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Heart transplantation (HT) is the gold standard for managing end-stage heart failure. Multiple quality metrics, including length of stay (LOS), have been used in solid organ transplantation. However, limited data are available regarding trends and factors influencing LOS after pediatric HT. We hypothesized that various donor, peri-transplant and recipient factors affect LOS after pediatric HT.We analyzed patients18years at time of HT from January 2005 to December 2018 in the Pediatric Heart Transplant Society database, and examined LOS trends, defined prolonged LOS (PLOS = LOS30days after HT), identified factors associated with PLOS and assessed outcomes.Of 4827 patients undergoing HT, 4414 patients were discharged and included for analysis. Overall median LOS was 19days[13,34]. Median LOS was longer in patients with congenital heart disease(CHD = 25days[15,43] than with cardiomyopathy(CM = 17days[12,27] across all ages. Median LOS in age1year was 26-days[16,45.5] and in age10year was 16days[11,26]. PLOS was seen in 1313 patients(30%). Patients with PLOS were younger, smaller and had longer CPB times. There was no difference in utilization of VAD at HT between groups, however, ECMO use at listing(8.45% vs 2.93%,p0.05) and HT was higher in the PLOS group(9.22% vs 1.58%,p0.05). PLOS was more common in patients with previous surgery, CHD, single ventricle physiology, recipient history of cardiac arrest or CPR, end organ dysfunction, lower GFR, use of mechanical ventilation at HT and Status 1A at HT.We present novel findings of LOS distribution and define PLOS after pediatric HT, providing a quality metric for individual programs to utilize and study in their practice.

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.

Increased circulating catecholamines are associated with worse exercise performance in adult heart failure patients. Patients with Fontan physiology have increased circulating catecholamines and theoretically could benefit from beta blockade. We hypothesized that carvedilol would improve exercise performance in Fontan patients. A double-blind, placebo-controlled, crossover trial of carvedilol was performed. Single ventricle patients between the ages of 10 and 35 years with a previous Fontan operation who were able to complete a maximal exercise test (respiratory exchange ratio > 1.0) were included. Two 12-week treatment arms were separated by a 6-week washout period. Exercise testing was performed at beginning and end of each treatment arm. Primary endpoint was improvement in peak oxygen consumption/kg (pVO2) from baseline. Of the 26 subjects enrolled, 23 completed the study. Four subjects did not reach goal maximum carvedilol dose, vs. 1 for placebo (p = 0.14). The mean change in pVO2 between treatments was not different (carvedilol = − 2.1 mL/kg/min v. placebo = − 1.42, p = 0.28). Carvedilol therapy decreased peak heart rate by 4.2 ± 20.2 bpm, (p

BACKGROUND The HeartMate 3 ventricular assist device (VAD) is a newer centrifugal continuous-flow VAD used for bridge-to-transplant and destination therapy in adults. However, there is limited experience regarding its use in children and adults with complex congenital heart disease (CHD). METHODS The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) is a multicenter learning network comprised of pediatric hospitals implanting VADs in children and adults with complex CHD. We examined the outcomes of patients undergoing HeartMate 3 implantation at an ACTION center between December 2017 and September 2019. RESULTS The HeartMate 3 was implanted in 35 patients at 9 ACTION centers, with a median age of 15.7 (8.8–47.3) years, median weight of 65.7 (19.1–114.1) kg, and median body surface area (BSA) of 1.74 (0.78–2.36) m2. Of the cohort, 14 patients (40%) weighed CONCLUSIONS Use of the HeartMate 3 in ACTION centers was associated with a low incidence of mortality and adverse events. Patients as small as 19 kg (BSA 0.78 m2) were successfully implanted and supported, indicating that this device may be appropriate for older children and small adults.

Cardiac disease results in significant morbidity and mortality in patients with muscular dystrophy (MD). Single centers have reported their ventricular assist device (VAD) experience in specific MDs and in limited numbers. This study sought to describe the outcomes associated with VAD therapy in an unselected population across multiple centers.We examined outcomes of patients with MD and dilated cardiomyopathy implanted with a VAD at Advanced Cardiac Therapies Improving Outcomes Network (ACTION) centers from 9/2012 to 9/2020.A total of 19 VADs were implanted in 18 patients across 12 sites. The majority of patients had dystrophinopathy (66%) and the median age at implant was 17.2 years (range 11.7-29.5). Eleven patients were non-ambulatory (61%) and 6 (33%) were on respiratory support pre-VAD. Five (28%) patients were implanted as a bridge to transplant, 4 of whom survived to transplant. Of 13 patients implanted as bridge to decision or destination therapy, 77% were alive at 1 year and 69% at 2 years. The overall frequencies of positive outcome (transplanted or alive on device) at 1 year and 2 years were 84% and 78%, respectively. Two patients suffered a stroke, 2 developed sepsis, 1 required tracheostomy, and 1 experienced severe right heart failure requiring right-sided VAD.This study demonstrates the potential utility of VAD therapies in patients with muscular dystrophy. Further research is needed to further improve outcomes and better determine which patients may benefit most from VAD therapy in terms of survival and quality of life.

Background The influence of ventricular assist device (VAD) use in the care of children with end-stage heart failure is growing rapidly through increasing numbers, new devices, expanding indications, and improving outcomes. Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs), a National Institutes of Health–sponsored United States database, provides a platform to understand this emerging population. Methods Between September 19, 2012, and December 31, 2017, 30 hospitals implanted 508 devices in 423 patients aged younger than 19 years. This past year was one of evolution for the database as its management was transitioned to The Society of Thoracic Surgery; therefore, this report does not include data from institutions not under contract by August 1, 2018. Results Of the 423 patients, the diagnosis was cardiomyopathy in 261 (62%), myocarditis in 48 (11%), other in 28 (7%), and congenital heart disease (CHD) in 86 (20%), with 52 of these patients having single-ventricle physiology. The two most common support strategies included left VAD in 342 (81%) and biventricular assist device in 64 (15%). Positive outcome (alive on device or bridge to transplantation/recovery) was 80% at 6 months (overall mortality of 20%). The patient cohort for implantable continuous-flow (IC) pumps (n = 197; age at implant, 13.4 ± 3.8 years; 19% Interagency Registry for Mechanically Assisted Circulatory Support [Intermacs] profile 1, 21% intubated at implant, and 12% with CHD) was significantly different from the paracorporeal continuous-flow (PC) pump cohort (n = 79; age, 3.9 ± 5.2 years; 49% Intermacs profile 1, 86% intubated at implant, and 38% with CHD) and the paracorporeal pulsatile (PP) pump cohort (n = 121; age, 3.3 ± 3.9 years; 41% Intermacs profile 1, 77% intubated at implant, and 21% with CHD). Consistent with their cohort composition, device type positive outcomes at 6 months were PC, 63%; PP, 77%; and IC, 92%. Parametric hazard modeling showed an early hazard for death was associated with Intermacs profile 1, biventricular assist device, percutaneous devices, PC devices, small-volume institutions, low age, and low weight, whereas a constant hazard was associated with intubation and liver dysfunction at time of implant. Conclusions IC VADs are the most common VAD type placed in children. The positive outcomes for the IC VADs exceed 90% at 6 months, which may represent our field’s maturation in both patient selection and timing of implantation. The PP/PC devices are currently limited to supporting our most challenging patients, those weighing less than 20 kg and those with CHD. The introduction of new devices and our communities’ commitment to shared learning and improvement will lead to more pediatric lives saved by VAD support and will also focus on improving the quality of life of children supported with VADs.

Background Freedom from rejection in pediatric heart transplant recipients is highly variable across centers. This study aimed to assess the center variation in methods used to diagnose rejection in the first-year post-transplant and determine the impact of this variation on patient outcomes. Methods The PHTS registry was queried for all rejection episodes in the first-year post-transplant (2010-2019). The primary method for rejection diagnosis was determined for each event as surveillance biopsy, echo diagnosis, or clinical. The percentage of first-year rejection events diagnosed by surveillance biopsy was used to approximate the surveillance strategy across centers. Methods of rejection diagnosis were described and patient outcomes were assessed based on surveillance biopsy utilization among centers. Results A total of 3985 patients from 56 centers were included. Of this group, 873 (22%) developed rejection within the first-year post-transplant. Surveillance biopsy was the most common method of rejection diagnosis (71.7%), but practices were highly variable across centers. The majority (73.6%) of first rejection events occurred within 3-months of transplantation. Diagnosis modality in the first-year was not independently associated with freedom from rejection, freedom from rejection with hemodynamic compromise, or overall graft survival . Conclusions Rejection in the first-year after pediatric heart transplant occurs in 22% of patients and most commonly in the first 3 months post-transplant. Significant variation exists across centers in the methods used to diagnose rejection in pediatric heart transplant recipients, however, these variable strategies are not independently associated with freedom from rejection, rejection with hemodynamic compromise, or overall graft survival.

Right heart failure (RHF) is a vexing problem in children after left ventricular assist device (LVAD) implantation that can negatively impact transplant candidacy and survival. Anticipation, prevention, early identification and appropriate medical and device management of RHF are important to successful LVAD outcomes. However, there is limited pediatric evidence to guide practice. This pediatric-focused review summarizes the relevant literature and describes the harmonized approach to RHF from the Advanced Cardiac Therapies Improving Outcomes Network (ACTION). This review seeks to improve RHF outcomes through the sharing of best practices and experience across the pediatric VAD community.

Mechanical support of patients with superior cavopulmonary connection is challenging; multiple factors contribute to failure: elevated pulmonary vascular resistance, aortopulmonary collateral flow, venovenous collaterals, ventricular dysfunction, and atrioventricular valve regurgitation. We report 2 cases of conversion from a single ventricle circulation to biventricular mechanical support by reestablishing caval continuity. Both patients have demonstrated recovery of end-organ function and participation in rehabilitation. This method of support results in improved systemic venous pressures and pulmonary blood flow compared with systemic mechanical circulatory support with a cavopulmonary connection and transfers some of the complexity of the transplant to the ventricular assist device implant.

Thrombotic and bleeding complications have historically been major causes of morbidity and mortality in pediatric ventricular assist device (VAD) support. Standard anticoagulation with unfractionated heparin is fraught with problems related to its heterogeneous biochemical composition and unpredictable pharmacokinetics. We sought to describe the utilization and outcomes in children with paracorporeal VAD support who are treated with direct thrombin inhibitors (DTIs) antithrombosis therapy. Retrospective multicenter review of all pediatric patients (aged

Significant inter- and intra-center practice variability is present in pediatric donor heart acceptability. This may contribute to variation in the donor refusal rate and may impact waitlist time, morbidity, mortality, and transplant rates. In order to reduce practice variability, our center developed and implemented a comprehensive strategy regarding donor acceptance in September 2017. The aim of this study was to assess the impact of this strategy on waitlist time and outcomes as well as early post-transplant outcomes. We performed a single-center, retrospective analysis of all pediatric (18 years) patients listed for single-organ heart transplant at our center from September 2015 to September 2018. Patients were divided into those listed before (Group 1) and after implementation of the comprehensive strategy (Group 2). The primary end-point was waitlist time. Secondary end-points included waitlist removal due to death or clinical deterioration, donor refusals per listed patient, early post-transplant outcomes (graft failure, mechanical ventilation time, inotropic support, length of hospital stay) and 1-year post-transplant survival. Of 78 listed patients, 54 were transplanted (29 in Group 1), 9 were removed due to death or clinical deterioration (7 in Group 1) and 15 were removed due to clinical improvement (12 in Group 1). The waitlist time was significantly shorter in Group 2 (17 days, IQR 7-53) vs Group 1 (90 days, IQR 14-162); P = .006. The number of donor refusals was lower in Group 2 (1, IQR 0-2.2) vs Group 1 (4, IQR 2-19); P .001. The percentage of refused donors with normal function (Left ventricular ejection fraction 50%) was lower in Group 2 vs Group 1 (53% vs 84%; P .001). Difference in removal from the waitlist for death or deterioration in Group 2 vs Group 1 (n = 2, 7% vs n = 7, 20%, P = .18) did not reach statistical significance. There was no difference in post-transplant outcomes between groups. The waitlist time and donor refusals significantly decreased after implementation of a comprehensive donor acceptance strategy without impacting transplant outcomes. This analysis supports the need for a comprehensive approach to donor organ acceptance within a pediatric transplant center.

Improving the outcomes of pediatric patients with congenital heart disease with end-stage heart failure depends on the collaboration of all stakeholders; this includes providers, patients and families, and industry representatives. Because of the rarity of this condition and the heterogeneity of heart failure etiologies that occur at pediatric centers, learnings must be shared between institutions and all disciplines to move the field forward. To foster collaboration, excel discovery, and bring data to the bedside, a new, collaborative quality improvement science network-ACTION (Advanced Cardiac Therapies Improving Outcomes Network)-was developed to meet the needs of the field. Existing gaps in care and the methods of improvement that will be used are described, along with the mission and vision, utility of real-world data for regulatory purposes, and the organizational structure of ACTION is described.

Ischemic cardiomyopathy with resultant refractory HF may occur in patients with WBS, often as the result of coronary involvement with SVAS. The rapid development of arteriopathy at a young age raises concerns regarding transplant candidacy due to progressive stenoses at other arterial sites with potential detrimental impact on long-term heart graft function. We report a 2-month-old male infant diagnosed with mild aortic stenosis during the neonatal period, but subsequently developed rapidly progressive supravalvar and coronary artery stenoses leading to cardiogenic shock due to myocardial ischemia. The presentation led to the diagnosis of WBS. He required prolonged CPR including ECMO therapy. He subsequently underwent LVAD implantation as bridge to transplant and 4 days later heart transplantation. His post-operative course was complicated by prolonged mechanical ventilation and extended intensive care unit and hospital stays. However, at follow-up 18 months post-transplant he continues to have normal graft function with mild, non-progressive residual coarctation of aorta and non-progressive moderately hypoplastic pulmonary arteries.

Background Expanded use of pediatric ventricular assist devices (VADs) has decreased mortality in children awaiting heart transplantation. Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs), a National Heart, Lung, and Blood Institute–sponsored North American database, provides a platform to understand this emerging population. Methods Between September 2012 and September 2016, patients aged younger than 19 years who underwent VAD implantation were enrolled in Pedimacs. FDA approved durable devices as well as temporary support devices were included. The second annual report updates the current Pedimacs data. Patients implanted with temporary devices are included in Pedimacs and this analysis includes this group of paracorporeal continuous flow VADs. Results Over the 4 years, 42 hospitals implanted 432 devices in 364 patients less than 19 yrs of age. Diagnoses included cardiomyopathy in 223 (61%), myocarditis in 41 (11%), and congenital heart disease in 77 (21%), of which 48 had single-ventricle physiology. At implant, 87% were at Intermacs patient profile 1 or 2. The age distribution of children (59% male) supported on VAD included 69 (19%) aged younger than 1 year, 66 (18%) aged 1 to 6 years, 56 (15%) aged 6 to 10 years, and 173 (48%) aged 11 to 19 years. Median follow-up was 2.2 months (range, 1 day to 41.5 months). Median (interquartile) age at implant was 1.7 (0.3–10.0) years for paracorporeal continuous-flow pumps ( n = 60), 1.7 (0.4–5.3) years for paracorporeal pulsatile pumps ( n = 105), and 15.0 (11.3–16.9) years for implantable continuous-flow pumps ( n = 174). Support strategies included LVAD in 293 (80%), biventricular device in 55 (15%), and total artificial heart in 8 (2%). Nearly 50% of patients underwent transplantation within 6 months, with overall mortality of 19%. Adverse event burden continues to be high. Conclusions Pedimacs constitutes the largest longitudinal pediatric VAD registry. Preimplant data across centers will be helpful at creating shared protocols with which to improve outcomes. Adverse events continue to be the major challenge, especially among the young critically ill children with complex congenital disease.

Pediatric end-stage heart failure is a field that has undergone immense change over the past decade as the emerging demand for advanced cardiac therapies has been met with the use of ventricular assist devices (VADs). Though heart transplantation remains the definitive therapy, VAD support has afforded pediatric heart failure patients clinical stability and improved outcomes. However, the use of mechanical circulatory devices designed and intended for adult patients necessitates adaptations in order to be feasible for pediatric support. The inherent limitations to safe and effective VAD support in pediatrics are largely related to patient size restrictions and the challenges presented in supporting patients with congenital heart disease. Though the age of pediatric focused device design is in sight, attempts to address these challenges have largely been through innovation and adaptation of device implantation techniques.

Purpose Lack of both relevant clinical trials and real-world data (RWD) make it difficult to assess the effectiveness of any intervention in pediatric ventricular assist devices (VADs) population. Advanced Cardiac Therapies Improving Outcomes Network (ACTION) registry offers a means to capture RWD outside of traditional clinical trials. ACTION registry has introduced a standardized blinded adjudication process to provide VAD related adverse events (AEs) data with improved consistency and reliability. This study reviews the outcomes of the process at the end of its first year. Methods The ACTION adjudication committee, comprised of experts in the field, reviews all critical adverse events, including neurological dysfunction (ND), device malfunctions (DM) and events that lead to death, on a quarterly basis. The committee also reviews a randomly selected subset (15%) of major bleeding (MB) and major infection (MI). Pre-adjudication reports are sent to the centers to upload source documents to a secure portal. Documents are de-identified by the Data Coordinating Center (DCC) and are shared with the chair and two assigned adjudication reviewers. Each AE is presented by the assigned reviewers at a virtual meeting followed by a period of discussion and final adjudication. Committee recommendations are sent as post-adjudication reports to make necessary changes to the AE data entered in registry. Results Total of 658 AEs were reported in the registry through June 2020. Thus far, 182 (28%) AEs were adjudicated (59 Neuro AE, 48 events leading to death, 37 DM, and 38 randomly selected from other AEs). Majority of AEs [150 (82%)] were adjudicated as classified, however, 25 (14%) were classified as non-AEs (DMs = 22, MB = 2, ND = 1). Eight (4.5%) reported events were reclassified in different categories (MI = 2, ND = 4, Events leading to cause of death = 2). As a result of this process, 34 additional events (Events leading to cause of death = 21; Stroke = 4; Other neurological events = 3; Bleeding = 4; Infection = 1; Device malfunction = 1) were identified by the committee that were not originally reported to the registry. Conclusion ACTION adjudication process identified 18% misclassified and ∼5% unreported events, highlighting limitations of any registry data. However, an expert-led adjudication process with a follow-up DCC to site communications and training has the potential to improve the quality of RWD.

Purpose Cardiac disease results in significant morbidity and mortality in patients with muscular dystrophy (MD). Single centers have described their ventricular assist device (VAD) experience in this population, however broader applicability and outcomes remain unknown. Methods We examined outcomes of all patients with MD and dilated cardiomyopathy implanted with a VAD at Advanced Cardiac Therapies Improving Outcomes Network (ACTION) centers 9/2012-9/2020. Results A total of 19 VADs were implanted in 18 patients across 10 ACTION sites. The median duration of support was 252 days (range 11-1681 days). The majority of pts had dystrophinopathy (66%) and the median age at implant was 17.2 years (Table). Device strategy was bridge to transplant in 5 (27.8%), 4 of whom survived to transplant. The frequency of a positive outcome (transplanted or alive on device) at 6 months and 1 year were 89% and 84%, respectively (Figure). A single patient suffered a stroke (hemorrhagic), 2 patients developed sepsis, 1 patient developed respiratory failure requiring tracheostomy and 4 patients patient developed right heart failure (1 of whom required temporary right VAD). Conclusion In selected MD patients, VADs can serve as effective bridges to HT and chronic therapy. Right heart failure and infectious complications were relatively common, while stroke and respiratory failure were rare. Further research is needed to understand the patients who may benefit most from VAD therapy in terms of survival and quality of life and how to mitigate the risks the of the adverse events identified in the current report.

Objective Patients with biventricular assist devices (BiVADs) have worse outcomes than those with left ventricular assist devices (LVADs). It is unclear whether these outcomes are due to device selection or patient factors. We used propensity score matching to reduce patient heterogeneity and compare outcomes in pediatric patients supported with BiVADs with a similar LVAD cohort. Methods The Pedimacs registry was queried for patients who were supported with BiVAD or LVAD. Patients were analyzed by BiVAD or LVAD at primary implant and the 2 groups were compared before and after using propensity score matching. Results Of 363 patients who met inclusion criteria, 63 (17%) underwent primary BiVAD support. After propensity score matching, differences between cohorts were reduced. Six months after implant, in the BiVAD cohort (LVAD cohort) 52.5% (42.5%) had been transplanted; 32.5% (40%) were alive with device, and 15% (10%) had died. Survival was similar between cohorts (P = .31, log-rank), but patients with BiVADs were more likely to experience a major adverse event in the form of bleeding (P = .04, log-rank). At 1 week and 1 and 3 months' postimplant, the percentage of patients on mechanical ventilation, on dialysis, or with elevated bilirubin was similar between the 2 groups. Conclusions When propensity scores were used to reduce differences in patient characteristics, there were no differences in survival but more major adverse events in the patients with BiVADs, particularly bleeding. Differences in unmatched patient outcomes between LVAD and BiVAD cohorts likely represent differences in severity of illness rather than mode of support.

Purpose The initial project of ACTION (Advanced Cardiac Therapies Improving Outcomes Network) is focused on improving stroke rates in patients implanted with a ventricular assist devices (VAD) in participating centers. The initial interventions targeted improving communication, anticoagulation, and blood pressure management. We sought to describe the characteristics and outcomes of patients implanted with intracorporeal, continuous flow VADs (cfVAD). Methods The ACTION registry was used to determine the stroke frequency in cfVAD implanted patients between April 2018 and September 2019, the time from development of the quality improvement bundle to the present. Results Sixty two patients (33 Heartmate3 [HM3] and 29 Heartware [HVAD]) were identified (Table). The majority had dilated cardiomyopathy (76%). Of the 12 (20%) patients with congenital heart disease (CHD), 9 (75%) had single ventricle (SV) physiology. The HM3 patients were older (16.5 yr vs 12.8 yr) and larger (64.2 kg vs 51.9 kg) than the HVAD patients. No significant difference was observed in diagnosis, duration of support, device strategy, or clinical outcome. One patient (2%) experienced a stroke during 6,920 days of support. Forty of the 45 (89%) patients to reach a clinical endpoint experienced a positive outcome (transplant or explant for recovery) while 17 (27%) patients remain on device. Conclusion The stroke rate is low and survival good among patients implanted with an intracorporeal cfVAD at ACTION centers using the clinical protocols developed within the network. The HVAD is currently being used more frequently in younger and smaller patients. There has been an appreciable increase in the number and frequency of implants in patients with CHD, especially SV disease, as compared to previous reports. Future efforts within ACTION will focus on improving clinical outcomes as devices are increasingly used at individual centers and as the number of VAD-supported patients with congenital heart disease continues to grow.

Purpose Mental health disorders have deleterious effects on outcomes in adult heart failure. Mental health is not systematically investigated or screened in pediatric heart failure and transplantation patients. Methods Our institution implemented universal mental health screening for all patients age 11 or older in our pediatric heart failure and transplant clinic. 17 items are answered on a tablet while the patient awaits cardiac testing. Validated mental health screening tools are utilized: the Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder scale (GAD-7). Scores for both scales range from 0-4 = no symptoms, 5-9 = mild symptoms, 10-14 = moderate symptoms, > 15 = severe symptoms. Scores are immediately available in the electronic health record. The presence of suicidal ideation, severe depression and/or anxiety leads to notification of the psychologist for further intervention. Results 94 patients have been screened to date. Median age was 16.25 years (IQR 14.7-18.4). Median PHQ-9 score was 2 (IQR 0-6) and 2 (IQR 0-5.3) for GAD-7. Four patients (4.3%) reported severe depression, 8 (8.5%) moderate depression, 15 (16%) mild, 67 (71.3%) reported no depressive symptoms. Seven patients reported suicidal ideation (7.5%). Six patients (6.4%) reported severe anxiety, 8 (8.5%) moderate anxiety, 14 (14.9%) mild anxiety and 66 (70.2%) reported no anxiety. There were no differences in mental health scores between heart failure and transplant patients (Table 1). Eighteen new behavioral health interventions were implemented due to screening. Conclusion Electronic mental health screening can successfully be employed in pediatric heart failure and transplant clinics. A significant portion have moderate to severe anxiety (14.9%) or moderate to severe depression (12.8%). Mental health screening has led to many behavioral health interventions in this population. Our initial experience supports the use of mental health screening in a pediatric heart failure and transplant clinic.

Purpose Ventricular assist device (VAD) interrogations allow clinicians to establish and maintain optimal VAD settings through the support course. There is currently no data regarding standards for establishing and modifying pediatric VAD settings, despite a heterogeneous population with variable diagnoses, anatomy and physiology. Methods The Advanced Cardiac Therapies Improving Outcomes Network (ACTION), a 37-center North American learning network, was surveyed in July 2019 regarding current practices for establishing, monitoring and modifying pediatric VAD settings. Results A total of 25 (68%) centers responded to the survey. Criteria for establishing intraoperative device settings varied between solely surgeon determined (36%) versus global imaging, surgeon, and VAD team driven (60%). Post-operative inpatient and outpatient interrogations were performed predominantly (80%) by a VAD physician or advanced practice provider (APP), but frequency ranged from daily (64%) to weekly (24%) to even monthly (4%). There was consensus (100%) on including device trends and alarm assessment for VAD interrogation, but many centers (88%) include log file interpretation in each interrogation as well. Factors used for optimization of post-operative settings were mixed. Several centers (28%) rely only on device interrogation and clinical course while many (24%) utilize echocardiogram only. The majority (44%) of sites use a combination of echocardiogram and device interrogation to determine optimal support. Outpatient practices were similar amongst sites with the exception of device wean trials which had significant variation with regards to use of echocardiogram (16%), hemodynamic catheterization (8%) or a combination of both studies (76%). Billing practices for VAD interrogation were inconsistent amongst centers, particularly regarding billing frequency. Conclusion VAD interrogation and optimization practices were highly variable amongst ACTION centers, most notably during inpatient hospitalizations. Given the majority of pediatric VAD patients remain hospitalized while on their device, a standardized approach to this process may minimize unnecessary variation. Furthermore, defining “standard” management approaches and device settings in varied pediatric populations may help define the optimal clinical approach to support.

This study aims to compare 2 common induction strategies, basiliximab and ATG. Analysis of the ISHLT transplant registry was performed. The database was queried for pediatric heart transplants from January 1, 2000, to June 30, 2015, who had received induction with basiliximab or ATG. Primary end-point was graft survival. Secondary end-points included 1-year survival and 1-year conditional survival. There were 3158 heart transplants who received induction with basiliximab or ATG. The ATG cohort was younger, more likely to have congenital heart disease or be a retransplant, have a higher PRA, longer ischemic time, and been transplanted earlier in the study period (all P

Purpose Elevated blood pressure (BP) is a risk factor for stroke in adult ventricular assist device (VAD) patients. There are currently no data or BP management guidelines for pediatric VAD patients. ACTION ( Advanced Cardiac Therapies Improving Outcomes Network) is the first pediatric VAD quality improvement network. The initial goal of ACTION is stroke reduction. This report describes the methods used to obtain BP and effectiveness of BP control among ACTION members. We also describe the development of a BP clinical decision support (CDS) tool to standardize BP reporting and goals. Methods The BP protocols among ACTION members were assessed. Process measures that may impact stroke rates were identified via anonymous surveys beginning June 2018. Statistical process control charts were used to assess baseline metrics. Results A total of 28 patients from 11 centers were identified with BP data. Including 12 Heartware, 10 Berlin, 2 Heartmate3, and 4 paracorporeal continuous flow (CF) devices. Height/age BP %iles were used to guide BP goal in 19 (68%) patients. Among CFVAD patients, BP measurement method (outside the perioperative period) and BP goal value varied, especially among the 11 patients (55%) with a palpable pulse (Figure 1). Patients had well controlled BP on 69% of support days (Figure 2). Conclusion The BP measurement methods and goals varied across ACTION, especially among patients on a CF-VAD with a pulse. A CDS tool has been developed to standardize BP measurement and management among ACTION members and will guide subsequent collaborative studies to assess the role of BP in stroke among pediatric VAD patients.

Purpose We sought to describe the off-label use to date of an intracorporeal, centrifugal, continuous flow ventricular assist device (cfVAD) characterized by a magnetically levitated impeller in US pediatric cardiac centers, in order to further inform device selection quality improvement initiatives. Methods Members of the ACTION (Advanced Cardiac Therapies Improving Outcomes Network) collaborative whose centers implanted ≥1 intracorporeal magnetically levitated cfVAD were identified. Centers submitted de-identified data on each implant through 10/21/18. Results are reported as count (percentage) or median (range) for summary statistics. Results Fourteen implants occurred at 6 centers; the number of implants per center was 1 - 4. Thirteen patients (93%) had dilated cardiomyopathy (DCM); one patient (7%) had congenital heart disease (CHD) with a Fontan circulation. Of the DCM patients, 3 had neuromuscular disease (2 with Duchenne and 1 with Becker muscular dystrophy). Device strategy included bridge to transplant in 8/14 (57%), bridge to candidacy in 4/14 (29%), and destination therapy in 2/14 (14%). Median age at implant was 15 y (12 y - 24 y), with median weight 70 kg (31 kg - 118 kg) and median body surface area (BSA) 1.8 m2 (1.3 m2 - 2.4 m2). Most patients (10/14, 71%) were INTERMACS category 2 at implant; 3/14 (21%) were category 3 and 1/14 (7%) was category 4. No biVADs were placed. Median support time was 32 d (5 d - 315 d). To date, 5/14 (36%) patients were discharged, 1/14 (7%) underwent heart transplantation, and 1/14 (7%) died on VAD support; the remainder are hospitalized with the device in place. For discharged patients, median hospital length of stay after implant was 26 d (12 d - 37 d). There were no episodes of stroke or pump thrombosis. Conclusion The intracorporeal, centrifugal, magnetically levitated cfVAD is a newer device being used with increasing frequency in the pediatric and CHD population. Utilization of the device has largely been limited to older, larger children with DCM. This preliminary data will contribute to our understanding of device selection in order to improve outcomes.

Mechanical circulatory support has revolutionized heart failure management for adult and pediatric patients alike. Though the field has been marked by near continuous technologic advances, its origins are undoubtedly inauspicious. First performed in 1966, Dr. Michael Debakey described the use of an extracorporeal, pulsatile device to support the circulation of a 37-year-old woman for a mere 10 days (DeBakey, 1971). However, it was not until the early 1990s that the use of ventricular assist device (VAD) technology became routine with the FDA approval of the HeartMate IP left ventricular assist system ( Fig. 55.1A ). This and other similar first generation VADs utilized pneumatically driven, pulsatile pumps to offload the failing ventricle and provide adequate blood flow to reverse the unrelenting course of end-stage heart failure.

BACKGROUND Pediatric ventricular assist device (VAD) support as bridge to transplant has improved waitlist survival, but the effects of pre-implant status and VAD-related events on post-transplant outcomes have not been assessed. This study is a linkage analysis between the PediMACS and Pediatric Heart Transplant Study databases to determine the effects of VAD course on post-transplant outcomes. METHODS Database linkage between October 1, 2012 and December 31, 2015 identified 147 transplanted VAD patients, the primary study group. The comparison cohort was composed of 630 PHTS patients without pre-transplant VAD support. The primary outcome was post-transplant survival, with secondary outcomes of post-transplant length of stay, freedom from infection and freedom from rejection. RESULTS At implant, the VAD cohort was INTERMACS Profile 1 in 33 (23%), Profile 2 in 89 (63%) and Profile 3 in 14 (10%) patients. The VAD cohort was older, larger, and less likely to have congenital heart disease (p < 0.0001). However, they had greater requirements for inotrope and ventilator support and increased liver and renal dysfunction (p < 0.0001), both of which normalized at transplant after device support. Importantly, there were no differences in 1-year post-transplant survival (96% vs 93%, p = 0.3), freedom from infection (81% vs 79%, p = 0.9) or freedom from rejection (71% vs 74%, p = 0.87) between cohorts. CONCLUSIONS Pediatric VAD patients have post-transplant outcomes equal to that of medically supported patients, despite greater pre-implant illness severity. Post-transplant survival, hospital length of stay, infection and rejection were not affected by patient acuity at VAD implantation or VAD-related complications. Therefore, VAD as bridge to transplant mitigates severity of illness in children.

Purpose Lack of standardization in organ donation acceptance can contribute to an increased donor refusal rate, which may impact waitlist (WL) time, morbidity, mortality and transplant rates. After a review of relevant data, in 9/2017, our center developed and implemented a standardized donor acceptance criteria. We hypothesized that standardization would result in a decrease in WL time and improved WL outcomes. Methods We performed a single center, retrospective analysis of all pediatric ( Results Of 78 listed, 54 were transplanted, 8 removed due to death/clinical deterioration, 16 removed to due clinical improvement. Patient characteristics were similar between the groups (Table 1). Difference in removal from the WL for death or deterioration in Group 2 vs. 1 (n=2, 7% vs. n=6, 17%, p=0.28) did not reach statistical significance. WL time was significantly shorter in Group 2 (17 days, IQR 6-55) vs. Group 1 (90, IQR 13-167; p=0.006). The median DOR was lower in Group 2 (2, IQR 0-3) vs. Group 1 (4, IQR 2-20; p=0.001). The percentage of DOR with LVEF > 55% was lower in Group 2 vs. Group 1 (53% vs. 84%, p=0.001). Post-transplant outcomes were similar between groups (table 1). Conclusion DOR and WL time significantly decreased after a standardized donor acceptance criteria. This analysis supports the need for a standardized approach to donor organ acceptance within a pediatric transplant center.

Purpose Approximately 40% of potential pediatric heart donations go unused, while waitlist mortality remains high. The aim of our study was to investigate associations between center refusal rate and waitlist outcomes. Methods Retrospective analysis was performed using UNOS/OPTN pediatric ( Results 5,639 listed patients in 59 centers met inclusion criteria. The lowest quartile of center had a median RR of 75th percentile had a RR ≥ 4. There was no association between RR quartile and transplant center volume (p=0.4). Centers in the highest RR quartile were more likely to remove patients from the waitlist due to death or clinical deterioration versus those at lowest RR quartile (24.1% vs 14.6%, p Conclusion Patients listed at high RR centers had worse survival from listing. High RR centers are more likely to remove patients from the waitlist due to death or clinical deterioration and are less likely to transplant patients. Refusal rate is not associated with center transplant volume.

Purpose Pediatric Ventricular Assist Device (VAD) therapy is associated with high rates of stroke and bleeding. There have been limited efforts to date, to define and implement optimal anticoagulation (AC) strategies in this population. ACTION (Advanced Cardiac Therapies Improving Outcomes Network) is the first pediatric VAD quality improvement network, with an initial goal of stroke reduction. This report describes baseline AC data from ACTION centers, including agents used and aggregate levels of performance, to inform development of specific interventions. Methods The AC practices of ACTION centers were assessed. Data collected included VAD type, weekly data characterizing AC agents used; time to achieve desired levels; and percentage of levels within the desired range. Results Data were collected from 11 centers, with a total of 30 patients. AC data were collected from 6/1-9/1/18, while strokes were collected retrospectively for the entire VAD support interval. Devices included: HVAD (12); EXCOR (10); Heartmate 3 (3); and 5 paracorporeal continuous flow devices. There were 5 strokes (16.7%). Intravenous AC included unfractionated heparin (36%), and bivalirudin (64%). There was wide variability between patients in the time to achieve first therapeutic AC level (Figure 1), with 15 patients at goal within 20 hours, while others required up to 170 hours. Heparin levels varied widely, with the percent of labs within range falling below 50%, in 50% of the weeks reported. For bivalirudin, levels were less variable, with percent of labs within range falling below 50% in only 14% of weeks reported. Conclusion At baseline, stroke rates remain high in the ACTION centers. Intravenous AC includes both heparin and bivalirudin, with high variability in time until therapeutic levels are achieved, and with high variability in subsequent levels, particularly for heparin. These data will inform interventions designed to reduce variability in AC performance as a basis for stroke reduction.

Background Biomarkers have been proposed to augment or replace endomyocardial biopsy (EMB) to diagnose acute transplant rejection (AR). A new, highly sensitive assay for troponin T detects levels of cardiac troponin T (cTnT) 10- to 100-fold lower than standard assays but has not been investigated in transplant patients. N-terminal pro-brain natriuretic peptide (NT-proBNP) has not been evaluated in pediatric transplant patients. The purpose of this pilot study was to evaluate the association of cTnT and NT-proBNP with AR in pediatric cardiac transplant patients. Methods Plasma was obtained at the time of EMB from pediatric patients ≥1 year old. N-terminal pro-brain natriuretic peptide was measured in fresh plasma at the time of biopsy, and cTnT was measured from frozen, stored samples using the highly sensitive assay for troponin T. Biomarker data were correlated with EMB results. Cellular AR was defined as an International Society for Heart and Lung Transplantation biopsy score of grade ≥2R. Results Fifty-three blood samples were obtained from 42 patients (mean age 11 years). Seven episodes of AR occurred in 5 patients. Biopsies with vs without AR were associated with higher cTnT (median [interquartile range {IQR}] 66 [45-139] vs 7 [2-13] pg/mL, P = .001) and NT-proBNP (median [IQR] 11,169 [280-23,317] vs 334 [160-650] pg/mL, P < .01). After successful treatment of AR in 5 patients, cTnT fell markedly (median [IQR] 53.5 [44.8-66.5] to 10.7 [1.5-16.4], P = .05). Conclusion In this pilot study, we found marked elevation of cTnT and NT-proBNP among children with AR. Moreover, reduction in cTnT levels after treatment paralleled improvement in EMB results. If these findings are confirmed in larger prospective studies, monitoring with these biomarkers may obviate surveillance EMB.

The ductus arteriosus is a specialized blood vessel containing highly differentiated and contractile vascular smooth muscle, derived largely from neural crest cells, that is essential for fetal life but typically closes after birth. Impaired development of the ductus arteriosus or disruption of signaling pathways that initiate postnatal closure can result in persistent patency of the ductus arteriosus, the third most common congenital heart defect. We found that Tfap2β, a transcription factor associated with patent ductus arteriosus in humans, was uniquely expressed in mouse ductal smooth muscle. Endothelin-1 and the hypoxia-induced transcription factor, Hif2 α were also highly enriched in ductal smooth muscle at embryonic day 13.5 and were dependent on Tfap2β for their expression in this domain. Hif2α functioned as a negative regulator of Tfap2β-induced transcription by disrupting protein–DNA interactions, suggesting a negative feedback loop regulating Tfap2β activity. Our data indicate that Tfap2β, Et-1, and Hif2α act in a transcriptional network during ductal smooth muscle development and that disruption of this pathway may contribute to patent ductus arteriosus by affecting the development of smooth muscle within the ductus arteriosus.

Background: The response to hypoxia in tissues is regulated by the heterodimeric transcription factor Hypoxia Inducible Factor-1 (HIF-1). Methodology/Principal Findings: We have created a strain of mice with inducible cardiomyocyte-specific expression of a mutated, oxygen-stable, form of HIF-1a. Cardiac function steadily decreased with transgene expression, but recovered after the transgene was turned off. Using long-oligo microarrays, we identified 162 transcripts more than 3-fold dysregulated in these hearts after transgene expression. Among the down-regulated genes the transcript for SERCA was reduced 46% and the protein 92%. This led us to an evaluation of calcium flux that showed diminished reuptake of cytoplasmic calcium in myocytes from these hearts, suggesting a mechanism for cardiac dysfunction. Conclusions/Significance: These results provide a deeper understanding of transcriptional activity of HIF in the heart, and show that enhanced HIF-1 activity is sufficient to cause contractile dysfunction in the adult heart. HIF is stabilized in the myocardium of patients with ischemic cardiomyopathy, and our results suggest that HIF could be contributing directly to the contractile dysfunction in this disease.