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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]

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]

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]

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]

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]

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]

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]

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]

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]

Background: Antithymocyte globulin (ATG) consists of polyclonal antibodies directed primarily against human T lymphocytes but may contain antibodies with affinity for other tissues in the transplanted organ, resulting in complement (C4d) deposition. This phenomenon has been demonstrated in endomyocardial biopsies (EMBs) of adult cardiac transplants. We examined the relationship of induction immunosuppression with ATG and C4d deposition in EMB of pediatric cardiac transplants. Methods: Results of C4d immunohistochemistry were available from all EMB of patients transplanted at our center between June 2012 and April 2018 (n = 48) who received induction immunosuppression with either ATG (n = 20) or basiliximab (n = 28) as the standard of care. Results: C4d deposition in the first year post–heart transplant was more commonly seen among patients who received ATG induction (20% of EMBs in ATG group vs 1% of EMBs in basiliximab group; p <.0001). C4d deposition related to ATG was observed early post‐transplant (50% ATG vs 0% basiliximab on first EMB; p <.0001 and 35% ATG vs 0% basiliximab on the second EMB; p =.0012). While this difference waned by the third EMB (5% ATG vs 0% basiliximab; p =.41), positive C4d staining persisted to the sixth EMB in the ATG group only (6%). Conclusion: C4d deposition is common on EMB up to 1 year post–pediatric cardiac transplant following ATG induction. This high rate of positive C4d staining in the absence of histologic AMR after ATG induction therapy must be accounted for in making clinical decisions regarding cardiac allograft rejection diagnosis and treatment. [ABSTRACT FROM AUTHOR]

A 16‐year‐old with new‐onset dilated cardiomyopathy underwent VAD placement, later complicated by low flow from outflow graft kinking. To expedite heart transplantation, TCV was calculated and compared with 141 normal patients pinpointing the upper weight threshold. He was transplanted 2 days later within the expanded weight range with no post‐transplant complications. [ABSTRACT FROM AUTHOR]

CMV infection remains a significant cause of morbidity among pediatric HTx recipients We explored the implications of CMV infection on post‐transplant outcomes among CMV risk‐stratified pediatric HTx recipients receiving VGC prophylaxis. Children who underwent HTx between January 2010 and October 2016 were stratified according to CMV risk at time of transplant and evaluated for evidence of post‐transplant CMV infection, rejection, CAV, and graft loss. Among 97 children, 41 (42%) were considered HR or IR risk for CMV infection and received VGC prophylaxis. CMV DNAemia was observed in 34% of children, including 71% HR, 40% IR, and 18% LR individuals. Median time to CMV DNAemia following VGC prophylaxis was 32D among HR vs 277D in IR subjects (P =.042). No difference in overall graft loss was noted among groups, but CMV HR children had decreased rejection‐free survival (3.5 years) compared to IR (6 years, P =.015) and LR children (8 years, P =.0003). CMV was noted on EMB in 13% of children but was not associated with increased CAV, rejection or graft loss. High‐risk CMV status was associated with decreased time to CMV infection despite VGC prophylaxis, compared to IR, and decreased rejection‐free survival times compared to both IR and LR recipients. Detection of CMV on EMB was not associated with increased rejection, CAV or graft loss. Additional studies are needed to explore the impact of CMV infection on rejection‐free survival in HTx recipients. [ABSTRACT FROM AUTHOR]

We aimed to review current literature on the discard rate of donor hearts offered to pediatric recipients and assess geographical differences. Consequences and ways to reduce the discard rate are discussed. A systemic review on published literature on pediatric transplantation published in English since 2010 was undertaken. Additionally, a survey was sent to international OPOs with the goal of incorporating responses from around the world providing a more global picture. Based on the literature review and survey, there is a remarkably wide range of discard and/or refusal for pediatric hearts offered for transplant, ranging between 18% and 57% with great geographic variation. The data suggest that that the overall refusal rate may have decreased over the last decade. Reasons for organ discard were difficult to identify from the available data. Although the refusal rate of pediatric donor hearts seems to be lower compared to that reported in adults, it is still as high as 57% with geographic variation. [ABSTRACT FROM AUTHOR]

Objectives: To correlate gene expression profiling scores obtained by AlloMap® with cardiac hemodynamics, cardiac allograft vasculopathy (CAV), and echocardiographic parameters in asymptomatic, rejection‐free pediatric heart transplant (HT) recipients. Methods: Single‐institution retrospective study of 210 AlloMap scores obtained concomitantly with cardiac catheterization and echocardiogram from 55 children during follow‐up after cardiac transplantation. Results: The median age at HT was 5.1 years (range, 0.9‐14.1), with 29 males and 26 females. AlloMap scores were high in <2 years vs ≥2 years of age at the time of HT (P =.001), and trending higher with time after HT (R2 =.04, P =.004). There was no significant difference in scores between ACR grades 0 and 1R or CAV. There was mild to modest correlation of AlloMap scores with the mean right atrial pressure (P =.002), and pulmonary capillary wedge pressure (P =.02), but no correlation was found with LV SF% (P =.3), LV EF% (P =.5), or RV FAC % (P =.8). Conclusions: Our study provides preliminary data that the AlloMap score must be studied carefully before it can be used in children, particularly in those under 2 years of age. Monitoring of serial scores for each patient could potentially reflect changes in allograft performance that may determine indications for catheterization and biopsy which needs to be validated in future studies. [ABSTRACT FROM AUTHOR]

Background: We sought to analyze brain death interval and outcomes of pediatric cardiac transplantation using national registry data. Methods: We retrospectively evaluated a pediatric cohort from the UNOS registry from 2005 to 2014. We restricted the donor cohort to those with a primary central nervous system event as the cause of hospitalization. Brain death interval (BDI) was defined as the time between hospital admission and organ procurement. Primary outcomes were recipient and graft survival time. Logistical regression modeling was used for multivariable analysis. Results: The donor cohort included 2565 cases. Multivariable analysis demonstrated no relationship between BDI and recipient or graft survival time. For patient survival time, the lowest HR was 0.94 (0.63‐1.39), P = 0.531; for graft survival time, the lowest HR was 0.89 (0.53‐1.49), P = 0.563. We obtained similar results using a non‐restricted donor cohort. Conclusions: There was no clear relationship between BDI and recipient or graft survival after pediatric cardiac transplantation. [ABSTRACT FROM AUTHOR]

Background: PGD is a complication after heart transplantation (OHT) and a significant cause of mortality, particularly in infant recipients. Lack of standardized definition of PGD in the pediatric population makes the prevalence and magnitude of impact unclear. Methods: ISHLT PGD consensus guidelines, which include inotrope scores and need for MCS, were applied retrospectively to 208 pediatric OHT recipients from a single institution from 1/2005‐5/2016. PGD was defined as: moderate PGD—inotrope score >10 on postoperative day 1 (24‐48 hours), and severe PGD—MCS within 24 hours (in the absence of detectable rejection). Results: PGD occurred in 34 patients (16.3%); 14 of which had severe PGD (6.7%). Multivariate risk factors for PGD included CPB time (OR 10.3/10 min, 95% 10.05, 10.2, P = 0.03), Fontan palliation (OR 1.9, 95% 1.2, 3.97), and PCM (OR 5.65, 95% 1.52, 22.4); but not age, weight, ischemic time, or donor characteristics. Upon sub‐analysis excluding patients with PCM, increased CPB was a significant multivariate risk factor (OR 10.09, 95% 9.89, 10.12, P = 0.003). Patients with PGD had decreased discharge survival compared to those without PGD (85% vs 96%, P < 0.01). Severe PGD was associated with the poorest 1‐year survival (57% vs 91% without PGD, P = 0.04). Conclusion: Patients with prolonged CPB are potentially at risk for developing PGD. Neither infant recipients nor donor characteristics were associated with an increased risk of PGD in the current era. [ABSTRACT FROM AUTHOR]

We aimed to determine whether malignancy after pediatric HTx for ACM affects overall post- HTx survival. Patients <18y listed for HTx for ACM in the PHTS database between 1993 and 2014 were compared to those with DCM. A 2:1 matched DCM cohort was also compared. Wait-list and post- HTx survival, along with freedom from common HTx complications, were compared. Eighty subjects were listed due to ACM, whereas 1985 were listed for DCM. Although wait-list survival was higher in the ACM group, post- HTx survival was lower for the ACM cohort. Neither difference persisted in the matched cohort analysis. Primary cause of death in the ACM group was infection, which was higher than the DCM group. Malignancy rates were not different. All ACM malignancies were due to PTLD without primary cancer recurrence or SMN. Long-term graft survival after pediatric HTx for ACM is no different than for matched DCM peers, nor is there an increased risk of any malignancy. However, risk of infection and death from infection after HTx are higher in the ACM group. Further studies are needed to assess the effects of prior chemotherapy on susceptibility to infection in this group. [ABSTRACT FROM AUTHOR]

In pediatric heart transplantation, the size of the donor organ is an important criterion for organ allocation. Oversized donor hearts are often accepted with good results, but some complications in relation to a high donor-recipient ratio have been described. Our patient was transplanted for progressive heart failure in dilated cardiomyopathy. The donor-to-recipient weight ratio was 3 (donor weight 65 kg, recipient weight 22 kg). The intra-operative echocardiography before chest closure showed excellent cardiac function, no tricuspid valve regurgitation, and a normal central venous pressure. After chest closure, central venous pressure increased substantially and echocardiography revealed a severe tricuspid insufficiency. As other reasons for right ventricular dysfunction, that is, myocardial ischemia, pulmonary hypertension, and rejection, were excluded, we assumed that the insufficiency was caused by an alteration of the right ventricular geometry. After 1 week, the valve insufficiency regressed to a minimal degree. In pediatric heart transplant patients with a high donor-to-recipient weight ratio, the outlined complication may occur. If other reasons for right ventricular heart failure can be ruled out, this entity is most likely caused by an acute and transient alteration of the right ventricular geometry that may disappear over time. [ABSTRACT FROM AUTHOR]

Despite the establishment of heart transplantation as a life-saving therapy for children and adolescents, little research has focused on the biopsychosocial impact of the transplant process. Few studies have captured the subjective experiences of young heart transplant recipients. This study examined the experiences and perspectives of children and adolescents during the pretransplant phase of waiting for a donor organ. Grounded theory methods guided data collection and analysis. A total of 27 adolescents participated in semistructured qualitative interviews. Findings illuminate the waiting period for pediatric heart transplantation to be a pervasive experience, with consequent impact on physical, psychological, and social well-being. Participants described various biopsychosocial processes and experiences that occurred during this time, with data analysis yielding themes reflecting notions of ' struggling to survive,' including physical limitations, lethargy, social isolation, discomfort with physical appearance, and academic issues. This research identifies the pretransplant experience as a period framed within a text of debilitation and negative self-perceptions related to health and well-being. Supporting children and their families as they navigate this complex and uncertain journey is merited, and results invite further interventional development and research. [ABSTRACT FROM AUTHOR]

Autoimmune and allergic diseases cause morbidity and diminished quality of life in pediatric organ transplant recipients. We hypothesize that younger age at transplantation and immunosuppression regimen play a role in the development of immune-mediated disease following heart transplant. A single institution retrospective review identified all patients undergoing heart transplant at ≤18 yr of age from 1987 to 2010 who survived ≥1 yr. Using medical record and database review, patients were evaluated for development of autoimmune or severe allergic disease. Of 129 patients who met criteria, seven patients (5.4%) with autoimmune or severe atopic disease were identified. Immune-mediated diseases included inflammatory bowel disease (n = 3), eosinophilic esophagitis/colitis (n = 4), and chronic bullous disease of childhood (n = 1). Patients <1 yr of age at transplant were at greater risk of developing autoimmune disease than patients 1-18 yr at transplant ( OR = 9.3, 95% CI 1.1-79.2, p = 0.02). All affected patients underwent thymectomy at <1 yr of age (7/71 vs. 0/58, p = 0.02). In our experience, heart transplantation in infancy is associated with the development of immune-mediated gastrointestinal and dermatologic diseases. Further study is needed to determine risk factors for the development of immune-mediated disease to identify best practices to decrease incidence. [ABSTRACT FROM AUTHOR]

Few studies compare HRQOL and PSA in children who have undergone different types of solid organ Tx. In this cross-sectional study, HRQOL and PSA were assessed in 74 Tx patients (16 heart, 44 kidney, 14 liver) at a mean age of 11.5 (range 6.3-16.7), 7.2 yr post-Tx (range 1.0-15.0). HRQOL was self-assessed using standardized health utility questionnaires (15D-17D). The patients' PSA was evaluated using the Child Behavior Checklist for parents, Youth Self-Report for patients aged 11-16 yr, and Teacher Report Form. Outcomes did not differ significantly between Tx groups. Preadolescents (8-11 yr) reported poorer HRQOL compared with same-age peers (p = 0.020). In contrast, adolescents reported similar HRQOL and PSA compared to the general population. Proxy-reports revealed more PSA problems compared with age expectations (p < 0.01), mainly in internalizing behavior (p < 0.01). Lower HRQOL was associated with shorter follow-up time since Tx, congenital disease, and a psychiatric or neurological diagnosis. PSA problems were associated with family-related variables, neurological diagnosis, shorter follow-up time, and in teacher-reports longer disease duration before Tx. Different pediatric Tx groups have similar outcome. Neurological comorbidity and shorter follow-up time are important risk factors, but the impact of family-related variables on PSA indicate the need of family interventions. [ABSTRACT FROM AUTHOR]

Chen C, Akanay-Diesel S, Schuster FR, Klee D, Schmidt KG, Donner BC. An unusual manifestation of post-transplant lymphoproliferative disorder in the lip after pediatric heart transplantation. Pediatr Transplantation 2012. © 2012 John Wiley & Sons A/S. Abstract: PTLD is a serious and frequently observed complication after solid organ transplantation. We present a six-yr-old girl with a rapidly growing, solid tumor of the lip four yr after orthotopic heart transplantation, which was classified as monomorphic PTLD with the characteristics of a diffuse large B-cell lymphoma. Treatment with reduction in immunosuppression, ganciclovir, and anti B-cell monoclonal antibody (rituximab) resulted in full remission since 12 months. To the best of our knowledge, this report is the first description of PTLD in the lip in a pediatric patient after heart transplantation in the English literature. [ABSTRACT FROM AUTHOR]

Urschel S, Rieck BD, Birnbaum J, Dalla Pozza R, Rieber N, Januszewska K, Fuchs A, West LJ, Netz H, Belohradsky BH. Impaired cellular immune response to diphtheria and tetanus vaccines in children after thoracic transplantation. Pediatr Transplantation 2011: 15: 272-280. © 2011 John Wiley & Sons A/S. Safety and immunogenicity of diphtheria and tetanus booster vaccination were evaluated in 28 children after thoracic transplantation. Adverse events were documented in a patient diary. Blood was collected prior to and four wk after vaccination. Specific antibody concentrations were measured by ELISA. Lymphocytes were investigated for expression of activation markers (CD25, HLA-DR) by flow cytometry and proliferation assays with and without stimulation. Post-vaccination antibody titers were higher than prevaccination (p < 0.001), with more patients having protective antibody levels against diphtheria (p < 0.02) and tetanus (p < 0.001). There was no increased proliferation in non-stimulated or stimulated cultures after vaccination. The number of T-lymphocytes activated by the vaccination antigens was similar pre- and post-vaccination, whereas HLA-DR-expression on stimulated and non-stimulated CD4 T-cells increased significantly. Increase in antibodies was negatively correlated with tacrolimus dose, and impaired cellular immunity was associated with higher tacrolimus dose and steroid use. Adverse events were similar to the general population; serious adverse events and rejection did not occur. Vaccination with inactivated vaccines can be performed safely in immunosuppressed children after thoracic transplantation and induces protective antibody levels in the majority of patients. Impaired induction of specific cellular immunity is correlated with intensity of immunosuppression and may explain reduced sustainability of antibodies. [ABSTRACT FROM AUTHOR]

Ohmann EL, Burckart GJ, Chen Y, Pravica V, Brooks MM, Zeevi A, Webber SA. Inosine 5′-monophosphate dehydrogenase 1 haplotypes and association with mycophenolate mofetil gastrointestinal intolerance in pediatric heart transplant patients. Pediatr Transplantation 2010: 14: 891-895. © 2010 John Wiley & Sons A/S. MMF, the most commonly used adjuvant immunosuppressant in pediatric heart transplantation, has frequent GI adverse events. SNPs in inosine 5′-monophosphate dehydrogenase I ( IMPDH1) may contribute to MMF GI intolerance. Phased haplotypes may have more utility than individual SNPs in candidate gene association studies for complex traits. This study defined common IMPDH1 haplotypes and investigated whether these haplotypes influence MMF GI intolerance in 59 pediatric heart recipients. Genotypes were assessed by Taqman analysis of IMPDH1 rs2288553, rs2288549, rs2278293, rs2278294, and rs2228075, and haplotypes were inferred using Arlequin 3.01 software. GI intolerance was defined as diarrhea, vomiting, nausea, or abdominal pain requiring MMF dose holding for > 48 h or MMF discontinuation. GI intolerance occurred in 21 patients (35.6%). Ten IMPDH1 haplotypes were identified in this population. In univariable analyses, one haplotype was strongly associated with MMF GI intolerance with 59.1% of carriers of this haplotype experiencing MMF GI intolerance compared to 21.6% of non-carriers (p = 0.005). In this study, we identify a common IMPDH1 haplotype associated with MMF GI intolerance in a population of pediatric heart transplant patients. This haplotype of interest did not demonstrate stronger association with MMF GI intolerance than an individual IMPDH1 SNP. [ABSTRACT FROM AUTHOR]

Tang L, Du W, Delius RE, L’Ecuyer TJ, Zilberman MV. Low donor-to-recipient weight ratio does not negatively impact survival of pediatric heart transplant patients. Pediatr Transplantation 2010: 14:741–745. © 2010 John Wiley & Sons A/S. A major limitation to success in pediatric heart transplantation is donor organ shortage. While the use of allografts from donors larger than the recipient is accepted, the use of undersized donor grafts is generally discouraged. Using the UNOS database, we wanted to evaluate whether using smaller donor hearts affects the short- and long-term survival of pediatric heart transplant patients. A retrospective analysis of data entered into the UNOS database from April 1994 to May 2008 was performed. Pediatric heart transplant recipients (ages 0–18 yr) with DRWR <2.0 were identified and divided into two groups: Low-DRWR (<0.8) and Ideal-DRWR (0.8–2.0). Patients’ demographics, pretransplant diagnoses, age at transplantation, severity of pretransplant condition, and rate of complications prior to hospital discharge after transplantation were noted. Fisher’s exact, chi-square, and Wilcoxon rank sum tests were used to compare patients’ baseline characteristics. Kaplan–Meier curves and Cox proportional hazard regression were used to compare patients’ survival and to identify independent risk factors for outcomes. There were 3048 patients (204 with Low- and 2844 with Ideal-DRWR). The Low-ratio group patients were older (8.3 vs. 6.9 yr; p = 0.001), there was a slight male predominance in the Low-DRWR group (p = 0.055). The Low-DRWR group had longer transplant wait time than the Ideal-DRWR group (97 vs. 85 days; p = 0.04). The groups did not differ in race, primary diagnoses, severity of pretransplant condition (medical urgency status, need for ventilation, inotropic support, ECMO, nitric oxide, or dialysis, the PVR for those with bi-ventricular anatomy), or post-transplant complications (length of stay, need for inotropic support, dialysis, and rate of infections). The Low-DRWR patients had less episodes of acute rejection during the first-post-transplant month. Infants with DRWR 0.5–0.59 had lower 30-day survival rate (p = 0.045). There was no difference in short- and long-term survival between the patients with DRWR 0.6–0.79 and DRWR 0.8–2.0. Use of smaller allografts (DRWR 0.6–0.8) has no negative impact on the short- and long-term survival of pediatric heart transplant patients. [ABSTRACT FROM AUTHOR]

Minimal data exist on the perioperative use of TG for induction in pediatric HTx recipients. We report our experience using continuous infusion of TG on (i) perioperative adverse events, (ii) rejection, (iii) CAV, and (iv) PTLD. TG was infused via peripheral intravenous intra- and perioperatively as a continuous infusion (24 h/day). Starting dose was 1.5 mg/kg/day titrated to achieve target lymphocyte count of 0.1–0.3 × 109/L. Fifty-five patients received TG; mean age at HTx was 4.4 yr (1 day–17.8 yr). The mean duration of TG was three and a half days (2–7 days). Median platelet count during TG infusion was 95 × 109/L (28–228). Five patients had TG stopped for low platelets (at 4–6 days post-HTx) – all started maintenance immunosuppression. There was no perioperative mortality due to infection. Mean follow-up of 46 survivors was 2.3 yr (0.6–5.8 yr). Fifty-one percent had ≥ ISHLT 2R rejection at a median time of 33 days post-HTx (7 days–2 yr). One patient developed PTLD 1.4 yr post-HTx; three patients developed mild-moderate CAV. TG as a continuous infusion appears to have a good safety profile. Though mild thrombocytopenia was prevalent, there was no bleeding attributable solely to TG. Whether early depletion of T-cell function will translate into long-term benefits remains to be determined. [ABSTRACT FROM AUTHOR]

This is the third review in a series whose purpose is to provide succinct summaries and informative commentaries of the recent medical literature pertinent to pediatric heart transplantation and directed toward the practicing clinician. It is meant to be comprehensive but not all-inclusive. Important articles published during 2005 and 2006 are summarized. [ABSTRACT FROM AUTHOR]

The levels and protein/lipid compositions of major lipoprotein particles of 19 pediatric cardiac transplant recipients (4–18 yr of age) were studied in this prospective, open clinical follow-up study before and at one yr of pravastatin therapy (10 mg/day). The recipients were grouped into those with (n = 6; group A) and those without (n = 13; group B) angiographically detectable vasculopathy. Twenty-one pediatric non-transplant controls were studied at baseline. At baseline, the group A recipients had 29% lower HDL-C concentrations (p = 0.031) and 29% higher apoB-100/apoA-I ratios (p = 0.034) than the group B recipients. At one yr of pravastatin, the respective figures were 29% (p = 0.013) and 33% (p = 0.005). Compared with the healthy pediatric controls, the transplant recipients had significantly higher serum TG before pravastatin [median (range): 1.3 mmol/L (0.6–3.2) vs. 0.7 mmol/L (0.3–2.4), p = 0.0002] and at one yr [1.3 mmol/L (0.5–3.5) vs. 0.7 mmol/L (0.3–2.4), p = 0.0004]. The baseline apoB-100/apoA1 ratios of the recipients were 33% higher (p = 0.005). In conclusion, low HDL-C and high apoB-100/apoA-I ratio were associated with angiographically detectable vasculopathy. Even though pravastatin effectively lowered the TC and LDL-C and improved compositional properties of LDL and HDL2 particles, it failed to normalize the elevated TG and, in some patients, to prevent the progression of transplant vasculopathy. [ABSTRACT FROM AUTHOR]

Immunosuppression after heart transplantation is implicated in development of post-transplant lymphoproliferative disorder (PTLD). Despite a higher prevalence of PTLD in children, there is scarce knowledge about incidence, pathophysiologic mechanisms and risk factors for PTLD in pediatric recipients of cardiac allografts. We examined retrospectively the medical records of all 143 pediatric patients (mean age 9.2 ± 6.1 yr) who received donor allografts between 1984 and 2002 and survived over 30 days. Five children (3.5%) developed PTLD over a mean follow-up period of 41.1 ± 46.0 months. Time from transplant to diagnosis of PTLD ranged from 3.9 to 112 months (mean 48.0 ± 41.9 months). Excluding PTLD, no other malignancies were found in this population. Actuarial freedom from PTLD was 99.2%, 99.2% and 96.2% at 1, 2, and 5 yr, respectively. Children who developed PTLD were more likely (by univariate analysis) to have been Rh negative (p = 0.01), Rh mismatched (p = 0.003), Epstein–Barr virus (EBV) seronegative (p = 0.001) and transplanted for congenital heart disease (p < 0.02). PTLD was associated with significant morbidity and mortality with a mean survival following diagnosis of 21.2 months. PTLD is a serious complicating outcome of cardiac transplantation that occurs in approximately 3.5% of children. Aside of immunosuppression, risk factors in this series for developing PTLD include EBV seronegativity and Rh negative status and mismatch. Non-hematogenous malignancies are rare in light of short allograft half-life. [ABSTRACT FROM AUTHOR]

Abstract: Mycophenolate mofetil (MMF) is emerging as an effective agent for the treatment of both established rejection and primary rejection prophylaxis in solid-organ transplantation (Tx). However, little data is available on the use of MMF in the pediatric population. We therefore report on our experience with MMF in 21 pediatric heart transplant recipients. Data were obtained by retrospective chart review. Median age at time of review was 12.3 yr (range 11 months to 16.9 yr). Median age at Tx was 10.7 yr (range 55 days to 16.7 yr). MMF was started at a median of 4.3 months after Tx (range 1 day to 4.5 yr). At the time of MMF institution, all patients were concurrently on prednisone and azathioprine; 20 of these patients were also undergoing treatment with tacrolimus (median dose 0.18 mg/kg, range 0.03–0.64 mg/kg) and one with cyclo-sporin A (10 mg/kg). Azathioprine was discontinued at the time of commencing MMF. The average MMF dose was 40 ± 14 mg/kg. The rationale for switching to MMF included rejection (International Society for Heart and Lung Transplantation [ISHLT] 3A/B), 66%; inability to wean steroids, 14%; ABO blood group donor–recipient mismatch, 10%; coronary artery disease (CAD), 5%; and side-effects of immuno-suppression, 5%. Of the patients switched for rejection, 93% demonstrated resolved or improving rejection. Both ABO donor–recipient mismatch patients were started on tacrolimus/MMF as primary therapy and had no significant episodes of rejection. Two patients had rejection classified as unchanged (one with CAD, one treated with addition of sirolimus prior to improvement). Corticosteroids were successfully discontinued in 28% of patients, and 20% are currently on a reduced dose. Fourteen per cent developed significant rejection while attempting to reduce the steroid dose. Steroid reduction has not yet been attempted in 38% of patients. The following side-effects were reported in 38% of the patients: diarrhea, 10%;... [ABSTRACT FROM AUTHOR]

Abstract: The exercise performance of pediatric heart transplant recipients and the effects of bicaval anastomosis were studied in 19 children using a Bruce protocol. Although all children had decreased exercise capacity and heart rates when compared with normals, the bicaval anastomosis patients had similar endurance and peak heart rates as the standard biatrial group. [ABSTRACT FROM AUTHOR]