Evaluating threshold for donor fraction cell-free DNA using clinically available assay for rejection in pediatric and adult heart transplantation.

BACKGROUND: The aims of the study were to assess the performance of a clinically available cell-free DNA (cfDNA) assay in a large cohort of pediatric and adult heart transplant recipients and to evaluate performance at specific cut points in detection of rejection. METHODS: Observational, non-interventional, prospective study enrolled pediatric and adult heart transplant recipients from seven centers. Biopsy-associated plasma samples were used for cfDNA measurements. Pre-determined cut points were tested for analytic performance. RESULTS: A total of 487 samples from 160 subjects were used for the analysis. There were significant differences for df-cfDNA values between rejection [0.21% (IQR 0.12-0.69)] and healthy samples [0.05% (IQR 0.01-0.14), p < .0001]. The pediatric rejection group had a median df-cfDNA value of 0.93% (IQR 0.28-2.84) compared to 0.09% (IQR 0.04-0.23) for healthy samples, p = .005. Overall negative predictive value was 0.94 while it was 0.99 for pediatric patients. Cut points of 0.13% and 0.15% were tested for various types of rejection profiles and were appropriate to rule out rejection. CONCLUSION: The study suggests that pediatric patients with rejection show higher levels of circulating df-cfDNA compared to adults and supports the specific cut points for clinical use in pediatric and adult patients with overall acceptable performance.

Clinical Variables Associated with Pre-Fontan Aortopulmonary Collateral Burden.

Aortopulmonary collaterals (APCs) develop universally, but to varying degrees, in patients with single ventricle congenital heart disease (CHD). Despite their ubiquitous presence, APCs remain poorly understood. We sought to evaluate the association between APC burden and common non-invasive clinical variables. We conducted a single center, retrospective study of patients with single ventricle CHD and previous Glenn palliation who underwent pre-Fontan cardiac magnetic resonance (CMR) imaging from 3/2018 to 3/2021. CMR was used to quantify APC flow, which was normalized to aortic (APC/QAo) and pulmonary vein (APC/QPV) blood flow. Univariate, multivariable, and classification and regression tree (CART) analyses were done to investigate the potential relationship between CMR-quantified APC burden and clinical variables. A total of 29 patients were included, all of whom had increased APC flow (APC/QAo: 26.9, [22.0, 39.1]%; APC/QPV: 39.4 [33.3, 46.9]%), but to varying degrees (APC/QAo: range 11.9-44.4%; APC/QPV: range 17.7-60.0%). Pulmonary artery size (Nakata index, at pre-Fontan CMR) was the only variable associated with APC flow on multivariable analysis (APC/QAo: p = 0.020, R2 = 0.19; APC/QPV: p = 0.0006, R2 = 0.36) and was the most important variable associated with APC burden identified by CART analysis (size inversely related to APC flow). APC flow is universally increased but highly variable in patients with single ventricle CHD and Glenn circulation. Small branch pulmonary artery size is a key factor associated with increased APC burden; however, the pathogenesis of APCs is likely multifactorial. Further research is needed to better understand APC pathogenesis, including predisposing and mitigating factors.

Prognostic utility of echocardiographically derived left ventricular strain in assessing neonatal enteroviral myocarditis outcome.

BACKGROUND: Neonatal enteroviral myocarditis is a rare but potentially fatal illness. We sought to identify echocardiographic markers at diagnosis that could help risk-stratify infants for poor outcome and to characterise late sequelae. METHODS: We reviewed data for infants <30 days of age diagnosed with enteroviral myocarditis between 1999 and 2019 at Children's Wisconsin. Echo measures were collected retrospectively from the initial neonatal study including left ventricular ejection fraction, shortening fraction, diastolic and systolic dimensions, and peak global circumferential and longitudinal strain. RESULTS: Fourteen neonates were diagnosed at an average age of 11 days. All had abnormal left ventricular ejection fraction (mean 38%; range 22-53%) at diagnosis. Three infants died, and one required transplantation during initial hospital. The 10 transplant-free survivors had significantly better global circumferential strain and global longitudinal strain at the initial echo compared to the 4 who died or needed transplant (global circumferential strain -13.2% versus -6.8%, p = 0.005; global longitudinal strain -8.8% versus -4.7%, p = 0.016). All other measures of left ventricular systolic function/dimensions were similar between the two groups. Follow-up data were available for 8/10 survivors; 5/8 had a persistently abnormal echo at an average interval of 8.3 years. 4/8 developed a left ventricular aneurysm that was consistently localised to the posterior basal wall. CONCLUSIONS: Neonatal enteroviral myocarditis carries a high risk of early mortality and late morbidity. Echo-derived left ventricular strain measures have utility in risk stratifying infants with enteroviral myocarditis. Most survivors continue to have late dysfunction necessitating cardiology surveillance and medical therapy.

Respiratory viral infections are prevalent but uncomplicated in single ventricle CHD.

BACKGROUND: Patients with single ventricle CHD have significant morbidity and healthcare utilisation throughout their lifetime, including non-cardiac hospital admissions. Respiratory viral infections are the main cause of hospitalisation in children, but few data exist for single ventricle patients. We sought to identify how respiratory viral infections impact patients with single ventricle CHD and potential differences between Glenn and Fontan circulation. METHODS: We conducted a retrospective study of patients seen from 01/01/2011-12/31/2020. We identified patients with a history of single ventricle CHD and Glenn palliation, and a normoxic control group with isolated atrial septal defect requiring surgical closure. We compared viral-related clinical presentations, admissions, and admission characteristics. RESULTS: A total of 312 patients were included (182 single ventricle, 130 atrial septal defect). Single ventricle patients were more likely than children with isolated atrial septal defect to be admitted with a respiratory virus (odds ratio 4.15 [2.30-7.46]), but there was no difference in mechanical ventilation or hospital length of stay (p = 0.4709). Single ventricle patients with Glenn circulation were more likely than those with Fontan circulation to present and be admitted (odds ratio 3.25 [1.62-6.52]), but there was no difference in ICU admission, mechanical ventilation, or hospital length of stay (p = 0.1516). CONCLUSIONS: Respiratory viral infections are prevalent but uncomplicated in patients with single ventricle CHD. Viral-related presentations and admissions are more prevalent during the period of Glenn circulation compared to Fontan circulation; however, rate of mechanical ventilation and hospital length of stay are similar.

Increase in nuclear cell-free DNA is associated with major adverse events in adult and pediatric heart transplant recipients.

BACKGROUND: Cell-free DNA is an emerging biomarker. While donor fraction may detect graft events in heart transplant recipients, the prognostic value of total nuclear cell-free DNA (ncfDNA) itself is largely unexplored. OBJECTIVE: Explore the relationship between ncfDNA and clinical events in heart transplant recipients. METHODS: We conducted a multi-center prospective study to investigate the value of cell-free DNA in non-invasive monitoring following heart transplantation. Over 4000 blood samples were collected from 388 heart transplant patients. Total ncfDNA and donor fraction were quantified. Generalized linear models with maximum likelihood estimation for repeated measures with subjects as clusters were used to explore the relationship of ncfDNA and major adverse events. Receiver operating characteristic curves were used to help choose cutpoints. RESULTS: A ncfDNA threshold (50 ng/ml) was identified that was associated with increased risk of major adverse events. NcfDNA was elevated in patients who suffered cardiac arrest, required mechanical circulatory support or died post heart transplantation as well as in patients undergoing treatment for infection. CONCLUSIONS: Elevated ncfDNA correlates with risk for major adverse events in adult and pediatric heart transplant recipients and may indicate a need for enhanced surveillance after transplant.

Relationship between donor fraction cell-free DNA and clinical rejection in heart transplantation.

BACKGROUND: Clinical rejection (CR) defined as decision to treat clinically suspected rejection with change in immunotherapy based on clinical presentation with or without diagnostic biopsy findings is an important part of care in heart transplantation. We sought to assess the utility of donor fraction cell-free DNA (DF cfDNA) in CR and the utility of serial DF cfDNA in CR patients in predicting outcomes of clinical interest. METHODS: Patients with heart transplantation were enrolled in two sequential, multi-center, prospective observational studies. Blood samples were collected for surveillance or clinical events. Clinicians were blinded to the results of DF cfDNA. RESULTS: A total of 835 samples from 269 subjects (57% pediatric) were included for this analysis, including 28 samples associated with CR were analyzed. Median DF cfDNA was 0.43 (IQR 0.15, 1.36)% for CR and 0.10 (IQR 0.07, 0.16)% for healthy controls (p < .0001). At cutoff value of 0.13%, the area under curve (AUC) was 0.82, sensitivity of 0.86, specificity of 0.67, and negative predictive value of 0.99. There was serial decline in DF cfDNA post-therapy, however, those with cardiovascular events (cardiac arrest, need for mechanical support or death) showed significantly higher levels of DF cfDNA on Day 0 (2.11 vs 0.31%) and Day 14 (0.51 vs 0.22%) compared to those who did not have such an event (p < .0001). CONCLUSION: DF cfDNA has excellent agreement with clinical rejection and, importantly, serial measurement of DF cfDNA predict clinically significant outcomes post treatment for rejection in these patients.

Educational and learning morbidity in pediatric heart transplant recipients: A pediatric heart transplant society study.

Educational development is an important component of quality of life for children with heart transplant. Aims include determining prevalence of and risk factors for modified education placement in a large representative sample of pediatric heart transplant recipients. Participants included 1495 patients (age 6-18 years) from the PHTS database. Data on education placement and clinical predictors were collected at listing and at 1 and 3 years post-transplant. At listing, 88% of patients were in typical education placement, while 12% were in modified education. Males (P = .02), those with CHD (P < .0001), those with non-private insurance (P < .0001), and those with longer hospital stay (P = .001) were more likely to be in a modified education placement at time of listing. Age, race, listing status, mechanical support, and waitlist time were not significantly associated with placement. The prevalence of typical education placement was similar (87% at 1-year and 86% at 3-year) post-transplant. Predictors of modified education placement at 3-year follow-up included placement at listing (OR = 12.9 [95% CI 7.6-21.9], P < .0001), non-private insurance (OR = 2.0 [95% CI 1.3-3.2], P = .001), CHD (OR = 1.8 [95% CI 1.1-2.7, P = .01), history of post-transplant infection (OR = 1.9 [95% CI 1.2-2.9, P = .007), and number of post-transplant infections (OR = 1.3 [95% CI 1.1-1.5, P = .002). Among pediatric heart transplant recipients, males, those with non-private insurance, those with CHD, and those who experience post-transplant infections are at greatest risk for modified academic placement, which persists for several years post-transplant and deserves targeted intervention.

Early changes in cell-free DNA levels in newly transplanted heart transplant patients.

Heart transplantation is a well-established therapy for end-stage heart failure in children and young adults. The highest risk of graft loss occurs in the first 60 days post-transplant. Donor fraction of cell-free DNA is a highly sensitive marker of graft injury. Changes in cell-free DNA levels have not previously been studied in depth in patients early after heart transplant. A prospective study was conducted among heart transplant recipients at a single pediatric heart center. Blood samples were collected from children and young adult transplant patients at three time points within 10 days of transplantation. DF and total cell-free DNA levels were measured using a targeted method (myTAIHEART ). In 17 patients with serial post-transplant samples, DF peaks in the first 2 days after transplant (3.5%, [1.9-10]%) and then declines toward baseline (0.27%, [0.19-0.52]%) by 6-9 days. There were 4 deaths in the first year among the 10 patients with complete sample sets, and 3 out of 4 who died had a late rise or blunted decline in donor fraction. Patients who died trended toward an elevated total cell-free DNA at 1 week (41.5, [34-65] vs 13.6, [6.2-22] P = .07). Donor fraction peaks early after heart transplant and then declines toward baseline. Patients without sustained decline in donor fraction and/or elevated total cell-free DNA at 1 week may have worse outcomes.

Marijuana in pediatric and adult congenital heart disease heart transplant listing: A survey of provider practices and attitudes.

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

Innominate Vein Turn-down Procedure for Failing Fontan Circulation.

After the Fontan, systemic venous hypertension induces pathophysiologic changes in the lymphatic system that can result in complications of pleural effusion, ascites, plastic bronchitis, and protein losing enteropathy. Advances in medical therapy and novel interventional approaches have not substantially improved the poor prognosis of these complications. A more physiological approach has been developed by decompression of the thoracic duct to the lower pressure common atrium with a concomitant increase of preload. Diverting the innominate vein to the common atrium increases the transport capacity of the thoracic duct, which in most patients enters the circulation at the left subclavian-jugular vein junction. Contrary to the fenestrated Fontan circulation, in which the thoracic duct is drained into the high pressure Fontan circulation, turn down of the innominate vein to the common atrium effectively decompresses the thoracic duct to the lower pressure system with "diastolic suctioning" of lymph. Innominate vein turn-down may be considered for medical-refractory post-Fontan lymphatic complications of persistent chylothorax, plastic bronchitis, and protein losing enteropathy. Prophylactic innominate vein turn-down may also be considered at time of the Fontan operation for patients that are higher risk for lymphatic complications.

Brain death interval and relationship to outcomes of pediatric cardiac transplantation.

BACKGROUND: We sought to analyze brain death interval and outcomes of pediatric cardiac transplantation using national registry data. METHODS: We retrospectively evaluated a pediatric cohort from the UNOS registry from 2005 to 2014. We restricted the donor cohort to those with a primary central nervous system event as the cause of hospitalization. Brain death interval (BDI) was defined as the time between hospital admission and organ procurement. Primary outcomes were recipient and graft survival time. Logistical regression modeling was used for multivariable analysis. RESULTS: The donor cohort included 2565 cases. Multivariable analysis demonstrated no relationship between BDI and recipient or graft survival time. For patient survival time, the lowest HR was 0.94 (0.63-1.39), P = 0.531; for graft survival time, the lowest HR was 0.89 (0.53-1.49), P = 0.563. We obtained similar results using a non-restricted donor cohort. CONCLUSIONS: There was no clear relationship between BDI and recipient or graft survival after pediatric cardiac transplantation.

New-onset diabetes after pediatric heart transplantation: A review of the Pediatric Heart Transplant Study.

NDT is a well-defined complication after solid organ transplantation. Little has been published describing the incidence, risk factors, and effect on outcome after pediatric heart transplantation. We performed a retrospective evaluation of pediatric patients from the PHTS registry from 2004 to 2014. Group comparison, associated factors, incidence using Kaplan-Meier method, and risk factor and outcome analysis for NDT at 1 year post-transplant. Of the 2185 recipients, 1756 were alive and followed at 1 year. Overall freedom from NDT was 98.9%, 94.7%, and 92.6% at 1, 5, and 10 years, respectively. Patients with NDT were more likely to be black (non-Hispanic; P = 0.002), older at time of transplant (P < 0.0001), and have a higher BMI percentile at time of transplant (P < 0.0001). Adjusted risk factors for NDT at 1 year were older age at transplant (years; >12 years, OR: 8.8 and 5-12 years, HR: 8.0), obese BMI percentile at time of transplant (OR: 3.8), and steroid use at 30 days after transplant (OR: 4.7). Though uncommon, NDT occurs with a constant hazard after pediatric heart transplant; it occurs more often in older patients at transplant, those who are of black race, those who are obese, and those who use steroids. Therefore, targeted weight reduction and selective steroid use in at-risk populations could reduce the incidence of early NDT. Further data are needed to determine the risk imparted by transplantation, factors that predict late-onset NDT, and whether NDT alters the outcome after transplant.

Chronotropic incompetence in paediatric heart transplant recipients with prior congenital heart disease.

BACKGROUND: Cardiopulmonary exercise testing has been used to measure functional capacity in children who have undergone a heart transplant. Cardiopulmonary exercise testing results have not been compared between children transplanted for a primary diagnosis of CHD and those with a primary diagnosis of cardiomyopathy despite differences in outcomes. This study is aimed to compare cardiopulmonary exercise testing performance between these two groups. METHODS: Patients who underwent heart transplant with subsequent cardiopulmonary exercise testing at least 6 months after transplant at our institution were identified. They were then divided into two groups based on primary cardiac diagnosis: CHD or cardiomyopathy. Patient characteristics, echocardiograms, cardiac catheterisations, outcomes, and cardiopulmonary exercise test results were compared between the two groups. RESULTS: From the total of 35 patients, 15 (43%) had CHD and 20 (57%) had cardiomyopathy. Age at transplant, kidney disease, lung disease, previous rejection, coronary vasculopathy, catheterisation, and echocardiographic data were similar between the groups. Mean time from transplant to cardiopulmonary exercise testing, exercise duration, and maximum oxygen consumption were similar in both groups. There was a difference in heart rate response with CHD heart rate response of 63 beats per minute compared to cardiomyopathy group of 78 (p = 0.028). Patients with CHD had more chronotropic incompetence than those with cardiomyopathy (p = 0.036). CONCLUSION: Primary diagnosis of CHD is associated with abnormal heart rate response and more chronotropic incompetence compared to those transplanted for cardiomyopathy.

Novel pathogenic variants in filamin C identified in pediatric restrictive cardiomyopathy.

Restrictive cardiomyopathy (RCM) is a rare and distinct form of cardiomyopathy characterized by normal ventricular chamber dimensions, normal myocardial wall thickness, and preserved systolic function. The abnormal myocardium, however, demonstrates impaired relaxation. To date, dominant variants causing RCM have been reported in a small number of sarcomeric or cytoskeletal genes, but the genetic causes in a majority of cases remain unexplained, especially in early childhood. Here, we describe two RCM families with childhood onset: one in a large family with a history of autosomal dominant RCM and the other a family with affected monozygotic, dichorionic/diamniotic twins. Exome sequencing found a pathogenic filamin C (FLNC) variant in each: p.Pro2298Leu, which segregates with disease in the large autosomal dominant RCM family, and p.Tyr2563Cys in both affected twins. In vitro expression of both mutant proteins yielded aggregates of FLNC containing actin in C2C12 myoblast cells. Recently, a number of variants in FLNC have been described that cause hypertrophic, dilated, and restrictive cardiomyopathies. Our data presented here provide further evidence for the role of FLNC in pediatric RCM, and suggest the need to include FLNC in genetic testing of cardiomyopathy patients including those with early ages of onset.

Haemodynamic profiles of children with end-stage heart failure.

AIMS: To evaluate associations between haemodynamic profiles and symptoms, end-organ function and outcome in children listed for heart transplantation. METHODS AND RESULTS: Children <18 years listed for heart transplant between 1993 and 2013 with cardiac catheterization data [pulmonary capillary wedge pressure (PCWP), right atrial pressure (RAP), and cardiac index (CI)] in the Pediatric Heart Transplant Study database were included. Outcomes were New York Heart Association (NYHA)/Ross classification, renal and hepatic dysfunction, and death or clinical deterioration while on waitlist. Among 1059 children analysed, median age was 6.9 years and 46% had dilated cardiomyopathy. Overall, 58% had congestion (PCWP >15 mmHg), 28% had severe congestion (PCWP >22 mmHg), and 22% low cardiac output (CI < 2.2 L/min/m2). Twenty-one per cent met the primary outcome of death (9%) or clinical deterioration (12%). In multivariable analysis, worse NYHA/Ross classification was associated with increased PCWP [odds ratio (OR) 1.03, 95% confidence interval (95% CI) 1.01-1.07, P = 0.01], renal dysfunction with increased RAP (OR 1.04, 95% CI 1.01-1.08, P = 0.007), and hepatic dysfunction with both increased PCWP (OR 1.03, 95% CI 1.01-1.06, P < 0.001) and increased RAP (OR 1.09, 95% CI 1.06-1.12, P < 0.001). There were no associations with low output. Death or clinical deterioration was associated with severe congestion (OR 1.6, 95% CI 1.2-2.2, P = 0.002), but not with CI alone. However, children with both low output and severe congestion were at highest risk (OR 1.9, 95% CI 1.1-3.5, P = 0.03). CONCLUSION: Congestion is more common than low cardiac output in children with end-stage heart failure and correlates with NYHA/Ross classification and end-organ dysfunction. Children with both congestion and low output have the highest risk of death or clinical deterioration.

HeartWare Ventricular Assist Device Implantation in Patients With Fontan Physiology.

We aim to describe the clinical course of a series of patients with hypoplastic left heart syndrome and refractory systolic heart failure supported with a HeartWare ventricular assist device (HVAD) following Fontan palliation. This is a retrospective review of three consecutive patients supported with a HVAD following Fontan palliation through February 2016. Data include patient characteristics, operative variables, postimplantation hemodynamic/device parameters, event outcomes, and duration of HVAD support. Patient ages were 11.7, 13.5, and 17.5 years, respectively, at the time of HVAD implant. The duration of HVAD support was 148, 272, and 271 days, respectively, of which 86, 222, and 211 were outpatient days. Inflow cannula position was the morphologic right ventricle with depth adjustment and manipulation of the tricuspid subvalvar apparatus to ensure good inflow. Echocardiographic, hemodynamic, and noninvasive oximetric monitoring resulted in high RPM settings for all patients. Despite various complications, all patients were successfully transplanted and discharged home alive. We present three patients bridged to transplantation using the HVAD following Fontan palliation. We demonstrate potential for durable support with transition to outpatient care while awaiting heart transplantation in a subset of patients status post Fontan surgery.

Mechanical Circulatory Support of the Fontan Patient.

Because of the inadequacies inherent to a circulation supported by a single ventricle, many Fontan patients will experience failure of their circulation. To date, there is no medical regimen that reliably and consistently restores circulatory function in these patients. Because of the shortage of donor organs and the fact that many of these patients present with features that either preclude or render heart transplantation a high risk, there is an intense need to better understand how mechanical circulatory support (MCS) may benefit these patients. In this report, we share our experience of successful MCS and transplantation of three patients. Our experience and that of others is very encouraging, but also preliminary. In general, a systemic ventricular assist device, with or without a Fontan fenestration, is a reasonable consideration for a patient presenting with predominantly systolic dysfunction. A pulmonary/systemic venous assist device may be sufficient for the patient with preserved systolic function and failure of the systemic venous/lymphatic system; however, this remains speculative. The more comprehensive approach of a total artificial heart or bilateral support is attractive in theory, but beset by the need for a more complex operation. In all scenarios, early referral, before organ failure, is paramount to successful MCS.

A contemporary review of paediatric heart transplantation and mechanical circulatory support.

Improvements in the care of children with cardiomyopathy, CHDs, and acquired heart disease have led to an increased number of children surviving with advanced heart failure. In addition, the advent of more durable mechanical circulatory support options in children has changed the outcome for many patients who otherwise would have succumbed while waiting for heart transplantation. As a result, more children with end-stage heart failure are being referred for heart transplantation, and there is increased demand for a limited donor organ supply. A review of important publications in the recent years related to paediatric heart failure, transplantation, and mechanical circulatory support show a trend towards pushing the limits of the current therapies to address the needs of this growing population. There have been a number of publications focussing on previously published risk factors perceived as barriers to successful heart transplantation, including elevated pulmonary vascular resistance, medication non-adherence, re-transplantation, transplantation of the failed Fontan patient, and transplantation in an infant or child bridged with mechanical circulatory support. This review will highlight some of these key articles from the last 3 years and describe recent advances in the understanding, diagnosis, and management of children with end-stage heart disease.

Eosinophilic esophagitis in children following cardiac transplantation: association with post-transplant lymphoproliferative disorder and other transplant outcomes.

Although cardiac transplantation is life-saving, morbidities from immunosuppression are significant. EoE is a complication of calcineurin inhibitors following liver transplant causing feeding intolerance, weight loss, vomiting, and dysphagia. There are limited reports of EoE following heart transplantation. We performed a retrospective single-center review of pediatric cardiac transplant patients from 2000 to 2010. A case-control analysis of patients with and without EoE was performed evaluating heart transplantation outcomes such as rates of rejection, CAV, PTLD, and graft loss. Eighty-six transplants were performed in 84 patients; 34 (40%) underwent diagnostic endoscopy, and 10 (12%) had EoE. Median time to diagnosis of EoE was 3.7 yr (IQR: 2.0-5.2). There were no differences in demographics or use of induction medications between patients with or without EoE. Patients with EoE had fewer episodes of treated rejection (1.0 vs. 2.5; p = 0.04). Four of 10 (40%) EoE patients had PTLD compared with only 2/24 (8%) of those without EoE (p = 0.048; OR 7.33 [95% CI: 1.1-50.2]). There were no differences in CAV or graft loss between groups. EoE should be considered as a cause of GI symptoms in children after cardiac transplantation and may be associated with fewer rejection episodes and increased rates of PTLD, thus representing a marker of over-immunosuppression.

School age and adolescent heart failure following the Norwood procedure.

BACKGROUND: Heart failure results in significant morbidity and mortality for young children with hypoplastic left heart syndrome (HLHS) following the Norwood procedure. The trajectory in later childhood is not well described. METHODS: We studied the outcome into adolescence of participants enrolled in the Single Ventricle Reconstruction trial who underwent the Fontan procedure or survived to 6 years without having undergone Fontan procedure. The primary outcome was heart failure events, defined as heart transplant listing or death attributable to heart failure. Symptomatic heart failure for participants surviving 10 or more years was also assessed utilizing the Pediatric Quality of Life Inventory (PedsQL). RESULTS: Of the 345 participants who underwent a Fontan operation or survived to 6 years without Fontan, 25 (7.2%) had a heart failure event before the age of 12 years. Among these, 21 were listed for heart transplant, and 4 died from heart failure. Nineteen participants underwent heart transplant, all of whom survived to age 12 years. Factors associated with a heart failure event included longer Norwood hospital length of stay, aortic atresia, and no Fontan operation by age 6 years. Assessment of heart failure symptoms at 12 years of age revealed that 24 (12.2%) of 196 PedsQL respondents "often" or "almost always" had difficulty walking more than one block. CONCLUSIONS: Heart failure events occur in over 5% of children with palliated HLHS between preschool age and adolescence. Outcomes for children listed for transplant are excellent. However, a substantial portion of palliated HLHS children have significant symptoms of heart failure at 12 years of age.