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BACKGROUND Indications for a heart‒liver transplantation (HLT) for Fontan recipients are not well defined. We compared listing characteristics, post-operative complications, and post-transplant outcomes of Fontan recipients who underwent HLT with those of patients who underwent heart-only transplantation (HT). We hypothesized that patients who underwent HLT have increased post-operative complications but superior survival outcomes compared with patients who underwent HT. METHODS We performed a retrospective review of Fontan recipients who underwent HLT or HT at a single institution. Characteristics at the time of listing, including the extent of liver disease determined by laboratory, imaging, and biopsy data, were compared. Post-operative complications were assessed, and the Kaplan‒Meier survival method was used to compare post-transplant survival. Univariate regression analyses were performed to identify the risk factors for increased mortality and morbidity among patients who underwent HT. RESULTS A total of 47 patients (9 for HLT, 38 for HT) were included. Patients who underwent HLT were older, were more likely to be on dual inotrope therapy, and had evidence of worse liver disease. Whereas ischemic time was longer for the group who underwent HLT, post-operative complications were similar. Over a median post-transplant follow-up of 17 (interquartile range: 5–52) months, overall mortality for the cohort was 17%; only 1 patient who underwent HLT died (11%) vs 7 patients who underwent HT (18%) ( p = 0.64). Among patients who underwent HT, cirrhosis on pre-transplant imaging was associated with worse outcomes. CONCLUSIONS Despite greater inotrope need and more severe liver disease at the time of listing, Fontan recipients undergoing HLT have post-transplant outcomes comparable with those of patients undergoing HT. HLT may offer a survival benefit for Fontan recipients with liver disease.

Acute kidney injury (AKI) is common following pediatric cardiac transplantation. Since no treatments exist, strategies focus on early identification and prevention. Kinetic glomerular filtration rate (kGFR) was developed to assess renal function in the non-steady state. Although used to predict AKI in adults, kGFR has not been explored in children. Our study examines AKI and the ability of kGFR to identify AKI risk in pediatric heart transplant recipients. One hundred and seventy-five patients under 21 years who underwent cardiac transplantation at Lucile Packard Children’s Hospital between September 2007–December 2017 were included. kGFR1 was calculated using pre-operative and immediate post-operative creatinines; kGFR2 was calculated with the first two post-operative creatinines. The primary outcome was AKI as defined by the Kidney Disease: Improving Global Outcomes criteria. One hundred and thirty-one (75%) and 78 (45%) patients developed AKI and severe AKI, respectively; 5 (2.9%) required dialysis. kGFR was moderately associated with post-operative AKI risk. The adjusted area under the curve (AUC) for kGFR1 was 0.72 (discovery) and 0.65 (validation). The AUC for kGFR2 was 0.72 (discovery) and 0.68 (validation). AKI is pervasive in children undergoing cardiac transplant, particularly in the 24 h after surgery. kGFR moderately identifies AKI risk and may represent a novel risk stratification technique.

Introduction Abulia is defined as a pathological state of amotivation, apathy, and global absence of willpower. It presents with a challenging array of overlapping symptoms, making effective identification and treatment difficult. Case presentation We describe the first known report of an adolescent with a ventricular assist device who developed abulia following a left middle cerebral artery (MCA) stroke who responded successfully to treatment with olanzapine. Discussion The neurobiological etiology of abulia is still unclear but is postulated to be related to deficits in the dopaminergic reward circuitry in the frontal-subcortical-mesolimbic regions. There have been reports of poststroke patients with abulia being treated by modulating this dopamine circuitry and in some cases with short-term low-dose olanzapine. Conclusion Further research is needed to develop a better understanding of the pathophysiology of abulia leading to more effective treatment algorithms including more specific diagnostic tools and effective pharmacological interventions.

Although renal function often improves after pediatric left ventricular assist device (LVAD) implantation, recovery is inconsistent. We aimed to identify hemodynamic parameters associated with improved renal function after pediatric LVAD placement. A single-center retrospective cohort study was conducted in patients less than 21 years who underwent LVAD placement between June 2004 and December 2015. The relationship between hemodynamic parameters and estimated glomerular filtration rate (eGFR) was assessed using univariate and multivariate modeling. Among 54 patients, higher preoperative central venous pressure (CVP) was associated with eGFR improvement after implantation (p = 0.012). However, 48 hours postimplantation, an increase in CVP from baseline was associated with eGFR decline over time (p = 0.01). In subgroup analysis, these associations were significant only for those with normal pre-ventricular assist device renal function (p = 0.026). In patients with preexisting renal dysfunction, higher absolute CVP values 48 and 72 hours after implantation predicted better renal outcome (p = 0.005). Our results illustrate a complex relationship between ventricular function, volume status, and renal function. Additionally, they highlight the challenge of using CVP to guide management of renal dysfunction in pediatric heart failure. Better methods for evaluating right heart function and volume status are needed to improve our understanding of how hemodynamics impact renal function in this population.

Background Although mortality has decreased considerably in pediatric heart transplantation, waitlist and post-transplant death rates remain notable. End-of-life focused research in this population, however, is very limited. This Pediatric Heart Transplant Society study aimed to describe the circumstances surrounding death of pediatric heart transplant patients. Methods A retrospective analysis of the multi-institutional, international, Pediatric Heart Transplant Society registry was conducted. Descriptive statistics and univariate analyses were performed to 1) describe end-of-life in pediatric pre- and post-heart transplant patients and 2) examine associations between location of death and technological interventions at end-of-life with demographic and disease factors. Results Of 9217 patients (0-18 years) enrolled in the registry between 1993 and 2018, 2804 (30%) deaths occurred; 1310 while awaiting heart transplant and 1494 post-heart transplant. The majority of waitlist deaths (89%) occurred in the hospital, primarily in ICU (74%) with most receiving mechanical ventilation (77%). Fewer post-transplant deaths occurred in the hospital (22%). Out-of-hospital death was associated with older patient age (p Conclusions ICU deaths with high use of technological interventions at end-of-life were common, particularly in patients awaiting heart transplant. In this high mortality population, findings raise challenging considerations for clinicians, families, and policy makers on how to balance quality of life amidst high risk for hospital-based death.

Background To evaluate the impact of a clinical pathway on the incidence and severity of acute kidney injury in patients undergoing heart transplant. Methods This was a 2.5-year retrospective evaluation using 3 years of historical controls within a cardiac intensive care unit in an academic children's hospital. Patients undergoing heart transplant between May 27, 2014, and April 5, 2017 (pre-pathway) and May 1, 2017, and November 30, 2019 (pathway) were included. The clinical pathway focused on supporting renal perfusion through hemodynamic management, avoiding or delaying nephrotoxic medications, and providing pharmacoprophylaxis against AKI. Results There were 57 consecutive patients included. There was an unadjusted 20% reduction in incidence of any acute kidney injury (p = .05) and a 17% reduction in Stage 2/3 acute kidney injury (p = .09). In multivariable adjusted analysis, avoidance of Stage 2/3 acute kidney injury was independently associated with the clinical pathway era (AOR -1.3 [95% CI -2.5 to -0.2]; p = .03), achieving a central venous pressure of or less than 12 mmHg (AOR -1.3 [95% CI -2.4 to -0.2]; p = .03) and mean arterial pressure above 60 mmHg (AOR -1.6 [95% CI -3.1 to -0.01]; p = .05) in the first 48 h post-transplant, and older age at transplant (AOR - 0.2 [95% CI -0.2 to -0.06]; p = .002). Conclusions This report describes a renal protection clinical pathway associated with a reduction in perioperative acute kidney injury in patients undergoing heart transplant and highlights the importance of normalizing perioperative central venous pressure and mean arterial blood pressure to support optimal renal perfusion.

BACKGROUND: Young adult heart transplant (HT) recipients transferring to adult care are at risk for poor health outcomes. We conducted a pilot randomized controlled trial to determine feasibility and test a transition intervention for young adults who underwent HT as children and transferred to adult care. METHODS: Participants were randomized to the transition intervention (4 months long, focused on HT knowledge, self-care, self-advocacy, and social support) or usual care. Self-report questionnaires and medical records data were collected at baseline and 3 and 6 months after the initial adult clinic visit. Longitudinal analyses comparing outcomes over time were performed using generalized estimating equations and linear mixed models. RESULTS: Transfer to adult care was successful and feasible (i.e., excellent participation rates). The average patient standard deviation of mean tacrolimus levels was similar over time in both study arms and < 2.5, indicating adequate adherence. There were no between group and within group differences in percent of tacrolimus bioassays within target range (>50%). Average overall adherence to treatment was similarly good for both groups. Rates of appointment keeping through 6 months after transfer declined over time in both groups. CONCLUSIONS: Feasibility of the study was demonstrated. Our transition intervention did not improve outcomes.

Objective To determine the association between continuous flow ventricular assist devices and the incidence of vasoplegia following orthotopic heart transplant in children. Moreover, to propose a novel clinical definition of vasoplegia for use in pediatric populations. Methods This is a single-center, retrospective cohort study set in the cardiovascular intensive care unit of a tertiary children's hospital. All patients aged 3 years and older who underwent orthotopic heart transplant at Stanford University between April 1, 2014, and July 31, 2017, were included. Vasoplegia was defined by the use of vasoconstrictive medication, diastolic hypotension, preserved systolic heart function, and absence of infection or right atrial pressure or central venous pressure Results Of 44 eligible patients, 21 were supported using a continuous flow ventricular assist device. Following heart transplant, 14 patients (32%) developed vasoplegia by the study definition. Development of vasoplegia was associated with pretransplant use of a continuous flow ventricular assist device (52% vs 13%) with a relative risk of 4.02 (95% confidence interval, 1.30-12.45; P = .009). No other variables were predictive of vasoplegia in univariable analysis. Presence of vasoplegia was not associated with adverse outcomes, although there were trends towards higher incidence of acute kidney injury and increased length of hospital stays. Conclusions Children receiving continuous flow ventricular assist device support are at increased risk for vasoplegia following orthotopic heart transplant, using a novel definition of vasoplegia. Anticipation of this complication will allow for prompt intervention, thereby minimizing hemodynamic instability and impact on patient outcomes.

Hypertrophic cardiomyopathy (HCM) has historically been diagnosed phenotypically. Through genetic testing, identification of a molecular diagnosis (MolDx) is increasingly common but the impact on pediatric patients is unknown. This was a retrospective study of next-generation sequencing data for 602 pediatric patients with a clinician-reported history of HCM. Diagnostic yield was stratified by gene and self-reported race/ethnicity. A MolDx of HCM was identified in 242 (40%) individuals. Sarcomeric genes were the highest yielding, but pathogenic and/or likely pathogenic (P/LP) variants in syndromic genes were found in 36% of individuals with a MolDx, often in patients without documented clinical suspicion for a genetic syndrome. Among all MolDx, 73% were in genes with established clinical management recommendations and 2.9% were in genes that conferred eligibility for clinical trial enrollment. Black patients were the least likely to receive a MolDx. In the current era, genetic testing can impact management of HCM, beyond diagnostics or prognostics, through disease-specific guidelines or clinical trial eligibility. Genetic testing frequently can help identify syndromes in patients for whom syndromes may not be suspected. These findings highlight the importance of pursuing broad genetic testing, independent of suspicion based on phenotype. Lower rates of MolDx in Black patients may contribute to health inequities. Further research is needed evaluating the genetics of HCM in underrepresented/underserved populations. Additionally, research related to the impact of genetic testing on clinical management of other diseases is warranted. Supplementary Information The online version contains supplementary material available at 10.1007/s00246-021-02764-1.

BACKGROUND Routine surveillance biopsy (RSB) is performed to detect asymptomatic acute rejection (AR) after heart transplantation (HT). Variation in pediatric RSB across institutions is high. We examined center-based variation in RSB and its relationship to graft loss, AR, coronary artery vasculopathy (CAV), and cost of care during the first year post-HT. METHODS We linked the Pediatric Health Information System (PHIS) and Scientific Registry of Transplant Recipients (SRTR, 2002-2016), including all primary-HT aged 0-21 years. We characterized centers by RSB frequency (defined as median biopsies performed among recipients aged ≥12 months without rejection in the first year). We adjusted for potential confounders and center effects with mixed-effects regression analysis. RESULTS We analyzed 2867 patients at 29 centers. After adjusting for patient and center differences, increasing RSB frequency was associated with diagnosed AR (OR 1.15 p = 0.004), a trend toward treated AR (OR 1.09 p = 0.083), and higher hospital-based cost (US$390 315 vs. $313 248, p

Context Compassionate deactivation (CD) of ventricular assist device (VAD) support is a recognized option for children when the burden of therapy outweighs the benefits. Objectives To describe the prevalence, indications, and outcomes of CD of children supported by VADs at the end of life. Methods Review of cases of CD at our institution between 2011 and 2020. To distinguish CD from other situations where VAD support is discontinued, patients were excluded from the study if they died during resuscitation (including extracorporeal membrane oxygenation), experienced brain or circulatory death prior to deactivation, or experienced a non-survivable brain injury likely to result in imminent death regardless of VAD status. Results Of 24 deaths on VAD, 14 (58%) were CD. Median age was 5.7 (interquartile range (IQR) 0.6, 11.6) years; 6 (43%) had congenital heart disease; 4 (29%) were on a device that can be used outside of the hospital. CD occurred after 40 (IQR: 26, 75) days of support; none while active transplant candidates. CD discussions were initiated by the caregiver in 6 (43%) cases, with the remainder initiated by a medical provider. Reasons for CD were multifactorial, including end-organ injury, infection, and stroke. CD occurred with endotracheal extubation and/or discontinuation of inotropes in 12 (86%) cases, and death occurred within 10 (IQR: 4, 23) minutes of CD. Conclusion CD is the mode of death in more than half of our VAD non-survivors and is pursued for reasons primarily related to noncardiac events. Caregivers and providers both initiate CD discussions. Ventilatory and inotropic support is often withdrawn at time of CD with ensuing death.

Introduction: The Institute of Medicine called for scientific investigation and the development of guidelines to improve end of life care for pediatric patients with serious illnesses. Despite high morbidity and mortality in pediatric heart transplantation (HTx), research on the end of life care needs of this population is extremely limited. Aims: This study aimed to describe the circumstances surrounding death of pediatric HTx patients and examine associations between location of death and technological interventions at end-of-life with demographic, disease, and HTx-related factors. Methods: This retrospective analysis of the Pediatric Heart Transplant Society registry utilized descriptive statistics and standard univariate analysis to examine associations between location of death and patient factors. Results: Of 9,217 registry entries, 2,804 (30%) deaths occurred; 1,310 while awaiting HTx; 1,494 post-HTx. Location of death was only recorded for 1,113 patients which included 804 waitlist deaths; 89% occurred in the hospital, primarily in ICU settings (74%) with most requiring mechanical ventilation (77%). A subset (39%) were supported by ECMO/VAD at time of death with 69% receiving inotrope support. Location of death was captured for 309 post-HTx patients with only 22% occurring in hospital; primarily in the ICU (74%) with half receiving mechanical ventilation (52%) and a smaller proportion supported by ECMO/VAD (18%) or inotropes (21%) at time of death. Overall, location of death was not associated with patient sex, race, ethnicity, insurance type, or primary etiology. Out of hospital death was associated with older patient age (p Conclusions: Death occurred in ~1/3 of patients captured in this pediatric HTx registry. ICU deaths with high use of technological interventions were common, particularly in waitlisted patients, but family decision to discontinue interventions was infrequently cited. Findings underscore the need for palliative care interventions and improved research strategies to better understand end of life in pre- and post-HTx pediatric populations.

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

Outcomes in pediatric patients with ventricular assist devices (VADs) for advanced heart failure (HF) are improving, but the risk of associated morbidity and mortality remains substantial. Few data exist on the involvement of pediatric palliative care (PPC) in this high-risk patient population. We aimed to characterize the extent of palliative care involvement in the care of patients requiring VAD placement at our institution. Single-center retrospective chart review analyzing all VAD patients at a large pediatric center over a 4 year period. Timing and extent of palliative care subspecialty involvement were analyzed. Between January 2014 and December 2017, 55 HF patients underwent VAD implantation at our institution. Pediatric palliative care utilization steadily increased over consecutive years (2014

The number of children needing heart transplantation continues to rise. Although improvements in heart failure therapy, particularly durable mechanical support, have reduced waitlist mortality, the number of children who die while waiting for a suitable donor organ remains unacceptably high. Roughly, 13% of children and 25% of infants on the heart transplant waitlist will not survive to transplantation. With this in mind, the Advanced Cardiac Therapies Improving Outcomes Collaborative Learning Network (ACTION), through its Waitlist Outcomes Committee, convened a 2-day symposium in Ann Arbor, Michigan, from 2-3 November 2019, to better understand the factors that contribute to pediatric heart transplant waitlist mortality and to focus future efforts on improving the organ allocation rates for children needing heart transplantation. Using improvement science methodology, the heart failure-transplant trajectory was broken down into six key steps, after which modes of failure and opportunities for improvement at each step were discussed. As a result, several projects aimed at reducing waitlist mortality were initiated.

BACKGROUND Currently, there are no simple tools to evaluate the acute heart failure (HF) symptom severity in children hospitalized with acute decompensated HF (ADHF). We sought to develop an inpatient HF score (HFS) that could be used as a clinical tool and for clinical trials. METHODS Pediatric HF clinicians at Stanford reviewed the limitations of existing HFSs, which include lack of calibration to the inpatient setting, omission of gastrointestinal symptoms, need for multiple age-based tools, and scores that prioritize treatment intensity over patient symptoms. To address these, we developed an acute HFS corresponding to the 3 cardinal symptoms of HF: difficulty with breathing, feeding, and activity. The score was iteratively improved over a 3-year pilot phase until no further changes were made. The inter-rater reliability (IRR) across a range of providers was assessed using the final version. Peak HFSs were analyzed against mortality and length of stay (LOS) for all pediatric HF discharges between July and October 2019. RESULTS The final HFS was a 4-point ordinal severity score for each of the 3 symptom domains (total score 0-12). Among clinicians who scored 12 inpatients with ADHF simultaneously, the intraclass correlation (ICC) was 0.94 (respiratory ICC = 0.89, feeding ICC = 0.85, and activity ICC = 0.80). Score trajectory reflected our clinical impression of patient response to HF therapies across a range of HF syndromes including 1- and 2-ventricle heart disease and reduced or preserved ejection fraction. Among the 28 patients hospitalized during a 3-months period (N = 28), quartiles of peak score were associated with LOS (p < 0.01) and in-hospital mortality (p < 0.01): HFS 0 to 3 (median LOS of 5 days and mortality of 0%), HFS 4 to 6 (median LOS of 18 days and mortality of 0%), HFS 5 to 9 (median LOS of 29 days and mortality of 23%), and HFS 10 to 12 (median LOS of 121 days and mortality of 50%). CONCLUSION This simple acute HFS may be a useful tool to quantify and monitor day-to-day HF symptoms in children hospitalized with ADHF regardless of etiology or age group. The score has excellent IRR across provider levels and is associated with major hospital outcomes supporting its clinical validity. Validation in a multicenter cohort is warranted.

Background Despite the routine use of hemodynamic assessment in pediatric heart transplant (HT) patients, expected intracardiac pressure measurements in patients free of significant complications are incompletely described. A better understanding of the range of intracardiac pressures in these HT patients is important for the clinical interpretation of these indices and consequent management of patients. Methods We conducted a retrospective chart review of pediatric HT recipients who had undergone HT between January 2010 and December 2015 at Lucile Packard Children's Hospital. We analyzed intracardiac pressures measured in the first 12 mo after HT. We excluded those with rejection, graft coronary artery disease, mechanical support, or hemodialysis. We used a longitudinal general additive model with bootstrapping technique to generate age and donor-recipient size-specific curves to characterize filling pressures through 1-y post-HT. Results Pressure measurements from the right atrium, pulmonary artery, and pulmonary capillary wedge pressure were obtained in 85 patients during a total of 829 catheterizations. All pressure measurements were elevated in the immediate post-HT period and decreased to a stable level by post-HT day 90. Pressure measurements were not affected by age group, donor-recipient size differences, or ischemic time. Conclusions Intracardiac pressures are elevated in the early post-HT period and decrease to levels typical of the native heart by 90 d. Age, donor-to-recipient size differences, and ischemic time do not contribute to differences in expected intracardiac pressures in the first year post-HT.

Background There is inadequate power to perform a valid clinical trial in pediatric heart transplantation (HT) using a conventional end-point, because the disease is rare and hard end-points, such as death or graft loss, are infrequent. We sought to develop and validate a surrogate end-point involving the cumulative burden of post-transplant complications to predict death/graft loss to power a randomized clinical trial of maintenance immunosuppression in pediatric HT. Methods Pediatric Heart Transplant Study (PHTS) data were used to identify all children who underwent an isolated orthotopic HT between 2005 and 2014 who survived to 6 months post-HT. A time-varying Cox model was used to develop and evaluate a surrogate end-point comprised of 6 major adverse transplant events (MATEs) (acute cellular rejection [ACR], antibody-mediated rejection [AMR], infection, cardiac allograft vasculopathy [CAV], post-transplant lymphoproliferative disease [PTLD] and chronic kidney disease [CKD]) occurring between 6 and 36 months, where individual events were defined according to international guidelines. Two thirds of the study cohort was used for score development, and one third of the cohort was used to test the score. Results Among 2,118 children, 6.4% underwent graft loss between 6 and 36 months post-HT, whereas 39% developed CKD, 34% ACR, 34% infection, 9% AMR, 4% CAV and 2% PTLD. The best predictive score involved a simple MATE score sum, yielding a concordance probability estimate (CPE) statistic of 0.74. Whereas the power to detect non-inferiority (NI), assuming the NI hazard ratio of 1.45 in graft survival was 10% (assuming 200 subjects and 6% graft loss rate), the power to detect NI assuming a 2-point non-inferiority margin was >85% using the MATE score. Conclusion The MATE score reflects the cumulative burden of MATEs and has acceptable prediction characteristics for death/graft loss post-HT. The MATE score may be useful as a surrogate end-point to power a clinical trial in pediatric HT.

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

Purpose There are limited data reporting outcomes of children with trisomy 21 undergoing heart transplantation (HTx). This project reports the waitlist and post-HTx outcomes of children with trisomy 21. Methods This is a retrospective cohort study of children with trisomy 21 listed for or who underwent HTx at 11 centers within North America and internationally. Demographic, medical, surgical, and post-HTx outcome data were collected and described. Results Twenty-one patients with trisomy 21 were listed for HTx from 1992 through 2019 (median age 8.5y, 43% male, 52% white). High-risk or failed repair of congenital heart disease was the indication for transplant in 16 (76%) patients with atrioventricular septal defect being the most common (N=12). Other diagnoses included dilated cardiomyopathy in 4 patients (secondary to anthracyclines in 2) and myocarditis in 1 patient. A total of 18 (86%) patients survived to transplant. Of this group, support at the time of transplant included inotropes (N=10, 56%), ventricular assist device (N=7, 39%), and mechanical ventilation (N=2, 11%). No patients required post-operative extracorporeal membrane oxygenation or dialysis. All centers reported the use of standard immunosuppression without alterations secondary to trisomy 21. All transplanted patients survived to hospital discharge with a median post-HTx length of stay of 19d. With a median follow-up of 2.9y, 16 (89%) patients were alive, 5 (28%) had rejection within the 1st year post-HTx, 2 (11%) developed post-transplant lymphoproliferative disorder (PTLD), and 7 (39%) were hospitalized for infection within the 1st year post-HTx. For the two post-HTx mortalities, the causes of death were 1) coronary allograft vasculopathy at 22y post-HTx and 2) multiple episodes of rejection and PTLD at 1.5y post-HTx (Figure). Conclusion Waitlist and intermediate post-HTx outcomes are acceptable in children with trisomy 21. The presence of trisomy 21 should not be an absolute contraindication to heart transplantation in the appropriate clinical setting.

Purpose Compassionate deactivation (CD) of ventricular assist device (VAD) support is a recognized option for children when the burden of ongoing therapy outweighs the benefits. The circumstances, indications, and outcomes of CD in pediatric VAD patients are insufficiently described. Methods Review of all cases of CD at our institution between 2011-2020. To distinguish CD of VAD from other situations where VAD support is discontinued, deactivations occurring after myocardial recovery, brain or cardiac death or while also on ECMO, were excluded. Results are presented descriptively. Results Of 24 deaths on VAD, 14 (58%) were CD. Median age was 5.7 (0.6, 11.6) years; 7 (50%) had congenital heart disease; 4 (29%) were on a “dischargeable” device. CD occurred after 40 (IQR: 26, 75) days of support, none while active transplant candidates. CD discussions were initiated by the patient/parent/caregiver in 6 (43%) cases, the remainder by a medical provider ( Table ). Reasons for CD were multifactorial, and included stroke, end-organ injury, and loss of transplant candidacy. ( Figure ). CD occurred with endotracheal extubation in 12(86%) cases, and death occurred within 10 (IQR: 4, 23) minutes of CD. Conclusion CD is the mode of death in more than half of our VAD non-survivors, and is chosen for reasons mainly related to noncardiac events. Patients, caregivers, and providers may initiate CD discussions. Ventilatory support is often withdrawn at time of CD with ensuing death.

We are currently utilizing a technique of heart transplantation in situs inversus/dextrocardia that maintains dextrocardia after implantation. Concerns may be technical difficulty and long-term complications. We have therefore obtained follow-up in our cohort up to 10 years. Between July 2007 and February 2017, we performed heart transplantation in five patients with situs inversus and dextrocardia. All had bilateral superior venae cavae (SVC). In all, the recipient left SVC was anastomosed to the donor SVC, and the recipient right SVC was anastomosed to the donor right atrial appendage. The normal donor heart was rotated 120° to the right to maintain a position of dextrocardia in the recipient. Three patients are alive and well to this date. One patient, who also had a pneumonectomy for recurrent infections at the time of transplant, died early postoperatively from a disseminated fungal infection. Another patient did well initially, however died from post-transplant lymphoproliferative disease 4 years posttransplantation. A third patient required stent implantation 4 years postoperatively to treat stenosis of the right SVC to right atrial anastomosis. There were no other complications related to the surgical technique and no other reinterventions. This technique maintains excellent long-term outcomes. It uses the existing pericardial cavity most effectively. It avoids pericardial resection, lung compression, or right ventricular compromise. Anastomotic obstruction of the SVC connection to the right atrium may occur, which is amenable to transcutaneous stenting.

The development of ventricular assist devices to sustain the circulation represents one of the great achievements in the treatment of heart failure. Though early (1st generation) pulsatile devices required that patients remain hospitalized while on support, newer 2nd and 3rd generation continuous-flow (CF) devices have allowed for hospital discharge, expanding their use beyond bridge to transplantation to include permanent support. This indication, referred to as “destination therapy” is emerging as a viable alternative to heart transplantation in adults, and more recently, children. Though no formal indications exist for destination therapy in children, it may be considered in lieu of transplantation in patients with non-cardiac life-limiting comorbidities, severe pulmonary hypertension, obesity (BMI > 35 kg/m 2 ), recurrent malignancy, or if it is their preference. One group for whom DT may be most appropriate is those with advanced dystrophinopathies for whom post-transplant outcomes remain poor. Outpatient management of the pediatric destination therapy patient requires close monitoring by a multidisciplinary team of physicians, nurses, pharmacists, social workers, nutritionists, and psychologists. Because destination therapy in children remains quite rare, little is known about long-term outcomes in this population, though studies of children supported as outpatients as a bridge to transplantation suggest that survival is excellent and functional status improves post-implantation. As ventricular assist devices continue to develop, the future will not only include application of this technology to a more diverse group of patients, but the additional challenge of supporting patients for increasingly longer durations, managing late complications, and facilitating improvements in quality of life.

Background Patients listed for heart transplant after their 18 th birthday purportedly wait longer to receive a donor heart compared to patients listed before their 18 th birthday. It is unclear whether there is an actual difference in wait times and whether any difference in wait time is associated with lower likelihood of transplant and/or higher risk of mortality. Methods Organ procurement and transplant network data were used to identify all patients listed for heart transplant between 2006 and 2014 within a one year period before and after their 18 th birthday. The primary study endpoint was the waiting time to receive a donor heart. Secondary endpoints included the probability of transplant and waitlist mortality. Regression discontinuity analysis was used to analyze the effect of age on either side of the sharp cut-off value of age 18 years (6,574 days of life), when allocation of donor hearts transitions from the pediatric to adult allocation system. Results A total of 360 patients met the study inclusion criteria, including 207 (57.5%) listed during the 12-month period prior to the 18 th birthday under the pediatric allocation system, and 153 (42.5%) listed during the 12 months after the 18 th birthday under the adult allocation system. The pediatric cohort was more likely to be listed status 1A. Otherwise, the two groups shared similar baseline characteristics. Overall, patients listed after the 18 th birthday waited 8.5 months longer to receive a transplant than adolescents listed before the 18 th birthday (P=0.01), had a 47% lower probability of receiving a transplant (P=0.001) but no difference in waitlist mortality (P=0.37). Conclusion Patients listed for heart transplant shortly after their 18 th birthday have significantly longer wait-times compared to patients listed shortly before their 18 th birthday, a lower probability of transplant but no significant difference in waitlist mortality. For medically fragile adolescents at high risk of death, birth date may be one factor to be aware of in timing of heart transplant listing.

As survival with pediatric left ventricular assist devices (LVADs) has improved, decisions regarding the optimal support strategy may depend more on quality of life and functional status (FS) rather than mortality alone. Limited data are available regarding the FS of children supported with LVADs. We sought to compare the FS of children supported with LVADs vs vasoactive infusions to inform decision making around support strategies.Organ Procurement and Transplant Network data were used to identify all United States children aged between 1 and 21 years at heart transplant (HT) between 2006 and 2015 for dilated cardiomyopathy and supported with an LVAD or vasoactive infusions alone at HT. FS was measured using the 10-point Karnofsky and Lansky scale.Of 701 children who met the inclusion criteria, 430 (61%) were supported with vasoactive infusions, and 271 (39%) were supported with an LVAD at HT. Children in the LVAD group had higher median FS scores at HT than children in the vasoactive infusion group (6 vs 5, p0.001) but lower FS scores at listing (4 vs 6, p0.001). The effect persisted regardless of patient location at HT (home, hospital, intensive care) or device type. Discharge by HT occurred in 46% of children in the LVAD group compared with 26% of children in the vasoactive infusion cohort (p = 0.001). Stroke was reported at HT in 3% of children in the LVAD cohort and in 1% in the vasoactive infusion cohort (p = 0.04).Among children with dilated cardiomyopathy undergoing HT, children supported with LVADs at HT have higher FS than children supported with vasoactive infusions at HT, regardless of device type or hospitalization status. Children supported with LVADs at HT were more likely to be discharged from the hospital but had a higher prevalence of stroke at HT.

Context Despite advances in therapies, many pediatric heart transplant (Htx) recipients will die prematurely. We characterized the circumstances surrounding death in this cohort, including location of death and interventions performed in the final 24 hours. Methods We reviewed all patients who underwent Htx at Lucile Packard Children's Hospital, Stanford, survived hospital discharge, and subsequently died between July 19, 2007 and September 13, 2015. The primary outcome studied was location of death, characterized as inpatient, outpatient, or emergency department. Circumstances of death (withdrawal of life-sustaining treatment, death during resuscitation, or death without resuscitation with/without do not resuscitate) and interventions performed in the last 24 hours of life were also analyzed. Results Twenty-three patients met the entry criteria. The median age at death was 12 (range 2–20) years, and the median time between transplant and death was 2.8 (range 0.8–11) years. Four (17%) died at home, and three (13%) died in the emergency department. Sixteen (70%) patients died in the hospital, 14 of 16 (88%) of whom died in an intensive care unit. Five of 23 (22%) patients experienced attempted resuscitation. Interventions performed in the last 24 hours of life included intubation (74%), mechanical support (30%), and dialysis (22%). Most patients had a recent outpatient clinical encounter with normal graft function within 60 days of dying. Conclusions/Lessons Learned Death in children after Htx often occurs in the inpatient setting, particularly the intensive care unit. Medical interventions, including attempted resuscitation, are common at the end of life. Given the difficulty in anticipating life-threatening events, earlier discussions with patients regarding end-of-life wishes are appropriate, even in those with normal graft function.

Background: There are limited data describing the functional status (FS) of children after heart transplant (HT). We sought to describe the FS of children surviving at least 1 year after HT, to evaluate the impact of HT on FS, and to identify factors associated with abnormal FS post-HT. Methods: Organ Procurement and Transplantation Network data were used to identify all US children Results: A total of 1633 children met study criteria. At the 1-year assessment, 64% were “fully active/no limitations” (FSS=10), 21% had “minor limitations with strenuous activity” (FSS=9); and 15% scored ≤8. In comparison with listing FS, FS at 1 year post-HT increased in 91% and declined/remained unchanged in 9%. A stepwise regression procedure selected the following variables for association with abnormal FS at 1 year post-HT: ≥18 years of age (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.2–2.7), black race (OR, 1.5; 95% CI, 1.1–2.0), support with ≥inotropes at HT (OR, 1.7; 95% CI, 1.2–2.5), hospitalization status at HT (OR, 1.5; 95% CI, 1.0–2.19), chronic steroid use at HT (OR, 1.5; 95% CI, 1.0–2.2), and treatment for early rejection (OR, 2.0; 95% CI, 1.5–2.7). Conclusion: Among US children who survive at least 1 year after HT, FS is excellent for the majority of patients. HT is associated with substantial improvement in FS for most children. Early rejection, older age, black race, chronic steroid use, hemodynamic support at HT, and being hospitalized at HT are associated with abnormal FS post-HT.

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

Purpose Infectious complications are a major cause of morbidity & mortality after heart transplantation (HT). Patients who have undergone Fontan palliation may have a higher susceptibility to post HT infections given thymectomy in infancy and known depletions of T-cell subsets. Methods This was a single-center, retrospective cohort analysis of pediatric patients undergoing HT for dilated cardiomyopathy (DCM) or failing Fontan physiology, who underwent post HT induction with anti-thymoglobulin (ATG). Repeat HTs and multi organ transplants were excluded. The primary endpoint was infection in the first 180 days post HT, defined as 1) positive blood, urine, or respiratory culture; 2) positive viral PCR (excluding CMV and EBV); 3) skin or wound infection; or 4) culture-negative infection if a full antibiotic course (≥ 5 days) was completed. Secondary endpoints included sensitivity to ATG as defined by 1) absolute lymphocyte (ALC) and CD3 counts after 5 doses; 2) the incidence of post transplant lymphoproliferative disorder (PTLD); and 3) rejection (>/= Grade 2R ACR or pAMR2) in the first 180 days post HT. Results From 1/2014 to 9/2019, 63 patients (30 Fontan, 33 DCM) underwent HT at a median of 15.4 (IQR 10.8, 20.1) and 11.7 (IQR 1.4, 13.6) years, respectively. The median total ATG received was 7.5 (IQR 6.7, 8.2) mg/kg vs 7.2 (IQR 4.7, 9.2) mg/kg (p=NS), respectively. The median CD3 [9 (IQR 3,14) vs 12 (IQR 6, 26); p=0.04, Figure 1A] and lymphocyte counts [172 (IQR 98, 354) vs 427 (IQR 205, 662); p=0.02] after ATG were lower in Fontan vs DCM patients. 28 patients (41%) developed at least one infection within 180 days after HT, with a higher rate of infection in Fontan patients (60% vs 24%, p=0.005; Figure 1B). There was no difference in the incidence of PTLD (10% vs 0%; p=0.1) or rejection (17% vs 27%; p=0.31) between Fontan vs DCM patients, respectively. Conclusion Compared to DCM patients, Fontan patients have a more pronounced suppression of CD3 counts after induction, as well as a higher risk of infection.

Purpose While combined heart-liver transplant (HLT) is being performed for Fontan patients, outcomes and indications remain poorly defined. We compared listing characteristics and post-transplant outcomes of Fontan patients with HLT to those with heart-only transplant (HT). Methods We retrospectively reviewed all Fontan patients undergoing HT or HLT at our institution between 2006-2019. Pre-transplant liver disease at the time of listing, as determined by laboratory and radiology data, and MELD-XI, Child Pugh, and VAST scores, were compared between groups. The Kaplan Meier survival method was used to compare post-transplant survival and freedom from rejection (ISHLT Grade 2R+ or pAMR2+). Results Forty-two patients (33 HT, 9 HLT) were included. HLT patients were older, more likely to be on dual-inotrope therapy, had worse Child Pugh and VAST scores, and were more likely to have varices, ascites, splenomegaly, and cirrhosis on imaging (Table 1). While not significant, HLT patients tended to be more sensitized, had higher total bilirubin and creatinine, and lower platelet count. Over a median post-transplant follow-up of 22 (5, 62) months, overall mortality for the entire cohort was 19%; only one HLT patient died (11%) versus 7 (21%) HT patients (p=0.58, Figure 1). None of the HLT patients experienced rejection, whereas 11 (33%) HT patients had rejection (p=0.06). Conclusion Despite a greater inotrope need and more severe liver disease at time of listing, patients undergoing HLT have post-transplant outcomes that are comparable, if not better, than Fontan patients with HT. There appears to be a protective effect from rejection with HLT.

Background Treprostinil, a prostacyclin analog, is a safe and effective therapy for children with PAH; however, the use of this agent in children with mild PVR elevations related to HF, including those with SV congenital heart disease awaiting HT, is understudied. We describe the hemodynamic and symptomatic changes in pediatric patients awaiting HT treated with treprostinil. Methods Single-center retrospective review of all patients was listed for HT who received treprostinil during the listing period. Changes in hemodynamic and functional indices between the baseline catheterization (prior to drug initiation), and prior to HT, and patient outcomes were analyzed. Results Among 16/17 (94%) who survived to HT, 8 (50%) were female, and 10 (63%) had SV physiology. The median age at drug initiation was 9 (IQR: 1, 14) years. The median duration of therapy prior to HT was 253 (IQR: 148, 504) days. Treprostinil significantly decreased PVR (3.8 vs 3.1 WU, P = .03), while mLA or mPCW pressure did not change (11 vs 13 mm Hg, P = .9). HF symptoms improved in 9/15 (60%) patients without VAD support prior to drug initiation, including 4/10 (40%) who did not receive a VAD any point while awaiting HT. Conclusions Treprostinil may be used safely in patients with mild PAH awaiting HT, including those with SV disease. PVR falls without substantial increases in mLA/mPCW pressure. HF symptoms improve in some patients.

BACKGROUND Malnutrition is common among children with single ventricle (SV) congenital heart disease (CHD). The impact of heart transplantation (HT) on nutritional status in SV patients is understudied. Our aim was to evaluate anthropometric changes in SV patients after HT, compared with those transplanted for cardiomyopathy (CM). METHODS We performed a single-center retrospective chart review of SV and CM patients

Purpose We sought to determine whether the presence of a systemic SA with potential complicating factors affects waitlist and post-HT outcomes in pediatric patients. Methods This is a single-center retrospective review of pediatric patients listed for HT between January 1, 2009, and July 1, 2018. Patients were selected based on the presence of any underlying syndromes, which included chromosomal anomalies, skeletal myopathies, connective tissue disorders, mitochondrial disease,and other systemic disorders. Waitlist and post-HT outcomes were compared to those without SA. Results A total of 243 patients were listed for HT, of which 21 (9%) patients had associated SA. Of those, 16 (76%) survived to transplant, 3 (14%) died while on the waitlist, 1 (5%) improved and was removed from the waitlist, and 1 (5%) patient is currently listed. Waitlist survival was not different between those with/without an associated syndrome (P = 1.0). Among those who survived to HT, there was no difference in listing days (70 vs 90, P = .8), survival to hospital discharge [14 (93%) vs 150 (95%), P = .6], post-HT intubation days (2 vs 2 days, P = .6), or post-HT hospital length of stay (18 vs 18 days, P = .8). Overall survival during the study period post-HT was not different between groups (P = .8). Conclusion A SA was present in 9% of pediatric patients wait-listed for HT, but was not associated with an increased waitlist mortality or post-HT hospital morbidity or long-term survival. For several anomalies, HT is safe and feasible.

Background Given poor outcomes, strategies to improve ventricular assist devices (VADs) for single-ventricle patients with bidirectional Glenn (BDG) palliation are needed. Methods This retrospective review describes an institutional experience with VAD support for patients with BDG from April 2011 to January 2019. Surgical strategies, complications, and causes of death are described. Survival to heart transplantation for various strategies are compared. Results A total of 7 patients with BDG (weights, 5.6 to 28.8 kg; ages, 7 months to 11 years) underwent VAD implantation. Three patients underwent implantation of Berlin Heart EXCOR devices (Berlin Heart, Inc, Spring, TX), 2 had HeartWare HVADs (Medtronic, Minneapolis, MN) implanted, and 2 patients underwent implantation of paracorporeal continuous flow devices. Four patients underwent ventricular inflow cannulation, and 3 underwent atrial inflow cannulation. At the time of VAD implantation, the BDG was left intact in 3 patients, taken down in 3 patients, and created de novo in 1 patient. Over a total of 420 VAD support days, 2 patients survived to heart transplantation, 1 patient with HeartWare ventricular cannulation and intact BDG (after 174 days) and another with Berlin Heart atrial cannulation and BDG take-down (after 72 days). There were 3 deaths within 2 weeks of VAD implantation (2 from respiratory failure, 1 from infection) and 2 deaths after 30 days as a result of strokes. Conclusions The surgical strategy and postoperative management of VAD with BDG are still evolving. Successful support can be achieved with (1) both pulsatile and continuous flow pumps, (2) atrial or ventricular cannulation, and (3) with or without BDG take-down. Surgical strategy should be determined by individual patient anatomy, physiology, and condition.

This study's objective was to investigate compassionate ventricular assist device deactivation (VADdeact) in children from the perspective of the pediatric heart failure provider.Pediatric VAD use is a standard therapy for advanced heart failure. Serious adverse events may affect relative benefit of continued support, leading to consideration of VADdeact. Perspectives and practices regarding VADdeact have been studied in adults but not in children.A web-based anonymous survey of clinicians for pediatric VAD patients (18 years) was sent to list-serves for the ISHLT Pediatric Council, the International Consortium of Circulatory Assist Clinicians Pediatric Taskforce, and the Pediatric Cardiac Intensivist Society.A total of 106 respondents met inclusion criteria of caring for pediatric VAD patients. Annual VAD volume per clinician ranged from4 (33%) to9 (20%). Seventy percent of respondents had performed VADdeact of a child. Response varied to VADdeact requests by parent or patient and was influenced by professional degree and region of practice. Except for the scenario of intractable suffering, no consensus on VADdeact appropriateness was reported. Age of child thought capable of making informed requests for VADdeact varied by subspecialty. The majority of respondents (62%) do not feel fully informed of relevant legal issues; 84% reported that professional society supported guidelines for VADdeact in children had utility.There is limited consensus regarding indications for VADdeact in children reported by pediatric VAD provider survey respondents. Knowledge gaps related to legal issues are evident; therefore, professional guidelines and educational resources related to pediatric VADdeact are needed.

Purpose In June 2018, the US Food and Drug Administration approved Prograf granules for pediatric solid-organ heart transplant without a US trial. This was due to concerns over compounding errors associated with pharmacy preparation of Prograf suspension for children who cannot swallow capsules. We reviewed our early experience converting children from Prograf suspension to granules to ensure safe transition practices. Methods All children transitioned from Prograf suspension to Prograf granules at a single center in 2019 were identified using pharmacy records. The starting dose for the transition from compounded liquid to granules was determined by using a one to one dosing conversion. The steady dose of Prograf pre and post conversion were compared, as was the time to reach a therapeutic level. Patients with modified target goals (e.g. secondary to infection) before or after conversion were excluded. Results Between January and September 2019, a total of 12 children were converted from Prograf suspension to Prograf granules of whom 9 met the inclusion criteria. Of these, the median age was 6.25 (IQR 4, 8) years, the median weight was 17 (15, 21) kg; 56% were female and 67% had prior congenital heart disease. Prior to conversion, the mean daily dose was 0.106 (SD 0.07) mg/kg. Following conversion, the mean daily dose was 0.112 (SD 0.08) mg/kg, a 15% increase on average. On average, 3 levels were obtained before a goal target level was achieved at a mean of 34 days after conversion. Conclusion Children transitioned from Prograf suspension to granules often required a dosing change to achieve the same target level on Prograf granules. The number of dose increases outnumbered dose decreases. Increasing the frequency of monitoring tacrolimus levels after conversion may help to foreshorten the period of time outside the goal range.

Purpose The match run is the automated mechanism by which UNOS prioritizes donor hearts to waitlist candidates for heart transplant (HT) based on medical urgency. We sought to determine how well match runs perform in sequencing patients according to their medical urgency after implementation of the 2016 pediatric heart allocation revisions. Methods OPTN data were used to identify all match runs between March 21, 2016 and June 9, 2020 for each pediatric donor heart offered through UNOS to US waitlist candidates. The rank-order of candidates on the match run was compared to the rank-order based on medical urgency alone defined as the probability of survival on the day of the match run using a risk prediction model developed and validated during the prior 6 years. Results Overall, 634 donors generated 2,524 unique match runs during the study period when a total of 2,608 candidates were listed for pediatric HT. The median age of donors was 5 years (Q1, Q3, 1, 13), median weight 21 (11, 54) kg with the most common cause of death natural causes (26%), non-motor vehicle accidents (MVA) (22%) and MVA (16%). The risk-prediction model for death or deterioration included 8 variables (age, weight, cardiac diagnosis and cardiac support). When the survival model was applied to the match run candidates within zone, 26% of candidates were ranked out of survival order (i.e. had a rank-reversal) (Table). Of these, 69% of rank-reversals involved candidates within the same UNOS status levels whereas 41% involved candidates spread across UNOS status levels. Conclusion There is evidence to suggest that the 2016 revision to the pediatric donor heart allocation system fails to sequence waitlisted candidates according to medical urgency, which affects a substantial fraction of match runs. Misclassification of patient risk by UNOS status level and within UNOS status levels each contribute rank-reversals. Rank-ordering patients based on a continuous survival probability model could address both problems.

Purpose To understand whether patients who have undergone Fontan palliation may have a higher susceptibility to post-HT infections given thymectomy in infancy and known depletions of T-cell subsets. Methods This was a single-center, retrospective cohort analysis of pediatric patients undergoing HT for dilated cardiomyopathy (DCM) or Fontan failure, who underwent induction with anti-thymoglobulin (ATG). The primary endpoint was infection in the first 180 days post-HT, defined as (1) positive blood/urine/respiratory culture; (2) positive viral PCR (excluding CMV and EBV); (3) skin or wound infection; and/or (4) culture-negative infection if a full antibiotic course (>5 days) was completed. Secondary endpoints included (1) absolute lymphocyte (ALC) and CD3 counts after 3 and 5 doses of anti-thymocyte gammaglobulin (ATG); (2) the incidence of post-transplant lymphoproliferative disorder (PTLD); and (3) rejection (≥ Grade 2R ACR or pAMR2) in the first 180 days post-HT. Results From 2014 to 2019, 59 pts (26 Fontan, 33 DCM) underwent HT at a median age of 14.7 (IQR 10.6, 19.5) and 11.7 (IQR 1.4, 13.6) years, respectively. The median total ATG received was 7.4 (IQR 4.9, 7.7) vs 7.5 (IQR 7.3, 7.6) mg/kg (p=NS). The median CD3 [8 (IQR 5, 14) vs 16 (IQR 10, 39); p=0.01] after 3 doses of ATG and ALC [172 (IQR 98, 400) vs 427 (IQR 205, 824); p=0.014] after 5 doses of ATG was lower in Fontan vs DCM patients (A,B). Twenty-three patients (39%) developed ≥1 infection within 180 days post-HT, with a higher rate of infection in Fontan patients (54% vs 27%, p=0.03; C, D). Adjusted for pre-transplant ALC, the risk for infection within 30 days post-HT for Fontan patients was OR 7.62, 95% CI 1.13-51.48, p=0.037. There was no difference in the incidence of PTLD (12% vs 0%; p=0.08) or rejection (12% vs 21%; p=0.49) between Fontan vs DCM patients. Conclusion Compared to DCM patients, Fontan patients have lower CD3 and ALC after induction, as well as a higher risk of infection. Modifications to induction therapy for Fontan patients may be considered.

Purpose As the use of pediatric ventricular assist devices (VAD) has increased, more children are being supported with VADs for transplant graft failure as a bridge to heart re-transplant (HT). Little is known about VAD outcomes for graft failure where left ventricular (LV) function is preserved, and LV chamber dilation is uncommon. We sought to examine VAD outcomes as a bridge to HT for this important subset of HF patients. Methods Organ Procurement and Transplant Network (OPTN) data were used to identify all children ≤21 years who underwent VAD placement between 2004 and 2020 as a bridge to heart re-transplant. Cox proportional hazard modeling was used to identify risk factors for mortality. Results Of 723 children listed for heart re-transplant, 144 were supported with MCS (87 with a VAD and 57 with ECMO alone). Of 87 VAD recipients, 41 (68%) received an LVAD alone, 29 (33%) received BIVADs, 9 (10%) received an TAH, and 7 (8%) an isolated RVAD. The most common isolated LVAD used was the Berlin Heart (N=16, 39%), a percutaneous LVAD (Impella or Tandem, N=11, 26%), and Heartware HVAD (N=6, 15%). The most common BIVAD configuration was bilateral Berlin Hearts (N=15, 52%) and bilateral CentriMag (10%). Since 2011 (when complete VAD survival data become available), overall survival to HT was 72%, with 61% reaching transplant while 11% remained on the waitlist. Survival was significantly worse compared to pediatric VAD patients supported for DCM and comparable to children with CHD (P=0.31) (Figure). For children supported with the Berlin Heart, outcomes for LVAD and BIVAD patients were similar (P=0.69) in contrast to other diagnoses where BIVAD outcomes are typically inferior to LVAD outcomes. Conclusion VAD outcomes for bridge to re-transplant are significantly worse than DCM patients and comparable to outcomes for CHD. While BIVAD outcomes are typically worse than LVAD outcomes for most cardiac diagnoses, outcomes appear similar for children supported for graft failure.

Despite increasing use of mechanical circulatory support in children, experience with biventricular device implantation remains limited. We describe our experience using the HeartWare HVAD to provide biventricular support to three patients and compare these patients with five patients supported with HeartWare left ventricular assist device (LVAD). At the end of the study period, all three biventricular assist device (BiVAD) patients had been transplanted and were alive. LVAD patients were out of bed and ambulating a median of 10.5 days postimplantation. The BiVAD patients were out of bed a median of 31 days postimplantation. Pediatric patients with both left ventricular and biventricular heart failure can be successfully bridged to transplantation with the HeartWare HVAD. Rapid improvement in functional status following HVAD implantation for isolated left ventricular support is seen. Patients supported with BiVAD also demonstrate functional recovery, albeit more modestly. In the absence of infection, systemic inflammatory response raises concern for inadequate support.

Acute kidney injury (AKI) is common in children following surgery for congenital heart disease and has been associated with poor long-term kidney outcomes. Children undergoing heart transplantation may be at increased risk for the development of both AKI and chronic kidney disease (CKD). This study examines AKI rates in children, adolescents, and young adults after heart transplantation and analyzes the relationship between AKI and CKD in this population.Retrospective cohort study.88 young patients who underwent heart transplantation at Lucile Packard Children's Hospital, Stanford, CA, September 1, 2007, to November 30, 2013.The primary independent variable was AKI within the first 7 postoperative days, ascertained according to the KDIGO (Kidney Disease: Improving Global Outcomes) creatinine criteria (increase in serum creatinine ≥ 1.5 times baseline within 7 days).Recovery from AKI at 3 months, ascertained as serum creatinine level 1.5 times baseline; and development of CKD at 6 and 12 months, ascertained as estimated glomerular filtration rate 60mL/min/1.73m(2) for more than 3 months.63 (72%) patients developed AKI; 57% had moderate (stage 2 or severe stage 3) disease. Recovery occurred in 39 of 63 (62%), 50% for stage 2 or 3 versus 78% for stage 1 (P=0.04). At 6 and 12 months, 3 of 82 (4%) and 4 of 76 (5%) developed CKD, respectively. At both time points, CKD was more common in those without recovery (3/22 [14%] vs 0/38 (0%); P=0.04, and 3/17 (18%) vs (0/34) 0%; P=0.03, respectively).Retrospective design, small sample size, and single-center nature of the study.AKI is common after heart transplantation in children, adolescents, and young adults. Nonrecovery from AKI is more common in patients with more severe AKI and is associated with the development of CKD during the first year.

SummaryBackground Combined heart and liver transplantation (CHLT) in the pediatric population involves a complex group of patients, many of whom have palliated congenital heart disease (CHD) involving single ventricle physiology. Objective The purpose of this study was to describe the perioperative management of pediatric patients undergoing CHLT at a single institution and to identify management strategies that may be used to optimize perioperative care. Methods We did a retrospective database review of all patients receiving CHLT at a children's hospital between 2006 and 2014. Information collected included preoperative characteristics, intraoperative management, blood transfusions, and postoperative morbidity and mortality. Results Five pediatric CHLTs were performed over an 8-year period. All patients had a history of complex CHD with multiple sternotomies, three of whom had failing Fontan physiology. Patient age ranged from 7 to 23 years and weight from 29.5 to 68.5 kg. All CHLTs were performed using an en-bloc technique where both the donor heart and liver were implanted together on cardiopulmonary bypass (CPB). The median operating room time was 14.25 h, median CPB time was 3.58 h, and median donor ischemia time was 4.13 h. Patients separated from CPB on dopamine, epinephrine, and milrinone infusions and two required inhaled nitric oxide. All patients received a massive intraoperative blood transfusion post CPB with amounts ranging from one to three times the patient's estimated blood volume. The patient who required the most transfusions was in decompensated heart and liver failure preoperatively. Four of the five patients received an antifibrinolytic agent as well as a procoagulant (prothrombin complex concentrate or recombinant activated Factor VII) to assist with hemostasis. There were no 30-day thromboembolic events detected. Postoperatively the median length of mechanical ventilation, ICU stay and stay to hospital discharge was 4, 8, and 37 days, respectively. All patients are alive and free from allograft rejection at this time. Conclusion Combined heart and liver transplantation in the pediatric population involves a complex group of patients with unique perioperative challenges. Successful management starts with thorough preoperative planning and communication and involves strategies to deal with massive intraoperative hemorrhage and coagulopathy in addition to protecting and supporting the transplanted heart and liver and meticulous surgical technique. An integrated multidisciplinary team approach is the cornerstone for successful outcomes.

Despite greatly improved survival in pediatric patients with end-stage heart failure through the use of ventricular assist devices (VADs), heart failure ultimately remains a life-threatening disease with a significant symptom burden. With increased demand for donor organs, liberalizing the boundaries of case complexity, and the introduction of destination therapy in children, more children can be expected to die while on mechanical support. Despite this trend, guidelines on the ethical and pragmatic issues of compassionate deactivation of VAD support in children are strikingly absent. As VAD support for pediatric patients increases in frequency, the pediatric heart failure and palliative care communities must work toward establishing guidelines to clarify the complex issues surrounding compassionate deactivation. Patient, family and clinician attitudes must be ascertained and education regarding the psychological, legal and ethical issues should be provided. Furthermore, pediatric-specific planning documents for use before VAD implantation as well as deactivation checklists should be developed to assist with decision-making at critical points during the illness trajectory. Herein we review the relevant literature regarding compassionate deactivation with a specific focus on issues related to children.

Alström Syndrome (AS) is a rare autosomal recessive disorder caused by mutations in the ALMS1 gene. We report monozygotic twin infants who presented concurrently with symptoms of congestive heart failure (CHF) due to dilated cardiomyopathy (DCM). Following their initial presentation, one twin improved both echocardiographically and functionally while the other twin showed a progressive decline in ventricular function and worsening CHF symptoms requiring multiple hospitalizations and augmentation of heart failure therapy. Concordant findings of nystagmus, vision loss, and developmental delay were noted in both twins. Additional discordant findings included obesity and signs of insulin resistance in one twin. Genetic testing on one sibling confirmed AS. These twins underscore the importance of considering AS in any child presenting with DCM, particularly in infancy, and highlights that, even in monozygotic twins, the clinical course of AS is variable with regard to both the cardiac and non-cardiac manifestations of the disease.

Purpose Routine surveillance biopsy (RSB) is performed to monitor for asymptomatic acute rejection (AR) after heart transplantation (HT). The optimal frequency of RSB in pediatrics is unknown and variation in RSB frequency is high. We hypothesized that higher frequency RSB centers have increased rates of AR and resource utilization, but no difference in graft survival. Methods We utilized a linked database (2002-2016) between Pediatric Health Information System (PHIS) and Scientific Registry of Transplant Recipients (SRTR). We designated centers as high- and low-RSB based on the observed median number of first-year biopsies (from procedural ICD and CPT coding) in recipients assumed to be standard risk: greater than 1 year old without rejection in their first year. The highest tertile of centers were classified as high-RSB and compared to the lowest two-thirds (low-RSB). We then compared outcomes amongst all primary recipients aged 0-21 by center type. Outcomes were HT admission length of stay (LOS), incidence of AR at one year, graft survival, estimated HT admission cost, and total cost in the first year. Regression analysis was used to adjust for potential confounders. Results We compared 834 patients at 10 high-RSB centers to 2,033 patients at 19 low-RSB centers. Baseline characteristics were similar except high-RSB center recipients had increased use of ventilator or ECMO at HT (23 vs 18%, p=0.039), fewer hispanic/asian/other race (20 vs 24% p=0.005), fewer positive crossmatch (13% vs 17% p=0.007). High-RSB centers had higher first-year incidence of all AR vs low-RSBs (36% vs 29%, p=0.001; OR 1.52 [95% CI 1.24-1.85] p Conclusion Centers with a high-frequency biopsy strategy during the first year diagnose AR more often during the first year after HT but have similar incidence of treated rejection. Early graft survival is unchanged. A low-frequency biopsy strategy is associated with lower cost. To determine the optimal biopsy frequency additional data are needed on long-term graft survival and graft performance.

BACKGROUND The use of ventricular assist devices (VADs) in children with heart failure may be of particular benefit to those with accompanying renal failure, as improved renal function is seen in some, but not all recipients. We hypothesized that persistent renal dysfunction at 7 days and/or 1 month after VAD implantation would predict chronic kidney disease (CKD) 1 year after heart transplantation (HT). METHODS Linkage analysis of all VAD patients enrolled in both the PEDIMACS and PHTS registries between 2012 and 2016. Persistent acute kidney injury (P-AKI), defined as a serum creatinine ≥1.5× baseline, was assessed at post-implant day 7. Estimated glomerular filtration rate (eGFR) was determined at implant, 30 days thereafter, and 12 months post-HT. Pre-implant eGFR, eGFR normalization (to ≥90 mL/min/1.73 m2 ), and P-AKI were used to predict post-HT CKD (eGFR