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Introduction:Iron deficiency is associated with worse outcomes in children and adults with systolic heart failure. While oral iron replacement has been shown to be ineffective in adults with heart failure, its efficacy in children with heart failure is unknown. We hypothesised that oral iron would be ineffective in replenishing iron stores in ≥50% of children with heart failure.Methods:We performed a single-centre retrospective cohort study of patients aged ≤21 years with systolic heart failure and iron deficiency who received oral iron between 01/2013 and 04/2019. Iron deficiency was defined as ≥2 of the following: serum iron 300 ng/mL, transferrin saturation Results:Fifty-one children with systolic heart failure and iron deficiency (median age 11 years, 49% female) met inclusion criteria. Heart failure aetiologies included cardiomyopathy (51%), congenital heart disease (37%), and history of heart transplantation with graft dysfunction (12%). Median dose of oral iron therapy was 2.9 mg/kg/day of elemental iron, prescribed for a median duration of 96 days. Follow-up iron testing was available for 20 patients, of whom 55% (11/20) remained iron deficient despite oral iron therapy.Conclusions:This is the first report on the efficacy of oral iron therapy in children with heart failure. Over half of the children with heart failure did not respond to oral iron and remained iron deficient.

Understanding optimal ventricular assist device (VAD) parameters for pediatric patients is valuable given the inherent issue of patient-device size mismatch and heterogeneous cardiac anatomy in children. We evaluated our center's experience of continuous-flow VAD (CF-VAD) optimization using cardiac catheterization. We performed a retrospective analysis of all patients on CF-VAD support who underwent hemodynamic heart catheterization from 2013 to 2018. Fifteen patients had 16 hemodynamic catheterizations performed. The indications for hemodynamic optimization by catheterization included clinical signs of heart failure while on CF-VAD (9 of 16, 56%), pretransplant evaluation of pulmonary hypertension (2 of 16, 13%), or assessment of myocardial recovery (5 of 16, 31%). The median age at catheterization was 12 years (interquartile range: 8-16). Median baseline speed of device was 2333 ± 253 rotations per minute. The goal was to find the speed at which optimal hemodynamics were achieved, defined by low wedge pressure with an acceptable central venous pressure. Of the 16 catheterizations, there were 9 (56%) speed increases to achieve optimal hemodynamics and 5 (33%) speed decreases for hemodynamic optimization or for potential explant. The speed was not changed in 2 (13%) catheterizations as the patients were determined to be at an optimal hemodynamic state. Overall, VAD settings were optimized in 75% (14 of 16) of hemodynamic catheterizations. There were no adverse events related to catheterization. Thus, we conclude that catheterization-based hemodynamic assessment is safe and effective for optimizing VAD speed and provides guidance on medical management in children supported on CF-VAD.

Survivors of childhood cancer are at risk of cancer therapy-related cardiac dysfunction (CTRCD) characterized by systolic impairment, with little known about diastolic function. Left atrial strain (LAS) is a surrogate measure of left ventricular filling. We hypothesized that survivors (1) have lower LAS versus controls, and (2) survivors exposed to higher anthracycline dosage have even lower LAS. Cross-sectional study of 45 survivors exposed to anthracyclines ≥ 1 year after chemotherapy and 45 healthy controls. Echo variables included mitral spectral and tissue Doppler, left ventricular ejection fraction (LV EF), LV dimension, LA volume, LV global longitudinal strain (GLS), and LAS. Peak strain (Ɛ) and strain rate (SR) at three phases were obtained: atrial contraction (ac), reservoir (res), and conduit (con). Two sub-analyses of cancer survivors were performed: (1) those with anthracycline dosage ≥ 250 mg/m2, and (2) those with Ɛres in the lowest quartile. On the whole, survivors had lower Ɛres and Ɛcon values. The majority of survivors had relatively normal LAS, while a subset had very low LAS values and were more likely to be older. Survivors exposed to ≥ 250 mg/m2 anthracycline also had lower Ɛres than those

Durable ventricular assist devices (VADs) have significantly improved survival to transplantation among children with advanced stages of heart failure. The fundamental goals of VAD therapy include decreasing mortality, minimizing adverse events, and improving quality of life. As the pediatric VAD experience has evolved with reduced device related complications and improved survival, VAD therapy is being considered not only as a bridge to transplantation (BTT) but also as a bridge to decision (BTD) and as destination therapy (DT). Data regarding pediatric DT VAD are limited to anecdotal or case reports of children being supported for long periods with VADs and by default being classified as DT VAD. This article reviews current trends in the use of DT VAD and adverse events in children vs adults on VAD, and provides a framework for patient selection with the use of a multidisciplinary approach including palliative care. The general approach to determining DT VAD candidacy should include: 1) a reasonable success that the patient will survive the peri- and postoperative state; and 2) a high likelihood that the patient will be able to be discharged out of hospital and have adequate caregiver support. Patients with muscular dystrophy and failing Fontan physiology are examples of pediatric populations for whom DT VAD may be considered and which require unique considerations.

BACKGROUND Pediatric sHKTx remains uncommon in the US. We examined outcomes of pediatric sHKTx compared to PHTx alone. Our objective was to identify a threshold eGFR that justified pediatric sHKTx. METHODS Data from the SRTR heart and kidney databases were used to identify 9245 PHTx, and 63 pediatric sHKTx performed between 1992 and 2017 (age ≤21 years). RESULTS The median age for sHKTx was 16 years, and included 31 males (31/63 = 49%). Over half of sHKTx (36/63 = 57%) were performed in cases where pretransplant dialysis was initiated. Among patients who required pretransplant dialysis, the risk of death in sHKTx recipients was significantly lower than PHTx alone (sHKTx vs. PHTx: HR 0.4, 95% CI [0.2, 0.9], p = .01). In those without pretransplant dialysis, there was no improvement in survival between sHKTx and PHTx (p = .2). When stratified by eGFR, PHTx alone recipients had worse survival than sHKTx in the group with eGFR ≤35 ml/min/1.73 m2 (p = .04). The 1- and 5-year actuarial survival rates in pediatric sHKTx recipients were 87% and 81.5% respectively and was similar to isolated PHTx (p = .5). One-year rates of treated heart (11%) and kidney (7.9%) rejection were similar in sHKTx compared to PHTx alone (p = .7) and pediatric kidney transplant alone (p = .5) respectively. CONCLUSION Pediatric sHKTx should be considered in HTx candidates with kidney failure requiring dialysis or eGFR ≤35 ml/min/1.73 m2 . The utility of sHKTx in cases of kidney failure not requiring dialysis warrants further study.

The evolution of cancer therapies has led to marked improvement in survival of those affected by childhood malignancies, while also increasing the recognition of early and late toxicities associated with cancer therapies. Cardiotoxicity can include cardiomyopathy/heart failure, coronary artery disease, stroke, pericardial disease, arrhythmias, and valvular and vascular dysfunction as a result of exposure to chemotherapy and/or radiation. Anthracyclines remain the most common cause of chemotherapy-induced cardiomyopathy (CCM) with varying clinical presentations including: acute, early onset, and late-onset. Many individuals develop cardiac dysfunction over the long-term, ranging from subclinical cardiac dysfunction to end-stage symptomatic heart failure. The focus of this review is on characterization of symptomatic heart failure in children with cancer therapy-related cardiac dysfunction (CTRCD) primarily due to CCM and utilization of advanced heart failure therapies, including ventricular assist device (VAD) support and heart transplantation, with consideration of unique patient-related factors.

The success of ventricular assist devices (VADs) in the treatment of end-stage heart failure in the adult population has led to industrial innovation in VAD design, focusing on miniaturization and the reduction of complications. A byproduct of these innovations was that newer generation devices could have clinical applications in the pediatric population. Over the last decade, VAD usage in the pediatric population has increased dramatically, and the newer generation continuous flow (CF) devices have begun to supplant the older, pulsatile flow (PF) devices, formerly the sole option for ventricular assist in the pediatric population. However, despite the increase in VAD implants in the pediatric population, patient numbers remain low, and the need to share data between pediatric VAD centers has become that much more important for the continued growth of VAD programs worldwide. The creation of pediatric VAD registries, such as the Pediatric Registry for Mechanical Circulatory Support (PediMACS), the European Registry for Patients with Mechanical Circulatory Support (EUROMACS) and the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) has enabled the collection of aggregate data from VAD centers worldwide, and provides a valuable resource for clinicians and programs, as more and more pediatric heart failure patients are considered candidates for VAD therapy.

Objective Predictors of right ventricle (RV) dysfunction after continuous-flow left ventricular assist device (CF-LVAD) implantation in children are not well described. We explored the association of preimplantation Pulmonary Artery Pulsatility index (PAPi) and other hemodynamic parameters as predictors of prolonged postoperative inotropes/pulmonary vasodilator use after CF-LVAD implantation. Design Retrospective chart review. Setting Single tertiary care pediatric referral center. Patients Patients who underwent CF-LVAD implantation from January 2012 to October 2017. Interventions Preimplantation invasive hemodynamic parameters were analyzed to evaluate the association with post-CF-LVAD need for prolonged (>72 hours) use of inotropes/pulmonary vasodilators. Measurements and main results Preimplantation cardiac catheterization data was available for 12 of 44 patients who underwent CF-LVAD implant during the study period. Median (IQR) age and BSA of the cohort were 15.3 years (10.2, 18) and 1.74 m2 (0.98, 2.03). Group 1 (n = 6) included patients with need for prolonged inotropes/pulmonary vasodilator use after CF-LVAD implantation and Group 2 (n = 6) included those without. Baseline demographic parameters, cardiopulmonary bypass time, and markers of RV afterload (pulmonary vascular resistance, PA compliance and elastance) were similar among the two groups. PAPi was significantly lower in group 1 compared to group 2 (0.96 vs 3.6, respectively; P = .004). Post-LVAD stay in the intensive care unit was longer for patients in group 1 (46 vs 23 days, P = .52). Brain natriuretic peptide was significantly higher at 3 months after implantation in group 1; P = .01. Conclusions The need for inotropes/pulmonary vasodilators in the postoperative period can be predicted by the preimplantation intrinsic RV contractile reserve as assessed by PAPi rather than the markers of RV afterload. Further investigation and correlation with clinical outcomes is needed.

Background Pediatric HLT remains uncommon in the United States and criteria for HLT are unclear. The objectives of this study were to review the indications, and outcomes of pediatric HLT. Methods Data from the Scientific Registry of Transplant Recipients heart and liver databases were used to identify 9245 pediatric isolated heart transplants (PHT), 14 134 pediatric isolated liver transplant (PLT), and 20 pediatric HLT (16 patients underwent sHLT [same organ donor] and four patients with a history of PHT followed by PLT [different organ donors]; age ≤21 years) between 1992 and 2017. Outcomes included patient survival, and 1-year rates of acute heart and liver rejection. Results The median age for pediatric HLT was 15.6 (IQR: 10.5, 17.9) years, and included 12 males (12/20 = 60%). In the HLT group, the most common indication for HT was CHD (12/20 = 60%), and the most common indication for liver transplant was cirrhosis (9/20 = 45%). The 1, 3, and 5 year actuarial survival rates in pediatric simultaneous HLT recipients (n = 16) were 93%, 93%, and 93%, respectively, and was similar to isolated PHT alone (88%, 81%, and 75.5%, respectively and isolated PLT alone (84%, 82%, and 80%), respectively. There was no heart or liver rejection reported in the HLT group versus 9.9% in heart and 10.6% in liver transplant-only groups, respectively. Conclusion Pediatric HLT is an uncommon but acceptable option for recipients with combined end-organ failure, with intermediate survival outcomes comparable to those of single-organ recipients.

Despite increasing utilization of continuous-flow pediatric ventricular assist devices (VAD) in children, data on exercise testing and cardiac rehabilitation (CR) are unknown. We described variation in CR practices and identified barriers to exercise testing and CR. A survey was performed through the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) representing pediatric VAD centers across North America. Descriptive statistics were performed. A multidisciplinary cohort of 52 respondents from 28 pediatric VAD centers responded. Although 38% reported performing exercise testing, most (65%) used 6 minute walk tests rather than formal cycle or treadmill exercise testing. While all respondents refer to physical therapy during the initial inpatient stay for VAD placement, only 52% refer to a CR program. When performed, CR was performed at an ACTION center (84%), a local specialized center (21%), or a home-based CR program (26%). Commonly cited barriers to either CR or exercise testing were inadequate resources, inadequate implementation logistics knowledge, concerns about safety, inability of patients to travel to a CR facility, and concern about utility of exercise testing or CR. Over 90% of centers were interested in implementing a standardized pediatric VAD CR program. Utilization of exercise testing and CR after VAD placement is variable. Despite perceived barriers, most pediatric VAD centers are interested in implementing a standardized CR program for recipients. In response to this interest, we plan to implement a standardized CR protocol to all ACTION pediatric VAD centers in an effort to improve pretransplant waitlist rehabilitation and post-transplant outcomes.

The Jarvik 2015 Ventricular Assist Device (VAD) (Jarvik Inc, New York, NY) is the first and currently only continuous-flow VAD specifically designed for small children, and it is being evaluated in the so-called Pump for Kids, Infants, and Neonates (PumpKIN) trial. Due to the strict inclusion criteria of the trial, there have been a group of patients who failed to meet the criteria and therefore received the Jarvik 2015 VAD under the designation of "compassionate use." This is the same phenomenon seen previously during the Berlin Heart EXCOR trial. While we await the results of the PumpKIN trial, which will report the device performance in a strictly selected population, the compassionate use cases represent actual "real world" experiences. We describe herein our experience of two compassionate use cases. In particular, this report has a special emphasis on the power consumption and hemolysis and inflammatory lab profile of the Jarvik 2015 VAD as hemocompatibility was the primary focus of the developmental and the preclinical phases.

Introduction and Background: Arrhythmogenic ventricular cardiomyopathy (AVC) is a hereditable disorder characterized by fibro-fatty infiltration of the right ventricular myocardial wall. The purpose of this study was to describe the clinicopathologic phenotype of AVC in pediatric end-stage heart failure patients who underwent heart transplantation (HTx). Hypothesis: We hypothesized that AVC is misclassified in the young population who require heart transplant. Methods: We investigated 371 consecutive cases of primary pediatric (≤21 years) heart transplantation performed at Texas Children’s hospital between 1989 and 2018. Heart re-transplants were excluded from the study. Explanted hearts and tissue blocks were examined by a cardiac pathologist after HTx. Histological Diagnosis of AVC was based on the presence of major and minor diagnostic criteria according to the 2010 Revised Task Force Criteria. Results: Over half of the patients who underwent HTx had cardiomyopathy (212/371=57%) as the underlying primary diagnosis. After comprehensive histological evaluation of explanted hearts, 8 cases (8/212=3.8%) were diagnosed with AVC. Predominantly right ventricular disease was seen in 2/8 (25%), and biventricular involvement in 6/8 (75%) patients on pathological examination. Six out of 8 patients (6/8=75%) were misclassified, 4 as dilated cardiomyopathy, 1 as viral myocarditis, and 1 as restrictive cardiomyopathy. The median age at heart transplant (AVC cohort) was 11 years. Four of 8 (50%) were males. Six of 8 (75%) had a significant ventricular arrhythmia burden manifesting as non-sustained ventricular tachycardia requiring antiarrhythmic therapy. Genetic testing was undertaken in 3 of 8 (37.5%); all three were found to have pathogenic mutations in the PKP2 gene. Conclusion: Arrhythmogenic ventricular cardiomyopathy is often misclassified in the young population who require heart transplant. Pediatric dilated and restrictive cardiomyopathy phenotypes with end-stage heart failure waitlisted for a heart transplant (HT) who have a significant ventricular arrhythmia burden should be investigated for AVC.

Discharging children on ventricular assist device (VAD) support offers advantages for quality of life. We sought to describe discharge and readmission frequency in children on VAD support. All VAD-implanted patients aged 10-21 years at Advanced Cardiac Therapies Improving Outcomes Network (ACTION) centers were identified from the Pediatric Health Information System database (2009-2018). Discharge frequency on VAD was calculated. Patients discharged on VAD were compared with those not discharged. Freedom from readmission was assessed using the Kaplan-Meier method. A total of 298 VAD-implanted patients from 25 centers were identified, of which 163 (54.7%) were discharged. Discharges increased over time (36.9% [2009-2012] vs. 59.7% [2013-2018], p = 0.001). Of 144 discharged patients with follow-up, 96 (66.7%) were readmitted for reasons other than transplantation. Heart failure was the most common reason for readmission (27.7%), followed by infection (25.8%) and hematologic concerns (16.8%). In-hospital mortality on readmission was uncommon (1.8%) and the median length of stay was 6 days (interquartile range 2-19 days). Discharge of children on VAD support has increased over time, although variability exists across centers. Readmissions are common with diverse indications; however, the risk of mortality is low. Further interventions, including collaboration in ACTION, are critical to increasing discharges and optimizing outpatient management.

Purpose End-stage heart failure is a leading cause of morbidity and mortality in adult congenital heart disease (ACHD) patients; however, advanced therapies such as ventricular assist devices (VADs) are rarely implemented in this population. The aim of this study was to examine the outcomes of ACHD patients supported by durable continuous-flow VADs. Methods We performed a retrospective review of patients with congenital heart disease >18 years of age at time of VAD implantation at Texas Children's Hospital and Baylor St. Luke's Medical Center from 2011-2020. Results In total, 13 patients (median age 34 years [IQR, 24-47]) received a VAD (Table). All devices were implanted in the subaortic ventricle; 2 patients (15%) and 11 patients (85%) had moderate and great complexity congenital heart disease, respectively. Prior to implantation, 11 patients (85%) required inotropic support and 5 patients (38%) required temporary mechanical circulatory support. 12 patients (92%) survived to hospital discharge with a median postoperative LOS of 36 days (IQR, 27-50). Among those who survived to hospital discharge, all (100%) were NYHA class I or II at follow-up and the median duration of support was 816 days (IQR, 160-1629). Patients experienced device-related complications including neurologic events (n = 5; n = 2 disabling stroke), driveline infections (n = 3), presumed device infections requiring chronic antibiotic therapy (n = 4; n = 1 associated pump exchange), GI bleeds (n = 6), and presumed pump thromboses (n = 5; n = 2 associated pump exchanges). Overall survival (heart transplant censored) at 1, 3, and 5 years was 82%, 70%, and 32%, respectively. 2 patients (50%) were successfully bridged to transplant and 1 patient initially implanted as destination therapy eventually received a transplant. Conclusion Our data demonstrate that durable VADs can be used effectively in ACHD patients with end-stage heart failure and support efforts to more readily utilize these therapies in this population.

Purpose Adult congenital heart disease (ACHD) patients are disproportionally affected by heart failure and cardiogenic shock compared to the general population. Despite a growing and aging cohort, experience with percutaneous continuous flow ventricular assist device (pVAD) use in ACHD patients is rarely described in the literature. Methods Retrospective chart review at Texas Children's Hospital and Baylor St. Luke's Medical Center from 1/2016 to 8/2020 for patients with congenital heart disease who were adult age at time of pVAD placement. Results Six patients with ACHD received 7 pVAD devices with a median age at placement of 34 [IQR 23- 38] years (Table). Five (83%) patients were male and 5 (83%) had complex congenital heart disease. Three (50%) patients had Fontan circulation. Devices included: 4 (57%) Impella CP®, 1 (14%) Impella 5.0® and 2 (29%) Impella 5.5®. Four (57%) devices were placed in patients with INTERMACS profile score 1. Four (57%) devices were placed in patients with acute decompensated heart failure in the setting of chronic heart failure and 3 (43%) devices were placed due to peri-procedural hemodynamic compromise. Three devices (43%) were placed via hybrid-surgical method with axillary artery grafts and 4 (57%) Impella CP® devices were placed percutaneously in the femoral artery. Median duration of patient support was 20 [IQR 3-44] days. Major pVAD-related complications included severe hemolysis requiring replacement of Impella CP® with Impella 5.0 device® and aortic valve replacement at time of Impella® 5.0 removal and durable ventricular assist device implantation in a neo-aortic valve with pre-existing regurgitation. There were no significant limb injuries/ischemia, stroke or bleeding events. Two (33%) patients were bridged to a durable ventricular assist device; all 6 (100%) patients survived to hospital discharge. Conclusion Percutaneous continuous flow ventricular assist devices can be successfully used to hemodynamically support ACHD patients in cardiogenic shock.

Purpose There is a concerted effort to increase discharges of children on ventricular assist device (VAD) support. Optimizing this process represents a quality improvement target of Advanced Cardiac Therapies Improving Outcomes Network (ACTION). We sought to describe discharge and readmission frequency in children on VAD support using a multicenter administrative database. Methods All VAD-implanted patients aged 10-21 years at ACTION centers were identified from the Pediatric Health Information System database (2009-2018). Discharge frequency on VAD was calculated. Patients discharged on VAD were compared to those not discharged. Freedom from readmission was assessed using the Kaplan Meier method, censoring at readmission for transplantation. The indications for readmission were determined using ICD diagnosis codes. Results A total of 298 patients from 25 centers were identified, of which 163 (54.7%) were discharged. The discharge frequency ranged from 8% to 100% across centers. The frequency of discharge increased over time (36.9% [2009-2012] vs. 59.7% [2013-2018], p=0.001). Of 144 discharged patients with follow-up data, 96 (66.7%) were readmitted for reasons other than transplantation with a median time to readmission of 45 days (IQR 18-79) [Figure]. Heart failure was the most common reason for readmission (27.7%), followed by infection (25.8%), hematologic concerns (16.8%), neurologic events (8.6%), arrhythmias (7.8%), and fluid/electrolyte problems (4.7%). In-hospital mortality on readmission was uncommon (1.8%) and the median length of stay was 6 days (IQR 2-19 days). Conclusion Patients discharged with VADs from ACTION centers has increased over time, with high variability across centers. Readmissions are common with diverse indications; however, the risk of mortality during a readmission encounter is low. Further collaboration in ACTION is critical to optimize the outpatient management of this vulnerable population.

To evaluate the prevalence of iron deficiency and its association with outcomes in children with heart failure.A single-center retrospective cohort study of patients with heart failure aged 1-21 years from July 2012 to June 2017 with available serum iron studies was performed. Subjects were analyzed in 2 groups: biventricular systolic heart failure (BiV) and single-ventricle congenital heart disease with systolic heart failure (SV). Iron deficiency was defined as ≥2 of the following: serum iron50 μg/dL, serum ferritin20 ng/mL, transferrin300 ng/mL, or transferrin saturation15%. The primary outcome was a composite adverse event (CAE) of ventricular assist device implantation, heart transplantation, or death, at 3 and 6 months from time of iron studies.Of the 107 subjects (77 BiV, 30 SV) included in the study, 56% were iron deficient. Demographics, etiology of heart failure, and chronicity of heart failure symptoms were not associated with iron deficiency. On multivariable analysis, in group BiV, iron deficiency was associated with CAE at 3 months (79% iron deficiency in CAE group vs 37% iron deficiency in non-CAE, P = .001, OR 7, 95% CI 2-21) and 6 months (76% iron deficiency in CAE vs 35% iron deficiency in non-CAE, P = .002, OR 7, 95% CI 2-24). In group SV, iron deficiency was associated with CAE at 6 months (79% iron deficiency in CAE vs 29% iron deficiency in non-CAE, P = .014, OR 8, 95% CI 2-32).Iron deficiency was present in 56% of the pediatric patients with heart failure who were evaluated with iron studies. Iron deficiency was associated with greater risk of ventricular assist device implantation, heart transplantation, or death.

Background With expanding use of clinical whole exome sequencing (WES), genetic variants of uncertain significance are increasingly identified. As pathologic mutations in genes associated with arrhythmogenic right ventricular cardiomyopathy (ARVC) carry a risk of sudden death, determining the diagnostic relevance of incidentally identified variants associated with these genes is critical. Methods WES variants from a large, predominantly pediatric cohort (N = 7,066 probands) were obtained for nine ARVC‐associated genes (Baylor Miraca). For comparison, a control cohort was derived from the gnomAD database and an ARVC case cohort (N = 1,379 probands) was established from ARVC cases in the literature. Topologic mapping was performed and signal‐to‐noise analysis was conducted normalizing WES, or case variants, against control variant frequencies. Retrospective chart review was performed of WES cases evaluated clinically (Texas Children's Hospital). Results Incidentally identified variants occurred in 14% of WES referrals and localized to genes which were rare among ARVC cases yet similar to controls. Amino acid‐level signal‐to‐noise analysis of cases demonstrated “pathologic hotspots” localizing to critical domains of PKP2 and DSG2 while WES variants did not. PKP2 ARM7 and ARM8 domains and DSG2 N‐terminal cadherin‐repeat domains demonstrated high pathogenicity while normalized WES variant frequency was low. Review of clinical data available on WES referrals demonstrated none with evidence of ARVC among variant‐positive individuals. Conclusions Incidentally identified variants are common among pediatric WES testing with gene frequencies similar to “background” variants. Incidentally identified variants are unlikely to be pathologic.

Noninvasive assessment of diastolic function in pediatric heart transplantation (PHTx) patients is important for monitoring of rejection, cardiac allograft vasculopathy, and nonspecific graft failure. We hypothesized that left atrial strain (LAS) would correlate with pulmonary capillary wedge pressure (PCWP) and that cutoff values to identify elevated left ventricular (LV) filling pressure could be derived for clinical practice and future testing.This was a secondary analysis of a prospectively collected cohort of PHTx patients undergoing same-day cardiac catheterization with biopsy and transthoracic echo. There were 70 patients with 85 clinical encounters. Traditional mitral inflow Doppler, LAS, LV diastolic strain and strain rate, and ratios for mitral E to LV diastolic strain and strain rate were assessed. Correlation with PCWP was performed, and receiver operator characteristic curves were generated for an elevated mean PCWP, acute rejection, and cardiac allograft vasculopathy.Decreased LAS during the atrial reservoir phase (Ɛres) correlated with higher invasively measured PCWP (r = -0.40, P .001). An Ɛres cutoff of 14.5% had good discriminatory ability for an elevated PCWP (sensitivity 75%, specificity 82%), and Ɛres 22.0% had 100% negative predictive value; Ɛres was superior to other measures of diastolic function. Subanalyses for recent acute rejection (n = 9) showed good discriminatory ability for Ɛres of 14.5% (sensitivity 89%, specificity 74%).LAS correlates with invasively measured PCWP and can identify elevated pressures better than traditional and other advanced diastolic function parameters. Use of LAS in PHTx patients may aid in noninvasive monitoring for rejection and nonspecific graft dysfunction.

BACKGROUND The first year after heart transplantation (HT) has the highest risk of mortality. We aim to derive and validate a recipient risk prediction tool for early mortality after pediatric HT. METHODS The International Society for Heart and Lung Transplantation (ISHLT) registry was used to identify patients (≤18 y) who underwent primary HT during January 2000-December 2014. Independent predictors of 1-year mortality were identified based on recipient characteristics at HT. Risk scores were assigned based on the magnitude of relative odds of 1-year mortality. The predictive capability of the ISHLT registry derived recipient risk score was externally validated using the Scientific Registry of Transplant Recipients registry data from 2015 to 2017 to ensure a cohort of patients completely exclusive from the derivation cohort. RESULTS A total of 5045 eligible patients were included in the analysis. The 20-point risk scoring system incorporated 8 recipient variables, including age at HT, diagnosis, pre-HT ventilator use, extracorporeal membrane oxygenation, inhaled nitric oxide use, infection, estimated glomerular filtration rate, and serum bilirubin. Compared with low-risk score group, high-risk group had 7-fold increased risk of 1-year mortality (hazard ratio 7.4; 95% CI [5.2-9.1]; P < 0.001). The C-statistics (0.77) and Hosmer-Lemeshow goodness of fit (0.9) for recipient risk score using derivation cohort from ISHLT registry performed well and was similar to the internal and external validation cohort (C-statistics 0.75, 0.78 and Hosmer-Lemeshow goodness of fit P = 0.4, 0.3, respectively). CONCLUSIONS This study derived and externally validated a simple risk predictive model based on recipient characteristics at HT that has good prediction characteristics for 1-year post-HT mortality. This model may help clinicians identify candidates who are at a higher risk for post-HT mortality and may optimize organ sharing.

1. Hari Tunuguntla, MD, MPH* 2. Aamir Jeewa, MD† 3. Susan W. Denfield, MD* 1. *Department of Pediatrics, Division of Pediatric Cardiology, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX 2. †Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada * Abbreviations: CMR: : cardiovascular magnetic resonance imaging DCM: : dilated cardiomyopathy ECG: : electrocardiogram EMB: : endomyocardial biopsy IVIg: : intravenous immunoglobulin MCS: : mechanical circulatory support PCR: : polymerase chain reaction PHIS: : Pediatric Health Care Information System VAD: : ventricular assist device 1. The diagnoses of myocarditis and pericarditis are often delayed because they are uncommon diseases in pediatrics and because symptoms in the early stages may be overlooked in the context of current or recent viral illnesses or other systemic diseases. Early suspicion for and recognition of signs and symptoms, particularly of myocarditis, are important because the disease process can rapidly become life-threatening. Although pericarditis can also be life-threatening, it is less commonly so than myocarditis. 2. Clinicians should be aware of the predisposing factors and the clinical signs and symptoms that should increase the index of suspicion for these entities because prompt referral to the emergency department, with access to specialists with expertise in the care and support of these patients, is imperative. After completing this article, readers should be able to: 1. Recognize the context in which myocarditis and pericarditis arise in a differential diagnosis. 2. Identify causes of myocarditis and pericarditis. 3. Recognize clinical signs and symptoms of myocarditis and pericarditis. 4. Appropriately refer patients to the emergency department for further evaluation. Myocardial and pericardial diseases are uncommon problems in childhood that can present as isolated diagnoses or as part of systemic diseases. Although they can have the same etiologies, and symptoms often overlap, their prognosis and treatment differ significantly. It is important to make an accurate diagnosis because clinically apparent myocarditis is much more likely to be life-threatening, and rapidly so, than pericarditis. Children with suspected myocarditis or pericarditis should be sent to an emergency department, where access to specialists with expertise in these diseases is available. The key is early suspicion for these entities to make a timely referral and diagnosis …

Purpose Angiotensin II type 1 receptor antibodies (AT1R-Ab) are associated with non-human leukocyte antigen (HLA) mediated antibody mediated rejection (AMR) and graft failure in adult renal transplantation. They can be stimulated by ventricular assist device (VAD) support, but data regarding AT1R-Ab in pediatric heart transplantation (HT) are scarce. The purpose of this study is to describe the incidence of non-HLA mediated AMR and identification of AT1R-Ab in a pediatric HT cohort. Methods We performed a single-center retrospective review of children who underwent primary HT from July 2016 to July 2020. AMR was defined by the presence of complement deposition (+C4d) on heart biopsy. Non-HLA mediated AMR was defined by the absence of donor-specific HLA antibodies (HLA-DSA). AT1R-Ab testing was defined as 17 positive (ELISA). Results There were 100 patients who underwent primary HT during the study period (median age 4.5 years). There were 19 episodes of AMR in 17 patients. HLA-DSA were present in 12 episodes (63%) and absent in 7 (37%) episodes. Non-HLA mediated AMR occurred earlier post-HT compared to AMR with HLA-DSA (median 7 days vs 244 days, p = 0.04). Four patients with AMR in the absence of HLA-DSA were tested for AT1R-Ab; 3 were positive and 1 was borderline. Of the 3 patients with positive AT1R-Ab, 2 were previously supported on VAD, 2 had symptomatic AMR, 2 subsequently received losartan, and none have had recurrence of AMR (Table). Conclusion Non-HLA mediated AMR accounted for 37% of AMR episodes and occurred earlier post-HT compared to AMR with HLA-DSA in a single-center cohort. AT1R-Ab were present in 3 of 4 patients with non-HLA mediated AMR in whom AT1R-Ab testing was performed. In light of the recent data regarding AT1R-Ab in renal transplantation, investigation of the prevalence and clinical significance of AT1R-Ab in pediatric HT, particularly in early non-HLA mediated AMR and in those bridged to HT with VAD, is warranted.

Introduction Development of an intracardiac thrombus (IT) has been reported following pediatric heart transplantation (HT), however the incidence and risk factors are unknown. Pre-HT ventricular assist device (VAD) support can result in a hypercoagulable state and can be associated with the development of anti-phospholipid (APL) antibodies. Over 200 transplants have been performed at our institution in the last 10 years with 2 cases of IT post-HT identified. Case Report Case 1: A 9 year old female was bridged to HTx with VAD. She developed cardiac allograft vasculopathy and recalcitrant arrhythmias 7 years post-HT. She underwent a repeat HTx with total ischemic time 236 minutes. She had normal biventricular function without arrhythmia. On post-operative day (POD) 8, an echocardiogram revealed 3 IT in the left atrium (LA) as seen in figure 1. She was emergently taken to the OR. Her previously normal coagulation profile prior to initial transplant was now notable for + IgM anti-cardiolipin, an antibody that is detected in APL syndrome. She never developed any neurological sequelae. No additional thrombotic compilations have occurred over 3 months on enoxaparin. Case 2: A 15 year old male with failing Fontan physiology was supported on VAD for 5 months prior to a technically challenging HT with total ischemic time 366 minutes. He had ventricular tachycardia and junctional rhythm treated with antiarrhythmics and pacing with normal biventricular function by POD 4. On POD 7, he developed altered mental status. Brain MRI showed multiple small ischemic infarcts and an IT extending from the LA appendage was found on echocardiogram. His IT was medically managed, and while no hypercoagulable workup was completed at the time, he was subsequently continued on enoxaparin as an outpatient without recurrence. Summary We postulate that each patient may have developed an acquired thrombophilia. These cases highlight the importance of future studies to risk stratify post-HTx patients who may warrant a pre-emptive hypercoagulable workup.

Introduction Valvular disease in pediatric donor hearts may be a relative contraindication to graft use. Outcomes following use of donor hearts with milder forms of valvular disease have not been previously reported. We describe 4 cases of pediatric heart transplantation (HTx) in which the donor heart had a bicuspid aortic valve (BAV). Case Report Of the 469 HTx performed at our center since 1985, 4 donor hearts had a BAV. All recipients were female; median age 11 years (range 0.3 to 19 years). In all cases, the BAV was not discovered until after HTx. All donors were less than 30 years old. The patients were followed for a median of 6 years (range 2 to 9 years) with all patients alive at last follow up. Two patients transferred to adult care and 2 patients are followed by our clinic. In follow up, no patient required an aortic valve intervention or had infective endocarditis. At last review, no patient had greater than mild aortic insufficiency or more than mild aortic stenosis. Three patients developed mild to moderate left ventricular hypertrophy in the first year post-transplant that improved over time. One patient experienced a peri-operative embolic stroke at time of transplant unrelated to the bicuspid aortic valve. Summary On short- and intermediate-term follow up, donor hearts with bicuspid aortic valve demonstrated acceptable graft longevity and valvular function. A functionally normal bicuspid aortic valve in a pediatric heart transplant donor should not be a contraindication to organ acceptance.

Purpose Graft failure after heart transplant (HTx) due to allograft rejection or coronary artery vasculopathy (CAV) can result in cardiogenic shock requiring mechanical circulatory support (MCS). We present our institutional experience with the Impella®, a percutaneous ventricular assist device (VAD), in HTx patients in cardiogenic shock due to graft failure. Methods This is a single center, retrospective review of HTx patients who underwent Impella implantation from 10/2014 to 4/2020. Demographics, device implant techniques, complications, and clinical outcomes were analyzed. Results There were 19 Impella implants in 11 HTx patients with median age and weight of 16 years (range 6-25) and 61 kg (range 23-124). Graft failure was due to rejection in 55% (6/11), CAV in 18% (2/11), and non-specific graft failure in 27% (3/11). Median time from HTx to Impella implant was 42 months (range 9-175). Impella devices included CP (n=11), 5.0 (n=5), 2.5 (n=1), and RP (n=2). Median length of support per implant was 5 days (range 3-21). Devices were placed via femoral (15/19) or axillary (4/19) arterial access. Seven patients received Impella support once with a single implant each. One patient required 3 distinct admissions for shock due to rejection and received Impella support each time. Three patients required 9 device implants during their course primarily for recurrence of heart failure (HF) after trial off device. Two of these received simultaneous support with CP and RP devices for biventricular HF. ECMO with Impella was required in 4 patients; 2 had Impella after ECMO for left heart decompression and 2 were placed on ECMO after Impella to augment cardiac support. Device related complications per patient included: device malfunction in 2, major bleeding requiring transfusion in 2, hemolysis in 5, extremity arterial thrombus in 2, intracardiac thrombus in 1, and transient foot drop in 3. There was no limb ischemia, stroke, infection, or increase in aortic insufficiency in the study cohort. Survival to hospital discharge was 91% (10/11). Six patients were explanted for recovery, 2 were transitioned to durable VAD, and 2 were bridged to HTx. Conclusion Impella is a promising temporary MCS option with an acceptable risk profile for adolescent and young adult HTx patients in cardiogenic shock due to graft failure with means to facilitate recovery or bridge to durable VAD or re-transplant.

Purpose Iron deficiency (ID) is associated with increased risk of ventricular assist device implantation, transplant, or death in children with systolic heart failure (HF). Oral iron replacement is standard therapy for ID. However retrospective studies in children with HF estimate its efficacy at ∼50%. There are no data comparing the efficacy of oral and intravenous (IV) iron therapy in children with systolic HF. Methods In July 2019, we instituted a screening and treatment protocol for ID in children with systolic HF. We performed a retrospective analysis of patients who were screened with this protocol between 07/2019 and 10/2020. ID was defined as the presence of ≥2 of the following 4 criteria on serum iron testing: iron 300 ng/mL, transferrin saturation Results Forty patients with systolic HF (21 male, median age 4.5 years, 28 cardiomyopathy and 12 congenital heart disease) met inclusion criteria. Nine received oral iron while 31 received IV iron. Post-therapy iron studies were available for 6/9 of the oral iron cohort and 28/31 of the IV iron cohort. The oral and IV iron cohorts were similar in terms of demographics, etiology or chronicity of HF, renal dysfunction, and mechanical ventilation. Pre-treatment serum BNP was higher in the IV iron cohort (median 1092 vs 55, p = 0.028) compared to the oral iron cohort. At 3 months, iron therapy was effective in 50% (3/6) of the oral iron cohort, compared to 86% (24/28) of those on IV iron (p = 0.086). By 6 months, ID was effectively treated in 50% (3/6) of patients on oral iron, compared to 89% (25/28) of patients on IV iron (p = 0.053). Demographics, etiology or chronicity of HF, BNP, renal dysfunction, and mechanical ventilation were not associated with efficacy of iron therapy at 3 or 6 months. Conclusion IV iron tended to be more effective than oral iron in treating ID in children with systolic HF, despite the IV iron cohort having higher BNP levels and being presumably sicker. This is the first pediatric data on the topic, although statistical significance was limited by small sample size. Larger studies are needed to guide effective therapy for ID in children with systolic HF.

The field of paediatric ventricular assist device (VAD) support is growing rapidly. Among paediatric patients, those with complex congenital heart disease represent a challenging population for VAD support. This report describes a patient with a remote history of an arterial switch operation for d-transposition of the great arteries who developed ischaemic cardiomyopathy necessitating centrifugal-flow VAD support as a bridge to cardiac transplantation. Because of the unique anatomy and the complicated vascular situation, implantation of the centrifugal-flow VAD and subsequent explantation for cardiac transplantation required modifications to the standard surgical approach. The details of surgical pitfalls encountered are described.

Purpose The use of intracorporeal continuous flow ventricular assist devices (CF-VAD) in pediatric patients with advanced heart failure has allowed for patients to be discharged home. However, currently only about 50% of pediatric patients are discharged from the hospital. We sought to examine the discharge practices across the Advanced Cardiac Therapies Improving Outcomes Network (ACTION). Methods Surveys were sent to the members of the ACTION collaborative in September 2018 to determine discharge practices in preparation for a quality improvement project. Results Surveys were sent to 28 sites, with respondents from 22 sites (response rate: 78.5%). The majority of centers had discharged 1-5 patients (59.1%, 13/22) in the preceding 24 months. The remaining centers’ discharge experience in the preceding 24 months was the following: 9.1% (2/22) with >5-15 patients, 9.1% (2/22) with >15 patients, and 22.7% (5/22) had not discharged a patient. The majority of patients discharged were on the HVAD (81.8%), followed by HeartMate 3 (13.6%), HeartMate II (9.1%), and SynCardia TAH (9.1%). Barriers to discharge identified were family readiness (72.7%), patient too sick (59.9%) and distance from VAD center to home (36.4%). At the time of the survey, 45.5% of sites were following 1-5 outpatients with 50% having no outpatients. Half of the programs manage patients from remote locations with most centers (63.6%) not sharing responsibility of care with a local cardiologist. A small number of centers, 27% (6/22), had VAD patients in the outpatient setting who were not listed for transplant due to reasons such as awaiting further rehabilitation, assessment of myocardial recovery, and family preference. The majority of centers allowed patients to return to school post discharge (95.5%), to drive (63.6%), and travel nationally (77.3%) but not internationally (36.4%). Conclusion Barriers perceived by health care providers and families continue to limit pediatric centers from discharging CF-VAD patients from the hospital. As discharge and maintenance of outpatient care for this unique population is a low frequency but resource intense process, collaboration among centers to gain knowledge of best practices is valuable.

Purpose Iron deficiency (ID) is associated with worse outcomes in children with systolic heart failure (HF). Oral iron replacement therapy (IRT) is first line therapy for ID in children but the efficacy of oral IRT in children with HF is unknown. We hypothesized that less than half of children with HF and ID would have replenishment of their iron stores with oral IRT. Methods We performed a single center retrospective cohort study of patients aged ≤ 21 years with systolic HF and ID who received oral IRT (2-5mg/kg/day) between 01/2017 and 12/2018. ID was defined as ≥2 of the following: serum iron 300 ng/mL, transferrin saturation Results Forty-two independent courses of oral IRT (in 40 patients) met inclusion criteria. The cohort was 52% male with median age 13 yrs (IQR 5 - 16 yrs). HF etiologies included cardiomyopathy (57%), congenital heart disease (31%), and history of heart transplantation with graft dysfunction (12%). Patients received ferrous sulfate (40/42) or ferrous gluconate (2/42). Median duration of IRT was 68d (IQR 32 - 145d). Twenty-nine patients received ≥6 weeks of IRT and were included for the analysis for response to oral IRT. Post IRT iron testing was available in 18 patients and post IRT hemogram was available in 26 patients. Serum iron and hematologic indices of the overall cohort as well as comparison of indices pre and post oral IRT are shown (Table). While there was an improvement in serum iron studies, 50% (9/18) of the patients remained iron deficient. Conclusion This is the first report about oral IRT in children with HF. Though median values of some iron parameters increased after 6weeks of oral IRT, half of the children with HF remained iron deficient and hence non-responsive to oral IRT. Further studies are needed to find the most suitable IRT for children with HF.

Purpose Advance care planning (ACP) is best practice for young adults with time-limited palliations such as heart transplant (HTx). A quality improvement (QI) project was previously conducted at our center to build a sustainable infrastructure for routine ACP discussions and advance directive (AD) documentation for young adults in our heart failure and transplant (HF-HTx) clinic. We describe a continuation of this QI project. Methods The study population was patients ≥18 years old seen in our HF-HTx clinic. The primary outcome measure was percentage of population with documented AD. The secondary outcome measure was percentage of patients with documented ACP discussion. The previous QI project (March 2016-February 2017) included a series of interventions implemented in our HF-HTx clinic: 1) identification of providers to conduct ACP 2) standardization of ACP conversation and EMR documentation 3) preparation of providers and patients for ACP. For the project continuation, baseline data were ascertained. PDSA cycle 1 consisted of refining the providers who led ACP discussions. In PDSA cycle 2, Voicing My Choices (an ACP guide) was introduced after face-to-face discussions with patients instead of prior to the encounter. Results During the previous QI project, the percent of adults seen per month with documented AD and ACP discussion peaked at 42% and 63% respectively. During the project continuation, the percent of adults seen per month with documented AD peaked at 59% (goal 50%). The percent of adults seen per month with a documented ACP discussion peaked at 97% (goal 100%). Conclusion ACP discussions can be successfully integrated and sustained at a busy clinical practice by engaging key stakeholders such as HTx coordinators and social workers. Patient engagement in ACP discussions is improved when the topic is introduced in person. Ongoing and timely discussion of ACP between patients and their healthcare team is warranted.

Background Loop diuretics are considered first-line therapy for congestion in children with heart failure, although some patients remain volume overloaded during treatment. We sought to characterize loop diuretic responsiveness (DR) in children hospitalized with acute decompensated failure and to determine whether a decreased response was associated with worse outcomes. Methods and results DR was calculated for 108 consecutive children ˂21 years of age who were hospitalized with acute decompensated heart failure. DR was defined as net fluid (mL) output per 1 mg of furosemide equivalents during the first 72 hours of treatment with a loop diuretic. The primary outcome was the composite end point of inpatient death or use of mechanical circulatory support. The median DR was 6.0 mL/mg (interquartile range -2.4 to 15.7 mL/mg). Thirty-two percent of patients remained in a positive fluid balance after 72 hours of treatment with a loop diuretic. Death or use of mechanical circulatory support occurred in 29 patients (27%). Low DR was associated with the composite end point, even after adjusting for net urine output and loop diuretic dose indexed to weight (odds ratio 5.3; P = .003). Patients with low DR also experienced longer length of hospital stay than patients with greater DR (median 33 days vs 11 days; P = .002). Conclusion In children hospitalized with acute decompensated heart failure, early diminished loop DR during decongestion therapy is common and portends a poor prognosis.

To determine frequency of missed heart failure diagnosis at first presentation among children with no known heart disease admitted with new-onset heart failure.Using a retrospective design, we reviewed electronic medical records of all patients aged21 years with no known heart disease, hospitalized with new-onset heart failure during 2003-2015 at a tertiary-quaternary care institution. We assessed records for missed diagnosis of heart failure (primary outcome), associated process breakdowns, and clinical outcomes using a structured data collection instrument.Of 191 patients meeting inclusion criteria, 49% (94/191) were missed on first presentation. Most common incorrect diagnostic labels given to "missed" patients were bacterial infection (29%; 27/94), followed by viral illness (22%; 21/94) and gastroenteritis/hepatitis (21%; 20/94). On multivariable analysis, presentation to primary care provider (PCP), longer duration of symptoms (median 7 days), more than 2 symptoms of heart failure, and nausea/emesis were associated with missed diagnosis. On examining process breakdowns, 49% had errors in history-taking and 50% had no documentation of differential diagnoses. There was no difference in hospital mortality, length of stay, or mechanical circulatory support in missed vs not-missed cohorts. Unnecessary noninvasive and invasive tests were performed in 18% and 4% of patients, respectively.Nearly one-half of children with no known heart disease hospitalized with systolic heart failure were missed at first presentation and underwent significant nonrelevant treatment and testing. Initial presentation to the PCP, longer duration of symptoms before presentation, and nausea/emesis were associated with missed diagnosis.

Background We reviewed our single institutional experience with pediatric ventricular assist device (VAD) support over the last 2 decades, with an aim to improve our current management and gain an insight into the future direction. Methods A retrospective review was conducted on all patients that had undergone VAD support between 1996 and 2017. Outcomes were analyzed based on the type of VADs, whether temporary or durable devices. Primary end points were positive outcomes, including bridge-to-transplantation, bridge-to-recovery, alive on device, and bridge-to-bridge to another VAD, or negative outcomes, including death during VAD support or in-hospital death after bridge-to-recovery. The Pediatric Interagency Registry for Mechanical Circulatory Support definition was used to classify adverse events. Results Overall, 201 VADs were implanted in 159 patients, with 82 (41%) and 119 (59%) being temporary and durable support, respectively. There has been a trend toward an increasing annual implant volume both with temporary and durable VADs. Positive outcomes were achieved in 80% (66 of 82) of those with temporary support, with bridge-to-recovery (53% [35 of 66]) and bridge-to-bridge to another VAD (38% [25 of 66]) being the predominant outcomes. Of those on durable support, 84% (100 of 119) achieved positive outcomes, with bridge-to-transplant (66% [78 of 119]) being the leading destination. The most notable change during the study period was the introduction of implantable continuous-flow VADs, resulting in outpatient management becoming a routine practice. No patients were discharged on VAD support before 2004, but 85% were discharged on VADs with discharge capability after 2013. Conclusions The present study has demonstrated the evolutional changes of pediatric VAD support and their effect on clinical outcomes over the last 2 decades.

Graft rejection is the most common factor that limits graft survival after transplantation. During infancy, the humoral immune system is partially suppressed and humoral rejection of a cardiac allograft has not been reported in the absence of risk factors such as prior transplantation, blood transfusions, ventricular assist devices, and elevation of panel reactive antibodies. We present a case of an infant with dilated cardiomyopathy who developed multiple episodes of acute humoral rejection after heart transplantation in the absence of risk factors.

The incidence of death by CA after PHTx is unknown. We aimed to determine the incidence and factors for fatal CA after PHTx, and whether a PM affects survival. Retrospective cohort study utilizing the United Network of Organ Sharing registry of patients transplanted ≤18 years. Multivariable analyses in hazard-function domain and Kaplan-Meier analyses were performed for an outcome of death due to CA. There were 7719 PHTx patients queried. CA was the reported cause of death in 11%. Age ≥13 years at time of transplant, presence of a PM, and depressed EF were identified as significant factors for fatal CA. Death due to CA beyond 10 years post-transplant was associated with depressed EF, CAV, and presence of a PM. Kaplan-Meier analysis demonstrated higher likelihood of fatal CA in patients with CAV and in those with a PM vs those without. In total, 15% of patients with a PM died from CA. CA is a relatively common cause of death after PHTx. The benefit of a PM remains unclear, but its presence does not confer complete protection. Patients with associated factors warrant vigilant surveillance and consideration for retransplantation.

Chemotherapy-induced cardiotoxicity in adults and children is a topic with a growing interest in the cardiology literature. The ability to detect cardiac dysfunction in a timely manner is essential in order to begin adequate treatment and prevent further deterioration. This article aims to provide a review on the myocardial injury process, chemotherapeutic agents that lead to cardiotoxicity, the definition of cardiotoxicity, and the methods of timely detection and treatment.

PURPOSE Elevated central venous pressure (CVP) has deleterious effects on several organ systems in patients with Fontan circulation. However, the relationship between CVP and estimated glomerular filtration rate (eGFR) has not been assessed in patients with Fontan circulation. METHODS Patients with Fontan circulation whose hemodynamics were assessed by catheterization between 1987 and 2015 and had a serum creatinine measured within 72 hours prior to the procedure were included for analysis. Patients with primary kidney disease were excluded. Renal function was calculated by "bedside Schwartz" equation in children (< 18 years) and Modification of Diet in Renal Disease equation in adults. Renal dysfunction (RD) was defined by eGFR

Purpose Pediatric simultaneous heart-kidney transplantation (sHKTx) remains uncommon in the US and criteria for sHKTx are unclear. We examined outcomes of pediatric sHKTx compared to pediatric heart transplant alone (PHTx). Our objective was to identify a threshold estimated glomerular filtration rate (eGFR) that justified pediatric sHKTx. Methods Data from the Scientific Registry for Transplant Recipients heart and kidney databases were used to identify 9245 PHTx, and 63 pediatric sHKTx between 1992 and 2017 (age ≤21 years). Outcomes included patient survival, acute heart and kidney rejection . Results The median age for pediatric sHKTx was 16 (IQR: 12, 19.5) years, and included 31 males (31/63=49%). Over half of sHKTx (36/63 = 57%) were performed in cases where pre-transplant dialysis was initiated. The risk of death in sHKTx recipients was significantly lower than PHTx alone, amongst patients who required pre-transplant dialysis (sHKTx vs. PHTx: HR 0.4, 95% CI [0.2, 0.9], p=0.01) (Figure 1a). There was no improvement in survival between sHKTx and PHTx in those without pre-transplant dialysis (HR 0.5, 95% CI [0.16, 1.51], p=0.2) (Figure 1b). When stratified by eGFR, PHTx alone recipients had worse survival than sHKTx in the group with eGFR ≤35 ml/min/1.73m2 (n = 37, p=0.04). The 1, 3, and 5 year actuarial survival rates in pediatric sHKTx recipients was 87%, 84%, and 83% respectively, and was similar to isolated PHTx (p=0.5). One-year rates of treated heart (11%) and kidney (7.9%) rejection were similar in sHKTx compared to PHTx alone (p =0.7) and pediatric kidney transplant alone ( p=0.5) respectively. Conclusion Pediatric sHKTx should be considered in heart transplant candidates with kidney failure requiring dialysis, whereas the usefulness of sHKTx in cases of kidney failure not requiring dialysis warrants further study. Pediatric sHKTx may be considered for eGFR ≤35 ml/min/1.73m2.

Purpose There has been a dramatic increase in adult continuous-flow ventricular assist device (cf-VAD) support in children. Adult VADs in children inevitably cause size mismatch. The unmet need for a pediatric cf-VAD led to initiation of an NIH-funded Pediatric Circulatory Support/PumpKIN program in 2004. The Jarvik 2015 is the only survivor of the program, reflecting the challenges of this initiative. We describe the first clinical experience with the Jarvik 2015 in North America. Methods Results A 4-year-old female (12 kg, BSA 0.5 m2) with a small, non-apex forming left ventricle (LV) with non-compaction and multiple ventricular septal defects (VSDs) required escalation of inotropic support for severe biventricular dysfunction and worsening end-organ function. She previously underwent various procedures including aortic arch repair with pulmonary artery (PA) banding, epicardial pacemaker, and multiple VSD occlusion devices. There were multiple residual defects in the ventricular septum, which was oriented in an axial plane with superior/inferior orientation of the ventricles. Via a 6th sternotomy and LV ventriculotomy, the residual VSDs were closed with a bovine pericardial patch. The LV incision was primarily closed except the most apical portion, leaving an opening for cf-VAD insertion. The outflow graft was anastomosed to the ascending aorta and the PA band was removed (Fig 1). The Jarvik 2015 was set at 15,000 RPMs, and post-op filling pressures were Conclusion This case represents the first Jarvik 2015 implant in North America and first ever implant for a complex congenital heart malformation, heralding the long-awaited PumpKIN trial.

Background Our institutional policy is to continue centrifugal-flow ventricular assist device support for 3 months or more without activation on the transplant wait-list for physical recovery and assessment of possible myocardial recovery. We evaluated our single-institutional outcomes with centrifugal-flow ventricular assist device support in children. Methods Prospectively collected outcomes data in consecutive patients aged 18 years or less with centrifugal-flow ventricular assist device support were reviewed. Results There were 40 implantations in 39 patients (28 with cardiomyopathy, 11 with congenital heart disease, including 3 with univentricular physiology). The median support was 8 months (range, 1-79), with 13 patients (33%) supported for 12 months or more and a cumulative duration of 41 patient-years. The median age and weight at implantation were 11 (4-18) years and 35 (14-98) kg, respectively. The median body surface area was 1.1 (0.7-2.2) m2, with 16 patients (40%) having a body surface area less than 1.0 m2. Thirty-four patients (85%) had Interagency Registry for Mechanically Assisted Circulatory Support 1 or 2. Children with congenital heart disease were significantly smaller (P Conclusions This study demonstrates favorable outcomes of centrifugal-flow ventricular assist device support in children, including those with congenital heart disease, with an increased incidence of cardiac recovery.

Purpose Little reported data exist regarding bivalirudin anticoagulation in pediatric patients supported with ventricular assist devices (VAD). Methods Single center retrospective cohort study of all patients supported with VAD who received bivalirudin for anticoagulation from 10/2016 to 10/2018. Demographic variables and clinical features, including indication for bivalirudin, details of therapy, and complications were analyzed. Results Bivalirudin was utilized in 19 HeartWare and 4 Berlin EXCOR patients (23 runs in 19 unique patients) - 39% (9/23) male, median age 13.6yr (IQR 6.3 - 17.2yr). Indications included: initial anticoagulation after VAD in 34% (4 HeartWare, 4 Berlin EXCOR), rescue anticoagulation for sub-therapeutic heparin in 26% (6 HeartWare), wash-out for pump thrombosis based on log file analysis and laboratory findings of hemolysis in 26% (6 HeartWare), and anticoagulation after a new ischemic stroke (once neurologically stable) in 14% (3 HeartWare). The overall median duration of bivalirudin was 23 days (IQR 12 - 35 days). The median starting dose was 0.15 mg/kg/hr (IQR 0.1 - 0.15 mg/kg/hr), and the median target activated partial thromboplastin time (PTT) Hepzyme was 60 - 70 sec. The median initial lactate dehydrogenase level was 1213 IU/mL (IQR 599 - 2072 IU/mL), and the median initial plasma hemoglobin level was 40 mg/dL (IQR 30 - 110 mg/dL). The median time to reach goal anticoagulation parameters was 1 day (IQR 1-2 days), and the median therapeutic dose was 0.2 mg/kg/hr (IQR 0.15 - 0.20 mg/kg/hr). Two of the 6 patients who received bivalirudin infusion for washout of pump thrombosis did not achieve therapeutic PTT hepzyme levels, and underwent pump exchange. The remaining 4 patients had normalization of flow patterns on their log file downloads after bivalirudin. While on bivalirudin, 1 patient had a bleeding complication (mediastinal hematoma in HeartWare), while 3 patients had thrombotic complications (all on bivalirudin for primary anticoagulation after VAD implantation - 1 embolic stroke in Berlin EXCOR, 1 embolic stroke in HeartWare, 1 VAD thrombus in HeartWare). Conclusion In this small pediatric series, bivalirudin use for post-operative anticoagulation as well as pump thrombosis achieved therapeutic success in 91% (21/23) cases, with complications in 4 cases. Increasing use of bivalirudin will help elucidate its role in pediatric VAD management.

Introduction Recognition of ventricular assist device (VAD) complications such as aortic insufficiency (AI) are important to optimize long-term management. We highlight a case of the treatment of severe AI in a pediatric continuous flow (CF) VAD patient using transcatheter aortic valve replacement (TAVR). Case Report A 9-year-old male with congenitally corrected transposition of the great arteries and pulmonary atresia underwent staged surgical palliation including a Mustard and Rastelli operation. He developed severe left ventricular (LV) dysfunction with refractory heart failure and underwent implant of a HeartWare (Medtronic, Minneapolis MN) in the morphologic LV on the right side at almost 5 years of age (weight 13.7 kg, BSA 0.64 m2). His waitlist time was prolonged due to significant allosensitization. After 4 years on support, clinical signs of congestive heart failure (CHF) developed and BNP rose (1000 pg/mL) despite optimal VAD performance. Cardiac catheterization showed severe AI and pulmonary hypertension. Mean pulmonary arterial pressure was 40 mmHg with pulmonary vascular resistance of 8.5 WUm2 that was responsive to pulmonary vasodilators. The pulmonary hypertension was attributed to the AI. To avoid a difficult redo sternotomy, TAVR was deemed the optimal way to replace his aortic valve. He underwent catheterization and a 29 mm Edwards SAPIEN 3 valve (Edwards Lifesciences, Irvine CA) was placed in the aortic valve position via right carotid artery cut down using a 21 French sheath. The VAD speed was reduced to 1800 RPM and rapid ventricular pacing allowed for stabilization during valve deployment. Post TAVR, angiography showed resolution of AI with only mild perivalvar leak around the aortic valve. After discharge, he was noted to have a transient rise in lactate dehydrogenase from baseline and increased bruising due to unclear etiology. Within 5 months of his TAVR, his diuretics were weaned with marked improvement in his BNP and resolution of his CHF. Summary AI is a significant complication of long-term CF VAD support that can lead to detrimental hemodynamics and worsening CHF. TAVR may be a reasonable therapy to mitigate AI in high-risk children.