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Many pediatric heart transplant (HT) recipients reach adulthood and may be interested in family planning; there is little data regarding safety of pregnancy post HT and clinicians' opinions differ. Pediatric HT clinicians are instrumental in early counseling. Thus, a better understanding of pediatric HT clinicians' practices regarding family planning and how well aligned these practices are with adult transplant centers is essential.We conducted a confidential, web-based survey of pediatric HT clinicians in fall 2021. We summarized and compared answers using Fisher's exact test.The survey was sent to 53 United States-based HT directors and to the International Society for Heart and Lung Transplantation and Pediatric Heart Transplant Society list serves. There were 69 respondents. The majority (77%) of respondents felt pregnancy was feasible in selected or all female HT recipients. Ten respondents reported that their institution had an established policy regarding pregnancy post HT. A majority (77%) of HT clinicians would either use a shared care model or recommend transition to their adult institution if pregnancy occurred, though 74% of respondents were either unaware of their corresponding adult institution's policy (62%) or had a counterpart adult program with a policy against pregnancy post HT (12%).While many clinicians feel pregnancy is feasible in pediatric HT recipients, there remains significant practice variation. Few pediatric programs have a policy regarding pregnancy post HT. Future efforts to provide consistent messaging between adult and pediatric HT programs regarding the feasibility and care of post HT pregnancy are warranted.

We conducted a scientific survey of paediatric practitioners who manage heart failure with dilated cardiomyopathy in children. The survey covered management from diagnosis to treatment to monitoring, totalling 63 questions. There were 54 respondents from 40 institutions and 3 countries. There were diverse selections of management options by the respondents in general, but also unanimity in some management options. Variation in practice is likely due to the relative paucity of scientific data in this field and lack of strong evidence-based recommendations from guidelines, which presents an opportunity for future research and quality improvement efforts as the evidence base continues to grow.

To understand the genetic contribution to primary pediatric cardiomyopathy, we performed exome sequencing in a large cohort of 528 children with cardiomyopathy. Using clinical interpretation guidelines and targeting genes implicated in cardiomyopathy, we identified a genetic cause in 32% of affected individuals. Cardiomyopathy sub-phenotypes differed by ancestry, age at diagnosis, and family history. Infants < 1 year were less likely to have a molecular diagnosis (p < 0.001). Using a discovery set of 1,703 candidate genes and informatic tools, we identified rare and damaging variants in 56% of affected individuals. We see an excess burden of damaging variants in affected individuals as compared to two independent control sets, 1000 Genomes Project (p < 0.001) and SPARK parental controls (p < 1 × 10(−16)). Cardiomyopathy variant burden remained enriched when stratified by ancestry, variant type, and sub-phenotype, emphasizing the importance of understanding the contribution of these factors to genetic architecture. Enrichment in this discovery candidate gene set suggests multigenic mechanisms underlie sub-phenotype-specific causes and presentations of cardiomyopathy. These results identify important information about the genetic architecture of pediatric cardiomyopathy and support recommendations for clinical genetic testing in children while illustrating differences in genetic architecture by age, ancestry, and sub-phenotype and providing rationale for larger studies to investigate multigenic contributions.

Cardiac disease has emerged as a leading cause of mortality in Duchenne muscular dystrophy in the current era. This survey sought to identify the diagnostic and therapeutic approach to DMD among pediatric cardiologists in Advanced Cardiac Therapies Improving Outcomes Network. Pediatric cardiology providers within ACTION (a multi-center pediatric heart failure learning network) were surveyed regarding their approaches to cardiac care in DMD. Thirty-one providers from 23 centers responded. Cardiac MRI and Holter monitoring are routinely obtained, but the frequency of use and indications for ordering these tests varied widely. Angiotensin converting enzyme inhibitor and aldosterone antagonist are generally initiated prior to onset of systolic dysfunction, while the indications for initiating beta-blocker therapy vary more widely. Seventeen (55%) providers report their center has placed an implantable cardioverter defibrillator in at least 1 DMD patient, while 11 providers (35%) would not place an ICD for primary prevention in a DMD patient. Twenty-three providers (74%) would consider placement of a ventricular assist device (VAD) as destination therapy (n = 23, 74%) and three providers (10%) would consider a VAD only as bridge to transplant. Five providers (16%) would not consider VAD at their institution. Cardiac diagnostic and therapeutic approaches vary among ACTION centers, with notable variation present regarding the use of advanced therapies (ICD and VAD). The network is currently working to harmonize medical practices and optimize clinical care in an era of rapidly evolving outcomes and cardiac/skeletal muscle therapies.

The number of potential pediatric heart transplant recipients continues to exceed the number of donors, and consequently the waitlist mortality remains significant. Despite this, around 40% of all donated organs are not used and are discarded. This document (62 authors from 53 institutions in 17 countries) evaluates factors responsible for discarding donor hearts and makes recommendations regarding donor heart acceptance. The aim of this statement is to ensure that no usable donor heart is discarded, waitlist mortality is reduced, and post-transplant survival is not adversely impacted.

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.

Introduction: Safety of vigorous exercise for individuals with appropriately-treated HCM remains debated. Physical activity practices in this population have not been described. The objective of this report is to describe physical activity pattern in HCM patients. Long term follow up which is ongoing will determine safety of vigorous exercise. Methods: The NIH-funded LIVE-HCM study prospectively enrolled individuals age 8-60 years with clinically overt HCM or patients with a positive genetic test for sarcomeric HCM. Participants (or parents, for children) answered surveys describing activity patterns. Vigorous exercise was defined as > 6 METS for > 60 hours per year. Clinical and demographic data were derived from medical record review. Results: Among 1798 participants, 745 (41%) reported exercising vigorously, including 296 competitive athletes, with 59 at high-school or college varsity level, 770 (43%) were exercising at moderate, and 283 (16%) at low levels. Of those working, 6% described jobs more active than walking, including 16 in protective services, and 11 in sports/coaching. Clinical/demographic data including imaging characteristics and treatments, are shown in Table, and were mostly similar amongst the exercise-groups. Conclusions: Many patients with HCM are engaged in vigorous exercise including competitive athletics. Prospective follow-up of this cohort is ongoing. Comparison of arrhythmic outcomes outcomes in vigorous exercisers vs moderate/low level exercisers will help determine the safety of exercise in HCM patients.

Introduction: Rejection remains a significant cause of graft loss after heart transplantation. The current prevalence of recurrent rejection and its impact on graft loss after pediatric heart transplantation is unknown. Methods: All pediatric heart transplants between 1/2000-6/2020 in the Pediatric Heart Transplant Society database were included. Rejection was defined as a clinical event determined by biopsy, echocardiogram or clinical findings that resulted in augmentation of immunosuppression. Recurrent rejection was defined as ≥ 2 episodes of rejection after heart transplant. Freedom from recurrent rejection in the early (2000-2009) and current (2010-2020) era were compared. Multiphase parametric hazard modeling was utilized to understand the effects of each additional episode of rejection on graft loss in addition to identifying other risk factors. Results: Of 6342 heart transplants during the study period, 3921 (62%) had 0, 1386 (21%) had 1 and 1035 (17%) had ≥2 rejection episodes. In the current era, recurrent rejection is less frequent [468/4206 (11.1%) vs. 567/2136 (26.5%); p Conclusions: Currently, recurrent rejection is experienced by 1 in 10 pediatric HT recipients. Each additional episode of rejection post-HT confers an increasing risk for graft loss. Identifying risk factors for recurrent rejection is paramount to improving graft longevity.

Myocarditis remains a clinical challenge in pediatrics. Originally, it was recognized at autopsy before the application of endomyocardial biopsy, which led to a histopathology-based diagnosis such as in the Dallas criteria. Given the invasive and low-sensitivity nature of endomyocardial biopsy, its diagnostic focus shifted to a reliance on clinical suspicion. With the advances of cardiac magnetic resonance, an examination of the whole heart in vivo has gained acceptance in the pursuit of a diagnosis of myocarditis. The presentation may vary from minimal symptoms to heart failure, life-threatening arrhythmias, or cardiogenic shock. Outcomes span full resolution to chronic heart failure and the need for heart transplantation with inadequate clues to predict the disease trajectory. The American Heart Association commissioned this writing group to explore the current knowledge and management within the field of pediatric myocarditis. This statement highlights advances in our understanding of the immunopathogenesis, new and shifting dominant pathogeneses, modern laboratory testing, and use of mechanical circulatory support, with a special emphasis on innovations in cardiac magnetic resonance imaging. Despite these strides forward, we struggle without a universally accepted definition of myocarditis, which impedes progress in disease-targeted therapy.

Background: Genetic testing is indicated for children with a personal or family history of hereditary cardiomyopathy to determine appropriate management and inform risk stratification for family members. The implications of a positive genetic result for children can potentially impact emotional well-being. Given the nuances of cardiomyopathy genetic testing for minors, this study aimed to understand how parents involve their children in the testing process and investigate the impact of genetic results on family dynamics. Methods: A survey was distributed to participants recruited from the Children’s Cardiomyopathy Foundation and 7 North American sites in the Pediatric Cardiomyopathy Registry. The survey explored adolescent and parent participants’ emotions upon receiving their/their child’s genetic results, parent-child result communication and its impact on family functionality, using the McMaster Family Assessment Device. Results: One hundred sixty-two parents of minors and 48 adolescents who were offered genetic testing for a personal or family history of cardiomyopathy completed the survey. Parents whose child had cardiomyopathy were more likely to disclose positive diagnostic genetic results to their child ( P =0.014). Parents with unaffected children and positive predictive testing results were more likely to experience negative emotions about the result ( P ≤0.001) but also had better family functioning scores than those with negative predictive results ( P =0.019). Most adolescents preferred results communicated directly to the child, but parents were divided about whether their child’s result should first be released to them or their child. Conclusions: These findings have important considerations for how providers structure genetic services for adolescents and facilitate discussion between parents and their children about results.

Background Pediatric cardiomyopathy is a genetically heterogeneous disease with substantial morbidity and mortality. Current guidelines recommend genetic testing in children with hypertrophic, dilated, or restrictive cardiomyopathy, but practice variations exist. Robust data on clinical testing practices and diagnostic yield in children are lacking. This study aimed to identify the genetic causes of cardiomyopathy in children and to investigate clinical genetic testing practices. Methods and Results Children with familial or idiopathic cardiomyopathy were enrolled from 14 institutions in North America. Probands underwent exome sequencing. Rare sequence variants in 37 known cardiomyopathy genes were assessed for pathogenicity using consensus clinical interpretation guidelines. Of the 152 enrolled probands, 41% had a family history of cardiomyopathy. Of 81 (53%) who had undergone clinical genetic testing for cardiomyopathy before enrollment, 39 (48%) had a positive result. Genetic testing rates varied from 0% to 97% between sites. A positive family history and hypertrophic cardiomyopathy subtype were associated with increased likelihood of genetic testing ( P =0.005 and P =0.03, respectively). A molecular cause was identified in an additional 21% of the 63 children who did not undergo clinical testing, with positive results identified in both familial and idiopathic cases and across all phenotypic subtypes. Conclusions A definitive molecular genetic diagnosis can be made in a substantial proportion of children for whom the cause and heritable nature of their cardiomyopathy was previously unknown. Practice variations in genetic testing are great and should be reduced. Improvements can be made in comprehensive cardiac screening and predictive genetic testing in first‐degree relatives. Overall, our results support use of routine genetic testing in cases of both familial and idiopathic cardiomyopathy. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01873963.

The objective of this study was to describe a cohort of patients with clinical myocarditis and normal left ventricular (LV) systolic function on admission. A retrospective chart review at seven tertiary pediatric hospitals identified patients aged

Background As survival and neuromuscular function in Duchenne Muscular Dystrophy (DMD) improve with glucocorticoid therapy and respiratory advances, the proportion of cardiac deaths is increasing. Little is known about the use and outcomes of advanced heart failure (HF) therapies in this population. Methods A retrospective cohort study of 436 males with DMD was performed, from January 1, 2005-January 1, 2018, with the primary outcome being use of advanced HF therapies including: implantable cardioverter defibrillator (ICD), left ventricular assist device (LVAD), and heart transplantation (HTX). Results Nine subjects had an ICD placed, 2 of whom (22.2%) had appropriate shocks for ventricular tachycardia; 1 and 968 days after implant, and all of whom were alive at last follow-up; median 18 (IQR: 12.5–25.5) months from implant. Four subjects had a LVAD implanted with post-LVAD survival of 75% at 1 year; 2 remaining on support and 1 undergoing HTX. One subject was bridged to HTX with ICD and LVAD and was alive at last follow-up, 53 months after HTX. Conclusion Advanced HF therapies may be used effectively in select subjects with DMD. Further studies are needed to better understand risk stratification for ICD use and optimal candidacy for LVAD implantation and HTX, with hopes of improving cardiac outcomes.

Cardiac arrhythmias occur in 3-40% of patients with acute myocarditis and cause significant morbidity and mortality. Myocardial injury also results in abnormal myocardial deformation. The relationship between left ventricular (LV) deformation, measured by two-dimensional speckle tracking echocardiography (2D-STE), and arrhythmia in pediatric myocarditis is unknown. We evaluated the association between 2D-STE and arrhythmias in children hospitalized with acute myocarditis. We reviewed patients ≤ 18 years hospitalized for acute myocarditis from 2008 to 2018. Arrhythmias were defined as 1) non-sustained or sustained ventricular tachycardia or ventricular fibrillation, 2) sustained supraventricular tachycardia (SVT), 3) high-grade or complete heart block, and 4) any arrhythmia treated with an antiarrhythmic medication. Systolic LV strain values (including LV global longitudinal strain (GLS), global circumferential strain (GCS), and six segments of LV regional long axis strain) were obtained from initial echocardiograms during hospitalization. Of 66 patients hospitalized, 23 (35%) had arrhythmias. SVT was the predominant arrhythmia (74%). Global and regional strain indices were reduced in the arrhythmia group: LV GLS [-8.9 (IQR -13.6, -6.1) vs. -13.7 (IQR -16.9, -9.7), p = 0.038]; basal inferior/septal [-10.7 (IQR -15.5, -7.8) vs. -16.4 (IQR -18, -11.8), p = 0.009]; basal anterior/lateral [-7.1 (IQR -12.8, -4.7) vs. -9.4 (IQR -16.7, -7.4), p = 0.025]; and mid inferior/septal segments [-9 (IQR -13, -7.7) vs. -14.1 (IQR -22.5, -10.7), p = 0.007]. After controlling for age, reductions in GLS and segmental strain in the two basal and two mid-segments were associated with increased arrhythmia occurrence (p0.05). Our findings suggest that echocardiographic LV deformation by 2D-STE may be useful in identifying pediatric patients with acute myocarditis at risk for arrhythmias.

Abnormal dystrophin production due to mutations in the dystrophin gene causes Duchenne Muscular Dystrophy (DMD). Cases demonstrate considerable genetic and disease progression variability. It is unclear if specific gene mutations are prognostic of outcomes in this population. We conducted a retrospective cohort study of DMD patients followed at 17 centers across the USA and Canada from 2005 to 2015 with goal of understanding the genetic variability of DMD and its impact on clinical outcomes. Cumulative incidence of clinically relevant outcomes was stratified by genetic mutation type, exon mutation location, and extent of exon deletion. Of 436 males with DMD, 324 (74.3%) underwent genetic testing. Deletions were the most common mutation type (256, 79%), followed by point mutations (45, 13.9%) and duplications (23, 7.1%). There were 131 combinations of mutations with most mutations located along exons 45 to 52. The number of exons deleted varied between 1 and 52 with a median of 3 exons deleted (IQR 1-6). Subjects with mutations starting at exon positions 40-54 had a later onset of arrhythmias occurring at median age 25 years (95% CI 18-∞), p = 0.01. Loss of ambulation occurred later at median age of 13 years (95% CI 12-15) in subjects with mutations that started between exons 55-79, p = 0.01. There was no association between mutation type or location and onset of cardiac dysfunction. We report the genetic variability in DMD and its association with timing of clinical outcomes. Genetic modifiers may explain some phenotypic variability.

We aimed to review current literature on the discard rate of donor hearts offered to pediatric recipients and assess geographical differences. Consequences and ways to reduce the discard rate are discussed. A systemic review on published literature on pediatric transplantation published in English since 2010 was undertaken. Additionally, a survey was sent to international OPOs with the goal of incorporating responses from around the world providing a more global picture. Based on the literature review and survey, there is a remarkably wide range of discard and/or refusal for pediatric hearts offered for transplant, ranging between 18% and 57% with great geographic variation. The data suggest that that the overall refusal rate may have decreased over the last decade. Reasons for organ discard were difficult to identify from the available data. Although the refusal rate of pediatric donor hearts seems to be lower compared to that reported in adults, it is still as high as 57% with geographic variation.

Infants with aortic coarctation may present with left ventricular (LV) dysfunction which may complicate the postoperative course and lead to increased healthcare costs. We aimed to define the prevalence of moderate to severe left ventricular (LV) systolic dysfunction, evaluate time to recovery, and compare health care costs. Single-center retrospective cohort study at a tertiary care hospital was conducted. Infants 6 months old at diagnosis with aortic coarctation were identified using surgical codes for coarctation repair between January 2010 and May 2018. Moderate to severe dysfunction was defined as ejection fraction (EF) 40%. Of 160 infants studied, 18 (11%) had moderate to severe LV dysfunction at presentation. Compared to those with better LV function, infants with moderate to severe LV dysfunction were older at presentation (12 vs. 6 days, p = 0.004), had more postoperative cardiac intensive care unit (ICU) days (5 vs. 3, p 0.001), and more ventilator days (3.5 vs. 1, p 0.001). The median time to normal LV EF (≥ 55%) was 6 days postoperatively (range 1-230 days). Infants presenting with moderate to severe LV dysfunction had higher index hospitalization costs ($90,560 vs. $59,968, p = 0.02), but no difference in cost of medical follow-up for the first year following discharge ($3,078 vs. $2,568, p = 0.46). In the current era, 10% of infants with coarctation present with moderate to severe LV dysfunction that typically recovers. Those with moderate to severe dysfunction had longer duration of mechanical ventilation and postoperative cardiac ICU stays, likely driving higher costs of index hospitalization.

This case describes an uncommon acute complication of diffuse thrombotic angiopathy and associated aHUS/TTP in an 11-year-old girl with Danon disease who underwent orthotopic heart transplant. Shortly after transplant, despite an uncomplicated operative course, the patient developed severe kidney injury and progressive altered mental status, culminating in cerebral edema, brain herniation, and death. She had received a single dose of tacrolimus (FK506) and a single dose of antithymocyte globulin. Sources of progressive somnolence, including oversedation from impaired renal clearance of opiates, and severe myopathy as has been previously described in Danon disease, were ruled out, and the patient continued to decline. Initial brain CT scan early after transplant showed no signs of cerebral edema, but repeat CT indicated severe cerebral edema. Based on autopsy, diffuse thrombotic angiopathy, with signs of hemolytic anemia with schistocytes, was likely responsible for her deterioration in the broader condition of aHUS/TTP.

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

Purpose Socioeconomic disparities negatively impacts outcomes in heart transplantation (HTx). However, the impact of insurance status and the social construct of race in pediatric patients has not been well studied. Methods The Pediatric Heart Transplant Society registry was queried between January 1, 2000- December 31, 2019. Patients were stratified by insurance status: US government (USG), US private (USP) and Single Payer (SP, UK & Canada) and race (black, white, other). Patients with a selection of more than one race were classified as other. Outcomes after HTx were assessed by Kaplan Meier log rank test including graft survival, time to first cardiac allograft vasculopathy (CAV), rejection, hemodynamic compromised (HC) rejection, and malignancy. Results 5879 children underwent HTx with insurance status as follows: 2800 USG (48%), 2431 USP (41%) and 648 SP (11%). Race breakdown included: 4086 white, 1052 black and 936 other. At 10 years post-transplant, graft survival (65.8% USG, 72.6% USP, 77% SP, p= .0005), time to first CAV (73.5% USG, 77.7% USP, 94.6% SP, p Conclusion In this multinational analysis of pediatric HTx patients, USG was associated with worse post-HTx outcomes. When stratified by race, graft survival was worse in black patients with USG and USP insurance. Both insurance and the social construct of race contribute to worse outcomes post heart transplant and may represent disparity in access to care and other racial bias. These results highlight the importance of further work in this area.

Purpose The incidence and risk factors for sudden cardiac death in Rasopathy patients with hypertrophic cardiomyopathy (Ras-HCM) are not well understood. We compared the cumulative incidence of sudden death and ICD therapy in Ras-HCM compared to primary HCM. Methods Phenotype-positive pediatric patients with Ras-HCM (n=157) and primary HCM (n=720) were included in this 22-center retrospective cohort study. The primary outcome was 5-year freedom from sudden death events, defined as a composite of sudden death, resuscitated sudden cardiac arrest, and aborted events i.e. appropriate shock from a primary prevention ICD, estimated using the Kaplan Meier method. Results There were 17 deaths in Ras-HCM patients - 8 sudden death, 9 from noncardiac causes. The 5-year freedom from sudden death events was higher in Ras-HCM than in primary HCM (97.2% vs 93.8% respectively, p=0.039) (Figure 1A). The median age at diagnosis was lower in Ras-HCM (1.1 yr) versus primary HCM (10 yrs) (p Conclusion The incidence of sudden cardiac death is lower in pediatric Rasopathy patients with HCM compared to primary HCM with most events occurring in infancy. It is less likely for Rasopathy patients to receive an ICD than a primary HCM patient even for secondary prevention, possibly due to younger patient age at the time of the event. Further research on risk factors for and mechanisms of sudden death in Ras-HCM is warranted.

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

Despite increasing legalization and use of marijuana, there is no consensus among pediatric heart transplant institutions or providers regarding users' eligibility for cardiac transplant. We sent a survey to pediatric and ACHD transplant providers (physicians, surgeons, transplant coordinators, and pharmacists) assessing their current institution's policies and their personal opinions about marijuana use in patients being considered for heart transplantation. Of the respondents, 84% practice in the United States and Canada. Most providers (80%) care for both pediatric and ACHD patients. Respondents included cardiologists (77%) and surgeons (11%), with the remaining being coordinators and pharmacists. Most providers (73%) reported their institution had no policy regarding marijuana use in heart transplant candidates. Only 20% of respondents' institutions consider mode of consumption, with 87% and 53% approving of oral and transdermal routes, respectively, and only 7% approving of vaporized or smoked routes. While 73% of providers would consider illegal marijuana use an absolute/relative contraindication to heart transplant listing, the number decreases to 57% for legal recreational users and 21% for legal medical users. Most providers personally believe marijuana to be physically and mentally/emotionally harmful to pediatric patients (67% and 72%, respectively). Many institutions lack a policy regarding marijuana use in pediatric and ACHD heart transplant candidates, and there is considerable disagreement among providers on the best practice. With increasing legalization and use of marijuana, each institution will have to address this issue thoughtfully to continue to provide high-quality, consistent, and equitable care for pediatric and ACHD heart transplant candidates.

There is considerable variability in donor acceptance practices among adult heart transplant providers; however, pediatric data are lacking. The aim of this study was to assess donor acceptance practices among pediatric heart transplant professionals. The authors generated a survey to investigate clinicians' donor acceptance practices. This survey was distributed to all members of the ISHLT Pediatric Council in April 2018. A total of 130 providers responded from 17 different countries. There was a wide range of acceptable criteria for potential donors. These included optimal donor-to-recipient weight ratio (lower limit: 50%-150%, upper limit: 120%-350%), maximum donor age (25-75 years), and minimum acceptable left ventricular EF (30%-60%). Non-US centers demonstrated less restrictive donor selection criteria and were willing to accept older donors (50 vs 35 years, P < 0.001), greater size discrepancy (upper limit weight ratio 250% vs 200%, P = 0.009), and donors with a lower EF (45% vs 50%, P < 0.001). Recipient factors were most influential in the decision to accept marginal donors including recipients requiring ECMO support, ventilator support, and highly sensitized patients with a negative XM. However, programmatic factors impacted the decision to decline marginal donors including recent programmatic mortalities and concerns for programmatic restrictions from regulatory bodies. There is significant variation in donor acceptance practices among pediatric heart transplant professionals. Standardization of donor acceptance practices through the development of a consensus statement may help to improve donor utilization and reduce waitlist mortality.

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.

Introduction Neonates requiring biventricular VAD (BiVAD) support remain a high-risk population. Common challenges include limited space for multiple cannulae, poor wound healing, and difficulties establishing adequate VAD fill and ejection. Given these concerns, we present a unique case using a hybrid procedure and SVAD implant in a neonate with two-ventricle(2V) circulation. Case Report Female term neonate (birth weight 3.2 kg; BSA 0.2 kg/m2) born with a moderate-sized ventricular septal defect (VSD), aortic arch hypoplasia, and severe biventricular dysfunction due to a MHY7 mutation. In light of her weight, likely need for biventricular support given her underlying cardiomyopathy and need for extensive arch repair, we elected to proceed with a hybrid SVAD support strategy. We hypothesized that this approach would decrease the duration of bypass and minimize the number of cannula over the traditional approach of VSD and arch repair with BiVAD support. We also hoped this strategy would provide improved LV decompression, thus improving pulmonary mechanics and nutritional support. On day 6 of life, she underwent atrial septectomy, bilateral PA band placement, and implant of a 10 ml Berlin EXCOR using a 6 mm EXCOR cannula in the right atrium and a 5 mm EXCOR cannula in the main pulmonary artery. A PDA stent was placed using a perventricular approach. She progressed well post-operatively with discontinuation of inotropic support on post-operative day (POD) 3 and extubation on POD 4. VAD fill and ejection have been appropriate. The clinical course is noteworthy for diaphragm paralysis requiring plication and ongoing BiPAP support. Additionally, she developed NEC on POD 23 and has only tolerated ∼30% of her nutritional needs enterally. To date, she has remained on VAD support > 100 days while awaiting transplant. Summary We present a unique case of a neonate with 2V congenital heart disease who has been supported with a hybrid SVAD strategy using a Berlin EXCOR. While this approach has been advantageous in avoidance of VSD and arch repair and requiring fewer cannulae, it also has had challenges; namely, the need for ongoing respiratory and feeding support. We speculate that this may reflect the challenges of optimal PA band placement as well as difficulties providing balanced systemic and pulmonary flow on SVAD support.

Purpose Our study aims to identify the utility of pre-implant MELD-XI score in identifying pediatric patients at higher risk for morbidity and mortality post-VAD implant. Methods We reviewed all patients listed in the PediMACS database from 9/19/12 to 3/31/19. Patients missing bilirubin or creatinine that precluded calculation of MELD-XI score (n=89) were excluded. Patients were divided into three cohorts based on MELD-XI score pre-implant - low (minimum score 9.4, 13.6, 75-100%-tile). Baseline clinical and hemodynamic data were compared; outcomes data on morbidity and mortality were compared across groups. Results Of 596 patients included, 42.5% were in the low, 29.2% in the intermediate and 28.3% in the high MELD-XI cohort. Compared to the low and intermediate cohorts, patients in the high MELD-XI cohort were significantly older (p Conclusion Pediatric patients with an elevated MELD-XI score have higher acuity of illness pre-implant. This easily calculated score based on routinely collected lab values serves as a promising risk assessment tool in identifying pediatric VAD recipients at increased risk for mortality post VAD implant. Trending the MELD-XI score in patients with advanced heart failure may aid clinicians in timing of VAD implantation.

Duchenne muscular dystrophy (DMD) is characterized by myocardial fibrosis and left ventricular (LV) dysfunction. Implantable cardioverter defibrillator (ICD) use has not been characterized in this population but is considered for symptomatic patients with severe LV dysfunction (SLVD) receiving guideline-directed medical therapy (GDMT). We evaluated ICD utilization and efficacy in patients with DMD. Retrospective cohort study of DMD patients from 17 centers across North America between January 2, 2005 and December 31, 2015. ICD use and its effect on survival were evaluated in patients with SLVD defined as ejection fraction (EF)

Purpose As survival and neuromuscular function in Duchenne Muscular Dystrophy (DMD) have improved with glucocorticoid therapy and advances in respiratory care, the proportion of cardiac deaths is increasing. Little is known about risk factors for cardiac causes of death in this population. Methods We conducted a retrospective cohort study of 436 males with DMD followed at 17 centers across North America, from January 1, 2005-December 31, 2015, and sought to identify risk factors for cardiac causes of death, including sudden cardiac death and progressive heart failure. Those dying of cardiac causes were compared to those who died of non-cardiac causes and to those alive at study end. Results There were 29 (6.8%) deaths during the study period at a median age of 19 (IQR: 15-31) years; 8 (27.6%) cardiac (SCD, n=5 and progressive HF, n=3) and 21 non-cardiac (respiratory failure, n=8, multi-organ failure, n=3, stroke, n=1, and other/unknown, n=9). Age at death did not differ based on cause; cardiac 18 (IQR: 15.5-24) years vs. non-cardiac 19 (IQR: 16.5-23) years, p=0.68, but those living were significantly younger (14.9 (IQR: 11.0-19.1) years vs. those who died of cardiac (p=0.03) and non-cardiac (p=0.002) causes). Genetic testing was available for 15/29 deceased (52%) and 292/379 (77%) of those living with all deceased having a deletion, however this did not differ from those living (228/292 (78%), p=0.13). Current or past steroid use was significantly lower in those dying of cardiac causes compared to those living (2/8 (25%) vs. 304/378 (80.4%), p=0.001). Ejection fraction (EF) at study end/death was significantly lower for those dying of cardiac causes compared to those living (mean 37.5% ±12.8 vs. 54.5% ±10.8, p=0.01) but not compared to those dying of non-cardiac causes (37.5% ±12.8 vs. 41.2% ± 19.3, p=0.58). Fractional shortening (FS) was also lower in those dying of cardiac causes compared to those living (mean 18.5% ±10.2 vs. 29.6% ±7.7, p=0.03) but not compared to those dying of non-cardiac causes (18.5% ±10.2 vs. 23.4 % ±9.2, p=0.3). Conclusion In a large cohort of males with DMD, approximately 1/3rd of deaths were from a cardiac cause. Lack of steroid use was associated with cardiac causes of death, while systolic dysfunction was associated with death from any cause. Future studies are needed to define optimal medical management of systolic dysfunction in males with DMD with hopes of extending survival.

Purpose There is variable practice and debate surrounding prophylactic heart failure (HF) therapy in Duchenne Muscular Dystrophy (DMD) patients with normal systolic function . We sought to determine the impact of HF medications including ACE inhibitors and ARB on the development of moderate systolic dysfunction or death in a cohort of DMD patients. Methods We performed a retrospective cohort study of DMD patients followed at 17 centers across North America from 1/1/2005-12/31/2015. Inclusion criteria were normal systolic function on baseline echocardiogram (ejection fraction (EF) ≥ 55%) and age ≥ 9 years during the study. Moderate systolic dysfunction was defined as an EF≤40% or shortening fraction ≤21% if EF was not available. We compared the composite outcome of moderate systolic dysfunction or death in patients who started HF therapies before evidence of systolic dysfunction (PPX) vs those who did not (non-PPX) using a Cox proportional hazards regression model adjusting for baseline age. We also compared prophylaxis with ACE/ARB (ACE/ARB PPX) to non-PPX. Results 277 males with DMD and normal systolic function were included. Prophylactic HF medications were used in 70 patients (25%) which included ACE/ARB (44, 63%), beta blocker (26, 37%), aldosterone blockade (6, 9%) and digoxin (5, 7%). Medications began at a mean (SD) age of 13.6 (4) years. Mean baseline ages were 10.7 (4.2) and 9.9 (3.9) years in the PPX and non-PPX groups (p=0.16), while mean age to develop moderate systolic dysfunction was 18.6 (5.4) and 16.8 (4.0) in the PPX and non-PPX groups (p=.005). The risk of developing moderate systolic dysfunction or death was 50% lower in the PPX group compared to the non-PPX group (HR=0.50; p=.044) and 79% lower in the ACE/ARB PPX group (N=38) compared to the non-PPX group (HR=0.21; p=0.035) (Figure 1). Conclusion There is variability in the use and choice of prophylactic HF medications in boys with DMD. This cohort showed a benefit to introduction of ACE/ARBs prior to evidence of systolic dysfunction.

There are limited data available on the bioequivalence of generic and brand-name tacrolimus in pediatric and heart transplant patients. We characterized changes in 12-hour trough concentrations and clinical outcomes after transition from brand to generic tacrolimus in pediatric thoracic organ transplant recipients. Patients with a pharmacy-confirmed date of switch between generic and brand tacrolimus were identified, as well as a matched control group that did not switch for comparison. We identified 18 patients with a confirmed date of switch, and in 12 patients that remained on the same dose, trough concentrations were 14% less than when they were on brand (p = 0.037). The average change was -1.15 ± 1.76 ng/mL (p = 0.045). The control group did not experience a change in trough concentration and was different than the switched group (p = 0.005). There were no differences in dosage changes or kidney or liver function. In the year after switch, 24% of patients who were switched to generic experienced a rejection event vs. 18% in the patients on brand. We suggest a strategy of monitoring around the time of transition, and education of the patient/family to notify the care team when changes from brand to generic or between generics occur.

1. Kataoka M, Inami T, Hayashida K, et al. Percutaneous transluminal pulmonary angioplasty for the treatment of chronic thromboembolic pulmonary hypertension. Circ Cardiovasc Interv 2012;5:756-62. 2. Inami T, Kataoka M, Shimura N, et al. Pressure-wire-guided percutaneous transluminal pulmonary angioplasty: a breakthrough in the catheter-interventional therapy for chronic thromboembolic pulmonary hypertension. JACC Cardiovasc Interv 2014;7:1297-306. 3. Kreutzer J, Landzberg MJ, Preminger TJ, et al. Isolated peripheral pulmonary artery stenoses in the adult. Circulation 1996;93:1417-23. 4. Rothman A, Levy DJ, Sklansky MS, et al. Balloon angioplasty and stenting of multiple intralobar pulmonary arterial stenoses in adult patients. Catheter Cardiovasc Interv 2003;58:252-60.

BACKGROUND: Heart failure results in significant morbidity and mortality for young children with hypoplastic left heart syndrome (HLHS) following the Norwood procedure. METHODS: We studied subjects enrolled in the prospective Single Ventricle Reconstruction (SVR) trial who survived to hospital discharge after the Norwood operation and were followed up to age 6 years. The primary outcome was heart failure, defined as heart transplant listing after Norwood hospitalization, death attributable to heart failure or symptomatic heart failure (NYHA class IV). Multivariate modeling was undertaken using Cox regression methodology to determine variables associated with heart failure. RESULTS: Of the 461 subjects discharged to home following Norwood procedure, 66 (14.3%) met criteria for heart failure. Among these, 15 died from heart failure, 39 were listed for transplant (22 had a transplant, 12 died after listing and 5 were alive and not yet transplanted), and 12 had NYHA Class IV heart failure but were never listed. The median age at heart failure identification was 1.28 yrs (interquartile range 0.30 - 4.69 years). Factors associated with heart failure included post-Norwood lower fractional area change, need for ECMO, non-Hispanic ethnicity, Norwood perfusion type and total support time (p

Pediatric cardiomyopathies are rare diseases with an annual incidence of 1.1 to 1.5 per 100 000. Dilated and hypertrophic cardiomyopathies are the most common; restrictive, noncompaction, and mixed cardiomyopathies occur infrequently; and arrhythmogenic right ventricular cardiomyopathy is rare. Pediatric cardiomyopathies can result from coronary artery abnormalities, tachyarrhythmias, exposure to infection or toxins, or secondary to other underlying disorders. Increasingly, the importance of genetic mutations in the pathogenesis of isolated or syndromic pediatric cardiomyopathies is becoming apparent. Pediatric cardiomyopathies often occur in the absence of comorbidities, such as atherosclerosis, hypertension, renal dysfunction, and diabetes mellitus; as a result, they offer insights into the primary pathogenesis of myocardial dysfunction. Large international registries have characterized the epidemiology, cause, and outcomes of pediatric cardiomyopathies. Although adult and pediatric cardiomyopathies have similar morphological and clinical manifestations, their outcomes differ significantly. Within 2 years of presentation, normalization of function occurs in 20% of children with dilated cardiomyopathy, and 40% die or undergo transplantation. Infants with hypertrophic cardiomyopathy have a 2-year mortality of 30%, whereas death is rare in older children. Sudden death is rare. Molecular evidence indicates that gene expression differs between adult and pediatric cardiomyopathies, suggesting that treatment response may differ as well. Clinical trials to support evidence-based treatments and the development of disease-specific therapies for pediatric cardiomyopathies are in their infancy. This compendium summarizes current knowledge of the genetic and molecular origins, clinical course, and outcomes of the most common phenotypic presentations of pediatric cardiomyopathies and highlights key areas where additional research is required. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifiers: NCT02549664 and NCT01912534.

Pediatric heart transplantation (HT) is resource intensive. Event-driven pediatric databases do not capture data on resource use. The objective of this study was to evaluate resource utilization and identify associated factors during initial hospitalization for pediatric HT. This multicenter retrospective cohort study utilized the Pediatric Health Information Systems database (43 children's hospitals in the United States) of children ≤19 years of age who underwent transplant between January 2007 and July 2013. Demographic variables including site, payer, distance and time to center, clinical pre- and post-transplant variables, mortality, cost, and charge were the data collected. Total length of stay (LOS) and charge for the initial hospitalization were used as surrogates for resource use. Charges were inflation adjusted to 2013 dollars. Of 1,629 subjects, 54% were male, and the median age at HT was 5 years (IQR [interquartile range] 0 to 13). The median total and intensive care unit LOS were 51 (IQR 23 to 98) and 23 (IQR 9 to 58) days, respectively. Total charge and cost for hospitalization were $852,713 ($464,900 to $1,609,300) and $383,600 ($214,900 to $681,000) respectively. Younger age, lower volume center, southern region, and co-morbidities before transplant were associated with higher resource use. In later years, charges increased despite shorter LOS. In conclusion, this large multicenter study provides novel insight into factors associated with resource use in pediatric patients having HT. Peritransplant morbidities are associated with increased cost and LOS. Reducing costs in line with LOS will improve health-care value. Regional and center volume differences need further investigation for optimizing value-based care and efficient use of scarce resources.

For many neuromuscular diseases (NMDs), cardiac disease represents a major cause of morbidity and mortality. The management of cardiac disease in NMDs is made challenging by the broad clinical heterogeneity that exists among many NMDs and by limited knowledge about disease-specific cardiovascular pathogenesis and course-modifying interventions. The overlay of compromise in peripheral muscle function and other organ systems, such as the lungs, also makes the simple application of endorsed adult or pediatric heart failure guidelines to the NMD population problematic. In this statement, we provide background on several NMDs in which there is cardiac involvement, highlighting unique features of NMD-associated myocardial disease that require clinicians to tailor their approach to prevention and treatment of heart failure. Undoubtedly, further investigations are required to best inform future guidelines on NMD-specific cardiovascular health risks, treatments, and outcomes.

As VAD have become an effective therapy for end-stage heart failure, their application in congenital heart disease has increased. Single ventricle congenital heart disease introduces unique physiologic challenges for VAD use. However, with regard to the mixed clinical results presented within this review, we suggest that patient selection, timing of implant, and center experience are all important contributors to outcome. This review focuses on the published experience of VAD use in single ventricle patients and details physiologic challenges and novel approaches in this growing pediatric and adult population.

Clinical practice variations are a barrier to the study of pediatric heart transplants and coordination of multicenter RCTs in this patient population. We surveyed centers to describe practice patterns, understand areas of variation, and willingness to modify protocol. Pediatric heart transplant centers were identified, and one survey was completed per center. Simple descriptive statistics were used. The response rate was 77% (40 responses from 52 contacted centers, 37 with complete responses). Median center volume of respondents was eight transplants/year (IQR 3-19). Most centers reported tacrolimus (36/38, 95%) and mycophenolate mofetil (36/38, 95%) as maintenance immunosuppression. Other immunosuppression agents reported were cyclosporine (7/38, 18%), everolimus or sirolimus (3/38, 8%), and azathioprine (2/38, 5%). Overall, respondents answered similarly for questions regarding clinical practices including induction therapy, maintenance immunosuppression, and rejection treatment threshold (>85% agreement for all). Additionally, willingness to change clinical practices was over 70% for all practices surveyed (35 total respondents), and 97% of centers (36/37) were willing to participate in a RCT of maintenance immunosuppression. In conclusion, we found many similar clinical practice protocols. Most centers are willing to collaborate on a common protocol in order to participate in a RCT and support a trial investigating maintenance immunosuppression.

Myocarditis is an important but incompletely understood cause of cardiac dysfunction. Children with fulminant myocarditis often require inotropic or mechanical circulatory support, and researchers in some studies suggest that up to 42% of children who die suddenly have evidence of myocarditis. Recurrent myocarditis is extremely rare, and the vast majority of reported cases involve adult patients. Pediatric providers who suspect a recurrence of myocarditis have limited evidence to guide patient management because the literature in this domain is sparse. Here we present a unique, illustrative pediatric case of recurrent myocarditis. A 14-year-old boy presented for the second time in 2 years with a clinical history strongly suggestive of myocarditis. Although myocarditis was suggested in the results of cardiac MRI, no pathogen was identified during his first presentation. During his second episode of myocarditis, parvovirus was confirmed by polymerase chain reaction testing of an endomyocardial specimen that also met Dallas criteria for myocarditis. With each presentation, he had decreased ventricular function that subsequently normalized. To the best of our knowledge, there are no reports of recurrent myocarditis in children in whom the diagnosis was confirmed by using MRI and/or biopsy data. Reviewing this distinctive case and the existing literature may help characterize this entity and raise awareness among care providers.

The objective of this study was to describe a contemporary cohort of pediatric patients hospitalized for clinically suspected myocarditis. A retrospective chart review was performed at seven tertiary pediatric hospitals. Electronic medical records were searched between 2008 and 2012 for patients ≤18 years admitted with an ICD-9 code consistent with myocarditis. Patients were excluded if the admitting or consulting cardiologist did not suspect myocarditis during the admission or an alternative diagnosis was determined. One hundred seventy-one patients were discharged or died with a primary diagnosis of myocarditis. Median age was 13.1 years (IQR 2.1, 15.9), with a bimodal distribution; 24%

Purpose Current guidelines for the management of left ventricular systolic dysfunction (LVSD) in Duchenne Muscular Dystrophy (DMD) recommend angiotensin converting enzyme (ACE) inhibitors (class IIa). Little is known about the historic use of HF medications in Duchenne Muscular Dystrophy (DMD) and LVSD. Methods We performed a retrospective cohort study of DMD patients followed at 17 centers across North America from January 1, 2005-December 31, 2015. LVSD was defined as an ejection fraction (EF) Results LVSD was present in 209/436 (47.9%) DMD males including 84 (19.3%) patients with LVSD on baseline echocardiogram with median age 14 (IQR 11-17). 125 (28.7%) patients developed LVSD during the study with a median age at diagnosis of 15 years (IQR 12-17). Of the 209 patients with LVSD, 48 (23.0%) were never on HF medications, 105 (50.2%), 44 (21.0%), 11 (5.3%) and 1 (0.5%) were on single, dual, triple and quad HF therapy respectively. HF medications prescribed during the study period for those with LVSD included angiotensin converting enzyme inhibitor/angiotensin receptor blocker (ACE/ARB) (134, 64.1%), aldosterone antagonist (17, 8.1%), beta blocker (55, 26.3%), and digoxin (12, 5.7%). 154 (73.7%) were not on heart failure medications at study entry (baseline visit) and first line therapies included ACE/ARB (77, 51.0%), beta blockers (32, 21.2%), aldosterone antagonist (2, 1.3%), and digoxin (6, 4.0%). Overall therapies for these 154 patients included ACE/ARB (84, 55.6%), beta blocker (46, 30.5%), aldosterone antagonist (8, 5.3%) and digoxin (8, 5.3%). Conclusion There is significant practice variability that is not consistent with current consensus guidelines in the utilization of HF medications in DMD patients with LVSD. Almost 65% of the cohort were started on an ACE/ARB, however 23% were never prescribed a HF medication. Further studies are needed within the DMD population to understand the efficacy and decision making related to the prescription of common HF medications.

Background: Pediatric heart transplantation (HT) is resource intensive. Event driven pediatric HT databases do not capture data on resource use. The objective of this study was to evaluate resource utilization and identify associated factors during initial hospitalization for pediatric HT in a large multi-institutional cohort. Methods: This is a multicenter retrospective cohort study using the PHIS database (43 US children’s hospitals) of children ≤ 19 years of age who underwent HT between 1/07 and 7/13. Data collected: Demographic variables including site, payer, distance and time to center, clinical pre and post-transplant variables, mortality, cost and charge. Total length of stay (LOS) and charge for initial hospitalization were used as surrogates for resource use. Charges were inflation adjusted to 2013 $. Gamma regression analysis was performed to evaluate factors associated with resource use. Results: Of 1629 subjects, 54% were male, and the median age at HT was 5 years (IQR 0-13). The median total and ICU LOS were 51 (IQR: 23-98) and 23 (IQR: 9-58) days respectively, and mortality occurred in 82 (5%). Total charge and cost for hospitalization were $852,713 ($464,900-$1,609,300) and $383,600 ($214,900-$681,000) respectively. Factors associated with resource use on multivariate analysis are shown in Table 1. Younger age, lower center volume, southern region, and comorbidities prior to HT were associated with higher resource use. In later years, costs increased despite shorter LOS. Conclusions: This large multicenter study provides novel insight into factors associated with resource use in pediatric HT that cannot be assessed in alternative event driven transplant databases. Peri-transplant morbidities are associated with increased cost and LOS. Reducing costs in line with LOS will improve health care value. Regional and center volume differences need further investigation for optimizing value-based care and efficient use of scarce resources.