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The Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs), supported by the Society of Thoracic Surgeons, provides detailed information on pediatric patients supported with ventricular assist devices (VADs).From September 19, 2012, to December 31, 2021, there were 1,355 devices in 1,109 patients (19 years) from 42 North American Hospitals.Cardiomyopathy was the most common underlying etiology (58%), followed by congenital heart disease (CHD) (26%) and myocarditis (9%). Regarding device type, implantable continuous (IC) VADs were most common at 40%, followed by paracorporeal pulsatile (PP) (28%), and paracorporeal continuous (PC) (27%). Baseline demographics differed, with the PC cohort being younger, smaller, more complex (ie. CHD), and sicker at implant (P.0001). At six months post-VAD implantation, a favorable outcome (transplant, recovery, or alive on device) was achieved in 84% of patients, which was greatest among those on IC VADs (92%) and least for PC VADs (69%). Adverse events (AEs) were not uncommon, with non-gastrointestinal bleeding (incidence of 14%) and neurological dysfunction (11% [Stroke 4%]), within 2 weeks post implant being the most prevalent. Stroke and bleeding had negative impacts on overall survival (p=0.002 and p0.001, respectively).This Sixth Pedimacs Report demonstrates the continued evolution of the pediatric field. The complexity of cardiac physiologies and anatomical constraint mandates the need for multiple types of devices utilized (PC, PP, IC). Detailed analyses of each device type in this report provide valuable information to further advance the care of this challenging and vulnerable population.

Single ventricle (SV) patients with pulmonary vascular disease (SV-PVD) are considered poor surgical candidates for Glenn or Fontan palliation. Given limited options for Stage 1 (S1) and Stage 2 (S2) SV patients with SV-PVD, we report on the use of subcutaneous treprostinil (TRE) to treat SV-PVD in this population. This single-center, retrospective cohort study examined SV patients who were not candidates for subsequent surgical palliation due to SV-PVD and were treated with TRE. The primary outcome was ability to progress to the next surgical stage; secondary outcomes included changes in hemodynamics after TRE initiation. Between 3/2014 and 8/2021, 17 SV patients received TRE for SV-PVD: 11 after S1 and 6 after S2 (median PVR 4.1 [IQR 3.2-4.8] WU*m

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.

Background Children 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 Results This 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). Conclusions Waitlist 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.

Sudden cardiac arrest (SCA) is a prevailing cause of mortality after pediatric heart transplant (HT) but remains understudied. We analyzed the incidence, outcomes, and risk factors for SCA at our center.Retrospective review of all pediatric HT patients at our center from January 1, 2009 to January 1, 2021. SCA was defined as an abrupt loss of cardiac function requiring cardiopulmonary resuscitation and/or mechanical circulatory support (MCS). Events that occurred in the setting of limited resuscitative wishes, or while on MCS were excluded. Patient characteristics and risk factors were analyzed.Fourteen of 254 (6%) experienced SCA at a median of 3 (1, 4) years post-HT. Seven (50%) events occurred out-of-hospital. Eleven (79%) died from their initial event, 2 (18%) after failure to separate from extracorporeal membrane (ECMO). In univariate analysis, black race, younger donor age, prior acute cellular rejection (ACR) episode, pacemaker and/or ICD in place, and pre-mortem diagnosis of allograft vasculopathy were associated with SCA (P = .003-0.02). In multivariable analysis, history of ACR, younger donor age, and black race retained significance. [OR = 6.3, 95% CI: 1.6-25.4, P = .01], [OR = 0.9, 95% CI: 0.8-1, P = .04], and [OR = 7.3, 95% CI: 1.1-49.9, P = .04], respectively. SCA occurred in 3 patients with a functioning ICD or pacemaker, which failed to restore a perfusing rhythm.SCA occurs relatively early after pediatric HT and is usually fatal. Half of events happen at home. Those who received younger donors, have a history of ACR, or are of black race are at increased risk. ICDs/pacemakers may offer limited protection.

The Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs) provides detailed information on pediatric patients supported with ventricular assist devices (VADs).From September 19, 2012, to December 31, 2020, 1229 devices in 1011 patients were reported to the registry from 47 North American Hospitals in patients aged younger than 19 years.Cardiomyopathy was the most common underlying etiology (58%), followed by congenital heart disease (CHD; 25%) and myocarditis (10%). The most common devices implanted were implantable continuous (IC; 419 [41%]), followed by paracorporeal pulsatile (PP; 269 [27%]), paracorporeal continuous (PC; 263 [26%]), and percutaneous (53 [5%]). Overall, at 6 months after VAD implantation, 83% had a positive outcome (transplant, explant, or alive on device). The freedom from stroke at 3 months was highest in IC VADs (93%), compared with PP VADs (84%) and with PC VADs (75%). There were differences in survival by device type, with patients on IC VADs having the best overall survival and those on PC having the lowest overall survival, though the patient populations being supported by each VAD type differed significantly from each other.This Fifth Pedimacs Report demonstrates the continued robust growth of VADs in the pediatric community, now with more than 1000 patients reported to the registry. The multiple available device types (PC, PP, IC) serve different populations with different pre-VAD risk profiles, which may account for differences in survival and adverse events between device types.

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.

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.

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 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 Studies suggest that pediatric heart transplant (HT) waitlist mortality has declined. The impact of factors like refinements to the heart allocation system, patient selection, greater ABO incompatible (ABO-I) HT and VAD support are unknown. We examined the 20-year trend in waitlist mortality to identify factors associated with declining mortality and whether allocational inefficiencies persist. Methods All children Results Overall 11,374 patients met inclusion criteria (3,248 in Era 1; 5,378 in Era 2; 2,748 in Era 3). Waitlist mortality declined significantly across eras (21%, 17%, 13%, P Conclusion Pediatric HT waitlist mortality has declined significantly over the past 20 years. There is evidence to suggest that greater VAD use, revisions to organ allocation, refinements in patient selection and ABO-I transplant may all contribute. Organ allocation inefficiencies persist under the current allocation system suggesting opportunities for allocation improvement may still exist.

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.

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 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.

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 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.

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 Data suggest that pediatric heart transplant (HT) centers can reduce waitlist time by expanding donor catchment vis expanded parameters including the maximal donor weight range. Contrary to donor weight ranges, little is known about the effect of increasing the donor distance (DD) range. We sought to determine whether increasing the DD range can reduce waitlist time and how well actual DD predicts ischemic time (IT). Methods All US children Results Among 4,240 children who met study criteria, the median age was 2 (IQR 0, 11) years, weight 12 (6, 35) kg, 53% had CHD. Centers varied considerably in their maximal DD range (1000-10,000 miles); median 1500 miles (Figure A). Overall, 86% of donors originated from ≤500 miles; 97% ≤1,000 miles (Figures A & B) with sharp drop-offs at 500 and 1000 miles (Figure B). After adjusting for patient factors, maximal DD range was associated with a shorter waitlist time. The correlation between actual DD and IT is fair (R=0.69) but explains only half (R2=0.49) of the variability in IT. Conclusion Pediatric HT centers vary considerably in their maximal donor distance ranges, though most donors still fall within 500-1000 miles of recipients. Increasing the maximal DD range appears is associated with a shorter waitlist time. Actual DD explains only half of the variability in IT. Further research is needed to understand the optimal regional sharing distance for organ allocation and whether contemporary navigational software could better predict IT than the linear distance to the donor hospital.

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.

Purpose 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, while recent literature on critical congenital heart disease and other life-threatening pediatric diseases suggest clear benefit of early PPC involvement. In this study we aimed to characterize the extend of palliative care service's participation in the care of patients requiring VAD placement at our institution. Methods A single-center retrospective chart review analyzing all VAD patients at a large pediatric center over a 4 year period was performed and assessed incidence, timing and extend of palliative care subspecialty involvement. Results Between January 2014 and December 2017, 55 HF patients underwent VAD implantation at our institution. Palliative care utilization in patient care steadily increased over consecutive years (2014 - Conclusion PPC services have been utilized in pediatric VAD patients with increasing frequency at our institution in recent years. Early involvement with advanced heart failure patients, prior to VAD implant, occurred in the majority of patients. While total numbers are small, palliative care support appears to lead to more frequent discussion of goals of care and advanced directives.

Background Single-center data on pediatric heart transplantation spanning long time frames is sparse. We attempted to analyze how risk profile and pediatric heart transplant survival outcomes at a large center changed over time. Methods We divided 320 pediatric heart transplants done at Stanford University between 1974 and 2014 into three groups by era: the first 20 years (95 transplants), the subsequent 10 years (87 transplants), and the most recent 10 years (138 transplants). Differences in age at transplant, indication, mechanical support, and survival were analyzed. Results Follow-up was 100% complete. Average age at time of transplantation was 10.4 years, 11.9 years, and 5.6 years in eras 1, 2, and 3, respectively. The percentage of infants who received transplants by era was 21%, 7%, and 18%, respectively. The indication of end-stage congenital heart disease vs cardiomyopathy was 24%, 22%, and 49%, respectively. Only 1 patient (1%) was on mechanical support at transplant in era 1 compared with 15% in era 2 and 30% in era 3. Overall survival was 72% at 5 years and 57% at 10 years. Long-term survival increased significantly with each subsequent era. Patients with cardiomyopathy generally had a survival advantage over those with congenital heart disease. Conclusions The risk profile of pediatric transplant patients in our institution has increased over time. In the last 10 years, median age has decreased and ventricular assist device support has increased dramatically. Transplantation for end-stage congenital heart disease is increasingly common. Despite this, long-term survival has significantly and consistently improved.

Background The evolution of pharmacologic therapies and mechanical support including ventricular assist devices (VADs) has broadened the scope of care available to children with advanced heart failure. At the present time, there are only limited means of quantifying disease severity or the concomitant morbidity for this population. This study describes the development of a novel pediatric treatment intensity score (TIS), designed to quantify the burden of illness and clinical trajectory in children on VAD support. Methods There were 5 clinical domains assessed: nutrition, respiratory support, activity level, cardiovascular medications, and care environment. A scale was developed through expert consensus. Higher scores indicate greater morbidity as reflected by intensity of medical management. To evaluate feasibility and face validity, the TIS was applied retrospectively to a subset of pediatric inpatients with VADs. The Bland-Altman method was used to assess limits of agreement. Results The study comprised 39 patients with 42 implantations. Bland-Altman interobserver and intraobserver comparisons showed good agreement (mean differences in scores of 0.02, limits of agreement ±0.12). Trends in TIS were concordant with the overall clinical impression of improvement. Scores remained ≥0.6 preceding VAD implantation and peaked at 0.71 3 days after VAD implantation. Conclusions We describe a pediatric VAD scoring tool, to assess global patient morbidity and clinical recovery. We demonstrate feasibility of using this TIS in a test population of inpatients on VAD support.

Young adult solid organ transplant recipients who transfer from pediatric to adult care experience poor outcomes related to decreased adherence to the medical regimen. Our pilot trial for young adults who had heart transplant (HT) who transfer to adult care tests an intervention focused on increasing HT knowledge, self-management and self-advocacy skills, and enhancing support, as compared to usual care. We report baseline findings between groups regarding (1) patient-level outcomes and (2) components of the intervention. From 3/14 to 9/16, 88 subjects enrolled and randomized to intervention (n = 43) or usual care (n = 45) at six pediatric HT centers. Patient self-report questionnaires and medical records data were collected at baseline, and 3 and 6 months after transfer. For this report, baseline findings (at enrollment and prior to transfer to adult care) were analyzed using Chi-square and t-tests. Level of significance was p

To evaluate associations between haemodynamic profiles and symptoms, end-organ function and outcome in children listed for heart transplantation.Children18 years listed for heart transplant between 1993 and 2013 with cardiac catheterization data [pulmonary capillary wedge pressure (PCWP), right atrial pressure (RAP), and cardiac index (CI)] in the Pediatric Heart Transplant Study database were included. Outcomes were New York Heart Association (NYHA)/Ross classification, renal and hepatic dysfunction, and death or clinical deterioration while on waitlist. Among 1059 children analysed, median age was 6.9 years and 46% had dilated cardiomyopathy. Overall, 58% had congestion (PCWP 15 mmHg), 28% had severe congestion (PCWP 22 mmHg), and 22% low cardiac output (CI 2.2 L/min/m2). Twenty-one per cent met the primary outcome of death (9%) or clinical deterioration (12%). In multivariable analysis, worse NYHA/Ross classification was associated with increased PCWP [odds ratio (OR) 1.03, 95% confidence interval (95% CI) 1.01-1.07, P = 0.01], renal dysfunction with increased RAP (OR 1.04, 95% CI 1.01-1.08, P = 0.007), and hepatic dysfunction with both increased PCWP (OR 1.03, 95% CI 1.01-1.06, P 0.001) and increased RAP (OR 1.09, 95% CI 1.06-1.12, P 0.001). There were no associations with low output. Death or clinical deterioration was associated with severe congestion (OR 1.6, 95% CI 1.2-2.2, P = 0.002), but not with CI alone. However, children with both low output and severe congestion were at highest risk (OR 1.9, 95% CI 1.1-3.5, P = 0.03).Congestion is more common than low cardiac output in children with end-stage heart failure and correlates with NYHA/Ross classification and end-organ dysfunction. Children with both congestion and low output have the highest risk of death or clinical deterioration.

Structured rehabilitation programs in adults after ventricular assist device (VAD) placement result in improvements in physical function and exercise capacity, and have been shown to improve survival and accelerate post-transplant recovery. The objective of this study was to determine the safety and feasibility of an acute inpatient rehabilitation program for children utilizing standardized, age-appropriate, family-centered care pathways after paracorporeal VAD placement in both the ICU and acute-care inpatient settings.Between November 12, 2010 and March 15, 2013, 17 patients were referred to therapy after VAD implantation, 14 of whom were medically stable enough to participate. Beginning in the ICU, a structured physical and occupational therapy program was implemented utilizing novel age-appropriate, standardized care pathways for infants (age1 year) and children (age 1 to 12 years). The infant and child pathways consisted of 8 and 10 goals, respectively. Retrospective review was conducted to ascertain the number of phases achieved per patient. Adverse events, defined as bleeding, physiologic instability, stroke, or device disruption during therapy, were also analyzed.The median age was 1.1 (range 0.5 to 14.4) years in the 14 patients considered medically stable enough to participate in rehabilitation. Nine of them were female. Eight patients participated in the infant standardized care pathway (SCP) and 6 participated in the child SCP. Seven patients were on biventricular support. Twelve patients were transplanted and survived. Two patients died while awaiting transplantation. There were 1,473 total days on the VAD (range 40 to 229 days). The median time to extubation was 2 days (range 1 to 8) and the median ICU stay was 6.5 days (range 3 to 152). Eleven patients achieved all goals of the SCP, including all of the patients in the child group. For the infant group, 5 patients achieved all goals of the SCP (range 5 to 8), and all but 1 patient achieved at least 7 goals of the SCP. There were no adverse events related to therapy.Standardized, family-centered inpatient rehabilitation care paths are safe for infants and children after paracorporeal device placement. Structured rehabilitation goals can be achieved by the majority of pediatric patients during VAD support. Early mobilization and inpatient rehabilitation in this cohort promotes normalization of function while awaiting cardiac transplantation.

Purpose Left ventricular assist device (LVAD) outcomes for hypertrophic (HCM) or restrictive cardiomyopathy (RCM) with a small LV are unsatisfactory due to difficulty draining via an LV apical cannula. We developed a new transeptal cannulation technique to decompress the left atrium where the atrial septum is cannulated via the right atrium. Methods Retrospective review of our institutional experience with LVAD/BiVAD implantation in HCM or RCM patients from October 2016 to Aug 2018. Outcomes following implantation were analyzed, including subsequent interventions, quality of VAD output, and patient outcomes. Results In total, 5 patients underwent LVAD implantation with trans-septal left-atrial cannulation techniques (HCM = 4 patients, RCM =1). Two patients received Berlin Heart BiVADs, 1 received a Berlin Heart LVAD, 1 patient received PediMag BiVADs, and 1 patient received a Heartware LVAD. Total support days were 485 days. Three patients underwent successful heart transplant after 275, 111 and 62 days of support. One neonate with HCM died from sepsis 27 days after PediMag BiVAD placement. One RCM patient died 10 days after Berlin Heart BiVAD placement following extracorporeal membrane oxygenation due to ARDS. Total survival rate is 60%. All three survivors did not develop any neurological deficits or complications related to thrombus and were discharged home after heart transplant. Conclusion This novel trans-septal left-atrial LVAD cannulation strategy is a viable alternative cannulation technique for HCM or RCM patients with a small left ventricular cavity. This technique can be applied to a variety of pediatric and adult devices in children ranging from infants to adults.