Revisiting the Effect of Udenafil on Exercise Performance in Patients With Fontan Circulation: Results of a Post Hoc Analysis of the FUEL Trial.

Background: In the FUEL (Fontan Udenafil Exercise Longitudinal) trial, a positive treatment effect was identified for outcomes at the ventilatory anaerobic threshold but not for the primary outcome, oxygen consumption (Vo) at peak exercise. This disparate response may be explained by the physiologic challenge of improving peak Vo in participants with near-normal baseline exercise performance.

Methods: Participants were divided into subgroups by baseline predicted peak Vo (<80% versus ≥80%).

Increased Endothelin-1 Is Associated With Morbidity in Single Ventricle Heart Disease in Children Undergoing Fontan Palliation.

Background: Endothelin-1 (ET1) is a potent vasoconstrictor and stimulator of pulmonary artery smooth muscle cell proliferation. We previously demonstrated that failure to suppress ET1 is associated with morbidity in infants with single ventricle heart disease (SVHD) undergoing stage 2 palliation.

Objectives: The aim of this study is to evaluate whether persistent failure to suppress ET1 is associated with impaired recovery among children with SVHD undergoing the stage 3 (Fontan) operation.

Diagnostic Accuracy Prior to Congenital Heart Defect Surgery: A Multicenter Collaboration.

Background: Echocardiography is the mainstay for diagnosing congenital heart disease (CHD). Diagnostic errors can lead to suboptimal surgical outcomes.

Objectives: This multicenter pediatric echocardiography collaborative learning initiative explores reasons for diagnostic errors, investigates associations between patient- and center-specific factors and errors, and relays the benefits of a multicenter approach to decrease these errors as a first step to improve CHD surgical outcomes.

Pleural Drainage, Clinical Characteristics, and Management Strategies in the Perioperative Fontan Patient: A Multicenter Report.

Prolonged pleural drainage and chylothorax are common in postoperative Fontan patients and are associated with increased morbidity and mortality. Multiple medical and interventional treatment strategies exist and vary between centers. This is a retrospective multicenter observational cohort study of pediatric patients who underwent Fontan operation at 8 pediatric cardiac surgical institutions from 1/1/2019 to 12/31/2021.

Perturbations of tryptophan catabolism via the kynurenine pathway are associated with stage 2 postoperative outcomes in single ventricle heart disease.

Preliminary evidence suggests perturbations of the kynurenine pathway (KP) of tryptophan metabolism in infants with single ventricle heart disease (SVHD). In 72 infants with SVHD undergoing stage 2 palliation (S2P) and 41 controls, we quantified serum KP metabolite concentrations via tandem mass spectroscopy pre-S2P and post-S2P at 2, 24, and 48 h and assessed metabolite relationships with post-S2P outcomes (length of stay, hypoxemia burden, and intubation duration). Pre-S2P, SVHD infants had lower tryptophan and serotonin levels and higher kynurenic acid, 3-hydroxykynurenine, and picolinic acid levels than controls.

Estimation of pulmonary vascular resistance for Glenn physiology.

Children with single ventricle heart disease typically require a series of three operations, (1) Norwood, (2) Glenn, and (3) Fontan, which ultimately results in complete separation of the pulmonary and systemic circuits to improve pulmonary/systemic circulation. In the last stage, the Fontan operation, the inferior vena cava (IVC) is connected to the pulmonary arteries (PAs), allowing the remainder of deoxygenated blood to passively flow to the pulmonary circuit. It is hypothesized that optimizing the Fontan anatomy would lead to decreased power loss and more balanced hepatic flow distribution.

Arginine-NO metabolites are associated with morbidity in single ventricle infants undergoing stage 2 palliation.

Background: Infants with single ventricle heart disease (SVHD) suffer morbidity from insufficient pulmonary blood flow, which may be related to impaired arginine metabolism. No prior study has reported quantitative mapping of arginine metabolites to evaluate the relationship between circulating metabolite levels and outcomes.

Methods: Prospective cohort study of 75 SVHD cases peri-Stage 2 and 50 healthy controls.

The proteomic fingerprint in infants with single ventricle heart disease in the interstage period: evidence of chronic inflammation and widespread activation of biological networks.

Introduction: Children with single ventricle heart disease (SVHD) experience significant morbidity across systems and time, with 70% of patients experiencing acute kidney injury, 33% neurodevelopmental impairment, 14% growth failure, and 5.5% of patients suffering necrotizing enterocolitis. Proteomics is a method to identify new biomarkers and mechanisms of injury in complex physiologic states.

Circulating biomarkers of extracellular matrix dysregulation are associated with adverse post-stage 2 outcomes in infants with single ventricle heart disease.

Children with single ventricle heart disease (SVHD) experience morbidity due to inadequate pulmonary blood flow. Using proteomic screening, our group previously identified members of the matrix metalloproteinase (MMP), tissue inhibitor of metalloproteinase (TIMP), and fibroblast growth factor (FGF) families as potentially dysregulated in SVHD. No prior study has taken a targeted approach to mapping circulating levels of these protein families or their relationship to pulmonary vascular outcomes in SVHD.

The Fontan Udenafil Exercise Longitudinal Trial: Subgroup Analysis.

The Pediatric Heart Network's Fontan Udenafil Exercise Longitudinal (FUEL) Trial (Mezzion Pharma Co. Ltd., NCT02741115) demonstrated improvements in some measures of exercise capacity and in the myocardial performance index following 6 months of treatment with udenafil (87.

Interstage Single Ventricle Heart Disease Infants Show Dysregulation in Multiple Metabolic Pathways: Targeted Metabolomics Analysis.

Background: Infants with SVHD experience morbidity related to pulmonary vascular inadequacy. Metabolomic analysis involves a systems biology approach to identifying novel biomarkers and pathways in complex diseases. The metabolome of infants with SVHD is not well understood and no prior study has evaluated the relationship between serum metabolite patterns and pulmonary vascular readiness for staged SVHD palliation.

Implications of attention and executive functioning weaknesses in youth with Fontan circulation.

Youth with Fontan circulation (Fontan) are at-risk for impairments in attention and executive functioning (EF) due to a confluence of genetic, prenatal, surgical, and medical risk factors. We sought to describe attention and EF in this population, measured via standardized performance-based tests and caregiver rating scales. We then examined how weaknesses in attention and EF were related to outcomes in other neurobehavioral domains, including adaptive behavior and academic achievement.

Pressure-Strain Loops, a Novel Non-invasive Approach for Assessment of Children with Cardiomyopathy.

Non-invasive myocardial work (MW) by left ventricular (LV) pressure-strain loops (PSL) is a novel method for assessing myocardial function while adjusting for afterload, yet pediatric data remain lacking. The aims of this study were to investigate the different patterns of LV PSL and non-invasive MW in pediatric patients with hypertrophic (HCM) and dilated cardiomyopathy (DCM) and their association with exercise tolerance. We included 110 pediatric subjects (mean age, 13 ± 4 years, 35 DCM, 40 HCM, and 35 healthy controls).

Increased Circulating Endothelin 1 Is Associated With Postoperative Hypoxemia in Infants With Single-Ventricle Heart Disease Undergoing Superior Cavopulmonary Anastomosis.

Background Inadequate pulmonary vascular growth results in morbidity for many children with single-ventricle heart disease (SVHD). Endothelin 1 (ET1) is a potent vasoconstrictor and stimulator of pulmonary artery smooth muscle proliferation. Circulating ET1 levels and their association with outcomes have not been studied during early SVHD palliation.

Diastolic inflow is associated with inefficient ventricular flow dynamics in Fontan patients.

Objective: This study used cardiac magnetic resonance imaging to evaluate flow characteristics and ventricular hemodynamics for children with single right (hypoplastic left heart syndrome) and single left (hypoplastic right heart syndrome) systemic ventricle anatomy after Fontan palliation compared with normal biventricular controls.

Methods: Twenty children with single ventricle anatomy (hypoplastic left heart syndrome, n = 10; hypoplastic right heart syndrome, n = 10) underwent standardized 4-dimensional flow cardiac magnetic resonance and were compared with age-matched controls (n = 10). End-diastolic volume was partitioned into 4 defined components of variable kinetic energy (direct flow, retained inflow, delayed ejection, and residual volume) and compared between groups.

Use of compressed sensing to reduce scan time and breath-holding for cardiac cine balanced steady-state free precession magnetic resonance imaging in children and young adults.

Background: Conventional pediatric volumetric MRI acquisitions of a short-axis stack typically require multiple breath-holds under anesthesia.

Objective: Here, we aimed to validate a vendor-optimized compressed-sensing approach to reduce scan time during short-axis balanced steady-state free precession (bSSFP) cine imaging.

Materials And Methods: Imaging was performed in 28 patients (16±9 years) in this study on a commercial 3-tesla (T) scanner using retrospective electrocardiogram-gated cine bSSFP.

Proteomic profiling identifies key differences between inter-stage infants with single ventricle heart disease and healthy controls.

Despite significant morbidity among infants with single ventricle heart disease (SVHD), clinical monitoring is limited by poor understanding of the underlying pathobiology. Proteomics can identify novel biomarkers and important pathways in complex disease. No prior study has evaluated whether the proteome of SVHD infants differs from healthy controls, how it shifts after stage 2 palliation, or whether differences can predict post-operative outcomes.

Activation of kynurenine pathway of tryptophan metabolism after infant cardiac surgery with cardiopulmonary bypass: a prospective cohort study.

Background: Serum kynurenic acid is associated with poor outcomes after infant cardiopulmonary bypass (CPB), but comprehensive mapping of the kynurenine pathway (KP) after CPB has yet to be performed.

Aims: To map changes in the KP induced by infant CPB.

Methods: Compared changes in serum KP metabolites through 48hrs post-op with liquid-chromatography-tandem mass spectrometry.

Results of the FUEL Trial.

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.

Comparison of creatinine and cystatin C for estimation of glomerular filtration rate in pediatric patients after Fontan operation.

Background: There are several limitations when using creatinine to estimate glomerular filtration rate, especially in children with chronic medical conditions who are at high risk of kidney dysfunction. Cystatin C has been the recent focus of research as a replacement biomarker for creatinine. Our objective was to compare the 2 biomarkers in pediatric single-ventricle heart disease patients who have undergone the Fontan operation.