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Purpose: Acute cellular (ACR) and antibody‐mediated (AMR) rejection are risk factors for allograft loss in heart transplant (HT) recipients. Endomyocardial biopsy (EMB), although considered the gold standard for rejection surveillance, is invasive and has high interobserver variability. Noninvasive donor‐derived cell‐free DNA (dd‐cfDNA) sampling has a high negative predictive value (NPV) for rejection in adults and is increasingly used in pediatrics. This single center study aimed to test the performance of dd‐cfDNA in screening for acute rejection (AR) and donor‐specific antibodies (DSAs) in pediatric HT recipients. Methods: Blood samples for dd‐cfDNA were obtained per clinical protocol for all eligible HT recipients in our center from July 1, 2022 to December 31, 2023. Primary endpoints were episodes of AR, pathology grading of EMBs temporally related to ddcfDNA sampling (0–150 days), and presence of DSAs. Results: There were 471 interpretable samples, in 192 unique patients. Of those, 199 dd‐cfDNA tests were paired with EMB ± DSA in 152 patients. Abnormal dd‐cfDNA (> 0.2%) was found in 77 samples (median 0.48%, range 0.21%–11%) and led to EMB, where one sample was positive for ACR (grade 2R), 13 for AMR, yielding an NPV of 97% for AMR. After excluding abnormal ddcfDNA testing associated with AR, 65 abnormal dd‐cfDNA tests were paired with DSA testing. The NPV of the test for detection of DSAs was 93%. Conclusion: Implementation of noninvasive rejection surveillance with dd‐cfDNA in a pediatric cohort demonstrates high NPV for AR and high DSAs, making it an ideal screening tool for long‐term monitoring of allograft health in pediatrics. [ABSTRACT FROM AUTHOR]

Background: There is a shortage of donor hearts in Switzerland, especially for pediatric recipients. However, the rate and reason for refusals of pediatric donor hearts offered in Switzerland has not been systematically analyzed. Methods: The national transplant database, Swiss Organ Allocation System, was searched for all hearts from Swiss and foreign donors younger than 16 years from 2015 to 2020. The numbers of accepted and refused hearts and early outcome were assessed, and the reasons for refusal were retrospectively analyzed. Results: A total of 136 organs were offered to the three Swiss pediatric heart centers and foreign donor procurement organizations. Of these, 26/136 (19%) organs were accepted and transplanted: 18 hearts were transplanted in Switzerland, and 13 of these were foreign. Reasons for refusal were (1) no compatible recipient due to blood group or weight mismatch, 89.4%; (2) medical, meaning organ too marginal for transplantation, 7.4%; (3) logistic, 1.4%; and (4) other, 1.8%. Five organs were refused in Switzerland by one center but later accepted and successfully transplanted by another center. Hearts from outside Switzerland were transplanted significantly less than Swiss hearts (n = 16/120 vs. 10/16, p <.001). Conclusion: The most common reason for refusing a pediatric donor heart is lack of compatibility with the recipient. Few hearts are refused for medical reasons. A more generous acceptance seems to be justified in selected patients. Switzerland receives a high number of foreign offers, but their rate of acceptance is lower than that of Swiss donations. [ABSTRACT FROM AUTHOR]

OBJECTIVES End-stage congenital heart disease (CHD) in children with heterotaxy syndrome might necessitate a heart transplant (HTx). An HTx in heterotaxy patients can be associated with several technical (e.g. redo, systemic/pulmonary-venous/situs anomalies, pulmonary artery reconstruction) and extra-cardiac (e.g. ciliary dyskinesia, infections, gastrointestinal) challenges. Our goal was to determine if heterotaxy syndrome is associated with increased early or late transplant risks. METHODS The United Network for Organ Sharing transplant database was merged with the Paediatric Health Information System administrative database to identify children with heterotaxy who received an HTx. Characteristics and outcomes were compared between children with heterotaxy and contemporaneous non-heterotaxy congenital and non-congenital cardiomyopathy control groups. RESULTS After we merged the databases, we divided our cohort of 1122 patients into 3 groups: the heterotaxy (n  = 143), group the non-heterotaxy congenital (n  = 428) group and the cardiomyopathy (n  = 551) group. There were differences in the characteristics between the 3 groups, with the heterotaxy group being comparable to the non-heterotaxy congenital group. The waiting list duration was longer for the heterotaxy than for the non-heterotaxy congenital and cardiomyopathy groups (91 vs 63 vs 56 days, P  < 0.001). Early post-transplant complications were similar for all groups except for operative mortality, which was 1% for the cardiomyopathy and 4% for the heterotaxy and non-heterotaxy congenital groups (P  < 0.001). The post-transplant hospital stay was shorter for the cardiomyopathy (57 days) compared to the non-heterotaxy congenital (99 days) and heterotaxy (89 days) groups (P  < 0.001). Whereas rejection prior to discharge was comparable between the heterotaxy and the CHD groups, it was higher at 1 year for the heterotaxy (22%) than for the non-heterotaxy congenital (19%) and cardiomyopathy (13%) groups (P  < 0.001). Survival at 5 years was superior for the cardiomyopathy (87%) compared to the heterotaxy (69%) and non-heterotaxy congenital groups (78%) (P  < 0.001). For the heterotaxy group, no risk factors affecting survival were identified on multivariable analysis. CONCLUSIONS Regardless of the complexity, an HTx in selected children with heterotaxy is associated with good mid-term outcomes. Despite early results that are comparable to those of other patients with CHD, the increasing rejection rate at 1 year and the relatively accelerated attrition at mid-term warrant further follow-up. Due to database limitations in defining morphologic and surgical details, further work is warranted to delineate anatomical and surgical variables that could affect survival. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction and objectives: Although cardiac catheterization (CC) has become a routine practice in pediatric heart transplantation (HT), there is still a shortage of widely used protocols and strong evidence on the number of procedures required and their impact on HT outcomes, as well as the need for further CC. This study aimed to analyze CC activity in pediatric HT recipients in a tertiary center and describe risk factors for a higher number of post-HT procedures. Methods: This retrospective study obtained data from medical reports and image files. The sample was composed of patients with cardiomyopathies and congenital heart diseases (CHD). Risk factor analysis for CCs was conducted with linear regression and the ANOVA test. Results: The sample included 61 children (36.07% with CHD). The CHD group had a higher mean number of CCs prior to HT. The most frequent activities prior to HT were diagnostic catheterizations, followed by endomyocardial biopsies for cardiomyopathies and aortopulmonary collaterals in CHD patients. There were 389 post-HT CCs (608 procedures). Most CCs were performed for rejection surveillance, accounting for 92.75% of procedures. The univentricular CHD subgroup was associated with a higher number of CC after HT (P = .03). Conclusions: Despite long life expectancy, pediatric HT recipients have...

COVID‐19 is a heterogenous infection—asymptomatic to fatal. While the course of pediatric COVID‐19 infections is usually mild or even asymptomatic, individuals after adult heart transplantation are at high risk of a severe infection. We conducted a retrospective, multicenter survey of 16 pediatric heart transplant centers in Germany, Austria and Switzerland to evaluate the risk of a severe COVID‐19 infection after pediatric heart transplantation between 02/2020 and 06/2021. Twenty‐six subjects (11 male) with a median age of 9.77 years at time of transplantation and a median of 4.65 years after transplantation suffered from COVID‐19 infection. The median age at time of COVID‐10 infection was 17.20 years. Fourteen subjects had an asymptomatic COVID‐19 infection. The most frequent symptoms were myalgia/fatigue (n = 6), cough (n = 5), rhinitis (n = 5), and loss of taste (n = 5). Only one subject showed dyspnea. Eleven individuals needed therapy in an outpatient setting, four subjects were hospitalized. One person needed oxygen supply, none of the subjects needed non‐invasive or invasive mechanical ventilation. No specific signs for graft dysfunction were found by non‐invasive testing. In pediatric heart transplant subjects, COVID‐19 infection was mostly asymptomatic or mild. There were no SARS‐CoV‐2 associated myocardial dysfunction in heart transplant individuals. [ABSTRACT FROM AUTHOR]

Background: There are conflicting data regarding the relationship between center volume and outcomes in pediatric heart transplantation. Previous studies have not fully accounted for differences in case mix, particularly in high‐risk congenital heart disease (CHD) groups. We aimed to evaluate the relationship between center volume and outcomes using the Pediatric Heart Transplant Society (PHTS) Registry and explore how case mix may affect outcomes. Methods: A retrospective cohort study of all pediatric patients in the PHTS Registry who received a heart transplant from 2009 to 2018 was performed. Centers were divided into 5 groups based on average yearly transplant volume. The primary outcome was time to death or graft loss and outcomes were compared using Kaplan–Meier analysis. Results: There were 4583 cases among 55 centers included. There was no difference in time to death or graft loss by center volume in the entire cohort (p =.75), in patients with CHD (p =.79) or in patients with cardiomyopathy (p =.23). There was also no difference in time to death or graft loss by center size in patients undergoing transplant after Norwood, Glenn or Fontan (log rank p =.17, p =.31, and p =.10 respectively). There was a statistically significant difference in outcomes by center size in the positive crossmatch group (p <.0001), though no discernible pattern related to high or low center volume. Conclusions: Outcomes are similar among transplant centers of all sizes, including for high‐risk patient groups with CHD. Future work is needed to understand how patient‐specific risk factors may vary among centers of various sizes and whether this influences patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Immunosuppression after heart transplantation (HTX) with mammalian target of rapamycin (mTOR) inhibitors serves as a prophylaxis against rejection and to treat coronary vascular injury. However, there is little data on the early, preventive use of everolimus after pediatric HTX. Methods: Retrospective study of 61 pediatric HTX patients (48 cardiomyopathy and 13 congenital heart disease), 28 females, median age 10.1 (range 0.1–17.9) years transplanted between 2008 and 2020. We analyzed survival, rejection, renal function, occurrence of lymphoproliferative disorder, and allograft vasculopathy together with adverse effects of early everolimus therapy combined with low‐dose calcineurin inhibitors. Results: Everolimus therapy was started at a median 3.9 (1–14) days after HTX. Median follow‐up was 4.3 (range 0.5–11.8) years, cumulative 184 patient years. The estimated 1‐ and 5‐year survival probability was 89% (CI 82%:98%) and 87% (CI 78%:97%). Four patients developed rejection (6.6%) (maximum 2R ISHLT criteria). No patient suffered from chronic renal failure. Three patients (4.9%) developed post‐transplant lymphoproliferative disorder. Five patients suffered relevant wound‐healing disorders after transplantation, four of them carrying relevant risk factors before HTX (mechanical circulatory support (n = 3), delayed chest closure after HTX (n = 3)). No recipient developed cardiac allograft vasculopathy. Conclusion: Initiating everolimus within the first 14 days after HTX seems to be well tolerated, enabling a low incidence of rejection, post‐transplant lymphoproliferative disorders, renal failure, and reveals no evidence of cardiac allograft vasculopathy as well as good overall survival in pediatric heart transplant recipients. [ABSTRACT FROM AUTHOR]

Background: Highly sensitized pediatric patients awaiting heart transplantation experience longer wait times and thus higher waitlist mortality. Similarly, children less than 2 years of age have increased waitlist times and mortality when compared to their older peers. To improve the likelihood of successful transplantation in these patients, various strategies have been utilized, including peri-operative plasmapheresis. However, limited data exists comparing plasmapheresis techniques for antibody reduction. This study’s aim was to compare the in vitro magnitude of isohemagglutinin titers (IT) and human leukocyte antigen (HLA) antibody removal and the time required between membrane-based plasmapheresis (MP) and centrifuge-based plasmapheresis (CP) incorporated into the extracorporeal (EC) circuit. Methods: Two MP (Prismaflex) and two CP (Spectra Optia, Terumo BCT) circuits were incorporated into four separate EC circuits primed with high titer, highly sensitized type O donor whole blood. Assays were performed to determine baseline IT and anti-HLA antibodies and then at 30-minute increments until completion of the run (two plasma volume exchanges) at two hours. Results: There was a decrease in anti-A and anti-B IgM and IgG titers with both MP and CP. Mean anti-A and anti-B titer reduction was by 4.625 titers (93.7% change) and 4.375 titers (93.8% change) using MP and CP, respectively. At 2 h of apheresis, CP reduced 62.5% of all ITs to ≤ 1:4, while MP reduced 50% of ITs to ≤ 1:4. Additionally, reduction of anti-HLA class II antibody to mean fluorescence intensity (MFI)

Cardiac allograft vasculopathy (CAV) is an important cause of mortality after pediatric heart transplantation (HT) but there is a paucity of data regarding its incidence and impact on survival in pediatric recipients transitioned to adult care. We conducted a retrospective review of consecutive pediatric HT patients from 1989 to 2017 at the Hospital for Sick Children who transitioned to adult care at ≥18 years at Toronto General Hospital. We evaluated the incidence of International Society of Heart and Lung Transplantation CAV grade ≥1 using competing risk models. We assessed the association between all-cause mortality and CAV using Cox proportional hazards and used Kaplan Meier methods to evaluate all-cause mortality stratified by CAV and transplant era (1989-2001, 2002-2017). Ninety-six patients were transitioned to adult care by January 2022, of which 53 underwent repeat coronary angiography as adults. CAV was newly diagnosed in 49% patients after transition to adult care. The overall incidence of CAV was 3.9 cases per 100 person-years. There was no difference in the adjusted incidence of CAV according to transplant era (subdistribution hazard ratios = 1.17, 95% confidence interval (CI) 0.54-2.66). CAV was associated with a higher risk of death in the early era (hazard ratio (HR) 10.29, 95% CI 2.16-49.96), but not in the recent era (HR 1.61, 95% 0.35-7.47). There is a role for continued CAV surveillance after the transition to adult care. The implications of diagnosing CAV after the transition to adult care require further study, particularly because the risk of death in pediatric HT recipients diagnosed with CAV in the more recent era may be attenuated compared to the earlier HT era. [ABSTRACT FROM AUTHOR]

Heart transplantation has become the standard of care for pediatric patients with end‐stage heart disease throughout the world. Since the first transplant was performed in 1967, the number of transplants has grown dramatically with 13 449 pediatric heart transplants being reported to The International Society of Heart and Lung Transplant (ISHLT) between January 1992 and June 30, 2018. Outcomes have consistently improved over the last few decades, specifically short‐term outcomes. Most recent survival data demonstrate that recipients who survive to 1‐year post‐transplant have excellent long‐term survival with more than 60% of those who were transplanted as infants being alive 25 years later. Nonetheless, the rates of graft loss beyond the first year have remained relatively constant over time; driven primarily by our poor understanding and lack of treatments for chronic allograft vasculopathy (CAV). Acute rejection, CAV, graft failure, and infection continue to be the major causes of death within the first 5 years post‐transplant. In addition, renal dysfunction, malignancy, and the need for re‐transplantation remain as significant issues that require close follow‐up. Looking forward, key challenges include improving donor utilization rates (including donation after cardiac death (DCD) and the use of ex vivo perfusion devices), the development of non‐invasive biomarkers for rejection, efforts to mitigate the long‐term effects of immunosuppression, and prevention of CAV. It is not possible to cover the entire evolution of pediatric heart transplantation over the last five decades, but in this review, we hope to touch on key observations, lessons learned, and practice changes that have advanced the field, as well as glance ahead to the next decade. [ABSTRACT FROM AUTHOR]

Background: Children listed for heart transplantation face the highest waitlist mortality among all solid organ transplant patients (14%). Attempts at decreasing donor allograft non‐utilization (41.5%) could potentially decrease waitlist mortality for pediatric heart transplant patients. Our aim was to quantify the non‐utilization risk of pediatric donor heart allografts at the time of initial offering. Methods: Using the United Network of Organ Sharing (UNOS) database, we retrospectively analyzed 8823 deceased donors (≤18 years old) data through univariable and multivariable analysis and logistic regression models. These factors were divided into a training (n = 5882) and validation set (n = 2941). Donor clinical characteristics and laboratory values were used to predict non‐utilization of donor hearts. The multivariable analysis used factors that were significant from the univariable analysis (p‐value <.05), and the pediatric non‐utilization risk index (pDRSI) included significant factors from the multivariable analysis, producing an overall risk score for non‐utilization. With these data, we created a non‐utilization risk index to predict likelihood of donor allograft non‐utilization. Results: From the 24 potential factors that were identified from univariable analysis, 17 were significant predictors (p <.05) of pediatric heart non‐utilization in the multivariable analysis. Low left ventricular ejection fraction (odds ratio (OR)‐35.3), hepatitis C positive donor (OR‐23.3), high left ventricular ejection fraction (OR‐3.29), and hepatitis B positive donor (OR‐3.27) were the most significant risk factors. The phDSRI has a C‐statistic of 0.80 for the training set and 0.80 for the validation set. Conclusion: Using over 8000 donors, the phDSRI uses 17 significant risk factors to predict risk of pediatric heart donor allograft non‐utilization. [ABSTRACT FROM AUTHOR]

Background: Pulmonary hypertension (PH) may limit the outcome of pediatric heart transplantation (pHTx). We evaluated pulmonary hemodynamics in children undergoing pHTx. Methods: Cross‐sectional, single‐center, observational study analyzing pulmonary hemodynamics in children undergoing pHTx. Results: Twenty‐three children (female 15) underwent pHTx at median (IQR) age of 3.9 (.9–8.2) years with a time interval between first clinical signs and pHTx of 1.1 (.4–3.2) years. Indications for pHTx included cardiomyopathy (CMP) (n = 17, 74%), congenital heart disease (CHD) (n = 5, 22%), and intracardiac tumor (n = 1, 4%). Before pHTx, pulmonary hemodynamics included elevated pulmonary artery pressure (PAP) 26 (18.5–30) mmHg, pulmonary capillary wedge pressure (PCWP) 19 (14–21) mmHg, left ventricular enddiastolic pressure (LVEDP) 17 (13–22) mmHg. Transpulmonary pressure gradient (TPG) was 6.5 (3.5–10) mmHg and pulmonary vascular resistance (Rp) 2.65 WU*m2 (1.87–3.19). After pHTx, at immediate evaluation 2 weeks after pHTx PAP decreased to 20.5 (17–24) mmHg, PCWP 14.5 (10.5–18) mmHg (p <.05), LVEDP 16 (12.5–18) mmHg, TPG 6.5 (4–12) mmHg, Rp 1.49 (1.08–2.74) WU*m2 resp.at last invasive follow up 4.0 (1.4–6) years after pHTx, to PAP 19.5 (17–21) mmHg (p <.05), PCWP 13 (10.5–14.5) mmHg (p <.05), LVEDP 13 (10.5–14) mmHg, TPG 7 (5–9.5) mmHg, Rp 1.58 (1.38–2.19) WU*m2 (p <.05). In CHD patients PAP increased (p <.05) after pHTx at immediate evaluation and decreased until last follow‐up (p <.05), while in CMP patients there was a continuous decline of mean PAP values immediately after HTx (p <.05). Conclusions: While PH before pHTx is frequent, after pHTx the normalization of PH starts immediately in CMP patients but is delayed in CHD patients. [ABSTRACT FROM AUTHOR]

Impact of pretransplantation risk factors on mortality in the first year after heart transplantation remains largely unknown. Using machine learning algorithms, we selected clinically relevant identifiers that could predict 1-year mortality after pediatric heart transplantation. Data were obtained from the United Network for Organ Sharing Database for years 2010-2020 for patients 0-17 years receiving their first heart transplant (N = 4150). Features were selected using subject experts and literature review. Scikit-Learn, Scikit-Survival, and Tensorflow were used. A train:test split of 70:30 was used. N-repeated k-fold validation was performed (N = 5, k = 5). Seven models were tested, Hyperparameter tuning performed using Bayesian optimization and the concordance index (C-index) was used for model assessment. A C-index above 0.6 for test data was considered acceptable for survival analysis models. C-indices obtained were 0.60 (Cox proportional hazards), 0.61 (Cox with elastic net), 0.64 (gradient boosting), 0.64 (support vector machine), 0.68 (random forest), 0.66 (component gradient boosting), and 0.54 (survival trees). Machine learning models show an improvement over the traditional Cox proportional hazards model, with random forest performing the best on the test set. Analysis of the feature importance for the gradient boosted model found that the top 5 features were the most recent serum total bilirubin, the travel distance from the transplant center, the patient body mass index, the deceased donor terminal Serum glutamic pyruvic transaminase/Alanine transaminase (SGPT/ALT), and the donor PCO 2. Combination of machine learning and expert-based methodology of selecting predictors of survival for pediatric heart transplantation provides a reasonable prediction of 1- and 3-year survival outcomes. SHapley Additive exPlanations can be an effective tool for modeling and visualizing nonlinear interactions. [ABSTRACT FROM AUTHOR]

Background: Recipient antibodies against mismatched donor-specific human leukocyte antigens (HLA) are known to be associated with antibody-mediated rejection (AMR), posing increased risks of cardiac allograft vasculopathy (CAV), graft dysfunction, and graft loss after heart transplant (HTx). However, the impact of non-HLA antibodies on HTx outcome is not yet well defined. Case description: Here we report a case of a pediatric patient, who was retransplanted after developing CAV in his first heart allograft. Five years post 2nd HTx, the patient presented with graft dysfunction and mild rejection (ACR 1R, AMR 1H, C4d Neg) in the cardiac biopsy in the absence of HLA donor-specific antibodies (DSAs). We detected strong antibodies against non-HLA antigens, including angiotensin II receptor type 1 (AT1R) and donorspecific MHC class I chain-related gene A (MICA), in the patient's serum that were implicated in the AMR and accelerated CAV of his second allograft, and likely played a role in the loss of his first allograft as well. Background: Recipient antibodies against mismatched donor-specific human leukocyte antigens (HLA) are known to be associated with antibody-mediated rejection (AMR), posing increased risks of cardiac allograft vasculopathy (CAV), graft dysfunction, and graft loss after heart transplant (HTx). However, the impact of non-HLA antibodies on HTx outcome is not yet well defined. Case description: Here we report a case of a pediatric patient, who was retransplanted after developing CAV in his first heart allograft. Five years post 2nd HTx, the patient presented with graft dysfunction and mild rejection (ACR 1R, AMR 1H, C4d Neg) in the cardiac biopsy in the absence of HLA donor-specific antibodies (DSAs). We detected strong antibodies against non-HLA antigens, including angiotensin II receptor type 1 (AT1R) and donorspecific MHC class I chain-related gene A (MICA), in the patient's serum that were implicated in the AMR and accelerated CAV of his second allograft, and likely played a role in the loss of his first allograft as well. Conclusion: This case report underscores the clinical relevance of non-HLA antibodies in heart transplantation and highlights the value of incorporating these tests in the immunological risk assessment and post-transplant monitoring of HTx recipients. Conclusion: This case report underscores the clinical relevance of non-HLA antibodies in heart transplantation and highlights the value of incorporating these tests in the immunological risk assessment and post-transplant monitoring of HTx recipients. [ABSTRACT FROM AUTHOR]

Introduction: Heart transplantation is the standard treatment for end‐stage heart disease. Despite advances in the field, patients remain under risk of developing complications, including opportunistic infections, such as tuberculosis. We present the unprecedented case of cerebral tuberculoma in a 9‐year‐old heart transplant recipient. Case Scenario: A 9‐year‐old female child, who underwent heart transplantation in December 2020, was admitted to the emergency department in September 2021 due to headache and vomiting. She had normal vital signs and a mild left hemiparesis. Laboratory findings included lymphopenia and a low C Reactive Protein and brain images showed expansive lesions. A biopsy of the intracranial lesion was performed and anatomopathological analysis was compatible with tuberculoma. After the diagnosis was established, treatment protocol for neurotuberculosis was initiated, the patient had a satisfactory clinical evolution and was discharged 22 days after admission. Discussion: Clinical manifestation of tuberculosis usually occurs up to 6 months after transplantation, the findings are commonly atypical and symptoms may be mild. We could not find in medical literature any description of the disease in a heart transplant recipient as young as the one presented in this case report. We documented great response to treatment, even though conventional antituberculosis therapy may interfere with immunosuppression. Conclusion: Patients in the postoperative period following heart transplantation are at high risk for developing opportunistic infections such as tuberculosis, which may present with atypical symptoms. Therefore the clinician must have a high index of suspicion in order to make the correct diagnosis and promptly start treatment. [ABSTRACT FROM AUTHOR]

Children of minority race and ethnicity experience inferior outcomes postheart transplantation (HTx). Studies have associated ventricular assist device (VAD) bridge-to-transplant (BTT) with similar-to-superior post-transplant-survival (PTS) compared to no mechanical circulatory support. It is unclear whether racial and ethnic discrepancies exist in VAD utilization and outcomes. The United Network for Organ Sharing (UNOS) database was used to identify 6,121 children (<18 years) listed for HTx between 2006 and 2021: black (B—22% of cohort), Hispanic (H—21%), and white (W—57%). VAD utilization, outcomes, and PTS were compared between race/ethnicity groups. Multivariable Cox proportional analyses were used to study the association of race and ethnicity on PTS with VAD BTT, using backward selection for covariates. Black children were most ill at listing, with greater proportions of UNOS status 1A/1 (p < 0.001 vs H & W), severe functional limitation (p < 0.001 vs H & W), and greater inotrope requirements (p < 0.05 vs H). Non-white children had higher proportions of public insurance. VAD utilization at listing was: B—11%, H—8%, W—8% (p = 0.001 for B vs H & W). VAD at transplant was: B—24%, H—21%, W—19% (p = 0.001 for B vs H). At transplant, all VAD patients had comparable clinical status (functional limitation, renal/hepatic dysfunction, inotropes, mechanical ventilation; all p > 0.05 between groups). Following VAD, hospital outcomes and one-year PTS were equivalent but long-term PTS was significantly worse among non-whites-(p < 0.01 for W vs B & H). On multivariable analysis, black race independently predicted mortality (hazard ratio 1.67 [95% confidence interval 1.22-2.28]) while white race was protective (0.54 [0.40-0.74]). Pediatric VAD use is, seemingly, equitable; the most ill patients receive the most VADs. Despite similar pretransplant and early post-transplant benefits, non-white children experience inferior overall PTS after VAD BTT. [ABSTRACT FROM AUTHOR]

Human leukocyte antigen (HLA) molecular mismatch is a powerful biomarker of rejection. Few studies have explored its use in assessing rejection risk in heart transplant recipients. We tested the hypothesis that a combination of HLA Epitope Mismatch Algorithm (HLA-EMMA) and Predicted Indirectly Recognizable HLA Epitopes (PIRCHE-II) algorithms can improve risk stratification of pediatric heart transplant recipients. Class I and II HLA genotyping were performed by next-generation sequencing on 274 recipient/donor pairs enrolled in the Clinical Trials in Organ Transplantation in Children (CTOTC). Using high-resolution genotypes, we performed HLA molecular mismatch analysis with HLA-EMMA and PIRCHE-II, and correlated these findings with clinical outcomes. Patients without pre-formed donor specific antibody (DSA) (n=100) were used for correlations with post-transplant DSA and antibody mediated rejection (ABMR). Risk cut-offs were determined for DSA and ABMR using both algorithms. HLA-EMMA cut-offs alone predict the risk of DSA and ABMR; however, if used in combination with PIRCHE-II, the population could be further stratified into low-, intermediate-, and high-risk groups. The combination of HLA-EMMA and PIRCHE-II enables more granular immunological risk stratification. Intermediate-risk cases, like low-risk cases, are at a lower risk of DSA and ABMR. This new way of risk evaluation may facilitate individualized immunosuppression and surveillance. [ABSTRACT FROM AUTHOR]

The existence of a "weekend effect" in heart transplantation (HTx) is understudied. The present study sought to determine whether the odds of (HTx) offer acceptance differed for adult and pediatric candidates depending upon the day on which the offer occurred. United Network for Organ Sharing data were used to identify all HTx offers to adult (listing age ≥18) and pediatric candidates from 2000-2019. Odds of offer acceptance were studied, comparing weekends, holidays, and conferences (Society of Thoracic Surgeons [STS], American Association for Thoracic Surgery [AATS], International Society for Heart and Lung Transplantation [ISHLT]) to "baseline" (all other days). Multivariable binary logistic regression analyses were performed to determine independent predictors of offer nonacceptance, controlling for the impacts of program transplant volume, region, and candidate characteristics. A total of 323,953 offers occurred – 298,405 to adults and 25,548 to pediatric candidates. Clinically significant differences did not exist in donor or candidate characteristics between baseline or other events. The number of offers per day was stable throughout the year for both adults (p = 0.191) and pediatrics (p = 0.976). In adults, independently lower odds of acceptance existed on weekends (OR 0.88 [95% CI 0.84-0.92]), conferences in aggregate (0.86 [0.77-0.95]), and holidays in aggregate (0.81 [0.72-0.91]). In children, independently lower odds of acceptance were seen on weekends (0.88 [0.79-0.98]), during STS (0.46 [0.25-0.83], and during Christmas (0.32 [0.14-0.76]). The day on which a HTx offer occurs significantly impacts its likelihood of acceptance. Further work can determine the impacts of human behavior or resource distribution, but knowledge of this phenomenon can inform efforts to ensure ideal organ allocation throughout the year. [ABSTRACT FROM AUTHOR]

Tricuspid annular plane systolic excursion (TAPSE) is important in the noninvasive echocardiographic assessment of right heart function. This retrospective observational study shows correlations of TAPSE with invasive right heart catheterization parameters after pediatric heart transplantation (HTx). The study included patients after pediatric HTx with cardiac catheterizations in 2018/2019 and measurement of TAPSE (n = 52 patients with 57 examinations; 50.9% adults, 52.6% female, median age: 18.54 years). TAPSE was compared with normal values. Stepwise, linear and multiple regression were used to show influencing variables on TAPSE. Mean TAPSE z‐score was −3.48 (SD: 2.25) and 68.4% of HTx‐recipients showed abnormally reduced TAPSE (z‐score ←2) compared to normal values. Multiple regression (p‐value <0.001; corrected R2 = 0.338) showed significant correlations of time since HTx (p‐value <0.001) and mPAP (p‐value: 0.008) with TAPSE z‐scores. Divided into subgroups (time since HTx <10 and ≥10 years), TAPSE and mPAP correlated only ≥10 years after HTx (p‐value = 0.002). This study provides data of TAPSE even ≥10 years after pediatric HTx. Most patients showed a decreased TAPSE early after HTx, which improved over time. TAPSE z‐scores correlated significantly with time since HTx and mPAP, especially ≥10 years post‐HTx. Therefore, TAPSE must be used carefully in the early follow‐up. [ABSTRACT FROM AUTHOR]

Cardiac allograft vasculopathy (CAV) sometimes leads to restenosis, even after percutaneous transcatheter intervention. Recently, drug-coated balloons (DCBs) have been successfully used to treat coronary artery disease, especially CAVs, in adults. However, no studies have used DCBs in pediatric CAVs. We encountered a patient with CAV who underwent cardiac transplantation for restrictive cardiomyopathy at the age of 2 years. Nine years after the transplantation, severe stenosis of the proximal left anterior descending branch was observed. Considering the patient's young age and the possibility of restenosis, we performed an intervention with DCB. Follow-up conducted 7 months after the intervention showed no restenosis. Cardiac coronary artery lesions following transplantation are more likely to result in restenosis earlier than arteriosclerotic lesions. In pediatric patients, restenosis might require multiple stents and prolonged antiplatelet therapy. Our findings provide evidence supporting the possibility of an effective treatment of CAV in children.

Human leukocyte antigen (HLA) molecular mismatch is a powerful biomarker of rejection. Few studies have explored its use in assessing rejection risk in heart transplant recipients. We tested the hypothesis that a combination of HLA Epitope Mismatch Algorithm (HLA-EMMA) and Predicted Indirectly Recognizable HLA Epitopes (PIRCHE-II) algorithms can improve risk stratification of pediatric heart transplant recipients. Class I and II HLA genotyping were performed by next-generation sequencing on 274 recipient/donor pairs enrolled in the Clinical Trials in Organ Transplantation in Children (CTOTC). Using high-resolution genotypes, we performed HLA molecular mismatch analysis with HLA-EMMA and PIRCHE-II, and correlated these findings with clinical outcomes. Patients without pre-formed donor specific antibody (DSA) (n=100) were used for correlations with post-transplant DSA and antibody mediated rejection (ABMR). Risk cut-offs were determined for DSA and ABMR using both algorithms. HLA-EMMA cut-offs alone predict the risk of DSA and ABMR; however, if used in combination with PIRCHE-II, the population could be further stratified into low-, intermediate-, and high-risk groups. The combination of HLA-EMMA and PIRCHE-II enables more granular immunological risk stratification. Intermediate-risk cases, like low-risk cases, are at a lower risk of DSA and ABMR. This new way of risk evaluation may facilitate individualized immunosuppression and surveillance.

PRES is a relatively rare complication of heart transplantation (HTx), and its clinical course and risk factors remain poorly understood. We sought to examine the incidence, natural history, and risk factors for PRES after pediatric HTx. Fourteen-center retrospective study of 42 PRES-cases and 1,502 HTx-recipients without PRES, between 2000 and 2018. Demographic and clinical data were collected into a central database. Factors associated with PRES were identified by Cox Proportional Hazard multivariable analysis. PRES occurred in 3.2% of HTx-recipients > 1 year of age; no infants developed PRES. Median onset of symptoms was 16 days (R 2-2468 days) after HTx, most commonly seizures (38/42) or altered mental status (24/42). Almost all recipients (40/42) recovered fully. MRI showed typical vasogenic edema in 33/39. Those with PRES had gradually worsening hypertension in the preceding 5 days, culminating in severely elevated blood pressure (>P99+5 mm Hg) for 34 recipients when presenting with PRES. Calcineurin inhibitor (CNI) levels were supratherapeutic in only 8/42, and CNI-management did not significantly impact outcome. Risk of PRES was 12.8x higher in those with pretransplant Glenn/Fontan (CI 1.69, 96.27; p =.013) compared to recipients with congenital heart disease without Glenn/Fontan, while sex, age, BMI or ischemic time did not contribute significantly. Pediatric PRES generally occurs early after HTx, with seizures as the most common presenting symptom. Most patients are severely hypertensive upon presentation, whereas only 19% have supratherapeutic CNI-levels. Pre-existing Glenn or Fontan physiology is a strong risk factor for PRES after HTx. Almost all recipients recovered fully within days of presentation. [ABSTRACT FROM AUTHOR]

Background: Both gender‐ and weight‐matching between donor and recipient are thought to impact survival in pediatric heart transplantation, with clinical dogma holding that male donor hearts and "ideal" weight‐matching yield superior survival. The composite impacts of gender and weight on post‐transplant survival (PTS) are understudied. Methods: All pediatric (age <18) heart recipients between 1989 and 2021 with the complete recipient and donor gender and weight data were identified in the United Network for Organ Sharing database. Patients were grouped by recipient–donor gender (M & F) and donor‐to‐recipient weight ratio (DRWR; undersized [<0.8], ideal‐sized [0.8–1.5], oversized [>1.5]). Results: A total of 10 697 patients were identified. Among male recipients, PTS was greatest with oversized DRWR from either male or female donors (median 22.4 and 20.6 years; p <.001 vs. others) and lowest for undersized DRWR from either male or female donors (median 13.4 and 13.2 years; p <.001 vs. others). The majority (64%) of male recipients received ideal‐sized DRWR, among which female donor hearts yielded superior survival to males (median 18.9 vs. 17.4 years, p =.014). No differences in PTS existed for female recipients on the basis of gender‐match, DRWR, and gender/DRWR together (all p >.1). Conclusions: When considered together, gender and DRWR pairings impact PTS in male—but not female—pediatric heart transplant recipients. For males receiving ideal‐sized DRWR organs (most common pairing, >60%), male recipients achieve superior survival when female donor hearts are transplanted. These findings suggest that if weight is being used for size‐matching, donor gender should also be considered, particularly for male recipients. [ABSTRACT FROM AUTHOR]

Pediatric heart transplantation is the standard treatment for children complicated with refractory heart failure which is difficult to be treated by conventional surgery or drugs. At present, an increasing quantity of pediatric heart transplantation is being performed worldwide, whereas relevant experience is still lacking in China. In recent 10 years, significant progress has been achieved in pediatric heart transplantation. On one hand, the number of pediatric heart transplantation has been increased year by year. On the other hand, ABO-incompatible heart transplantation, application of ventricular assist device in children, and recipient-donor weight mismatch transplantation have been widely employed to resolve the shortage of donor heart in pediatric heart transplantation. However, relevant experience of pediatric heart transplantation is lacking in China, especially in understanding the indications of pediatric heart transplantation and the application of specific strategies for pediatric heart transplantation, etc. In this article, the development history, advances in therapeutic strategy and clinical prognosis of pediatric heart transplantation were reviewed. [ABSTRACT FROM AUTHOR]

Objectives: Induction therapy has been increasingly used in pediatric heart transplantation. This study evaluated the impact of anti‐thymocyte globulin (ATG) versus basiliximab as induction therapy on post‐transplant cytomegalovirus (CMV) infection, rejection at 1 year, coronary allograft vasculopathy (CAV), and mortality in pediatric heart transplant recipients receiving antiviral prophylaxis. Results: Of the 96 patients (age < 18 years) analyzed, 46 (47.9%) patients received basiliximab, and 50 (52.1%) received ATG. Median follow‐up was 3.0 (IQR, 1.7–4.9) years with 32.3% reporting CMV infection. The ATG group, as compared with the basiliximab group, had similar incidences of CMV infection (36% vs. 28.3%, p =.418), CMV viremia (22% vs. 19.6%, p =.769), and CMV‐positive tissue biopsy (30% vs. 22%, p =.486). The ATG group had lower incidences of rejection at 1 year (16% vs. 36.9%, p =.022) and CAV (4% vs. 23.9%, p =.006) with no difference in mortality (8% vs. 15.2%, p =.343), compared with the basiliximab group. Multivariate analysis showed that induction with ATG was associated with a lower risk of rejection at 1 year (OR,.31; 95% CI,.09–.94; p =.039) with no impact on the incidences of CMV infection (HR, 2.06; 95% CI,.54–7.89; p =.292), CAV (HR,.30; 95% CI,.04–2.58; p =.275), and mortality (HR,.39; 95% CI,.09–1.82; p =.233) compared to basiliximab induction. Discussion and conclusions: In conclusion, induction with ATG was associated with reduction in risk of rejection at 1 year with no effects on CMV infection, CAV, and mortality in pediatric heart transplant recipients with universal antiviral prophylaxis compared with basiliximab induction therapy. [ABSTRACT FROM AUTHOR]

Posterior reversible encephalopathy syndrome (PRES) is a clinical-radiographic syndrome reported in children with hypertension due to renal diseases, immunosuppression after solid organ transplant, cytotoxic agents for chemotherapy, and many others rare instances. We described PRES in a 6-year-old child with hypertension secondary to an incidental postoperative coarctation of the aorta after heart transplantation (HT). Her blood pressure was well controlled with amlodipine during the outpatient visits and home monitoring of blood pressure, but she had hypertension when presented with neurological symptoms. This case's unique feature is that although PRES has been described after pediatric HT, this is the first case report due to a postoperative coarctation of the proximal descending aorta related to scarring from previous multiple sternotomies leading to inadvertent external compression of the aorta with scar tissue. We discussed the risk factors associated with hypertension before PRES and the correlation of brain magnetic resonance imaging findings with clinical outcomes.

Background Heart transplantation with a donation after circulatory death (DCD) heart is complicated by substantial organ ischemia and ischemia–reperfusion injury. Exenatide, a glucagon‐like peptide−1 receptor agonist, manifests protection against cardiac ischemia–reperfusion injury in other settings. Here we evaluate the effects of exenatide on DCD hearts in juvenile pigs. Methods and Results DCD hearts with 15‐minutes of global warm ischemia after circulatory arrest were reperfused ex vivo and switched to working mode. Treatment with concentration 5‐nmol exenatide was given during reperfusion. DCD hearts treated with exenatide showed higher myocardial oxygen consumption (exenatide [n=7] versus controls [n=7], over 60–120 minutes of reperfusion, P

Posterior reversible encephalopathy syndrome (PRES) is a clinical-radiographic syndrome reported in children with hypertension due to renal diseases, immunosuppression after solid organ transplant, cytotoxic agents for chemotherapy, and many others rare instances. We described PRES in a 6-year-old child with hypertension secondary to an incidental postoperative coarctation of the aorta after heart transplantation (HT). Her blood pressure was well controlled with amlodipine during the outpatient visits and home monitoring of blood pressure, but she had hypertension when presented with neurological symptoms. This case's unique feature is that although PRES has been described after pediatric HT, this is the first case report due to a postoperative coarctation of the proximal descending aorta related to scarring from previous multiple sternotomies leading to inadvertent external compression of the aorta with scar tissue. We discussed the risk factors associated with hypertension before PRES and the correlation of brain magnetic resonance imaging findings with clinical outcomes. [ABSTRACT FROM AUTHOR]

Pediatric heart transplantation (HTx) faces challenges such as limited donor availability and the need for complex reconstructions, particularly in patients with congenital anomalies. Ex vivo perfusion offers a promising approach to minimize graft ischemic time and potentially expand the donor pool. We report our single-center experience using the TransMedics Organ Care System (OCS) for ex vivo perfusion in pediatric HTx. From 2020-2024, eight pediatric patients received OCS-perfused donor hearts. Median recipient age was 13 years (range 9-18), and median weight was 58.8 kg (33.2-127.8). Indications for HTx included dilated cardiomyopathy (n=4), hypertrophic cardiomyopathy (n=1), graft vasculopathy (n=1), and Fontan failure (n=2). Median OCS time was 273 minutes (195-328), and recipient ischemic time was 85 minutes (64-139). Post-transplant, all patients had normal LV function at discharge. Over a median follow-up of 11.9 months, there were no deaths. These findings suggest that ex vivo perfusion is a valuable technique in pediatric HTx., (Copyright © 2024. Published by Elsevier Inc.)

Background: The use of early mechanical circulatory support (MCS) following pediatric heart transplantation is not well-published. This paper attempts to uncover the incidence, predisposing factors, and outcomes of MCS in a large, international cohort., Methods: The Pediatric Heart Transplant Society Database (an international, prospective, event-driven database) was retrospectively analyzed for all cases of primary heart transplant over an 11-year period (2010-2020), dividing the cohort based on need for MCS within 30 days of transplantation., Results: Of 4,321 primary transplants, 249 (5.8%) required MCS (230 ECMO (Extracoporeal Membranous Oxygenation), 19 ventricular assist device). In a Cox proportional hazard model, congenital heart disease (p = 0.0002), older donor age (p < 0.0001), and longer ischemic time (p = 0.018) were each related to an increased need for MCS; increasing recipient body surface area (p < 0.0001) and increasing donor left ventricular ejection fraction (p = 0.016) were both correlated with less MCS use. One-year survival in those requiring MCS was 54.2%, compared with 94.8% in those who did not need MCS (p < 0.0001). Later survival in patients surviving to 1 year was similar between the groups., Conclusions: MCS is used infrequently following pediatric heart transplant and is related to donor, recipient, and transplant factors. Although mortality is high, those surviving the first year post transplant have excellent outcomes. Judicious use in those patients who would otherwise perish is therefore justified., (Copyright © 2024 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Abstract Background The progressive risk of graft failure in pediatric heart transplantation (PHT) necessitates close surveillance for rejection and coronary allograft vasculopathy (CAV). The current gold standard of surveillance via invasive coronary angiography is costly, imperfect and associated with complications. Our goal was to assess the safety and feasibility of a comprehensive multi-parametric CMR protocol with regadenoson stress perfusion in PHT and evaluate for associations with clinical history of rejection and CAV. Methods We performed a retrospective review of 26 PHT recipients who underwent stress CMR with tissue characterization and compared with 18 age-matched healthy controls. CMR protocol included myocardial T2, T1 and extracellular volume (ECV) mapping, late gadolinium enhancement (LGE), qualitative and semi-quantitative stress perfusion (myocardial perfusion reserve index; MPRI) and strain imaging. Clinical, demographics, rejection score and CAV history were recorded and correlated with CMR parameters. Results Mean age at transplant was 9.3 ± 5.5 years and median duration since transplant was 5.1 years (IQR 7.5 years). One patient had active rejection at the time of CMR, 11/26 (42%) had CAV 1 and 1/26 (4%) had CAV 2. Biventricular volumes were smaller and cardiac output higher in PHT vs. healthy controls. Global T1 (1053 ± 42 ms vs 986 ± 42 ms; p

International consensus guidelines to vaccinate children after solid organ transplant with the live-attenuated varicella (VZV) vaccine exclude pediatric heart transplant recipients due to insufficient evidence for safety, seroconversion rate, or adverse event profile. Caution is also recommended in the setting of mycophenolate mofetil (MMF) immunosuppression. However, VZV infection in these patients can be serious or even fatal. We report our novel early experience with VZV vaccination in a cohort of 31 children following heart transplantation, 42% of who were on MMF. The early seroconversion rate was 16/17 (94%) with no major adverse events. Though a rash of some description was reported in 29%, spots were few and self-resolving in 1-3 days. Select pediatric heart transplant patients can be safely vaccinated with VZV vaccine with a high early seroconversion rate and a mild adverse event profile. [ABSTRACT FROM AUTHOR]

We analyzed the early and long-term survival after ABO-compatible heart transplantation in children under 3 years of age from 1991 to 2021 at our center. This retrospective and descriptive study aimed to identify serious adverse events associated with mortality after pediatric heart transplantation. 46 patients with congenital heart failure (37%) in end-stage heart failure have undergone a pediatric heart transplantation. Primary outcome of interest was survival at follow-up time. Median (IQR) follow-up time (y), age (y), body-weight (kg) and BMI (kg/cm2) were 13.2 (5.7–19.5), 0.9 (0.2–2.0), 6.8 (4.3–10.0) and 14.2 (12.3–15.7). Twenty-four (52%) patients were male. 15 patients (33%) had a single ventricle physiology. At 30- days survival rate was 94 ± 4%. Survival rate at 1, 5, 10 and 15 years post HTx was 87 ± 5%, 84 ± 6%, 79 ± 6% and 63 ± 8%. One child underwent re-transplantation after 4 years, and another one after 11 years – in both cases due to graft failure. Higher early mortality in patients under 3 months of age and in patients with single ventricle physiology. Transplant free survival at 15 years was in children with cardiomyopathy better (71 ± 10%) than in those with congenital heart disease (50 ± 13%). One or more previous heart surgeries prior to HTx (n = 21) were associated to more mortality. Pediatric heart transplantation has acceptable long-term results and is still the best therapeutic option in children with end-stage cardiac failure. Underlying anomalies and single ventricle physiology, age below 3 months had a significant impact on survival. • First because, patients with congenital heart disease in end-stage heart failure have already undergone one or more previous heart operations. • Second, because of shortage suitable donors many patients need mechanically assist device support as bridge to transplantation. • Heart transplantation in infants and young children remains one of the majority challenges in pediatric cardiac surgery. • Our goal was to identify serious adverse events associated with mortality and graft failure after pediatric heart transplantation. [ABSTRACT FROM AUTHOR]

Background: Studies have shown that the optimal ischemia time (IT) threshold in pediatric heart transplantation (PHT) is up to 4 h, independent of other donor organ factors. The purpose of this study was to examine the relationship between IT and donor left ventricular ejection fraction (LVEF) and study their impact on PHT outcomes. Methods: This is a retrospective cohort study of PHT (<18 years) identified in UNOS between January 2000 and March 2020. Post‐transplantation survival analysis of patients receiving donor hearts with IT<4, 4–6, and >6 h was performed using Kaplan–Meier curves. Cohort was divided according to donor LVEF median value, and survival was analyzed. Cox regression was performed. Results: Median LVEF was 65% in the study cohort (6669 PHT). Overall, IT>6 h was associated with worse survival compared to <4 h regardless of donor LVEF. For allografts with LVEF < 65%, IT = 4–6 h was associated with worse survival compared with IT < 4 h (p =.006) but had similar survival compared with IT > 6 h (p =.315). For allografts with LVEF ≥ 65%, IT = 4–6 h had similar survival compared with <4 h (p =.175) but improved survival compared with >6 h (p =.003). After adjusting for donor and recipient variables, Cox regression showed that IT = 4–6 h was not associated with increased mortality for LVEF ≥ 65%. Conclusions: The IT threshold of 4 h does not apply to all allografts. Recipients of hearts with LVEF≥65% can tolerate an IT up to 6 h without any detriment to survival. Routine acceptance of these donor hearts could mitigate longer waiting times and poor donor availability for many candidates. [ABSTRACT FROM AUTHOR]

Background: Clinical rejection (CR) defined as decision to treat clinically suspected rejection with change in immunotherapy based on clinical presentation with or without diagnostic biopsy findings is an important part of care in heart transplantation. We sought to assess the utility of donor fraction cell‐free DNA (DF cfDNA) in CR and the utility of serial DF cfDNA in CR patients in predicting outcomes of clinical interest. Methods: Patients with heart transplantation were enrolled in two sequential, multi‐center, prospective observational studies. Blood samples were collected for surveillance or clinical events. Clinicians were blinded to the results of DF cfDNA. Results: A total of 835 samples from 269 subjects (57% pediatric) were included for this analysis, including 28 samples associated with CR were analyzed. Median DF cfDNA was 0.43 (IQR 0.15, 1.36)% for CR and 0.10 (IQR 0.07, 0.16)% for healthy controls (p <.0001). At cutoff value of 0.13%, the area under curve (AUC) was 0.82, sensitivity of 0.86, specificity of 0.67, and negative predictive value of 0.99. There was serial decline in DF cfDNA post‐therapy, however, those with cardiovascular events (cardiac arrest, need for mechanical support or death) showed significantly higher levels of DF cfDNA on Day 0 (2.11 vs 0.31%) and Day 14 (0.51 vs 0.22%) compared to those who did not have such an event (p <.0001). Conclusion: DF cfDNA has excellent agreement with clinical rejection and, importantly, serial measurement of DF cfDNA predict clinically significant outcomes post treatment for rejection in these patients. [ABSTRACT FROM AUTHOR]

Advances in surgical techniques and outpatient cardiac care have led to a growing population of pediatric patients surviving well into adulthood with previous single-ventricle palliation. Continued improvement in survival has resulted in subsequent increases in the number of patients with single-ventricle physiology listed for heart transplantations. Some of these patients require mechanical circulatory support as a bridge to transplantation, although establishing successful mechanical circulatory support in these complex patients remains challenging. Only limited published data exist describing the perioperative anesthetic management and key considerations dedicated to patients with failing single-ventricle physiology presenting for ventricular assist devices. This clinical review aims to provide a focused evaluation of the vital perioperative considerations encountered in this novel population. [ABSTRACT FROM AUTHOR]

A six-year-old heart transplant recipient with additional significant co-morbidities, including severe hypoxic-ischemic injury, gastrostomy, tracheostomy, and mechanical ventilation dependency, encountered SARS-CoV-2 infection. The patient received tacrolimus and mycophenolate to prevent graft rejection, presented initially with SARS-CoV-2 positive and presumed pseudomonas aeruginosa pneumonia. Twenty-three days later, the patient presented with fever recurrence with evidence for systemic inflammation, which resolved rapidly with high-dose methylprednisolone. Interestingly, while IgM to SARS-CoV-2 was present, IgG was not detected even three months after his first positive test for SARS-CoV-2. The author discusses potential immune mechanisms that might have affected the course of multi-system inflammatory syndrome children (MIS-C) in this patient.

Background: Pediatric heart transplant (PHT) patients have the highest waitlist mortality of solid organ transplants, yet more than 40% of viable hearts are unutilized. A tool for risk prediction could impact these outcomes. This study aimed to compare and validate the PHT risk score models (RSMs) in the literature. Methods: The literature was reviewed to identify RSMs published. The United Network for Organ Sharing (UNOS) registry was used to validate the published models identified in a pediatric cohort (<18 years) transplanted between 2017 and 2019 and compared against the Scientific Registry of Transplant Recipients (SRTR) 2021 model. Primary outcome was post‐transplant 1‐year mortality. Odds ratios were obtained to evaluate the association between risk score groups and 1‐year mortality. Area under the curve (AUC) was used to compare the RSM scores on their goodness‐of‐fit, using Delong's test. Results: Six recipient and one donor RSMs published between 2008 and 2021 were included in the analysis. The validation cohort included 1,003 PHT. Low‐risk groups had a significantly better survival than high‐risk groups as predicted by Choudhry (OR = 4.59, 95% CI [2.36–8.93]) and Fraser III (3.17 [1.43–7.05]) models. Choudhry's and SRTR models achieved the best overall performance (AUC = 0.69 and 0.68, respectively). When adjusted for CHD and ventricular assist device support, all models reported better predictability [AUC > 0.6]. Choudhry (AUC = 0.69) and SRTR (AUC = 0.71) remained the best predicting RSMs even after adjustment. Conclusion: Although the RSMs by SRTR and Choudhry provided the best prediction for 1‐year mortality, none demonstrated a strong (AUC ≥ 0.8) concordance statistic. All published studies lacked advanced analytical approaches and were derived from an inherently limited dataset. [ABSTRACT FROM AUTHOR]

Since the initial International Society of Heart Lung Transplantation registry was published in 1982, the number of pediatric heart transplantations has increased markedly, reaching a steady state of 500–550 transplantation annually and occupying up to 10% of total heart transplantations. Heart transplantation is considered an established therapeutic option for patients with end-stage heart disease. The long-term outcomes of pediatric heart transplantations were comparable to those of adults. Issues affecting long-term outcomes include acute cellular rejection, antibody-mediated rejection, cardiac allograft vasculopathy, infection, prolonged renal dysfunction, and malignancies such as posttransplant lymphoproliferative disorder. This article focuses on medical issues before pediatric heart transplantation, according to the Korean Network of Organ Sharing registry and as well as major problems such as graft rejection and cardiac allograft vasculopathy. To reduce graft failure rate and improve long-term outcomes, meticulous monitoring for rejection and medication compliance are also important, especially in adolescents.

Cardiac allograft vasculopathy (CAV) sometimes leads to restenosis, even after percutaneous transcatheter intervention. Recently, drug-coated balloons (DCBs) have been successfully used to treat coronary artery disease, especially CAVs, in adults. However, no studies have used DCBs in pediatric CAVs. We encountered a patient with CAV who underwent cardiac transplantation for restrictive cardiomyopathy at the age of 2 years. Nine years after the transplantation, severe stenosis of the proximal left anterior descending branch was observed. Considering the patient's young age and the possibility of restenosis, we performed an intervention with DCB. Follow-up conducted 7 months after the intervention showed no restenosis. Cardiac coronary artery lesions following transplantation are more likely to result in restenosis earlier than arteriosclerotic lesions. In pediatric patients, restenosis might require multiple stents and prolonged antiplatelet therapy. Our findings provide evidence supporting the possibility of an effective treatment of CAV in children. [ABSTRACT FROM AUTHOR]

Background: We aimed to describe the incidence, risk factors, and clinical outcomes of pericardial effusions within 6 months after pediatric heart transplantation (HT). Methods: A single‐center retrospective cohort study was performed on all pediatric HT recipients from 2004 to 2018. Logistic regression was used to identify factors associated with pericardial effusions post‐HT, and survival was compared using log‐rank test. Results: During the study period, 97 HTs were performed in 93 patients. Fifty patients (52%) had a ≥small pericardial effusion within 6 months, 16 of which were, or became, ≥moderate in size. Pericardial drain was placed in 8 patients. In univariate analysis, larger recipient body surface area (p =.01) and non‐congenital heart disease (p =.002) were associated with pericardial effusion development. Donor/recipient size ratios, post‐HT hemodynamics, and rejection did not correlate with pericardial effusion development. In multivariable analysis, non‐congenital heart disease (adjusted odds ratio 3.3, p =.01) remained independently associated with development of pericardial effusion. There were no significant differences in post‐HT survival between patients with and without ≥small (p =.68) or ≥moderate pericardial effusions (p =.40). Conclusions: Pericardial effusions are common after pediatric HT. Patients with cardiomyopathy, or non‐congenital heart disease, were at higher risk for post‐HT pericardial effusions. Pericardial effusions increased morbidity but had no effect on mortality in our cohort. The risk factors identified may be used for anticipatory guidance in pediatric HT. [ABSTRACT FROM AUTHOR]

Summary: Reduced adherence after heart transplantation increases the risk for acute rejection. Therefore, the aim of this study was to evaluate the patient's satisfaction with outpatient care and quality of life (QOL) after pediatric and adult heart transplantation. Observational study after pediatric (n = 22) and adult (n = 65) heart transplantation and the parents of the pediatric patients (n = 22) to evaluate the patients' satisfaction with outpatient care and QOL. Established standardized questionnaires were used for patient satisfaction (ZAP survey) and QOL (SF36); the latter was compared with the cohort of the BGS98 survey (BGS98 cohort). ZAP score: excellent results with almost all values >80. QOL: pediatric cohort showed significantly higher values in physical functioning (P = 0.041) and role physical (P = 0.003) but significantly lower values in the sub‐scale general health (P = 0.02) compared to adult cohort. In comparison with BGS98 cohort, children showed almost similar results, whereas adult cohort showed worse values in physical and emotional functioning, but higher values regarding general health. The QOL of patients after pediatric heart transplantation is comparable to a standardized reference population in Germany, whereas adult patients show reduced physical and emotional functioning, but better values regarding general health. The patients' satisfaction with the outpatient care is very high. [ABSTRACT FROM AUTHOR]

Background: CNI‐free immunosuppression with conversion to mTORi‐based immunosuppression has been demonstrated to reduce CNI‐toxicity and to exhibit anti‐proliferative properties. However, the experience of CNI‐free immunosuppression in paediatric heart transplantation is limited. Methods: A retrospective analysis was conducted of 129 paediatric heart transplants performed between 1997 and 2015. Fifteen patients with clinically indicated conversion from CNI‐based to CNI‐free immunosuppression were identified. Survival data, rejection episodes, renal function, post‐transplantation lymphoproliferative disorder and CAV, including examination with OCT were analysed. Results: Immunosuppression conversion was successful in all patients. Fourteen of 15 patients (93%) are currently living with good graft function. Median post‐transplant survival was 15 years (range, 5–23 years), and median follow‐up since conversion was 6 years (range, 1–11 years). Mild (grade 1R) ACR was present in three patients after discontinuation of CNIs. The recovery of renal function with a significant increase in eGFR was observed at 1 and 3 years after conversion. No patient had angiographic signs of macroscopic CAV according to the current ISHLT classification; however, OCT showed the signs of angiographically silent CAV in all patients. CAV did not progress in any patient, implying CAV was stabilised by mTORi‐based CNI‐free immunosuppression. Conclusions: CNI‐free immunosuppression based on mTORis is a safe and appropriate strategy for maintenance therapy in selected paediatric patients, significantly improves renal function and stabilises CAV. OCT revealed early development of angiographically silent CAV. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study is to evaluate HHV-6 and PVB19 infection using polymerase chain reaction (PCR) and immunofluorescent assay (IFA) in the myocardium of pediatric patients with dilated cardiomyopathy (DCM) and the impact of viral persistence in the cardiac allograft after heart transplantation (HT). Methods: Multiplex droplet digital PCR was used to analyze the prevalence of viral sequences in myocardial samples from 48 pediatric DCM patients and 10 control subjects. Of the 48 DCM patients, 44 underwent HT. After HT, consecutive endomyocardial biopsy (EMB) samples were analyzed for the presence of PVB19 and HHV-6 antigens using IFA and the patients were evaluated for rejections, coronary vasculopathy, and graft loss. Results: Of the 48 DCM patients, 14 had positive viral PCR results in explanted/autopsy hearts. Among them, PVB19 was found in 8/48, HHV6 in 4/48, both PVB19 and HHV6 in 1/48, and enterovirus in one, but no adenovirus was found. The EMB samples obtained after HT were positive for PVB19 and HHV-6 in 7/44 and 3/44 cases, respectively. Viral presence in both the explanted heart and the cardiac allograft was demonstrated in 4 patients, 3 of whom were positive for PVB19, and one of whom was positive for HHV-6 pretransplant. Coronary vasculopathy and graft loss were more common in patients with PVB19-positive myocardial tissues versus those who were PVB19-negative. Conclusions: There is an association between PVB19 and HHV-6 infection and DCM in children. The study suggests the persistence of PVB19 and HHV-6 in the host can lead to subsequent viral reactivation in the transplanted heart, even in those recipients who do not have active myocarditis. PVB19 in the cardiac allograft tended toward higher adverse post-HT events.