Search

BACKGROUND: While sex-related differences in transplant outcomes have been well characterized amongst adults, there are no sex-specific pediatric heart transplant studies over the last decade and none evaluating waitlist outcomes. In a contemporary cohort of children undergoing heart transplantation in the United States, this analysis was performed to determine if there were sex disparities in waitlist and/or post-transplant outcomes. METHODS: Retrospective review of Scientific Registry of Transplant Recipients database from December 16, 2011 to February 28, 2019 to compare male and female children after listing and after transplant. Demographic, clinical characteristics and outcomes were compared unadjusted and after 1:1 propensity matching for selected covariates. RESULTS: Of 4089 patients, 2299 (56%) were males. At listing, males were more likely to be older, have congenital heart disease (58% vs 48%), renal dysfunction (49% vs 44%) and implantable cardioverter defibrillator (9% vs 7%). At transplant, males were more likely to have renal (42 % vs 35%) and liver dysfunction (13% vs 10%), PRA >10% (29% vs 22%) and ischemic time >3.5 hours (p

BACKGROUND: There is a paucity of data regarding the antibody response to SARS-CoV-2 vaccination in children after solid organ transplant.We retrospectively reviewed the SARS-CoV-2 Anti-Spike IgG antibodies measured following SARS-CoV-2 vaccination at our pediatric heart transplant (HTx) center.Among patients (median age 17.1 years) in whom antibody testing was performed (median 118 days post-vaccine completion), a SARS-CoV-2 Anti-Spike IgG antibody was detected in 28 of 40 (70%) post-HTx recipients (median antibody level 10.9 AU/ml). Neutropenia, diabetes mellitus, and previous use of rituximab were associated with absence of a detectable antibody. All 7 post-HTx patients with a known pre-vaccination SARS-CoV-2 viral infection had a detectable SARS-CoV-2 Anti-Spike IgG. All 12 vaccinated pre-HTx patients had a detectable antibody (median antibody level 11.6 AU/ml) including 5 patients that maintained detectable antibodies post-HTx. There were no cases of myocarditis among the total of 17 pre-HTx and 81 post-HTx patients that underwent SARS-CoV-2 vaccination.Our data suggest that a significant proportion of pediatric HTx recipients have no detectable antibody response after SARS-CoV-2 vaccination and support the recommendation to complete the vaccination series prior to HTx in those pediatric patients waiting for HTx.

Despite considerable progress in heart transplantation, pediatric waiting list mortality is still high, and often patients do not have enough time to wait. We hypothesized that extending the donor criteria regarding age and weight mismatch does not significantly affect the early follow-up.We retrospectively analyzed our pediatric heart transplantation patients operated on from 2014 to 2020 for high (3.0) or low (0.6) donor-recipient weight ratio (DRWR) or chronological age mismatches (donor organ5 years older than recipient age). This patient cohort constituted "mismatched heart transplantations" (mHTX). We compared mHTX preoperative status, postoperative course, 1-year survival, and early clinical follow-up to standard pediatric heart transplantations (sHTX).We performed 20 pediatric heart transplantations-10 mHTX and 10 sHTX. The minimum DRWR was 0.44, the maximum was 5.60, and the maximum age mismatch was 42.6 years. Median days in the intensive care unit (p = .436) and time-to-first-rejection episode (p = .925) were comparable. Nine patients in each group were alive after 1 year, two patients were operated within 1 year of follow-up. One mHTX patient developed cardiac allograft vasculopathy after 15 months and died 648 days after transplantation (p = .237). All other patients were alive at the end of follow-up and in good clinical conditions (median follow-up for mHTX was 732.5 days, 1149.5 days for sHTX).Postoperative course and early follow-up after mHTX were comparable to sHTX. In urgent clinical situations, extended donor criteria may be considered an additional option for pediatric heart transplantation.

BACKGROUND Intracoronary imaging enables an early detection of intimal changes. To what extend the development of absolute and relative intimal hyperplasia in intracoronary imaging differs depending on age and post-transplant time is not known. METHODS Aim of our retrospective study was to compare findings between 24 pediatric (cohort P) and 21 adult HTx patients (cohort A) using optical coherence tomography (OCT) at corresponding post-transplant intervals (≤5 years: P1 (n = 11) and A1 (n = 10); >5 and ≤ 10 years: P2 (n = 13) and A2 (n = 11),. Coronary intima thickness (IT), media thickness (MT) and intima to media ratio (I/M) were assessed per quadrant. Maximal IT >0.3 mm was considered absolute, I/M > 1 relative intimal hyperplasia. RESULTS Compared to A1, I/M was significantly higher in P1 (maximal I/M: P1: 5.41 [2.81-13.39] vs. A1: 2.30 [1.55-3.62], p = 0.005), whereas absolute IT values were comparable. In contrast, I/M was comparable between P2 and A2, but absolute IT were significantly higher in A2 (maximal IT: P2: 0.16 mm [0.11-0.25] vs. A2: 0.40 mm [0.30-0.71], p

Atrial size and function are closely correlated with atrial contributions to cardiovascular performance. Therefore, in this study, we aimed to assess atrial size and function in pediatric heart transplantation (HTx) patients using three-dimensional echocardiography (3DE). We enrolled 33 clinically well pediatric HTx patients and 33 healthy controls with a similar distribution of sex and age to the HTx patients. All patients underwent two-dimensional echocardiography (2DE) and 3DE. 2DE- and 3DE-derived biatrial maximal volume (Vmax), minimal volume (Vmin), ejection volume (EV), ejection fraction (EF), volume before atrial contraciton (VpreA), passive EV, passive EF, active EV and active EF were obtained in all patients. The 3D left atrail (LA) Vmax, Vmin and VpreA increased significantly in HTx patients after being indexed by BSA, while 3D LAEV and passive EV decreased significantly (P

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.

This article is a review of the highlights of pertinent literature published in 2019, which is of interest to the pediatric cardiac anesthesiologist. After a search of the United States National Library of Medicine PubMed database, several topics emerged in which significant contributions were made in 2019. The authors of this manuscript considered the following topics noteworthy and were included in this review: advances in pediatric heart transplantation, blood management in pediatric cardiac surgery, the impact of nutrition on outcomes in congenital heart surgery, and the use of vasopressin in patients after Fontan palliation.

Endomyocardial biopsy (EMB) is the current standard for rejection surveillance in heart transplant recipients. The quantification of donor-specific cell-free DNA (cfDNA) may be an appropriate biomarker for non-invasive rejection surveillance. A multicenter prospective blinded study (DNA-Based Transplant Rejection Test, DTRT) investigated the value of donor fraction (DF), defined as the ratio of cfDNA specific to the transplanted organ to the total amount of cfDNA present in a blood sample.A total of 241 heart transplant patients were recruited from 7 centers. Age at transplant ranged from 8 days to 73 years, with 146 subjects18 years and 95 ≥18 years. All the patients were followed for at least 1 year, with blood samples drawn at routine and for-cause biopsies. A total of 624 biopsy-paired samples were included for analysis through a commercially available cfDNA assay (myTAIDF in acute cellular rejection (ACR) 1R/2R (n = 15) was higher than ACR 0R (n = 42) (p = 0.02); DF in antibody-mediated rejection pAMR1 (n = 8) and pAMR2 (n = 12) (p = 0.05) were higher than pAMR0 (n = 466) (p = 0.04 and p = 0.05 respectively). An optimal DF threshold was determined by the use of an ROC analysis, which ruled out the presence of either ACR or antibody-mediated rejection.The cell-free DNA DF holds promise as a non-invasive diagnostic test to rule out acute rejection in both adult and pediatric heart transplant populations.

The number of potential pediatric heart transplant recipients continues to exceed the number of donors, and consequently the waitlist mortality remains significant. Despite this, around 40% of all donated organs are not used and are discarded. This document (62 authors from 53 institutions in 17 countries) evaluates factors responsible for discarding donor hearts and makes recommendations regarding donor heart acceptance. The aim of this statement is to ensure that no usable donor heart is discarded, waitlist mortality is reduced, and post-transplant survival is not adversely impacted.

Treatment options for children with end-stage heart failure are limited. We report the first case of a successful pediatric heart transplantation bridged with a durable left ventricu-lar assist device in Korea. A 10-month-old female infant with dilated cardiomyopathy and left ventricular non-compaction was listed for heart transplantation. During the waiting period, the patient’s status deteriorated. Therefore, we decided to provide support with a durable left ventricular assist device as a bridge to transplantation. The patient was suc-cessfully bridged to heart transplantation with effective support and without any major adverse events.

Pediatric heart transplant has become the standard of care for end-stage heart disease in children throughout the world. The number of transplants has grown dramatically since the first transplant was performed, and over the last two decades, outcomes have consistently improved with progression in knowledge enhancing the clinical course and outcomes of these patients. Short-term outcomes in the most recent era have been excellent resulting in a renewed focus towards medium- and long-term outcomes. This article will review the most up-to-date literature on overall heart transplantation outcomes and specific long-term outcomes including rejection, cardiac allograft vasculopathy, graft failure, infection, renal dysfunction, malignancy, and the need for re-transplantation. The article also explores the post-transplantation outcomes of special populations, including Fontan patients, ABO-incompatible recipients, sensitized recipients, extracorporeal membrane oxygenation, and ventricular assist devices. The article concludes with a look at transition from pediatric to adult care and medication adherence, which are becoming major issues related to long-term outcomes as post-transplant survival increases.

Background: Given the shortage of donor organs in pediatric heart transplantation (HTx), pretransplant risk stratification may assist in organ allocation and recipient optimization. We sought to construct a scoring system to preoperatively stratify a patient’s risk of one-year mortality after HTx. Methods: The United Network for Organ Sharing database was queried for pediatric (Results: A total of 5,700 patients underwent HTx; one-year mortality was 10.7%. There was a similar distribution of variables between derivation (n = 4,560) and validation (n = 1,140) cohorts. Of the 12 covariates included in the final model, nine were allotted point values. The low-risk (score 0-9), intermediate-risk (10-20), and high-risk (>20) groups had a 5.18%, 10%, and 28% risk of one-year mortality ( P < .001), respectively. Both intermediate-risk (OR = 2.46, 95% confidence interval [95% CI]: 1.93-3.15; P < .001) and high-risk (OR = 9.24, 95% CI: 6.92-12.35; P < .001) scores were associated with an increased risk of one-year mortality when compared to the low-risk group. Conclusions: The Children’s Heart Assessment Tool for Transplantation score represents a pediatric-specific, recipient-based system to predict one-year mortality after HTx. Its use could assist providers in identification of patients at highest risk of poor outcomes and may aid in pretransplant optimization of these children.

There are limited published data addressing the costs associated with pediatric heart transplantation and no studies evaluating the variation in costs across centers. We aimed to describe center variation in pediatric heart transplant costs and assess the association of transplant hospitalization costs with patient outcomes. Using a linkage between the Pediatric Health Information System and Scientific Registry of Transplant Recipients databases, hospital costs were assessed for patients (

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 Conclusion In a PHT population with low incidence of rejection or high-grade CAV, CMR demonstrates important differences in myocardial structure, function and perfusion compared to age-matched healthy controls. Regadenoson stress perfusion CMR could be safely and reliably performed. Increasing T2 values were associated with worsening left ventricular function and increasing T1/ECV values were associated with rejection history and low-grade CAV. These findings warrant larger prospective studies to further define the role of CMR in PHT graft surveillance.

Background: Pediatric heart transplantation (HT) is resource-intensive. Adult studies have shown an increase in the proportion of adult HT funded by public insurance with outcomes inferior to those with private coverage. Trends in the funding of pediatric HT and associations with outcomes in children have not been described. Methods: We queried the United Network for Organ Sharing (UNOS) database for patients less than 18 years of age, listed for and undergoing HT from 1994 to 2018. We identified primary payer at listing (TCR), transplant (TRR), 1 year follow up, and between 1-5 years following HT. Trends in primary payer were analyzed using generalized logit regression. Cox regression was used to evaluate the impact of insurance on survival. Results: An increase in the proportion of patients with public insurance at the time of HT was observed. Forty eight percent of HT patients in 1994 and 59% in 2018 were publicly insured (P Conclusion: There has been a statistically significant trend towards increasing public insurance for patients awaiting, at the time of, and after HT. Patients that maintain or transition to public insurance following transplant have worse long term outcomes. As the number of patients undergoing HT with public insurance funding continues to increase, understanding of how insurance status impacts long-term outcomes is important.

Introduction: Traditional weight & height ratios as measures of donor-recipient (D-R) matching have been challenged in adult heart transplantation (HT). The optimal metrics for D-R matching in pediatric HT remain unclear, and were evaluated in the present study. Methods: All primary pediatric HT recipients in the Pediatric Heart Transplant Society database transplanted from 1993-2019 were included. Multiple metrics of size matching - height, weight, body mass index (BMI), body surface area (BSA), predicted heart mass (PHM) and total cardiac volume (TCV) were assessed to identify the metrics that would best predict 1-year post-transplant (PTx) graft loss (death/re-transplant). Kaplan-Meier analyses (risk unadjusted) and multivariate Cox proportional hazard models (risk adjusted) were used to assess the effect of differences of various size matching metrics on survival. Results: Among 6903 D-R pairs, multivariable hazard modeling identified the following risk factors for PTx mortality: female sex, black race, bilirubin, ECMO, VAD, mechanical ventilation, ICU admission at the time of transplant, presence of congenital heart disease, early era of transplant, donor ischemic time and cardiopulmonary bypass time. After adjusting for all covariates, increasing size mismatch by height, BSA, or PHM was associated with increased 1-year PTx graft loss, with a disproportionately higher hazard for undersized donors than oversized donors (Figure). Weight, BMI and TCV were not predictive of 1-year PTx graft loss on multivariate analysis. Conclusions: In pediatric HT recipients, increasing size mismatch by height, BSA and PHM is associated with increased 1-year PTx graft loss. Undersizing donors appears to carry a higher risk than oversizing.

Introduction: The shortage of available donor organs means we must re-consider our current policies on donor selection. There is a broad variation in practice between centers as to the acceptable limit to ischaemia time (IT) in pediatric cardiac transplantation, with no recommendations in international guidelines. Hypothesis: We hypothesised that a prolonged ischaemia time was not associated with impaired post-transplant outcomes. Methods: Data from the Pediatric Heart Transplantation Society was analysed for all pediatric patients receiving heart transplants (Jan 1993 - June 2019). Transplants were separated into 5 categories depending on the IT (hours): < 2.4, 2.5-3.4, 3.5-4.4, 4.5-6.0, >6. Risk-adjusted outcomes were assessed by multivariable analysis, adjusting for donor, recipient, and peri-operative characteristics. Results: Data for 6,903 transplants were assessed (IT < 2.4 in 980, 2.5-3.4 in 2032, 3.5-4.4 in 2310, 4.5-6.0 in 1162, >6 in 281). In univariate analysis, increasing IT was associated with reduced 1-year survival (90.1%, 87.7% and 84.6%; p6 groups, respectively. Similar findings, of a deleterious association with prolonged IT, were observed for freedom from infection (73.0%, 66.8% and 56.4%; p 6 hours was associated with graft failure in cardiomyopathy (HR: 2.87, 95% CI: 1.34 - 6.15, p=0.007), but not congenital heart disease patients. Conclusions: In this large multi-centre cohort study, we found a deleterious association between prolonged IT and post-transplant outcomes. We recommend that an IT greater than 6 hours should be avoided in pediatric cardiac transplantation.

Introduction: Despite improvements in pediatric heart transplant outcomes, respiratory syncytial virus (RSV) and vaccine preventable infections (R/VPI) are a major cause of morbidity and hospital resource use. The frequency and risk factors for hospitalizations due to R/VPI in heart transplant recipients are unknown. Methods: Patients ≤18 years who underwent heart transplantation at hospitals contributing to the Pediatric Health Information System database from 9/2003 to 12/2018 were identified. The transplant hospitalization and subsequent hospitalizations for R/VPI through 12/2018 were analyzed. Risk factors for R/VPI hospitalizations were evaluated using negative regression binomial models adjusted for potential demographic and clinical confounders. Total hospital costs were determined adjusted for 2018 US $. Results: Of 3,815 transplant recipients, 681 (17.9%) had a R/VPI hospitalization during 23,746 available person-years of follow-up after transplant. There were 984 R/VPIs diagnosed during 951 hospitalizations, and 440 (44.7%) occurred in the first year after transplant (Figure). The most common causes were RSV (n=380; 38.6%), influenza (n=265; 26.9%), and pneumococcus (n=105; 10.7%). In adjusted analyses, there was an increased risk of R/VPI hospitalization in patients requiring mechanical circulatory support prior to transplant, those who received induction with ≥ 2 immunosuppressive agents, and patients Conclusions: Hospitalization for R/VPIs occurred frequently following pediatric heart transplantation and were associated with significant cost. Potential strategies to minimize R/VPI could include expanding vaccine use through accelerated immunization schedules in younger patients and routine monitoring of immunogenicity after vaccination.

Introduction: While CMV infection has been associated with graft loss in adult heart transplants, its role in children is less understood. We aim to better understand the effect of donor and recipient CMV immune status at transplant on survival in pediatric recipients. Methods: We analyzed 6,951 pediatric heart-only transplants in the Scientific Registry of Transplant Recipients (1987-2019). Patients were stratified by recipient and donor CMV status at transplant. The primary endpoint was freedom from graft loss. Results: Of the various donor and recipient CMV statuses, only CMV-positive recipients had decreased graft survival compared to CMV-negative ones (at 15-yrs: 47% vs. 53%, HR 1.14). However, when fully adjusted by Cox regression, recipient status was no longer a risk factor ( p = 0.12). In this model, anti-CMV treatment with ganciclovir or valganciclovir was associated with a lower risk of graft loss (HR 0.80, CI 0.71 - 0.90, p < 0.005). When stratified by the four donor-recipient CMV status combinations, antiviral use was associated with improved survival in both donor-positive groups: most strongly in donor-positive/recipient-positive transplants (at 15-yrs: 51% vs. 39%, p < 0.005) and to a lesser extent in donor-positive/recipient-negative transplants (at 15-yrs: 53% vs. 51%, p < 0.005). The association is maintained when examined by era, such as with more frequent use of anti-CMV therapy after 1995. No association with antiviral use was observed in either donor-negative transplant group. Conclusion: CMV-positive recipients had greater long-term graft loss, although this may be confounded by other transplant characteristics. Anti-CMV therapy is associated with improved long-term graft survival in transplants with CMV-positive donors. This finding may explain the lack of association between donor CMV status and graft loss in that an association may be masked by antiviral use. Further investigation of anti-CMV therapy may mitigate risk of graft loss.

Introduction: Recent studies have suggested a relationship between mortality and center volume in pediatric heart transplantation; however, these studies utilize databases that lack granularity to assess patient risk profiles. Hypothesis: Utilizing the Pediatric Heart Transplant Society (PHTS) database, we hypothesized that there would be a difference in outcomes among centers based on yearly transplant volume, and that the patient’s clinical profiles would differ by center volume. Methods: We performed a retrospective analysis of the PHTS dataset from all pediatric (≤ 18 years of age) cases from 2009-2018. Centers were stratified into 5 groups based on annual volume: ≤ 4, 4-6, 6-9, 9-14, and > 14 transplants. We evaluated specific variables, including those identified as significant risk factors in previous PHTS studies including mechanical ventilation, PRA > 10%, high BUN, gender, and Fontan completion, within each group. We used Kaplan Meier for survival, contingency tables with Pearson Chi-square test for association, and analysis-of-variance to compare means. P< 0.05 was considered statistically significant. Results: There were 6800 cases among 55 centers. Table 1 demonstrates that there was no significant difference in one-year post transplant survival among the groups, and the patient variables showing statistically significant differences followed no specific pattern among the center volume groups. It also demonstrates that there is no clear association between cumulative risk factors within individual patients and center volume. Conclusions: One-year post transplant survival is similar within the PHTS for all centers regardless of case volume. These group differences were different for different variables and did not segregate consistently between lower volume and higher volume groups suggesting there exists a complicated relationship among risk factors and center volume.

Purpose Routine surveillance biopsy (RSB) is performed to detect asymptomatic acute rejection (AR) after heart transplantation (HT). Variation in pediatric RSB across institutions is high. We examined center-based variation in RSB use and its relationship to graft loss, AR, coronary artery vasculopathy (CAV), and cost of care during the first year post-HT. Methods We linked the Pediatric Health Information System (PHIS) and Scientific Registry of Transplant Recipients (SRTR, 2002-2016), including all primary-HT aged 0-21. We scored institutional RSB strategy by the median number of first-year biopsies in recipients aged ≥12 months without rejection. Mixed effects regression analysis was used to adjust for potential confounders and center effects. Results Of 2,867 patients at 29 centers, we identified an inflection at the top-tertile of centers (834 patients at 10 centers with RSB-score≥4). Higher-RSB centers (i.e. those in the top-tertile) had more patients on pre-HT ventilator/ECMO (23% vs 18% p=0.04) and fewer with a positive crossmatch (13% vs 17% p=0.007). After adjusting for patient and center differences, higher RSB frequency was associated with diagnosed AR (OR 1.15 p=0.004), a trend toward treated AR (OR 1.09 p=0.083) and higher cost (US$450,708 vs 342,170, p Conclusion Higher RSB frequency is associated with increased diagnosis, but not treatment, of AR one-year post-HT. Graft survival and CAV appear unchanged at medium term follow-up. De-intensification at high-frequency institutions may be safe and reduce costs, but further study of differences in treated rejections are necessary.

Purpose 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. Methods We performed a retrospective cohort study of 96 consecutive patients status-post primary HTx (age Results 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). Conclusion 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.

Purpose 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. Methods 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). Results 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). Conclusion 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.

Purpose Studies on the efficacy of pre-recovery donor thyroxine (T4) treatment for adult heart transplant recipients report inconsistent results. Guidelines for T4 therapy in donors designated for pediatric heart transplantation (PHT) remain undefined. This study investigates the age-dependent impact of donor T4 therapy on the survival of PHT recipients. Methods The UNOS Registry was queried for PHT recipients ( Results A total of 7,999 PHT recipients were identified. 51.5% received a T4-treated donor heart. Median age of patients receiving a T4-treated heart (5 yrs) was significantly higher than those transplanted with non-treated hearts (3 yrs; p Conclusion Survival benefit of donor T4 treatment in PHT depends mainly on recipient age, demonstrating a nonlinear relationship according to donor age. Better survival is seen in infants transplanted with T4-treated hearts. Future clinical trials are warranted to confirm indications for T4 therapy.

BACKGROUND The pediatric heart transplant community uses weight-based donor-to-recipient size matching almost exclusively, despite no evidence to validate weight as a reliable surrogate of cardiac size. Donor size mismatch is the second most common reason for the refusal of donor hearts in current practice (∼30% of all refusals). Whereas case-by-case segmentation of total cardiac volume (TCV) by computed tomography (CT) for direct virtual transplantation is an attractive option, it remains limited by the unavailability of donor chest CT. We sought to establish a predictive model for donor TCV on the basis of anthropomorphic and chest X-ray (CXR) cardiac measures. METHODS Banked imaging studies from 141 subjects with normal CT chest angiograms were obtained and segmented using 3-dimensional modeling to derive TCV. CXR data were available for 62 of those subjects. A total of 3 predictive models of TCV were fit through multiple linear regression using the following variables: Model A (weight only); Model B (weight, height, sex, and age); Model C (weight, height, sex, age, and 1-view anteroposterior CXR maximal horizontal cardiac width). RESULTS Model C provided the most accurate prediction of TCV (optimism corrected R2 = 0.99, testing set R2 = 0.98, mean absolute percentage error [MAPE] = 8.6%) and outperformed Model A (optimism corrected R2 = 0.94, testing set R2 = 0.94, MAPE = 16.1%) and Model B (optimism corrected R2 = 0.97, testing set R2 = 0.97, MAPE = 11.1%). CONCLUSIONS TCV can be predicted accurately using readily available anthropometrics and a 1-view CXR from donor candidates. This simple and scalable method of TCV estimation may provide a reliable and consistent method to improve donor size matching.

Rehospitalization following pediatric heart transplantation is common. However, existing data remain somewhat limited. Using a novel linkage between administrative and clinical databases, pediatric heart transplant (HT) recipients from 29 centers who survived to discharge were retrospectively reviewed to determine the frequency, timing of, and indication for all-cause rehospitalizations in the year following transplant discharge. Of 2870 pediatric HT recipients, 1835 (63.9%) were rehospitalized in the first year post-discharge (5429 total readmissions). Rehospitalization rates varied significantly across centers (46% to 100%) and were inversely correlated to center transplant volume (r(2) 0.25, p < 0.01). The median number of rehospitalizations per patient was 2 (IQR 1–4) and the median time to first rehospitalization was 29 days (IQR 9–99 days). Independent risk factors for rehospitalization included younger age at HT (HR 0.99, 95% CI 0.97–0.99), congenital heart disease (HR 1.2, 95% CI 1.1–1.4), listing status 1B at transplant (HR 1.3, 95% CI 1.1–1.5), and post-transplant complications including rejection prior to discharge (HR 1.5 95% CI 1.3–1.8) and chylothorax (HR 1.3, 95% CI 1.0–1.6). Cardiac diagnoses were the most common indication for rehospitalization (n = 1600, 29.5%), followed by infection (n = 1367, 25.2%). These findings may serve to guide the development of interventions aimed at reducing post-HT hospitalizations.

Heart transplantation from ABO incompatible (ABOi) donors has evolved into a progressively accepted therapy in young children. We assessed the recent practice of ABOi listing impact on waitlist and post-transplant outcomes.Using the Pediatric Heart Transplant Society registry, we compared clinical presentation, waitlist parameters, and post-transplant survival of children2 years of age listed for ABOi vs ABO compatible (ABOc) heart transplant between January 2010 and June 2018 with sub-analysis of blood group O recipients.Among 2,039 patients, ABOi listing increased significantly with time from 49% (2010) to 72% (2017). ABOi-listed patients had lower age and body surface area, and higher proportion of congenital heart disease, mechanical ventilation, and high urgency status (all p0.01). Use of mechanical circulatory support was similar between groups. Of 1,288 patients reaching transplant, 239 (18.6%) received an ABOi organ (15%-40%/year). Death while waiting, removal from the waitlist, and waitlist survival were similar between groups. Time to transplant was significantly shorter for ABOi listing in blood group O patients (p0.02), approaching significance (p = 0.057) for all blood groups. Post-transplant survival was similar except for lower survival of patients listed ABOc but transplanted ABOi. These patients showed increasing need for mechanical circulatory support and high urgency listing while waiting.In the current era, primary listing for ABOi heart transplant has become routine for the majority of children2 years old, resulting in shorter waitlist time, especially in blood group O. Post-transplant survival is similar despite ABOi-listed children still showing a higher risk profile.

Pediatric heart transplantation is a complex endeavor with a large amount of knowledge requirements and preparation. Success of the decision making leading up to the transplant and readiness for discharge post-transplant relies on adequate education and preparation [1]. The population is at high risk for medical non-adherence which is directly linked to poor patient outcomes [2]. Discrepancies in patient and family education and preparation lead to unmet care needs, medication errors, increased risk for complications and readmissions. This article will review the importance of preparation, assessment of education needs, and effective transfer of knowledge in pediatric heart transplantation.

In this study we sought to quantify hazards associated with various donor factors into a cumulative risk scoring system (the Pediatric Heart Donor Assessment Tool, or PH-DAT) to predict 1-year mortality after pediatric heart transplantation (PHT).PHT data with complete donor information (5,732) were randomly divided into a derivation cohort and a validation cohort (3:1). From the derivation cohort, donor-specific variables associated with 1-year mortality (exploratory p-value0.2) were incorporated into a multivariate logistic regression model. Scores were assigned to independent predictors (p0.05) based on relative odds ratios (ORs).The final model had an acceptable predictive value (c-statistic = 0.62). The significant 5 variables (ischemic time, stroke as the cause of death, donor-to-recipient height ratio, donor left ventricular ejection fraction, glomerular filtration rate) were used for the scoring system. The validation cohort demonstrated a strong correlation between the observed and expected rates of 1-year mortality (r = 0.87). The risk of 1-year mortality increases by 11% (OR 1.11 [1.08 to 1.14]; p0.001) in the derivation cohort and 9% (OR 1.09 [1.04 to 1.14]; p = 0.001) in the validation cohort with an increase of 1-point in score. Mortality risk increased 5 times from the lowest to the highest donor score in this cohort. Based on this model, a donor score range of 10 to 28 predicted 1-year recipient mortality of 11% to 31%.This novel pediatric-specific, donor risk scoring system appears capable of predicting post-transplant mortality. Although the PH-DAT may benefit organ allocation and assessment of recipient risk while controlling for donor risk, prospective validation of this model is warranted.

Background Large clinical, research, and administrative databases are increasingly utilized to facilitate pediatric heart transplant (HTx) research. Linking databases has proven to be a robust strategy across multiple disciplines to expand the possible analyses that can be performed while leveraging the strengths of each dataset. We describe a unique linkage of the Scientific Registry of Transplant Recipients (SRTR) database and the Pediatric Health Information System (PHIS) administrative database to provide a platform to assess resource utilization in pediatric HTx. Methods All pediatric patients (1999-2016) who underwent HTx at a hospital enrolled in the PHIS database were identified. A linkage was performed between the SRTR and PHIS databases in a stepwise approach using indirect identifiers. To determine the feasibility of using these linked data to assess resource utilization, total and post-HTx hospital costs were assessed. Results A total of 3188 unique transplants were identified as being present in both databases and amenable to linkage. Linkage of SRTR and PHIS data was successful in 3057 (95.9%) patients, of whom 2896 (90.8%) had complete cost data. Median total and post-HTx hospital costs were $518,906 (IQR $324,199-$889,738), and $334,490 (IQR $235,506-$498,803) respectively with significant differences based on patient demographics and clinical characteristics at HTx. Conclusions Linkage of the SRTR and PHIS databases is feasible and provides an invaluable tool to assess resource utilization. Our analysis provides contemporary cost data for pediatric HTx from the largest US sample reported to date. It also provides a platform for expanded analyses in the pediatric HTx population.

Purpose Pediatric heart transplant (PHT) patients have the highest waitlist mortality of all solid organ transplants yet more than 40% of viable hearts are unutilized. A tool for risk prediction is therefore necessary to improve organ matching in PHT. This study aims to compare and validate the PHT risk scores found in the literature. Methods The literature was searched for PHT risk prediction models. The UNOS registry was used to validate the models with a pediatric cohort ( Results Five recipient and one donor risk scores were published between 2008-2019 (Davies et al 2008, Almond et al 2012, Butts et al 2015, Zafar et al 2018, Fraser III et al 2019 and Choudhry et al 2019). The validation cohort included 1,003 PHT identified in UNOS. 50.5% of patients had a diagnosis of CHD and 42.8% of cardiomyopathy. With exception of Butts et al's model, all other models significantly predicted 1-year mortality for low- vs high-risk patients. Choudhry et al (ROC=0.70) and Davies et al (ROC=0.66) models had the highest predictive power (figure 1). Fraser III et al model was the best predictor for non-CHD patients (ROC=0.71) compared to Choudhry et al (ROC= 0.68) and Davies et al (ROC=0.67) models. Conclusion The risk model by Choudhry et al provided the best prediction for 1-year mortality. However, all published validated studies lacked advanced analytical approaches in their models. Using machine learning algorithms is important to develop an advanced tool that can risk stratify a given donor-to-recipient match for any PHT candidate.

Purpose Functional status at listing predicts waitlist survival in adult heart transplant candidates including those on mechanical circulatory support. This has not been studied in pediatric heart transplantation although it is an independent predictor of outcomes in pediatric liver transplantation. We aimed to determine the association of: 1) functional status at listing with waitlist and post-transplant outcomes, and 2) functional status at transplant with post-transplant outcomes in pediatric heart transplant candidates. Methods Retrospective registry study of 5754 patients ≤18 years old listed for heart transplant between 1995 and 2019 with Lansky/Karnofsky Play Performance Scale (LPPS) scores in the UNOS database. Standard statistical methods were used to assess relationships of LPPS scores at listing and transplant with waitlist and post-transplant outcomes. A positive waitlist outcome was defined as transplantation, removal from waitlist due to clinical improvement, or remaining on waitlist. Results At listing, 1463 patients had the ability to carry out normal activities (LPPS 80-100), 2338 had mild-moderate restriction in functional status (LPPS 50-70), and 1953 had moderate-severe restriction (LPPS 10-40). Normal activity and mild-moderate restriction at listing were associated with a higher positive waitlist outcome rate compared with moderate-severe restriction (90% vs 80%, p Conclusion Candidate functional status is associated with waitlist as well as post-transplant outcomes. Improvement in functional status between listing and transplant is associated with better outcomes 1-year post-transplant. These data suggest that interventions targeting functional impairment (e.g. physical rehabilitation) have the potential to improve pediatric heart transplant outcomes.

Primary graft failure has been broadly defined as cardiac and circulatory insufficiency in the immediate postoperative period after cardiac transplantation. Risk factors for primary graft failure have been identified in the donor, recipient, and within the perioperative period. Donor serum biomarkers have been identified. The use of donor serum cardiac troponin levels, while most studied, is of questionable value. Basic markers of renal and hepatic function in the recipient are associated with risk of hospital mortality after transplant. HLA antibodies in the recipient to donor HLA antigens are a marker of primary graft failure. Accumulating experience and investigation suggest that cardiac transplantation may be performed in the presence of low levels of donor specific antibodies. Increasing sophistication in the assessment of HLA antibodies may allow for a more precise assessment of their impact on allograft function and survival and increase the capability to transplant these sensitized children.

Donors are matched for weight in pediatric heart transplantation (PHT), yet age differences are not considered in this decision. In this study we attempt to identify the effect of age differences in weight-matched patients and the effect these differences have on post-transplant survival.The United Network of Organ Sharing (UNOS) database was queried for the period from October 1987 to March 2014 for all pediatric heart transplant patients. Transplants with donor-to-recipient (D-R) weight ratios of 0.8 to 1.5 were identified (weight-matched). D-R age differences were categorized as: donors 5 years younger than recipients (DR-5); donors within 5 years of recipients (D=R±5); and donors 5 years older than recipients (DR+5).A total of 4,408 patients were identified as weight-matched transplants. Of these transplants, 681 were DR+5, 3,596 were D=R±5 and 131 were DR-5. DR+5 transplants were found to be associated with decreased post-transplant survival compared with D=R±5 (p = 0.002). Rates of acute rejection were similar among all groups but post-transplant coronary allograft vasculopathy (CAV) was more prevalent in DR+5 than D=R±5 patients (28% and 18%, respectively; p0.001). Increasing age difference by each year was associated with decreasing median post-transplant survival time (p0.001; hazard ratio 1.018, range 1.011 to 1.025). The overall negative association with mortality was due to the adolescent cohort (11 to 17 years), specifically DR+5 transplants, utilizing organs from donors25 of age.In PHT, increasing D-R age difference decreases survival; however, this effect is driven by recipients 11 to 17 years old and donors25 years old. Allocation of younger donor organs to adolescent recipients should be a priority.

The effect of age at transplant on rejection detected by routine surveillance biopsy (RSB) in pediatric heart transplant (HT) recipients is unknown. We hypothesized there would be low diagnostic yield and decreased prevalence of rejection detected on RSB in infants (age1 year) when compared with children (age 1 to 9 years) and adolescents (age 10 to 18 years).We utilized Pediatric Heart Transplant Study (PHTS) data from 2010 to 2013 to analyze moderate-to-severe (ISHLT Grade 2R/3R) cellular rejection (MSR) detected only on RSB (RSBMSR).RSB detected 280 of 343 (81.6%) episodes of MSR. RSBMSR was detected in all age groups even5 years after HT. Infant RSBMSR had a greater proportion (p = 0.0025) occurring5 years after HT (39.2 vs 18.4 vs 10.8%) and a lower proportion (p = 0.0009) occurring in the first year after HT (25.5 vs 60.6 vs 51.7%) compared with children and adolescents, respectively. Freedom from RSBMSR was 87 ± 7% in infants, 76 ± 6% in children and 73 ± 7% in adolescents 4 years after HT. In 1-year survivors who had RSBMSR in the first year after HT, the risk of RSBMSR occurring in Years 2 to 4 was significantly (p0.0001) greater than patients without RSBMSR in the first year (hazard ratio 21.28, 95% confidence interval 10.87 to 41.66), regardless of recipient age.RSBMSR exists in all age groups after pediatric HT with long-term follow-up. The prevalence in infant recipients is highest5 years after HT. Those with RSBMSR in the first year after HT are at a high risk for recurrent rejection regardless of age at HT.

Purpose Currently there are no-FDA approved immunosuppressants specific to pediatric heart transplantation (HT). In recent years, everolimus (EVL) has emerged as an alternative to tacrolimus (TAC) as a primary immunosuppressant to prevent rejection that may also prevent kidney and coronary disease. However, the two regimens have never been evaluated systematically. Methods The TEAMMATE Trial (IND 127980) is designed to evaluate the safety and efficacy of EVL and low-dose (LD-TAC) compared to standard-therapy TAC and mycophenolate mofetil (MMF). The study design and rationale are reviewed in light of challenges inherent in rare disease research. Results The TEAMMATE trial is the first multicenter randomized clinical trial (RCT) in pediatric HT. The primary purpose is to evaluate the risk-benefit profile of the two regimens to prevent major adverse transplant events (MATE), and to support FDA approval of 1 or both regimens for pediatric HT. Children Conclusion The TEAMMATE trial is the first RCT in pediatric HT. It is anticipated that the study will provide important information about the safety and effectiveness of EVL and TAC and provide valuable lessons into the design and conduct of future trials in pediatric HT.

Purpose Donor utilization rates continue to be low for pediatric heart transplantation (pHT) however efforts to expand the donor acceptance criteria have shown mixed results in single institution studies in pediatric and adult transplantation. Methods We analyzed pHT UNOS data (2008-2018) to compare the recipient characteristics, donor characteristics and outcomes, based on donor ejection fraction of less than 50% (low EF) and or ischemic time of greater than 4 hours (prolonged IT). Results A total of 4345 pHT were performed of which 1309 (30.1%) were with prolonged IT and 122 (2.8%) in low EF. Additionally, 58 (1.3%) were performed with both low EF and prolonged IT (combined risk). Recipients of combined risk were more likely to be younger, have post-surgical congenital heart disease, be on ECMO or ventilator but less likely on VAD (all p l 0.01). Figure 1. There was no significant difference in donor characteristics such as mode of death, gender mismatch, race mismatch or inotrope use. Waitlist time was significantly lower for low EF (mean 39 days, range 15-109) or combined risk group (36 days, 15-80) compared to other groups (60 days, 23-125) (p=0.01). 1 year mortality was 8% in low risk group, 12% in prolonged IT, 14% in reduced EF and 28% in combined risk patients (p l 0.01). Additionally, 9% of low risk patients had episode of treated rejection, while 15% of prolonged IT, 5% of low EF and 15% in combined group had rejection (pl0.01).The KM survival analysis performed is shown in the figure 1. Conclusion Lower EF donors performed similar to prolonged IT donor, but were uncommonly used. Acceptance of risk was common in recipients deemed higher risk for waitlist mortality and led to shorter wait times. However, episodes of treated rejection as well as 1 year mortality was higher with the higher risk transplants, specifically with combined risk donors. Caution should be used in accepting combined risk transplants and further analysis will help balance the waitlist mortality with post-transplant outcomes.

Purpose Pediatric lung transplantations (LTx) consists of a relatively small but significant population. Without pooling of multi-institutional data, setting expectations for length of stay (LOS) is difficult. This study aims to investigate the LOS in LTx over the last 20 years to help benchmarking and quality improvement work. Methods The United Network for Organ Sharing (UNOS) database was used to identify patients ages 0-18 at time of listing for LTx between 2000 and 2019. This timeframe was divided into two eras: first (2000-2009) and second (2010-2019) eras. LOS was defined as number of days from LTx to discharge. Results 905 LTx were identified. 471 transplantations occurred in the first era and 434 in the second. Overall length of stay [median days (IQR)] was 19 (13-31) and comparable between the eras [18 (13-29) vs 20 (14-35), p=0.082]. Specifically by age, LOS for infants was 44 (29-80), for ages 2-11 was 21 (13-37), and for ages 12-18 was 17 (12-26). Compared to patients who did not have each of the following, LOS was increased in patients on ECMO (p Conclusion Over the past two decades, lung transplantation patients who are younger or who have pre- or post-transplantation end-organ dysfunction consistently have longer LOS. With these stable patterns, healthcare moving towards a bundled-care system, and an increase in UNOS required & institutional Quality Improvement projects, establishing benchmarks and expectations in pediatric post-lung transplant LOS is important.

Purpose In adults, female (F) and African American (AA) heart transplant (HT) recipients have higher waitlist (WL) and post-transplant (PT) mortality. Our study aims to evaluate gender and racial disparities in pediatric recipients and its effect on survival in the WL and PT period in the current era. Methods Pediatric ( Results 1435 (44%) F were listed for HT during the study period. Compared to males (M), F recipients listed for HT were younger, more likely AA (19 vs. 22%), and cardiomyopathy [CMP] (41.3 vs. 51.4%) [p 0.05 for all]. 663 (20%) AA HT candidates were listed. Compared to Caucasian, AA recipients more likely had CMP (41.3 vs. 49.5%), listed Status 1A (68.7 vs. 72.9%), had renal dysfunction (47.4 s. 53.4%) and were on Medicaid (33.3 vs. 65%) [p Conclusion In the current era, pediatric heart transplant recipients who are F and AA continue to have higher waitlist mortality. Such disparities do not exist post-transplant.

Purpose PRES is an uncommon complication of organ transplantation. Little is known about its clinical course and risk factors. We sought to examine the natural history and risk factors for PRES in pediatric heart transplant (HTx) recipients. Methods 14-center international retrospective study of 46 pediatric PRES cases between 2000-2018, compared with 1372 HTx recipients without PRES between 2000-2018. Demographic and clinical data were entered into a central database. PRES diagnosis was based on a combination of seizures, headache, altered mental status or focal neurological deficits, and required confirmation, either by MRI or resolution of neurological symptoms after CNI withdrawal. Factors associated with PRES were identified by Cox Proportional Hazard multivariable analysis. Results Median onset of symptoms was 16 days (R, 2-2468 d) after HTx; 23 (50%) developed PRES in the first 2 weeks, 32 (70%) in the first month, and 40 (87%) within the first year after HTx. Symptoms at presentation included seizures (40/46, 87%), altered mental status (27/46, 59%), headache (18/46, 39%), focal neurological deficits (16/46, 35%), and lasted for a median of 4 days (R 1-1772d), with almost all recipients (44/46, 96%) making a full recovery. MRI was obtained in 43/46, showing a vasogenic pattern of edema characteristic of PRES in 37 recipients (80%). Recipients with PRES tended to be older (9.1 y vs 5.9 y, p=0.06). Hypertension (SBP>95%ile) was present in 40/44 (91%) recipients with PRES at presentation, with severe hypertension (SBP>99%ile plus 5mmHG) in 37 (85%). Though all cases occurred in the setting of CNI use (TAC 40, CSA 6), levels were supratherapeutic in only 13/42 (31%). Cox analysis revealed a 5.3x increased hazard for PRES with Glenn (CI 1.54,18.01; p=0.008) and a 3.8x increased hazard with Fontan (1.08,13.00; p=0.038), while age, underlying cardiac diagnosis, BMI, ischemic time and type of CNI did not appear to contribute significantly. Conclusion 2/3 of pediatric PRES cases occur in the first month after HTx with seizures as the most common presenting symptom. An overwhelming majority of patients were severely hypertensive, whereas less than a third had supratherapeutic CNI levels. Almost all recipients recovered fully within days. Recipients with pre-existing Glenn or Fontan have a higher rate of developing PRES after HTx.

Noninvasive assessment of diastolic function in pediatric heart transplantation (PHTx) patients is important for monitoring of rejection, cardiac allograft vasculopathy, and nonspecific graft failure. We hypothesized that left atrial strain (LAS) would correlate with pulmonary capillary wedge pressure (PCWP) and that cutoff values to identify elevated left ventricular (LV) filling pressure could be derived for clinical practice and future testing.This was a secondary analysis of a prospectively collected cohort of PHTx patients undergoing same-day cardiac catheterization with biopsy and transthoracic echo. There were 70 patients with 85 clinical encounters. Traditional mitral inflow Doppler, LAS, LV diastolic strain and strain rate, and ratios for mitral E to LV diastolic strain and strain rate were assessed. Correlation with PCWP was performed, and receiver operator characteristic curves were generated for an elevated mean PCWP, acute rejection, and cardiac allograft vasculopathy.Decreased LAS during the atrial reservoir phase (Ɛres) correlated with higher invasively measured PCWP (r = -0.40, P .001). An Ɛres cutoff of 14.5% had good discriminatory ability for an elevated PCWP (sensitivity 75%, specificity 82%), and Ɛres 22.0% had 100% negative predictive value; Ɛres was superior to other measures of diastolic function. Subanalyses for recent acute rejection (n = 9) showed good discriminatory ability for Ɛres of 14.5% (sensitivity 89%, specificity 74%).LAS correlates with invasively measured PCWP and can identify elevated pressures better than traditional and other advanced diastolic function parameters. Use of LAS in PHTx patients may aid in noninvasive monitoring for rejection and nonspecific graft dysfunction.

Echocardiographic follow-up after pediatric heart transplantation is important because of the lifelong risk for rejection and resultant ventricular dysfunction. Although adult studies have shown that echocardiographic measures of right ventricular function are changed after transplantation, similar results have not been reported in the pediatric population.A single-center retrospective study of echocardiograms obtained among pediatric heart transplant recipients was conducted. All echocardiograms were selected remote from transplantation, rejection, or graft vasculopathy. These criteria identified 127 patients. Right ventricular systolic function was measured using tricuspid annular plane systolic excursion, fractional area change (FAC), and peak systolic tricuspid annular tissue velocity (S'). Results were compared with those in 380 healthy age-matched echocardiographic control subjects.Tricuspid annular plane systolic excursion values in pediatric heart transplant recipients were significantly lower than in control subjects at all ages (P .0001), with a mean Z score of -3.38. FAC and S' did not vary by age in control patients6 months of age. FAC values in transplantation patients were significantly decreased compared with those in control subjects (P .0001), but 83% of transplantation patients had FAC values within the control-derived normal range. S' values were also significantly lower in transplantation patients than control subjects (P .0001).Heart transplantation patients have significantly decreased quantitative metrics of right ventricular function relative to healthy control subjects; longitudinal shortening (tricuspid annular plane systolic excursion and S') is particularly affected. FAC is relatively preserved and may be a better metric in this population. These results establish nomograms of RV function in pediatric heart transplantation patients and in normal pediatric control subjects, which may allow quantification of changes in this vulnerable population.