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Fontan associated liver disease (FALD) potentially impacts Fontan patients undergoing heart transplant. This multi-center study sought to identify pre-transplant risk factors and characterize any post-transplant liver recovery in those patients undergoing heart-alone transplant.Review of Fontan patients at 12 pediatric institutions who underwent heart transplant between 2001-2019. Radiologists reviewed pre and post-transplant liver imaging for fibrosis. Laboratory, pathology and endoscopy studies were reviewed.156 patients underwent transplant due to decreased ventricular function (49%), protein losing enteropathy (31%) or plastic bronchitis (10%); median age at transplant was 13.6 years (interquartile range IQR 7.8, 17.2) with a median of 9.3 years (IQR 3.2, 13.4) between the Fontan operation and transplant. Few patients had pre-transplant endoscopy (18%), and liver biopsy (19%). There were 31 deaths (20%). The median time from transplant to death was 0.5 years (95% Confidence Interval CI 0.0, 3.6). The five-year survival was 73% (95% CI 64%, 83%). Deaths were related to cardiac causes in 68% (21/31) and infection in 6 (19%). A pre-transplant elevation in bilirubin was a predictor of death. Higher platelet levels were protective. Immediate post-transplant elevations in creatinine, AST, ALT, and INR were predictive of death. Advanced liver fibrosis identified on ultrasound, computed tomography, or magnetic resonance imaging was not predictive of death. Liver imaging suggested some improvement in liver congestion post-transplant.Elevated bilirubin, but not fibrosis on liver imaging, was associated with post-heart transplant mortality in Fontan patients in this multicenter retrospective study. Additionally, heart transplant may alter the progression of FALD.

Adult experience evaluating left ventricular diastolic function (LVDFx) includes volume administration during catheterization while obtaining pulmonary capillary wedge pressures (PCWP) or left ventricular end diastolic pressures (LVEDP). Catheterization is inherently challenging in pediatric patients, making echocardiographic assessment ideal. Pediatric echocardiographic studies predicting LVDFx have variable hemodynamic and hydration conditions and have produced inconsistent results. We evaluated the association between simultaneous echocardiographic and catheterization assessment of LVDFx, using a fluid bolus for optimal loading conditions.Prospective cohort study of pediatric heart transplant recipients receiving echocardiogram simultaneous with routine cardiac catheterization. Mitral valve inflow velocities, septal and lateral wall tissue Doppler indices, and PCWP and/or LVEDP were obtained and repeated following a 10 ml/kg bolus. Echocardiographic parameters were evaluated for an association with changes in PCWP or LVEDP following the bolus. Abnormal LVDFx was defined as PCWP or LVEDP ≥12 mm Hg.Twenty-nine patients underwent catheterization. Median pre-bolus PCWP and LVEDP were 11.0 mm Hg and 10.0 mm Hg, respectively. After bolus, median PCWP and LVEDP increased to 14.0 mm Hg (p .001) and 13 mm Hg (p .001), respectively. Of 21 patients with normal pre-bolus catheterization hemodynamics, 14 (66.7%) increased to abnormal following fluid bolus. Using area under an ROC, no echocardiographic parameter of LVDFx, or their ratios, were associated with predetermined abnormal LVEDP and/or PCWP.After bolus, our cohort demonstrated significant increases in LVEDP and/or PCWP, unmasking diastolic dysfunction. Fluid challenges should be considered in pediatric patients undergoing cardiac catheterization with suspected diastolic dysfunction. Echocardiographic measurements were unable to discriminate between normal and abnormal LVEDP and/or PCWP.

Patients with Duchenne muscular dystrophy are living longer and are increasingly seen in Emergency Departments. Though the most common cause of death remains progressive respiratory failure, increased life expectancies have unmasked the significance of progressive myocardial dysfunction, now associated with nearly 40% of mortalities in the DMD population. Cardiac complications such as arrhythmias and cardiomyopathy are becoming ever more widely recognized. Emergency physicians may encounter DMD patients with untreated, undiagnosed or worsening of known heart disease. This review will initially familiarize the emergency physician with the pathophysiology and lifetime trajectory of care for these patients before describing specific emergency department evaluation and treatment.

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

Immune reconstitution inflammatory syndrome can be a complication of cryptococcal meningitis after immune reconstitution from antiretroviral therapy in HIV or reduced immune suppression in transplant recipients. In this case report, the authors discuss the diagnosis and management of cryptococcal-associated immune reconstitution inflammatory syndrome in a 10-year-old pediatric heart transplant recipient.

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

There is substantial need to increase donor heart utilization in pediatric heart transplantation. Almost half of pediatric heart donors are discarded, despite nearly 20% waitlist mortality. Physicians have limited time to view heart condition data and decide to accept the donor heart once the heart becomes available. Due to the large amount of data associated with each donor heart and the lack of data-driven guidelines, physicians often do not have adequate metrics to determine acceptable heart quality. This research characterizes the differences in the clinical course between accepted and rejected pediatric donor hearts. A longitudinal study assessing the effect of static and dynamic measurements on the donor heart’s function from the time of declaration of brain death to either disposal or heart procurement is developed by analyzing donor data via DonorNet, the system used by the United Network for Organ Sharing (UNOS) to match donors to a ranked order of recipients based on blood type, heart size, urgency status of the recipient, and other factors. Cardiovascular milieu (i.e. blood pressure, heart rate, medical management) and surrogate markers of organ perfusion, such as kidney and liver function, also inform our analyses and determine whether there are direct or indirect associations between these myriad markers and heart function. It also analyzes the proportion of measurements in stable and acceptable ranges over time, as well as typical minimum, maximum, and final measurements for different functions. All analyses are compared between accepted and rejected hearts using logistic regression and statistical analysis. Using the most recent measurements for each donor at 24 hours after brain death, the analysis identified significant factors in predicting donor heart acceptance: Left Ventricular Valve Dysfunction, Age, Shortening Fraction, and 4 Chamber Ejection Fraction. Additionally, visual tools were created as deliverables to aid physicians to decrease decision time and increase confidence in donor heart acceptance or rejection.

Background Freedom from rejection in pediatric heart transplant recipients is highly variable across centers. This study aimed to assess the center variation in methods used to diagnose rejection in the first-year post-transplant and determine the impact of this variation on patient outcomes. Methods The PHTS registry was queried for all rejection episodes in the first-year post-transplant (2010-2019). The primary method for rejection diagnosis was determined for each event as surveillance biopsy, echo diagnosis, or clinical. The percentage of first-year rejection events diagnosed by surveillance biopsy was used to approximate the surveillance strategy across centers. Methods of rejection diagnosis were described and patient outcomes were assessed based on surveillance biopsy utilization among centers. Results A total of 3985 patients from 56 centers were included. Of this group, 873 (22%) developed rejection within the first-year post-transplant. Surveillance biopsy was the most common method of rejection diagnosis (71.7%), but practices were highly variable across centers. The majority (73.6%) of first rejection events occurred within 3-months of transplantation. Diagnosis modality in the first-year was not independently associated with freedom from rejection, freedom from rejection with hemodynamic compromise, or overall graft survival . Conclusions Rejection in the first-year after pediatric heart transplant occurs in 22% of patients and most commonly in the first 3 months post-transplant. Significant variation exists across centers in the methods used to diagnose rejection in pediatric heart transplant recipients, however, these variable strategies are not independently associated with freedom from rejection, rejection with hemodynamic compromise, or overall graft survival.

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

Objective Newborns with Trisomy 21 (T21) often require NICU hospitalization. Oxygen desaturations are frequently observed in these infants, even in the absence of congenital heart defects (CHD). We hypothesized that T21 NICU patients have more hypoxemia than those without T21. Design All infants with T21 without significant CHD discharged home from the NICU between 2009–2018 were included (n=23). Controls were matched 20:1 for gestational age and length of stay. We compared daily severe hypoxemia events (SpO2

Background Infants with heart failure remain at significant risk for wait list mortality, despite mechanical circulatory support (MCS). It is unclear if the outcomes are influenced by modality of support or underlying diagnosis. We sought to compare the outcomes of infants Methods and Results Using the Pediatric Heart Transplant Society database, we evaluated survival following first MCS device in children P =0.2; 5.4% versus 6.4%; P =0.4). However, there was a significant difference in the use of VAD both at listing (8% versus 2.4%; P P P P =0.01) for the CHD or the cardiomyopathy group ( P =0.38), but patients with cardiomyopathy demonstrated better survival on both forms of support. Conclusions Survival for patients

As survival and neuromuscular function in Duchenne muscular dystrophy (DMD) have improved with glucocorticoid (GC) therapy and ventilatory support, cardiac deaths are increasing. Little is known about risk factors for cardiac and non-cardiac causes of death in DMD. A multi-center retrospective cohort study of 408 males with DMD, followed from January 1, 2005 to December 31, 2015, was conducted to identify risk factors for death. Those dying of cardiac causes were compared to those dying of non-cardiac causes and to those alive at study end. There were 29 (7.1%) deaths at a median age of 19.5 (IQR: 16.9–24.6) years; 8 (27.6%) cardiac, and 21 non-cardiac. Those living were younger [14.9 (IQR: 11.0–19.1) years] than those dying of cardiac [18 (IQR 15.5–24) years, p = 0.03] and non-cardiac [19 (IQR: 16.5–23) years, p = 0.002] causes. GC use was lower for those dying of cardiac causes compared to those living [2/8 (25%) vs. 304/378 (80.4%), p = 0.001]. Last ejection fraction prior to death/study end was lower for those dying of cardiac causes compared to those living (37.5% ± 12.8 vs. 54.5% ± 10.8, p = 0.01) but not compared to those dying of non-cardiac causes (37.5% ± 12.8 vs. 41.2% ± 19.3, p = 0.58). In a large DMD cohort, approximately 30% of deaths were cardiac. Lack of GC use was associated with cardiac causes of death, while systolic dysfunction was associated with death from any cause. Further work is needed to ensure guideline adherence and to define optimal management of systolic dysfunction in males with DMD with hopes of extending survival.

Acyanotic congenital heart diseases or left-to-right shunting lesions are the most common form of congenital heart disease. Although most resolve spontaneously, many will remain hemodynamically significant, particularly in the premature infant. Understanding the difference in pathophysiology, diagnosis, and management between the term and preterm infant is imperative to minimize the risk of secondary organ dysfunction and ensure proper growth and development.

Obstructive cardiac lesions are a common type of congenital heart disease ranging in severity from asymptomatic, mild valvular stenosis to valvar atresia with congestive heart failure and cyanosis. Understanding the pathophysiology and initial management of right and left ventricular outflow tract obstruction is imperative to minimize morbidity and mortality in term and preterm infants.

Purpose Allosensitization to human leukocyte antigen (HLA) in pediatric heart transplant candidates is associated with higher waitlist, post-transplantation mortality and antibody mediated rejection. As limited safety/efficacy data exist on pre-transplant desensitization regimen, we reviewed our institution's experience. Methods We reviewed the medical records of 12 highly sensitized (average cPRA = 68%) pediatric heart transplant candidates who underwent desensitization therapy at the University of Virginia Hospital between 2014 and 2020. The following data were collected: individual immunosuppression regimen, pre and post desensitization levels of antibody burden, documented side effects, and incidence of antibody mediated rejection. Results The majority of patients received an oral immunosuppressive regimen of Prednisone (0.3 mg/kg/day to max dose of 12.5 mg) and an antimetabolite (Cellcept 60 mg/kg/dose q12 up to 1,000 mg q12 or Imuran 1-2 mg/kg/day) followed by a single infusion of Rituximab (375 mg/m2) and monthly intravenous immunoglobulin (IVIG 2 g/kg) infusions; plasmapheresis was used in one patient and Bortezomib was used in two. cPRA decreased by an average of nearly 20% after an average of 17.5 weeks (Table 1). HLA I antibodies were more susceptible to desensitization than HLA II antibodies (60% vs 36% average antibody reduction, respectively). Immunosuppression medications were well tolerated with only one patient requiring Rituximab discontinuation due to hypotension, tachycardia and respiratory distress. There were no cases of antibody mediated rejection in those patients who underwent transplantation. Conclusion In our cohort, B-cell/ antibody targeted therapies were safe and effective in improving allosensitization and allowing for successful transplantation, though HLA II antibodies were more resistant to therapy. Larger scale studies are needed.

Background: Pediatric echocardiographic studies attempting to predict gold standard cardiac catheterization measures of left ventricular diastolic function (LVDFx) (pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure (LVEDP)) are often retrospective, evaluated under variable hemodynamic and hydration conditions, and have demonstrated inconsistent results. We are unaware of any pediatric studies comparing echocardiographic measures of LVDFx with PCWP or LVEDP under the same loading conditions. We hypothesize, standard echocardiographic measurements of LVDFx can predict abnormal cardiac catheterization derived LVEDP or PCWP, when obtained under similar loading conditions and following …

There is a shortage of pediatric donor hearts for waitlisted children, and yet nearly 50% of organs offered are not transplanted. Donor quality is often cited as a reason for declining organs offered from donors infected with influenza, presumably due to concern about disease transmission at transplant leading to severe disease. We previously described an excellent outcome after heart transplant from a donor infected with influenza B that had been treated with a complete course of oseltamivir. In this report, we describe a similar outcome after transplantation of an organ from an influenza A‐positive donor with symptomatic disease incompletely treated with oseltamivir. Due to the availability of effective antiviral treatment, we suggest that influenza A is also a manageable donor infection that need not preclude heart placement.

Respiratory failure requiring extracorporeal membranous oxygenation in the newborn is commonly seen secondary to severe pathology such as congenital diaphragmatic hernia, meconium aspiration syndrome, pulmonary hypertension and pulmonary hypoplasia. However, atypical causes of respiratory failure, such as pulmonary arterial thrombi, are often refractory to traditional management and require careful multidisciplinary evaluation. We report a case of respiratory failure secondary to congenital pulmonary arterial thrombosis of unknown aetiology in an otherwise healthy neonate. We discuss the abnormal anatomy and pathophysiology that presented in our patient secondary to this condition and discuss our diagnostic process, management and outcomes. Additionally, we review the literature for reported cases and discuss current hypotheses on the development of congenital pulmonary arterial thrombi. Given the rare occurrence of this event, we hope to contribute to the understanding of future similar cases and emphasise the importance of keeping pulmonary arterial thrombi in the clinical differential.

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

Through this study, we aimed to assess the ability of routine neonatal screening at time of bronchopulmonary dysplasia (BPD) diagnosis to predict the development of late pulmonary hypertension (PHTN). This is a retrospective longitudinal cohort study of 37 premature infants with BPD assessing the utility of screening serum brain natriuretic peptide (BNP) and echocardiograms performed at the time of BPD diagnosis (‘early PHTN’) to predict ‘late PHTN’ at the last follow-up. Screening evaluation demonstrated early PHTN in 9/37 patients. At an average follow-up interval of 52.7 ± 38.7 weeks, 4/9 had late PHTN; one patient without early PHT had late PHT. At initial screening, infants with late PHTN were significantly more likely to have demonstrated elevated BNP values (p = 0.003), and echocardiographic evidence of right atrial dilatation (p = 0.01), right ventricular hypertrophy (p = 0.01), lower right ventricular area change percentage (p = 0.03), and larger main pulmonary artery Z-scores (p = 0.02). Serum BNP and echocardiographic evaluation performed at the time of BPD diagnosis can detect patients at increased risk of late PHTN. Large, prospective studies are necessary to further address this question.

Background Pulmonary blood flow during Stage 1 (Norwood) palliation for hypoplastic left heart syndrome (HLHS) is achieved via modified Blalock–Taussig shunt (MBT) or right ventricle to pulmonary artery conduit (RVPA). Controversy exists regarding the differential impact of shunt type on outcome among those who require transplantation early in life. In this study we explored waitlist and post-transplant outcomes within this sub-population stratified by shunt type. Methods Eligible patients were enrolled through the Pediatric Heart Transplant Study (PHTS) database. Patients included those listed for heart transplantation at 1 of 35 participating centers, all of whom were Results Between 2010 and 2013, 190 patients were identified. Compared with the RVPA group ( n = 111), the MBT group ( n = 79) was less likely to have undergone a Glenn palliation (41% vs 73%, p p = 0.05), had lower median weight (7.9 vs 9.4 kg, p = 0.02), and were more likely to be mechanically ventilated at listing (35% vs 22%, p = 0.04). There were no significant differences in median waitlist time (1.7 vs 2.6 months, p = 0.2) or rate of transplantation (61% vs 60%, p = 1.0). Among waitlisted patients, 3-month survival was less for MBT compared with RVPA patients (74% vs 91%, p = 0.02). Patients who had not yet achieved Glenn palliation before listing had lower waitlist 3-month survival (76% vs 90%, p = 0.02). In MBT infants p = 0.08). Early post-transplant mortality rates were similar between the RVPA and MBT groups ( p = 0.4) with overall survival 84% at 1 year. Conclusions Among HLHS patients, the need for transplant before Glenn palliation is associated with poorer waitlist survival. Waitlist survival is poorer in the MBT group, with this difference driven by pre-Glenn MBT infants. Post-transplant outcomes were unaffected by shunt type.

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

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

Objectives To determine whether children with type 1 diabetes mellitus (T1DM) have evidence of increased aortic stiffness or early atherosclerosis as measured by magnetic resonance imaging (MRI). Background T1DM increases risk for cardiovascular disease in adults but whether this process starts in childhood is unknown. Subjects A total of 54 T1DM patients (15.4 ± 2.6 yr) and 30 age-matched controls (14.8 ± 2.7 yr) participated. Methods MRI was performed to assess aortic arch pulse wave velocity (PWV), strain, and distensibility of the ascending and descending thoracic aorta and measures of atherosclerosis. Results Groups were well-matched for age, pulse pressure, and gender. Low-density lipoprotein-cholesterol (LDL-C) was higher in T1DM (119.3 ± 50 vs. 76.1 ± 13.5 mg/dL, p < 0.0001). There was a trend toward decreased strain and distensibility in T1DM vs. controls in the ascending (distensibility: T1DM 62.2 ± 19.9 kPa−1 × 10−3, control 71.6 ± 26.4 kPa−1 × 10−3, p = 0.08) and descending aorta (strain: T1DM 25.8 ± 6.2% vs. control 28.3 ± 6.8%, p = 0.09). There was no difference in arch PWV. Advancing age and male gender was negatively associated with aortic stiffness. Hemoglobin A1c (HbA1c) was inversely related to descending aorta strain and distensibility (p < 0.05). Children with diabetes in the lowest two tertiles of insulin sensitivity demonstrated thoracic descending aortas with significantly lower strain (p = 0.027) and distensibility (p = 0.039) and increased measures of wall irregularity (p = 0.005). There were no differences in measurements of atherosclerosis between the two groups. Conclusions Adolescents with T1DM, especially those with lower insulin sensitivity, demonstrated a trend toward stiffer, less compliant thoracic aortas, which was inversely associated with diabetes control. These data suggest large vessel aortopathy starts early in T1DM.

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

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

As heart transplantation demand is increasing without subsequent growth of the donor pool, need for expansion of acceptance criteria is paramount, particularly when considering critically ill, highly sensitized patients. We present a case report of a pediatric heart transplant recipient of an organ refused by 197 prior potential recipients due to the donor being infected with influenza virus. We perform a literature review of recent solid organ transplant cases from influenza-positive donors and conclude that the donor pool may be expandable by allowing donors with treatable infections to be included.

Background and Aims Chylothorax (CTX) occurs in 3% to 6% of children after surgery for congenital heart disease with significant morbidity and mortality. Octreotide has been proposed as therapy, but there are no predictors of response. The objective of this study was to identify possible predictors of response to octreotide. Methods Single-center retrospective review of patients who developed CTX after cardiac surgery. Data collected included demographics, cardiac lesion, surgical data, hospital course, CTX volume and duration, and interventions for CTX. Patients who received octreotide as part of their therapy were compared to those who did not. Results A total of 1150 patients underwent 1455 cardiac surgeries with 67 (4.6%) episodes of CTX. Patients with CTX were younger, lower weight, more likely to undergo cardiopulmonary bypass, and had higher RACHS-1 scores and mortality. Nineteen patients with CTX received octreotide as part of their treatment and six (32%) had at least 50% reduction in CTX volume. Patients who responded to octreotide had lower CTX volume (18 mL/kg/day vs. 55 mL/kg/day, p = 0.023) and a higher proportion of patients with single ventricle anatomy (67% vs. 18%, p = 0.046). Conclusions There is a subset of patients who seem to respond to octreotide, but they have lower CTX volume and may have already been improving before octreotide therapy. Patients with single ventricle anatomy seemed to respond to octreotide and may benefit from its use. doi: 10.1111/jocs.12263 (J Card Surg 2014;29:259–264)

United Network for Organ Sharing (UNOS) policy enables listing exceptions to avoid penalizing patients with waitlist mortality not captured by standard criteria. Outcomes among patients listed by exception have not been analyzed.We performed a retrospective analysis of pediatric (≤17 years of age, n = 4,706) listings (2006 to 2015) for primary, isolated heart transplantation within the UNOS data set, assessing Status 1A exception (n = 211, 4.5%) use across regions and patient characteristics and evaluating waitlist outcomes compared with candidates listed using standard criteria.Death or removal for reason other than transplant did not differ between exception and standard criteria patients at 1 month (11.7% vs 16.2%, p = not statistically significant [NS]), 2 months (18.2% vs 29.0%, p = 0.11) or overall (16.1% vs 22.0%, p = NS) on the waitlist. Rates were higher than among Status 1B patients (1 month: 2.8%; 2 months: 5.6%; overall: 14.9%; p0.0001). The cumulative incidence of competing risks (transplantation, death/removal for reasons other than transplant and removal) did not differ when comparing Status 1A exception patients with Status 1A standard criteria patients. Use of 1A exceptions varied across UNOS regions (1.9% to 22.3%, p0.0001). Risk-adjusted modeling identified patients more (hypertrophic cardiomyopathy: odds ratio [OR] = 2.8, 95% confidence interval [CI] 1.5 to 5.0; restrictive cardiomyopathy: OR = 2.7, 95% CI 1.7 to 4.3) and less (low socioeconomic status: OR = 0.7, 95% CI 0.5 to 1.0) likely to use an exception. Use of exceptions was uncorrelated with regional outcomes.Waitlist mortality among Status 1A exception patients is similar to that among those listed by standard criteria. However, variation in exception use across geography and demography may contribute to inequities in access to transplantation, particularly for those with low socioeconomic status. Standardization of practices may decrease regional variation and minimize inequities.

Research in central nervous system (CNS) biology and pathology requires in vitro models, which, to recapitulate the CNS in vivo, must have extensive myelin and synapse formation under serum-free (defined) conditions. However, finding such a model has proven difficult. The technique described here produces dense cultures of myelinated axons, with abundant synapses and nodes of Ranvier, that are suitable for both morphological and biochemical analysis. Cellular and molecular events were easily visualised using conventional microscopy. Ultrastructurally, myelin sheaths were of the appropriate thickness relative to axonal diameter (G-ratio). Production of myelinated axons in these cultures was consistent and repeatable, as shown by statistical analysis of multiple experimental repeats. Myelinated axons were so abundant that from one litter of embryonic mice, myelin was produced in amounts sufficient for bulk biochemical analysis. This culture method was assessed for its ability to generate an in vitro model of the CNS that could be used for both neurobiological and neuropathological research. Myelin protein kinetics were investigated using a myelin fraction isolated from the cultures. This fraction was found to be superior, quantitatively and qualitatively, to the fraction recovered from standard cultures of dissociated oligodendrocytes, or from brain slices. The model was also used to investigate the roles of specific molecules in the pathogenesis of inflammatory CNS diseases. Using the defined conditions offered by this culture system, dose-specific, inhibitory effects of inflammatory cytokines on myelin formation were demonstrated, unequivocally. The method is technically quick, easy and reliable, and should have wide application to CNS research.

This study tested the hypothesis that pediatric patients who develop chylothorax (CTX) after surgery for congenital heart disease (CHD) have an elevated incidence and risk profile for central venous thrombosis (CVT). We evaluated 30 patients who developed CTX after surgery for CHD. All but one CTX patient were surgery-, anatomy-, and age-matched with two controls (NON-CTX) to compare their relative risk and incidence of CVT. Using conditional logistic regression analyses, CTX development was associated with significantly longer ventilator dependence (14.8 +/- 10.9 vs. 6.1 +/- 5.9 days, p = 0.003) and a non-significant trend towards more days of central venous catheters (CVC) (19.1 +/- 16.6 vs. 12.2 +/- 10.0 days; p = 0.16) when comparing the period prior to CTX development with the entire hospitalization in NON-CTX patients. CTX development was associated with a significantly elevated mortality risk (Odds Ratio 6.2, 95% CI 1.3-30.9). Minimum and mean daily central venous pressures were significantly higher in the CTX group. Post operative need for extracorporeal membrane oxygenation conferred an increased risk of CTX development in this sample of patients (Odds Ratio 9.9, 95% CI 2.2-44.8). Incidence of documented CVT was 26.7% in the CTX group versus 5.1% in the NON-CTX group. Prospective screening for CVT risk and formation, combined with early removal of CVC may help reduce the incidence of CTX.

Mechanical circulatory support options for infants and children are very limited in the United States. Existing circulatory support systems have proven successful for short-term pediatric assist, but are not completely successful as a bridge-to-transplant or bridge-to-recovery. To address this substantial need for alternative pediatric mechanical assist, we are developing a novel, magnetically levitated, axial flow pediatric ventricular assist device (PVAD) intended for longer-term ventricular support. Three major numerical design and optimization phases have been completed. A prototype was built based on the latest numerical design (PVAD3) and hydraulically tested in a flow loop. The plastic PVAD prototype delivered 0.5-4 lpm, generating pressure rises of 50-115 mm Hg for operating speeds of 6,000-9,000 rpm. The experimental testing data and the numerical predictions correlated well. The error between these sets of data was found to be generally 7.8% with a maximum deviation of 24% at higher flow rates. The axial fluid forces for the numerical simulations ranged from 0.5 to 1 N and deviated from the experimental results by generally 8.5% with a maximum deviation of 12% at higher flow rates. These hydraulic results demonstrate the excellent performance of the PVAD3 and illustrate the achievement of the design objectives.

Summary Background Spinal deformity is one of the secondary musculoskeletal problems that occur with cerebral palsy (CP). Of the co morbidities associated with CP and spinal deformity, cardiac function is of theoretical concern. Objective The goal of our study was to determine the clinical relevance of routine preoperative cardiology evaluation via echocardiogram for patients with CP presenting for posterior spine fusion (PSF) surgery. Methods A retrospective chart review was performed of CP patients presenting for scoliosis surgery. The data collected for each patient included: age, sex, height, weight, Cobb angle, and medical history. All patients had a preoperative cardiac evaluation. Results Seventy-two patients were included. The mean age was 13.6 ± 3.4 years. Left ventricular systolic function was normal in all patients; the mean shortening fraction was 39.3 ± 6.2%. No patient had more than mild insufficiency of either the semilunar or atrioventricular valve. One patient was diagnosed with aortic root dilation as well as aortic valve insufficiency. All patients had PSF surgery without changes in anesthetic or surgical plans, and no patient experienced complications attributable to a cardiac origin. Conclusion The results suggest that routine preoperative cardiology evaluation via echocardiogram for children with CP in the absence of clinical history or physical examination findings suggestive of cardiac disease is not necessary.

Rapid passage signals exhibiting saturation effects have been observed when a low-pressure sample of ethylene, within a multiple pass absorption cell, is subjected to radiation from a repetitively pulsed 10.25 micron quantum-cascade laser. Within each pulse the laser frequency sweeps 36 GHz from high to low frequency in a time of 140 ns. At the low gas pressures, less than 20 mTorr, in the absorption cell the sweep rate through a Doppler-broadened absorption line (ca. 0.5 ns), is much faster than the collisional relaxation time of the ethylene and this leads to rapid passage effects. Examples are given of the complex rapid passage signals observed in pure and nitrogen broadened spectra. The rapid passage effects, which lead to the variety of the observed signals, have been modelled by numerical solution of the coupled Maxwell–Bloch equations for four sets of two-level systems.

The Virginia Artificial Heart Institute continues to design and develop an axial-flow pediatric ventricular assist device (PVAD) for infants and children in the United States. Our research team has created a database to track potential PVAD candidates at the University of Virginia Children's Hospital. The findings of this database aided with need assessment and design optimization of the PVAD. A numerical analysis of the optimized PVAD1 design (PVAD2 model) was also completed using computational fluid dynamics (CFD) to predict pressure-flow performance, fluid force estimations, and blood damage levels in the flow domain. Based on the PVAD2 model and after alterations to accommodate manufacturing, a plastic prototype for experimental flow testing was constructed via rapid prototyping techniques or stereolithography. CFD predictions demonstrated a pressure rise range of 36-118 mm Hg and axial fluid forces of 0.8-1.7 N for flows of 0.5-3 l/min over 7000-9000 rpm. Blood damage indices per CFD ranged from 0.24% to 0.35% for 200 massless and inert particles analyzed. Approximately 187 (93.5%) of the particles took less than 0.14 seconds to travel completely through the PVAD. The mean residence time was 0.105 seconds with a maximum time of 0.224 seconds. Additionally, in a water/glycerin blood analog solution, the plastic prototype produced pressure rises of 20-160 mm Hg for rotational speeds of 5960 +/- 18 rpm to 9975 +/- 31 rpm over flows from 0.5 to 4.5 l/min. The numerical results for the PVAD2 and the prototype hydraulic testing indicate an acceptable design for the pump, represent a significant step in the development phase of this device, and encourage manufacturing of a magnetically levitated prototype for animal experiments.

Children who have had surgical correction for congenital heart disease can present to the ED with an acute illness that could be associated with their cardiac lesion. There is no data available to summarize complications that could be associated with surgically corrected congenital heart disease. This work was undertaken to describe the common procedures used, list known complications of these procedures, and review general management principles in caring for the acutely ill child who has had heart surgery.