Pediatric HTx Recipients Research Articles

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.

Dapagliflozin Use in Children with Advanced Heart Failure Undergoing Heart Transplantation: A Matched Case-Control Study.

Dapagliflozin has been associated with euglycemic ketoacidosis in adults with diabetes contributing to poor outcomes when continued prior to surgery. It is unknown if preoperative use of dapagliflozin may lead to adverse events (AE) in nondiabetic children with advanced heart failure (HF) undergoing heart transplantation (HTx). We performed a single-center, matched case-control analysis of nondiabetic primary pediatric HTx recipients < 21years-old who underwent HTx and followed through postoperative day (POD) 3. Cases who received dapagliflozin leading up to HTx (n = 22) were matched by age and cardiac diagnosis to two historical controls who did not receive dapagliflozin (n = 44). Median age at HTx was 13.8years (range 0.36-20.7) and 48% were female. Cardiac diagnoses included cardiomyopathy (45%), Fontan failure (41%), and single ventricle status post stage I palliation (14%). Cases received median dapagliflozin dose of 0.17mg/kg once daily; therapy was stopped one day prior to HTx. There were no significant differences in blood glucose nadirs, arterial blood gas indices including nadirs of pH, bicarbonate, or peaks of arterial blood lactic acid POD0-3. Vasopressor, inotrope, and insulin infusion usage were not different. No patients were treated for severe hypoglycemia, euglycemic ketoacidosis, or urinary tract infections. There were no deaths. Length of stay in ICU and time from HTx to hospital discharge did not differ between cohorts. Use of dapagliflozin in children with advanced HF until HTx is not associated with AE in the immediate postoperative period nor increased length of hospitalization post-HTx. Potential cardiovascular benefits of dapagliflozin in patients awaiting HTx should be prioritized.

Prevalence of iron deficiency and anemia in pediatric heart transplant recipients.

The prevalence of iron deficiency and anemia in the setting of modern-day maintenance immunosuppression in pediatric heart transplant (HTx) recipients is unclear. The primary aim was to determine the prevalence of iron deficiency (serum ferritin<30ng/mL±transferrin saturation<20%) and anemia per World Health Organization diagnostic criteria and associated risk factors. Single-center, cross-sectional analysis of 200 consecutive pediatric HTx recipients(<21 years old) from 2005 to 2021. Data were collected at 1-year post-HTx at the time of annual protocol biopsy. Median age at transplant was 3 years (IQR.5-12.2). The median ferritin level was 32ng/mL with 46% having ferritin<30ng/mL. Median transferrin saturation (TSAT) was 22% with 47% having TSAT<20%. Median hemoglobin was 11g/dL with 54% having anemia. Multivariable analysis revealed lower absolute lymphocyte count, TSAT<20%, and estimated glomerular filtration rate<75mL/min/1.73m2 were independently associated with anemia. Ferritin<30ng/mL in isolation was not associated with anemia. Ferritin<30ng/mL may aid in detecting absolute iron deficiency while TSAT<20% may be useful in identifying patients with functional iron deficiency±anemia in pediatric HTx recipients. Iron deficiency and anemia are highly prevalent in pediatric HTx recipients. Future studies are needed to assess the impact of iron deficiency, whether with or without anemia, on clinical outcomes in pediatric HTx recipients.

Effects of WuZhi preparations on tacrolimus in pediatric and adult patients carrying the CYP3A5*1 allele of heart transplant during the early period after transplantation.

Wuzhi preparations (WZP) are commonly administrated with tacrolimus (TAC) in China to improve the liver function and increase the exposure of TAC. This study aims to investigate the effects of WZP on TAC in pediatric heart transplantation (HTx) patients carrying the CYP3A5*1 allele during the early period after transplantation and also make a comparison with these effects in adult recipients. A total of 81 recipients with CYP3A5*1 allele were included and divided into the pediatric group (n=29) and adult group (n=52). The changes in TAC dose-corrected trough blood concentrations (C0 /D), dose requirement as well as intra-patient variability(IPV) of C0 /D after co-therapy with WZP were evaluated. The TAC C0 /D was significantly increased 1.7 and 1.8 times after co-administration of WZP in the pediatric and adult groups, respectively. We further analyzed the pediatric patients, found that no statistical difference was observed in TAC C0 /D before and after co-therapy with WZP in children <6years old. The changes of C0 /D increased with the dose of the active ingredient (Schisantherin A) in adult patients, but not in pediatric patients. TAC IPV was reduced by 10.5% in pediatric patients and 4.8% in adult patients when co-administrated with WZP. Furthermore, after taking WZP, the AST and TB were dramatically lowered in pediatric recipients. Our study is the first attempt to demonstrate the effects of WZP on TAC in pediatric HTx recipients. By comparing these effects to those observed in adult recipients, valuable insights can be gained regarding the efficacy and potential benefits of WZP in the pediatric population.

Mycophenolic acid therapeutic drug monitoring using area under the curve in pediatric heart transplant recipients.

Pharmacokinetics of mycophenolic acid (MPA) display substantial interpatient variability, with up to 10-fold difference of exposure in individual patients under a fixed-dose regimen. MPA trough level (C0) monitoring is common in clinical practice but has not proven sufficiently informative in predicting MPA exposure or patient outcomes, especially in children. No limited sampling strategies (LSSs) have been generated from pediatric heart transplant (HTx) recipients to estimate MPA AUC. Single-center, observational analysis of 135 de novo pediatric HTx recipients ≤21years old who underwent MPA AUC between 2011 and 2021. Median age was 4years (IQR .6-12.1). Median time from transplant to MPA AUC sampling was 15days (IQR 11-19). MMF doses (mg or mg/day) had low, negative Pearson correlation coefficients (r) while doses adjusted for weight or body surface area had low correlation with Trapezoidal MPA AUC0-24h (r=.3 and .383, respectively). MPA C0 had weak association (r=.451) with Trapezoidal MPA AUC0-24h . LSS with two pharmacokinetic sampling time points at 90 (C3 ) and 360 (C5 )min after MMF administration (estimated AUC0-24h =32.82+4.12×C3 +11.53×C5 ) showed strong correlation with Trapezoidal MPA AUC0-24h (r=.87). MMF at fixed or weight-adjusted doses, as well as MPA trough levels, correlate poorly with MPA AUC0-24h . We developed novel LSSs to estimate Trapezoidal MPA AUC from a large cohort of pediatric HTx recipients. Validation of our LSSs should be completed in a separate cohort of pediatric HTx recipients.

Assessment of the adverse effects of sirolimus versus everolimus in pediatric heart transplant recipients

Literature is limited comparing adverse effects (AEs) of the proliferation signal inhibitors (PSIs) sirolimus (SRL) and everolimus (EVL) in pediatric heart transplant (HTx) recipients. Single-center, observational cohort analysis assessing first use of SRL or EVL in pediatric HTx recipients <21 years of age with up to 2 years follow-up between 2009 and 2020. Eighty-seven patients were included, with 52 (59.8%) receiving EVL and 35 (40.2%) receiving SRL. Tacrolimus with PSI was the most common regimen. Intergroup comparison revealed lower baseline estimated glomerular filtration rate (eGFR) and greater increase in eGFR from baseline to 6 months and latest follow-up in SRL cohort compared to EVL cohort. There was greater increase in HDL cholesterol in SRL cohort compared to EVL cohort. Intragroup analysis revealed eGFR and HDL cholesterol increased significantly within SRL cohort, triglycerides and glycosylated hemoglobin increased in EVL cohort, and LDL cholesterol and total cholesterol increased in both cohorts (all p < .05). There were no differences in hematological indices or rates of aphthous ulcers, effusions, or infections between cohorts. Incidence of proteinuria was not significantly different among those screened within cohorts. Of those included in our analysis, one patient in SRL cohort (2.9%) and two in EVL cohort (3.8%) had PSI withdrawn due to AE. Low-dose PSIs in calcineurin inhibitor minimization regimens appear well-tolerated with low withdrawal rate secondary to AE in pediatric HTx recipients. While incidence of most AE was similar between PSI, our results suggest EVL may be associated with less favorable metabolic impact than SRL in this population.

Early aspirin use and the development of cardiac allograft vasculopathy in pediatric heart transplant recipients: A pediatric heart transplant society analysis.

Cardiac allograft vasculopathy (CAV) remains a leading cause of graft loss in pediatric heart transplant (HTx) recipients. Adult literature suggests that aspirin (ASA) use in the early post-HTx period may reduce the risk of CAV. This study aimed to determine the impact of early ASA use on the development of CAV in pediatric HTx recipients. All subjects <17 years of age at time of primary HTx who survived ≥3 years without evidence of CAV were identified for inclusion from the Pediatric Heart Transplant Society database (1996-2019). Early ASA use was defined as ASA started within the first 3 years post-HTx and was classified as continuous or intermittent. Frequency of ASA use was described across centers. Kaplan-Meier method assessed freedom from CAV and overall graft survival. Multiphase parametric hazard analyses and propensity score matched analysis were used to identify independent risk factors. 3,011 patients were included with 387 (13%) receiving continuous ASA, 676 (22%) receiving intermittent ASA, and 1,948 (65%) receiving no ASA. ASA use was highly variable across centers (0%-100%). At baseline patients receiving continuous ASA therapy demonstrated inferior graft survival (p < 0.001) and worse freedom from CAV (p=0.002), but with lower CAV grades (p=0.05). In multiphase parametric hazard modeling continuous ASA use was not independently associated with CAV, but remained associated with inferior graft survival. Propensity-matched sub-analysis between continuous and no ASA groups demonstrated no difference in freedom from CAV or overall graft loss. ASA use varies widely across pediatric HTx centers. Early ASA use did not reduce the risk of CAV or graft loss in pediatric heart transplant recipients.

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.

Prognostic Value of Exercise Stress Echocardiography in Pediatric Cardiac Transplant Recipients

Cardiac allograft vasculopathy (CAV) is a leading cause of long-term morbidity and mortality in pediatric heart transplant (HTx) recipients. Exercise stress echocardiography (ESE) has been shown to be useful in the detection of angiographically confirmed coronary artery disease in children. However, the prognostic utility of ESE for prediction of cardiac events in HTx survivors is unknown. We aim to assess whether an abnormal (positive) ESE is be associated with a higher risk of future cardiovascular (CV) outcomes in pediatric HTx recipients. We conducted a retrospective review of CV outcomes in a cohort of 95 pediatric HTx recipients who underwent 188 ESEs over a 10-year period. A composite endpoint for CV events including myocardial infarction, hospitalization for nonrejection heart failure, coronary revascularization, need for repeat transplantation, and death was used. Based on the interpretation of the ESE results, each ESE study was classified for this study as either positive (abnormal) or negative (normal) for ischemia. Results of the coronary angiograms performed near the time of ESE were also assessed and classified for this study as positive (abnormal) or negative (normal) for CAV according to standard HTx criteria for CAV. Fifty-one (27%) ESEs were positive for ischemia. There was a total of 35 CV events in 23 patients. A positive ESE was associated with increased risk of any CV event (hazard ratio=3.55; 95% CI, 1.52, 8.28), as well as an increased risk of CV death (hazard ratio=3.19; 95% CI, 1.23, 8.28). Freedom from composite CV outcome at 1, 2, and 3years following a positive ESE was 89.9% (95% CI=77.3%, 95.7%), 81.5% (95% CI=65.9%, 90.5%), and 63.2% (95% CI=41.9%, 78.5%), respectively. Freedom from composite CV outcome at 1, 2, and 3years following a negative ESE was 99.3% (94.8, 99.9), 98.4% (93.6, 99.6), and 97.0% (90.6, 99.1), respectively. No patient died within 1year of a negative ESE. In this largest study of ESE in pediatric HTx recipients, a positive or abnormal ESE is associated with increased future CV morbidity and mortality. Conversely, a negative ESE can help predict CV event-free survival. Even in the setting of a normal coronary angiogram, our pilot data show that an abnormal ESE may still be clinically important. Use of ESE in follow-up may improve risk stratification and management of pediatric HTx recipients.

Heart Transplantation in Children With Down Syndrome.

BackgroundChildren with Down syndrome (DS) have a high risk of cardiac disease that may prompt consideration for heart transplantation (HTx). However, transplantation in patients with DS is rarely reported. This project aimed to collect and describe waitlist and post– HTx outcomes in children with DS.Methods and ResultsThis is a retrospective case series of children with DS listed for HTx. Pediatric HTx centers were identified by their participation in 2 international registries with centers reporting HTx in a patient with DS providing detailed demographic, medical, surgical, and posttransplant outcome data for analysis. A total of 26 patients with DS were listed for HTx from 1992 to 2020 (median age, 8.5 years; 46% male). High‐risk or failed repair of congenital heart disease was the most common indication for transplant (N=18, 69%). A total of 23 (88%) patients survived to transplant. All transplanted patients survived to hospital discharge with a median posttransplant length of stay of 22 days. At a median posttransplant follow‐up of 2.8 years, 20 (87%) patients were alive, 2 (9%) developed posttransplant lymphoproliferative disorder, and 8 (35%) were hospitalized for infection within the first year. Waitlist and posttransplant outcomes were similar in patients with and without DS (P=non‐significant for all).ConclusionsWaitlist and post‐HTx outcomes in children with DS selected for transplant listing are comparable to pediatric HTx recipients overall. Given acceptable outcomes, the presence of DS alone should not be considered an absolute contraindication to HTx.

Predicted Heart Mass is Not the Optimal Metric for Size Matching in Pediatric Heart Transplantation

<h3>Purpose</h3> The ratio of donor to recipient predicted heart mass (PHM) has been validated as an independent predictor of all-cause mortality and readmissions post cardiac transplantation (HTx) in adults. We assessed the ability of PHM to predict 1- and 3-year all-cause mortality in pediatric HTx recipients. <h3>Methods</h3> 4997 pediatric heart transplant recipients undergoing initial isolated orthotopic HTx between 1989 and 2017 were identified (9.5 ± 5.4 years; 56% male) from the United Network for Organ Sharing (UNOS) registry. Subjects were grouped into 5 equally sized groups by PHM ratio; severely undersized (.86 ± .08), undersized (1.03 ± .04), size-matched (1.16 ± .04), oversized (1.33 ± .06) and severely oversized (1.68 ± .22). <h3>Results</h3> 1417 patients (28%) received hearts undersized by PHM. PHM mismatch as defined by the five equally sized groups was not significantly associated with survival at 1 (P=0.109) or 3 years (P=0.108) in univariate Kaplan-Meier analysis. When defined as a continuous variable, PHM ratio was a significant predictor for 1-year mortality in univariate Cox proportional hazards analysis (HR, 1.50; 95% CI, 1.149-1.958; P=0.003) but not after adjustment for relevant covariates (HR, 1.273; 95% CI, 0.947-1.710; P=0.109). There was no increased risk of death at 3 years due to PHM mismatch after adjustment (HR, 1.076; 95% CI, 0.845-1.372; P=0.551). <h3>Conclusion</h3> These data are the first to show that donor-recipient predicted heart mass ratio mismatch is not associated with reduced 1-year or 3 year survival in pediatric heart transplant recipients. Future studies validating the echocardiography-based equation with pediatric patients may be warranted as the initial equation for calculating predicted heart mass was derived from an adult population.

Early report from the Pediatric Heart Transplant Society on COVID-19 infections in pediatric heart transplant candidates and recipients

BackgroundReports focused on adult heart transplant (HTx) recipients with COVID-19 suggest an increased risk of severe disease, however; it is unclear if this holds true for pediatric HTx patients, given the typically milder course of illness in children in general with COVID-19. We sought to rapidly implement a system for multi-center data collection on pediatric HTx candidates and recipients, with the aim of describing the patient population and infection related outcomes.MethodsThe Pediatric Heart Transplant Society (PHTS) is a multi-center collaboration that seeks to improve the outcomes of children who are listed and undergo HTx. The society consists of pediatric HTx centers in North America (n = 53), UK (n = 2), and Brazil (n = 1). In response to the pandemic, PHTS developed a web-based platform to collect COVID-19 specific data on pediatric HTx candidates and recipients. Non-PHTS centers were also invited to submit data. Data fields included pre-and post-HTx patient characteristics, presumed versus documented infection, need for hospitalization (including ICU and ventilator use), treatments administered, and 30-day outcome (resolution, death, sequelae, and or unresolved)ResultsData collection was initiated on 4/30/20. As of 03/15/21 there were 225 patients [19 pre-HTx and 206 post-HTx, median age 14 years (IQR 7, 18)] reported from 41 centers. Hospitalization occurred in 42% (n = 8) of the pre-HTx and 21% (n=43) of the post-HTx patients. Among the patients listed for HTx, 21% (n = 4) required ICU and 10.5% (n = 2) were mechanically ventilated. Among post-HTx patients, 7% (n = 14) required ICU and 1% (n = 3) were mechanically ventilated. At 30 days, the majority of patients had resolution of symptoms (94.7% pre-HTx, 95.6% post-HTx). One death was reported in a post-HTx patient prior to 30 days from onset of COVID-19 illness.ConclusionsThese data demonstrate the ability to rapidly adapt the PHTS data collection infrastructure in response to a novel infection and represent the first known multi-center report of characteristics and early outcomes for patients listed and following pediatric HTx with COVID-19. Hospitalization appears to be more common for both candidates and recipients due to COVID-19 than for the general pediatric population though stays were short and mortality minimal.

SARS-CoV-2 anti–spike antibodies after vaccination in pediatric heart transplantation: A first report

BackgroundBACKGROUND: There is a paucity of data regarding the antibody response to SARS-CoV-2 vaccination in children after solid organ transplant.METHODSWe retrospectively reviewed the SARS-CoV-2 Anti–Spike IgG antibodies measured following SARS-CoV-2 vaccination at our pediatric heart transplant (HTx) center.RESULTSAmong 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.CONCLUSIONOur 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.

Aspirin Use and the Development of Cardiac Allograft Vasculopathy in Pediatric Heart Transplant Recipients

<h3>Purpose</h3> Cardiac allograft vasculopathy (CAV) has limited treatment options and results in significant mortality. Data in adult heart transplant (HTx) recipients suggests that aspirin (ASA) use may reduce the risk of CAV. However, there are limited pediatric data on this topic. This study aimed to assess the use of ASA in pediatric HTx recipients and its association with CAV. <h3>Methods</h3> All patients in the Pediatric Heart Transplant Society database < 17 years of age who underwent primary HTx and had > 3 years of follow up were included. ASA use during the first 3 years post-transplant was defined as continuous, intermittent, or no ASA use. Time to CAV and graft loss was compared across groups using the Kaplan Meier method. A multivariable survival model was constructed for each outcome to assess the impact of early post-HTx ASA use. <h3>Results</h3> A total of 3,011 patients were identified for inclusion with 387 (13%) continuous, 676 (22%) intermittent, and 1948 (65%) with no ASA use. ASA use was more common in older patients (p<0.001). Patients receiving continuous ASA were less likely to receive induction therapy at HTx compared to other groups (p<0.001). ASA use was highly variable across centers, ranging from 0% to 100% (Figure 1a). Patients receiving continuous ASA therapy demonstrated worse freedom from CAV (p= 0.002) and inferior graft survival (p<0.001) (Figures 1b-c). In multivariable analyses, early ASA use was not associated with improvements in freedom from CAV or graft survival. <h3>Conclusion</h3> ASA use varies widely across pediatric HTx centers. Early ASA use did not reduce the risk of CAV or graft loss.

Abstract 16060: Cardiac Magnetic Resonance Imaging Diastolic Indices Correlate With Cardiac Catheterization Filling Pressures in Pediatric Heart Transplant Recipients

Background: Atrial and ventricular filling pressures are routinely used in pediatric heart transplant (HTx) recipients to assess graft function. Cardiac magnetic resonance (CMR) can provide a non-invasive assessment of diastolic function, but data are lacking in pediatric HTx. We hypothesized that CMR indices of diastolic function correlate with filling pressures, providing a non-invasive approach to assessment of ventricular dysfunction. Method: Pediatric HTx recipients were prospectively enrolled at the time of cardiac catheterization. Pulmonary capillary wedge pressure (PCWP) and right atrial pressure (RAP) were measured. CMR included standard volumetric analysis and T1 and extracellular volume (ECV) mapping in the short axis at the mid-left ventricle (LV) to evaluate extracellular matrix expansion. Filling curves were calculated by contouring every phase in the short axis stack and global longitudinal and circumferential strain (GLS, GCS) were calculated using feature tracking. Correlations were analyzed using Spearman’s correlation. Results: A total of 31 patients with a mean age of 16.2 y/o were included, 9 with biopsy-proven acute rejection. The median time from transplant was 6.9 years and the mean LVEF was 58%. Peak LV ejection rate/end-diastolic volume (PER/EDV) correlated with PCWP (rho=-0.43, p=0.02, Fig 1) and RAP (rho=-0.40, p=0.03). GLS and GCS correlated with RAP (rho=0.51 p=0.007, and rho=0.38 p=0.05, respectively); GLS also correlated with PCWP (rho=0.46, p=0.02). Native T1 time-correlated with PCWP (rho=0.54, p=0.003), while the correlation between ECV and PCWP did not reach statistical significance (rho=0.37, p=0.06). Conclusion: CMR can be a useful non-invasive modality to assess for early signs of diastolic dysfunction in patients after pediatric HTx. Further research is needed to describe the clinical significance of these associations.

Sleep-disordered breathing in pediatric heart transplant recipients.

Sleep-disordered breathing is commonly found in adults with heart failure both before and after HTx. Untreated sleep-disordered breathing post-transplant has been linked to late graft dysfunction, reduced quality of life, and increased morbidity. Sleep-disordered breathing has not been investigated in pediatric HTx recipients. We conducted retrospective review of patients <21yo who underwent primary HTx at our center from 2009 to 2019 to describe clinical characteristics, cardiac history, and PSG results. One hundred and fifty patients were included; 60% had congenital heart disease, and 40% had cardiomyopathy. Fifty patients had PSG performed at median age of 6.1years. Forty-one were referred for symptoms of sleep-disordered breathing. Obstructive sleep apnea was diagnosed in 45 patients and central sleep apnea in 3 patients. Of those with first PSG post-transplant (n=36), median AHI was 9.1/h, and 19 (53%) were diagnosed with moderate or severe sleep apnea. Patients diagnosed with obstructive sleep apnea on PSG had more post-transplant ventilator days (median 3 vs 2days, P<.05) and longer post-transplant lengths of stay (median 28 vs 22days, P<.05). In this single-center cohort of pediatric HTx recipients, sleep-disordered breathing was common and associated with longer peri-transplant respiratory support and length of stay. Given the high incidence of moderate and severe OSA detected in this population, clinicians should regularly screen for SDB and consider PSG testing more frequently in children who have undergone HTx. Further study into the long-term impact of sleep-disordered breathing in pediatric HTx recipients is needed.

Early school-age cognitive performance post-pediatric heart transplantation.

As survival in pediatric heart transplantation (HTx) has improved due to medical advances, the analysis of long-term outcomes impacting quality of life such as cognition and development becomes increasingly important. Neuropsychological assessments provide a comprehensive understanding of individual needs, allowing for the development of tailored recommendations and interventions. Routine neuropsychological assessment was completed between 5 and 7years of age in this cohort of pediatric HTx recipients at our center (Jan 2014-Oct 2018), including tests of general intellect (WPPSI-IV, WISC-V), academics (WIAT-II/III), perceptual-motor abilities (Beery VMI), and memory (CMS). Relevant medical variables were collected. Among 25 children, the median age at testing was 6.7 (IQR:5.8-7.4) years, with a median time since HTx of 5.2 (IQR:4.8-6.8) years. Medical diagnoses included congenital heart disease (CHD; 56%) and cardiomyopathy (44%). Cognitive functioning across the intellectual, academic, and perceptual-motor domains fell within the low-average range, while memory abilities fell within the average range. DSM-5 clinical diagnoses were provided for 14 (56%) children: Intellectual Disability-Mild (20%), Learning Disability (20%), Language Disorder (8%), and Attention-Deficit/Hyperactivity Disorder (12%). The presence of neurological issues and/or CHD predicted poorer performance on various neuropsychological domains. Over 50% of this cohort of pediatric heart transplant recipients seen for routine post-HTx neuropsychological assessment received a clinical psychological diagnosis, notably higher than rates in the general population. This population requires monitoring to ensure that high risk children are identified and successfully supported in school and their community.

The impact of psychiatric disorders on outcomes following heart transplantation in children.

Psychiatric disorders are common in pediatric HTx recipients. However, the impact of psychiatric comorbidities on patient outcomes is unknown. We aimed to assess the impact of disorders of adjustment, depression, and anxiety on HTx outcomes in children; hypothesizing that the presence of psychiatric disorders during or preceding HTx would negatively impact outcomes. All pediatric HTx recipients ≥8years of age who survived to hospital discharge were identified from a novel linkage between the PHIS and SRTR databases (2002-2016). Psychiatric disorders were identified using ICD codes during or preceding the HTx admission. Post-transplant graft survival, freedom from readmission, and freedom from rejection were analyzed using the Kaplan-Meier method. Multivariable Cox proportional hazard models were used to adjust for covariates. A total of 1192 patients were included, of which 133 (11.2%) had depression, 197 (16.5%) had anxiety, and 218 (18.3%) had adjustment disorders. The presence of depression was independently associated with higher rates of readmission (60.9% vs 54.1% at 6months) (AHR 1.63, 95% CI 1.22-2.18, P=.001) and inferior graft survival (70.2% vs 83.4% at 5years) (AHR 1.62, 95% CI 1.14-2.3, P=.007). Anxiety was independently associated with higher rates of readmission (60.4% vs 53.9% at 6months) (AHR 1.46, 95% CI 1.09-1.94, P=.01). Anxiety and depression in the pretransplant period are independently associated with outcomes following HTx in children. Evaluation and management of psychiatric comorbidities represents an important component of care in this vulnerable population.

Cytomegalovirus infection and allograft rejection among pediatric heart transplant recipients in the era of valganciclovir prophylaxis.

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

Prevalence and Risk Factors of Proteinuria in Pediatric Heart Transplantation

Renal dysfunction is a common complication of heart transplantation (HTx) in children that affects overall outcome. Proteinuria reflects renal glomerular and tubular damage and is an early marker of renal dysfunction, even when excreted in small amounts, termed microalbuminuria. The prevalence of microalbuminuria in pediatric HTx has not been previously described. We report the prevalence of proteinuria as measured by microabuminuria to creatinine ratio (UACR) and its associated risk factors in pediatric HTx recipients. Since 2015, UACR is collected annually at rejection surveillance catheterization. Patients aged <21 years with at least one UACR were identified. Patients with dual heart/kidney transplant retransplantation, and presence of diabetes pre-transplant were excluded. 116 patients were identified, of whom 51 (44%) were female and 68 (58%) Caucasian. Mean age at HTx was 5.4 ± 6.2 years. Ninety-two (79%) were listed status 1A, and 74 (64%) had congenital heart disease. Perioperative therapies included mechanical circulatory support in 23 (20%), dialysis in 4 (3%), mechanical ventilation in 34 (29%). No patients had insulin dependent diabetes pre-HTx and 2 (2%) developed diabetes in the first year post-HTx. Mean pre-HTx eGFR was 99 ± 35.5 ml/min/1.73m2. At a latest follow-up of 5.8 ± 3.8 years, 7 (6%) patients developed diabetes, 42% (n=35) had an abnormal UACR (≥ 31 units). Mean UACR was 85 ± 182.5 and 25% had eGFR <60 ml/min/1.73m2. Using univariate regression adjusted for time from HTx, younger age at HTx was protective against abnormal UACR (RR 0.94, p <0.05) and post-HTx dialysis was associated with abnormal UACR (R 3.1, p<0.001).Development of diabetes in the first year post-txp was associated with abnormal UACR (β -80, p=0.001). Microalbuminuria as a marker of renal injury is a highly prevalent finding in medium-term follow up of pediatric HTx. Post-Htx dialysis and diabetes is a risk factor for developing microalbuminuria and younger age at transplant may be protective. These observations may have implications on early identification of chronic renal disease and its medical intervention.