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Background: There is no FDA-approved left ventricular assist device (LVAD) for smaller children permitting routine hospital discharge. Smaller children supported with LVADs typically remain hospitalized for months awaiting heart transplant-a major burden for families and a challenge for hospitals. We describe the initial outcomes of the Jarvik 2015, a miniaturized implantable continuous flow LVAD, in the NHLBI-funded Pumps for Kids, Infants, and Neonates (PumpKIN) study, for bridge-to-heart transplant., Methods: Children weighing 8 to 30 kg with severe systolic heart failure and failing optimal medical therapy were recruited at 7 centers in the United States. Patients with severe right heart failure and single-ventricle congenital heart disease were excluded. The primary feasibility endpoint was survival to 30 days without severe stroke or non-operational device failure., Results: Of 7 children implanted, the median age was 2.2 (range 0.7, 7.1) years, median weight 10 (8.2 to 20.7) kilograms; 86% had dilated cardiomyopathy; 29% were INTERMACS profile 1. The median duration of Jarvik 2015 support was 149 (range 5 to 188) days where all 7 children survived including 5 to heart transplant, 1 to recovery, and 1 to conversion to a paracorporeal device. One patient experienced an ischemic stroke on day 53 of device support in the setting of myocardial recovery. One patient required ECMO support for intractable ventricular arrhythmias and was eventually transplanted from paracorporeal biventricular VAD support. The median pump speed was 1600 RPM with power ranging from 1-4 Watts. The median plasma free hemoglobin was 19, 30, 19 and 30 mg/dL at 7, 30, 90 and 180 days or time of explant, respectively. All patients reached the primary feasibility endpoint. Patient-reported outcomes with the device were favorable with respect to participation in a full range of activities. Due to financial issues with the manufacturer, the study was suspended after consent of the eighth patient., Conclusion: The Jarvik 2015 LVAD appears to hold important promise as an implantable continuous flow device for smaller children that may support hospital discharge. The FDA has approved the device to proceed to a 22-subject pivotal trial. Whether this device will survive to commercialization remains unclear because of the financial challenges faced by industry seeking to develop pediatric medical devices. (Supported by NIH/NHLBI HHS Contract N268201200001I, clinicaltrials.gov 02954497)., (Copyright © 2024 International Society for the Heart and Lung Transplantation. All rights reserved.)

Background: Pediatric heart transplant (HT) candidates experience high waitlist mortality due to a limited donor pool that is constrained in part by anti-HLA sensitization. We evaluated the impact of CDC and Flow donor-specific crossmatch (XM) results on pediatric HT outcomes., Methods: All pediatric HTs between 1999 and 2019 in the OPTN database were included. Donor-specific XM results were sub-categorized based on CDC and Flow results. Primary outcomes were treated rejection in the first year and time to death or allograft loss. Propensity scores were utilized to adjust for differences in baseline characteristics., Results: A total of 4,695 pediatric HT patients with T-cell XM data were included. After propensity score adjustment, a positive T-cell CDC-XM was associated with 2 times higher odds of treated rejection (OR 2.29 (1.56, 3.37)) and shorter time to death/allograft loss (HR 1.50 (1.19, 1.88)) compared to a negative Flow-XM. HT recipients who were Flow-XM positive with negative/unknown CDC-XM did not have higher odds of rejection or shorter time to death/allograft loss. An isolated positive B-cell XM was also not associated with worse outcomes. Over the study period XM testing shifted from CDC- to Flow-based assays., Conclusions: A positive donor-specific T-cell CDC-XM was associated with rejection and death/allograft loss following pediatric HT. This association was not observed with a positive T-cell Flow-XM or B-cell XM result alone. The shift away from performing the CDC-XM may result in loss of important prognostic information unless the clinical relevance of quantitative Flow-XM results on heart transplant outcomes is systematically studied., (Copyright © 2024 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Functional status predicts waitlist survival in adult heart transplantation and is an independent predictor of outcomes in pediatric liver transplantation. This has not been studied in pediatric heart transplantation. Study aims were to determine the association of: (1) functional status at listing with waitlist and post-transplant outcomes, and (2) functional status at transplant with post-transplant outcomes in pediatric heart transplantation., Methods: Retrospective United Network of Organ Sharing database study of pediatric patients listed for heart transplant between 2005 and 2019 with Lansky Play Performance Scale (LPPS) scores at listing. Standard statistical methods were used to assess relationships between LPPS and outcomes (waitlist and post-transplant). Negative waitlist outcome was defined as death or removal from waitlist due to clinical deterioration., Results: There were 4,169 patients identified, including 1,080 with LPPS 80-100 (normal activity), 1,603 with LPPS 50-70 (mild limitations), and 1,486 with LPPS 10-40 (severe limitations). LPPS 10-40 correlated with negative waitlist outcomes (HR 1.69, CI 1.59-1.80, p < 0.0001). While LLPS at listing had no association with post-transplant survival, those with LPPS 10-40 at transplant had inferior 1-year post-transplant survival compared to those with LPPS ≥50 (92% vs 95%-96%, p = 0.0011). Functional status was an independent predictor of post-transplant outcomes in patients with cardiomyopathy. A functional improvement of ≥20 points between listing and transplant (N = 770, 24%) was associated with higher 1-year post-transplant survival (HR 1.63, 95% CI: 1.10-2.41, p = 0.018)., Conclusions: Functional status is associated with waitlist and post-transplant outcomes. Interventions targeting functional impairment may improve pediatric heart transplantation outcomes., (Copyright © 2023 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: 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., Methods: 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., Results: 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., Conclusions: 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., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Aim: To describe the clinical and hemodynamic characteristics of Fontan failure in children listed for heart transplant., Methods: In a nested study of the Pediatric Heart Transplant Society, 16 centers contributed information on Fontan patients listed for heart transplant between 2005and 2013. Patients were classified into four mutually exclusive phenotypes: Fontan with abnormal lymphatics (FAL), Fontan with reduced systolic function (FRF), Fontan with preserved systolic function (FPF), and Fontan with "normal" hearts (FNH). Primary outcome was waitlist and post-transplant mortality., Results: 177 children listed for transplant were followed over a median 13 (IQR 4-31) months, 84 (47%) were FAL, 57 (32%) FRF, 22 (12%) FNH, and 14 (8%) FPF. Hemodynamic characteristics differed between the 4 groups: Fontan pressure (FP) was most elevated with FPF (median 22, IQR 18-23, mmHg) and lowest with FAL (16, 14-20, mmHg); cardiac index (CI) was lowest with FRF (2.8, 2.3-3.4, L/min/m 2 ). In the entire cohort, 66% had FP >15 mmHg, 21% had FP >20 mmHg, and 10% had CI <2.2 L/min/m 2 . FRF had the highest risk of waitlist mortality (21%) and FNH had the highest risk of post-transplant mortality (36%)., Conclusions: Elevated Fontan pressure is more common than low cardiac output in pediatric failing Fontan patients listed for transplant. Subtle hemodynamic differences exist between the various phenotypes of pediatric Fontan failure. Waitlist and post-transplant mortality risks differ by phenotype., Competing Interests: Disclosure Statement This study complies with the Declaration of Helsinki and the research was approved by Stanford University Institutional Review Board. Participating centers contributed supplemental data to the Pediatric Heart Transplant Society under Institutional Review Board approval or waiver of consent where applicable., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2020. Published by Elsevier Inc.)

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., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2018. Published by Elsevier Inc.)

Background: 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)., Methods: 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-value < 0.2) were incorporated into a multivariate logistic regression model. Scores were assigned to independent predictors (p < 0.05) based on relative odds ratios (ORs)., Results: 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]; p < 0.001) 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%., Conclusion: 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., (Copyright © 2018 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Management of mechanical circulatory support in children with congenital heart disease (CHD) is challenging due to physiologic variations and anatomic limitations to device placement. In this study we examine the use of Berlin Heart EXCOR in CHD patients., Methods: CHD patients were identified from the EXCOR Pediatric Study data set (2007 to 2010). Mortality and serious adverse events were compared between CHD and non-CHD cohorts, and predictors of poor outcomes in the CHD cohort were identified., Results: CHD was present in 29% (n = 59, 18 with 1-ventricle physiology) of all EXCOR patients (N = 204). Successful bridge (transplant or wean) was less likely in CHD patients compared with non-CHD patients (48% vs 80%; p < 0.01). Among CHD patients, no neonates, 25% of infants (30 days to 1 year) and 65% of children (>1 year) were successfully bridged. Pre-implant congenital heart surgery (CHS) and extracorporeal membrane oxygenation (ECMO) on the same admission occurred in 60% of children ≤1 year of age (83% of neonates, 50% of infants), with 8% survival. Regardless of age, patients who did not have CHS and ECMO had 61% survival. Smaller pump, pre-implant bilirubin >1.2 mg/dl and renal dysfunction were independently associated with mortality., Conclusions: End-organ function at implant reliably predicts adverse outcomes and should be considered when making implant decisions. EXCOR use in neonates and infants with CHD should be approached cautiously. If patients have undergone pre-implant CHS and ECMO, EXCOR support may not provide any survival benefit. EXCOR support in non-infants with CHD is challenging but can be consistently successful with appropriate patient selection., (Copyright © 2017 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Patients listed for heart transplant after their 18th birthday purportedly wait longer to receive a donor heart compared with patients listed before their 18th 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 1-year period before and after their 18th birthday. The primary study end-point was the waiting time to receive a donor heart. Secondary end-points 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 before their 18th birthday under the pediatric allocation system, and 153 (42.5%) listed during the 12 months after their 18th birthday under the adult allocation system. The pediatric cohort was more likely to be listed Status 1A. Otherwise, the 2 groups shared similar baseline characteristics. Overall, patients listed after their 18th birthday waited 8.5 months longer to receive a transplant than adolescents listed before their 18th birthday (p = 0.01) and had a 47% lower probability of receiving a transplant (p = 0.001), but there was no difference in waitlist mortality (p = 0.37)., Conclusions: Patients listed for heart transplant shortly after their 18th birthday have significantly longer wait-times compared with patients listed shortly before their 18th birthday and 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 a relevant factor in the timing of heart transplant listing., (Copyright © 2017. Published by Elsevier Inc.)

Background: Stroke is the most feared complication associated with the Berlin Heart EXCOR pediatric ventricular assist device (VAD), the most commonly used VAD in children, and affects 1 in 3 children. We sought to determine whether a modified anti-thrombotic guideline, involving more intense platelet inhibition and less reliance on platelet function testing, is associated with a lower incidence of stroke., Methods: All children supported with the EXCOR at Stanford from 2009 to 2014 were divided into 2 cohorts based on the primary anti-thrombotic guideline used to prevent pump thrombosis: (1) the Edmonton Anti-thrombotic Guideline (EG) cohort, which included children implanted before September 2012 when dual anti-platelet therapy was used with doses titrated to Thromboelastrography/PlateletMapping (TEG/PM); and (2) the Stanford Modified Anti-thrombotic Guideline (SG) cohort, which included children implanted on or after September 2012 when triple anti-platelet therapy was used routinely and where doses were uptitrated to high, weight-based dosing targets, with low-dose steroids administered as needed for inflammation., Results: At baseline, the EG (N = 16) and SG (N = 11) cohorts were similar. The incidence rate of stroke in the SG cohort was 84% lower than in the EG cohort (0.8 vs 4.9 events per 1,000 days of support, p = 0.031), and 86% lower than in the previous Investigational Device Exemption trial (p = 0.006). The bleeding rate was also lower in the SG cohort (p = 0.015). Target doses of aspirin, clopidogrel and dipyridamole were higher (all p < 0.003), with less dosing variability in the SG cohort than in the EG cohort. There was no difference in adenosine diphosphate inhibition by TEG/PM, but arachidonic acid inhibition was higher in the SG cohort (median 75% vs 39%, p = 0.008)., Conclusions: Stroke was significantly less common in pediatric patients supported with the Berlin Heart EXCOR VAD using a triple anti-platelet regimen uptitrated to high, weight-based dosing targets as compared with the dual anti-platelet regimen titrated to PM, and without a higher risk of bleeding. Larger studies are needed to confirm these findings., (Copyright © 2017 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: 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., Methods: 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., Results: 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, p < 0.001) but lower FS scores at listing (4 vs 6, p < 0.001). 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)., Conclusions: 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., (Copyright © 2017 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Life-threatening arrhythmia events (LTEs) occur in ~5% of children with dilated cardiomyopathy (DCM). While prolonged QRS duration has been shown to be associated with LTEs, electrocardiographic (ECG) repolarization findings have not been examined., Objective: We sought to determine the associations between ECG repolarization abnormalities and LTEs in children with DCM., Methods: A single-center retrospective review of children with DCM was performed. LTEs were defined as documented ventricular tachycardia or fibrillation requiring medical intervention. Three pediatric cardiologists, blinded to clinical events, evaluated ECGs obtained at the time of initial referral. Kaplan-Meier survival and Cox proportional hazards analyses were used to evaluate time to LTEs., Results: A total of 137 patients (mean age 7.8 ± 6.7 years; 75(55%) male patients) with DCM (mean ejection fraction 35% ± 16%) were included; 67 patients (49%) had a corrected JT (JTc) interval of ≥340 ms, 72 (53%) had a corrected QT (QTc) interval of ≥450 ms, and 41 (30%) had abnormal T waves. LTEs occurred in 15 patients at a median of 12 months (interquartile range 3-36 months) after the initial ECG. Patients with LTEs had a longer JTc interval (371 ± 77 ms vs 342 ± 41 ms; P = .02) and a longer QTc interval (488 ± 96 ms vs 453 ± 44 ms; P = .01). In survival analysis, a JTc interval of ≥390 ms (hazard ratio [HR] 4.07; 95% confidence interval [CI] 1.12-14.83; P = .03), a QTc interval of ≥510 ms (HR 6.95; 95% CI 1.53-31.49; P = .01), abnormal T-wave inversion (HR 11.62; 95% CI 2.75-49.00; P = .001), and ST-segment depression (HR 6.91; 95% CI 1.25-38.27; P = .03) were associated with an increased risk of LTEs, even after adjusting for QRS duration and amiodarone use., Conclusion: Repolarization abnormalities are common in children with DCM. Certain ECG repolarization abnormalities, such as significantly prolonged JTc and QTc intervals, may be useful in identifying patients at risk of LTEs., (Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Ventricular assist devices (VADs) have been used in children on an increasing basis in recent years. One-year survival rates are now >80% 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 are <19 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., Results: 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., Conclusions: 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., (Copyright © 2016 International Society for Heart and Lung Transplantation. All rights reserved.)

Background: Use of mechanical circulatory support in children has increased as more options have become available. A national account of the use of mechanical support in children and adolescents is essential to understanding outcomes, refining patient selection and improving quality of care., Methods: The Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS) is a National Heart, Lung, and Blood Institute-supported nationwide registry for temporary and durable ventricular assist device (VAD) use in patients <19 years of age. Between the launch in September 2012 and June 2015, 37 hospitals in the USA have enrolled patients. This first report of data from PediMACS analyzed pre-implant patient characteristics, survival using competing outcomes, and adverse events., Results: Two hundred pediatric patients underwent 222 durable VAD implants. Patients' characteristics and outcomes of children supported with a temporary device (n = 41) were not analyzed in this report. The etiology of heart disease included 146 (73%) patients with cardiomyopathy and 35 (18%) with congenital heart disease. Thirty patients (15%) transitioned from extracorporeal membrane oxygenation (ECMO) and 76 (38%) had previous cardiac surgery. Most patients were Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Level 1 (27%) or Level 2 (56%) at implant, with 13% at Level 3. Of the 200 patients supported with a durable device, 91 (46%) were supported with a pulsatile-flow device and 109 (55%) with a continuous-flow (CF) device. Patient age at first implant included 30 patients (15%) <1 year of age, 37 (19%) 1 to 5 years, 32 (16%) 6 to 10 years and 101 (51%) 10 to 18 years. Patients were supported with left ventricular assist device alone in 161 (81%), biventricular ventricular assist device in 29 (15%), right ventricular assist device in 4 (2.0%) and total artificial heart in 6 (3%), together comprising 783 months of follow-up. The 200 patients receiving primary durable devices had an actuarial survival of 81% at 6 months. Competing risk analysis at 6 months revealed that 58% of patients had been transplanted, 28% were alive on support, 14% had died and 0.6% recovered. In the overall cohort, there were 28 deaths. Reported serious adverse events included infection (n = 78), bleeding (n = 68), device malfunction (n = 79) and neurologic dysfunction (n = 52)., Conclusions: PediMACS constitutes the largest single data repository with detailed information of pediatric patients implanted with VADs. The first PediMACS report reveals favorable outcomes despite the varying patient characteristics and pump types. However, the rate of adverse events remains high. With further data collection, analysis of patient risk factors critical to improving outcomes will be possible., (Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Although ventricular assist devices (VADs) restore hemodynamics in those with heart failure, reversibility of end-organ dysfunction with VAD support is not well characterized. Renal function often improves in adults after VAD placement, but this has not been comprehensively explored in children., Methods: Sixty-three children on VAD support were studied. Acute kidney injury (AKI) was defined by Kidney Disease: Improving Global Outcomes criteria. Estimated glomerular filtration rate (eGFR) was determined by the Schwartz method. Generalized linear mixed-effects models compared the pre-VAD and post-VAD eGFR for the cohort and sub-groups with and without pre-VAD renal dysfunction (pre-VAD eGFR < 90 ml/min/1.73 m(2))., Results: The pre-VAD eGFR across the cohort was 84.0 ml/min/1.73 m(2) (interquartile range [IQR] 62.3-122.7), and 55.6% (34 of 63) had pre-VAD renal dysfunction. AKI affected 60.3% (38 of 63), with similar rates in those with and without pre-existing renal dysfunction. Within the cohort, the nadir eGFR occurred 1 day post-operatively (62.9 ml/min/1.73 m(2); IQR, 51.2-88.9 ml/min/1.73 m(2); p < 0.001). By Day 5, however, the eGFR exceeded the baseline (99.0 ml/min/1.73 m(2); IQR, 59.3-146.7 ml/min/1.73 m(2); p = 0.03) and remained significantly higher through the first post-operative week. After adjusting for age, gender, and AKI, the eGFR continued to increase throughout the entire 180-day study period (β = 0.0025; 95% confidence interval, 0.0015-0.0036; p < 0.001). Patients with pre-VAD renal dysfunction experienced the greatest improvement in the eGFR (β = 0.0051 vs β = 0.0013, p < 0.001)., Conclusions: Renal dysfunction is prevalent in children with heart failure undergoing VAD placement. Although peri-operative AKI is common, renal function improves substantially in the first post-operative week and for months thereafter. This is particularly pronounced in those with pre-VAD renal impairment, suggesting that VADs may facilitate recovery and maintenance of kidney function in children with advanced heart failure., (Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Limited availability of donor organs has led to the use of ventricular assist devices (VADs) to treat heart failure in pediatric patients, primarily as bridge to transplantation. How effective VAD therapy is in promoting functional recovery in children is currently not known., Methods: We report morbidity and mortality as defined by the Interagency Registry for Mechanically Assisted Circulatory Support Modified for Pediatrics (PediMACS) and the use of the Treatment Intensity Score to assess functional status for 50 VAD patients supported at a single pediatric program from 2004 to 2013., Results: In this cohort, 30-day survival on VAD was 98%, and 180-day survival was 83%. Stroke occurred in 11 patients (22%), with 8 (16%) resulting in persistent neurologic deficit or death. The adverse event rate was 2-fold to 3-fold higher in the first 7 days of support compared with the subsequent support period. Functional status, as measured by the Treatment Intensity Score, improved with duration of support. Successful bridge to transplantation was associated with fewer adverse events during support and greater improvement in the Treatment Intensity Score during the period of support., Conclusions: Overall survival in this cohort is excellent. The risk of serious adverse events decreases over the first month of support. However, a clinically significant risk of morbidity and mortality persists for the duration of pediatric VAD support. Measures of functional status improve with duration of support and are associated with survival to transplantation., (Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

The use of ventricular assist devices (VADs) in children is increasing. Stroke and device-related thromboembolism remain the most feared complications associated with VAD therapy in children. The presence of a VAD causes dysregulation of hemostasis due to the presence of foreign materials and sheer forces intrinsic to the device resulting in hypercoagulability and potentially life-threatening thrombosis. The use of antithrombotic therapy in adults with VADs modulates this disruption in hemostasis, decreasing the risk of thrombosis. Yet, differences in hemostasis in children (developmental hemostasis) may result in variances in dysregulation by these devices and preclude the use of adult guidelines. Consequently, pediatric device studies must include safety and efficacy estimates of device-specific antithrombotic therapy guidelines. This review will discuss mechanisms of hemostatic dysregulation as it pertains to VADs, goals of VAD antithrombotic therapy for children and adults, and emerging antithrombotic strategies for VAD use in children., (© 2015 International Society on Thrombosis and Haemostasis.)

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., (Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Little is known about the outcomes in patients who are removed from the heart transplant (HT) waiting list before receiving a transplant. We sought to analyze outcomes in such patients in the United States (U.S.) in the current era., Methods: All patients aged ≥ 18 years old listed for a primary HT in the U.S. between July 2004 and September 2010 were identified. Outcomes in those removed from the list by March 2011 (survival, relisting, HT) were examined using time-to-event analyses., Results: Of 15,061 patients listed for primary HT, 10,168 (68%) received a HT, 1,393 (9%) died on the waiting list, and 1,871(12%) were removed before receiving HT. Of patients removed from the list, 560 (30%) were removed due to clinical improvement, 692 (37%) due to deterioration, and 619 (33%) due to other reasons. After removal, 30-day and 1-year survival were 99.6% and 94%, respectively, in patients removed due to improvement and 44% and 26%, respectively, in patients removed due to deterioration. Multivariable predictors of death after removal were removal due to clinical deterioration, hypertrophic or restrictive cardiomyopathy, United Network of Organ Sharing status 1A/1B at listing, and renal dysfunction. Only 27 patients (4.8%) among those removed due to improvement, 21 (3.0%) removed due to deterioration, and 46 (7.4%) removed due to other reasons were relisted., Conclusions: One in 8 patients listed for HT in the U.S. are removed from the waiting list before receiving HT. The indication for removal (clinical deterioration vs improvement) is the strongest independent predictor of survival after removal from the list., (Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Medication non-adherence (NA) can result in life-threatening illness in children after solid-organ transplantation. Little is known about the incidence, risk factors and outcomes of NA in large numbers of pediatric heart transplant (HT) recipients., Methods: Organ Procurement Transplant Network (OPTN) data were used to identify all children <18 years of age in the U.S.A. who underwent HT from October 1999 to January 2007. Cox proportional hazards analysis was used to identify risk factors for NA and the effect on graft survival., Results: Of 2,070 pediatric heart transplants performed the median age at transplant was 6 years (interquartile range [IQR] 0 to 13 years); 40% had congenital heart disease (CHD), 7% were re-transplants, 42% were non-white and 43% had Medicaid insurance. Overall, 186 (9%) children had a report of NA at a median age of 15 years with more than two-thirds of NA episodes occurring after 12 years of age. Factors independently associated with NA were: adolescent age at transplant (hazard ratio [HR] 7.0, 95% confidence interval [CI] 4.1 to 12, compared with infants); black race (HR 2.3, 95% CI 1.7 to 3.3, compared with white); Medicaid insurance (HR 2.0, 95% CI 1.5 to 2.7, compared with non-Medicaid insurance); and ventilator or ventricular assist device (VAD) support at transplant. The risk of mortality conditional upon report of NA was 26% at 1 year and 33% at 2 years., Conclusions: Medication NA is an important problem in pediatric HT recipients and is associated with high mortality. Adolescent age, black race, Medicaid insurance and invasive hemodynamic support at transplant were associated with NA, whereas time on the wait list and gender were not. Targeted interventions among at-risk populations may be warranted., (Copyright © 2013 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

We sought to develop and validate a quantitative risk-prediction model for predicting the risk of posttransplant in-hospital mortality in pediatric heart transplantation (HT). Children <18 years of age who underwent primary HT in the United States during 1999-2008 (n = 2707) were identified using Organ Procurement and Transplant Network data. A risk-prediction model was developed using two-thirds of the cohort (random sample), internally validated in the remaining one-third, and independently validated in a cohort of 338 children transplanted during 2009-2010. The best predictive model had four categorical variables: hemodynamic support (ECMO, ventilator support, VAD support vs. medical therapy), cardiac diagnosis (repaired congenital heart disease [CHD], unrepaired CHD vs. cardiomyopathy), renal dysfunction (severe, mild-moderate vs. normal) and total bilirubin (≥ 2.0, 0.6 to <2.0 vs. <0.6 mg/dL). The C-statistic (0.78) and the Hosmer-Lemeshow goodness-of-fit (p = 0.89) in the model-development cohort were replicated in the internal validation and independent validation cohorts (C-statistic 0.75, 0.81 and the Hosmer-Lemeshow goodness-of-fit p = 0.49, 0.53, respectively) suggesting acceptable prediction for posttransplant in-hospital mortality. We conclude that this risk-prediction model using four factors at the time of transplant has good prediction characteristics for posttransplant in-hospital mortality in children and may be useful to guide decision-making around patient listing for transplant and timing of mechanical support., (© Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Renal function deteriorates in some children awaiting heart transplantation. This study was initiated to assess the effects of worsening renal function (WRF) on post-heart transplantation outcomes and to determine the effect of waiting-list associated WRF on survival after heart transplantation., Methods: All children aged <18 years who underwent their first heart transplantation between 1999 and 2009, had reported plasma creatinine concentrations at listing and at transplantation, and were free of renal replacement therapy at listing were identified using the Organ Procurement and Transplant Network database. The independent effects of WRF on in-hospital mortality and post-discharge survival were assessed using logistic regression and log-rank analyses, respectively., Results: Of the 2,216 children included in the analysis, WRF occurred in 334 (15%) awaiting heart transplantation: WRF was mild (stage 1) in 210 (63%), moderate (stage 2) in 40 (12%), and severe (stage 3) in 84 (25%). All WRF stages were independently associated with in-hospital, post-transplant mortality: mild WRF with adjusted odds ratio (AOR) of 2.1 (95% confidence interval [CI], 1.2-3.5); moderate WRF, 2.7 (95% CI, 1.1-6.7); and severe WRF, 3.6 (95% CI, 2.0-6.5). WRF was not associated with death after discharge (hazard ratio, 1.2; 95% CI, 0.9-1.7) at a median follow-up of 2.7 years., Conclusions: WRF occurs in 15% of children awaiting heart transplantation and is associated with early but not late post-transplant mortality., (Copyright © 2012 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Sudden death is a well-recognized complication of heart transplantation. Little is known about the incidence and risk factors for sudden death after transplant in children. The purpose of this study was to determine the incidence of and risk factors for sudden death., Methods: This retrospective multicenter cohort study used the Pediatric Heart Transplant Study Group (PHTS) database, an event-driven registry of children aged <18 at listing undergoing heart transplantation between 1993 and 2007. Standard Kaplan-Meier and parametric analyses were used for survival analysis. Multivariate analysis in the hazard-function domain was used to identify risk factors for sudden death after transplant., Results: Of 604 deaths in 2,491 children who underwent heart transplantation, 94 (16%) were classified as sudden. Freedom from sudden death was 97% at 5 years, and the hazard for sudden death remained constant over time at 0.01 deaths/year. Multivariate risk factors associated with sudden death included black race (hazard ratio [HR], 2.6; p < 0.0001), United Network of Organ Sharing (UNOS) status 2 at transplant (HR, 1.8; p = 0.008), older age (HR, 1.4/10 years of age; p = 0.03), and an increased number of rejection episodes in the first post-transplant year (HR, 1.6/episode; p = 0.03)., Conclusion: Sudden death accounts for 1 in 6 deaths after heart transplant in children. Older recipient age, recurrent rejection within the first year, black race, and UNOS status 2 at listing were associated with sudden death. Patients with 1 or more of these risk factors may benefit from primary prevention efforts., (Copyright © 2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

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 <18 years old listed for primary HT in the US during 1989-2009 (N = 8096, 62% White, 19% Black, 13% Hispanic and 6% Other) using the Organ Procurement and Transplant Network database. Wait-list mortality was assessed in four successive eras (1989-1994, 1995-1999, 2000-2004 and 2005-2009). Overall wait-list mortality declined in successive eras (26%, 23%, 18% and 13%, respectively). The decline across eras remained significant in adjusted analysis (hazard ratio [HR] 0.70 in successive eras, 95% confidence interval [CI], 0.67-0.74) and was 67% lower for children listed during 2005-2009 versus those listed during 1989-1994 (HR 0.33; CI, 0.28-0.39). In models stratified by race, wait-list mortality decreased in all racial groups in successive eras. In models stratified by era, minority children were not at higher risk of wait-list mortality in the most recent era. We conclude that the risk of wait-list mortality among US children listed for HT has decreased by two-thirds during the last 20 years. Racial gaps in wait-list mortality present variably in the past are not present in the current era., (©Copyright 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: 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., Methods: All children aged <18 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., Results: 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 IT > 3.5 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., Conclusions: 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., (2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Beginning in 2000 and accelerating in 2004, the Berlin Heart EXCOR (Berlin Heart Inc Woodlands, TX) became the first pediatric-specific ventricular assist device (VAD) applied throughout North America for children of all sizes. This retrospective study analyzed the initial Berlin Heart EXCOR pediatric experience as a bridge to transplantation., Methods: Between June 2000 and May 2007, 97 EXCOR VADs were implanted in North America at 29 different institutions. The analysis is limited to 73 patients (75%) from 17 institutions, for which retrospective data were available., Results: Median age and weight at VAD implant were 2.1 years (range, 12 days-17.8 years) and 11 kg (range, 3-87.6 kg), respectively. The primary diagnoses were dilated cardiomyopathy in 42 (58%), congenital heart disease in 19 (26%), myocarditis in 7 (10%), and other cardiomyopathies in 5 (7%). Pre-implant clinical condition was critical cardiogenic shock in 38 (52%), progressive decline in 33 (45%), or other in 2 (3%). Extracorporeal membrane oxygenation was used as a bridge to EXCOR in 22 patients (30%). Device selection was left VAD (LVAD) in 42 (57%) and biventricular assist devices (BiVAD) in 31 (43%). The EXCOR bridged 51 patients (70%) to transplant and 5 (7%) to recovery. Mortality on the EXCOR was 23% (n = 17) overall, including 35% (11 of 31) in BiVAD vs 14% (6 of 42) in LVAD patients (p = 0.003). Multivariate analysis showed younger age and BiVAD support were significant risk factors for death while on the EXCOR., Conclusions: This limited but large preliminary North American experience with the Berlin Heart EXCOR VAD as a bridge to cardiac transplantation for children of all ages and sizes points to the feasibility of this approach. The prospective investigational device evaluation trial presently underway will further characterize the safety and efficacy of the EXCOR as a bridge to pediatric cardiac transplantation., (Copyright © 2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

We assessed whether the improvement in posttransplant survival in pediatric heart transplant (HT) recipients during the last two decades has benefited the major racial groups in the United States equally. We analyzed all children <18 years of age who underwent their first HT in the US during 1987-2008. We compared trends in graft loss (death or retransplant) in white, black and Hispanic children in five successive cohorts (1987-1992, 1993-1996, 1997-2000, 2001-2004, 2005-2008). The primary endpoint was early graft loss within 6 months posttransplant. Longer-term survival was assessed in recipients who survived the first 6 months. The improvement in early posttransplant survival was similar (hazard ratio [HR] for successive eras 0.80, 95% confidence interval [CI] 0.7, 0.9, p = 0.24 for black-era interaction, p = 0.22 for Hispanic-era interaction) in adjusted analysis. Longer-term survival was worse in black children (HR 2.2, CI 1.9, 2.5) and did not improve in any group with time (HR 1.0 for successive eras, CI 0.9, 1.1, p = 0.57; p = 0.19 for black-era interaction, p = 0.21 for Hispanic-era interaction). Thus, the improvement in early post-HT survival during the last two decades has benefited white, black and Hispanic children equally. Disparities in longer-term survival have not narrowed with time; the survival remains worse in black recipients., (©2010 The Authors Journal compilation©2010 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: 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., Methods: This retrospective multicenter cohort study used data from the Organ Procurement and Transplant Network (OPTN). All infants aged < 12 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)., Results: 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., Conclusions: 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., (Copyright © 2010 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

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., (Copyright (c) 2010 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Infants awaiting heart transplantation (HT) face the highest wait-list mortality among all children and adults listed for HT in the USA. We sought to determine the risk of death for infants <12 months old while awaiting HT in the current era, and to identify the principle risk factors associated with wait-list mortality., Methods: We analyzed outcomes for all infants listed for HT in the USA from January 1999 to July 2006, using data reported to the U.S. Scientific Registry of Transplant Recipients., Results: Of the 1,133 listed infants, 61% were <3 months of age, 80% were listed as Status 1A, 64% had a congenital heart disease (CHD) and 31% had cardiomyopathy. Of 724 infants with CHD, 25% were on prostaglandin (PG) and 27% had a history of prior surgery. By 6 months after listing, 23% died on the wait-list and 54% were transplanted. Multivariate factors associated with wait-list mortality were weight <3 kg (hazard ratio [HR] 1.4, 95% confidence interval [CI] 1.0 to 1.9), extracorporeal membrane oxygenation (ECMO) support (HR 5.6, CI 4.0 to 7.9), ventilator support (HR 2.1, 95% CI 1.6 to 2.8), CHD with PG support (HR 2.8, 95% CI 1.8 to 4.3), CHD without prior surgery (HR 2.8, 95% CI 1.9 to 3.9) and non-white race/ethnicity (HR 1.8, 95% CI 1.4 to 2.3)., Conclusions: One in four infants listed for HT in the USA die before a donor heart can be identified. Wait-list mortality is associated with weight <3 kg, level of invasive support and CHD, but not listing status, which captures medical urgency poorly. Measures to expand infant organ donation, especially among neonates, are urgently needed.

Racial differences in outcomes are well known in children after heart transplant (HT) but not in children awaiting HT. We assessed racial and ethnic differences in wait-list mortality in children <18 years old listed for primary HT in the United States during 1999-2006 using multivariable Cox models. Of 3299 listed children, 58% were listed as white, 20% as black, 16% as Hispanic, 3% as Asian and 3% were defined as 'Other'. Mortality on the wait-list was 14%, 19%, 21%, 17% and 27% for white, black, Hispanic, Asian and Other children, respectively. Black (hazard ratio [HR] 1.6, 95% confidence interval [CI] 1.3, 1.9), Hispanic (HR 1.5, CI 1.2, 1.9), Asian (HR, 2.0, CI 1.3, 3.3) and Other children (HR 2.3, CI 1.5, 3.4) were all at higher risk of wait-list death compared to white children after controlling for age, listing status, cardiac diagnosis, hemodyamic support, renal function and blood group. After adjusting additionally for medical insurance and area household income, the risk remained higher for all minorities. We conclude that minority children listed for HT have significantly higher wait-list mortality compared to white children. Socioeconomic variables appear to explain a small fraction of this increased risk.

Background: Fontan takedown to an intermediate palliative circulation is an important treatment option for patients with acute or subacute failure of a Fontan circulation from a variety of causes. Little is known about the subsequent outcome of these patients or their potential candidacy for a second attempt at Fontan completion., Methods: Patients followed up at Children's Hospital Boston who underwent takedown of a Fontan circulation to an intermediate palliative circulation within 1 year of Fontan completion were reviewed., Results: Between 1979 and 2006, 53 patients underwent Fontan takedown at a median age of 2.3 years (range, 0.3 to 36.5 years). Takedown was performed during the Fontan procedure itself in 12 patients (22%), within the first postoperative month in 31(58%), and between 1 month and 1 year in 10 (18%). Overall, 29 patients (55%) survived the early period after takedown, and 19 ultimately underwent successful Fontan completion a median of 4.6 years after takedown; all but one was alive a median of 6.4 years later. Thirteen (68%) of the 19 had treatable abnormalities contributing to Fontan failure., Conclusions: Fontan takedown can provide effective stabilization of the acutely or subacutely failing Fontan circulation, although a substantial number of patients die early despite Fontan takedown. Subjects surviving the perioperative period can often undergo uneventful redo Fontan. A thorough evaluation for treatable abnormalities should be performed in all patients with a failing Fontan circulation and in patients who undergo Fontan takedown.

Bivalirudin, a direct thrombin inhibitor, has recently emerged as a promising option for anti-coagulation during cardiopulmonary bypass in patients who cannot receive heparin. There is limited experience with the use of bivalirudin in children. We present the case of a child with heparin-induced thrombocytopenia with thrombosis (HIT Type II) who underwent successful orthotopic cardiac transplantation using bivalirudin as the primary anti-coagulant for cardiopulmonary bypass.