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Research evaluating hemostatic agents for the treatment of clinically significant bleeding has been hampered by inconsistency and lack of standardized primary clinical trial outcomes. Clinical trials of hemostatic agents in both cardiac surgery and mechanical circulatory support, such as extracorporeal membrane oxygenation and ventricular assist devices, are examples of studies that lack implementation of universally accepted outcomes.A subgroup of experts convened by the National Heart, Lung, and Blood Institute and the US Department of Defense developed consensus recommendations for primary outcomes in cardiac surgery and mechanical circulatory support.For cardiac surgery the primary efficacy endpoint of total allogeneic blood products (units vs mL/kg for pediatric patients) administered intraoperatively and postoperatively through day 5 or hospital discharge is recommended. For mechanical circulatory support outside the perioperative period the recommended primary outcome for extracorporeal membrane oxygenation is a 5-point ordinal score of thrombosis and bleeding severity adapted from the Common Terminology Criteria for Adverse Events version 5.0. The recommended primary endpoint for ventricular assist device is freedom from disabling stroke (Common Terminology Criteria for Adverse Events AE ≥ grade 3) through day 180.The proposed composite risk scores could impact the design of upcoming clinical trials and enable comparability of future investigations. Harmonizing and disseminating global consensus definitions and management guidelines can also reduce patient heterogeneity that would confound standardized primary outcomes in future research.

Individuals with Fontan circulation are at risk of late mortality from both cardiac and noncardiac causes. Despite the known risk of mortality, referral indications for advanced heart failure care vary between centers, and many individuals die from Fontan circulation-related complications either after late consideration for advanced heart failure therapies or having never seen a heart failure specialist. There is a critical need for guidelines to direct appropriately timed referral for advanced heart failure consultation. The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) Fontan Committee has developed recommended thresholds for advanced heart failure referral to guide primary cardiologists. These recommendations are divided into 4 categories of clinical Fontan circulatory dysfunction including (1) cardiac/systemic ventricular dysfunction, (2) Fontan pathway dysfunction, (3) lymphatic dysfunction, and (4) extracardiac dysfunction.

High-quality evidence guiding optimal transfusion and other supportive therapies to reduce bleeding is needed to improve outcomes for patients with either severe bleeding or hemostatic disorders that are associated with poor outcomes. Alongside challenges in performing high-quality clinical trials in patient populations who are at risk of bleeding or who are actively bleeding, the interpretation of research evaluating hemostatic agents has been limited by inconsistency in the choice of primary trial outcomes. This lack of standardization of primary endpoints or outcomes decreases the ability of clinicians to assess the validity of endpoints and compare research results across studies, impairs meta-analytic efforts, and, ultimately, delays the translation of research results into clinical practice. To address this challenge, an international panel of experts was convened by the National Heart Lung and Blood Institute and the US Department of Defense on September 23 and 24, 2019, to develop expert opinion, consensus-based recommendations for primary clinical trial outcomes for pivotal trials in pediatric and adult patients with six categories in various clinical settings. This publication documents the conference proceedings from the workshop funded by the National Heart Lung and Blood Institute and the US Department of Defense that consolidated expert opinion regarding clinically meaningful outcomes across a wide range of disciplines to provide guidance for outcomes of future trials of hemostatic products and agents for patients with active bleeding.

Ventricular assist device (VAD) support for children with single ventricle (SV) heart disease remains challenging. We performed a single-center retrospective review of SV patients on VAD support and examined survival to transplant using the Kaplan-Meier method. Patients transplanted were compared with those who died on support. Between 2009 and 2017, there were 14 SV patients with 1,112 patient-days of VAD support. Stages of palliation included pre-Glenn (n = 5), Glenn (n = 5), and Fontan (n = 4). Eight patients (57%) were successfully bridged to transplant at a median 107 days. Deaths occurred early (n = 6, median 16 days) and in smaller patients (10.1 vs. 28.3 kg, P = 0.04). All Fontan patients survived to transplant, whereas only 20% of Glenn patients survived to transplant. Adverse events occurred in 79% (n = 11). Five patients met hospital discharge criteria, with two patients (one pre-Glenn, one Glenn) discharged and transplanted after 219 and 174 days of VAD support. All transplanted patients were discharged at a median 21 days posttransplant. SV patients in various stages of palliation can be successfully bridged to transplant with VAD support. With use of intracorporeal continuous-flow devices, longer-term support and hospital discharge are possible.

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.

Introduction: Gaps in insurance coverage have been associated with diminished access to health care for children with chronic illness. Continuity of coverage is associated with improved long-term clinical outcomes among adolescent heart transplant (HT) recipients, but the relationship between insurance status and post-transplant outcomes has not been described across all pediatric HT recipients. Hypothesis: HT recipients with changes in insurance status will have worse outcomes as opposed to those with continuous coverage. Methods: We queried the United Network for Organ Sharing (UNOS) registry for patients age 0-18 receiving isolated HT or heart re-transplant between 2006 and 2019 and included them in the analysis if they survived at least one year post-transplant. Patients were categorized by insurance coverage at wait listing, HT, and one year follow-up. Cox proportional hazards models were used to characterize the association between coverage pattern and long-term patient survival. Results: Among the 3,247 patients in the analysis, insurance coverage patterns included continuous private (37%), continuous public (46%), gain of private (6%), and loss of private (11%). Patients who had continuous public insurance were more likely to be Black or Hispanic, adolescent, and require ICU care. In a multivariate Cox model, continuous public insurance was associated with increased mortality risk (HR = 1.46, P = 0.014), while loss of private insurance trended towards increased risk (HR = 1.14, P = 0.014). Figure 1 illustrates Kaplan-Meier conditional survival curves according to insurance trajectory. Multivariate sub-group analysis by Black race demonstrated no differences in outcomes by coverage pattern. Conclusions: In comparison to those with continuous private insurance, having continuous public insurance is associated with higher risk of adverse outcomes in pediatric HT recipients, but it does not account for disparate outcomes in Black patients.

Background - Cardiac resynchronization therapy (CRT) studies in pediatric and/or congenital heart disease (CHD) patients have shown an improvement in ejection fraction and heart failure symptoms. However, a survival benefit of CRT in this population has not been established. This study aimed to evaluate the impact of CRT upon heart transplant-free survival in pediatric and CHD patients, using a propensity score-matched analysis. Methods - This single-center study compared CRT patients (implant date 2004-2017) and controls, matched by 1:1 propensity-score matching (PSM) using 21 comprehensive baseline indices for risk stratification. CRT patients were Results - Of 133 patients who received CRT during the study period, 84 met all study inclusion criteria. 133 controls met all criteria at an outpatient encounter. Following PSM, 63 matched CRT-control pairs were identified with no significant difference between groups across all baseline indices. Heart transplant or death occurred in 12 (19%) PSM-CRT subjects and 37 (59%) PSM-controls with a median follow-up of 2.7 years (quartiles 0.8-6.1 years). CRT was associated with markedly reduced risk of heart transplant or death (hazard ratio 0.24 [95% CI 0.12-0.46], p Conclusions - In pediatric and CHD patients with symptomatic systolic heart failure and electrical dyssynchrony, CRT was associated with improved heart transplant-free survival.

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.

In this study we sought to quantify hazards associated with various donor factors into a cumulative risk scoring system (the Pediatric Heart Donor Assessment Tool, or PH-DAT) to predict 1-year mortality after pediatric heart transplantation (PHT).PHT data with complete donor information (5,732) were randomly divided into a derivation cohort and a validation cohort (3:1). From the derivation cohort, donor-specific variables associated with 1-year mortality (exploratory p-value0.2) were incorporated into a multivariate logistic regression model. Scores were assigned to independent predictors (p0.05) based on relative odds ratios (ORs).The final model had an acceptable predictive value (c-statistic = 0.62). The significant 5 variables (ischemic time, stroke as the cause of death, donor-to-recipient height ratio, donor left ventricular ejection fraction, glomerular filtration rate) were used for the scoring system. The validation cohort demonstrated a strong correlation between the observed and expected rates of 1-year mortality (r = 0.87). The risk of 1-year mortality increases by 11% (OR 1.11 [1.08 to 1.14]; p0.001) in the derivation cohort and 9% (OR 1.09 [1.04 to 1.14]; p = 0.001) in the validation cohort with an increase of 1-point in score. Mortality risk increased 5 times from the lowest to the highest donor score in this cohort. Based on this model, a donor score range of 10 to 28 predicted 1-year recipient mortality of 11% to 31%.This novel pediatric-specific, donor risk scoring system appears capable of predicting post-transplant mortality. Although the PH-DAT may benefit organ allocation and assessment of recipient risk while controlling for donor risk, prospective validation of this model is warranted.

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.

Objectives The objective was to review the use of Impella devices (Abiomed Inc, Danvers, MA) for temporary circulatory support in pediatric and adolescent patients (age ≤ 21 yrs). Background Options for minimally invasive circulatory support in children are limited, and published data are confined to case reports and small case series. Methods This was a retrospective, multicenter review of Impella implants in pediatric and adolescent patients from 2009-15, using standardized data collection and INTERMACS definitions. Results A total of 39 implants were performed in 38 patients from 16 centers. Median age and weight were 16 yrs (4–21 yrs) and 62 kg (15–134 kg). The primary indication for implant was cardiogenic shock in 28 patients (72%). Cardiac allograft rejection, myocarditis, or cardiomyopathy were the underlying diagnosis in 23 patients (59%); 11 patients had congenital heart disease. The median duration of support was 45 hr (1–1224 hr). Indications for explant included ventricular recovery in 16 patients, transition to another device in 12, death in 5, and transplant in 1. Survival was 85% at 7 days and 68% at 30 days. Major adverse events occurred in 8 patients: hemolysis in 3, bleeding in 2, stroke in 1 (unclear if related to Impella), sepsis in 1, and critical leg ischemia in 1. An increase in aortic regurgitation was noted in three patients, with no evidence of valve injury. Conclusion Temporary circulatory support with Impella devices is feasible in pediatric and adolescent patients, with acceptable risk profiles. More experience and follow up is needed to improve technical performance and patient selection. © 2017 Wiley Periodicals, Inc.

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.

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 Malnutrition is an important complication of heart failure (HF) and associated with significant mortality. The serum pre-albumin level is often performed to evaluate patient nutritional status in HF, however its association with clinical malnutrition severity has not be determined. We sought to evaluate the association between pre-albumin and malnutrition severity using contemporary definitions of malnutrition. Methods All children listed for heart transplant (HT) between 2014 and 2017 were identified using a hospital database at a single center. Clinical malnutrition severity was determined by a certified pediatric dietitian using the American Society of Parenteral and Enteral Nutrition (ASPEN) guidelines. The pre-albumin level drawn around the time of the nutritional assessment was recorded. ANOVA for K groups with the Bonferroni correction was used to compare groups. Results Among 73 children who met the inclusion criteria, the median age at nutrition evaluation was 7.8 (Q1-Q3 1.3-12.6) years, the median weight-for-age Z-score was -1.5 (-2.3, 0.1), 36% were female, and 68% had congenital heart disease. Overall, malnutrition status by ASPEN guidelines was mild (25%), moderate (30%), severe (21%), or normal or obese (24%). Among the 73 subjects, the mean pre-albumin level was 20 (SD 10) mg/dl including 50% classified as normal. By ANOVA, there was no association between pre-albumin and clinical nutrition severity in children with HF (Figure). Variation within individual patients was high. Conclusion Pre-albumin does not appear to be a meaningful marker of malnutrition status in children with advanced heart failure. Pre-albumin levels vary markedly across malnutrition groups and within individual patients at a constant nutrition status, variability which may reflect its tendency to rise and fall as an acute phase reactant. Alternative strategies for estimating nutritional status are warranted.

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 Several centers have considered the potential benefits of atrial inflow cannulation to provide mechanical circulatory support (MCS) among pediatric patients with small or restrictive ventricles particularly in those with potential for myocardial recovery. Limited pediatric data are available on contemporary outcomes of atrial cannulation. We sought to describe the characteristics, complications, and outcomes of children supported with atrial cannulation using the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) ventricular assist device (VAD) database. Methods Data were collected from the ACTION VAD database for all patients who underwent VAD implantation via atrial cannulation from 8/16/2012 to 9/8/2020. Patient characteristics, VAD types, complications, and outcomes were analyzed. Results Forty-one patients met the study criteria with 52 implants. Median age was 3.6 years (range 0.02 - 25.32), weight 13.6 kg (2.7-106), and BSA 0.6 (0.15 - 2.2). Diagnoses included dilated cardiomyopathy (42%), congenital heart disease (37%), transplant graft dysfunction (7%), restrictive and hypertrophic cardiomyopathies (5% each). VAD indications were bridge to decision (42%), bridge to transplant (42%), and bridge to recovery (17%). Eighty-four percent of patients were INTERMACS 1 or 2, 44% were on ECMO, and 63% were mechanically ventilated. Devices utilized included Berlin Heart Excor (40%), paracorporeal continuous flow devices (38%), Heartware (19%) and one Heartmate 3. Median support duration was 43.5 days (range 0-307). Overall mortality was 22%. Twenty patients (49%) were successfully transplanted, 7 (17%) recovered, and 5 (12%) are still alive on the device. Adverse events included major bleeding (24%), stroke (12%), sepsis (10%), right heart failure requiring RVAD (5%), and one instance of pump thrombosis. Conclusion Atrial cannulation in pediatric MCS can be performed across a variety of anatomic substrates and age ranges with outcomes and complication rates that are comparable to left ventricular cannulation strategies. This method may be advantageous in certain circumstances including patients with small or restrictive ventricles, potential for myocardial recovery, or multiple prior sternotomies to minimize surgical dissection. Further studies are needed to delineate the ideal patient population and benefits of varying atrial cannulation techniques.

Purpose As the use of pediatric ventricular assist devices (VAD) has increased, more children are being supported with VADs for single-ventricle heart disease (SVD). Little is known about outcomes for this rapidly growing population of advanced HF patients. We sought to examine trends in VAD use for SVD and to assess outcomes. Methods Organ Procurement and Transplant Network (OPTN) data were used to identify all children ≤21 years who underwent VAD placement between 2004 and 2020 for SVD. Cox proportional hazard modeling was used to identify risk factors for mortality defined as death or clinical deterioration. Results Of 1955 children with SVD, 315 were supported with an MCS device (145 SVADs and 170 ECMO only). Of the SVADs, 142 (97%) received an SVAD alone as the primary device, 2 (1%) received BIVADs and 1 (1%) a TAH. The most common VAD brands were the Berlin Heart EXCOR (N=44, 30%), the CentriMag/PediMag (N=40, 28%), Heartware HVAD (N=35, 24%), and the CentriMag/PediMag (ZZ%) and the Heartmate III (N=8, 6%). Since 2011 (when complete VAD survival data become available), overall survival to HT was 62% of whom 58% reached transplant; 38% died or deteriorated, and 2% recovered. Survival was significantly worse compared to pediatric VAD patients supported for DCM and comparable to patients supported for 2-ventricle CHD (P=0.79) (Find). Survival to transplant was highest for adult continuous flow devices (77%) and lower for the CentriMag/PediMag system (63%) and the Berlin Heart EXCOR (63%). Conclusion VAD outcomes for bridge to transplant for single-ventricle heart disease patients are similar to other forms of 2-ventricle CHD but inferior to DCM. The highest survival appears to be in patients receiving adult CF devices with room for improvement in smaller patients receiving non-dischargeable devices.

Purpose No valid, reliable, and publicly available patient-reported outcome measure (PROM) exists to assess the pediatric heart failure (HF) experience. We sought to understand this experience in order to develop a PROM that can reliably capture and track outcomes for adolescent patients. Methods Semi-structured individual or group interviews were conducted at two pediatric HF and transplant centers in the US. Patient ages 12-21 who had a record of symptomatic HF in the past 2 years were eligible to participate. Caregivers of participants were also eligible. Symptom experiences and their impact on daily activities were explored. Transcripts were analyzed by members of a multidisciplinary team using thematic analysis. Results 16 patients and 9 caregivers participated. 22 completed individual interviews in-person or by phone, and 3 participated in a web-based focus group. Patient participants were 31% male, and median age was 16.5 years. 31% (n=5) had HF from cardiomyopathy and 69% (n=11) had HF due to congenital heart disease, with 7 having single ventricle physiology. 5 participants were interviewed post-transplant. Preliminary analysis revealed consistent themes across interviews. Common symptoms included fatigue, shortness of breath, and chest discomfort. Symptoms limited ability to perform daily tasks (e.g. climbing stairs at school), participate in certain extracurricular activities (e.g. sports, dance) and keep up with peers. Participants described social and emotional impacts from being treated differently by others due to surgical scars, medical devices, or functional limitations. They also reported burden of frequent medical visits and treatments, and expressed worry and uncertainty about the need for future interventions. Caregivers reported similar impacts on patient function and wellbeing, and they further described social exclusion by peers and anxiety about the future (e.g. limited life expectancy or career limitations). Conclusion The unique personal and social impacts of HF symptoms on adolescents and young adults may necessitate development of unique items for PRO measurement in this population. These findings will be used to draft a developmentally-relevant PROM that will subsequently be tested in this population and validated for use in clinical care and regulatory evaluation of new medical products.

Ventricular assist devices (VADs) have been used in children on an increasing basis in recent years. One-year survival rates are now80% in multiple reports. In this report we describe adverse events experienced by children with durable ventricular assist devices, using a national-level registry (PediMACS, a component of INTERMACS) METHODS: PediMACS is a national registry that contains clinical data on patients who are19 years of age at the time of VAD implantation. Data collection concludes at the time of VAD explantation. All FDA-approved devices are included. PediMACS was launched on September 1, 2012, and this report includes all data from launch until August 2014. Adverse events were coded with a uniform, pre-specified set of definitions.This report comprises data from 200 patients with a median age of 11 years (range 11 days to 18 years), and total follow-up of 783 patient-months. The diagnoses were cardiomyopathy (n = 146, 73%), myocarditis (n = 17, 9%), congenital heart disease (n = 35, 18%) and other (n = 2, 1%). Pulsatile-flow devices were used in 91 patients (45%) and continuous-flow devices in 109 patients (55%). Actuarial survival was 81% at 6 months. There were 418 adverse events reported. The most frequent events were device malfunction (n = 79), infection (n = 78), neurologic dysfunction (n = 52) and bleeding (n = 68). Together, these accounted for 277 events, 66% of the total. Although 38% of patients had no reported adverse event and 16% of patients had ≥5 adverse events. Adverse events occurred at all time-points after implantation, but were most likely to occur in the first 30 days. For continuous-flow devices, there were broad similarities in adverse event rates between this cohort and historic rates from the INTERMACS population.In this study cohort, the overall rate of early adverse events (within 90 days of implantation) was 86.3 events per 100 patient-months, and of late adverse events it was 20.4 events per 100 patient-months. The most common adverse events in recipients of pulsatile VADs were device malfunction, neurologic dysfunction, bleeding and infection. For continuous-flow VADs, the most common adverse events were infection, bleeding, cardiac arrhythmia, neurologic dysfunction and respiratory failure. Compared with an adult INTERMACS cohort, the overall rate and distribution of adverse events appears similar.

While most children can be supported with a left ventricular assist device (LVAD) alone, a minority require BIVAD support. We sought to examine recent trends in BIVAD support in children to support decision-making. OPTN data were used to identify all children ≤21 years who underwent BIVAD while

Due to limited and conflicting data in pediatric patients, long-term routine surveillance endomyocardial biopsy (RSB) in pediatric heart transplant (HT) remains controversial. We sought to characterize the rate of positive RSB and determine factors associated with RSB-detected rejection. Records of patients transplanted at a single institution from 1995 to 2015 with >2 year of post-HT biopsy data were reviewed for RSB-detected rejections occurring >2 year post-HT. We illustrated the trajectory of significant rejections (ISHLT Grade ≥3A/2R) among total RSB performed over time and used multivariable logistic regression to model the association between time and risk of rejection. We estimated Kaplan-Meier freedom from rejection rates by patient characteristics and used the log-rank test to assess differences in rejection probabilities. We identified the best-fitting Cox proportional hazards regression model. In 140 patients, 86% did not have any episodes of significant RSB-detected rejection >2 year post-HT. The overall empirical rate of RSB-detected rejection >2 year post-HT was 2.9/100 patient-years. The percentage of rejection among 815 RSB was 2.6% and remained stable over time. Years since transplant remained unassociated with rejection risk after adjusting for patient characteristics (OR = 0.98; 95% CI 0.78-1.23; P = 0.86). Older age at HT was the only factor that remained significantly associated with risk of RSB-detected rejection under multivariable Cox analysis (P = 0.008). Most pediatric patients did not have RSB-detected rejection beyond 2 years post-HT, and the majority of those who did were older at time of HT. Indiscriminate long-term RSB in pediatric heart transplant should be reconsidered given the low rate of detected rejection.

Infections in adult ventricular assist device patients increase subsequent mortality and stroke risk. Less is known about outcomes after infections in younger patients, where diabetes and obesity, risk factors associated with poor outcomes, are less prevalent. The purpose of this study was to examine outcomes after infections in adolescents and young adults with continuous-flow left ventricular assist devices (VAD) bridged to transplant. From Pediatric Interagency Registry for Mechanically Assisted Circulatory Support and Interagency Registry for Mechanical Circulatory Support registries, we identified patients aged 12-29 years with continuous-flow VADs implanted as bridged to transplant from September 2012 to March 2016. The primary predictor variable was first reported infection. The primary outcome was death on VAD support; secondary outcome was clinical stroke. Kaplan-Meier and Cox proportional hazard methods were used to compare outcomes between patients before or without infection and patients after infection. Ninety-two adolescents (12-18 years of age) and 224 young adults (19-29 years of age) with 3,748 patient-months of follow-up were included. Adolescents were smaller (body surface area 1.7 vs. 2.0 m, p < 0.01) and implanted at higher Interagency Registry for Mechanical Circulatory Support profiles (p = 0.005); there were no differences in diabetes and obesity, and survival on VAD was similar (p = 0.22). Among adolescents but not young adults, mortality increased after infection (hazard ratio 8.2, 95% confidence interval 1.6-42.6, p = 0.01). In contrast, stroke risk increased after infection in young adults (hazard ratio 3.1, 95% confidence interval 1.3-7.6, p = 0.01) but not in adolescents. Despite similar underlying risk factors, adolescents have increased mortality after infections, whereas young adults have increased strokes after infections. Both pre- and postimplant factors likely contribute to the discrepancy in outcomes between the two age cohorts.

Background— Current organ allocation algorithms direct hearts to the sickest recipients to mitigate death while waiting. This may result in lower post-transplant (Tx) survival for high-risk candidates mandating close examination to determine the appropriateness of different technologies as a bridge to Tx. Methods and Results— We analyzed all patients (P P Conclusions— Pediatric patients requiring ECMO support before heart Tx have poor outcomes. Prioritization of donor hearts to children waitlisted on ECMO warrants careful consideration because of ECMO’s high pre- and post-Tx mortality.

Background— Pediatric data on the impact of pre–heart transplantation (HTx) risk factors on early post-HTx outcomes remain inconclusive. Thus, among patients with previous congenital heart disease or cardiomyopathy, disease-specific risk models for graft loss were developed with the use pre-HTx recipient and donor characteristics. Methods and Results— Patients enrolled in the Pediatric Heart Transplant Study (PHTS) from 1996 to 2006 were stratified by pre-HTx diagnosis into cardiomyopathy and congenital heart disease cohorts. Logistic regression identified independent, pre-HTx risk factors. Risk models were constructed for 1-year post-HTx graft loss. Donor factors were added for model refinement. The models were validated with the use of patients transplanted from 2007 to 2009. Risk factors for graft loss were identified in patients with cardiomyopathy (n=896) and congenital heart disease (n=965). For cardiomyopathy, independent risk factors were earlier year of transplantation, nonwhite race, female sex, diagnosis other than dilated cardiomyopathy, higher blood urea nitrogen, and panel reactive antibody >10%. The recipient characteristic risk model had good accuracy in the validation cohort, with predicted versus actual survival of 97.5% versus 95.3% (C statistic, 0.73). For patients with congenital heart disease, independent risk factors were nonwhite race, history of Fontan, ventilator dependence, higher blood urea nitrogen, panel reactive antibody >10%, and lower body surface area. The risk model was less accurate, with 86.6% predicted versus 92.4% actual survival, in the validation cohort (C statistic, 0.63). Donor characteristics did not enhance model precision. Conclusions— Risk factors for 1-year post-HTx graft loss differ on the basis of pre-HTx cardiac diagnosis. Modeling effectively stratifies the risk of graft loss in patients with cardiomyopathy and may be an adjunctive tool in allocation policies and center performance metrics.

© 2015 Elsevier Inc. All rights reserved. Background Cardiac disease is a leading cause of stroke in children, yet limited data support the current stroke prevention and treatment recommendations. A multidisciplinary panel of clinicians was convened in February 2014 by the International Pediatric Stroke Study group to identify knowledge gaps and prioritize clinical research efforts for children with cardiac disease and stroke. Results Significant knowledge gaps exist, including a lack of data on stroke incidence, predictors, primary and secondary stroke prevention, hyperacute treatment, and outcome in children with cardiac disease. Commonly used diagnostic techniques including brain computed tomography and ultrasound have low rates of stroke detection, and diagnosis is frequently delayed. The challenges of research studies in this population include epidemiologic barriers to research such as small patient numbers, heterogeneity of cardiac disease, and coexistence of multiple risk factors. Based on stroke burden and study feasibility, studies involving mechanical circulatory support, single ventricle patients, early stroke detection strategies, and understanding secondary stroke risk factors and prevention are the highest research priorities over the next 5-10 years. The development of large-scale multicenter and multispecialty collaborative research is a critical next step. The designation of centers of expertise will assist in clinical care and research. Conclusions There is an urgent need for additional research to improve the quality of evidence in guideline recommendations for cardiogenic stroke in children. Although significant barriers to clinical research exist, multicenter and multispecialty collaboration is an important step toward advancing clinical care and research for children with cardiac disease and stroke.

Fluid overload (FO) is common after neonatal congenital heart surgery and may contribute to mortality and morbidity. It is unclear if the effects of FO are independent of acute kidney injury (AKI).This was a retrospective cohort study which examined neonates (age 30 days) who underwent cardiopulmonary bypass in a university-affiliated children's hospital between 20 October 2010 and 31 December 2012. Demographic information, risk adjustment for congenital heart surgery score, surgery type, cardiopulmonary bypass time, cross-clamp time, and vasoactive inotrope score were recorded. FO [(fluid in-out)/pre-operative weight] and AKI defined by Kidney Disease Improving Global Outcomes serum creatinine criteria were calculated. Outcomes were all-cause, in-hospital mortality and median postoperative hospital and intensive care unit lengths of stay.Overall, 167 neonates underwent cardiac surgery using cardiopulmonary bypass in the study period, of whom 117 met the inclusion criteria. Of the 117 neonates included in the study, 76 (65%) patients developed significant FO (10%), and 25 (21%) developed AKI ≥ Stage 2. When analyzed as FO cohorts (10%,10-20%,20% FO), patients with greater FO were more likely to have AKI (9.8 vs. 18.2 vs. 52.4%, respectively, with AKI ≥ stage 2; p = 0.013) and a higher vasoactive-inotrope score, and be premature. In the multivariable regression analyses of patients without AKI, FO was independently associated with hospital and intensive care unit lengths of stay [0.322 extra days (p = 0.029) and 0.468 extra days (p 0.001), respectively, per 1% FO increase). In all patients, FO was also associated with mortality [odds ratio 1.058 (5.8% greater odds of mortality per 1% FO increase); 95% confidence interval 1.008,1.125;p = 0.032].Fluid overload is an important independent contributor to outcomes in neonates following congenital heart surgery. Careful fluid management after cardiac surgery in neonates with and without AKI is warranted.

Extracorporeal membrane oxygenation (ECMO) has long served as the standard of care for short-term mechanical circulatory support in pediatrics. It is unknown whether newer-generation temporary circulatory support (TCS) devices afford children a meaningful survival advantage over ECMO.This study sought to determine whether bridge-to-heart transplant survival with a TCS device is superior to ECMO after adjusting for patient differences.All children ≤21 years of age listed for heart transplant from 2011 to 2015 who received a TCS device or ECMO as a bridge to transplant were identified using Organ Procurement and Transplantation Network data. Children supported with a TCS device were compared with a propensity score (PS)-matched cohort of children supported with ECMO as a bridge to transplant. The primary endpoint was Kaplan-Meier survival to transplant.The number of TCS devices implanted in children increased from ≤3 per year before 2011 to 50 in 2015. Overall, 93 patients implanted with TCS devices were included for analysis (59% left ventricular assist devices, 23% right ventricular assist devices, 18% biventricular assist devices). The most commonly used device was the CentriMag-PediMag system (65%), followed by TandemHeart (18%), Rotaflow (6%), and Impella (5%). Among 164 PS-matched patients, support duration was longer for the TCS cohort (median 19 days vs. 6 days; p 0.001), and was longest for the CentriMag-PediMag (24 days vs. 6 days; p 0.001) with 27% supported for60 days. Compared with the ECMO cohort, the PS-matched TCS cohort had longer survival to transplant (hazard ratio: 0.49; 95% confidence interval: 0.30 to 0.79) and longer overall survival (hazard ratio: 0.61; 95% confidence interval: 0.39 to 0.96), with 90-day mortality before transplant that was modestly reduced (from 45% with ECMO to 39% with TCS).The use of TCS devices in children as a bridge to transplant has risen rapidly in recent years, led by the growth of magnetically levitated centrifugal flow pumps. Compared with conventional ECMO, TCS durations are longer, and more importantly, patient survival is superior.

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.

We report an infant with hypertrophic cardiomyopathy who underwent biventricular assist device placement with two 15-mL Berlin Heart EXCOR pediatric ventricular assist devices using an alternative atrial cannulation strategy. The systemic circulation was supported by left atrium (LA) to aorta cannulation. The LA was accessed through the right atrium by extending a 6-mm EXCOR cannula with a Gore-Tex graft connected to an atrial septal defect. The pulmonary circulation was supported with cannulation of the right atrium to pulmonary artery. This alternative cannulation strategy facilitated effective biventricular support and may be applicable to other patients with hypertrophic or restrictive physiology.

ObjectivesThe aim of this study was to assess the survival benefit from heart transplantation (HT), defined as reduction in the risks for 90-day and 1-year mortality on undergoing HT close to listing, in candidates stratified by their risk for waiting list mortality.BackgroundAmong patients listed for HT, those at higher risk for death without transplantation are also at higher risk for early post-transplantation mortality.MethodsAll patients age ≥18 years listed for HT in the United States from 2007 to 2010 were analyzed. A model was developed to predict the risk for waiting list mortality within 90 days, and listed patients were stratified into 10 risk groups (deciles). All groups were followed for 1 year to assess cumulative 1-year mortality while on the waiting list. Models of 90-day and 1-year post-transplantation mortality were developed using recipient data, and these risks were estimated at listing in all listed candidates.ResultsOf 10,159 patients listed for HT, 596 (5.9%) died within 90 days and 1,054 (10.4%) within 1 year without undergoing transplantation. Of 5,720 recipients of transplants with 1-year follow-up, 576 (10.1%) died within 1 year. The risk for death while on the waiting list within 90 days increased from 1.6% to 19% across the 10 risk groups. The survival benefit from HT increased progressively with higher risk for death without transplantation (p < 0.001 for trend), but there was no benefit in the first 6 risk groups.ConclusionsThe risk for waiting list mortality varies considerably among HT candidates. Although the survival benefit of HT generally increases with increasing risk for waiting list mortality, there is no measurable benefit in many candidates at the lower end of the risk spectrum.

Background— The sickest children among those listed for heart transplant (HT) are also at higher risk of post-transplant mortality. We hypothesized that transplant benefit, defined as percentage reduction in risk of 1-year mortality on receiving HT, increases with higher risk of wait-list mortality. Methods and Results— We analyzed all children aged P Conclusions— Sicker children on the wait-list benefit more from HT unless the post-transplant mortality is predicted to be very high. Whether consideration of transplant benefit in allocation policy can improve overall survival among listed children requires further analysis.

Introduction: Heart disease is the leading cause of stroke in children; however, little is known about the distribution of cardiac conditions associated with stroke. Hypothesis: We assessed the hypothesis that patients requiring cardiac surgery, catheterization, or mechanical support account for the majority of strokes in children with heart disease. Methods: All patients admitted to Lucile Packard Children’s Hospital at Stanford were included. A new diagnosis of stroke was identified using hospital data. Descriptive statistics were used to evaluate the characteristics of the population and tabulate common causes of stroke and stroke sub-types. Results: Between September 1, 2009 and February 1, 2014, a total of 36 patients with congenital or acquired heart disease had a new diagnosis of stroke. The median age was 4.18 years (IQR 0.32 - 10.6 years); 64% were male. Overall, 50% of strokes were arterial ischemic, 17% hemorrhagic and 25% had both ischemic and hemorrhagic components. Transient ischemic attacks accounted for the remaining 8%. Patients on mechanical support accounted for the majority of strokes (33%; ECMO 22%, ventricular assist device 11%) followed by left-sided cardiac catheterization (22%). Single-ventricle palliation procedures (Norwood or Glenn) accounted for 11% and septal defect repair 8%. Associated cardiac conditions included cardiomyopathy (28%), single-ventricle physiology (28%), septal defects (14%), myo/endocarditis (11%), heart transplantation (6%), and left-sided valvular disease (5%). Overall, 47.2% of patients were receiving anticoagulant therapy at the time of their stroke. Among those patients, 32% with arterial ischemic strokes and 60% with hemorrhagic strokes were within goal anticoagulation levels. Conclusions: Mechanical circulatory support, cardiac catheterizations and single-ventricle palliation procedures account for two-thirds of strokes observed in patients with cardiac disease. Many strokes occur in patients receiving anticoagulant therapy in accordance with contemporary anticoagulation guidelines. Re-evaluation of these guidelines and studies to reduce the risk of strokes in vulnerable sub-groups of cardiac patients is warranted.

Background Advances in centrifugal blood pump technology have led to increased use of centrifugal pumps in extracorporeal membrane oxygenation (ECMO) circuits. Their efficacy and safety in critically ill neonates remains unknown. Blood cell trauma leading to hemolysis may result in end-organ injury in critically ill neonates receiving centrifugal pump ECMO. We hypothesized that neonates undergoing ECMO support using centrifugal pumps were at increased odds of hemolysis and subsequent end-organ injury. Methods Children 30 days of age or younger who received support with venoarterial ECMO and were reported to the Extracorporeal Life Support Registry during 2007 to 2009 underwent propensity score matching (Greedy matching 1:1) using pre-ECMO support characteristics. Results A total of 1,592 neonates receiving ECMO (centrifugal pump=163 and roller pump=1,492) were identified. Significant differences in demographic, presupport, and cannulation variables were present before matching. One hundred seventy-six neonates who were supported using either centrifugal (n = 88) or roller pumps (n = 88) were matched using propensity scoring. No significant differences in demographic, presupport, or cannulation variables were present after matching. Neonates undergoing support using centrifugal pumps had increased odds of hemolysis (odds ratio [OR], 7.7 [2.8–21.2]), hyperbilirubinemia (OR, 20.8 [2.7–160.4]), hypertension (OR, 3.2 [1.3–8.0]), and acute renal failure (OR, 2.4 [1.1–5.6]). Survival to discharge was not different between pump types. Conclusions Use of ECMO using centrifugal pumps is associated with increased odds of hemolysis that likely contributes to other end-organ injury. Research into the optimal use of centrifugal pumps and strategies to prevent support-related complications need to be investigated.

Background— Previous studies have reported worse outcomes in children with nondilated cardiomyopathy (CMP) listed for heart transplant compared with children with dilated CMP. We sought to compare wait-list and posttransplant outcomes in these groups in the current era. Methods and Results— We analyzed all children P =0.17, log-rank test). In adjusted analysis, the risk of posttransplant graft loss was higher in nondilated CMP (hazard ratio, 1.8; CI, 1.2–2.7) versus dilated CMP. Conclusions— The increased risk of wait-list mortality in children with nondilated CMP is limited to those on ventilator support at listing. Although the risk of graft loss is modestly higher in children with nondilated forms of CMP, their short-term transplant outcomes are good.

Background— Racial differences in long-term survival after heart transplant (HT) are well known. We sought to assess racial/ethnic differences in wait-list outcomes among patients listed for HT in the United States in the current era. Methods and Results— We compared wait-list and posttransplant in-hospital mortality among white, black, and Hispanic patients ≥18 years of age listed for their primary HT in the United States between July 2006 and September 2010. Of 10 377 patients analyzed, 71% were white, 21% were black, and 8% were Hispanic. Black and Hispanic patients were more likely to be listed with higher urgency (listing status 1A/1B) in comparison with white patients ( P Conclusions— Hispanic patients listed for HT in the United States appear to be at higher risk of dying on the wait-list or becoming too sick for a transplant in comparison with white patients. Black patients are not at higher risk of wait-list mortality, but they have higher early posttransplant mortality.

Background— Risk factors for early mortality after heart transplant (HT) have not been used for quantitative risk prediction. We sought to develop and validate a risk prediction model for posttransplant in-hospital mortality in HT recipients. Methods and Results— We derived the model in subjects aged ≥18 years who underwent primary HT in the United States from January 2007 to June 2009 (n=4248) and validated it internally using a bootstrapping technique (200 random samples, n=4248). We then assessed the model's performance in patients receiving an HT from July 2009 to October 2010 (external validation cohort, n=2346). Posttransplant in-hospital mortality was 4.7% in the model derivation cohort. The best-fitting model based on recipient characteristics at transplant had 6 variables: age, diagnosis, type of mechanical support, ventilator support, estimated glomerular filtration rate, and total serum bilirubin. Model discrimination for survivors versus nonsurvivors was acceptable during derivation and internal validation (C statistic, 0.722 and 0.731, respectively) as was model calibration during derivation (Hosmer Lemeshow [HL] P =0.47). Model performance was reasonable in the external validation cohort (predicted mortality, 4.9%; actual mortality, 4.3%; R 2 =0.95; C statistic, 0.68; HL P =0.48). Adding the donor-related variables of age and ischemic time to the model improved its performance in both the model derivation (C statistic, 0.742; HL P =0.70) and the external validation (C statistic, 0.695; HL P =0.42) cohorts. Conclusions— The proposed model allows risk stratification of HT candidates for early posttransplant mortality and may be useful in counseling patients with regard to their posttransplant prognosis. The model with additional donor-related variables may be useful during donor selection.

We sought to evaluate trends in overall and race-specific pediatric heart transplant (HT) wait-list mortality in the United States (US) during the last 20 years. We identified all children

Previous studies have found no association between graft ischemic time (IT) and survival in pediatric heart transplant (HTx) recipients. However, previous studies were small or analyzed risk only at the extremes of IT, where observations are few. We sought to determine whether graft IT is independently associated with graft survival in a large cohort of children with no a priori assumptions about where the risk threshold may lie.All children aged18 years in the U.S. undergoing primary HTx (1987 to 2008) were included. The primary end point was graft loss (death or retransplant) within 6 months. Multivariate analysis was performed to analyze the association between graft IT and graft loss within 6 months after transplant. A secondary end point of longer-term graft loss was assessed among recipients who survived the first 6 months after transplant.Of 4,716 pediatric HTxs performed, the median IT was 3.5 hours (interquartile range, 2.7-4.3 hours). Adjusted analysis showed that children with an IT3.5 hours were at increased risk of graft loss within 6 months after transplant (hazard ratio, 1.3; 95% confidence interval, 1.1-1.5; p = 0.002). Among 6-month survivors, IT was not associated with longer-term graft loss.IT beyond 3.5 hours is associated with a 30% increase in risk of graft loss within 6 months in pediatric HT recipients. Although the magnitude of risk associated with IT is small compared with the risk associated with recipient factors, these findings may be important during donor assessment for high-risk transplant candidates.

Uncertainty exists whether hearts from infants who have died of sudden infant death syndrome (SIDS) are acceptable for transplantation because the mechanism of death in SIDS remains unclear. We analyzed post-transplant outcomes in infants who received a heart from a donor where SIDS was the primary cause of brain death.This retrospective multicenter cohort study used data from the Organ Procurement and Transplant Network (OPTN). All infants aged12 months undergoing heart transplant between 1994 and 2008 were included. A Cox proportional hazards model was used to determine whether donor SIDS was independently associated with post-transplant graft loss (death or retransplant).During the study period, 66 of 1033 infants (6.4%) who underwent heart transplant received an allograft from a SIDS donor. These infants were similar to the remaining infants with respect to age, diagnosis, blood type, and invasive support. In multivariable analysis, graft loss was associated with congenital heart disease (hazard ratio [HR], 1.6; 95% confidence interval [CI], 1.2-2.1), ventilator (HR, 1.4; 95% CI, 1.1-1.9), and extracorporeal membrane oxygenation support (HR, 3.0; 95% CI, 2.2-4.3), but not donor SIDS (HR, 1.0; 95% CI, 0.6-1.5), suggesting graft survival in SIDS-donor heart recipients was similar to the remaining infants. Primary causes of post-transplant death in infants receiving SIDS-donor hearts and the remaining infants were similar.Graft survival was similar in infants who received SIDS-donor hearts compared with those who received hearts from donors who died of other causes. There was no increase in incidence of non-rejection-related cardiac deaths after transplant in these children.

Biopsy-diagnosed pAMR has been observed in over half of pediatric HT recipients within 6 years of transplantation. We report the incidence and outcomes of pAMR at our center. All endomyocardial biopsies for all HT recipients transplanted between 2010 and 2015 were reviewed and classified using contemporary ISHLT guidelines. Graft dysfunction was defined as a qualitative decrement in systolic function by echocardiogram or an increase of ≥3 mm Hg in atrial filling pressure by direct measurement. Among 96 patients, pAMR2 occurred in 7 (7%) over a median follow-up period of 3.1 years, while no cases of pAMR3 occurred. A history of CHD, DSA at transplant, and elevated filling pressures were associated with pAMR2. Five-sixths (83%) of patients developed new C1q+ DSA at the time of pAMR diagnosis. There was a trend toward reduced survival, with 43% of patients dying within 2.3 years of pAMR diagnosis.

Background Long-term oral corticosteroids have been a mainstay of maintenance immunosuppression in pediatric heart transplantation. In this study, we report early clinical outcomes in a cohort of pediatric heart transplant recipients managed using a steroid-avoidance protocol. Methods Of the 70 patients who underwent heart transplantation during the study period, 55 eligible recipients, including 49 non-sensitized and 6 sensitized (all 55 with negative crossmatch) patients, entered a steroid-avoidance immunosuppression protocol consisting of thymoglobin induction followed by a 2-drug, tacrolimus-based, corticosteroid-free regimen. The primary outcome variable was freedom from moderate rejection (International Society for Heart and Lung Transplantation [ISHLT] Grade 2R/3A or antibody-mediated rejection). Results The median age at transplant was 7.1 years (range 2 weeks to 22 years) and median follow-up was 19 months (range 2 to 46 months). Fifty patients survived to discharge after transplantation. Of these patients, 2 (4%) were discharged on steroids and 8 (16%) started on maintenance steroids at follow-up. Rejection was diagnosed in 8 patients (Grade 2R cellular rejection in 3 and antibody-mediated rejection in 5). Freedom from rejection was 92% at 6 months (95% confidence interval [CI] 80% to 97%) and 87% at 1 year (CI 73% to 94%). Post-transplant survival was 91% at 6 months (CI 79% to 96%) and 88% at 12 and 24 months (CI 75% to 95%). There was 1 death due to rejection (antibody-mediated) 8 months after transplantation. Conclusions An immunosuppression protocol consisting of induction followed by corticosteroid avoidance appears to achieve acceptable rejection rates during the first year post-transplant in pediatric heart transplant recipients.

Studies suggest that tighter INR control can be achieved with a centralized pharmacist-led warfarin monitoring program. No data are available in children with cardiac disease where the age of patients varies significantly and high-risk indications are common. We sought to characterize the time-in

Background— Children listed for heart transplantation face the highest waiting list mortality in solid-organ transplantation medicine. We examined waiting list mortality since the pediatric heart allocation system was revised in 1999 to determine whether the revised allocation system is prioritizing patients optimally and to identify specific high-risk populations that may benefit from emerging pediatric cardiac assist devices. Methods and Results— We conducted a multicenter cohort study using the US Scientific Registry of Transplant Recipients. All children Conclusions— US waiting list mortality for pediatric heart transplantation remains unacceptably high in the current era. Specific high-risk subgroups can be identified that may benefit from emerging pediatric cardiac assist technologies. The current pediatric heart-allocation system captures medical urgency poorly. Further research is needed to define the optimal organ-allocation system for pediatric heart transplantation.