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Background: The significance of atypical infiltrates (eosinophils or plasma cells) on endomyocardial biopsy (EMB) after pediatric heart transplant (HTx) is not known. We hypothesized that atypical infiltrates are associated with worse post-HTx outcomes., Methods: We performed a retrospective cohort study of consecutive patients <21 years old who underwent primary HTx between 2013 and 2017. Multiorgan transplants were excluded. The presence of atypical infiltrates and burden of atypical infiltrates (rare vs predominant) on EMB were recorded. Primary outcome was a composite of cardiac allograft vasculopathy, graft failure (relisting or retransplant), or death. Presence of atypical infiltrates was evaluated: (1) overall using Cox regression with time-dependent covariates and (2) if present by 1 year post-HTx using Kaplan-Meier analysis., Results: Atypical infiltrates were present in 24 out of 95 patients (25%) and were associated with a higher likelihood of reaching the composite outcome (hazard ratio (HR) 6.22, 95% confidence interval (CI) 2.60-14.89, p < 0.0001). This persisted when controlling for rejection in multivariable analysis. There was also a greater risk of the composite outcome if ≥2 nonconsecutive EMBs had atypical infiltrates (HR 11.80, 95%CI 3.17-43.84, p = 0.0002) or if atypical infiltrates were the predominant feature on EMB (HR 30.58, 95%CI 9.34-100.06, p < 0.0001). Patients with atypical infiltrates by 1-year post-HTx had a 5-year freedom from the composite outcome of 48%, compared to 90% if no atypical infiltrates had been present by this timepoint (log rank p = 0.002)., Conclusions: The presence of atypical infiltrates on EMB is associated with significantly worse outcomes in children following HTx. These patients require closer follow-up to assess for developing graft dysfunction., (Copyright © 2023 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Guidance and data on ventricular assist device (VAD) support for children with chemotherapy-induced cardiomyopathy, particularly within the first 2 years after chemotherapy, are limited., Methods: We performed a single-center retrospective case series, reviewing medical records of children <18 years of age with chemotherapy-induced cardiomyopathy and advanced heart failure (HF) who received durable VAD support., Results: Six patients met inclusion criteria-5 HeartWare™ HVAD, 1 Berlin Heart EXCOR ® . Median age at cancer diagnosis was 6 years (IQR 4.5-10 years). Median dose of anthracycline received was 540 mg/m 2 (IQR 450-630 mg/m 2 ). All patients developed HF within 1 year after initiation of cancer treatment (median 8 months, IQR 6-11.5 months) and were initiated on durable VAD support at a median of 8 months after completion of cancer treatment (IQR 3.3-43.5 months). Four patients had significant right ventricular dysfunction needing oral pulmonary vasodilator therapy, one patient had a major bleeding complication, and two patients had thromboembolic strokes while on VAD support. Median duration of VAD support was 7.5 months (IQR 3-11.3 months). Two patients underwent VAD explant due to recovery of LV function, one died due to cancer progression, and three underwent heart transplantation., Conclusions: Durable VAD support should be considered as a therapeutic option for children who have advanced HF due to chemotherapy-induced cardiomyopathy, even within 2 years of completing cancer treatment. A multi-disciplinary approach is essential for appropriate patient selection prior to implant and to ensure comprehensive care throughout the duration of VAD support., (© 2022 Wiley Periodicals LLC.)

Background: Valvular disease in pediatric and young adult donor hearts may be a relative contraindication to graft use. Outcomes following the use of donor hearts with bicuspid aortic valve (BAV) have not been previously reported in children. We describe 4 cases of pediatric heart transplantation (HTx) utilizing a donor heart with a BAV., Case Series: Of the 469 HTx included in this study, 4 utilized a donor heart with a BAV. All recipients were female; median age was 11 years (range 0.3 to 19 years). In all cases, the BAV was not discovered until after HTx. All donors were less than 30 years old. The patients were followed for a median of 6 years (range 2 to 9 years) with all patients alive at last follow-up. Two patients have transitioned to adult care, and 2 patients continue to follow in our clinic. In follow-up, no patient has required an aortic valve intervention or had infective endocarditis. At last review, no patient had greater than mild aortic insufficiency or more than mild aortic stenosis. Three patients developed mild-to-moderate left ventricular hypertrophy in the first year post-transplant that improved over time. One patient experienced a peri-operative embolic stroke at time of transplant unrelated to the BAV., Conclusion: On short- and intermediate-term follow-up, pediatric and young adult donor hearts with BAV demonstrated acceptable graft longevity and valvular function. A functionally normal BAV in a pediatric heart transplant donor should not be a contraindication to organ acceptance., (© 2021 Wiley Periodicals LLC.)

Tracheostomy is associated with increased mortality and resource utilization in children with CHD. However, the prevalence and hospital outcomes of tracheostomy in children with HTx are not known. We describe the prevalence and compare the post-HTx hospital outcomes of pediatric patients with Pre-TT and Post-TT to those without tracheostomy. A multi-institutional retrospective cohort study was performed using the Pediatric Health Information System database. Hospital mortality, mediastinitis, LOS, and costs were compared among patients with Pre-TT, Post-TT, and no tracheostomy. Pre-TT was identified in 29 (1.1%) and Post-TT was identified in 41 (1.6%) of 2603 index HTx hospitalizations. Patients with Pre-TT were younger and more likely to have CHD, a non-cardiac birth defect, or an airway anomaly compared to those without Pre-TT. Pre-TT was not independently associated with increased post-HTx in-hospital mortality. Age at HTx < 1 year, CHD, and Post-TT were associated with increased in-hospital mortality. Pre-TT that occurred during the HTx hospitalization and Post-TT were associated with increased resource utilization. Tracheostomy was not associated with mediastinitis., (© 2020 Wiley Periodicals LLC.)

Autoimmune-mediated bowel disease has been reported after pediatric heart transplantation. Recognition and treatment of these patients has been difficult. We describe a patient who responded to steroids and basiliximab therapy after an inflammatory process secondary to abnormal T-cell activation. Our patient is a 28-month-old female who received a heart transplant at five wk of age. At 24 months post-transplant, she developed fever and bloody stools. Initial investigations were significant for an elevated ESR (>120) and CRP (15.2). Symptoms persisted despite bowel rest and mycophenolate discontinuation. Endoscopic evaluation revealed discontinuous ulcerative disease involving esophagus, terminal ileum, right and left colon, necessitating extensive bowel resection. She had additional airway inflammation leading to a TEF at the site of esophageal ulceration, requiring tracheostomy. Immune evaluation revealed autoimmune dysregulation that responded to parenteral methylprednisolone. Chronic basiliximab therapy allowed for successful weaning of steroids with sustained remission. She has been transitioned to sirolimus and tacrolimus maintenance immunosuppression with plans to discontinue basiliximab once off steroids. In conclusion, bowel disease in the setting of pediatric heart transplantation can be severe and refractory to traditional treatment methods. Tailoring immune therapy to activated T cells can result in remission. Basiliximab therapy was used in our patient to maintain steroid-induced remission, but long-term complications of this disease process are unknown., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The intent of this study was to examine if there are any factors associated with clearance of antibody mediated rejection (AMR) and to identify the optimal time for follow up biopsy after a diagnosis of AMR. A retrospective single-center cohort analysis of patients < 18 years of age who underwent heart transplant (HTx) between 08/2013 - 9/2021 was performed. AMR was defined as positive C4d on endomyocardial right ventricular biopsy (EMB). Concurrent ACR was recorded. Time until clearance was measured in days until follow up EMB was C4d negative. The number of biopsies performed until clearance was also recorded to account for clinical variation in timing for follow up biopsies. Thirty-five unique patients developed AMR with a total of 41 unique episodes of AMR. All patients received pulse steroids. Additional treatments included IVIG, rituximab, daratumumab, eculizumab, and plasmapheresis, depending on the degree of illness and persistence of AMR. The cohort was 62% male, 27% non-Hispanic White, 51% Hispanic, 20% non-Hispanic Black, and 2% Other. Median age at HTx was 4.6 years (IQR 0 - 12.3), and median days from HTx until AMR was 80 days (IQR 16 - 765 days). The median duration to clear AMR was 28 days (IQR: 17 - 56), 56% of AMR episodes cleared on the first biopsy; and the mean number of biopsies to clear AMR was 1.8. AMR did not resolve in 10% (4/41). Patients with unresolved AMR tended to have a history of prior AMR (50% vs 11%, p = 0.095) and be older at HTx (median age 15yrs, IQR 12.5 - 17.1 vs median 4.3yr, IQR 0.7 to 11.4 yrs, p = 0.01). Analyzing those who had resolution of AMR, there was no association of sex, age at HTx or time since HTx with time to resolution. Those with recurrent AMR took longer to resolve (median 162 days vs 28 days, p = 0.01). Patients with concurrent ACR had a shorter time to AMR resolution (median 16 days vs 33 days, p = 0.01). There does not appear to be an association between time to clear AMR with patient demographics or time after transplant of the index case of AMR. Patients with prior resolved AMR take longer to clear recurrent cases of AMR. Concurrent ACR was associated with quicker time to clear AMR for reasons that remain unclear. The optimal time period to reassess for AMR clearance, based on this single-center data, is 1 month. [ABSTRACT FROM AUTHOR]

Iron deficiency (ID) is associated with worse outcomes in children with systolic heart failure (HF). Oral iron replacement therapy (IRT) is first line therapy for ID in children but the efficacy of oral IRT in children with HF is unknown. We hypothesized that less than half of children with HF and ID would have replenishment of their iron stores with oral IRT. We performed a single center retrospective cohort study of patients aged ≤ 21 years with systolic HF and ID who received oral IRT (2-5mg/kg/day) between 01/2017 and 12/2018. ID was defined as ≥2 of the following: serum iron <50 mcg/dL, serum ferritin <20 ng/mL, transferrin >300 ng/mL, transferrin saturation <15%. Iron studies and hematologic indices pre and post IRT were compared in patients who received ≥6 weeks of therapy (to allow adequate duration of IRT to assess response) using paired-samples Wilcoxon test. Forty-two independent courses of oral IRT (in 40 patients) met inclusion criteria. The cohort was 52% male with median age 13 yrs (IQR 5 - 16 yrs). HF etiologies included cardiomyopathy (57%), congenital heart disease (31%), and history of heart transplantation with graft dysfunction (12%). Patients received ferrous sulfate (40/42) or ferrous gluconate (2/42). Median duration of IRT was 68d (IQR 32 - 145d). Twenty-nine patients received ≥6 weeks of IRT and were included for the analysis for response to oral IRT. Post IRT iron testing was available in 18 patients and post IRT hemogram was available in 26 patients. Serum iron and hematologic indices of the overall cohort as well as comparison of indices pre and post oral IRT are shown (Table). While there was an improvement in serum iron studies, 50% (9/18) of the patients remained iron deficient. This is the first report about oral IRT in children with HF. Though median values of some iron parameters increased after 6weeks of oral IRT, half of the children with HF remained iron deficient and hence non-responsive to oral IRT. Further studies are needed to find the most suitable IRT for children with HF. [ABSTRACT FROM AUTHOR]

Factors predicting survival after pediatric combined heart-kidney transplantation (HKTx) are unclear. We examined pre-transplant recipient characteristics that determine survival following pediatric combined HKTx. The Scientific Registry for Transplant Recipients heart and kidney databases were used to identify 159 combined heart-kidney transplants, between 1992 and 2018 (age ≤21 years). Cox regression analysis was performed to identify pre-transplant recipient characteristics associated with reduced 1-year survival following pediatric combined HKTx. Using the relative risks calculated in regression analysis, points were assigned for each risk factor. Points for each risk factor were combined allowing for the construction of a total risk score (low-risk <4, moderate-risk 4 to 5, and high-risk ≥6). Risk factors associated with reduced 1-year survival included the recipient's age ≥12 years, African American race, diabetes mellitus, and chronic dialysis (defined as dialysis for 6 months or longer) at the time of transplantation. Further stratification by estimated glomerular filtration rate (eGFR) was performed based on a previous study showing decreased survival of patients undergoing isolated heart transplants with a preoperative eGFR of <35 mL/min/1.73m2. Low-risk score patients with an eGFR of <35 mL/min/1.73m2 undergoing combined HKTx had significantly better 1-year survival compared with isolated heart transplants with similar range eGFR and risk score (86.6% [66.3, 92.1] versus 68.7% (64.3, 72.7), P=0.01). There was no survival advantage for combined HKTx over heart-alone transplant in patients with the high-risk score (63.9% [59.3, 68.1] versus 60.3% [55.6, 64.6], P=0.7). Low-risk score patients with combined heart and kidney failure (eGFR <35 mL/min) have a survival benefit from pediatric combined HKTx. On the other hand, there is no significant advantage for combined HKTx over heart-alone transplant in patients classified as high-risk and associated with poor survival. [ABSTRACT FROM AUTHOR]

Cardiac allograft vasculopathy (CAV) is a leading cause of death and retransplant after heart transplantation (HTx). Coronary aneurysms are not typically seen in CAV. We present a case of atypical CAV with coronary aneurysms resulting in premature death. A 4-year-old male underwent HTx after failed single ventricle palliation. His first year after HTx was uneventful with no cellular rejection score greater than 1R and no antibody mediated rejection on multiple surveillance endomyocardial biopsies. Coronary angiography was normal at 3 months. At 1-year post-HTx, surveillance coronary angiography demonstrated a diffusely dilated appearance with multiple aneurysmal segments of the right and left coronary systems (Figure). No filling defects or areas of focal stenosis were appreciated. His pulmonary capillary wedge pressure was elevated at 15 mmHg, but stable from previous assessments. There was no known history of Kawasaki disease in the donor. The patient had no history of prolonged fevers or other symptoms of vasculitis. He was placed on enoxaparin and aspirin for anticoagulation. He remained asymptomatic with no regional wall abnormalities and normal systolic function by echocardiogram. He denied episodes of palpitations and had a Holter without any ectopy or arrhythmias. While awaiting further evaluation with additional advanced imaging, he had a sudden cardiac arrest and died 10 months after coronary aneurysms were found. His autopsy revealed segmental fusiform aneurysmal expansion with severe concentric intimal fibrosis and luminal narrowing of multiple segments of the right and left coronary systems consistent with severe CAV. Left ventricular histopathology exhibited chronic ischemic changes to the subendocardium. Our patient with severe CAV presented with coronary aneurysm formation within 1 year of HTx. Coronary aneurysm formation may be an atypical and more severe form of CAV that should prompt close monitoring and early consideration for retransplant. [ABSTRACT FROM AUTHOR]

The significance of atypical infiltrates, defined as eosinophils or plasma cells on endomyocardial biopsy (EMB) after pediatric heart transplant (HTx) is not known. We hypothesize that atypical infiltrates are associated with worse post-HTx outcomes. We performed a retrospective cohort study of 96 consecutive patients status-post primary HTx (age <18 years) from 2013 to 2017 who underwent total of 753 EMBs. Clinical characteristics and pathologic findings were reviewed. Patients status-post heart re-transplant or multi-organ transplant were excluded. The number of EMBs with atypical infiltrates and whether atypical infiltrates were rare versus abundant by pathologist review were noted. Primary outcome was a composite of cardiac allograft vasculopathy (CAV), graft failure (defined as re-listing or re-transplant), or death. Groups were compared using Cox regression with time-dependent covariates. Atypical infiltrates were seen in 24/96 (25%) patients. Of these patients, 14/24 (58%) had 1 EMB and 10/24 (42%) had >2 EMB with atypical infiltrates. Atypical cells were abundant in 6/24 (25%), while they were a rare cell type in 18/24 (75%). The presence of atypical infiltrates on EMB was associated with higher likelihood of reaching the composite outcome compared to no atypical infiltrates (HR 6.9 [2.9-16.3], Fig 1A). Two or more EMBs with atypical infiltrates were associated with greater risk of composite outcome compared to no atypical infiltrates (HR 11.1 [4.2-29.1], Fig 1B). All patients with abundant atypical infiltrates met the composite outcome within the study period (HR 21.6 [7.7-60.2], Fig 1C, compared to no atypical infiltrates). Atypical infiltrates on EMB are associated with increased risk of CAV, graft failure, or death after HTx. The risk is higher with increasing frequency and greater extent of atypical infiltrates on EMB. Patients with atypical infiltrates are an at-risk population that require close follow up. [ABSTRACT FROM AUTHOR]

The hemodynamic profiles (HDPs) among pediatric heart transplant (HT) recipients after the 1st year post-HT is understudied. We aim to describe HDPs following the 1st year post-HT and assess associations with long term outcomes. HDPs were collected from patients who underwent HT between 2013-2020. Patients were excluded if they did not have at least 2 catheterizations 1-year after HT. LOESS graphs were created to trend HDPs >1 year. Linear mixed models were used to assess the effects of selected variables on HDPs. In total, 435 studies from 115 patients were included (median 3 studies/patient and median time of cath since HT: 839 days). The "normal control group" post-HT HDPs (Fig 1, Black Trendline) were created from 212 studies from 67 patients with no history of rejection or known CAV at any point. In multivariate analysis, those who later develop CAV (Fig 1; Blue Trendline) had lower cardiac index (CI) values (mean difference: -0.523±0.238, p=0.030) prior to angiographic diagnosis of coronary artery vasculopathy (CAV). Other factors found to influence HDPs included rejection (n=41), and angiographic evidence of CAV (n=44) which were associated with higher filling pressures and lower CI; Table 1. Independent of other variables, right atrial mean, right ventricular end diastolic, and wedge pressures increased and CI decreased with time (Table). Our study establishes normal expected HDPs following 1-year post-pediatric HT. Compared to those with no CAV, those who later develop CAV have decreased CI prior to angiographic diagnosis and may warrant more frequent surveillance. [ABSTRACT FROM AUTHOR]

Epitope-based human leukocyte antigen (HLA) molecular typing techniques now permit the assessment of a donor-recipient "match". We sought to determine the HLA epitope mismatch load among different pediatric heart transplant (PHT) donor-recipient race/ethnicity pairs. We performed high resolution HLA typing and epitope mismatch analysis (HLA Matchmaker) on all primary PHT (2014-2020) at a single center. Race/Ethnicity categories were defined as Non-Hispanic White (NHW), Non-Hispanic Black (NHB), and Hispanic; patients categorized as other, mixed, or missing were excluded. HLA epitope mismatch load was compared between those with and without a donor/recipient (D/R) race/ethnicity (R/E) mismatch and among all donor-recipient race/ethnicity pairs. Data were available to assess D/R R/E pairs and HLA epitope mismatch load among 119 patients (29% NHW; median age 5.8 years). There were 45 (38%) D/R R/E matched organs. There was no difference in the number of HLA epitope mismatches at any locus among those who received a D/R R/E matched pair vs those that did not (Table). When comparing among all D/R R/E matched pairs, there was no difference in the HLA epitope mismatch load at any locus (Class I, Class II, and DQ shown in Figure). There was no difference in the HLA epitope mismatch load between pediatric patients receiving a donor-recipient race/ethnicity matched organ or among any donor-recipient race/ethnicity pair. HLA diversity transcends the social construct of race, and non-immunologic factors such as social determinants of health should be addressed to help improve PHT outcomes. [ABSTRACT FROM AUTHOR]

The significance of atypical infiltrates, defined as eosinophils or plasma cells on endomyocardial biopsy (EMB) after pediatric heart transplant (HTx) is not known. We hypothesized that atypical infiltrates are associated with worse post-HTx outcomes. We performed a retrospective cohort study of 96 consecutive patients aged <18 years who underwent primary HTx from 2013 to 2017. Patients who underwent heart re-transplant or multi-organ transplant were excluded. The number of EMBs with atypical infiltrates and burden of atypical infiltrates (rare vs predominant on pathologist review) were recorded. Primary outcome was a composite of cardiac allograft vasculopathy, graft failure (defined as re-listing or re-transplant), or death. Groups were compared using Cox regression with time-dependent covariates and mixed effects logistic regression accounting for repeated measures. Atypical infiltrates were seen in 27/96 patients (28%). The presence of atypical infiltrates on EMB was associated with higher likelihood of reaching the composite outcome compared to no atypical infiltrates (HR 5.82, 95% CI 2.5-13.6, p<0.001). This finding persisted when accounting for rejection. Two or more EMBs with atypical infiltrates were associated with greater risk of composite outcome compared to no atypical infiltrates (HR 10.5, 95% CI 2.86-38.5, p=0.001), as was having atypical infiltrates as the predominant feature on EMB (HR 19.1, 95% CI 6.51-56.0, p<0.001). Patients with atypical infiltrates by their 1-year post-transplant biopsy had survival free of primary outcome of 48% at 5 years, compared to 90% if no atypical infiltrates had been seen by the 1-year post-transplant biopsy (log rank = 0.002, Figure). Atypical infiltrates on EMB are associated with poor outcomes following HTx. The risk is higher with increasing frequency and greater extent of atypical infiltrates. Patients with atypical infiltrates are an at-risk population that require close follow up. [ABSTRACT FROM AUTHOR]

Recent data in adult solid organ transplantation suggest that epitope-based human leukocyte antigen (HLA) matching may permit better risk assessment of de novo donor‐specific antibody (dnDSA) development compared to antigen-based HLA matching, but data in pediatric heart transplantation (PHTx) are scarce. We evaluated the association between epitope mismatches and dnDSA in PHTx. We performed high resolution HLA typing and epitope mismatch analysis (HLA Matchmaker) in children undergoing primary PHTx at a single center from 2014 - 2020. DSA >1000 MFI (Luminex Single Antigen Bead Assay; One Lambda) were considered positive. Data are presented as median (interquartile range). Epitope and dnDSA data were available in 109 transplants (age 5.8 years [1-12], 66% male, 32% non-Hispanic White, follow-up 2.5 years [1.3 - 4.7]). There was significant diversity in the number of epitope mismatches within each HLA locus (Fig 1A), and the number of mismatches were: A 20 (13-28), B 17 (12-22), C 10 (6-15), DR 16 (8-30), DQ 12 (8-16), and DP 8 (3-13). The number of epitope mismatches did not differ among any donor-recipient race combination (not shown). The development of dnDSA was not associated with a higher number of epitope mismatches at any HLA-loci (Fig 1B). However, patients with antibody mediated rejection (AMR) had more DQ mismatches (15 vs 11; p=0.04) than those without AMR, and there were more anti-DQB1 DSA than any other DSA in the cohort (Figure 1C). There is significant variability in the number of HLA epitope mismatches within each HLA locus. These data suggest that it may not be the total number of epitope mismatches but rather epitope mismatches at specific loci that vary in location and function that are of immunogenic importance. Further investigation of epitope-matching in PHTx may permit a more personalized immunosuppressive approach based on individualized alloimmune risk assessment in the future. [ABSTRACT FROM AUTHOR]

Determine the association of socioeconomic disadvantage (SED) and race/ethnicity with post-heart transplant (HTx) outcomes in children. A retrospective single-center cohort study of patients &lt 18 years of age who underwent HTx between 1/2006-12/2020 was performed. The Area Deprivation Index (ADI), a validated census-based neighborhood deprivation tool (higher value = more disadvantaged) that incorporates income, education, employment, and housing quality, was used to determine SED status. Patients were divided into less disadvantaged ("no SED"; ADI &lt 25%-ile) and more disadvantaged ("SED"; ADI &gt 25%-ile) as previously described. Outcomes included post-HTx survival (Kaplan-Meier curves and cox-proportional regression) and rejection (total episodes per year of follow-up were compared using linear regression). The cohort included 290 HTx (median age 5 yr [IQR 1- 13 yr], median weight 16kg [IQR 8 - 43 kg]). Median follow-up time from HTx was 4.3 yr (IQR: 1.7 - 7.3 yr). The cohort was 40% Hispanic, 33% Non-Hispanic White (NHW), 20% Non-Hispanic Black (NHB) and 7% Other. Median ADI was 63 (IQR: 43 - 83). Patients with SED had a significantly greater risk of death (HR: 4.2, 95% CI: 1.01 - 17.3) compared to those with no SED; Fig 1A. After adjusting for ADI, patients identifying as NHB (HR: 2.2, 95% CI: 1.03 - 4.6) and Other (HR: 3.8, 95% CI: 1.4 - 10.2) had a significantly higher risk of death compared to NHW (Fig 1B). Compared to NHW, only "Other" had an increased frequency of rejection (p = 0.01). Patients with SED did not have more episodes of rejection per year of follow up (0.21 vs 0.18; p = 0.8). Socioeconomic disadvantage and race/ethnicity (independent of ADI) are associated with worse post-HTx survival. Socioeconomic disadvantage was not associated with frequency of rejection; neither was NHB norHispanic race/ethnicity. Identifying and addressing any potentially modifiable determinants of SED is imperative to improve survival after pediatric HTx. [ABSTRACT FROM AUTHOR]

Angiotensin II type 1 receptor antibodies (AT1R-Ab) are associated with non-human leukocyte antigen (HLA) mediated antibody mediated rejection (AMR) and graft failure in adult renal transplantation. They can be stimulated by ventricular assist device (VAD) support, but data regarding AT1R-Ab in pediatric heart transplantation (HT) are scarce. The purpose of this study is to describe the incidence of non-HLA mediated AMR and identification of AT1R-Ab in a pediatric HT cohort. We performed a single-center retrospective review of children who underwent primary HT from July 2016 to July 2020. AMR was defined by the presence of complement deposition (+C4d) on heart biopsy. Non-HLA mediated AMR was defined by the absence of donor-specific HLA antibodies (HLA-DSA). AT1R-Ab testing was defined as < 10 negative, 10-17 borderline, and > 17 positive (ELISA). There were 100 patients who underwent primary HT during the study period (median age 4.5 years). There were 19 episodes of AMR in 17 patients. HLA-DSA were present in 12 episodes (63%) and absent in 7 (37%) episodes. Non-HLA mediated AMR occurred earlier post-HT compared to AMR with HLA-DSA (median 7 days vs 244 days, p = 0.04). Four patients with AMR in the absence of HLA-DSA were tested for AT1R-Ab; 3 were positive and 1 was borderline. Of the 3 patients with positive AT1R-Ab, 2 were previously supported on VAD, 2 had symptomatic AMR, 2 subsequently received losartan, and none have had recurrence of AMR (Table). Non-HLA mediated AMR accounted for 37% of AMR episodes and occurred earlier post-HT compared to AMR with HLA-DSA in a single-center cohort. AT1R-Ab were present in 3 of 4 patients with non-HLA mediated AMR in whom AT1R-Ab testing was performed. In light of the recent data regarding AT1R-Ab in renal transplantation, investigation of the prevalence and clinical significance of AT1R-Ab in pediatric HT, particularly in early non-HLA mediated AMR and in those bridged to HT with VAD, is warranted. [ABSTRACT FROM AUTHOR]