Ameduri, Rebecca

Purpose of review To summarize important papers published in the pediatric heart transplantation in the last year. Recent findings While advances have been made for pediatric patients who need heart transplantation, considerable challenges remain. Donor availability remains a key challenge, and work to both increase the number of donors and the quality of donor organs is ongoing. The field of pediatric heart transplantation benefits from registries such as the Pediatric Heart Transplant Society (PHTS) and learning networks such as the Advanced Cardiac Therapies Improving Outcomes Network (ACTION), allowing for multisite collaboration to optimize survival both before and after transplant, and to share learning about complex cases. Psychosocial evaluations of potential recipients and families can be challenging, and a consensus framework is now available for these evaluations, to provide appropriate oversight and management of a scarce resource. Looking ahead, heart transplant specialists are anticipating advances in xenotransplantation, which has the potential to revolutionize current standards of care. Summary Donor availability and organ scarcity are the dominant challenges we face, with many recent impactful papers addressing this issue either directly or indirectly. It will be critical to maintain the forward progress made in addressing these challenges, while readying the field for big changes to come.

ImportanceStudies suggest that everolimus may reduce the risk of rejection, cardiac allograft vasculopathy (CAV), chronic kidney disease (CKD), and cytomegalovirus (CMV) after heart transplant. Everolimus use is controversial because of data demonstrating higher infection deaths when everolimus is introduced de novo after transplant. It is unclear whether everolimus is safe and effective when initiated at 6 months posttransplant in children, a population in which median graft survival is limited to 15 years and randomized clinical trials are lacking.ObjectiveTo evaluate the safety and efficacy of everolimus combined with low-dose tacrolimus to prevent major adverse transplant events (MATEs) in children after heart transplant.Design, Setting, and ParticipantsMulticenter, randomized, open-label, clinical trial enrolling 211 patients who were alive 6 months after pediatric heart transplant at 25 US sites from February 2018 to August 2020. The last date of follow-up was April 17, 2023.InterventionsParticipants were randomized to receive everolimus and low-dose tacrolimus (n = 107) or standard-dose tacrolimus and mycophenolate mofetil (n = 104) for 30 months.Main Outcomes and MeasuresThe primary efficacy end point was the MATE-3 score at 30 months, a validated composite ordinal end point including acute cellular rejection, CAV, and CKD. The primary safety end point was the MATE-6 score, encompassing the MATE-3 score plus antibody-mediated rejection, infection, and posttransplant lymphoproliferative disorder.ResultsAmong 211 children randomized, the mean age was 8.2 (SD, 6.3) years, 97 (46%) underwent transplant for congenital heart disease, and 49 (23%) were treated for rejection before 6 months. At 30 months, the mean MATE-3 score did not differ between the 2 treatment groups (mean difference, −0.32; 95% CI, −0.90 to 0.20; P = .16). The mean MATE-6 score was no higher in the everolimus group than in the mycophenolate group (baseline-adjusted mean difference, −0.40; 95% CI, −1.81 to 0.93), meeting the success criterion for safety (noninferiority margin <3). There were no differences in graft survival, MATE-free survival, or freedom from any individual MATE. Everolimus was associated with greater improvement in estimated glomerular filtration rate at 12 months (mean difference, 10.5 mL/min/1.73 m2; 95% CI, 1.09-19.91 mL/min/1.73 m2) and a lower incidence of CMV infection (hazard ratio, 0.50; 95% CI, 0.26-0.93).Conclusions and RelevanceAmong 6-month pediatric heart transplant survivors, everolimus and low-dose tacrolimus did not differ from tacrolimus and mycophenolate in preventing the composite of cellular rejection, CAV, and CKD at 30 months. However, everolimus and low-dose tacrolimus appear to be safe based on the total burden of 6 MATEs and may be associated with improved kidney function and less CMV infection.Trial RegistrationClinicalTrials.gov Identifier: NCT03386539

ABSTRACT Background Risk for medication error increases during care transitions. Error susceptibility increases in pediatrics due to age and weight‐based dosing. Governing bodies acknowledge errors endanger patients, and transplant pharmacotherapy experts are mandated by the Center for Medicare and Medicaid Services (CMS). Pharmacist‐led medication histories reduce errors; however, pharmacists' roles in the transitions of care between transplant centers are unaddressed by CMS. We assessed the impact of transplant pharmacist involvement in medication histories for pediatrics transitioning between transplant centers. Methods Pediatric patients pre‐ or post‐heart transplant transitioning to our center were proactively identified. Transplant pharmacists conducted medication histories by phone with caregivers and tracked discrepancies between existing medication lists and interview responses. Descriptive statistical analyses were completed. Results Of 27 patients identified, seven caregivers were uncontactable, one declined participation, and 19 underwent transplant pharmacist medication history. Medication list errors were detected in 100% of patients ( n = 19), with a median [IQR] of 5 [3–11] issues per patient. Of 122 issues, 72 (59%) were inaccurate or missing data, 17.2% ( n = 21) listed stopped drugs, 9.8% ( n = 12) revealed incorrect administration routes, 7.4% ( n = 9) were duplicate medications, and 6.6% ( n = 8) of errors were medications needing to be added. Corrections included updating 84 inaccuracies (68.8%); removing/adding drugs (30 [24.6%] and 8 [6.6%], respectively); and team communication. Conclusions Complex dosing strategies in pediatrics confer error vulnerability. Designing transition of care processes with transplant pharmacist involvement in medication histories can assist in ensuring medication list accuracy, thereby improving pediatric patient safety.

ABSTRACT Introduction Improving organ preservation is essential for expanding the donor pool and enhancing outcomes for pediatric transplant recipients. This report presents three pediatric patients who received donor hearts preserved using the Organ Care System (OCS). All donor hearts were prepared, placed, and monitored on OCS according to standard protocols. Heart function and myocardial edema were visually assessed during monitoring. Case Reports Patient 1: A 17‐year‐old female patient with hypertrophic cardiomyopathy utilized OCS technology due to donor distance. She experienced an uncomplicated post‐transplant course and was discharged on post‐transplant day 10. Patient 2: A 14‐year‐old male patient with complex congenital heart disease, palliated with Fontan circulation, underwent orthotopic heart transplantation (OHT) with OCS support due to both the complexity of the procedure and donor heart distance. His post‐transplant course was complicated by a revision of the ascending aorta anastomosis and prolonged milrinone infusion for diastolic dysfunction. He was discharged on post‐transplant day 31. Patient 3: A 16‐year‐old male patient with hypoplastic left heart syndrome, also palliated with Fontan circulation, underwent OHT using OCS technology due to the complexity of the surgical procedure. His post‐transplant recovery was unremarkable, and he was discharged on post‐transplant day 15. Conclusions All three pediatric patients demonstrated favorable short‐term outcomes using OCS technology. The OCS system facilitated shorter ischemic times despite the need for extended transport distances or complex surgical procedures. However, further studies with larger patient cohorts and longer follow‐up are needed to better understand the long‐term impact of OCS on pediatric heart transplantation outcomes.

Background. The Fontan procedure has transformed the management of congenital heart defects characterized by single ventricle physiology, yet it predisposes individuals to Fontan-associated liver disease. Combined heart and liver transplantation (CHLT) emerges as a therapeutic option, but evidence of its efficacy and safety remains limited. This study aimed to comprehensively evaluate CHLT in Fontan patients, focusing on patient characteristics, perioperative outcomes, and posttransplant morbidity and mortality. Methods. Following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, a systematic search of PubMed, Embase, and the Cochrane Central Register of Controlled Trials was conducted. Studies meeting the intervention of CHLT in Fontan patients were included, and data were collected and synthesized using proportion meta-analysis techniques. Statistical analysis was carried out using R software. Results. Four studies met inclusion criteria, comprising 67 Fontan patients undergoing CHLT. All included studies were observational retrospective cohorts performed in the United States. The 1-y survival rate post-CHLT was 88% (95% confidence interval [CI], 70%-98%). Liver graft rejection rates were low, 4% (95% CI, 0%-22%), and no heart graft rejection greater than mild was reported. Postoperative complications included acute kidney injury 75% (95% CI, 50%-93%), temporary dialysis 27% (95% CI, 9%-51%), neurologic events 7% (95% CI, 0%-26%), infection 23% (95% CI, 3%-55%), and unplanned medical procedures 40% (95% CI, 23%-59%). Conclusions. CHLT in Fontan patients demonstrates promising survival rates, but graft rejection and postoperative complications pose challenges. The rate of renal complications is particularly notable and requires further evaluation. Future research should prioritize comparative different management strategies and long-term follow-up to refine protocols and optimize outcomes.

ABSTRACT Background In recent years, transcatheter implantation devices to restrict pulmonary arterial flow have emerged as a potential alternative to surgical pulmonary artery banding. Case Presentation A term male was diagnosed with critical aortic stenosis (AS) and severely reduced left ventricle (LV) systolic function. He underwent aortic balloon valvuloplasty on day 2 of life, resulting in some antegrade flow, but LV ejection fraction only improved to 15%. He remained ductal dependent for systemic perfusion. Pulmonary over‐circulation ensued with systemic steal evident in his second week of life. On day 14, he underwent a transcatheter stage 1 procedure including the placement of bilateral pulmonary flow restrictor (PFR) devices and ductal stenting. Post‐procedure, he improved clinically, weaned off respiratory support, and transitioned to oral feeds while awaiting cardiac transplant. Twelve days later, he received a donor heart, with an uneventful recovery. He is now 3 years post‐transplant and has excellent graft function, and his transplant course has been unremarkable. Conclusion Transcatheter‐based palliation for a neonate with critical AS, utilizing endoluminal PFRs, proved effective in stabilizing the infant and successfully bridging him to transplant. This highlights an opportunity for the utilization of PFRs in neonatal conditions where control of pulmonary blood flow is imperative as a bridge to transplantation.

Background: The Fontan procedure has transformed the management of congenital heart defects (CHD) characterized by single ventricle physiology, yet it predisposes individuals to Fontan-associated liver disease (FALD), potentially leading to end-stage liver disease (ESLD). Combined heart and liver transplantation (CHLT) emerges as a therapeutic option, but evidence on its efficacy, safety, and outcomes remains limited. Objectives: This systematic review and single-arm meta-analysis aims to comprehensively evaluate the literature on CHLT in Fontan patients, focusing on patient characteristics, perioperative outcomes, and post-transplant morbidity and mortality. Methods: A systematic search of PubMed, Embase, and Cochrane Central Register of Controlled Trials was conducted following PRISMA guidelines. Studies meeting the intervention of CHLT in Fontan patients were included and data were collected and synthesized using proportion meta-analysis techniques. Statistical analysis was carried out using R software. Results: Four studies met inclusion criteria, comprising 67 Fontan patients undergoing CHLT. All included studies were observational retrospective cohorts performed in the United States. One-year survival rate post-CHLT was 84% (95% CI 66%-94%), Figure 1A. Rates of liver and heart graft rejection were low 10% (95% CI 3%-33%) and 8% (95% CI 2%-31%), respectively, Figure 1B. Postoperative complications included acute kidney injury 72% (95% CI 46%-88%), temporary dialysis 31% (95% CI 14%-55%), neurologic events 14% (95% CI 5%-34%), infection 24% (95% CI 6%-63%), and unplanned medical procedures 41% (95% CI 24%-60%), Figure 1C. Conclusion: CHLT in Fontan patients demonstrates promising survival rates, but graft rejection and postoperative complications pose challenges. The rate of renal complications is particularly notable and requires further evaluation. Future research should prioritize comparative different management strategies and long-term follow-up to refine protocols and optimize outcomes.

Context.— Cardiac and pulmonary allograft recipients represent a unique population, frequently interacting with support groups and exhibiting intense curiosity about their pathology. Like other solid organ transplant patients, they have enduring and frequent interaction with the laboratory for routine allograft surveillance. Objective.— To address patient requests to understand what happens to their explanted organ and to better understand their disease while simultaneously improving awareness of pathologists’ roles in their continuing care. Design.— At routine follow-up appointments, transplant nurse coordinators offer each allograft recipient the opportunity to interact with a pathologist in our “ On My Path ” program. Organ viewing occurs in a private setting, in a specialized room. Relevant pathology is discussed, and questions are answered, with documentation in the medical record. The patient is subsequently gifted a 3-dimensional model of their explanted organ. Transplant coordinators were surveyed for their feedback on the experience. Results.— One hundred fifty-eight interactions have been documented (2017–2022) at our institution, including patients who underwent cardiac transplant (96, 61%), single or bilateral lung transplant (54, 34%), or combination lung and heart transplant (8, 5%). Transplant coordinators reported an increase in patient understanding of their disease and emotional closure related to the disease through the On My Path program. Conclusions.— Pathologists providing direct patient care is a feasible model that addresses currently unmet desires of the transplant population to better understand their pathology. Providing a 3-dimensional model helps to empower patients and drives satisfaction. These interactions also improve awareness about pathology as a discipline and its importance in the continued care of transplant recipients.

Solitary myofibromas are rare, benign, mesenchymal tumors typically found in the head and neck regions. We report an exceptionally rare case of a solitary cardiac myofibroma and its short-term management and outcome. A two-month-old infant was referred due to a murmur. Echocardiography revealed a 2 × 1 cm solitary mass originating from a mitral papillary muscle, causing severe regurgitation. Magnetic resonance imaging showed the mass to be homogeneous on T1, hyperintense on T2, and hypointense on first-pass perfusion imaging with no enhancement on delayed postcontrast imaging. The mass was surgically excised partially due to its involvement with the mitral valve. Postoperative recovery was uneventful, with echocardiography four months later showing no tumor recurrence and trivial mitral regurgitation. This report provides valuable imaging and pathology examples to aid in the recognition of this rare tumor and demonstrates that successful surgical excision is possible, even with significant cardiac involvement.

AbstractIntroductionPediatric heart transplant patients are routinely followed in dermatology clinics due to elevated risk of cutaneous malignancy. However, transplant patients may experience other, non‐cancer‐related dermatologic conditions including skin infections, inflammatory diseases, and drug eruptions that can cause significant medical and psychosocial comorbidity.MethodsA retrospective chart review of all pediatric heart transplant patients at Mayo Clinic Children's Center in Rochester, MN, was performed to determine the prevalence and spectrum of non‐cancer dermatologic conditions. Statistical analysis was conducted to look for associations between episodes of rejection and skin condition development.ResultsOf the 65 patients who received heart transplants under the age of 18 and were followed at Mayo Clinic, 69% (N = 45) were diagnosed with at least one skin condition between transplant and the time of most recent follow‐up. Sixty‐two percent (N = 40) of patients were diagnosed with an inflammatory skin condition (most commonly acne and atopic dermatitis), 45% (N = 29) with an infectious skin condition (most commonly warts and dermatophyte infection), and 32% (N = 21) with a drug eruption (most commonly unspecified rash and urticaria). No association was found between presence of skin disease and number of rejection episodes.ConclusionsNon‐cancer dermatologic conditions are prevalent within pediatric heart transplant recipients and may directly impact their medical needs and quality of life. Dermatologist involvement in the care of post‐transplant pediatric patients is important, not only for cancer screening but also for diagnosis and treatment of common infectious and inflammatory skin conditions.