Pediatric Heart Transplant Recipients Research Articles

Racial and socioeconomic disparities in pediatric heart transplant outcomes in the era of anti-thymocyte globulin induction.

Black race is associated with worse outcomes across solid organ transplantation. Augmenting immunosuppression through antithymocyte globulin (ATG) induction may mitigate organ rejection and graft loss. We investigated whether racial and socioeconomic outcome disparities persist in children receiving ATG induction. Using the Pediatric Heart Transplant Society registry, we compared outcomes in Black and White children who underwent heart transplant with ATG induction between 2000 and 2020. The primary outcomes of treated rejection, rejection with hemodynamic compromise (HC), and graft loss (death or re-transplant). We explored the association of these outcomes with race and socioeconomic disparity, assessed using a neighborhood deprivation index [NDI] score at 1-year post-transplant (high NDI score implies more socioeconomic disadvantage). The study cohort included 1,719 ATG-induced pediatric heart transplant recipients (22% Black, 78% White). There was no difference in first year treated rejection (Black 24.5%, White 28.1%, p=0.2). During 10 year follow up, the risk of treated rejection was similar; however, Black recipients were at higher risk of HC rejection (p=0.009) and graft loss (p=0.02). Black recipients had a higher mean NDI score (p < 0.001). Graft loss conditional on 1-year survival was associated with high NDI score in both White and Black recipients (p < 0.0001). In a multivariable Cox model, both high NDI score (HR 1.97, 95% CI 1.23-3.17) and Black race (HR 2.22, 95% CI 1.40-3.53) were associated with graft loss. Black race and socioeconomic disadvantage remain associated with late HC rejection and graft loss in children with ATG induction. These disparities represent important opportunities to improve long term transplant outcomes.

Immune cell function assay and T lymphocyte counts lack association with rejection or infection in pediatric heart transplant recipients.

Immune cell function assay (ICFA) and CD3 lymphocyte counts have been considered to be useful in discerning the overall intensity of immunosuppression in pediatric orthotopic heart transplant (OHT) recipients. The aim of this retrospective analysis was to evaluate trends of ICFA and CD3 lymphocyte counts and their association with adverse outcomes post-OHT. A total of 381 ICFA and 493 CD3 laboratory values obtained in 78 patients within six months post-OHT were analyzed. There were 14 patients treated for biopsy-proven acute rejection, four of whom had ISHLT grade 2R/3A rejection. In patients with rejection versus those without, CD3 and ICFA values were 122 (IQR 74.5-308) cells/mm2 and 224.5 (IQR 132-343.5) ng/ml compared to 231.8 (IQR 68-421) cells/m2 and 191 (IQR 81.5-333) ng/mL (p=NS for both). Twenty-six patients had at least one detectable cytomegalovirus or Epstein-Barr virus DNAemia within the study timeframe. In patients with viremia versus those without, CD3 and ICFA values were 278.5 (IQR 68-552) cells/mm2 and 130 (IQR 48-284) ng/ml compared to 195 (IQR 74.5-402.5) cells/mm2 and 212 (IQR 89-342) ng/ml (p=NS for both). No association was found between these immune markers and adverse outcomes. In the absence of larger pediatric studies justifying the role of these tests in identifying elevated risk profiles post OHT, we do not recommend their routine use.

Basiliximab as maintenance immunosuppression in heart transplant recipients: A single pediatric center experience.

Pediatric heart transplant recipients are at risk for complications from prolonged exposure to immunosuppressive drugs, pharmacokinetic challenges in maintaining consistent immunosuppression, and medication non-adherence. Basiliximab (BAS), an interleukin-2 receptor antagonist, is used for induction therapy across many pediatric heart transplant centers, but use as maintenance immunosuppression has not been well described. This was a retrospective, single pediatric center cohort study of heart transplant recipients who received BAS for maintenance immunosuppression (defined as >2 monthly doses) from January 1, 2011, to December 31, 2021. Ten patients met study criteria with a median age of 17.5 (5-22)years and median 9.6 (1.2-18.9)years since transplant at time of BAS initiation. The primary indications for BAS use were recurrent rejection (n=4), fluctuating immunosuppression levels (n=3), and renal dysfunction (n=3). A median of 5.5 (3-32) monthly BAS doses were received. Three patients had a rejection event while on BAS. Calcineurin inhibitor exposure was reduced in 70% of patients. Three of the 10 patients were alive at last follow-up. There was one documented infection during BAS use, and no hypersensitivity reactions. Monthly BAS infusions were well tolerated and allowed for reduced calcineurin inhibitor exposure in most patients. Mortality commonly occurred despite BAS use, potentially reflecting the acuity of this patient cohort. BAS can be considered for maintenance immunosuppression in pediatric patients with fluctuating immunosuppressive levels and/or renal dysfunction. More studies are needed to determine long-term outcomes and explore expanded use of BAS in the pediatric heart transplant population.

Hemorrhagic Pancreatitis in Pediatric Heart Transplant Recipients

Abstract Introduction/Objective Acute pancreatitis is a known side effect of tacrolimus in solid organ transplant recipients, but can be difficult to detect as symptoms may be vague and poorly localized, or overlap with the underlying condition. This phenomenon has most frequently been described in adult kidney transplant recipients. We present two autopsy cases in which pediatric patients with history of orthotopic heart transplantation both developed hemorrhagic pancreatitis shortly following operative procedures. Both had received immunosuppressants including tacrolimus during therapy. Although the etiology of pancreatitis in these medically complex cases is likely multifactorial, tacrolimus may be an important contributor. Methods/Case Report Case 1: A 6-year-old male with hypoplastic left heart syndrome was admitted for two years for medical management while awaiting transplant. Prior to and following transplantation he received immunosuppressants including tacrolimus to reduce risk of transplant rejection. Two weeks post-operatively, he developed abdominal pain and elevated pancreatic enzymes, leading to a diagnosis of pancreatitis. Imaging revealed hemorrhage. Tacrolimus was suspected to have caused this, and was discontinued. Despite medical management and multiple attempts to embolize vessels around the pancreas, the decedent remained unstable and ultimately went into hypotensive bradycardic cardiac arrest. Autopsy revealed a large hemorrhagic cavity confluent with a necrotic pancreas, as well as coagulum adherent to bowel loops throughout the abdomen. Case 2: A 13-year-old male status post two orthotopic heart transplants presented for a dental procedure. Following this, he developed an anaphylactic-type reaction to medication, with hives and bradycardia followed by cardiac arrest. He was resuscitated, however, his cardiac function steadily declined throughout the remainder of his stay. Heart biopsy revealed no evidence of cell-mediated transplant rejection. Pancreatic enzymes were mildly elevated, and abdominal imaging was unremarkable. His tacrolimus levels were noted to be supratherapeutic, and this was discontinued. Shortly before passing, he developed severe abdominal pain with distension, nausea and vomiting. At autopsy, he was found to have nearly two liters of hemorrhage and clot within the peritoneum emanating from a necrotic and hemorrhagic pancreas. Results (if a Case Study enter NA) NA. Conclusion Close clinical monitoring of pancreatic function should be considered in solid organ transplant recipients receiving tacrolimus.

Impact of induction therapy on cytomegalovirus infection and post-transplant outcomes in pediatric heart transplant recipients receiving routine antiviral prophylaxis.

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

Abstract 14074: Unique Circulating microRNA Profile in Pediatric Heart Transplant Recipients

Introduction: MicroRNAs (miRs) are small noncoding RNAs capable of modulating the expression of many genes. Hypothesis: Our hypothesis was that circulating miRs would be a biomarker of acute cellular rejection (ACR) in pediatric heart transplant recipients (PHTR). Methods: An array for 381 miRs was performed using serum from 52 PHTR and 21 healthy pediatric controls (HC). ACR was defined as ISHLT biopsy score ≥2R. Patients with antibody mediated rejection were excluded. RNA was extracted using the miRNeasy Mini Kit (Qiagen), and arrays were performed using the TaqMan Open Array miR panel (Thermo Fisher Scientific). Statistical analysis included Random Forest (RF) with area under the receiver operator curve (AUC) based on the top 3 differentiating miRs by RF, and Wilcoxon rank-sum t-test (significant q-value &lt; 0.05). Results: Of the 52 PHTR, median age 8.5 years, 44% female, race/ethnicity white in 83%, 12% African American, 13% Asian/other, and 13% Hispanic; 22 PHTR had ACR at time of serum collection. There were 21 HC, median age 5.6 years, 38% female, race/ethnicity white in 76%, 24% Asian/other, and 19% Hispanic. There were 66 miRs significantly different between HC and all PHTR (AUC of 0.91). For HC vs PHTR without ACR there were 50 differential miRs (AUC of 0.94), and for HC vs PHTR with ACR there were 51 differential miRs (AUC 0.96). Table 1 demonstrates miRs that are differentially expressed compared to HC based on the presence or absence of ACR. Circulating miRs were not different between PHTR with (n=22) and without ACR (n=30). Conclusions: The circulating miR profile of PHTR is unique compared to HC, suggesting a strong influence of the transplant mileu on miR expression. There were 17 miRs with differential expression compared to HC based on the presence or absence of ACR. These results support future investigations in larger populations to determine if circulating miRs could serve as biomarkers of ACR in PHTR, and whether these miRs contribute to the pathophysiology of ACR.

Abstract 13193: Prevalence of Late Gadolinium Enhancement Following Pediatric Heart Transplantation Increases With Time Since Transplantation

Introduction: Chronic graft failure in pediatric heart transplant recipients (PHT) is associated with myocardial fibrosis on explanted specimens. Cardiac magnetic resonance imaging (CMR) is a validated, non-invasive method to detect myocardial fibrosis via the presence of late-gadolinium enhancement (LGE). In adult heart transplant recipients, LGE is associated with increased risk of hospitalization and death. We describe LGE on CMR among PHT and its associations with clinical and graft characteristics. Methods: We performed a retrospective chart review of all PHT who underwent CMR over a 6-year period at a single center (81 CMR studies, 59 unique patients). Two independent reviewers assessed the presence and distribution of LGE using the AHA 17-segment model. Clinical history and CMR-derived volumetry/ejection fraction were obtained; differences between LGE+ and LGE- PHT were evaluated. Results: Mean age at CMR was 14.8±4.6y; mean time since transplant was 7.3±5.0y. CMR indication was routine surveillance (without active rejection or history of cardiac allograft vasculopathy) in 63% (51/81) of studies. LGE was present in 36% (29/81). LGE patterns included: posterior hinge-point 27% (22/81), lateral wall 15% (12/81), and extensive, involving &gt;4 AHA segments, 7% (6/81) (Figure). Reviewing initial CMR per PHT (n=59), LGE+ patients were older (17 vs. 13y; p=0.001), with greater time since transplant (8.3 vs. 5.7y; p= 0.041). They demonstrated increased indexed LV end-systolic volume (35 vs. 29 ml/m2; p=0.011) and decreased LV ejection fraction (56.2 vs 60.6%; p=0.015). There were no significant differences in history of moderate/severe rejection or cardiac allograft vasculopathy. Conclusions: LV LGE was seen in about a third of PHT patients, more commonly in older patients with longer time since transplantation. Grafts with LGE show remodeling with lower LV ejection fraction. CMR-derived LGE may improve surveillance of chronic graft failure in PHT.

Impact of occurrence of cardiac arrest in the donor on long-term outcomes of pediatric heart transplantation.

The impact of cardiac arrest in the donor on long-term outcomes of pediatric heart transplantation has not been studied. The UNOS database was queried for primary pediatric heart transplantation (1999-2020). The cohort was divided into recipients who received a cardiac allograft from a donor who had a cardiac arrest (CA) versus a donor who did not (NCA). Univariable and multivariable analysis was done to compare recipient outcomes, followed by survival analysis using the Kaplan-Meier method. A total of 7300 patients underwent heart transplantation, of which 579 (7.9%) patients belonged to the CA group. The CA group was younger (median 3 vs. 5 years, p < .001), male (51% vs. 47%, p = .03), and smaller in weight (13 vs. 17 kg, p < .001) and height (101 vs. 109 cm, p < .001) than the NCA group. The groups were similar in recipient heart failure diagnosis and blood type. The CA donors were younger (3 vs. 6 years, p < .001) versus nonwhite (48% vs. 45%, p = .003) and died from drowning and asphyxiation compared to blunt injury and intracranial hemorrhage in the NCA group. The left-ventricular ejection fraction was similar between the groups. There was no difference in VAD and ECMO use before the transplant. The listing status, waitlist days, and allograft ischemic times were similar. Posttransplant morbidity such as stroke, dialysis, pacemaker implantation, and treated rejection were similar. Donor cardiac arrest (hazard ratio = 0.93, p = .5) was not an independent predictor of mortality on multivariable analysis. There was no survival difference even beyond 20 years of follow-up between the groups (p = .88). The occurrence of donor cardiac arrest has no impact on long-term survival in pediatric heart transplant recipients.

Abstract 10642: Hemodynamics One Year Post Pediatric Heart Transplant Are Associated With Pre-Transplant Variables and Correlate With Mortality

Background: Hemodynamics (HDS) after pediatric heart transplant (PHT) are understudied and may predict future outcomes. We sought to identify variables associated with normalization (NML) of HDS in the 1 st year post-HT and determine association with post-HT outcomes. Methods: HDS were collected from patients who underwent HT between 2013-2020 without a history of pre-HT mechanical support and with at least 3 catheterizations in the 1st year post-HT. NML was defined as 2 consecutive catheterizations with pulmonary vascular resistance index (PVRi) &lt; 3Wu/m 2 , cardiac index (CI) &gt; 2.5L/min/m 2 , and pulmonary wedge pressure (PCWP) &lt;12 mmHg. Freidman repeated measure was used to assess HDS over time and Cox regression associations with NML and long-term mortality. Results: Among 97 patients included, PCWP decreased, CI increased, and PVR remained stable over the 1 st year post-HT (Figure 1A). Only 50% (n=47) had NML by 1 year. Median time to NML was 181 days (IQR 355). Mean PCWP and PVR over the 1st year were higher in non-NML vs NML patients (13.3 vs. 10.8, p&lt;0.001; 2.2 vs. 1.8, p=0.024). On multivariate analysis, patients with retransplant (HR 2.91, p&lt;0.001) and normal HDS at the 1 st post-HT catheterization (HR 4.08, p&lt;0.001) were more likely to have NML, while those with pre-HT congenital heart disease (HR 0.46, p=0.043) were less likely (Table 1/Figure 1B). NML by 1 year-post-HT was not associated with long-term mortality (p=0.794), but lower CI (HR 0.10, p=0.048) and higher PCWP (HR 1.44, p=0.006) at 1 year post-HT were associated with mortality. Conclusion: Only half of PHT recipients have NML of HDS at 1-year post-HT. The CI and PCWP at 1 year post-HT correlated with long-term mortality.

Not all durations of preheart transplant mechanical ventilation portend inferior post-transplant survival in children.

Mechanical ventilation prior to pediatric heart transplantation predicts inferior post-transplant survival, but the impact of ventilation duration on survival is unclear. Data from the United Network for Organ Sharing and Pediatric Health Information System were used to identify pediatric (<18 years) heart transplant recipients from 2003 to 2020. Patients ventilated pretransplant were first compared to no ventilation, then ventilation durations were compared across quartiles of ventilation (≤1 week, 8 days-5 weeks, >5 weeks). At transplant, 11% (511/4506) of patients required ventilation. Ventilated patients were younger, had more congenital heart disease, more urgent listing-status, and greater rates of nephropathy, TPN-dependence, and inotrope and ECMO requirements (p< .001 for all). Post-transplant, previously ventilated patients experienced longer ventilation durations, ICU and hospital stays, and inferior survival (all p< .001). Hospital outcomes and survival worsened with longer pretransplant ventilation. One-year and overall survival were similar between the no-ventilation and ≤1 week groups (p=.703 & p=.433, respectively) but were significantly worse for ventilation durations >1 week (p < .001). On multivariable analysis, ventilation ≤1 week did not predict mortality (HR 0.98 [95% CI 0.85-1.43]), whereas ventilation >1 week did (HR: 1.18 [1.01-1.39]). Longer pretransplant ventilation portends worse outcomes, although only ventilation >1 week predicts mortality. These findings can inform pretransplant prognostication.

Attitudes & practices surrounding pregnancy post heart transplant among pediatric providers.

Many pediatric heart transplant (HT) recipients reach adulthood and may be interested in family planning; there is little data regarding safety of pregnancy post HT and clinicians' opinions differ. Pediatric HT clinicians are instrumental in early counseling. Thus, a better understanding of pediatric HT clinicians' practices regarding family planning and how well aligned these practices are with adult transplant centers is essential. We conducted a confidential, web-based survey of pediatric HT clinicians in fall 2021. We summarized and compared answers using Fisher's exact test. The survey was sent to 53 United States-based HT directors and to the International Society for Heart and Lung Transplantation and Pediatric Heart Transplant Society list serves. There were 69 respondents. The majority (77%) of respondents felt pregnancy was feasible in selected or all female HT recipients. Ten respondents reported that their institution had an established policy regarding pregnancy post HT. A majority (77%) of HT clinicians would either use a shared care model or recommend transition to their adult institution if pregnancy occurred, though 74% of respondents were either unaware of their corresponding adult institution's policy (62%) or had a counterpart adult program with a policy against pregnancy post HT (12%). While many clinicians feel pregnancy is feasible in pediatric HT recipients, there remains significant practice variation. Few pediatric programs have a policy regarding pregnancy post HT. Future efforts to provide consistent messaging between adult and pediatric HT programs regarding the feasibility and care of post HT pregnancy are warranted.

Virtual cardiac fitness training in pediatric heart transplant patients: A pilot study.

Cardiac fitness training in pediatric heart transplant recipients can improve functional capacity. Widespread implementation has been limited mostly due to logistical constraints, specifically related to travel. The aim of this study was to implement and assess a virtual cardiac fitness program for pediatric heart transplant patients. Participants were between the age of 10 and 20 years old. All subjects completed an initial 6MWT, strength/flexibility assessment, and QOL assessment with the PROMIS measurement. Participants then underwent a 16-week intervention with exercise sessions twice weekly for 30 min with a trained exercise physiologist over a virtual platform. At the end of the intervention period, participants repeated a 6MWT, strength/flexibility assessment, and PROMIS measurement. Throughout the study, patients wore a FitBit accelerometer to monitor daily activity levels. Thirteen individuals were enrolled. Mean age was 15.4 years (SD =3.4) with a mean post-transplant period of 9.7 years (SD = 4.3). Session attendance was 83%. Post-intervention measurements showed improvements in 6MWT (median, +21 m, p=.02), push-up repetitions (median, +5 rep, p=.0005), wall-sit duration (median, +10 s, p=.001), plank duration (median, +9 s, p=.03), sit-up repetitions (median, +7 rep, p=.002), and sit and reach distance (median, +5 cm, p=.04). PROMIS measurement showed significant improvements in self-reported fatigue (Δz-score, -7.7, p=.008) and sleep impairment (Δz-score, -5.9, p=.002). Average daily step count increased 1464 steps per day per patient (p=.008). We have demonstrated the successful implementation of a virtual cardiac fitness with excellent adherence and improvement in physical fitness and QOL metrics.

Female donor hearts can improve survival for male pediatric heart transplant recipients.

Both gender- and weight-matching between donor and recipient are thought to impact survival in pediatric heart transplantation, with clinical dogma holding that male donor hearts and "ideal" weight-matching yield superior survival. The composite impacts of gender and weight on post-transplant survival (PTS) are understudied. All pediatric (age <18) heart recipients between 1989 and 2021 with the complete recipient and donor gender and weight data were identified in the United Network for Organ Sharing database. Patients were grouped by recipient-donor gender (M & F) and donor-to-recipient weight ratio (DRWR; undersized [<0.8], ideal-sized [0.8-1.5], oversized [>1.5]). A total of 10697 patients were identified. Among male recipients, PTS was greatest with oversized DRWR from either male or female donors (median 22.4 and 20.6 years; p < .001 vs. others) and lowest for undersized DRWR from either male or female donors (median 13.4 and 13.2 years; p < .001 vs. others). The majority (64%) of male recipients received ideal-sized DRWR, among which female donor hearts yielded superior survival to males (median 18.9 vs. 17.4 years, p=.014). No differences in PTS existed for female recipients on the basis of gender-match, DRWR, and gender/DRWR together (all p > .1). When considered together, gender and DRWR pairings impact PTS in male-but not female-pediatric heart transplant recipients. For males receiving ideal-sized DRWR organs (most common pairing, >60%), male recipients achieve superior survival when female donor hearts are transplanted. These findings suggest that if weight is being used for size-matching, donor gender should also be considered, particularly for male recipients.

Pediatric Heart Transplant Waiting List Times in the US During the COVID-19 Pandemic

This cohort study investigates the association between the COVID-19 pandemic and waiting list times among pediatric heart transplant recipients in the US.

CARDIAC ALLOGRAFT VASCULOPATHY AND SURVIVAL IN PEDIATRIC HEART TRANSPLANT RECIPIENTS TRANSITIONED TO ADULT CARE

Cardiac allograft vasculopathy (CAV) is an important cause of mortality after pediatric heart transplantation (HT) but there is a paucity of data regarding its incidence and impact on survival in children once they reach adulthood. Differences in outcomes according to transplant era are also not well characterized. Our objectives were to describe the incidence of CAV overall and according to transplant era and to evaluate the impact of CAV on mortality in pediatric HT recipients transitioned to adult care.

Eplet matching in pediatric heart transplantation: The SickKids experience.

Epitope-based tissue matching may be superior to HLA antigen matching. We compared antigen to molecular-level HLA matching on outcomes following pediatric heart transplantation (HTx). This is a retrospective, single centre cohort study (2013-2020). HLA antigen and eplet mismatch analyses were performed in HTx patients <18 years old. Primary endpoint was graft loss; secondary endpoints were rejection and cardiac allograft vasculopathy (CAV). A multivariable Cox regression analysis was used to examine associations between eplet or antigen mismatching and outcomes. A logistic regression analysis was performed to examine associations between eplet or antigen mismatching and outcomes. Seventy-seven patients (40% males) were included, with a median age at HTx 4.3 years [range 0.05-18]. Median HLA class I and II eplet mismatches were 10 (1-22) and 11 (1-23). Median class I and II antigen mismatches were 5 (1-6) and 4 (0-6). 9 patients (11.7%) died [median time 4 months (range 0.1-46)]. Eight (10.4%) patients developed AMR [median time 22 days (IQR=168)]. Twenty-one patients (27.3%) had acute cellular rejection [median time 40 days (IQR=85.5)]. In univariate analysis, patients with HLA Class II DPB eplet mismatches above the median for this cohort had an increased risk of graft loss (OR 5.3 [95%CI: 1.03-27.5], p=0.039). HLA eplet mismatching was not associated with rejection; antigen mismatching was not associated with either graft loss or rejection. In multivariable analysis, patients with HLA Class II DPB eplet mismatches above the median had an increased risk of graft loss (HR 8.14 [95% CI: 1.26-49], p=0.02). HLA eplet mismatching was not associated with rejection; antigen mismatching was not associated with graft loss or rejection. A logistic regression analysis including 'number of HLA Class II DPB eplet mismatches' correctly predicted 95.8% of the outcomes. In our cohort of pediatric heart transplant recipients, the number of HLA Class II DPB eplet mismatches was associated with graft loss. Molecular-level HLA matching is an emerging tool for graft loss risk stratification, but further study is required.

Enhancing a Rehabilitation Pathway for Pediatric Heart Transplant Recipients: An Improvement Project to Increase Adherence, Satisfaction, and Outcomes

Aims To refine a cardiac rehabilitation pathway for pediatric heart transplant recipients; assess clinician knowledge and adherence to the program; and evaluate patient outcomes. Methods The center has utilized a rehabilitation pathway for pediatric heart transplant recipients. Challenges in practice include access to centers, lack of data tracing, and adherence to the pathway. The quality initiative focused on program refinements: implementation of text templates to improve data collection, collection of the Pediatric Cardiac Quality of Life Inventory (PCQLI), Functional Independence Measure (WeeFIM) and Child Occupational Self-Assessment (COSA), development of an outreach program, and creation of an educational program for therapists to increase content knowledge and improve clinician satisfaction. Results In the evaluation of rehabilitation follow-up post-transplant, there was no statistical significance between the pre- and post-implementation groups. After the implementation of the refined pathway, there was an increase in the completion of the six-minute walk test post-transplant (p = 0.048). Clinicians’ responses post educational session noted familiarity with the pathway (88%), documentation (78.8%), and outcome measures (97%). Results of outcomes noted improvement in six-minute walk distances and a decrease in the rate of perceived exertion post-transplant. To ensure future pathway adherence, clinical support should be implemented, and key players identified to maintain sustainability.

Association of Donors With US Public Health Service Risk Criteria and Outcomes After Adult vs Pediatric Cardiac Transplant

The United Network for Organ Sharing (UNOS) evaluates donor risk for acute transmission of HIV, hepatitis B, or hepatitis C based on US Public Health Services (PHS)-specific criteria. However, recent data regarding use and outcomes of those donors with PHS risk criteria among pediatric and adult heart transplant recipients are lacking. To compare use and outcomes of graft from donors with PHS risk criteria vs those with a standard-risk donor (SRD) in children vs adults in a contemporary cohort. This cohort was a nationwide analysis of heart transplants in the US that used data from the UNOS database. Participants were children (<18 years old) and adults (≥18 years old) who received a heart transplant from January 1, 2010, to December 31, 2021. UNOS-defined donor risk status. Trend analysis compared changes in PHS risk criteria use among children and adults. Patient survival was analyzed using Kaplan-Meier curves with log rank and Cox proportional hazards to compare PHS risk-criteria outcomes vs SRD-criteria outcomes in children and adult heart transplant recipients. Additional analysis was performed among adults who received a PHS-risk criteria graft that was previously declined for pediatric recipients. Of 5115 pediatric transplant recipients (donor without PHS risk median [IQR] age, 5 [0-13] years and donor with PHS risk median [IQR] age, 8 [0-14] years) and 30 289 adult heart transplant recipients (donor without PHS risk median [IQR] age, 56 [46-63] years and donor with PHS risk median [IQR] age, 57 [47-63] years), PHS risk criteria comprised 8% in children vs 25% in adults. PHS criteria are being increasingly used over the past decade with the proportion of recipients transplanted with PHS risk-criteria donors being approximately 3 times greater among adult recipients than children recipients. Pediatric recipients of a PHS risk-criteria donor had greater pretransplant ventilatory support, whereas adult recipients of a PHS risk-criteria donor had greater pretransplant extracorporeal membrane oxygenation use. Patient survival was similar between pediatric recipients of PHS risk-criteria grafts vs SRD-criteria grafts and slightly higher among adult recipients of PHS risk-criteria grafts vs SRD-criteria grafts. The 1778 adult recipients who received a PHS criteria-risk donor that was previously declined for pediatric recipients had similar patient survival recipients compared with SRD-criteria donors (HR, 0.92; 95% CI, 0.81-1.03; P = .18). In the current era, a 3-fold greater proportion of adult recipients receive a PHS risk-criteria graft compared with children despite similar posttransplant patient survival. The ongoing organ donor shortage underscores the need for consideration of PHS risk criteria where these donors remain underused.

Exercise capacity in pediatric heart transplant recipient

Most pediatric heart transplantation (HTx) recipients will reach adulthood. Exercise capacity measurement is essential during follow-up; however, there are few data available in the literature. Our study presents a monocentric, descriptive analysis of exercise capacity after pediatric HTx. Results of cardiopulmonary exercise testing (CPET) using cycle ergometry, performed between January and October 2021 as routine follow-up, were collected for exercise capacity analyses. VO2peak ≤ 80% predicted defined abnormal exercise capacity. Logistic regression and Pearson correlation were used to determine associated factors. Fifteen patients were included, and the age at CPET was 13.2 ± 3.2 years. One third of patients with maximal testing had low exercise capacity. The peripheral musculoskeletal function was the major limiting exercise factor. Resting HR was high for age at 108 ± 14.19 bpm. The mean percent predicted VO2peak (ppVO2peak) was 80.2 ± 20.8%. A linear correlation between age at transplant and ppVO2peak ( r = −0.53, P -value = 0.021) was found independent of time since transplant. Concurrent chronic diseases were a risk factor for abnormal VO2peak (odds-ratio = 17.5). Heart transplant recipients (HTR) in our study appeared to have better outcomes than that previously reported. The exercise capacity of pediatric HTR is above the lower limit. Patients younger at transplant have higher post-HTx exercise capacity, possibly due to the growth plasticity promoting nerve regeneration. Improved patient management or cardiac reinnervation may contribute to the better CPET results found in our study. Longitudinal or comparative studies with a larger sample size are required in the future.

CYP3A4/5 genotypes and age codetermine tacrolimus concentration and dosage in pediatric heart transplant recipients

Tacrolimus (TAC) is the cornerstone of immunosuppressive therapy for pediatric heart transplantation (HTx) recipients. However, little information is known on the interaction of developmental and genetic variants on TAC disposition in this population, which makes TAC dose optimization more difficult. The aim of study was to investigate the relationship between genotypes and age on TAC concentrations and dosage during the early post-operation period in pediatric HTx recipients. Sixty-six pediatric HTx recipients were enrolled and divided into three groups according to the age (<6, ≥6-≤12, 12–18 years old). CYP3A4/5, POR and ABCB1 polymorphisms were genotyped. The associations between genotypes and age on TAC dose-adjusted trough concentrations (C0/D), dose requirement as well as acute kidney injury (AKI) were evaluated. CYP3A5*3 and CYP3A4*1G were significantly correlated with TAC C0/D and dose requirement in the pediatric recipients ≥ 6 years. The C0/D in children aged ≥ 6-≤12 years and 12–18 years is 2.8 and 4.2 fold of these < 6 years old, respectively. TAC dose requirements in children aged < 6 years were 2.4 times and 3.5 times of these aged ≥ 6-≤12 years and 12–18 years, respectively. Among the same CYP3A5*3 or CYP3A4*1G genotypes, age was positively increased with TAC C0/D and negatively correlated with targeted dose. No genetic variants were found to be associated with AKI during the early post-operation period. CYP3A4/5 genotypes and age should be taken into consideration to TAC dosage in pediatric HTx recipients.