Pediatric Heart Transplant Recipients Research Articles

Abstract 4136754: Psychoactive medication use in pediatric heart transplant recipients: An assessment of prevalence, risk factors, and outcomes

Background: There is increasing recognition of the mental health burden experienced by pediatric heart transplant (HTx) recipients. Mental health concerns can impact physical health and increase risk of poor health outcomes. Using the Pediatric Heart Transplant Society (PHTS) database, we assessed the use of psychoactive medications as a proxy for mental health issues. We assessed the prevalence of psychoactive medication usage, pre- and post HTx factors, and post HTx outcomes associated with psychoactive medication usage. Methods: We queried the PHTS database for patients >5 years of age at time of follow-up who underwent HTx between January 2015 and June 2023. Patients with use of any psychoactive medication were identified. Sub-analyses were performed for use of antianxiety/antidepressant and attention-deficit/hyperactivity disorder (ADHD) medications. Multivariate logistic regression models were utilized to assess risk factors and impact on outcomes, including graft survival, coronary artery vasculopathy (CAV), and rejection at 1, 3, and 5 years post-HTx. Results: Among 1792 patients older than 5 at 1 year post HTx, 301 (16.8%) were prescribed at least one psychoactive medication; 246 (13.7%) were prescribed medication for antianxiety/antidepressant medications and 59 (3.3%) for ADHD. Utilization of psychoactive medication decreased at 3 years (14.8%, N= 240 of 1629) and 5 years post HTx (11.3%, N=230 of 2029). Patients on psychoactive medications at 1 year post HTx tended to be older (OR=2.1, p<0.001), had higher priority listing status (OR=2.3, p<0.05), and longer bypass time (OR=1.6, p<0.05). Black patients were less likely to be prescribed psychoactive medication at 3-years post HTx than white patients (OR=0.57, p<0.05) or other races (OR=0.43, P <0.001). There was no association of psychoactive medication usage on graft survival, CAV, or rejection at 1 year post HTx. At 3 years post HTx psychoactive medication usage was associated with significantly higher prevalence of CAV (p<0.05). At 5 years post HTx graft loss (p<0.005) and CAV (p<0.05) were significantly increased in patients on psychoactive medications. Conclusions: A significant proportion of pediatric HTx patients take psychoactive medications. This population may be at risk for worse long-term outcomes. There is a need to assess the mental health burden of pediatric HTx and to identify modifiable factors to improve assessment and treatment of mental health issues and its impact on outcomes.

A qualitative account of mothers of pediatric heart transplant recipients' experience at a pilot mindfulness-based retreat: insights for implementation.

To explore participants' shared experience attending a pilot mindfulness-based retreat (MBR) intervention supporting the psychological well-being of mothers of pediatric heart transplant (HTx) recipients. A qualitative description approach was used within a larger hybrid mixed-methods pilot study evaluating the implementation-effectiveness of a 2-day MBR tailored specifically for a pediatric HTx population. A purposive sample of mothers was recruited from a leading Canadian pediatric HTx center, and each represented a primary, female-identifying caregiver, sharing residence with a pediatric HTx recipient of at least 4 months post-transplant. Two focus groups were conducted after and 16 individual interviews 3 months after the MBR to elicit participants' in-depth experience attending the MBR. Reflexive thematic data analysis led to theme development through an iterative process with consensus among team members. Sixteen mothers of pediatric HTx recipients (mean patient age 9.8 years; mean time post-transplant 8.2 years) participated in the MBR held in Ontario, Canada. Qualitative findings illuminated mothers' shared experience attending the MBR, reflecting three themes that describe key intervention elements beyond those affiliated with mindfulness practice alone: "respite," "readiness," and "relationships." Findings highlight acceptability and appropriateness as distinct yet interrelated implementation outcomes. Elements of "respite," "readiness," and "relationships" are key components of the MBR experience that offer valuable intervention and clinical considerations related to mothers' psychological well-being. Aligning intervention acceptability and appropriateness through tailored strategies may aid implementation. Future research considering maternal readiness relative to support intervention participation is warranted.

Invasive Fungal Disease in Pediatric Heart Transplant Recipients

Abstract Background The epidemiology of IFD following pediatric heart transplantation (pHT) is poorly characterized. We sought to evaluate use of antifungal prophylaxis and describe the epidemiology of IFD in pHT at two large children’s hospitals. Methods We performed a retrospective cohort study of pediatric and young adult (≤21 years) patients undergoing heart transplantation at Cincinnati Children’s Hospital Medical Center (CCHMC) and Children’s Hospital of Philadelphia (CHOP) between 2012 and 2021. We recorded demographic, clinical, medication, and laboratory data for pHT patients through 12 months post-transplant. We identified use of topical (oral nystatin) and systemic antifungal prophylaxes in the peri-transplant period (7 days prior through 14 days following transplant) and analyzed if certain transplant variables were associated with the administration of systemic antifungals during this period using rank sum and chi squared tests. Applying published definitions, we quantified the incidence of proven and probable IFD and explored the characteristics of these cases. Results A total of 201 patients underwent heart transplant at CCHMC and CHOP. The majority were male (60.2%), White (66.7%), and not Hispanic or Latino (88.1%). Median age at time of transplant was 7.4 years (IQR 0.9-14.2). During the peri-transplant period, 143 (71.1%) patients received oral nystatin and 37 (18.4%) received systemic antifungal prophylaxis, not including PJP prophylaxis. 41 individuals (20.4%) were not on any antifungal prophylaxis throughout this period. Delayed chest closure was significantly associated with the administration of systemic antifungals (p<0.001) while several other variables (age, hospital, immunosuppression medication, ECMO/LVAD pre-transplant) were not. In total, 8 patients (4%) developed proven (n=5) or probable (n=3) IFD. In our cohort, the incidence rate of proven/probable IFD in the first year post-transplant was 44.8 per 1000 patient-years. The characteristics of these cases are shown in Table 1. Time from pHT to IFD ranged from 11 days to 196 days (median time = 25.5 days). All cases of proven IFD occurred within 28 days of transplant. In three cases of proven/probable IFD, patients were receiving a systemic antifungal or PJP prophylaxis in the seven days prior to IFD onset. Two cases met the definition of probable IFD but the infections resolved without directed therapies. Four patients with proven IFD died within 1 year following transplant, although in only 3 cases was IFD a contributing factor. The one-year all-cause mortality rate among pHT patients with proven/probable IFD (50%) was higher than that in pHT patients without IFD (10.3%; Fisher’s exact p=0.008). Conclusion Over a 10-year period at CCHMC and CHOP, 4% of pHT patients developed proven or probable IFD within one-year post-transplant. All proven IFD cases occurred within a month of transplant while probable cases occurred more than 100 days post-transplant. Delayed chest closure was significantly associated with the administration of systemic antifungal prophylaxis. Patients with proven IFD had poor outcomes despite receipt of appropriate antifungal treatment. Given the low incidence of IFD at these two centers, we were unable to evaluate risk factors for IFD in this population and so larger studies would be needed.

Socioeconomic Status and Major Adverse Transplant Events in Pediatric Heart Transplant Recipients

Low socioeconomic status (SES) has been associated with higher risk of rejection and graft loss in pediatric heart transplant (HT) recipients. The association of SES with other posttransplant morbidities is unknown. To assess whether low SES is associated with higher risk of a major adverse transplant event (MATE) among pediatric HT recipients. Retrospective single-center cohort study at a children's hospital in Boston with consecutive primary HT recipients from 2006 to 2019 and follow-up through 2022. Data were analyzed from June 2023 to March 2024. Very low or low, moderate, and high or very high Childhood Opportunity Index (COI) for neighborhood (census tract) of patient residence. Primary outcome was 3-year MATE-6 score assessed in 6-month survivors as cumulative burden of acute cellular rejection, antibody-mediated rejection, coronary vasculopathy, lymphoproliferative disease, kidney dysfunction, and infection, each as an ordinal score from 0 to 4 (24 for death or retransplant). Secondary outcomes were freedom from rejection during first 6 months, freedom from death or retransplant, MATE-3 score for events 1 to 3 (under immune suppression) and events 4 to 6 (chronic immune suppression effects), and each MATE component. Of 153 children analyzed, the median (IQR) age at HT was 7.2 (1.5-14.8) years, 99 (65%) were male, 16 (10%) were Black, 17 (11%) were Hispanic, and 106 (69%) were White. Fifty patients (33%) lived in very low or low, 17 (11%) in moderate, and 86 (56%) in high or very high COI neighborhoods. There was no significant group difference in mean (SD) 3-year MATE-6 score (very low or low COI, 3.4 [6.5]; moderate COI, 2.4 [6.3]; and high or very high COI, 4.0 [6.9]). Furthermore, there was no group difference in mean (SD) MATE-3 scores for underimmune suppression (very low or low COI, 1.9 [3.5]; moderate COI, 1.2 [3.2]; and high or very high COI, 2.2 [3.6]), chronic immune suppression effects (very low or low COI, 1.6 [3.3]; moderate COI, 1.1 [3.2]; and high or very high COI, 1.8 [3.6]), individual MATE components, rejection during the first 6 months, or death or retransplant. In this cohort study of pediatric HT recipients, there was no difference in posttransplant outcomes among recipients stratified by SES, a notable improvement from prior studies. These findings may be explained by state-level health reform, standardized posttransplant care, and early awareness of outcome disparities.

Progress in Noninvasive Surveillance for Acute Rejection in Pediatric Heart Transplant Recipients: A Real-World Analysis of Donor-Derived Cell-Free DNA-Based Surveillance Protocol.

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

Prevalence and Impact of Recurrent Rejection on Pediatric Heart Transplant Recipients: A PHTS Multi-Institutional Analysis

BackgroundStudies evaluating the prevalence and impact of recurrent rejection (RR) in pediatric heart transplant (HT) are sparse. ObjectivesThe purpose of this study was to describe prevalence and impact of RR on cardiac allograft vasculopathy (CAV) and graft loss after pediatric HT. MethodsData on HT from January 1, 2000, to June 30, 2020, in the Pediatric Heart Transplant Society database were included. Freedom from RR (≥2 rejection episodes) was compared by era (early: 2000-2009; current: 2010-2020). Outcomes for children experiencing RR were compared with those experiencing 0 or 1 rejection episodes and by type of RR (antibody-mediated rejection [AMR], acute cellular rejection [ACR], mixed [ACR/AMR]). ResultsOf 6,342 HT recipients, 1,035 (17%) experienced RR. In the current era, pediatric HT recipients were less likely to experience RR (P < 0.001). Freedom from CAV was similar for those experiencing RR to those experiencing 0 or 1 episode (96.6% vs 95.3% vs 96.6%); and similar regardless of the type of RR (AMR, ACR, or mixed) (65.5% vs 82.9% vs 100%) (P > 0.05). Freedom from graft loss was significantly lower for those experiencing RR to those experiencing 0 or 1 episode (56.3% vs 72.3% vs 82.3%) and lower for those experiencing recurrent mixed rejection or recurrent AMR compared with those experiencing recurrent ACR (65.3% vs 50% vs 81.8%). Black children experiencing RR subsequently had lower freedom from CAV and graft loss than White children (P < 0.05 for all). ConclusionsAlthough prevalence of RR has decreased, children experiencing RR are at greatly increased risk for losing their graft, particularly those who have recurrent mixed or antibody-mediated rejection.

Role of Angiopoietins in Pediatric Heart Transplant Recipients with and without Kidney Dysfunction

Role of Angiopoietins in Pediatric Heart Transplant Recipients with and without Kidney Dysfunction

Importance of optimizing routine immunization schedules in pediatric heart transplantation

ObjectiveVaccination is the most effective preventive measure to reduce the risk of infection in patients receiving immunosuppressive treatment, such as heart transplant (HT) patients. The objectives of this study are to describe and evaluate the vaccination status of a group of pediatric HT recipients. Material and methodsRetrospective descriptive study of 75 pediatric patients who underwent HT at a tertiary hospital between January 2000 and September 2020. Demographic, clinical (immunization before and after HT, and attendance to vaccination counselling consultation), and analytical (hepatitis A and B serology before and after HT) variables were collected. ResultsPatients >12 months reached the HT with better vaccination coverage than those <12 months: 78.9 % versus 60.7 % had a complete vaccination schedule (P=.15). Post-HT vaccination update rate is low; only 13.3 % of patients had a complete schedule according to their age. The post-HT vaccination update of the human papillomavirus vaccine is higher in women (P=.02). We did not find statistical differences between other vaccines according to sex. A total of 13.3 % of patients attended post-HT vaccination counselling consultation, being better immunised than those who did not (P=.01). ConclusionsThe evaluation and optimization of vaccination schedules of patients with HT remains suboptimal. A follow-up of these patients and their relatives in vaccination specialised consultations can improve the immunization status of pediatric HT recipients.

The Implementation-Effectiveness of a Mindfulness-Based Retreat for Mothers of Pediatric Heart Transplant Recipients: A Pilot Hybrid Mixed Methods Study

The Implementation-Effectiveness of a Mindfulness-Based Retreat for Mothers of Pediatric Heart Transplant Recipients: A Pilot Hybrid Mixed Methods Study

Association Between High Sensitivity Troponin I and NTproBNP With Rejection and Graft Loss in Pediatric Heart Transplant Recipients.

Troponin I is a blood biomarker of cardiac injury and levels measured using a high-sensitivity assay after pediatric heart transplantation (HT) have not been described. We sought to assess the association between high-sensitivity troponin I (hsTnI) and N-terminal pro-B-type natriuretic peptide (NTproBNP) with treated acute rejection (AR) and graft loss in pediatric heart transplant (HT) recipients. Serum was collected and banked from pediatric HT recipients prior to cardiac catheterization. Patients with samples drawn within 365 days post-HT were included and followed for up to 5 years. Generalized linear mixed-effect models examined the association between hsTnI and treated AR using a random intercept per patient. Cox proportional hazards models tested the association between maximal hsTnI and NT-proBNP and death/graft loss. HsTnI and NTproBNP values decline in the weeks following HT, after which these biomarkers stabilize. HsTnI was higher in AR versus no AR (6.2 vs. 3.5 ng/L, p < 0.001); doubling of hsTnI increased the odds of AR by 33% (p = 0.004). HsTnI showed moderate discrimination for AR with an AUC of 0.811 (95% CI 0.76, 0.87) and a NPV of 96.4% (95% CI 93.0, 98.1). Elevation in NT-proBNP was not associated with AR. In multivariable Cox modeling, a doubling of maximal NT-proBNP was associated with graft loss (HR 8.96, p = 0.014). In this pediatric HT cohort, HsTnI was moderately discriminative for AR and higher maximal NT-proBNP was associated with graft loss. HsTnI may add value in pediatric HT non-invasive AR surveillance, and elevated NTproBNP could suggest an increased risk of graft loss.

Donor-derived Cell-free DNA Evaluation in Pediatric Heart Transplant Recipients: A Single-center 12-mo Experience.

Endomyocardial biopsy (EMB) is considered the gold-standard method to diagnose rejection after heart transplantation. However, the many disadvantages and potential complications of this test restrict its routine application, particularly in pediatric patients. Donor-derived cell-free DNA (dd-cfDNA), released by the transplanted heart as result of cellular injury, is emerging as a biomarker of tissue damage involved in ischemia/reperfusion injury and posttransplant rejection. In the present study, we systematically evaluated dd-cfDNA levels in pediatric heart transplant patients coming for follow-up visits to our clinic for 12 mo, with the aim of determining whether dd-cfDNA monitoring could be efficiently applied and integrated into the posttransplant management of rejection in pediatric recipients. Twenty-nine patients were enrolled, and cfDNA was obtained from 158 blood samples collected during posttransplant follow-up. dd-cfDNA% was determined with a droplet-digital polymerase chain reaction assay. EMB scores, donor-specific antibody measurements, and distress marker quantification were correlated with dd-cfDNA, together with echocardiogram information. The percentage of dd-cfDNA increased when EMBs scored positive for rejection (P = 0.0002) and donor-specific antibodies were present (P = 0.0010). N-terminal pro-B-type natriuretic peptide and high-sensitive troponin I elevation were significantly associated with dd-cfDNA release (P = 0.02 and P < 0.0001, respectively), as were reduced isovolumetric relaxation time (P = 0.0031), signs of heart failure (P = 0.0018), and treatment for rejection (P = 0.0017). By determining a positive threshold for rejection at 0.55%, the test had a negative predictive value maximized at 100%. Collectively, results indicate that dd-cfDNA monitoring has a high negative prognostic value, suggesting that in heart transplanted children with dd-cfDNA levels of <0.55% threshold, protocol EMBs may be postponed.

Clinical outcomes after a biopsy diagnosis of antibody-mediated rejection in pediatric heart transplant recipients

BackgroundExtending graft survival after heart transplant (HT) is of paramount importance to achieve survival well into adulthood for childhood recipients. Acute rejection is a significant adverse event, and biopsy remains the most specific means for diagnosing acute cellular rejection (ACR) versus antibody-mediated rejection (AMR). MethodsAll children in the Pediatric Heart Transplant Society (PHTS) Registry who underwent HT between 1/2015 and 6/2022 and had ≥1 episode of treated rejection were included. Survival after rejection was compared between those with AMR and those with ACR-only. Secondary outcomes of infection, malignancy, and cardiac allograft vasculopathy (CAV) were assessed. Risk factors for graft loss after AMR were identified using Cox proportional hazard modeling. ResultsAmong 906 children treated for rejection during follow-up through 12/2022, 697 (77%) with complete biopsy information were included. AMR was present on biopsy in 261 (37%) patients; ACR-only was present in 436 (63%) patients. Time to treated rejection was earlier in those with AMR, median time from HT to rejection 0.11 versus 0.29 years, p=0.0006. When rejection occurred within the 1st year, survival after AMR was lower than survival after ACR-only. Predictors of graft loss after AMR were younger age at HT, diagnosis of congenital heart disease, and rejection with hemodynamic compromise. There was no difference in time to CAV, infection, or malignancy after treated rejection between groups. ConclusionsThe largest analysis of pediatric HT recipients treated for rejection with biopsy data to identify AMR underscores the continued importance of AMR on survival. AMR is associated with higher graft loss versus ACR when occurring in the first-year post HT. Predictors of graft loss after AMR identify patients who may benefit from increased surveillance, more aggressive rejection treatment, or augmented maintenance immunosuppression.

Post-Transplant Lymphoproliferative Disorder Presenting as a Gastrointestinal Fistulous Tract in a Heart Transplant Recipient: Case Report and Literature Review

We present a challenging case of Epstein-Barr virus-related isolated small bowel post-transplant lymphoproliferative disorder (PTLD) in a pediatric heart transplant recipient presenting as recurrent gastrointestinal (GI) bleeding and subsequently a GI fistulous tract with associated intra-abdominal abscess. Diagnosis was not confirmed until exploratory laparoscopy was performed, with excision of the fistulous tract revealing evidence of PTLD on pathology. Early diagnosis of GI-PTLD remains a challenge, especially if isolated in the small intestine. Diagnosis may rely on positron emission tomography/ computed tomography scan (PET/CT) or invasive intervention to obtain appropriate tissue samples for pathology diagnosis.

Outcome of cardiac implantable electronic devices in pediatric heart transplant recipients

Outcome of cardiac implantable electronic devices in pediatric heart transplant recipients

Acute Kidney Injury Requiring Dialysis After Pediatric Heart Transplant.

Acute kidney injury (AKI) is a common complication of pediatric heart transplant, with a subset of patients developing severe AKI requiring dialysis (AKI-D). We aimed to identify the epidemiology, risk factors, and outcomes of postoperative AKI-D in pediatric heart transplant recipients. We retrospectively identified all pediatric first-time, single-organ heart transplants at our institution from 2014 to 2022. Postoperative AKI was defined as AKI within 2 weeks of transplant. Unadjusted and adjusted logistic regression were used to identify characteristics associated with AKI-D, and unadjusted time-to-event analyses were used to determine the association between AKI-D and survival free of kidney failure. Among 177 patients included, 116 (66%) developed postoperative AKI of any stage, including 13 (7%) who developed AKI-D with median time from transplant to dialysis initiation of 6 days (IQR 3-13). In adjusted models, increased cardiopulmonary bypass time (OR 1.19, 95% CI 1.04-1.37, per 15 min increase in bypass time) and higher weight at transplant were associated with higher odds of AKI-D, whereas patient demographics and pretransplant kidney function were not associated with AKI-D. AKI-D was associated with greater mortality during initial hospitalization (46% vs. 1%, p < 0.001) and a lower rate of survival free of kidney failure. The incidence of AKI-D after pediatric heart transplant was 7%, with extended cardiopulmonary bypass time associated with postoperative AKI-D even in adjusted models. Further research is needed to improve the prediction and management of AKI-D in this population.

Changes in waiting time, need for mechanical circulatory support and outcomes in paediatric heart transplant recipients.

Heart transplantation is a well-established treatment for end-stage heart failure in paediatric patients, demonstrating excellent long-term outcomes. This retrospective study analyses 35years of data on 244 paediatric recipients (<18years) at a single institution from 1986 to 2022. The analysis explores changes in diagnoses, survival, waiting times and mechanical circulatory support (MCS) over three decades (1991-2000, 2001-2010 and 2011-2020). Survival outcomes significantly improved over the study period, with 1-year survival rates increasing from 79.3% (1991-2000) to 92.3% (2011-2020, P=0.041). The median overall survival was 18.0years, and median conditional survival to 1year post-transplant was 20.9years. Survival differences were noted among age groups, with infants under 1year of age experiencing higher early mortality, and adolescents (aged 11-17years) facing increased long-term risks, possibly linked to adult donor characteristics. Waiting times for heart transplantation increased, especially for younger age groups (0-5 and 6-10years), reflecting the growing demand for donor organs. The use of MCS, including ventricular assist devices (VAD), surged, with 67% of recipients in the most recent decade receiving pre-transplant VAD support. Importantly, despite prolonged waiting times and increased VAD use, overall survival continued to be favourable. Early and long-term results after paediatric heart transplantation have been continuously improving over the past decades. Despite an increased demand for donor organs and the growing reliance on VAD as bridge to transplantation, post-transplantation survival is not compromised.

SARS-CoV-2 Vaccination Rates and Uptake of Tixagevimab-Cilgavimab Among a Cohort of Pediatric Solid Organ Transplant Recipients.

There is a lack of data regarding SARS-CoV-2 vaccination rates and tixagevimab-cilgavimab (TC) uptake among pediatric solid organ transplant recipients. The purpose of our study was to assess these rates. We reviewed vaccination records of pediatric recipients of heart, kidney, and liver transplants at Mayo Clinic, Rochester, MN, who received a transplant between January 2011 and December 2021. All SARS-CoV-2 vaccines and doses of TC received on or before September 1, 2022, the date of approval of the bivalent SARS-CoV2 vaccine, were included. We also assessed whether patients had been seen by an infectious diseases physician (ID) in the preceding 6 months. Our study included 110 patients: 47 kidney, 36 heart, and 27 liver transplant recipients. All vaccine doses recorded were monovalent SARS-CoV-2 vaccines. Sixty-eight (61.8%) patients received at least one vaccine. This varied by age group, with f of≥12 years olds, 40.9% of 5-11 year olds and 14.3% of under 5 year olds (p=0.001). Seven patients (6.4%) were up-to-date (UTD) for age. There was no difference in UTD status by organ type (p=0.335). Patients who saw ID were significantly more likely to be UTD (13.2% versus 2.8%; p=0.047). Among those eligible, 14 (18.2%) received TC, with rates not different based on transplanted organ type (p=0.158) or whether they saw ID (p=0.273). Despite the availability of vaccines, nearly 40% of pediatric solid organ transplant recipients remained unvaccinated against SARS-CoV-2 at time of the bivalent vaccine release. Less than a fifth of eligible patients received TC. Strategies to increase uptake of SARS-CoV-2 vaccines as well as adjunctive agents among this vulnerable group should be further explored.

Longitudinal Cognitive and Motor Delay after Pediatric Heart Transplantation and Associated Survival

We investigated factors associated with the longitudinal presence of neurodevelopmental delays in pediatric heart transplant (HTx) recipients. The United Network for Organ Sharing Registry was queried for patients <18 years who received a first-time isolated HTx between March 2008 and December 2022. Two patient cohorts were developed, those with/without: 1) definitive motor delay (MD) and 2) definitive cognitive delay (CD). A total of 3847(n=3267[no MD], n=580[definitive MD]) and 3446(n=2689[no CD], n=757[definitive CD]) patients were included across MD and CD cohorts, respectively. Cohorts shared 3189 patients. Compared to intracohort non-delayed patients, definitive MD and CD cohorts each independently had higher rates of congenital heart disease, ventilator support at transplant, and stroke prior to discharge (p<0.001 for all). Patients with a definitive delay at follow-up had worse longitudinal survival, with hazard ratios of 2.82(95% CI: 2.32-3.44, p<0.001) and 1.67(95% CI: 1.32-2.05, p<0.001) for MD and CD cohorts, respectively. Both stroke prior to discharge and symptomatic cerebrovascular disease at listing were predictors of CD and MD at follow-up. Definitive MD and CD cohorts each independently had higher rates of stroke prior to discharge (MD cohort, 57/580=9.8% versus 48/3267=1.5%; CD cohort, 53/757=7.0% versus 42/2689=1.6%, p<0.001 for both), and symptomatic cerebrovascular disease at listing was a predictor of CD and MD at follow-up (CD cohort, OR=4.16[95% CI: 2.62-6.58]; MD cohort, OR=3.30[95% CI: 2.06-5.22]. Patients with MD and/or CD following HTx share several characteristics (including increased stroke prior to discharge) and have decreased longitudinal survival compared to their non-delayed counterparts.

Mycophenolate Metabolite Trough Concentrations Are Not Well Correlated With Dosing or Adverse Outcomes in Pediatric Heart Transplant Recipients.

Although mycophenolate metabolite trough concentrations in serum are routinely obtained for pediatric orthotopic heart transplant (OHT) recipients, limited data support this practice. We sought to investigate the relationship of mycophenolic acid (MPA) and MPA glucuronide (MPAG) serum concentrations to dosing and adverse outcomes among pediatric OHT patients. This retrospective study included OHT recipients ages 0 to 21 years who received mycophenolate mofetil (MMF) with MPA and MPAG serum trough concentration monitoring. The primary outcome was the relationship between MPA and MPAG serum concentrations and dosing. Secondary outcomes included the relationship of adverse outcomes to either MPA and MPAG concentrations or dosing. A total of 98 patients with 1287 MPA and MPAG trough serum concentrations (each) were included. The median initial MMF dose was 40.3 mg/kg/day (IQR, 35.12-51.83) and 1164.4 mg/m2/day (IQR, 1080.77-1206.86). There was no correlation between either MPA or MPAG serum concentrations and mg/kg dosing, or mg/m2 dosing. When comparing the adverse effect of bone marrow suppression with no adverse effect, the median MPA serum trough concentration was 2 (IQR, 1.1-3.2) versus 1.6 (IQR, 0.8-2.5), p = 0.003. When comparing the adverse effect of infection with no adverse effect, median MPA serum trough concentration was 0.9 (IQR, 0.49-1.7) versus 1.6 (IQR, 0.8-2.5), p < 0.001. The clinical utility of this finding is of uncertain benefit. There was no association between MPAG serum concentrations and any adverse outcome (p = 0.053). We did not identify a correlation between mycophenolate serum trough concentrations and either adverse outcomes or dosing. Based on these results, we discourage routine monitoring of mycophenolate trough concentrations.

Kidney transplant outcomes in children with simultaneous versus sequential heart-kidney transplants.

Heart transplant recipients frequently require kidney transplantation for concomitant advanced chronic kidney disease. Data on simultaneous (heart and kidney transplants performed simultaneously) versus sequential (heart transplant performed before kidney) heart-kidney transplants in children are limited. Herein, we compare kidney transplant outcomes between the two groups. We used the Scientific Registry of Transplant Recipients to identify all pediatric (age <21 years) heart transplant recipients who also received a kidney transplant within 10 years of the heart transplant. We divided the study cohort into simultaneous heart-kidney and sequential heart-kidney recipients. We compared patient and death-censored graft survival using the Cox regression, adjusting for age at kidney transplant, sex, race, pre-transplant dialysis, donor type, and prior kidney transplant. We evaluated delayed graft function (defined as dialysis within the first week posttransplant) using logistic regression. Our analysis cohort included 165 recipients (86 simultaneous and 79 sequential). The incidence of delayed graft function was higher in simultaneous recipients (22.4 vs. 7.7%, p=0.017), but the difference lost statistical significance on multivariable analysis. We found no difference in patient survival (aHR 0.97; 95% CI 0.39, 2.41; p=0.95) after kidney transplant but higher death-censored kidney graft survival in sequential heart-kidney recipients compared with simultaneous heart-kidney recipients (aHR 4.26; 95% CI 1.21, 14.9; p=0.02). Sequential heart-kidney transplants are associated with higher death-censored kidney allograft survival in children compared with simultaneous heart-kidney transplants.