In this cohort of children with complex congenital heart disease, a significant proportion of the children were at risk for inattention and hyperactivity, and nearly half were using remedial school services. We did not identify any perioperative risk factors, which correlated with high-risk scores or the use of remedial school services. Ongoing neurodevelopmental follow-up and screening are recommended in this vulnerable population.

The causes of these late developmental abnormalities are most likely sequential, cumulative and multifactorial.

Microcephaly is a marker of abnormal fetal cerebral development, and a known risk factor for cognitive dysfunction. Patients with hypoplastic left heart syndrome have been found to have an increased incidence of abnormal neurodevelopmental outcomes. We hypothesized that reduced cerebral blood flow from the diminutive ascending aorta and transverse aortic arch in the setting of hypoplastic left heart syndrome may influence fetal growth of the brain. The purpose of our study, therefore, was to define the prevalence of microcephaly in full-term infants with hypoplastic left heart syndrome, and to investigate potential cardiac risk factors for microcephaly. We carried out a retrospective review of full-term neonates with hypoplastic left heart syndrome. Eligible patients had documented indexes of birth weight, and measurements of length, and head circumference, as well as adequate echocardiographic images for measurement of the diameters of the ascending aorta and transverse aortic arch. We used logistic regression for analysis of the data. A total of 129 neonates met the criteria for inclusion, with 15 (12%) proving to have microcephaly. The sizes of their heads were disproportionately smaller than their weights (p less than 0.001) and lengths (p less than 0.001) at birth. Microcephaly was associated with lower birth weight (p less than 0.001), lower birth length (p equal to 0.007), and a smaller diameter of the ascending aorta (p equal to 0.034), but not a smaller transverse aortic arch (p equal to 0.619), or aortic atresia (p equal to 0.969). We conclude that microcephaly was common in this cohort of neonates with hypoplastic left heart syndrome, with the size of the head being disproportionately smaller than weight and length at birth. Microcephaly was associated with a small ascending aorta, but not a small transverse aortic arch. Impairment of somatic growth may be an additional factor in the development of microcephaly in these neonates.

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.