Longitudinal Follow-Up of Children With HLHS and Association Between Norwood Shunt Type and Long-Term Outcomes: The SVR III Study.

OBJECTIVE: In the SVR trial (Single Ventricle Reconstruction), newborns with hypoplastic left heart syndrome were randomly assigned to receive a modified Blalock-Taussig-Thomas shunt (mBTTS) or a right ventricle-to-pulmonary artery shunt (RVPAS) at Norwood operation. Transplant-free survival was superior in the RVPAS group at 1 year, but no longer differed by treatment group at 6 years; both treatment groups had accumulated important morbidities. In the third follow-up of this cohort (SVRIII [Long-Term Outcomes of Children With Hypoplastic Left Heart Syndrome and the Impact of Norwood Shunt Type]), we measured longitudinal outcomes and their risk factors through 12 years of age. METHODS: Annual medical history was collected through record review and telephone interviews. Cardiac magnetic resonance imaging (CMR), echocardiogram, and cycle ergometry cardiopulmonary exercise tests were performed at 10 through 14 years of age among participants with Fontan physiology. Differences in transplant-free survival and complication rates (eg, arrhythmias or protein-losing enteropathy) were identified through 12 years of age. The primary study outcome was right ventricular ejection fraction (RVEF) by CMR, and primary analyses were according to shunt type received. Multivariable linear and Cox regression models were created for RVEF by CMR and post-Fontan transplant-free survival. RESULTS: Among 549 participants enrolled in SVR, 237 of 313 (76%; 60.7% male) transplant-free survivors (mBTTS, 105 of 147; RVPAS, 129 of 161; both, 3 of 5) participated in SVRIII. RVEF by CMR was similar in the shunt groups (RVPAS, 51±9.6 [n=90], and mBTTS, 52±7.4 [n=75]; P=0.43). The RVPAS and mBTTS groups did not differ in transplant-free survival by 12 years of age (163 of 277 [59%] versus 144 of 267 [54%], respectively; P=0.11), percentage predicted peak Vo2 for age and sex (74±18% [n=91] versus 72±18% [n=84]; P=0.71), or percentage predicted work rate for size and sex (65±20% versus 64±19%; P=0.65). The RVPAS versus mBTTS group had a higher cumulative incidence of protein-losing enteropathy (5% versus 2%; P=0.04) and of catheter interventions (14 versus 10 per 100 patient-years; P=0.01), but had similar rates of other complications. CONCLUSIONS: By 12 years after the Norwood operation, shunt type has minimal association with RVEF, peak Vo2, complication rates, and transplant-free survival. RVEF is preserved among the subgroup of survivors who underwent CMR assessment. Low transplant-free survival, poor exercise performance, and accruing morbidities highlight the need for innovative strategies to improve long-term outcomes in patients with hypoplastic left heart syndrome. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT0245531.

Impact of ventricular assist device use on pediatric heart transplant waitlist mortality: Analysis of the scientific registry of transplant recipients database.

BACKGROUND: Children awaiting heart transplant (Tx) have a high risk of death due to donor organ scarcity. Historically, ventricular assist devices (VADs) reduced waitlist mortality, prompting increased VAD use. We sought to determine whether the VAD survival benefit persists in the current era. METHODS: Using the Scientific Registry of Transplant Recipients, we identified patients listed for Tx between 3/22/2016 and 9/1/2020. We compared characteristics of VAD and non-VAD groups at Tx listing. Cox proportional hazards models were used to identify risk factors for 1-year waitlist mortality. RESULTS: Among 5054 patients, 764 (15%) had a VAD at Tx listing. The VAD group was older with more mechanical ventilation and renal impairment. Unadjusted waitlist mortality was similar between groups; the curves crossed ~90 days after listing (p = .55). In multivariable analysis, infant age (HR 2.77, 95%CI 2.13-3.60), Black race (HR 1.57, 95%CI 1.31-1.88), congenital heart disease (HR 1.23, 95%CI 1.04-1.46), renal impairment (HR 2.67, 95%CI 2.19-3.26), inotropes (HR 1.28, 95%CI 1.09-1.52), and mechanical ventilation (HR 2.23, 95%CI 1.84-2.70) were associated with 1-year waitlist mortality. VADs were not associated with mortality in the first 90 waitlist days but were protective for those waiting ≥90 days (HR 0.43, 95%CI 0.26-0.71). CONCLUSIONS: In the current era, VADs reduce waitlist mortality, but only for those waitlisted ≥90 days. The differential effect by race, size, and VAD type is less clear. These findings suggest that Tx listing without VAD may be reasonable if a short waitlist time is anticipated, but VADs may benefit those expected to wait >90 days.

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.

Impact of donor-specific anti-HLA antibody on cardiac hemodynamics and graft function 3 years after pediatric heart transplantation: First results from the CTOTC-09 multi-institutional study.

The aim of this study (CTOTC-09) was to assess the impact of "preformed" (at transplant) donor-specific anti-HLA antibody (DSA) and first year newly detected DSA (ndDSA) on allograft function at 3 years after pediatric heart transplantation (PHTx). We enrolled children listed at 9 North American centers. The primary end point was pulmonary capillary wedge pressure (PCWP) at 3 years posttransplant. Of 407 enrolled subjects, 370 achieved PHTx (mean age, 7.7 years; 57% male). Pre-PHTx sensitization status was nonsensitized (n = 163, 44%), sensitized/no DSA (n = 115, 31%), sensitized/DSA (n = 87, 24%), and insufficient DSA data (n = 5, 1%); 131 (35%) subjects developed ndDSA. Subjects with any DSA had comparable PCWP at 3 years to those with no DSA. There were also no significant differences overall between the 2 groups for other invasive hemodynamic measurements, systolic graft function by echocardiography, and serum brain natriuretic peptide concentration. However, in the multivariable analysis, persistent first-year DSA was a risk factor for 3-year abnormal graft function. Graft and patient survival did not differ between groups. In summary, overall, DSA status was not associated with worse allograft function or inferior patient and graft survival at 3 years, but persistent first-year DSA was a risk factor for late graft dysfunction.

The pediatric heart network's study on long-term outcomes of children with HLHS and the impact of Norwood Shunt type in the single ventricle reconstruction trial cohort (SVRIII): Design and adaptations.

BACKGROUND: The Single Ventricle Reconstruction (SVR) Trial was the first randomized clinical trial of a surgical approach for treatment of congenital heart disease. Infants with hypoplastic left heart syndrome (HLHS) and other single right ventricle (RV) anomalies were randomized to a modified Blalock Taussig Thomas shunt (mBTTS) or a right-ventricular-to-pulmonary-artery shunt (RVPAS) at the time of the Norwood procedure. The aim of the Long-term Outcomes of Children with HLHS and the Impact of Norwood Shunt Type (SVR III) study is to compare early adolescent outcomes including measures of cardiac function, transplant-free survival, and neurodevelopment, between those who received a mBTTS and those who received an RVPAS. METHODS: Transplant-free survivors of the SVR cohort were enrolled at 10 to 15 years of age for multifaceted in-person evaluation of cardiac function (cardiac magnetic resonance [CMR], echocardiogram and exercise test) and neurodevelopmental evaluation. Right ventricular ejection fraction measured by CMR served as the primary outcome. Development of arrhythmias, protein losing enteropathy, and other comorbidities were assessed through annual medical history interview. Through the course of SVR III, protocol modifications to engage SVR trial participants were designed to enhance recruitment and retention. CONCLUSIONS: Evaluation of long-term outcomes will provide important data to inform decisions about the shunt type placed at the Norwood operation and will improve the understanding of cardiovascular and neurodevelopmental outcomes for early adolescents with HLHS.

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.

Developmental Care Practice and Documentation Variability in the Cardiac ICU.

OBJECTIVES: Describe variability in developmental care practices, as documented in the electronic health record, for infants undergoing congenital heart surgery. DESIGN: Multicenter, retrospective, cohort study. SETTING: Six pediatric cardiac centers. PATIENTS: One hundred eighty-two infants undergoing one of three index operations: Norwood palliation, aortic arch reconstruction with ventricular septal defect closure, or arterial switch. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Core domains of developmental care encompassing pain assessment, feeding, infant holding, caregiver involvement, therapy, and psychosocial services were reviewed. Practices varied across individuals, institutions, and the hospital stay. At five of six sites, greater than 90% of individuals had physical or occupational therapy services as part of their care, but the day of first evaluation ranged from day of admission to postoperative day 28. Similar patterns were seen in feeding team and social work involvement. Consistent documentation of developmental care was dependent on the domain and site. Of the total days reviewed (n = 1,192), pain scores were documented in 95%. In those same days, documentation of whether or not a patient was out of the crib to be held varied by site from 11% to 93%. Type of oral feeding, breast versus bottle, was documented on the day prior to discharge 48% of the time. CONCLUSIONS: There are significant, quantifiable variations in documented developmental care practices at both the individual and site level. More reliable documentation of developmental care practices is required to associate these variables with later outcomes and investigate disparities in individualized developmental care practices.

Autologous Cardiac Stem Cell Injection in Patients with Hypoplastic Left Heart Syndrome (CHILD Study).

Mortality in infants with hypoplastic left heart syndrome (HLHS) is strongly correlated with right ventricle (RV) dysfunction. Cell therapy has demonstrated potential improvements of RV dysfunction in animal models related to HLHS, and neonatal human derived c-kit+ cardiac-derived progenitor cells (CPCs) show superior efficacy when compared to adult human cardiac-derived CPCs (aCPCs). Neonatal CPCs (nCPCs) have yet to be investigated in humans. The CHILD trial (Autologous Cardiac Stem Cell Injection in Patients with Hypoplastic Left Heart Syndrome) is a Phase I/II trial aimed at investigating intramyocardial administration of autologous nCPCs in HLHS infants by assessing the feasibility, safety, and potential efficacy of CPC therapy. Using an open-label, multicenter design, CHILD investigates nCPC safety and feasibility in the first enrollment group (Group A/Phase I). In the second enrollment group, CHILD uses a randomized, double-blinded, multicenter design (Group B/Phase II), to assess nCPC efficacy based on RV functional and structural characteristics. The study plans to enroll 32 patients across 4 institutions: Group A will enroll 10 patients, and Group B will enroll 22 patients. CHILD will provide important insights into the therapeutic potential of nCPCs in patients with HLHS.Clinical Trial Registration https://clinicaltrials.gov/ct2/home NCT03406884, First posted January 23, 2018.

Implementation of a practice plan for the outpatient cardiac evaluation of children after acute SARS-CoV-2 infection and a report of outcomes.

SARS-CoV-2 infection has been associated with cardiovascular disease in children, but which children need cardiac evaluation is unclear. We describe our experience evaluating 206 children for cardiac disease following SARS-CoV-2 infection (one of whom had ventricular ectopy) and propose a new guideline for management of these children. Routine cardiac screening after SARS-CoV-2 infection in children without any cardiac signs or symptoms does not appear to be high yield.

Pretransplantation and Post-Transplantation Liver Disease Assessment in Adolescents Undergoing Isolated Heart Transplantation for Fontan Failure.

OBJECTIVE: To describe the assessment of Fontan-associated liver disease and determine the clinical and imaging measures that may identify hepatic morbidity risk in isolated heart transplantation candidates and trend those measures post-isolated heart transplantation. STUDY DESIGN: Retrospective analysis of pre-isolated heart transplantation and post-isolated heart transplantation Fontan-associated liver disease (FALD) status using blood tests, magnetic resonance imaging (MRI), and liver biopsy analysis within 6 months before isolated heart transplantation and 12 months after isolated heart transplantation in 9 consecutive patients with Fontan. Pre- and post-isolated heart transplantation standard laboratory values; varices, ascites, splenomegaly, thrombocytopenia (VAST) score; Fontan liver MRI score; liver biopsy scores; Model for End-stage Liver Disease (MELD); MELD excluding the International Normalized Ratio (MELD-XI); AST to platelet ratio index, and cardiac catheterization data were compared. RESULTS: Pretransplantation maximum MELD and MELD-XI was 15 and 16, respectively. Central venous pressures and VAST scores decreased significantly post-transplantation. In 5 paired studies, Fontan liver MRI score maximum was 10 pretransplantation and decreased significantly post-transplantation. Arterially enhancing nodules on MRI persisted in 2 patients post-transplantation. Pretransplantation and post-transplantation liver biopsy scores did not differ in 4 paired biopsy specimens. CONCLUSIONS: Patients with FALD and MELD <15, MELD-XI <16, Fontan liver MRI score <10, and VAST score ≤2 can have successful short-term isolated heart transplantation outcomes. Liver MRI and VAST scores improved post-transplantation. Post-transplantation liver biopsy scores did not change significantly. Pretransplantation liver biopsy demonstrating fibrosis alone should not exclude consideration of isolated heart transplantation. The persistence of hepatic vascular remodeling and fibrosis post-isolated heart transplantation suggests that continued surveillance for hepatic complications post-transplantation for patients with Fontan is reasonable.

The Association of Workload and Outcomes in the Pediatric Cardiac ICU.

OBJECTIVES: Healthcare workload has emerged as an important metric associated with poor outcomes. To measure workload, studies have used bed occupancy as a surrogate. However, few studies have examined frontline provider (fellows, nurse practitioners, physician assistants) workload and outcomes. We hypothesize frontline provider workload, measured by bed occupancy and staffing, is associated with poor outcomes and unnecessary testing. DESIGN: A retrospective single-center, time-stamped orders, ordering provider identifiers, and patient data were collected. Regression was performed to study the influence of occupancy on orders, length of stay, and mortality, controlling for age, weight, admission type, Society of Thoracic Surgery-European Association for Cardio-Thoracic Surgery Congenital Heart Surgery Mortality score, diagnosis, number of surgeries, orders, provider staffing, attending experience, and time fixed effects. SETTING: Twenty-seven bed tertiary cardiac ICU in a free-standing children's hospital. PATIENTS: Patients (0-18 yr) admitted to the pediatric cardiac ICU, January 2018 to December 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 16,500 imaging and 73,113 laboratory orders among 1,468 patient admissions. Median age 6 months (12 d to 5 yr), weight 6.2 kg (3.7-16.2 kg); 840 (57.2%) surgical and 628 (42.8%) medical patients. ICU teams consisted of 16 attendings and 31 frontline providers. Mortality 4.4%, median stay 5 days (2-11 d), and median bed occupancy 89% (78-93%). Every 10% increase in bed occupancy had 7.2% increase in imaging orders per patient (p < 0.01), 3% longer laboratory turn-around time (p = 0.015), and 3 additional days (p < 0.01). Higher staffing (> 3 providers) was associated with 6% less imaging (p = 0.03) and 3% less laboratory orders (p = 0.04). The number of "busy days" (bed occupancy > 89%) was associated with longer stays (p < 0.01), and increased mortality (p < 0.01). CONCLUSIONS: Increased bed occupancy and lower staffing were associated with increased mortality, length of stay, imaging orders, and laboratory turn-around time. The data demonstrate performance of the cardiac ICU system is exacerbated during high occupancy and low staffing.

Spillover of Early Extubation Practices From the Pediatric Heart Network Collaborative Learning Study.

OBJECTIVES: The Pediatric Heart Network Collaborative Learning Study used collaborative learning strategies to implement a clinical practice guideline that increased rates of early extubation after infant repair of tetralogy of Fallot and coarctation of the aorta. We assessed early extubation rates for infants undergoing cardiac surgeries not targeted by the clinical practice guideline to determine whether changes in extubation practices spilled over to care of other infants. DESIGN: Observational analyses of site's local Society of Thoracic Surgeons Congenital Heart Surgery Database and Pediatric Cardiac Critical Care Consortium Registry. SETTING: Four Pediatric Heart Network Collaborative Learning Study active-site hospitals. PATIENTS: Infants undergoing ventricular septal defect repair, atrioventricular septal defect repair, or superior cavopulmonary anastomosis (lower complexity), and arterial switch operation or isolated aortopulmonary shunt (higher complexity). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Aggregate outcomes were compared between the 12 month pre-clinical practice guideline and 12 months after study completion (Follow Up). In infants undergoing lower complexity surgeries, early extubation increased during Follow Up compared with Pre-Clinical Practice Guideline (30.2% vs 18.8%, p = 0.006), and hours to initial postoperative extubation decreased. We observed variation in these outcomes by surgery type, with only ventricular septal defect repair associated with a significant increase in early extubation during Follow Up compared with Pre-Clinical Practice Guideline (47% vs 26%, p = 0.006). Variation by study site was also seen, with only one hospital showing an increase in early extubation. In patients undergoing higher complexity surgeries, there was no difference in early extubation or hours to initial extubation between the study eras. CONCLUSIONS: We observed spillover of extubation practices promoted by the Collaborative Learning Study clinical practice guideline to lower complexity operations not included in the original study that was sustainable 1 year after study completion, though this effect differed across sites and operation subtypes. No changes in postoperative extubation outcomes following higher complexity surgeries were seen. The significant variation in outcomes by site suggests that center-specific factors may have influenced spillover of clinical practice guideline practices.

A Collaborative Learning Assessment of Developmental Care Practices for Infants in the Cardiac Intensive Care Unit.

OBJECTIVE: Assess differences in approaches to and provision of developmental care for infants undergoing surgery for congenital heart disease. STUDY DESIGN: A collaborative learning approach was used to stratify, assess, and compare individualized developmental care practices among multidisciplinary teams at 6 pediatric heart centers. Round robin site visits were completed with structured site visit goals and postvisit reporting. Practices of the hosting site were assessed by the visiting team and reviewed along with center self-assessments across specific domains including pain management, environment, cue-based care, and family based care coordination. RESULTS: Developmental care for infants in the cardiac intensive care unit (CICU) varies at both a center and individual level. Differences in care are primarily driven by variations in infrastructure and resources, composition of multidisciplinary teams, education of team members, and use of developmental care champions. Management of pain follows a protocol in most cardiac intensive care units, but the environment varies across centers, and the provision of cue-based infant care and family-based care coordination varies widely both within and across centers. The project led to proposed changes in clinical care and center infrastructure at each participating site. CONCLUSIONS: A collaborative learning design fostered rapid dissemination, comparison, and sharing of strategies to approach a complex multidisciplinary care paradigm. Our assessment of experiences revealed marked variability across and within centers. The collaborative findings were a first step toward strategies to quantify and measure developmental care practices in the cardiac intensive care unit to assess the association of complex inpatient practices with long-term neurodevelopmental outcomes.

Futility in the paediatric cardiac ICU.

INTRODUCTION: Studies have suggested 5-20% of paediatric ICU patients may receive care felt to be futile. No data exists on the prevalence and impact of futile care in the Paediatric Cardiac ICU. The aim is to determine the prevalence and economic impact of futile care. MATERIALS AND METHOD: Retrospective cohort of patients with congenital cardiac disease 0-21 years old, with length of stay >30 days and died (2015-2018). Documentation of futility by the medical team was retrospectively and independently reviewed. RESULTS: Of the 127 deaths during the study period, 51 (40%) had hospitalisation >30 days, 13 (25%) had received futile care and 26 (51%) withdrew life-sustaining treatment. Futile care comprised 0.69% of total patient days with no difference in charges from patients not receiving futile care. There was no difference in insurance, single motherhood, education, income, poverty, or unemployment in families continuing futile care or electing withdrawal of life-sustaining treatment. Black families were less likely than White families to elect for withdrawal (p = 0.01), and Hispanic families were more likely to continue futile care than non-Hispanics (p = 0.044). CONCLUSIONS: This is the first study to examine the impact of futile care and characteristics in the paediatric cardiac ICU. Black families were less likely to elect for withdrawal, while Hispanic families more likely to continue futile care. Futile care comprised 0.69% of bed days and little burden on resources. Cultural factors should be investigated to better support families through end-of-life decisions.

Transplant-Free Survival and Interventions at 6 Years in the SVR Trial.

BACKGROUND: In the SVR trial (Single Ventricle Reconstruction), 1-year transplant-free survival was better for the Norwood procedure with right ventricle-to-pulmonary artery shunt (RVPAS) compared with a modified Blalock-Taussig shunt in patients with hypoplastic left heart and related syndromes. At 6 years, we compared transplant-free survival and other outcomes between the groups. METHODS: Medical history was collected annually using medical record review, telephone interviews, and the death index. The cohort included 549 patients randomized and treated in the SVR trial. RESULTS: Transplant-free survival for the RVPAS versus modified Blalock-Taussig shunt groups did not differ at 6 years (64% versus 59%, P=0.25) or with all available follow-up of 7.1±1.6 years (log-rank P=0.13). The RVPAS versus modified Blalock-Taussig shunt treatment effect had nonproportional hazards (P=0.009); the hazard ratio (HR) for death or transplant favored the RVPAS before stage II surgery (HR, 0.66; 95% confidence interval, 0.48-0.92). The effect of shunt type on death or transplant was not statistically significant between stage II to Fontan surgery (HR, 1.36; 95% confidence interval, 0.86-2.17; P=0.17) or after the Fontan procedure (HR, 0.76; 95% confidence interval, 0.33-1.74; P=0.52). By 6 years, patients with RVPAS had a higher incidence of catheter interventions (0.38 versus 0.23/patient-year, P<0.001), primarily because of more interventions between the stage II and Fontan procedures (HR, 1.72; 95% confidence interval, 1.00-3.03). Complications did not differ by shunt type; by 6 years, 1 in 5 patients had had a thrombotic event, and 1 in 6 had had seizures. CONCLUSIONS: By 6 years, the hazards of death or transplant and catheter interventions were not different between the RVPAS versus modified Blalock-Taussig shunt groups. Children assigned to the RVPAS group had 5% higher transplant-free survival, but the difference did not reach statistical significance, and they required more catheter interventions. Both treatment groups have accrued important complications. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00115934.

Hospital readmission following pediatric heart transplantation.

The frequency, indications, and outcomes for readmission following pediatric heart transplantation are poorly characterized. A better understanding of this phenomenon will help guide strategies to address the causes of readmission. Data from the Clinical Trials in Organ Transplantation for Children (CTOTC-04) multi-institutional collaborative study were utilized to determine incidence of, and risk factors for, hospital readmission within 30 days and 1 year from initial hospital discharge. Among 240 transplants at 8 centers, 227 subjects were discharged and had follow-up. 129 subjects (56.8%) were readmitted within one year; 71 had two or more readmissions. The 30-day and 1-year freedom from readmission were 70.5% (CI: 64.1%, 76.0%) and 42.2% (CI: 35.7%, 48.7%), respectively. The most common indications for readmissions were infection followed by rejection and fever without confirmed infection, accounting for 25.0%, 10.6%, and 6.2% of readmissions, respectively. Factors independently associated with increased risk of first readmission within 1 year (Cox proportional hazard model) were as follows: transplant in infancy (P = .05), longer transplant hospitalization (P = .04), lower UNOS urgency status (2/IB vs 1A) at transplant (P = .04), and Hispanic ethnicity (P = .05). Hospital readmission occurs frequently in the first year following discharge after heart transplantation with highest risk in the first 30 days. Infection is more common than rejection as cause for readmission, with death during readmission being rare. A number of patient factors are associated with higher risk of readmission. A fuller understanding of these risk factors may help tailor strategies to reduce unnecessary hospital readmission.

Management of Cardiac Involvement Associated With Neuromuscular Diseases: A Scientific Statement From the American Heart Association.

For many neuromuscular diseases (NMDs), cardiac disease represents a major cause of morbidity and mortality. The management of cardiac disease in NMDs is made challenging by the broad clinical heterogeneity that exists among many NMDs and by limited knowledge about disease-specific cardiovascular pathogenesis and course-modifying interventions. The overlay of compromise in peripheral muscle function and other organ systems, such as the lungs, also makes the simple application of endorsed adult or pediatric heart failure guidelines to the NMD population problematic. In this statement, we provide background on several NMDs in which there is cardiac involvement, highlighting unique features of NMD-associated myocardial disease that require clinicians to tailor their approach to prevention and treatment of heart failure. Undoubtedly, further investigations are required to best inform future guidelines on NMD-specific cardiovascular health risks, treatments, and outcomes.

Study rationale, design, and pretransplantation alloantibody status: A first report of Clinical Trials in Organ Transplantation in Children-04 (CTOTC-04) in pediatric heart transplantation.

Anti-HLA donor-specific antibodies are associated with worse outcomes after organ transplantation. Among sensitized pediatric heart candidates, requirement for negative donor-specific cytotoxicity crossmatch increases wait times and mortality. However, transplantation with positive crossmatch may increase posttransplantation morbidity and mortality. We address this clinical challenge in a prospective, multicenter, observational cohort study of children listed for heart transplantation (Clinical Trials in Organ Transplantation in Children-04 [CTOTC-04]). Outcomes were compared among sensitized recipients who underwent transplantation with positive crossmatch, nonsensitized recipients, and sensitized recipients without positive crossmatch. Positive crossmatch recipients received antibody removal and augmented immunosuppression, while other recipients received standard immunosuppression with corticosteroid avoidance. This first CTOTC-04 report summarizes study rationale and design and relates pretransplantation sensitization status using solid-phase technology. Risk factors for sensitization were explored. Of 317 screened patients, 290 were enrolled and 240 underwent transplantation. Core laboratory evaluation demonstrated that more than half of patients were anti-HLA sensitized. Greater than 80% of sensitized patients had class I (with or without class II) HLA antibodies, and one-third of sensitized patients had at least 1 HLA antibody with median fluorescence intensity of ≥8000. Logistic regression models demonstrated male sex, weight, congenital heart disease history, prior allograft, and ventricular assist device are independent risk factors for sensitization.

Posterior Cerebellar Volume and Executive Function in Young Adults With Congenital Heart Disease.

OBJECTIVES: As the number of adolescents and young adults (AYAs) surviving congenital heart disease (CHD) grows, studies of long-term outcomes are needed. CHD research documents poor executive function (EF) and cerebellum (CB) abnormalities in children. We examined whether AYAs with CHD exhibit reduced EF and CB volumes. We hypothesized a double dissociation such that the posterior CB is related to EF while the anterior CB is related to motor function. We also investigated whether the CB contributes to EF above and beyond processing speed. METHODS: Twenty-two AYAs with CHD and 22 matched healthy controls underwent magnetic resonance imaging and assessment of EF, processing speed, and motor function. Volumetric data were calculated using a cerebellar atlas (SUIT) developed for SPM. Group differences were compared with t tests, relationships were tested with Pearson's correlations and Fisher's r to z transformation, and hierarchical regression was used to test the CB's unique contributions to EF. RESULTS: CHD patients had reduced CB total, lobular, and white matter volume (d=.52-.99) and poorer EF (d=.79-1.01) compared to controls. Significant correlations between the posterior CB and EF (r=.29-.48) were identified but there were no relationships between the anterior CB and motor function nor EF. The posterior CB predicted EF above and beyond processing speed (ps<.001). CONCLUSIONS: This study identified a relationship between the posterior CB and EF, which appears to be particularly important for inhibitory processes and abstract reasoning. The unique CB contribution to EF above and beyond processing speed alone warrants further study. (JINS, 2018, 24, 939-948).