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Background: Chronic kidney disease (CKD) is common after heart transplantation (HT). There are scarce studies looking at longitudinal changes in estimated glomerular filtration rate (eGFR) after repeat HT (RT) and risk factors for the presence of CKD3 post-RT., Methods: First-time HT recipients (FT) were matched with RT, based on age at transplant, sex, race, and transplant era. eGFR was derived from CKiD-U25 formula using creatinine. Changes in eGFR were measured within and between patients using a mixed effects model. Logistic regression and survival analysis were performed to identify significant risk factors for CKD3 presence post-RT., Results: The unmatched cohort included 393 HT recipients and 47 RT. 29 patients in both groups with at least 2 years of follow-up data underwent matching. Over 6 years, the mean eGFR for FT and RT did not significantly change overtime. For those with CKD3 or higher prior to RT, 73% improved to CKD2 or lower at 2 years post-RT. Risk factors for CKD3 post-RT included female sex (OR 17.5 [1.7-181.9], p = 0.017) and greater than two acute kidney injuries (AKI) between FT and RT (OR 1.77 [1.06-2.95], p = 0.03). Approximately 50% of females and those with greater than two AKIs maintained or developed CKD3 at 7.5 and 3 years, respectively., Conclusion: This study provides data on longitudinal changes in eGFR over 6 years and finds that female sex and repeat HT recipients with greater 2 AKIs between transplants are at greatest risk for CKD3 presence post-RT., (© 2024 Wiley Periodicals LLC.)

Adverse events (AEs) experienced by children and adults with congenital heart disease (CHD) on ventricular assist devices (VADs) are sometimes unique to these populations. The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) and the Academic Research Consortium (ARC) aimed to harmonize definitions of pediatric and CHD AEs for use in clinical trials, registries, and regulatory evaluation. Data from the ACTION registry and adjudication committee were used to adapt general mechanical circulatory support ARC definitions. This ACTION-ARC international expert panel of trialists, clinicians, patients, families, statisticians, biomedical engineers, device developers, and regulatory agencies drafted and iterated definitions harmonized to ACTION data and existing literature during sessions conducted between December 2022 and May 2023, followed by dissemination across clinical/research audiences and professional organizations and further revision. Both email-linked, internet-based surveys and in-person discussions were used as a modified Delphi process. Nineteen AE types were identified and defined, including seven new event types and six event types that were deleted and will no longer be collected, achieving consensus. ACTION-ARC paired rigorous development with methodical stakeholder involvement and dissemination to define pediatric VAD AEs to facilitate assimilation of data across future clinical trials and evaluation of devices for VAD-supported children and adults with CHD., Competing Interests: Disclosure: A.L. is a consultant for Bayer, Abbott, Abiomed, Berlin Heart, and Syncardia and is the primary investigator for the Berlin ACTIVE driver trial. I.A. is a consultant for Abbott, Abiomed, Bivacor, and Berlin Heart. P.M.A.A. is Treasurer of the Board of Directors of the Extracorporeal Life Support Organization (ELSO) and immediate past-chair of PediECMO, a research collaborative between ELSO and the Pediatric Acute Lung Injury and Sepsis Investigators. P. Alexander’s institution received funding from the National Institutes of Health (NICHD R13HD104432) and the U.S. Department of Defense (U.S. DoD PRMRP Clinical Trial Award #W81XWH2210301). R.P.B. reports grants from the National Institutes of Health (NIH) R01 HL153519 and is a member of the Extracorporeal Life Support Organization (ELSO) Board of Directors. S.B. is a full-time employee of Abiomed, Inc. a part of Johnson and Johnson. K.B. is an Abbott employee. J.C. receives an unrestricted education grant—from Abbott and is a medical monitor for Pumpkin Trial. R.R.D. is a paid consultant for Abbott, Inc. and Abiomed, Inc. R.L.K. is an employee at Abbott, Inc. R.K. is an employee at Berlin Heart Inc. M.K. is involved in Grants & Consulting for Medtronic, Abbott Vascular, Johnson & Johnson, Boston Scientific, and Getinge. J.L. is a consultant for Abbott. D.L.S.M. is a consultant for Abbott Inc., Syncardia Inc., and Berlin Heart Inc. R.A.N. uses Berlin Heart of North America travel funds to attend the annual user’s group meeting. F.D.P. is a non-compensated ad-hoc scientific advisor for Abbott, BrioHealth Solutions, FineHeart, and Medtronic, a non-compensated medical monitor for Abiomed, a member—Data Safety Monitoring Board for Carmat, receives grant funding from the National Heart, Lung, and Blood Institute and the Agency for Healthcare Research and Quality, and receives partial salary support from Blue Cross/Blue Shield of Michigan as Associate Director of the Michigan Society of Thoracic and Cardiovascular Surgeons Quality Collaborative. D.M.P. is on the Data Safety Monitoring Board for the Berlin Active Driver Trial. D.R. is associated with ACTION, DSMB for Parexel (unrelated to topic of AE manuscript), and Medicolegal consultation (unrelated to topic of AE manuscript). J.W.R. is a consultant for American Regent, AskBio, BioMarin, Bayer, Merck, Bristol Myers Squibb, and Enzyvant. E.S. reports institutional contracts for which he receives no direct compensation with Boston Scientific, Cardiawave, Edwards Lifesciences, Medtronic, Shanghai Microport Medical Co. Ltd., NVT GmBH, Pie Medical Imaging, Siemens Healthcare GmBH. M.E.S. is involved in a Medtronic educational contract, Octapharma advisory panel, and NIH DSMB for PumpKIN trial (completed). J.M.T. is a Berlin Heart CEC member. C.V. is on the Merck scientific advisory committee and a consultant for Abiomed. C.R.V. is a consultant for PTC therapeutics (previous), Antisense (current), and Capricor (current). The other authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)

Background: Impacts of ischemic time (IT) on pediatric heart transplant outcomes are multifactorial. We aimed to analyze the effect of prolonged IT on graft loss after pediatric heart transplantation. We hypothesized that graft survival with prolonged IT has improved across eras., Methods: Patients <18 years old in the Pediatric Heart Transplant Society database were included (N=6,765) and stratified by diagnosis and era (1993-2004, 2005-2009, and 2010-2019). Severe graft failure (SGF) was defined as death, retransplant, or need for mechanical circulatory support in the first 7 days post-transplant. Descriptive statistical methods were used to compare differences between patient characteristics and IT. Kaplan-Meier survival analysis compared freedom from graft loss, rejection, and infection. Multivariable analysis was performed for graft loss and SGF (hazard and logistic regression modeling, respectively)., Results: Diagnoses were cardiomyopathy (N = 3,246) and congenital heart disease (CHD; N = 3,305). CHD were younger, more likely to have an IT ≥4.5 hours, and more likely to require extracorporeal membrane oxygenation or mechanical ventilation at transplant (all p < 0.001). Median IT was 3.6 hours (interquartile range 2.98-4.31; range 0-10.5). IT was associated with early graft loss (HR 1.012, 95% CI 1.005-1.019), but not when analyzed only in the most recent era. IT was associated with SGF (OR 1.016 95%CI 1.003-1.030)., Conclusions: Donor IT was independently associated with an increased risk of graft loss, albeit with a small effect relative to other risk factors. Graft survival with prolonged IT has improved in the most recent era but the risk of SGF persists., (Copyright © 2024 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

SARS-CoV-2 infection during the Omicron period was frequent amongst a cohort of vaccinated pediatric solid organ transplant recipients (pSOTRs) despite robust anti-receptor-binding domain (anti-RBD) antibody response, suggesting poor neutralizing capacity against Omicron subvariants. Breakthrough infections among pSOTRs were overall limited in severity., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Renal function is reduced in patients undergoing heart transplant due to hemodynamic compromise, cardiorenal syndrome, and nephrotoxin exposure. No current studies evaluate renal function in retransplants., Methods: We reviewed all heart transplants at our center from 1995 to 2021 and matched first-time heart transplants with retransplants, based on age at transplant, sex, and race. Estimated glomerular filtration rate (eGFR) was derived from CKiD-U25 calculator using creatinine and measured prior to transplant, 1-week post-transplant, 1-3, 6, and 12 months post-transplant, and recent follow-up. Changes in eGFR were measured within and between patients using a piecewise linear mixed effect model with matching. Exploratory univariate analysis was performed to evaluate pre-transplant risk factors for decreased eGFR., Results: The unmatched cohort included 393 heart transplant recipients, with 47 being retransplants. Thirty-eight patients in both groups with at least 1 year of follow-up underwent matching. Both retransplants and first-time transplants had an initial decline in eGFR. eGFR rebounded to baseline or above baseline at 1-3 months post-transplant, but eGFR in retransplants remained significantly lower. At 1-year post-transplant, the average eGFR was 67.8 ± 4.3 mL/min/1.73 m 2 versus 104.7 ± 4.3 mL/min/1.73 m 2 (p < .001) in the retransplants and first-time transplants group, respectively., Conclusion: This study provides data on anticipated renal trajectory following retransplantation., (© 2023 Wiley Periodicals LLC.)

Background: The Pediatric Heart Transplant Society (PHTS) Registry was founded 30 years ago as a collaborative effort among like-minded providers of this novel life-saving technique for children with end-stage heart failure. In the intervening decades, the data from the Registry have provided invaluable knowledge to the field of pediatric heart transplantation. This report of the PHTS Registry provides a comprehensive look at the data, highlighting both the longevity of the registry and one unique aspect of the PHTS registry, allowing for exploration into children with single ventricle anatomy., Methods: The PHTS database was queried from January 1, 1993 to December 31, 2019 to include pediatric (age < 18 years) patients listed for HT. For our analysis, we primarily analyzed patients by era. The early era was defined as children listed for HT from January 1, 1993 to December 31, 2004; middle era January 1, 2005 to December 31, 2009; and recent era January 1, 2010 to December 31, 2019. Outcomes after listing and transplant, including mortality and morbidities, are presented as unadjusted for risk, but compared across eras., Results: Since 1993, 11 995 children were listed for heart transplant and entered into the PHTS Registry with 9755 listed during the study period. The majority of listings occurred within the most recent era. Waitlist survival improved over the decades as did posttransplant survival. Other notable changes over time include fewer patients experiencing allograft rejection or infection after transplant. Waitlist and posttransplant survival have changed dramatically in patients with single ventricle physiology and significantly differ by stage of single ventricle palliation., Summary: Key points from this PHTS Registry summary and focus on patients with single ventricle congenital heart disease in particular, include the changing landscape of candidates and recipients awaiting heart transplant. There is clear improvement in waitlist and transplant outcomes for children with both cardiomyopathy and congenital heart disease alike., (© 2023 Wiley Periodicals LLC.)

Background: Adolescent solid organ transplant recipients (aSOTRs) who received three doses of the COVID-19 mRNA vaccine experience high seroconversion rates and antibody persistence for up to 3 months. Long-term antibody durability beyond this timeframe following three doses of the SARS-CoV-2 mRNA vaccine remains unknown. We describe antibody responses 6 months following the third vaccine dose (D3) of the BNT162b2 mRNA vaccination among aSOTRs., Methods: Participants in a multi-center, observational cohort who received the third dose of the vaccine were analyzed for antibodies to the SARS-CoV-2 spike protein receptor-binding domain (Roche Elecsys anti-SARS-CoV-2-S positive: ≥0.8, maximum: >2500 U/mL). Samples were collected at 1-, 3-, and 6-months post-D3. Participants were surveyed at each timepoint and at 12-months post-D3., Results: All 34 participants had positive anti-RBD antibody titers 6 months post-D3. Variations in titers occurred between 3 and 6 months post-D3, with 8/28 (29%) having decreased antibody levels at 6 months compared to 3 months and 2/28 (7%) reporting increased titers at 6 months. The remaining 18/28 (64%) had unchanged antibody titers compared to 3-month post-D3 levels. A total of 4/34 (12%) reported breakthrough infection within 6 months and 3/32 (9%) reported infection after 6-12 months following the third dose of the SARS-CoV-2 mRNA vaccine., Conclusions: The results suggest that antibody durability persists up to 6 months following three doses of the SARS-CoV-2 mRNA in aSOTRs. Demography and transplant characteristics did not differ for those who experienced antibody weaning. Breakthrough infections did occur, reflecting immune-evasive nature of novel variants such as Omicron., (© 2024 Wiley Periodicals LLC.)

Given the numerous opportunities and the wide knowledge gaps in pediatric heart failure, an international group of pediatric heart failure experts with diverse backgrounds were invited and tasked with identifying research gaps in each pediatric heart failure domain that scientists and funding agencies need to focus on over the next decade., Competing Interests: DECLARATION OF COMPETING INTEREST S.A. is a site PI for a multicenter study led by the University of Michigan (reports no salary support). J.H. is the president of the Ohio College of Clinical Pharmacy and reports reimbursement for attending the annual meeting. S.C. reports honoraria for her speaking engagements by Enduring Hearts. J.R. is a consultant for Bayer, Merck, Bristol Myers Squibb, CRI Biotech, and American Regent; and reports payment for medical legal review. J.S. serves on the leadership committee for the Advanced Cardiac Therapies Improving Outcomes Network (ACTION). J.P. is a board member for the myocarditis foundation. S.M. is funded by the NIH/NHLBI, American Heart Association, and Additional Ventures; patents issued: CU2150H (Co-inventor for: “microRNA expression in pediatric heart failure patients), CU2650H (Co-inventor for: “Selective Inhibition of Beta-Adrenergic Receptors for the Treatment of Pediatric Heart Failure), patent pending: CU3250H (Co-inventor for: “microRNAs as a Prognostic Biomarker in Pediatric Heart Failure); and serves on the advisory board for Children's cardiomyopathy foundation, and Additional Ventures. K.L. serves as Chair of the Pediatric heart failure committee, American Heart Association Young Hearts Council. J.C. serves on the DSMB for the PumpKIN and reports unrestricted educational grant from Abbott. M.K.C. receives research funding and salary support from NHLBI (5K23HL145096), reports funding from Additional Ventures and Enduring Hearts, and serves on leadership for ISHLT, Transplant Families, Enduring Hearts. and ACTION. F.Z. reports research funding from National Institutes of Health (R01HL147957) and has stock in TransMedics, Inc. R.S. reports consulting fees from Novartis, CRI Biotech, American Regent, and Rocket Pharmaceuticals. K.S. serves on the scientific advisory board for Enduring Hearts. D.P. serves on the DSMB for Berlin EXCOR Active Driving system study. J.G. reports consulting fees from Daiichi Sankyo and has stock in Abbott. M.C. is funded by NIH/NHLBI, Additional Ventures, and Enduring Hearts. The other authors report no conflicts/disclosures., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The removal of the HeartWare ventricular assist device (HVAD) due to pump malfunctions and inferior outcomes compared to HeartMate 3 (HM3) in adults has created a care gap for younger patients. It is unclear if the reported HVAD survival differs by age and if the initial experience with HM3 can bridge the gap., Methods: Using the Society of Thoracic Surgeons (STS) Intermacs and Pedimacs registries, durable ventricular assist device (VAD) implants between September 2012 and December 2021 were identified. Young adults (YA) were defined as <40 years old in Intermacs. Patients were excluded if they had an isolated right VAD (RVAD) or were implanted as destination therapy (DT). Survival analysis by Kaplan-Meier (KM) and competing outcomes curves was performed, and 1-year survival is reported., Results: The Intermacs cohort consisted of YA (n = 1226; HVAD 818; HM3 408) with a median age of YA of 32.07 (26.66-36.27) years and weight (wt) of 83.2 (68-104.2) kg. Most had cardiomyopathy (CM) (92.2%). The Pedimacs cohort was 668 patients (median age 9.47 [1.82-14.23] years, wt 27.2 [10-57.05] kg), and most also had CM (70.5%). Device breakdown included HVAD (n = 326), Berlin EXCOR (n = 277), and HM3 (n = 65). HVAD survival differed by age in adults, with YA fairing better than adults >40 years old (88.8% vs 79.4% at 1 year, p < 0.0001). YA survival was also better compared to Pedimacs patient (88.9% vs 83.7%, p = 0.0002), but when competing events were analyzed, mortality was similar to YA (9.2% vs 9.6%, p = 0.1) with a higher proportion of patient undergoing transplant at 1 year in Pedimacs (74% vs 31.3%, p < 0.0001). Survival by device differed between HVAD and HM3 in YA (88.8% vs 94.4%, p = 0.0025). This difference in device survival was not seen in all children (83.7% vs 87.3%, p = 0.21), including those ≥25 kg. Adverse event profiles also differed across the groups with adults seeing less adverse events with the HM3, but the same was not found (including stroke) in the pediatric cohort. Survival outcomes for patients between 10 and 25 kg were similar with the HVAD compared to the Berlin Heart EXCOR (p = 0.4290), with similarities in stroke risk., Conclusion: The removal of the HVAD device may result in a care gap in younger patient whose survival outcomes do not mirror that of older adults. The HM3 can fill a portion of this gap with good survival, but there remains a subset of pediatric patients that, based on initial HM3 use, will no longer have access to intracorporeal support and therefore, despite reasonable outcomes with the Berlin Heart EXCOR, will not be able to be discharged home. Lastly, it is essential that future changes to the availability of devices take into account the various patient populations that utilize the device to avoid unintended consequences of access inequality., (Copyright © 2023 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: We report current outcomes in patients supported with the HeartMate 3 (HM3) ventricular assist device in a multicenter learning network., Methods: The Advanced Cardiac Therapies Improving Outcomes Network database was queried for HM3 implants between 12/2017 and 5/2022. Clinical characteristics, postimplant course, and adverse events were collected. Patients were stratified according to body surface area (BSA) (<1.4 m 2 , 1.4-1.8 m 2 , and >1.8 m 2 ) at device implantation., Results: During the study period, 170 patients were implanted with the HM3 at participating network centers, with median age 15.3years; 27.1% were female. Median BSA was 1.68 m 2 ; the smallest patient was 0.73 m 2 (17.7 kg). Most (71.8%) had a diagnosis of dilated cardiomyopathy. With a median support time of 102.5days, 61.2% underwent transplantation, 22.9% remained supported on device, 7.6% died, and 2.4% underwent device explantation for recovery; the remainder had transferred to another institution or transitioned to a different device type. The most common adverse events included major bleeding (20.8%) and driveline infection (12.9%); ischemic and hemorrhagic stroke were encountered in 6.5% and 1.2% of patients, respectively. Patients with BSA <1.4 m 2 had a higher incidence of infection, renal dysfunction, and ischemic stroke., Conclusions: In this updated cohort of predominantly pediatric patients supported with the HM3 ventricular assist device, outcomes are excellent with <8% mortality on device. Device-related adverse events including stroke, infection, and renal dysfunction were more commonly seen in smaller patients, highlighting opportunities for improvements in care., (Copyright © 2023 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Social factors like race and insurance affect transplant outcomes. However, little is known in pediatric heart transplantation. We hypothesized that race and insurance coverage impact listing and waitlist outcomes across eras., Methods: Data from the Pediatric Heart Transplant Society multi-center registry prospectively collected between January 1, 2000-December 31, 2019 were analyzed. Patients were divided by race as Black, White and other and by insurance coverage at listing (US governmental, US private and non-US single payer systems (UK, Canada). Clinical condition at listing and waitlist outcomes were compared across races and insurance coverages. Categorical variables were compared using a chi-square test and continuous variables using the Wilcoxon rank sum test. Risk factors for waitlist mortality were examined using multiphase parametric hazard modeling. A sensitivity analysis using parametric hazard explored the interaction between race and insurance., Results: At listing, compared to Whites (n = 5391) and others (n = 1167), Black patients (n = 1428) were older, more likely on US governmental insurance and had cardiomyopathy as the predominant diagnosis (p < 0.0001). Black patients were more likely to be higher status at listing, in hospital, on inotropes or a ventricular assist device (p < 0.0001). Black patients had significantly shorter time on the waitlist compared to other races (p < 0.0001) but had higher waitlist mortality (p = 0.0091), driven by the earlier era (2000-2009) (p = 0.0005), most prominently within the US private insurance cohort (p = 0.015). Outcomes were not different in other insurance cohorts or in the recent era (2010-2019)., Conclusion: Black children are older and sicker at the time of listing, deteriorate more often and face a higher wait list mortality, despite a shorter waitlist period and favorable clinical factors, with improvement in the recent era associated with the recent US healthcare reforms. The social construct of race appears to disadvantage Black children by limiting referral, consideration or access to pediatric cardiac transplantation., (Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

SARS-CoV-2 vaccine-associated myocarditis/myocardial injury should be evaluated in the contexts of COVID-19 infection, other types of viral myocarditis, and other vaccine-associated cardiac disorders. COVID-19 vaccine-associated myocardial injury can be caused by an inflammatory immune cell infiltrate, but other etiologies such as microvascular thrombosis are also possible. The clinical diagnosis is typically based on symptoms and cardiac magnetic resonance imaging. Endomyocardial biopsy is confirmatory for myocarditis, but may not show an inflammatory infiltrate because of rapid resolution or a non-inflammatory etiology. Myocarditis associated with SARS-COVID-19 vaccines occurs primarily with mRNA platform vaccines, which are also the most effective. In persons aged >16 or >12 years the myocarditis estimated crude incidences after the first 2 doses of BNT162b2 and mRNA-1273 are approximately 1.9 and 3.5 per 100 000 individuals, respectively. These rates equate to excess incidences above control populations of approximately 1.2 (BNT162b2) and 1.9 (mRNA-1273) per 100 000 persons, which are lower than the myocarditis rate for smallpox but higher than that for influenza vaccines. In the studies that have included mRNA vaccine and SARS-COVID-19 myocarditis measured by the same methodology, the incidence rate was increased by 3.5-fold over control in COVID-19 compared with 1.5-fold for BNT162b2 and 6.2-fold for mRNA-1273. However, mortality and major morbidity are less and recovery is faster with mRNA vaccine-associated myocarditis compared to COVID-19 infection. The reasons for this include vaccine-associated myocarditis having a higher incidence in young adults and adolescents, typically no involvement of other organs in vaccine-associated myocarditis, and based on comparisons to non-COVID viral myocarditis an inherently more benign clinical course., Competing Interests: Disclosures M.R. Bristow is an Officer and shareholder of ARCA Biopharma, a precision therapeutics biotechnology company developing pharmacogenetic heart failure drugs. The other authors report no conflicts.

Purpose: 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., Methods: 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., Results: 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., Conclusions: 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., (Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

The use of mechanical circulatory support (MCS) for pediatric patients who have undergone heart transplant has grown rapidly in the past decade. This includes support in the immediate post-transplant period and "rescue" therapy for patient later in their transplant course. Extracorporeal membrane oxygenation (ECMO) remains a standard modality of support for intraoperative concerns and for acute decompensation in the immediate post-transplant period. However, both pulsatile and continuous flow ventricular assist devices (VADs) have been used with increasing success in transplant patients for longer durations of support. Centers participating in the Pediatric Heart Transplant Society (PHTS) were queried to provide their internal protocols and rationale for mechanical circulatory support following heart transplant. These protocols coupled with evidence-based literature were used to provide the following description of clinical approaches to MCS in the transplant patient highlighting areas of both broad consensus and significant practice variation., (© 2022 Wiley Periodicals LLC.)

Background: We evaluated the impact of pediatric heart-allocation policy changes over time and the approval of the Berlin ventricular assist device (VAD) on waitlist (WL) outcomes for children with congenital heart disease (CHD)., Methods: The Scientific Registry of Transplant Recipients database was evaluated to include all children (age < 18) with CHD and cardiomyopathy (CMP) on the WL between 1999 and 2019, divided into 4 eras: Era 1 (1999-2008); Era 2 (2009-2011); Era 3 (2012-2016); and Era 4 (2016-2019). WL characteristics and survival outcomes were evaluated for patients with CHD over time and were compared to those with CMP listed currently (Era 4)., Results: We included 5185 children with CHD on the WL during the study period; 1999 (39%) were listed in Era 1; 693 (13%) in Era 2; 1196 (23%) in Era 3; and 1297 (25%) in Era 4. Compared to the CHD WL in eras 1 and 2, those in Era 4 were less likely to be infants (48% vs 49% vs 43%), on mechanical ventilation (30% vs 26% vs 19%), on extracorporeal membrane oxygenation (15% vs 9.7% vs 6.2%), and were more likely to be on a VAD (2.4% vs 2.2% vs 6.0%) (P < .05 for all). WL survival improved in children with CHD from Era 1 to Era 4 (P < .001). However, in Era 4, children with CHD had lower WL survival than those with CMP (P < .001)., Conclusion: Children with CHD are increasingly being listed with less advanced heart failure, and they have had improved WL survival over time; however, WL outcomes remain inferior to those with CMP. Advances in pediatric medical and VAD therapy may improve future WL outcomes., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Reports focused on adult heart transplant (HTx) recipients with COVID-19 suggest an increased risk of severe disease, however; it is unclear if this holds true for pediatric HTx patients, given the typically milder course of illness in children in general with COVID-19. We sought to rapidly implement a system for multi-center data collection on pediatric HTx candidates and recipients, with the aim of describing the patient population and infection related outcomes., Methods: The Pediatric Heart Transplant Society (PHTS) is a multi-center collaboration that seeks to improve the outcomes of children who are listed and undergo HTx. The society consists of pediatric HTx centers in North America (n = 53), UK (n = 2), and Brazil (n = 1). In response to the pandemic, PHTS developed a web-based platform to collect COVID-19 specific data on pediatric HTx candidates and recipients. Non-PHTS centers were also invited to submit data. Data fields included pre-and post-HTx patient characteristics, presumed versus documented infection, need for hospitalization (including ICU and ventilator use), treatments administered, and 30-day outcome (resolution, death, sequelae, and or unresolved) RESULTS: Data collection was initiated on 4/30/20. As of 03/15/21 there were 225 patients [19 pre-HTx and 206 post-HTx, median age 14 years (IQR 7, 18)] reported from 41 centers. Hospitalization occurred in 42% (n = 8) of the pre-HTx and 21% (n=43) of the post-HTx patients. Among the patients listed for HTx, 21% (n = 4) required ICU and 10.5% (n = 2) were mechanically ventilated. Among post-HTx patients, 7% (n = 14) required ICU and 1% (n = 3) were mechanically ventilated. At 30 days, the majority of patients had resolution of symptoms (94.7% pre-HTx, 95.6% post-HTx). One death was reported in a post-HTx patient prior to 30 days from onset of COVID-19 illness., Conclusions: These data demonstrate the ability to rapidly adapt the PHTS data collection infrastructure in response to a novel infection and represent the first known multi-center report of characteristics and early outcomes for patients listed and following pediatric HTx with COVID-19. Hospitalization appears to be more common for both candidates and recipients due to COVID-19 than for the general pediatric population though stays were short and mortality minimal., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

To describe the impact of infectious adverse events (IAEs) during ventricular assist device (VAD) support on graft loss, infection, and rejection after pediatric heart transplant (HT). Pedimacs data were linked to Pediatric Heart Transplant Society (PHTS) data for patients receiving a VAD followed by HT between September 2012 and December 2016. Linked patients were categorized into IAE on VAD (group A) and no IAE on VAD (group B). Infectious adverse event locations included nondevice, device (external or internal), and sepsis. Post-HT outcomes for analysis were graft loss, infection, and rejection. Time-dependent analysis included Kaplan-Meier and multiphase parametric hazard function analysis. We linked 207 patients (age 9.4 ± 6.3 years). Post-HT follow-up was 19.4 patient-months (<8 days-4.1 years). Group A included 42 patients (20%) with 62 IAEs. Group B included 165 patients without an IAE. Group A patients were younger (7.4 ± 6.1 vs. 9.5 ± 6.3 years; p = 0.03), waited longer for HT (5.3 ± 4.1 vs. 2.9 ± 2.5 months; p = 0.0005), and were hospitalized longer post-HT (42 ± 59 vs. 23 ± 22 days; p = 0.05). VAD-related IAEs were rare (N = 11). Groups A and B had similar freedom from first post-HT infection, rejection, and graft loss (all p > 0.1). However, patients with VAD-related IAE were somewhat more likely to experience rejection (p = 0.03) and graft loss (p = 0.01). Children with an IAE on VAD who survive to HT are younger, wait longer for HT, and remain hospitalized longer than those without an IAE on VAD. Overall, IAE on VAD did not impact post-HT outcomes, but VAD-related IAE may be associated with graft loss and rejection., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2021.)

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., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Advanced Cardiac Therapies Improving Outcomes Network (ACTION) is the first pediatric ventricular assist device (VAD) quality improvement network (46 centers). We aimed to describe outcomes with the HeartWare HVAD from ACTION centers. Patients with an HVAD implant in the ACTION registry (April 2018-April 2020) were analyzed. Baseline characteristics, adverse events, and survival were described. There were 50 patients implanted with a HVAD during the study period [36 cardiomyopathy, 8 congenital heart disease (CHD), and 6 other] and 21 (42%) had a prior sternotomy. Median age (range) was 12.9 years (3.4-19.1), body surface area was 1.3 m2 (0.56-2.62), and weight was 41.8 kg (12.8-135.3). Most were INTERMACS profile 2 (n = 26, 52%). Mechanical ventilation and ECMO were used pre-HVAD in 13 (26%) and 6 (12%), respectively. Median time on VAD was 71 (5-602) days. Survival was 96% at 1 year; 3 deaths were recorded, all of whom had CHD (p = 0.001). Neither ECMO nor mechanical ventilation were associated with death (p > 0.29). Most frequent AEs were bleeding (n = 7, 14%) and infection (n = 7, 14%). Stroke was rare (n = 2, 4%). ACTION Network HVAD outcomes were excellent, with 96% survival at 1 year and only 4% occurrence of stroke. Major bleeding and infection were the most common adverse events., (Copyright © ASAIO 2021.)

Background: The size of the Fontan population with end-stage heart failure is growing. In this population, heart transplantation has been the only option. This study sought to investigate the efficacy of ventricular assist device (VAD) support in Fontan patients., Methods: We conducted a retrospective study of Fontan patients in the Advanced Cardiac Therapies Improving Outcomes Network. We evaluated patient characteristics, and the clinical and physiologic outcomes after VAD implantation., Results: We identified 45 Fontan patients implanted with VAD. The average age of patients was 10 years (interquartile range: 4.5-18) and 30% were female. The majority had a morphologic right ventricle (69%), moderate or greater ventricular dysfunction (83%), and moderate or greater atrioventricular valve regurgitation (65%). The majority of implants were as a bridge to transplantation (76%), and the majority of patients were Interagency Registry for Mechanically Assisted Circulatory Support Profile 2 (56%). The most commonly employed device was the Medtronic HeartWare HVAD (56%). A total of 13 patients were discharged on device support, and 67% of patients experienced adverse events, the most common of which were neurologic (25%). At 1 year after device implantation, the rate of transplantation was 69.5%, 9.2% of patients continued to be VAD supported, and 21.3% of patients had died. Hemodynamically, VAD was effective in decreasing both Fontan and ventricular end-diastolic pressures in some individuals., Conclusions: VAD is effective in supporting patients with end-stage Fontan failure awaiting heart transplantation. Future research should focus on identifying clinical and physiologic characteristics predictive of a favorable response to VAD support., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Our purpose was to determine the complication rate from intravascular ultrasound (IVUS) in a large, multicenter cohort of pediatric heart transplant (PHT) patients., Methods: We retrospectively reviewed all PHT who underwent IVUS at 5 institutions (2006-2014). Rates of major and minor complications were calculated. All adverse events (AE) were graded from 1 to 5 using a previously published AE severity scale., Results: There were 1380 catheterizations in 505 patients and 32 AE (2.3%); 9 major (0.6%) and 23 AE (1.7%). The major AE attributed to IVUS were all coronary artery vasospasm (7). Major and minor AE rates directly related to IVUS were 0.5% and 0.7%, respectively. Minor AE possibly attributable to IVUS included excessive fluoroscopy (3) and transient ST segment changes (7). Of AE related to IVUS, only 3 were of moderate severity. The rest were ≤ minor in severity. There were no reports of coronary artery dissection or death., Conclusion: Most AE during routine PHT coronary evaluation with IVUS were minor and not directly related to the use of IVUS. The number of coronary related AE was similar to a registry-based report of coronary angiography alone. Efforts to minimize IVUS-related complications should be focused on preventing coronary artery vasospasm., (© 2020 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

Background: Duchenne muscular dystrophy is associated with progressive cardiorespiratory failure, including left ventricular dysfunction., Methods and Results: Males with probable or definite diagnosis of Duchenne muscular dystrophy, diagnosed between 1 January, 1982 and 31 December, 2011, were identified from the Muscular Dystrophy Surveillance Tracking and Research Network database. Two non-mutually exclusive groups were created: patients with ≥2 echocardiograms and non-invasive positive pressure ventilation-compliant patients with ≥1 recorded ejection fraction. Quantitative left ventricular dysfunction was defined as an ejection fraction <55%. Qualitative dysfunction was defined as mild, moderate, or severe. Progression of quantitative left ventricular dysfunction was modelled as a continuous time-varying outcome. Change in qualitative left ventricle function was assessed by the percentage of patients within each category at each age. Forty-one percent (n = 403) had ≥2 ejection fractions containing 998 qualitative assessments with a mean age at first echo of 10.8 ± 4.6 years, with an average first ejection fraction of 63.1 ± 12.6%. Mean age at first echo with an ejection fraction <55 was 15.2 ± 3.9 years. Thirty-five percent (140/403) were non-invasive positive pressure ventilation-compliant and had ejection fraction information. The estimated rate of decline in ejection fraction from first ejection fraction was 1.6% per year and initiation of non-invasive positive pressure ventilation did not change this rate., Conclusions: In our cohort, we observed that left ventricle function in patients with Duchenne muscular dystrophy declined over time, independent of non-invasive positive pressure ventilation use. Future studies are needed to examine the impact of respiratory support on cardiac function.

Background Duchenne muscular dystrophy incurs nearly universal dilated cardiomyopathy by the third decade of life, preceded by myocardial damage and impaired left ventricular strain by cardiac magnetic resonance. It has been shown that (1) mineralocorticoid receptor antagonist therapy with spironolactone attenuated damage while maintaining function when given early in a mouse model and (2) low-dose eplerenone stabilized left ventricular strain in boys with Duchenne muscular dystrophy and evident myocardial damage but preserved ejection fraction. We hypothesized that moderate-dose spironolactone versus eplerenone would provide similar cardioprotection in this first head-to-head randomized trial of available mineralocorticoid receptor antagonists, the AIDMD (Aldosterone Inhibition in Duchenne Muscular Dystrophy) trial. Methods and Results This was a multicenter, double-blind, randomized, noninferiority trial. Subjects were randomized to eplerenone, 50 mg, or spironolactone, 50 mg, orally once daily for 12 months. The primary outcome was change in left ventricular systolic strain at 12 months. Among 52 enrolled male subjects, aged 14 (interquartile range, 12-18) years, spironolactone was noninferior to eplerenone (∆strain, 0.4 [interquartile range, -0.4 to 0.6] versus 0.2 [interquartile range, -0.2 to 0.7]; P =0.542). Renal and pulmonary function remained stable in both groups, and no subjects experienced serious hyperkalemia. Infrequent adverse events included gynecomastia in one subject in the spironolactone arm and facial rash in one subject in the eplerenone arm. Conclusions In boys with Duchenne muscular dystrophy and preserved left ventricular ejection fraction, spironolactone added to background therapy is noninferior to eplerenone in preserving contractile function. These findings support early mineralocorticoid receptor antagonist therapy as effective and safe in a genetic disease with high cardiomyopathy risk. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02354352.

Background: Rejection with severe hemodynamic compromise (RSHC) carries a mortality risk approaching 50%. We aimed to identify current risk factors for RSHC and predictors of graft failure after RSHC., Methods: Data from 3,259 heart transplant (HT) recipients between January 2005 and December 2015 in the Pediatric Heart Transplant Study (PHTS) were analyzed. Predictors for RSHC and outcome after RSHC were sought. Time to RSHC was analyzed using the Cox proportional hazards regression model. Cardiac allograft vasculopathy (CAV) after HT and CAV after RSHC were analyzed as time-dependent covariates. Timing of RSHC was analyzed as occurring before and after 4 years after RSHC., Results: There were 309 patients (9.5%) with ≥ 1 RSHC episodes. In 143 patients with RSHC, the first episode was within 1 year after HT. Independent risk factors for RSHC were age 1 to 5 years at HT (hazard ratio [HR], 1.51; 95% confidence interval [CI], 1.04-2.18), age > 10 years at HT (HR, 1.83; 95% CI, 1.29-2.60), black race (HR, 1.64; 95% CI, 1.25-2.15), prior cardiac surgery (HR, 1.55; 95% CI, 1.03-2.31), ventricular assist device support at HT (HR, 1.65; 95% CI, 1.18-2.29), maintenance steroids (HR, 1.39; 95% CI, 1.06-1.82), and recipient on inotropes, pressors, or thyroid hormones (HR, 1.45; 95% CI, 1.09-1.94). Graft survival at 5 years after RSHC was 45.7%. RSHC was a greater risk factor for earlier CAV (HR, 7.78; 95% CI, 5.82-10.40) than other rejection types (HR, 2.31; 95% CI, 1.79-3.00). Patients with late RSHC, after 1 year after RSHC had increased risk of graft loss 4 years after RSHC (HR, 7.12; 95% CI, 2.18-23.22). The 5-year graft survival after RSHC was 50.5% for early RSHC and 39.0% for late RSHC., Conclusions: Mortality after RSHC is high in the current treatment era. Many patient risk factors for RSHC cannot be modified, including age, race, prior cardiac surgery, and ventricular assist device support. After RSHC, CAV is the only predictor of graft failure. Patients who have late RSHC fare worse than those who have RSHC within the first year after HT., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: There is inadequate power to perform a valid clinical trial in pediatric heart transplantation (HT) using a conventional end-point, because the disease is rare and hard end-points, such as death or graft loss, are infrequent. We sought to develop and validate a surrogate end-point involving the cumulative burden of post-transplant complications to predict death/graft loss to power a randomized clinical trial of maintenance immunosuppression in pediatric HT., Methods: Pediatric Heart Transplant Study (PHTS) data were used to identify all children who underwent an isolated orthotopic HT between 2005 and 2014 who survived to 6 months post-HT. A time-varying Cox model was used to develop and evaluate a surrogate end-point comprised of 6 major adverse transplant events (MATEs) (acute cellular rejection [ACR], antibody-mediated rejection [AMR], infection, cardiac allograft vasculopathy [CAV], post-transplant lymphoproliferative disease [PTLD] and chronic kidney disease [CKD]) occurring between 6 and 36 months, where individual events were defined according to international guidelines. Two thirds of the study cohort was used for score development, and one third of the cohort was used to test the score., Results: Among 2,118 children, 6.4% underwent graft loss between 6 and 36 months post-HT, whereas 39% developed CKD, 34% ACR, 34% infection, 9% AMR, 4% CAV and 2% PTLD. The best predictive score involved a simple MATE score sum, yielding a concordance probability estimate (CPE) statistic of 0.74. Whereas the power to detect non-inferiority (NI), assuming the NI hazard ratio of 1.45 in graft survival was 10% (assuming 200 subjects and 6% graft loss rate), the power to detect NI assuming a 2-point non-inferiority margin was >85% using the MATE score., Conclusion: The MATE score reflects the cumulative burden of MATEs and has acceptable prediction characteristics for death/graft loss post-HT. The MATE score may be useful as a surrogate end-point to power a clinical trial in pediatric HT., (Copyright © 2018. Published by Elsevier Inc.)

Our objective was to understand the scope of pediatric heart failure (HF) and the current staffing environment of HF programs. An online survey was distributed to members of the Pediatric Heart Transplant Study and the Pediatric Council of the International Society for Heart and Lung Transplantation. All participants received the primary 23-question survey. Additionally, HF program directors received a 32-question supplemental survey. Of 235 invitations sent, there were 69 (29%) primary surveys and 34 program director surveys completed (24 U.S. programs, 9 outside non-U.S., and one non-specified location). A formal HF program was reported by 88% of directors. There were 150 [IQR 50-200] outpatients/institution and 40% [25-50] of patients had congenital heart disease. Inpatient HF census was 3 [2-4] patients. Most programs (70%) used a consulting service model to provide HF specialty care, while only 10 (30%) utilized an inpatient HF service. Inpatient HF service programs had a higher daily inpatient census versus consult service model programs (4 [3-7] vs. 2 [1-4], respectively; p = 0.022) and had a higher number of full-time equivalents dedicated to HF (5.5 [2-7] vs. 2.5 [1-4], respectively; p = 0.024). Only 47% of programs report a general fellowship rotation devoted to HF. Advanced practice providers (APP) were utilized in 15 programs, nurse coordinators in 2, and both in 3. Most HF programs are formalized, utilize APP, and have inadequate HF staffing to utilize a separate inpatient HF service. Exposure of general pediatric cardiology fellows to HF care is variable between institutions.

Background: Infections are frequent in pediatric ventricular assist device (VAD) patients. In this study we aimed to describe infections in durable VAD patients reported to Pedimacs., Methods: Durable VAD data from the Pedimacs registry (September 19, 2012 to December 31, 2015) were analyzed. Infections were described with standard descriptive statistics, Kaplan-Meier analysis and competing outcomes analysis., Results: There were 248 implants in 222 patients, with a mean age and a median follow-up of 11 ± 6.4 years and 2.4 patient-months (<1 day to 2.6 years), respectively. Device types were pulsatile flow (PF) in 91 (41%) patients and continuous flow (CF) in 131 (59%) patients. PF patients were younger (4 ± 4 vs 14 ± 4 years; p < 0.0001) and were more likely to have congenital heart disease (25% vs 12%; p = 0.03), prior surgery (53% vs 26%; p < 0.0001) and prior extracorporeal membrane oxygenation (24% vs 7%; p = 0.0003). Infection accounted for 17% (96 of 564) of the reported adverse events (AEs). A non-device infection was most common (51%), followed by sepsis (24%), external pump component infection (20%) and internal pump component infection (5%). Most infections were bacterial (73%) and required intravenous therapy only (77%). The risk of infection in the constant phase was higher in patients with a history of prior infection and in patients with a history of a non-infectious major AEs. Survival was lower after infection only in CF patients (p = 0.008)., Conclusions: Infection was the most common AE after pediatric VAD implantation. Non-device infections were most common. The best predictor of a future infection was a past infection. CF patients have higher risk of death after an infection., (Copyright © 2018 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

We aimed to describe worldwide DCD HT experience in children using the International Society for Heart and Lung Transplantation Registry. The Registry was queried for primary HT performed in children (2005-2014). Kaplan-Meier analysis was used to assess survival for recipients grouped by DCD or DBD hearts. Recipient characteristics were compared between DCD and DBD and between survivors and non-survivors of DCD HT. Among 3877 pediatric HT performed, 21 (0.5%) were DCD. DCD 1-year survival was 61% vs 91% DBD, P < .01. DCD recipients were more often supported by ECMO pre-HT (24% vs 6%, P < .001) and more often receiving inhaled nitric oxide (10% vs 0.6%, P < .001) compared to DBD. Older DCD recipients had significantly lower 1-year survival of 57% vs 93% for DBD, P < .01. Survival for infant DCD recipients was not statistically different to DBD recipients (survival 62% at 1 year and 62% at 5 years for DCD vs 85% at 1 year and 77% at 5 years for DBD, P = .15). Recipients of DCD HT who died were more often supported by ECMO pre-HT (56% non-survivors vs 0% survivors, P = .004) and receiving mechanical ventilation (44% vs 0%, P = .012). DCD HT is uncommon in children. DCD-independent factors in recipients may have contributed to worse survival as DCD recipients who died were more often supported by ECMO and mechanical ventilation. More research is needed to identify donor factors and recipient factors that contribute to mortality after DCD HT., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Ventricular assist devices (VADs) have been used in children on an increasing basis in recent years. One-year survival rates are now >80% in multiple reports. In this report we describe adverse events experienced by children with durable ventricular assist devices, using a national-level registry (PediMACS, a component of INTERMACS) METHODS: PediMACS is a national registry that contains clinical data on patients who are <19 years of age at the time of VAD implantation. Data collection concludes at the time of VAD explantation. All FDA-approved devices are included. PediMACS was launched on September 1, 2012, and this report includes all data from launch until August 2014. Adverse events were coded with a uniform, pre-specified set of definitions., Results: This report comprises data from 200 patients with a median age of 11 years (range 11 days to 18 years), and total follow-up of 783 patient-months. The diagnoses were cardiomyopathy (n = 146, 73%), myocarditis (n = 17, 9%), congenital heart disease (n = 35, 18%) and other (n = 2, 1%). Pulsatile-flow devices were used in 91 patients (45%) and continuous-flow devices in 109 patients (55%). Actuarial survival was 81% at 6 months. There were 418 adverse events reported. The most frequent events were device malfunction (n = 79), infection (n = 78), neurologic dysfunction (n = 52) and bleeding (n = 68). Together, these accounted for 277 events, 66% of the total. Although 38% of patients had no reported adverse event and 16% of patients had ≥5 adverse events. Adverse events occurred at all time-points after implantation, but were most likely to occur in the first 30 days. For continuous-flow devices, there were broad similarities in adverse event rates between this cohort and historic rates from the INTERMACS population., Conclusions: In this study cohort, the overall rate of early adverse events (within 90 days of implantation) was 86.3 events per 100 patient-months, and of late adverse events it was 20.4 events per 100 patient-months. The most common adverse events in recipients of pulsatile VADs were device malfunction, neurologic dysfunction, bleeding and infection. For continuous-flow VADs, the most common adverse events were infection, bleeding, cardiac arrhythmia, neurologic dysfunction and respiratory failure. Compared with an adult INTERMACS cohort, the overall rate and distribution of adverse events appears similar., (Copyright © 2016 International Society for Heart and Lung Transplantation. All rights reserved.)

Background: Predicting later outcome around time of diagnosis of acute dilated cardiomyopathy (DCM) is difficult. We hypothesized that strain and strain rate on initial and follow-up echoes were worse in patients with acute DCM from all causes with poor one-year outcomes., Methods: This was a retrospective study including all patients with DCM aged 0-18 years with left ventricle dilation, low ejection fraction, or low fractional shortening on initial echo. Longitudinal and circumferential strain and systolic and diastolic strain rate were measured on echo at presentation, 1-3 weeks after presentation, and at 1 year. Patients were separated into "Stable" (survivors) and "Progressive" (referred for transplant or died) outcome groups, and results were analyzed to determine whether strain or strain rate at each echo was worse in the "Stable" group compared with the "Progressive" group., Results: The patient population included patients with DCM from idiopathic causes, myocarditis, iron deficiency anemia, lupus, chemotherapy, and LV noncompaction. Longitudinal and circumferential strain and systolic strain rate were significantly better in the "Stable" (n = 7) compared with the "Progressive" (n = 8) outcome group on 1- to 3-week echo. Longitudinal strain more negative than -10% had 87% specificity and 100% sensitivity for predicting "stable" outcome (AUC 0.98), while circumferential strain more negative than -8% had 60% specificity and 100% sensitivity (AUC 0.83)., Conclusions: Longitudinal and circumferential strain and systolic strain rate measured 1-3 weeks after starting therapy are worse in acute dilated cardiomyopathy patients with poor one-year outcomes. Further studies with less heterogeneity and more study subjects are needed., (© 2015, Wiley Periodicals, Inc.)

Background: Maintenance steroid (MS) use in pediatric heart transplantation is variable. The purpose of this study was to evaluate the impact of MS use on graft outcomes., Methods: All patients <18 years old in the Pediatric Heart Transplant Study database at the time of first heart transplant between 1993 and 2011 who survived ≥30 days post-transplant and were from centers with a protocolized approach to MS use were included (N = 2,178). Patients were grouped by MS use at 30 days post-transplant as MS+ or MS- (no MS use). Propensity score analysis was used to generate matched groups of MS+ and MS- patients based on pre-transplant and peri-transplant factors. Kaplan-Meier survival analysis was used to compare freedom from graft loss, graft loss secondary to rejection, rejection, rejection with severe hemodynamic compromise (RSHC), malignancy, and infection between groups., Results: Of patients, 1,393 (64%) were MS+ and 785 (36%) were MS-. There were 315 MS- patients who had propensity matched MS+ controls. Kaplan-Meier estimates showed no difference in graft loss (p = 0.9) or graft loss secondary to rejection (p = 0.09). At 1 year post-transplant, there was no difference in freedom from rejection (p = 0.15) or malignancy (p = 0.07), but there was lower freedom from RSHC and infection in the MS- group (p = 0.05 and p = 0.02, respectively)., Conclusions: MS use at 30 days post-transplant was not associated with enhanced graft survival after pediatric heart transplant. MS- patients had a higher incidence of RSHC and infection. These risks should be taken into consideration when determining MS use for pediatric recipients of heart transplants., (Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Respiratory failure after ventricular assist device (VAD) placement may threaten transplant candidacy and can be lethal. Refractory respiratory failure may require addition of extracorporeal membrane oxygenation (ECMO) support. Providing ECMO in a VAD-supported patient is uniquely challenging, particularly in the case of LVAD inflow cannula obstruction in a pediatric patient who may be more prone to cannula obstruction. Surgical intervention to alleviate obstruction may not be feasible. Here, we present a novel nonsurgical strategy for conversion to ECMO in a VAD-supported pediatric patient with respiratory failure because of LVAD inflow cannula obstruction.

Background: MicroRNAs (miRNAs) are short regulatory RNAs that control gene expression through interacting with the 3'UTR of target messenger RNAs. The purpose of this study was to determine if circulating miRNAs are useful biomarkers of outcome in children with dilated cardiomyopathy (DCM)., Methods: An array for 754 miRNAs and real time polymerase chain reaction confirmation of select miRNAs were performed. Serum from 55 children <18 years old with DCM was analyzed. Samples were drawn from all patients with DCM when undergoing heart transplant evaluation and/or at the time of transplantation. Patients with DCM were categorized based on when their blood was drawn (Pre-Transplant or Transplant) and outcome (Transplant/died or Recovered)., Results: Two miRNAs were significantly up-regulated (hsa-miR-155 and hsa-miR-636) and 2 miRNAs were down-regulated (hsa-miR-646 and hsa-miR-639) in patients with DCM who were transplanted or died compared with patients with DCM who recovered their ventricular function. Receiver operator curves, performed for differences in any 1 of these 4 differentially regulated miRNAs in patients who were transplanted or died compared with patients who recovered, resulted in an area under the receiver operating characteristic curve of 0.875 for the Pre-Transplant blood draw time point and an area under the receiver operating characteristic curve of 0.93 for the day of Transplant time point., Conclusions: We identified specific miRNAs that are differentially regulated between children with DCM who need a transplant compared with children with DCM who recover. A unique biomarker signature of miRNAs that are specific to children with DCM who have the potential to recover would be valuable in risk stratification of this challenging patient population., (Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Maintenance steroid (MS) use in pediatric heart transplantation (HT) varies across centers. The purpose of this study was to evaluate the impact of steroid-free maintenance immunosuppression (SF) on graft outcomes in pediatric HT., Methods: Patients younger than 18 years in the United States undergoing a first HT during 1990 to 2010 were analyzed for conditional 30-day graft loss (death or repeat HT) and death based on MS use by multivariable analysis. A propensity score was then given to each patient using a logistic model, and propensity matching was performed using pre-HT risk factors, induction therapy, and nonsteroid maintenance immunosuppression. Kaplan-Meier graft and patient survival probabilities by MS use were then calculated., Results: Of 4894 patients, 3962 (81%) were taking MS and 932 (19%) SF. Of the 4530 alive at 30 days after HT, 3694 (82%) and 836 (18%) were in the MS and SF groups, respectively. Unmatched multivariable analysis showed no difference in 30-day conditional graft survival between MS and SF groups (hazard ratio=1.08, 95% confidence interval=0.93-1.24; P=0.33). Propensity matching resulted in 462 patients in each MS and SF group. Propensity-matched Kaplan-Meier survival analysis showed no difference in graft or patient survival between groups (P=0.3 and P=0.16, respectively)., Conclusions: We found no difference in graft survival between SF patients and those taking MS. An SF regimen in pediatric HT avoids potential complications of steroid use without compromising graft survival, even after accounting for pre-HT risk factors.

Background: Dexmedetomidine, an α-2 receptor agonist, is widely used in children with cardiac disease. Significant hemodynamic responses, including systemic and pulmonary vasoconstriction, have been reported after dexmedetomidine administration. Our primary goal of this prospective, observational study was to quantify the effects of dexmedetomidine initial loading doses on mean pulmonary artery pressure (PAP) in children with and without pulmonary hypertension., Methods: Subjects were children undergoing cardiac catheterization for either routine surveillance after cardiac transplantation (n = 21) or pulmonary hypertension studies (n = 21). After anesthetic induction with sevoflurane and tracheal intubation, sevoflurane was discontinued and anesthesia was maintained with midazolam 0.1 mg/kg i.v. (or 0.5 mg/kg orally preoperatively) and remifentanil i.v. infusion 0.5 to 0.8 μg/kg/min. Ventilation was mechanically controlled to maintain PCO2 35 to 40 mm Hg. When end-tidal sevoflurane was 0% and fraction of inspired oxygen (FIO2) was 0.21, baseline heart rate, mean arterial blood pressure, PAP, right atrial pressure, pulmonary artery occlusion pressure, right ventricular end-diastolic pressure, cardiac output, and arterial blood gases were measured, and indexed systemic vascular resistance, indexed pulmonary vascular resistance, and cardiac index were calculated. Each subject then received a 10-minute infusion of dexmedetomidine of 1 μg/kg, 0.75 μg/kg, or 0.5 μg/kg. Measurements and calculations were repeated at the conclusion of the infusion., Results: Most hemodynamic responses were similar in children with and without pulmonary hypertension. Heart rate decreased significantly, and mean arterial blood pressure and indexed systemic vascular resistance increased significantly. Cardiac index did not change. A small, statistically significant increase in PAP was observed in transplant patients but not in subjects with pulmonary hypertension. Changes in indexed pulmonary vascular resistance were not significant., Conclusion: Dexmedetomidine initial loading doses were associated with significant systemic vasoconstriction and hypertension, but a similar response was not observed in the pulmonary vasculature, even in children with pulmonary hypertension. Dexmedetomidine does not appear to be contraindicated in children with pulmonary hypertension.

Background: The effect of surgical history on graft outcomes in patients with functionally univentricular hearts (UH) is not well understood. We compared graft outcomes after heart transplantation in children with a UH between patients who received allografts without prior cardiac surgery (Group A) and patients who underwent transplantation after prior cardiac surgery (Group B)., Methods: We reviewed all patients who received allografts for UH at our institution from 1990 to 2009. Differences in the probability of acute rejection (AR), incidence of graft vasculopathy (GV), and incidence of death or retransplantation were compared between Group A and Group B. Student's t-test, Mann-Whitney U-test, the log-rank test, logistic regression, and Cox proportional hazards modeling were used as appropriate., Results: During the study period, 180 patients with a UH received allografts: 105 in Group A and 75 in Group B at a median (interquartile range) age of 84 (47-120) days vs 584 (168-2,956) days, respectively (p < 0.001). The odds of AR were higher in Group B (odds ratio, 2.7, 95% confidence interval, 1.3-5.4). Group A had lower univariable risks of GV (p = 0.034) and graft loss (p = 0.003). Median graft survival was 18 years in Group A vs 8 years in Group B. The risk of graft loss after 5 years post-transplant was higher in Group B patients who were aged ≥ 1 year at time of transplant (p < 0.001)., Conclusions: Heart transplantation without prior cardiac surgery in patients with a UH was associated with better graft survival and lower probability of AR. The effect of age is complex and time-dependent, with age affecting outcomes after 5 years., (Copyright © 2012 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Identification of heart transplant recipients at highest risk for a poor outcome could lead to improved posttransplantation survival. A chart review of primary heart transplantations from 1993 to 2006 was performed. Analysis was performed to evaluate the risk of graft loss for those with a transplantation age less than 1 year, congenital heart disease (CHD), elevated pulmonary vascular resistance (index > 6), positive panel reactive antibody or crossmatch, liver or renal dysfunction, mechanical ventilation, or mechanical circulatory support (MCS). Primary transplantation was performed for 189 patients. Among these patients, 37% had CHD, 23% had mechanical ventilation, and 6% had renal dysfunction. Overall graft survival was 82% at 1 year and 68% at 5 years. The univariate risk factors for graft loss included mechanical ventilation (hazard ratio [HR], 1.9; 95% confidence interval [CI], 1.15-3.18), CHD (HR, 1.68; 95% CI, 1.04-2.70), and renal dysfunction (HR, 3.05; 95% CI, 1.34-6.70). The multivariate predictors of graft loss were CHD (HR, 1.8; 95% CI, 1.02-2.64), mechanical ventilation (HR, 1.9; 95% CI, 1.13-3.10), and the presence of two or more statistically significant univariate risk factors (SRF) (HR, 3.8; 95% CI, 2.00-7.32). Mechanical ventilation, CHD, and the presence of two or more SRFs identify pediatric patients at higher risk for graft loss and should be considered in the management of children with end-stage heart failure.

Background: The ability of serum B-type natriuretic peptide levels (BNP) to predict outcomes in children with heart failure (HF) has not been well demonstrated. This study was designed to determine whether BNP levels predict outcomes in patients with moderate symptomatic HF., Methods and Results: We investigated whether enrollment BNP levels for the Pediatric Carvedilol Trial were associated with baseline characteristics. Freedom from a composite end point of HF hospitalization, death, or transplantation at 9 months was compared using a threshold BNP level identified using receiver operating curve analysis. Median BNP level was 110 pg/mL (interquartile range, 22.4 to 342.0 pg/mL) in 138 subjects. Median age was 3.4 years (interquartile range, 1.1 to 11.0 years). Diagnoses were cardiomyopathy (60%) and congenital heart disease (40%); 73% had a systemic left ventricle. BNP levels correlated moderately with left ventricular ejection fraction (R=0.39, P<0.001) but did not differ by HF class, age, diagnosis, sex, ventricular morphology, or left ventricular end-diastolic dimension Z-score (R=0.19). Outcome events included 25 HF hospitalizations, 4 deaths, and 2 transplants. Sensitivity was 71% and specificity 63%, for a BNP cutoff value of 140 pg/mL. BNP ≥140 pg/mL (hazard ratio, 3.7; 95% confidence interval, 1.62 to 8.4; P=0.002) and age >2 years (hazard ratio, 4.45; 95% confidence interval, 1.68 to 12.04; P=0.003) were independently associated with worse outcomes., Conclusions: In children with moderately symptomatic HF, BNP ≥140 pg/mL and age >2 years identified subjects at higher risk for worse outcome. Further validation is needed to determine the BNP levels necessary to stratify risk in other pediatric cohorts.

Objectives: This study sought to investigate the influence of recipient renin-angiotensin-aldosterone system (RAAS) genotype on cardiac function, rejection, and outcomes after heart transplantation., Background: The RAAS influences cardiac function and up-regulates inflammatory/immune pathways. Little is known about the effect of recipient RAAS polymorphisms in pediatric cardiac transplantation., Methods: Patients <25 years of age, after cardiac transplantation, were enrolled (2003 to 2008) and genotyped for polymorphisms in genes associated with RAAS upregulation: AGT-G, ACE-D, AGTR1-C, CYP11B2-G, and CMA-A. Presence of at least 1 high-risk allele was defined as a high-risk genotype. Univariable and multivariable associations between genotypes and outcomes were assessed in time-dependent models using survival, logistic, or linear regression models. Biopsy samples were immunostained for interleukin (IL)-6, transforming growth factor (TGF)-beta, and tumor necrosis factor (TNF)-alpha during rejection and quiescence., Results: A total of 145 patients were studied, 103 primary cohort and 42 replication cohort; 81% had rejection, 51% had graft dysfunction, and 13% had vasculopathy, 7% died and 8% underwent re-transplantation. A higher number of homozygous high-risk RAAS genotypes was associated with a higher risk of graft dysfunction (hazard ratio [HR]: 1.5, p = 0.02) and a higher probability of death (HR: 2.5, p = 0.04). The number of heterozygous high-risk RAAS genotypes was associated with frequency of rejection (+0.096 events/year, p < 0.001) and rejection-associated graft dysfunction (+0.37 events/year, p = 0.002). IL-6 and TGF-beta were markedly upregulated during rejection in patients with >/=2 high-risk RAAS genotypes., Conclusions: Recipient RAAS polymorphisms are associated with a higher risk of rejection, graft cytokine expression, graft dysfunction, and a higher mortality after cardiac transplantation. This may have implications for use of RAAS inhibitors in high-risk patients after transplantation.

Obtaining or maintaining vascular access for continuous hemofiltration can sometimes be problematic, especially in the child or adult in multiple organ failure with edema and/or coagulopathy. Problems commonly encountered include obstruction of the femoral vein by the catheter, insertion difficulties, safety concerns when cannulating the subclavian vein in coagulopathy, and catheter and circuit occlusion due to disseminated intravascular coagulation. For access in infants we describe a technique utilizing two single-lumen thin-walled vascular sheaths. For infants and small children initial access to the vein may be difficult due to edema or poor perfusion. For this situation we describe the 'mini-introducer' technique of securing the vein and facilitating subsequent insertion of a relatively large guide wire. At any age an alternative route to the subclavian vein, from above the clavicle, is potentially 'compressible' in the event of hemorrhage during the procedure. We remind the reader of the utility of ultrasound guidance for cannulation of the internal jugular and subclavian veins. And lastly we review the options for venous return via the umbilical vein in infants, and via the antecubital vein in larger children and adults.