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Ventricular assist device (VAD) support for failing Glenn circulation represents a unique challenge.We conducted a retrospective review of clinical outcomes in patients with VAD support for failing Glenn circulation between 2010 and 2020 at a tertiary pediatric institution.Ten patients were included: INTERMACS profiles were 1 in 3 patients and 2 in 7 patients. The median age, weight, and body surface area were 3.2 years, 13.0 kg, and 0.5 mOur experience suggests the feasibility of durable VAD support for failing Glenn circulation. Concomitant Fontan completion may be considered in select patients to improve oxygen delivery.

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.

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.

Although ventricular failure is a late finding in adults with AC, we hypothesize that this is a presenting symptom in pediatric heart failure patients who undergo HT and that their ventricular arrhythmia burden could differentiate AC from other cardiomyopathies.We performed a single-center retrospective cohort study reviewing 457 consecutive pediatric (≤18 years) HT recipients at our institution. Explanted hearts were examined to establish the primary diagnosis, based on pathologic findings. Demographic and clinical variables were compared between AC versus non-HCM cardiomyopathy cases.Forty-five percent (n = 205/457) had non-HCM cardiomyopathies as the underlying primary diagnosis. Ten cases (10/205 = 4.9%) were diagnosed with AC. All 10 had biventricular disease. In 8/10 patients (80%), AC diagnosis was unrecognized pre-HT. Compared with non-AC cardiomyopathies, the AC group was older at diagnosis (9.3 years vs. 4.3 years, p = .012) and transplant (11.1 years vs. 6.5 years, p = .010), had more ventricular arrhythmias (80.0% vs 32.8%, p = .003), and required more anti-arrhythmic use (80.0% vs 32.3%, p = .001). Genetic testing yielded causative pathogenic variants in all tested individuals (n = 5/5, 100%).AC is often an unrecognized cardiomyopathy pretransplant in children who undergo HT. Pediatric non-HCM phenotypes with heart failure who have a significant ventricular arrhythmia burden should be investigated for AC.

Serum chloride plays an important role in fluid homeostasis and is associated with impaired diuretic responsiveness and mortality in adults with heart failure (HF). We sought to characterize the relationship of serum chloride and diuretic efficiency (DE) and to determine its prognostic importance in children hospitalized with acute decompensated HF (ADHF). We studied DE, defined as net fluid output/kg+constant per mg of loop diuretic/kg, in 200 children hospitalized with ADHF. Median serum chloride at admission was 102 mmol/L (interquartile range 99 to 105 mmol/L), and hypochloremia (chloride ≤96 mmol/L) was present in 16% of the population at admission. Serum chloride correlated with serum sodium (r = 0.66; p0.001) and bicarbonate (r = -0.39; p0.001). In the adjusted analysis, lower chloride was associated with reduced DE (p0.001). Serum sodium was associated with DE on the unadjusted analysis; however, the association was eliminated when added to the model with chloride (p = 0.442). Lower chloride was also associated with features of inadequate decongestion during hospitalization: a positive fluid balance (p = 0.003), greater cumulative loop diuretic dose per weight (p = 0.001), addition of a thiazide diuretic during hospitalization (p0.001), less weight loss (p = 0.025), and longer length of stay (p = 0.003). Chloride concentration was independently associated with death or transplant 1 year after admission (hazard ratio 0.94; p0.001). As a dichotomous variable, hypochloremia was independently associated with reduced DE (p0.001) and decreased 1-year transplant-free survival (hazard ratio 2.3, p0.001). Lower serum chloride at hospital admission is strongly and independently associated with impaired DE and reduced transplant-free survival in children hospitalized with ADHF.

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.

Background: Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiomyopathy and can predispose individuals to sudden death. Most pediatric HCM patients host a known pathogenic variant in a sarcomeric gene. With the increase in exome sequencing (ES) in clinical settings, incidental variants in HCM-associated genes are being identified more frequently. Diagnostic interpretation of incidental variants is crucial to enhance clinical patient management. We sought to use amino acid-level signal-to-noise (S:N) analysis to establish pathogenic hotspots in sarcomeric HCM-associated genes as well as to refine the 2015 American College of Medical Genetics (ACMG) criteria to predict incidental variant pathogenicity. Methods and Results: Incidental variants in HCM genes (MYBPC3, MYH7, MYL2, MYL3, ACTC1, TPM1, TNNT2, TNNI3, and TNNC1) were obtained from a clinical ES referral database (Baylor Genetics) and compared to rare population variants (gnomAD) and variants from HCM literature cohort studies. A subset of the ES cohort was clinically evaluated at Texas Children’s Hospital. We compared the frequency of ES and HCM variants at specific amino acid locations in coding regions to rare variants (MAF < 0.0001) in gnomAD. S:N ratios were calculated at the gene- and amino acid-level to identify pathogenic hotspots. ES cohort variants were re-classified using ACMG criteria with S:N analysis as a correlate for PM1 criteria, which reduced the burden of variants of uncertain significance. In the clinical validation cohort, the majority of probands with cardiomyopathy or family history hosted likely pathogenic or pathogenic variants. Conclusions: Incidental variants in HCM-associated genes were common among clinical ES referrals, although the majority were not disease-associated. Leveraging amino acid-level S:N as a clinical tool may improve the diagnostic discriminatory ability of ACMG criteria by identifying pathogenic hotspots.

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.

Introduction: Children with dilated cardiomyopathy (DCM) are increasingly bridged to heart transplant (Tx) with intracorporeal continuous flow ventricular assist devices (VADs), but there continues to be variability in hospital discharge. We sought to assess the impact of a quality improvement (QI) project promoting hospital discharge in pediatric VAD patients with DCM. Methods: Patients enrolled at sites participating in the Discharge and De-Escalation QI project of the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) registry were eligible. Patients with a HeartWare (HVAD) or HeartMate3 (HM3) VAD, implanted between April 2018 and February 2021, were included. Patient characteristics and outcomes were compared before and after the QI initiative, which targeted team and family expectations, was implemented in November 2019. Results: There were 85 patients (75%) with DCM and/or myocarditis who were included in this study (median age 14 years; median weight 57.1 kg; 67% male). Among 57 patients in the baseline group, 56% (n=32) were discharged with a mean post-implant hospital length of stay (LOS) of 36 days and 44% (n=25) underwent Tx during index VAD admission, with a mean of 52 days on device. There were 28 patients in the intervention group; 64% (n=18) were discharged with a mean LOS of 45 days, while 29% (n=8) patients underwent Tx during index VAD admission, with a mean of 44 hospital days on device. There was no significant difference in the frequency of hospital discharge or in hospital LOS between groups. Conclusions: Pediatric centers discharged just over half of DCM patients supported on an HVAD or HM3, with nearly one third of patients undergoing transplant during the index VAD admission. The QI intervention did not significantly alter the discharge rate. Further work is required to understand practice variation between centers with respect to Tx listing and organ acceptance for children on intracorporeal continuous flow VADs.

Introduction: Discharge of pediatric ventricular assist device (VAD) patients is lagging behind adults, especially pediatric patients with concurrent congenital heart disease (CHD). This quality improvement project aimed to increase discharge rates and decrease time to discharge for pediatric patients with CHD on VAD support. Methods: Patients with CHD implanted with HeartWare HVAD or HeartMate 3 at participating Advanced Cardiac Therapies Improving Outcomes Network (ACTION) centers were included. Baseline demographics and outcomes including explant, transplant, or death, and time to outcome was collected from April 2018 until October 2019. QI interventions (VAD Flight Plan and Discharge Journey Map) were initiated in November 2019. Percentage discharged on VAD as well as time to outcome were compared before and after intervention. Results: Twenty-six patients with CHD (18 single ventricle physiology) were identified (14 pre-intervention and 12-post). The mean age was 16 years old with 27% implanted as Intermacs profile 1. Mortality on device was high at 38%. There were 77% (n=20) considered discharge eligible (alive on device > 30 days) while 42% (n=11) achieved discharge (Table 1). Mean length of stay post-implant for discharged patients was 33 days. A higher percentage of biventricular physiology were discharged (63%) compared to univentricular (33%). QI interventions did not change discharge rate (43% vs 42%), mean time to discharge (46.3 vs 43.4 days), transplant before discharge (17% vs 21%), or death before discharge (42% vs 43%) in the post-intervention group. Conclusion: Discharging CHD patients on VAD support from the hospital remains a challenge largely due to the complex and heterogenous nature of this population at the time of implant. Interventions to address optimal timing of VAD implantation and patient selection could impact outcomes.

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.

Key Clinical Message Variants of unknown significance in cardiomyopathic disease should be analyzed systematically based on the prevalence of the variant in the population compared to prevalence of disease, evidence that other variants in the gene are pathologic, consistency of prediction software on pathogenicity, and the current clinical consensus.

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.

Background: TTN , the largest gene in the human body, encodes TTN (titin), a protein that plays key structural, developmental, and regulatory roles in skeletal and cardiac muscle. Variants in TTN , particularly truncating variants (TTNtvs), have been implicated in the pathogenicity of cardiomyopathy. Despite this link, there is also a high burden of TTNtvs in the ostensibly healthy general population. This complicates the diagnostic interpretation of incidentally identified TTNtvs, which are of increasing abundance given expanding clinical exome sequencing. Methods: Incidentally identified TTNtvs were obtained from a large referral database of clinical exome sequencing (Baylor Genetics) and compared with rare population variants from genome aggregation database and cardiomyopathy-associated variants from cohort studies in the literature. A subset of TTNtv-positive children evaluated for cardiomyopathy at Texas Children’s Hospital was retrospectively reviewed for clinical features of cardiomyopathy. Amino acid-level signal-to-noise analysis was performed. Results: Pathological hotspots were identified within the A-band and N-terminal I-band that closely correlated with regions of high percent-spliced in of exons. Incidental TTNtvs and population TTNtvs did not localize to these regions. Variants were reclassified based on current American College of Medical Genetics and Genomics criteria with incorporation of signal-to-noise analysis among Texas Children’s Hospital cases. Those reclassified as likely pathogenic or pathogenic were more likely to have evidence of cardiomyopathy on echocardiography than those reclassified as variants of unknown significance. Conclusions: Incidentally found TTNtvs are common among clinical exome sequencing referrals. Pathological hotspots within the A-band of TTN may be informative in determining variant pathogenicity when incorporated into current American College of Medical Genetics and Genomics guidelines.

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.

BACKGROUND -: TTN, the largest gene in the human body, encodes titin (TTN), a protein that plays key structural, developmental, and regulatory roles in skeletal and cardiac muscle. Variants in TTN, particularly truncating variants (TTNtvs), have been implicated in the pathogenicity of cardiomyopathy (CM). Despite this link, there is also a high burden of TTNtvs in the ostensibly healthy general population. This complicates the diagnostic interpretation of incidentally identified TTNtvs which are of increasing abundance given expanding clinical exome sequencing (ES). METHODS -: Incidentally identified TTNtvs were obtained from a large referral database of clinical ES (Baylor Genetics) and compared to rare population variants from gnomAD and CM-associated variants from cohort studies in the literature. A subset of TTNtv-positive children evaluated for cardiomyopathy at Texas Children’s Hospital (TCH) were retrospectively reviewed for clinical features of cardiomyopathy. Amino acid-level signal-to-noise analysis (S:N) was performed. RESULTS -: Pathologic hotspots were identified within the A-band and N-terminal I-band that closely correlated with regions of high percent spliced in (PSI) of exons. Incidental TTNtvs and population TTNtvs did not localize to these regions. Variants were re-classified based on current ACMG criteria with incorporation of S:N analysis among TCH cases. Those re-classified as likely pathogenic or pathogenic were more likely to have evidence of CM on echocardiography than those re-classified as variants of unknown significance. CONCLUSIONS: Incidentally found TTNtvs are common among clinical ES referrals. Pathologic hotspots within the A-band of TTN may be informative in determining variant pathogenicity when incorporated into current ACMG guidelines.

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.

With the increasing use of long-term mechanical circulatory support in the management of pediatric heart failure, there is a growing patient population with unique qualities and needs. The objective of this review is to better understand the experience of having a ventricular assist device from the perspective of the child. The literature findings were categorized into the following themes: the persistent threat of mortality, identification with the device, the perception of life pre-device, and caregiver strain. While there is a large area that remains to be studied in future research, these findings can be utilized in the development of education and support programs to effectively meet the needs of this unique population.

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 Recent data in adult solid organ transplantation suggest that epitope-based human leukocyte antigen (HLA) matching may permit better risk assessment of de novo donor‐specific antibody (dnDSA) development compared to antigen-based HLA matching, but data in pediatric heart transplantation (PHTx) are scarce. We evaluated the association between epitope mismatches and dnDSA in PHTx. Methods We performed high resolution HLA typing and epitope mismatch analysis (HLA Matchmaker) in children undergoing primary PHTx at a single center from 2014 - 2020. DSA >1000 MFI (Luminex Single Antigen Bead Assay; One Lambda) were considered positive. Data are presented as median (interquartile range). Results Epitope and dnDSA data were available in 109 transplants (age 5.8 years [1-12], 66% male, 32% non-Hispanic White, follow-up 2.5 years [1.3 - 4.7]). There was significant diversity in the number of epitope mismatches within each HLA locus (Fig 1A), and the number of mismatches were: A 20 (13-28), B 17 (12-22), C 10 (6-15), DR 16 (8-30), DQ 12 (8-16), and DP 8 (3-13). The number of epitope mismatches did not differ among any donor-recipient race combination (not shown). The development of dnDSA was not associated with a higher number of epitope mismatches at any HLA-loci (Fig 1B). However, patients with antibody mediated rejection (AMR) had more DQ mismatches (15 vs 11; p=0.04) than those without AMR, and there were more anti-DQB1 DSA than any other DSA in the cohort (Figure 1C). Conclusion There is significant variability in the number of HLA epitope mismatches within each HLA locus. These data suggest that it may not be the total number of epitope mismatches but rather epitope mismatches at specific loci that vary in location and function that are of immunogenic importance. Further investigation of epitope-matching in PHTx may permit a more personalized immunosuppressive approach based on individualized alloimmune risk assessment in the future.

Purpose The number of patients with failing single ventricle physiology is increasing, and ventricular assist device (VAD) support in this population is challenging. The purpose of this study was to describe our clinical experience with VAD for failing Glenn physiology. Methods A retrospective review of clinical outcomes was conducted in patients that underwent durable VAD placement for failing Glenn circulation between 2010 and 2020 at Texas Children's Hospital. Results Ten patients met inclusion criteria; all had a morphologic right ventricle (RV): 6 hypoplastic left heart syndrome/variant and 4 with isomerism with RV dominant atrioventricular septal defect. INTERMACS profiles were 1 in 3 patients (1 with ECMO) and 2 in 7 patients. Four patients were intubated. Age, weight, and body surface area at VAD implantation were 3.2 (0.9-10.1) years, 13.0 (7.7-22.8) kg, and 0.50 (0.36-0.90) m2, respectively. The device-strategy included HVAD in 6, Jarvik 2015 in 1, and Berlin cannula (with Berlin and/or Rotaflow pumps) in 3. Concomitant Fontan completion was performed in 5 patients (1 with fenestration), while the other 5 remained with Glenn circulation. PaO2/FiO2 ratio (median, range) on postoperative day 1 was significantly higher with Fontan completion [192 (53-336)] than without [76 (59-78), p=0.05] except a patient with Glenn circulation on ECMO. The median duration of mechanical ventilation after VAD was 2 days (range, 1 - 14). There was 1 early mortality 8 days after HVAD placement with Fontan completion due to neurologic insult intraoperatively. The remaining 9 patients (90%) were bridged to transplant at a median support duration of 3.8 (0.1-16.6) months. Five of the 6 HVAD patients were able to be discharged home prior to transplant. One patient encountered a pump thrombus requiring pump exchange and 1 patient suffered a thromboembolic stroke due to a mobile intraventricular thrombus. One patient had a subdural and subarachnoid hemorrhage 27 days after VAD implantation, with complete neurologic recovery without deficits. Conclusion This single-institutional experience suggests long term VAD support is sustainable for failing Glenn physiology with accompanying Fontan completion in selected patients. Further studies are warranted to optimize long term VAD support in this challenging population.

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 Pulmonary hypertension (PH) is a risk factor for mortality after heart transplantation (HTx). We present a case of treatment of post-capillary PH in a small pediatric patient with restrictive physiology using continuous flow ventricular assist device (VAD) support to achieve candidacy for HTx. Case Report A 4.5 year old female (0.57m2) with a history of acute myeloid leukemia and anthracycline chemotherapy in infancy developed mildly depressed left ventricular (LV) function at 2 years of age. Hemodynamic catheterization (cath) showed pre- and post-capillary PH secondary to LV diastolic dysfunction and restrictive physiology (Table). She was cautiously initiated on PDE5 inhibitor therapy (sildenafil) while maintaining LV reverse remodeling therapies. Her heart failure (HF) symptoms and biventricular systolic function worsened over the subsequent 2 years. Subsequent caths showed increasing PVRi, which was responsive to 100% FiO2 and inhaled nitric oxide (iNO), but also accompanied by increase in LV end-diastolic pressures (LVEDP). She was transitioned to endothelin receptor antagonist therapy (bosentan), but continued to worsen clinically, requiring initiation of milrinone. Due to her underlying restrictive physiology leading to worsening PH and severely depressed right ventricular (RV) function, a HeartWare HVAD (cannulation LV to Aorta) was implanted to allow aggressive optimization of PH therapies with simultaneous LV decompression. This enabled up-titration of bosentan as well as re-addition of sildenafil. After PH therapies including VAD implantation, PVRi decreased from a high of 10.7 WU.m2 to 4.7 WU.m2, and marked decline of LVEDP from 22 mmHg pre-VAD to 5 mmHg. She underwent HTx 6 months after VAD implantation, and was discharged home 12 days post-HTx on sildenafil. Summary VAD support in tandem with optimal PH therapies is a feasible strategy to treat post-capillary PH, optimize pulmonary vasculature to reduce RV dysfunction, and enable a successful bridge to HTx.

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.