathogenic variants but were more variable for variants of uncertain significance. Efforts to better incorporate genetic expertise and resources into the clinical practice of pediatric cardiomyopathy may help to standardize the interpretation of genetic information and better inform clinical decision-making surrounding heritable cardiomyopathies.

INTRODUCTION/BACKGROUND:Duchenne muscular dystrophy is a devastating neuromuscular disorder characterized by the loss of dystrophin, inevitably leading to cardiomyopathy. Despite publications on prophylaxis and treatment with cardiac medications to mitigate cardiomyopathy progression, gaps remain in the specifics of medication initiation and optimization. METHOD/METHODS:This document is an expert opinion statement, addressing a critical gap in cardiac care for Duchenne muscular dystrophy. It provides thorough recommendations for the initiation and titration of cardiac medications based on disease progression and patient response. Recommendations are derived from the expertise of the Advance Cardiac Therapies Improving Outcomes Network and are informed by established guidelines from the American Heart Association, American College of Cardiology, and Duchenne Muscular Dystrophy Care Considerations. These expert-derived recommendations aim to navigate the complexities of Duchenne muscular dystrophy-related cardiac care. RESULTS:Comprehensive recommendations for initiation, titration, and optimization of critical cardiac medications are provided to address Duchenne muscular dystrophy-associated cardiomyopathy. DISCUSSION/CONCLUSIONS:The management of Duchenne muscular dystrophy requires a multidisciplinary approach. However, the diversity of healthcare providers involved in Duchenne muscular dystrophy can result in variations in cardiac care, complicating treatment standardization and patient outcomes. The aim of this report is to provide a roadmap for managing Duchenne muscular dystrophy-associated cardiomyopathy, by elucidating timing and dosage nuances crucial for optimal therapeutic efficacy, ultimately improving cardiac outcomes, and improving the quality of life for individuals with Duchenne muscular dystrophy. CONCLUSION/CONCLUSIONS:This document seeks to establish a standardized framework for cardiac care in Duchenne muscular dystrophy, aiming to improve cardiac prognosis.

BACKGROUND:A viral vector recombinant gene transfer therapy (GTT) has recently been approved by the FDA for males of all ages with Duchenne Muscular Dystrophy (DMD) without limitations regarding preexisting cardiac impairment. Acute myocarditis is a potential life-threatening short-term complication that has been reported following GTT. This immune mediated response can range from troponin elevation to rapid cardiovascular compromise and death, particularly in those with abnormal cardiac status at baseline. Early detection of cardiac compromise is essential to optimize outcomes. OBJECTIVES/OBJECTIVE:The primary objective of this consensus statement is to advocate for caution with DMD GTT patient selection and to initiate preemptive monitoring for those who may be at increased risk for cardiac adverse events. Secondary objective is to deepen our understanding of short and long-term impact of DMD gene therapies on the heart. METHODS:A national learning network of pediatric cardiologists with expertise in DMD developed recommendations for cardiac surveillance of DMD males receiving GTT based on available evidence and expert consensus opinion. A monitoring and treatment plan for standard and high cardiac risk patients was developed. CONCLUSION/CONCLUSIONS:Partnership of cardiologists with GTT prescribers is essential to identify patient-specific considerations that might influence risk for adverse cardiac events and alter post infusion monitoring and management plans. Consistency in cardiac surveillance practices across centers will expedite our knowledge regarding potential short- and long-term cardiac effects of GTT for DMD.

INTRODUCTION/BACKGROUND:The present study aimed to assess the clinical outcomes of pediatric heart transplant patients whose donor hearts were preserved with the SherpaPakCardiac Transport System. METHODS:All pediatric patients undergoing heart transplantation at our center between January 2020 and June 2024 were included and described. Vasoactive inotropic score (VIS) was calculated. The cohort was divided into two groups by recipient diagnoses (cardiomyopathy vs. congenital heart disease [CHD]). They were compared based on demographics, operative details, and postoperative outcomes. The χ2 and Fisher exact tests were used for categorical variables and the Mann-Whitney U test or t-test for continuous variables. RESULTS:A total of 18 patients were included. The median recipient age was 11.9 years (IQR: 2.5, 13.9). Half had cardiomyopathy, median total ischemic time was 236 min (IQR: 211.5, 283.5). Upon comparing the two groups, there were no significant differences observed in VIS or primary graft dysfunction (PGD) even though the median circulatory arrest time and bypass times were significantly longer in the CHD group (p < 0.05). Three patients experienced early rejection (all with CHD), but there was no mortality. CONCLUSIONS:The SherpaPak Cardiac Transport System provides safe outcomes for pediatric heart transplant patients, including those with complex CHD. Further multi-institutional and registry studies are needed to evaluate this method for pediatric heart transplantation.

BACKGROUND/UNASSIGNED:Waitlist mortality (WM) remains elevated in pediatric heart transplantation. Allocation policy is a potential tool to help improve WM. This study aims to identify patients at highest risk for WM to potentially inform future allocation policy changes. METHODS/UNASSIGNED:was defined as death while awaiting transplant or removal from the waitlist due to clinical deterioration. Because WM is low after the first year, analysis was limited to the first 12 months on the heart transplant list. Kaplan-Meier analysis and log-rank testing was conducted to compare unadjusted survival between groups. Cox proportional hazard models were created to determine risk factors for WM. Subgroup analysis was performed for status 1A patients based on body surface area (BSA) at time of listing, cardiac diagnosis, and presence of mechanical circulatory support. RESULTS/UNASSIGNED:BSA groups. VAD support was associated with lower WM other than in the single ventricle cohort, where VAD was associated with higher WM. Extracorporeal membrane oxygenation and mechanical ventilation were associated with increased risk of WM in all cohorts. CONCLUSIONS/UNASSIGNED:There is significant variability in WM among status-1A patients. Potential refinements to current allocation system should factor in the increased WM risk we identified in patients supported by extracorporeal membrane oxygenation or mechanical ventilation, single ventricle congenital heart disease on VAD support and small children with congenital heart disease, restrictive cardiomyopathy, or hypertrophic cardiomyopathy.

Survival of patients after repair of coarctation of Aorta (CoA) has improved significantly over the decades, but patients have decreased life expectancy as compared to the general population. This has been attributed to increased hypertension, cerebrovascular disease, and coronary artery disease. There has also been an increasing concern of overweight and obesity in patients with adult congenital heart disease. While there have been studies looking at the impact of long-term hypertension on myocardial performance and outcomes in this population, this study aims to assess the impact of obesity in these patients on their myocardial performance. Ventriculo-arterial coupling is used as a measure of myocardial performance which reflects the interaction between cardiac contractility and arterial elastance. Patients after CoA repair are known to have hypertension affecting the arterial elastance. Obesity affects cardiac contractility as well. This study demonstrated that in a group of young patients after CoA repair, body mass index (BMI) has a relationship with left ventricular (LV) contractility and myocardial performance. This relationship was independent of blood pressure. BMI itself was not seen to affect the determinants of diastolic function in this study, suggesting that LV contractility may be affected before one can notice a change in the diastolic function secondary to BMI.