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Objectives Approximately 0.2% to 2.7% of children with congenital heart disease require a tracheostomy after cardiac surgery with the majority having single ventricle (SV) type heart lesions. Tracheostomy in SV patients is reported to be associated with high mortality. We hypothesized that short- and long-term survival of patients with SV heart disease would vary according to tracheostomy indication. Methods This is a single center, 20-year, retrospective review of all patients with SV heart disease who underwent tracheostomy. Demographic, cardiac anatomy, surgical, intensive care unit, and hospital course data were collected. The primary outcome was survival following tracheostomy. Secondary outcome was the completion of staged palliation to Fontan. Results In total, 25 patients with SV heart disease who underwent tracheostomy were included. Indications for tracheostomy included one or more of the following: tracheobronchomalacia (n = 8), vocal cord paralysis (n = 7), tracheal/subglottic stenosis (n = 6), primary respiratory insufficiency (n = 4), diaphragm paralysis (n = 3), suboptimal hemodynamics (n = 2), and other upper airway issues (n = 1). Survival at six months, one year, five years, and ten years was 76%, 68%, 63%, and 49%, respectively. Most patients completed Fontan palliation (64%). Patients who underwent tracheostomy for suboptimal hemodynamics and/or respiratory insufficiency had a higher mortality risk compared to those with indications of upper airway obstruction or diaphragm paralysis (hazard ratio 4.1, 95% confidence interval 1.2-13.7; P = .02). Conclusions Mortality risk varies according to tracheostomy indication in patients with SV heart disease. Tracheostomy may allow staged surgical palliation to proceed with acceptable risk if it was indicated for anatomic or functional airway dysfunction.

Background: Burnout is well characterised in physicians and residents but not in paediatric cardiology fellows, and few studies follow burnout longitudinally. Training-specific fears have been described in paediatric cardiology fellows but also have not been studied at multiple time points. This study aimed to measure burnout, training-specific fears, and professional fulfilment in paediatric cardiology fellows with the attention to time of year and year-of-training. Methods: This survey-based study included the Professional Fulfillment Index and the Impact of Events Scale as well as an investigator-designed Fellow Fears Questionnaire. Surveys were distributed at three-time points during the academic year to paediatric cardiology fellows at a large Midwestern training programme. Fellow self-reported gender and year-of-training were collected. Descriptive analyses were performed. Results: 10/17 (59%) of fellows completed all surveys; 60% were female, 40% in the first-year class, 40% in the second-year class, and 20% in the third-year class. At least half of the fellows reported burnout at each survey time point, with lower mean professional fulfilment scores. The second-year class, who rotate primarily in the cardiac ICU, had higher proportions of burnout than the other two classes. At least half of fellows reported that they “often” or “always” worried about not having enough clinical knowledge or skills and about work–life balance. Conclusions: Paediatric cardiology fellows exhibit high proportions of burnout and training-specific fears. Interventions to mitigate burnout should be targeted specifically to training needs, including during high-acuity rotations.

Introduction: Health-related quality of life in children who have undergone the Ross procedure has not been well characterised. The aim of this study was to characterise health-related quality of life in this cohort and compare to children with other CHD. Method: In this cross sectional, single-centre study, health-related quality of life was assessed in patients who underwent a non-neonatal Ross procedure using the Pediatric Quality of Life Inventory. Ross cohort scores were compared with healthy norms, patients with CHD requiring no surgical intervention or had curative surgery (Severity 2, S2) and patients who were surgically repaired with ≥1 surgical procedure and with significant residual lesion or need for additional surgery (Severity 3, S3). Associations between Pediatric Quality of Life Inventory score and patient factors were also examined. Results: 68 patients completed surveys. Nearly one-sixth of patients had overall scores below the cut-off for at-risk status for impaired health-related quality of life. There was no difference in overall health-related quality of life score between the Ross cohort and healthy children (p = 0.56) and S2 cohort (p = 0.97). Health-related quality of life was significantly higher in the Ross cohort compared to S3 cohort (p = 0.02). This difference was driven by a higher psychosocial health-related quality of life in the Ross cohort as compared to S3 cohort (p = 0.007). Anxiety scores were significantly worse in the Ross cohort compared to both S2 (p = 0.001) and S3 (p = 0.0017), respectively. Conclusion: Children who have undergone a Ross procedure report health-related quality of life equivalent to CHD not requiring therapy and superior to CHD with residual lesions. Despite these reassuring results, providers should be aware of potential anxiety among Ross patients.

Background: Prolonged effusions post-Fontan procedure are associated with morbidity. Fontan patients have higher pro-inflammatory cytokines in chest tube drainage compared to controls. Colchicine, an anti-inflammatory medication, decreases effusions in adults after cardiac surgery. We hypothesised that patients post-Fontan treated with colchicine would have decreased pro-inflammatory cytokine levels and shorter duration of chest tube drainage. Methods: This pilot clinical trial enrolled nine patients (intention to treat); five completed the protocol (per protocol). Post-operative Fontan patients 20 months to 5 years receiving colchicine were compared to a previously published control cohort (n = 25). Per protocol patients received 0.6 mg colchicine daily starting post-operative day 2, ending 1 day after chest tube removal. Chest tube samples were taken on days 1–4, 7 and 10, or until removal and analysed with a 17-cytokine Bio-Plex Assay. Descriptive statistics and basic univariate comparisons were made. Results: There was no difference in duration of chest tube drainage or length of stay between intention to treat patients and controls. Per protocol patients had shorter duration of chest tube drainage compared to controls (6 days [interquartile range 4.7–7], versus 10 days [7–11], p = 0.007) and shorter length of stay (7 days [5.5–9] versus 9 days [9–13], p = 0.005). Pro-inflammatory cytokines trended lower in per protocol patients. Conclusions: In this pilot cohort, patients who completed the colchicine protocol post-Fontan procedure had shortened duration of chest tube drainage and length of stay. A decrease of pro-inflammatory cytokines may contribute to the mechanism of this change. ClinicalTrials.gov: Colchicine in Postoperative Fontan Patients (CPFP); NCT03575572; https://clinicaltrials.gov/ct2/show/NCT03575572.

Under-diagnosis of pediatric hypertension remains pervasive due to difficulty recognizing elevated systolic blood pressures (SBPs). We performed a retrospective review comparing recognition of and response to elevated SBPs ≥95th percentile before and after development of a clinical decision support tool (CDST) in an academic pediatric system. Of 44,351 encounters, 477 had elevated SBPs with documented recognition of an elevated SBP in 17.9% of encounters pre-CDST that increased to 33.7% post-CDST ( P = .001). Post-CDST, 75.5% of elevated SBPs had repeat measurement, with 90.8% of initially elevated SBPs normalizing to

Individuals with Fontan circulation are at risk of late mortality from both cardiac and noncardiac causes. Despite the known risk of mortality, referral indications for advanced heart failure care vary between centers, and many individuals die from Fontan circulation-related complications either after late consideration for advanced heart failure therapies or having never seen a heart failure specialist. There is a critical need for guidelines to direct appropriately timed referral for advanced heart failure consultation. The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) Fontan Committee has developed recommended thresholds for advanced heart failure referral to guide primary cardiologists. These recommendations are divided into 4 categories of clinical Fontan circulatory dysfunction including (1) cardiac/systemic ventricular dysfunction, (2) Fontan pathway dysfunction, (3) lymphatic dysfunction, and (4) extracardiac dysfunction.

There are conflicting data on how delivery location impacts outcomes in neonates with ductal-dependent heart disease. Our goal was to evaluate the impact of delivery location on hospital length of stay and survival in infants with prenatally diagnosed hypoplastic left heart syndrome (HLHS) after stage 1 palliation (S1P). A multicenter cohort study was performed utilizing the National Pediatric Cardiology Quality Improvement Collaborative dataset for infants with prenatally diagnosed HLHS who underwent S1P from August 2016 to December 2018. Univariate comparisons of demographics, clinical, and outcome data were made and multivariable logistic regression was performed between groups stratified by distance from surgical center. A total of 790 patients from 33 centers were analyzed: 85% were born

Fontan palliation has improved survival for single ventricle patients, but long-term complications persist including cardiovascular dysfunction, neurohormonal abnormalities, and protein-losing enteropathy (PLE). Although chronic inflammation contributes to morbidity, an association between inflammation and vascular dysfunction has not been studied. We assessed inflammation and vascular function in 31 Fontan-palliated patients (52% male, median age 14.3 years), including 10 PLE+. Fontan circulation was associated with altered inflammatory cytokines (TNF-α: mean 2.5 ± 1.4 vs. 0.7 ± 0.2 pg/ml, p0.0001; sTNFR2: 371 ± 108 vs. 2694 ± 884 pg/ml, p0.0001) and vascular dysfunction [log-transformed reactive hyperemia index (lnRHI) 0.28 ± 0.19 vs. 0.47 ± 0.26, p0.01; augmentation index (AI) -2.9 ± 13.8 vs. -16.3 ± 12.0, p = 0.001; circulating endothelial progenitor cells (cEPCs) 5.0 ± 8.1 vs. 22.8 ± 15.9, p = 0.0002)]. Furthermore, PLE+ patients showed greater inflammation (IFN-γ 6.3 ± 2.2 vs. 11.5 ± 7.9 pg/ml, p = 0.01; sTNFR1: 1181 ± 420 vs. 771 ± 350 pg/ml, p = 0.01) and decreased arterial compliance (AI: 5.4 ± 17.1 vs. -6.8 ± 10.2, p = 0.02) than PLE- patients. Circulating EPCs, but not inflammatory cytokines, were inversely associated with arterial stiffness in Fontan patients. In conclusion, chronic inflammation and vascular dysfunction are observed after Fontan operation, with greater inflammation and arterial stiffness in Fontan patients with active PLE. However, there is no clear association between inflammatory cytokines and vascular dysfunction, suggesting these pathophysiologic processes are not mechanistically linked.

To determine the prevalence and influence of clinically significant airway and/or respiratory abnormalities in patients with trisomy 13 and 18 undergoing cardiac surgery.We performed a retrospective, case-control cohort study of all patients with known trisomy 13 or 18 who underwent cardiac operations at our institution from 1994 to 2014. Cases were matched 3:1 by age, surgical date, and cardiac lesion with nontrisomy 13/18 patients. Baseline clinical characteristics and patient outcomes, including postoperative course and management were compared. Descriptive statistics and Wilcoxon rank-sum test or Fisher exact test as appropriate were used to determine significant differences.In the 14 trisomy 13/18 patients who underwent cardiac surgery, there was an increased incidence of postoperative complications. Specifically, 93% had airway or pulmonary complications, including prolonged mechanical ventilation (n = 8), prolonged noninvasive positive pressure ventilation (n = 6), re-intubation (n = 7), tracheitis/pneumonia (n = 6), and tracheostomy (n = 2). The duration of intubation was longer (7.5 vs 2 days; P .0001) as was the duration of noninvasive positive pressure ventilation (8 vs 2 days; P .04) with longer hospital length of stay in the trisomy 13/18 cohort. There was 1 in-hospital mortality, with none in the control group.Although most trisomy 13/18 patients survive cardiac surgery, these patients have an increased incidence of airway complications, requiring longer intensive respiratory support postoperatively that contributes to longer length of stay. Parental guidance before cardiac surgery should include a discussion about postoperative airway management.

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.

ImportanceDespite high disease morbidity and mortality and complex treatment decisions, little is known about the medical and end-of-life decision-making preferences of adolescents and young adults (AYA) with advanced heart disease. AYA decision-making involvement is associated with important outcomes in other chronic illness groups.ObjectiveTo characterize decision-making preferences of AYAs with advanced heart disease and their parents and determine factors associated with these preferences.Design, Setting, and ParticipantsCross-sectional survey between July 2018 and April 2021 at a single-center heart failure/transplant service at a Midwestern US children’s hospital. Participants were AYAs aged 12 to 24 years with heart failure, listed for heart transplantation, or posttransplant with life-limiting complications and a parent/caregiver. Data were analyzed from May 2021 to June 2022.Main Outcomes and MeasuresSingle-item measure of medical decision-making preferences, MyCHATT, and Lyon Family-Centered Advance Care Planning Survey.ResultsFifty-six of 63 eligible patients enrolled in the study (88.9%) with 53 AYA-parent dyads. Median (IQR) patient age was 17.8 (15.8-19.0) years; 34 (64.2%) patients were male, and 40 patients (75.5%) identified as White and 13 patients (24.5%) identified as members of a racial or ethnic minority group or multiracial. The greatest proportion of AYA participants (24 of 53 participants [45.3%]) indicated a preference for active, patient-led decision-making specific to heart disease management, while the greatest proportion of parents (18 of 51 participants [35.3%]) preferred they and physician(s) make shared medical decisions on behalf of their AYA, representing AYA-parent decision-making discordance (χ2 = 11.7; P = .01). Most AYA participants stated a preference to discuss adverse effects or risks of treatment (46 of 53 participants [86.8%]), procedural and/or surgical details (45 of 53 participants [84.9%]), impact of condition on daily activities (48 of 53 participants [90.6%]), and their prognosis (42 of 53 participants [79.2%]). More than half of AYAs preferred to be involved in end-of-life decisions if very ill (30 of 53 participants [56.6%]). Longer time since cardiac diagnosis (r = 0.32; P = .02) and worse functional status (mean [SD] 4.3 [1.4] in New York Heart Association class III or IV vs 2.8 [1.8] in New York Heart Association class I or II; t-value = 2.7; P = .01) were associated with a preference for more active, patient-led decision-making.Conclusions and RelevanceIn this survey study, most AYAs with advanced heart disease favored active roles in medical decision-making. Interventions and educational efforts targeting clinicians, AYAs with heart disease, and their caregivers are needed to ensure they are meeting the decision-making and communication preferences of this patient population with complex disease and treatment courses.

BACKGROUND The size of the Fontan population with end-stage heart failure is growing. In this population, heart transplantation has been the only option. This study sought to investigate the efficacy of ventricular assist device (VAD) support in Fontan patients. METHODS We conducted a retrospective study of Fontan patients in the Advanced Cardiac Therapies Improving Outcomes Network. We evaluated patient characteristics, and the clinical and physiologic outcomes after VAD implantation. RESULTS We identified 45 Fontan patients implanted with VAD. The average age of patients was 10 years (interquartile range: 4.5–18) and 30% were female. The majority had a morphologic right ventricle (69%), moderate or greater ventricular dysfunction (83%), and moderate or greater atrioventricular valve regurgitation (65%). The majority of implants were as a bridge to transplantation (76%), and the majority of patients were Interagency Registry for Mechanically Assisted Circulatory Support Profile 2 (56%). The most commonly employed device was the Medtronic HeartWare HVAD (56%). A total of 13 patients were discharged on device support, and 67% of patients experienced adverse events, the most common of which were neurologic (25%). At 1 year after device implantation, the rate of transplantation was 69.5%, 9.2% of patients continued to be VAD supported, and 21.3% of patients had died. Hemodynamically, VAD was effective in decreasing both Fontan and ventricular end-diastolic pressures in some individuals. CONCLUSIONS VAD is effective in supporting patients with end-stage Fontan failure awaiting heart transplantation. Future research should focus on identifying clinical and physiologic characteristics predictive of a favorable response to VAD support.

BACKGROUND The Berlin Heart EXCOR Pediatric (EXCOR) ventricular assist device (VAD) was introduced in North America nearly 2 decades ago. The EXCOR was approved under Humanitarian Device Exemption status in 2011 and received post-market approval (PMA) in 2017 from Food and Drug Administration. Since the initial approval, the field of pediatric mechanical circulatory support has changed, specifically with regard to available devices, anticoagulation strategies, and the types of patients supported. This report summarizes the outcomes of patients supported with EXCOR from the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) registry. These data were part of the PMA surveillance study (PSS) required by the Food and Drug Administration. METHODS ACTION is a learning collaborative of over 40 pediatric heart failure programs worldwide, which collects data for all VAD implantations as one of its initiatives. All patients in North America with EXCOR implants reported to ACTION from 2018 to 2020 ( n = 72) who had met an outcome were included in the EXCOR PSS group. This was compared with a historical, previously reported Berlin Heart EXCOR study group (Berlin Heart study [BHS] group, n = 320, 2007‒2014). RESULTS Patients in the PSS group were younger, were smaller in weight/body surface area, were more likely to have congenital heart disease , and were less likely to receive a bi-VAD than those in the BHS group. Patients in the PSS group were less likely to be in Interagency Registry for Mechanically Assisted Circulatory Support Profile 1 and were supported for a longer duration. The primary anticoagulation therapy for 92% of patients in the PSS group was bivalirudin . Success, defined as being transplanted, being weaned for recovery, or being alive on a device at 180 days after implantation, was 86% in the PSS group compared with 76% in the BHS group. Incidence of stroke was reduced by 44% and the frequency of pump exchange by 40% in the PSS group compared with those in the BHS group. Similarly, all other adverse events , including major bleeding, were reduced in the PSS group. CONCLUSIONS The PSS data, collected through ACTION, highlight the improvement in outcomes for patients supported with EXCOR compared with the outcomes in a historical cohort. These findings may be the result of changes in patient care practices over time and collaborative learning.

Protein-losing enteropathy (PLE) is a devastating complication of the Fontan circulation. Although orthotopic heart transplantation (HTx) typically results in resolution of PLE symptoms, isolated cases of PLE relapse have been described after HTx.Patients with Fontan-related PLE who had undergone HTx at participating centers and experienced relapse of PLE during follow-up were retrospectively identified. Available data related to pre- and post-HTx characteristics and PLE events were collected.Eight patients from four different centers were identified. Median time from Fontan procedure to the development of PLE was 8 years, and median age at HTx was 17 years (range 7.7-21). In all patients, PLE resolved at a median time of 1 month after HTx (0.3-5). PLE recurrences occurred at a median time of 7.5 months after HTx (2-132). Each occurrence was associated with one or more significant clinical events; most commonly cellular- or antibody-mediated rejection; and less commonly graft dysfunction, infection, thrombosis, and posttransplant lymphoproliferative disease. PLE recurrences resolved after the successful treatment of the concomitant event, after a median time of 2 months in seven cases, while persisted and recurred in one patient in association with atypical mycobacterium infection and subsequent PTLD onset and relapses. Six patients were alive during follow-up at a median time of 4 years (1.3-22.5) after HTx.This is the largest series of PLE recurrence after HTx. All cases were associated with one or more concomitant and significant clinical events. PLE typically resolved after resolution of the inciting clinical event.

Heart failure metrics specific to the pediatric population are required to successfully implement quality improvement initiatives in children with heart failure. Medication use at the time of discharge following admission for decompensated heart failure has been identified as a potential quality metric in this population. This study aimed to report medication use at discharge in the current era for children admitted with acute decompensated heart failure. All patients

The Norwood operation is a complex neonatal surgery. There are limited data to inform the timing of sternal closure. After the Norwood operation, delayed sternal closure (DSC) is frequent. We aimed to examine the association of DSC with outcomes, with a particular interest in how sternal closure at the time of surgery compared with the timing of DSC. Our outcomes included mortality, length of ventilation, length of stay, and postoperative complications.This retrospective study included neonates who underwent a Norwood operation reported in the Pediatric Cardiac Critical Care Consortium registry from February 2019 through April 2021. Outcomes of patients with closed sternum were compared to those with sternal closure prior to postoperative day 3 (early closure) and prior to postoperative day 6 (intermediate closure).The incidence of DSC was 74% (500 of 674). The median duration of open sternum was 4 days (interquartile range 3-5 days). Comparing patients with closed sternum to patients with early sternal closure, there was no statistical difference in mortality rate (1.1% vs 0%) and the median hospital postoperative stay (30 days vs 31 days). Compared with closed sternum, patients with intermediate sternal closure required longer mechanical ventilation (5.9 days vs 3.9 days) and fewer subsequent sternotomies (3% vs 7.5%).For important outcomes following the Norwood operation there is no advantage to chest closure at the time of surgery if the chest can be closed prior to postoperative day 3.

Background:Patients with single ventricle heart disease are living into adulthood due to medical and surgical advancements but have significant physical comorbidities and an increased risk for psychological comorbidities compared to healthy subjects or those with other CHD diagnoses. This study aimed to systematically review psychological functioning in paediatric single ventricle heart disease.Methods:Literature was searched using PubMed, Embase, PsycInfo, CINAHL Complete and Scopus. Peer-reviewed articles that included patients ages 0–25 years with single ventricle heart disease, and quantitative measures of psychological outcomes were included. Meta-analysis using a fixed-effect model was conducted for internalising and externalising t-scores, utilised by the Achenbach Child Behavior Checklist.Results:Twenty-nine records met the criteria for inclusion. 13/24 studies demonstrated increased risk for internalising disorders, such as anxiety/depression; 16/22 studies demonstrated risk for externalising disorders, such as attention or behavioural problems. Meta-analysis of four studies revealed that paediatric single ventricle heart disease patients had no significant difference in internalising and externalising t-scores compared to normative values.Conclusions:The current review demonstrates the need for further studies to better understand psychological functioning in patients with single ventricle heart disease, with a majority of studies showing increased risk for psychological problems despite no difference seen in a small meta-analysis. This summary of the literature underscores the need for regular psychological screening, earlier intervention and integrated mental health therapies in paediatric single ventricle heart disease.

The Fontan Outcomes Network was created to improve outcomes for children and adults with single ventricle CHD living with Fontan circulation. The network mission is to optimise longevity and quality of life by improving physical health, neurodevelopmental outcomes, resilience, and emotional health for these individuals and their families. This manuscript describes the systematic design of this new learning health network, including the initial steps in development of a national, lifespan registry, and pilot testing of data collection forms at 10 congenital heart centres.

Background: The Fontan operation creates a total cavopulmonary connection, a circulation in which the importance of pulmonary vascular resistance is magnified. Over time, this circulation leads to deterioration of cardiovascular efficiency associated with a decline in exercise performance. Rigorous clinical trials aimed at improving physiology and guiding pharmacotherapy are lacking. Methods: The FUEL trial (Fontan Udenafil Exercise Longitudinal) was a phase III clinical trial conducted at 30 centers. Participants were randomly assigned udenafil, 87.5 mg twice daily, or placebo in a 1:1 ratio. The primary outcome was the between-group difference in change in oxygen consumption at peak exercise. Secondary outcomes included between-group differences in changes in submaximal exercise at the ventilatory anaerobic threshold, the myocardial performance index, the natural log of the reactive hyperemia index, and serum brain-type natriuretic peptide. Results: Between 2017 and 2019, 30 clinical sites in North America and the Republic of Korea randomly assigned 400 participants with Fontan physiology. The mean age at randomization was 15.5±2 years; 60% of participants were male, and 81% were white. All 400 participants were included in the primary analysis with imputation of the 26-week end point for 21 participants with missing data (11 randomly assigned to udenafil and 10 to placebo). Among randomly assigned participants, peak oxygen consumption increased by 44±245 mL/min (2.8%) in the udenafil group and declined by 3.7±228 mL/min (–0.2%) in the placebo group ( P =0.071). Analysis at ventilatory anaerobic threshold demonstrated improvements in the udenafil group versus the placebo group in oxygen consumption (+33±185 [3.2%] versus –9±193 [–0.9%] mL/min, P =0.012), ventilatory equivalents of carbon dioxide (–0.8 versus –0.06, P =0.014), and work rate (+3.8 versus +0.34 W, P =0.021). There was no an improvement in myocardial performance index (–0.02 vs 0.01, P =0.030), but no change in reactive hyperemia index, or serum brain-type natriuretic peptide level. Conclusions: In the FUEL trial, treatment with udenafil (87.5 mg twice daily) was not associated with an improvement in oxygen consumption at peak exercise but was associated with improvements in multiple measures of exercise performance at the ventilatory anaerobic threshold. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02741115.

Background: Adolescents and young adults undergoing heart transplantation experience risks of morbidity and mortality both pre- and post-transplant. To improve end-of-life care for this population, it is necessary to understand their medical and end-of-life decision-making preferences. Aim: (1) To examine adolescent/young adult decision-making involvement specific to heart transplant listing, and (2) to characterize their preferences specific to medical and end-of-life decision making. Design: This cross-sectional research study utilized survey methods. Data were collected from October 2016 to March 2018. Setting/participants: Twelve adolescent and young adult patients listed for heart transplant (ages = 12–19 years) and one parent for each were enrolled at a single-center, US children’s hospital. Results: Consistent with their preferences, the majority of adolescent/young adult participants (82%) perceived a high level of involvement in the decision to be listed for transplant. Patient involvement in this decision was primarily by way of seeking advice or information from their parents and being asked to express their opinion from parents. Despite a preference among patients to discuss their prognosis and be involved in end-of-life decision making if seriously ill, only 42% of patients had discussed their end-of-life wishes with anyone. Few parents recounted having such discussions. Preferences regarding the timing and nature of end-of-life decision-making discussions varied. Conclusions: Although young people are involved in the decision to pursue heart transplantation, little attention is paid to involving them in discussions regarding end-of-life decision making in a manner that is consistent with individual preferences.

Background Although mortality has decreased considerably in pediatric heart transplantation, waitlist and post-transplant death rates remain notable. End-of-life focused research in this population, however, is very limited. This Pediatric Heart Transplant Society study aimed to describe the circumstances surrounding death of pediatric heart transplant patients. Methods A retrospective analysis of the multi-institutional, international, Pediatric Heart Transplant Society registry was conducted. Descriptive statistics and univariate analyses were performed to 1) describe end-of-life in pediatric pre- and post-heart transplant patients and 2) examine associations between location of death and technological interventions at end-of-life with demographic and disease factors. Results Of 9217 patients (0-18 years) enrolled in the registry between 1993 and 2018, 2804 (30%) deaths occurred; 1310 while awaiting heart transplant and 1494 post-heart transplant. The majority of waitlist deaths (89%) occurred in the hospital, primarily in ICU (74%) with most receiving mechanical ventilation (77%). Fewer post-transplant deaths occurred in the hospital (22%). Out-of-hospital death was associated with older patient age (p Conclusions ICU deaths with high use of technological interventions at end-of-life were common, particularly in patients awaiting heart transplant. In this high mortality population, findings raise challenging considerations for clinicians, families, and policy makers on how to balance quality of life amidst high risk for hospital-based death.

The optimal timing for neonatal cardiac surgery is a potentially modifiable factor that may affect outcomes. We studied the relationship between age at surgery (AAS) and outcomes across multiple hospitals, focusing on neonatal operations where timing appears is not emergency.We studied neonates ≥37 weeks' gestation and ≥2.5 kg admitted to a treating hospital on or before day of life 2 undergoing selected index cardiac operations. The impact of AAS on outcomes was evaluated across the entire cohort and a standard risk subgroup (ie, free of preoperative mechanical ventilation, mechanical circulatory support, or other organ failure). Outcomes included mortality, major morbidity (ie, cardiac arrest, mechanical circulatory support, unplanned cardiac reintervention, or neurologic complication), and postoperative cardiac intensive care unit and hospital length of stay. Post hoc analyses focused on operations undertaken between day of life 2 and 7.We studied 2536 neonates from 47 hospitals. AAS from day of life 2 through 7 was not associated with risk adjusted mortality or major morbidity among the entire cohort and the standard risk subgroup. Older AAS, although associated with modest increases in postoperative cardiac intensive care unit and hospital length of stay in the entire cohort, was not associated with hospital length of stay in the standard risk subgroup.Among select nonemergency neonatal cardiac operations, AAS between day of life 2 and 7 was not found to be associated with risk adjusted mortality or major morbidity. Although delays in surgical timing may modestly increase preoperative resource use, studies of AAS and outcomes not evident at the time of discharge are needed.

BACKGROUND We aimed to describe the incidence, risk factors, and clinical outcomes of pericardial effusions within 6 months after pediatric heart transplantation (HT). METHODS A single-center retrospective cohort study was performed on all pediatric HT recipients from 2004 to 2018. Logistic regression was used to identify factors associated with pericardial effusions post-HT, and survival was compared using log-rank test. RESULTS During the study period, 97 HTs were performed in 93 patients. Fifty patients (52%) had a ≥small pericardial effusion within 6 months, 16 of which were, or became, ≥moderate in size. Pericardial drain was placed in 8 patients. In univariate analysis, larger recipient body surface area (p = .01) and non-congenital heart disease (p = .002) were associated with pericardial effusion development. Donor/recipient size ratios, post-HT hemodynamics, and rejection did not correlate with pericardial effusion development. In multivariable analysis, non-congenital heart disease (adjusted odds ratio 3.3, p = .01) remained independently associated with development of pericardial effusion. There were no significant differences in post-HT survival between patients with and without ≥small (p = .68) or ≥moderate pericardial effusions (p = .40). CONCLUSIONS Pericardial effusions are common after pediatric HT. Patients with cardiomyopathy, or non-congenital heart disease, were at higher risk for post-HT pericardial effusions. Pericardial effusions increased morbidity but had no effect on mortality in our cohort. The risk factors identified may be used for anticipatory guidance in pediatric HT.

In single-ventricle patients with native-to-neoaortic anastomoses, the native aortic root serves as a conduit to the coronary arteries. Thrombosis of the native aortic root has been described only in small, limited reports. We described our center's experience with this rare adverse event. All single-ventricle patients who underwent native-to-neoaortic anastomosis from 2002 to 2017 were compiled from institutional databases. Chart review identified cases of native aortic root thrombosis. Of 467 patients, there were 9 (2%) cases of native aortic root thrombosis; all had hypoplastic left heart syndrome. Timing of thrombosis varied and occurred following each stage of single-ventricle palliation. For treatment, 8 patients received systemic anticoagulation and one patient did not receive any treatment. One patient also underwent percutaneous thrombectomy. Three patients (33.3%) died during the follow-up period. Among survivors, 4/6 had right ventricular systolic function that was mildly depressed or worse at a median follow-up of 8.3 years (interquartile range 1.3-10.8). Native aortic root thrombosis is a rare complication occurring at various stages of single-ventricle palliation. In this series, 6 of 9 patients (66.6%) survived; however, ventricular function was often compromised. No risk factors were identified to focus preventative therapies.

Lymphatic vessel dysplasia is associated with Fontan-associated protein-losing enteropathy. Extra nodal non-Hodgkin lymphomas including mucosa-associated lymphoid tissue (MALT lymphoma) are associated with lymphatic vessel dysplasia. Here, we describe the case of a 7-year-old with Fontan-associated protein-losing enteropathy who developed MALT lymphoma with a clinical course indicative of interaction between these pathologies and improvement in protein-losing enteropathy after MALT lymphoma treatment. This case suggests a pathophysiologic overlap which has implications for the management of Fontan-associated protein-losing enteropathy.

We sought to assess acute hemodynamic changes after implementation of negative extrathoracic pressure (NEP) in spontaneously breathing ambulatory Fontan patients with symptomatic heart failure. We hypothesized that application of NEP would result in an acute decrease in pulmonary artery pressure. Ten patients with clinical evidence of Fontan failure underwent baseline hemodynamic catheterization while breathing spontaneously. Hemodynamic measurements were then repeated after 30 min of continuous NEP. After 30 min of continuous NEP, 4/10 patients had a decrease in their Fontan pressure by 2 mmHg and one patient had a decrease by 1 mmHg. There were three patients that had an increase in Fontan pressure by 2 mmHg. In 7/10 patients, indexed pulmonary vascular resistance decreased by an average of 31%. In symptomatic Fontan patients with a favorable hemodynamic response to NEP during catheterization, potential benefit of longer-term NEP to improve clinical status should be explored.

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.

BACKGROUND The influence of Fontan-associated protein-losing enteropathy's (PLE) severity, duration, and treatment on heart transplant (HTx) outcomes is unknown. We hypothesized that long-standing PLE and PLE requiring more intensive therapy are associated with increased post-HTx mortality. METHODS This 12-center, retrospective cohort study of post-Fontan patients with PLE referred for HTx from 2003 to 2015 involved collection of demographic, medical, surgical, and catheterization data, as well as PLE-specific data, including duration of disease, intensity/details of treatment, hospitalizations, and complications. Factors associated with waitlist and post-HTx outcomes and PLE resolution were sought. RESULTS Eighty patients (median of 5 per center) were referred for HTx evaluation. Of 68 patients listed for HTx, 8 were removed due to deterioration, 4 died waiting, and 4 remain listed. In 52 patients undergoing HTx, post-HTx 1-month survival was 92% and 1-year survival was 83%. PLE-specific factors, including duration of PLE pre-HTx, pre-HTx hospitalizations, need for/frequency of albumin replacement, PLE therapies, and growth parameters had no association with post-HTx mortality. Immunosuppressant regimen was associated with mortality; standard mycophenolate mofetil immunotherapy was used in 95% of survivors compared with only 44% of non-survivors (p = 0.03). Rejection (53%) and infection (42%) post-HTx were common, but not associated with PLE-specific factors. PLE resolved completely in all but 1 HTx survivor at a median of 1 month (interquartile range 1 to 3 months); resolution was not affected by PLE-specific factors. CONCLUSIONS PLE severity, duration, and treatment do not influence post-HTx outcome, but immunosuppressive regimen may have an impact on survival. PLE resolves in nearly all survivors.

There are limited published data addressing the costs associated with pediatric heart transplantation and no studies evaluating the variation in costs across centers. We aimed to describe center variation in pediatric heart transplant costs and assess the association of transplant hospitalization costs with patient outcomes. Using a linkage between the Pediatric Health Information System and Scientific Registry of Transplant Recipients databases, hospital costs were assessed for patients (

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.

Background/Purpose: There is conflicting data on how geographic distance from delivery location to the cardiac surgical center impacts outcomes in neonates with ductal-dependent heart disease. Our goal was to describe national current practices in delivery location of neonates with a prenatal diagnosis of hypoplastic left heart syndrome (HLHS) and evaluate the impact of delivery location and age at admission to the surgical center ICU on post-operative length of hospital stay and transplant-free survival after the Norwood operation. Methods: A multicenter cohort study was performed utilizing the National Pediatric Cardiology Quality Improvement …

Background In a stable, inotrope-dependent pediatric patient with dilated cardiomyopathy, we evaluated the cost-effectiveness of continuous-flow VAD implantation compared to a watchful waiting approach using chronic inotropic therapy. Methods We used a state-transition model to estimate the costs and outcomes of 14-year-old (INTERMACS profile 3) patients receiving either VAD or watchful waiting. We measured benefits in terms of lifetime QALYs gained. Model inputs were taken from the literature. We calculated the ICER, or the cost per additional QALY gained, of VADs and performed multiple sensitivity analyses to test how our assumptions influenced the results. Results Compared to watchful waiting, VADs produce 0.97 more QALYs for an additional $156 639, leading to an ICER of $162 123 per QALY gained from a healthcare perspective. VADs have 17% chance of being cost-effective given a cost-effectiveness threshold of $100 000 per QALY gained. Sensitivity analyses suggest that VADs can be cost-effective if the costs of implantation decrease or if hospitalization costs or mortality among watchful waiting patients is higher. Conclusions As a bridge to transplant, VADs provide a health benefit to children who develop stable, inotrope-dependent heart failure, but immediate implantation is not yet a cost-effective strategy compared to watchful waiting based on commonly used cost-effectiveness thresholds. Early VAD support can be cost-effective in sicker patients and if device implantation is cheaper. In complex conditions such as pediatric heart failure, cost-effectiveness should be just one of many factors that inform clinical decision-making.

AIM To describe the clinical and hemodynamic characteristics of Fontan failure in children listed for heart transplant. METHODS In a nested study of the Pediatric Heart Transplant Society, 16 centers contributed information on Fontan patients listed for heart transplant between 2005and 2013. Patients were classified into four mutually exclusive phenotypes: Fontan with abnormal lymphatics (FAL), Fontan with reduced systolic function (FRF), Fontan with preserved systolic function (FPF), and Fontan with "normal" hearts (FNH). Primary outcome was waitlist and post-transplant mortality. RESULTS 177 children listed for transplant were followed over a median 13 (IQR 4-31) months, 84 (47%) were FAL, 57 (32%) FRF, 22 (12%) FNH, and 14 (8%) FPF. Hemodynamic characteristics differed between the 4 groups: Fontan pressure (FP) was most elevated with FPF (median 22, IQR 18-23, mmHg) and lowest with FAL (16, 14-20, mmHg); cardiac index (CI) was lowest with FRF (2.8, 2.3-3.4, L/min/m2). In the entire cohort, 66% had FP >15 mmHg, 21% had FP >20 mmHg, and 10% had CI

Introduction: Traditional weight & height ratios as measures of donor-recipient (D-R) matching have been challenged in adult heart transplantation (HT). The optimal metrics for D-R matching in pediatric HT remain unclear, and were evaluated in the present study. Methods: All primary pediatric HT recipients in the Pediatric Heart Transplant Society database transplanted from 1993-2019 were included. Multiple metrics of size matching - height, weight, body mass index (BMI), body surface area (BSA), predicted heart mass (PHM) and total cardiac volume (TCV) were assessed to identify the metrics that would best predict 1-year post-transplant (PTx) graft loss (death/re-transplant). Kaplan-Meier analyses (risk unadjusted) and multivariate Cox proportional hazard models (risk adjusted) were used to assess the effect of differences of various size matching metrics on survival. Results: Among 6903 D-R pairs, multivariable hazard modeling identified the following risk factors for PTx mortality: female sex, black race, bilirubin, ECMO, VAD, mechanical ventilation, ICU admission at the time of transplant, presence of congenital heart disease, early era of transplant, donor ischemic time and cardiopulmonary bypass time. After adjusting for all covariates, increasing size mismatch by height, BSA, or PHM was associated with increased 1-year PTx graft loss, with a disproportionately higher hazard for undersized donors than oversized donors (Figure). Weight, BMI and TCV were not predictive of 1-year PTx graft loss on multivariate analysis. Conclusions: In pediatric HT recipients, increasing size mismatch by height, BSA and PHM is associated with increased 1-year PTx graft loss. Undersizing donors appears to carry a higher risk than oversizing.

Background: The Pediatric Heart Network’s Fontan Udenafil Exercise Longitudinal (FUEL) Trial (Mezzion Pharma Co. Ltd., NCT 02741115) demonstrated improvements in exercise capacity and ventricular performance following six months of treatment with udenafil (87.5 mg twice daily). In this analysis we evaluated whether subgroups within the population experienced a differential effect on exercise performance in response to treatment. Methods: The effect of udenafil on exercise was evaluated within subgroups defined by gender, race, ventricular morphology, and baseline peak oxygen consumption (VO 2 ). Linear regression modeling evaluated for differential response to udenafil (interaction of subgroup with treatment arm). Individual subgroups were excluded if the number of participants was Results: Subgroup analyses demonstrated qualitative improvements in peak VO 2 , work rate at the ventilatory anaerobic threshold (VAT), VO 2 at VAT, and ventilatory efficiency (VE/VCO 2 ) for those randomized to udenafil compared to placebo in all subgroups (Table). There was not a differential response to udenafil based on gender, race, ventricular morphology, or baseline peak VO 2 , although participants in the lowest tertile of baseline peak VO 2 and those with single left ventricles trended toward larger improvements. Conclusion: The relatively uniform improvement among subgroups in response to treatment with udenafil is consistent with the findings from the primary analysis of the FUEL trial. While the absence of a statistically significant differential effect between subgroups suggests that the effect of udenafil may not be gender, race, or morphology specific, and may not vary based on baseline exercise performance, the possibility of a larger improvements in those with poor baseline peak VO 2 and those with single left ventricle warrants further investigation.

Introduction: The Institute of Medicine called for scientific investigation and the development of guidelines to improve end of life care for pediatric patients with serious illnesses. Despite high morbidity and mortality in pediatric heart transplantation (HTx), research on the end of life care needs of this population is extremely limited. Aims: This study aimed to describe the circumstances surrounding death of pediatric HTx patients and examine associations between location of death and technological interventions at end-of-life with demographic, disease, and HTx-related factors. Methods: This retrospective analysis of the Pediatric Heart Transplant Society registry utilized descriptive statistics and standard univariate analysis to examine associations between location of death and patient factors. Results: Of 9,217 registry entries, 2,804 (30%) deaths occurred; 1,310 while awaiting HTx; 1,494 post-HTx. Location of death was only recorded for 1,113 patients which included 804 waitlist deaths; 89% occurred in the hospital, primarily in ICU settings (74%) with most requiring mechanical ventilation (77%). A subset (39%) were supported by ECMO/VAD at time of death with 69% receiving inotrope support. Location of death was captured for 309 post-HTx patients with only 22% occurring in hospital; primarily in the ICU (74%) with half receiving mechanical ventilation (52%) and a smaller proportion supported by ECMO/VAD (18%) or inotropes (21%) at time of death. Overall, location of death was not associated with patient sex, race, ethnicity, insurance type, or primary etiology. Out of hospital death was associated with older patient age (p Conclusions: Death occurred in ~1/3 of patients captured in this pediatric HTx registry. ICU deaths with high use of technological interventions were common, particularly in waitlisted patients, but family decision to discontinue interventions was infrequently cited. Findings underscore the need for palliative care interventions and improved research strategies to better understand end of life in pre- and post-HTx pediatric populations.

Background: Acute decompensated heart failure (ADHF) is a highly morbid condition among adults. Little is known about outcomes in children with ADHF. We analyzed the Pediatric Cardiac Critical Care Consortium registry to determine the epidemiology, contemporary treatments, and predictors of mortality in critically ill children with ADHF. Methods: Cardiac intensive care unit (CICU) patients ≤18 years of age meeting Pediatric Cardiac Critical Care Consortium criteria for ADHF were included. ADHF was defined as systolic or diastolic dysfunction requiring continuous vasoactive or diuretic infusion, respiratory support, or mechanical circulatory support. Demographics, diagnosis, therapies, complications, and mortality are described for the cohort. Predictors of CICU mortality were identified using logistic regression. Results: Among 26 294 consecutive admissions (23 centers), 1494 (6%) met criteria for analysis. Median age was 0.93 years (interquartile range, 0.1–9.3 years). Patients with congenital heart disease (CHD) comprised 57% of the cohort. Common therapies included the following: vasoactive infusions (88%), central venous catheters (86%), mechanical ventilation (59%), and high flow nasal cannula (46%). Common complications were arrhythmias (19%), cardiac arrest (10%), sepsis (7%), and acute renal failure requiring dialysis (3%). Median length of CICU stay was 7.9 days (interquartile range, 3–18 days) and the CICU readmission rate was 22%. Overall, CICU mortality was 15% although higher for patients with CHD versus non-CHD (19% versus 11%; P Conclusions: ADHF in children is characterized by comorbidities, high mortality rates, and frequent readmission, especially among patients with CHD. Opportunities exist to determine best practices around appropriate use of mechanical support, cardiac arrest prevention, and optimal heart transplantation candidacy to improve outcomes for these patients.

Coronary allograft vasculopathy (CAV) is a leading cause of mortality after heart transplantation (HT) in children. Variation in CAV screening practices may impact detection rates and patient outcomes.Among 50 Pediatric Heart Transplant Society (PHTS) sites from 2001 to 2016, coronary evaluations were classified as angiography or non-invasive testing, and angiograms were designated as routine or symptom based. CAV detection rates stratified by routine vs symptom-based angiograms were calculated. Freedom from CAV and mortality after CAV diagnosis, stratified by study indication, were calculated.A total of 3,442 children had 13,768 coronary evaluations; of these, 97% (n = 13,012) were for routine surveillance, and only 3% (n = 333) were for cause. Over the study period, CAV was detected in 472 patients (14%). Whereas 58% (n = 29) of PHTS sites evaluate by angiography alone, 42% reported supplementing with a non-invasive test, although only 423 non-invasive studies were reported. Angiographic detection of CAV was higher for symptom-based testing than for routine testing (29% vs 4%, p0.0001), although routine testing identified a majority of cases (88%; n = 414). The 10-year freedom from CAV was 77% overall. Once CAV is detected, 5-year graft survival was 58%, with lower survival for patients diagnosed after symptoms angiogram than after routine angiogram (30% vs 62%; p0.0001).Development of a robust model for CAV risk should allow low-risk patients to undergo less frequent invasive angiography without adverse impact on CAV detection rates or outcomes.