Christopher J. Petit

BACKGROUND: Preoperative brain injury is an increasingly recognized phenomenon in neonates with complex congenital heart disease. Recently, reports have been published that associate preoperative brain injury in neonates with transposition of the great arteries with the performance of balloon atrial septostomy (BAS), a procedure that improves systemic oxygenation preoperatively. It is unclear whether BAS is the cause of brain injury or is a confounder, because neonates who require BAS are typically more hypoxemic. We sought to determine the relationship between preoperative brain injury in neonates with transposition of the great arteries and the performance of BAS. We hypothesized that brain injury results from hypoxic injury, not from the BAS itself. METHODS AND RESULTS: Infants with transposition of the great arteries (n=26) were retrospectively included from a larger cohort of infants with congenital heart disease who underwent preoperative brain MRI as part of 2 separate prospective studies. Data collected included all preoperative pulse oximetry recordings, all values from preoperative arterial blood gas measurements, and BAS procedure data. MRI scans were performed on the day of surgery, before the surgical repair. Of the 26 neonates, 14 underwent BAS. No stroke was seen in the entire cohort, whereas 10 (38%) of 26 patients were found to have hypoxic brain injury in the form of periventricular leukomalacia. Periventricular leukomalacia was not associated with BAS; however, neonates with periventricular leukomalacia had lower preoperative oxygenation (P=0.026) and a longer time to surgery (P=0.028) than those without periventricular leukomalacia. CONCLUSIONS: Preoperative brain injury in neonates with transposition of the great arteries is associated with hypoxemia and longer time to surgery. We found no association between BAS and brain injury.

Background: Infants with ductal-dependent pulmonary blood flow may undergo palliation with either a patent ductus arteriosus (PDA) stent or a modified Blalock-Taussig (BT) shunt. A balanced multicenter comparison of these 2 approaches is lacking. Methods: Infants with ductal-dependent pulmonary blood flow palliated with either a PDA stent or a BT shunt from January 2008 to November 2015 were reviewed from the 4 member centers of the Congenital Catheterization Research Collaborative. Outcomes were compared by use of propensity score adjustment to account for baseline differences between groups. Results: One hundred six patients with a PDA stent and 251 patients with a BT shunt were included. The groups differed in underlying anatomy (expected 2-ventricle circulation in 60% of PDA stents versus 45% of BT shunts; P =0.001) and presence of antegrade pulmonary blood flow (61% of PDA stents versus 38% of BT shunts; P <0.001). After propensity score adjustment, there was no difference in the hazard of the primary composite outcome of death or unplanned reintervention to treat cyanosis (hazard ratio, 0.8; 95% confidence interval [CI], 0.52–1.23; P =0.31). Other reinterventions were more common in the PDA stent group (hazard ratio, 29.8; 95% CI, 9.8–91.1; P <0.001). However, the PDA stent group had a lower adjusted intensive care unit length of stay (5.3 days [95% CI, 4.2–6.7] versus 9.19 days [95% CI, 7.9–10.6]; P <0.001), a lower risk of diuretic use at discharge (odds ratio, 0.4; 95% CI, 0.25–0.64; P <0.001) and procedural complications (odds ratio, 0.4; 95% CI, 0.2–0.77; P =0.006), and larger (152 mm 2 /m 2 [95% CI, 132–176] versus 125 mm 2 /m 2 [95% CI, 113–138]; P =0.029) and more symmetrical (symmetry index, 0.84 [95% CI, 0.8–0.89] versus 0.77 [95% CI, 0.75–0.8]; P =0.008] pulmonary arteries at the time of subsequent surgical repair or last follow-up. Conclusions: In this multicenter comparison of palliative PDA stent and BT shunt for infants with ductal-dependent pulmonary blood flow adjusted for differences in patient factors, there was no difference in the primary end point, death or unplanned reintervention to treat cyanosis. However, other markers of morbidity and pulmonary artery size favored the PDA stent group, supporting PDA stent as a reasonable alternative to BT shunt in select patients.

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.

OBJECTIVES: To devise a classification scheme for ductal morphology in patients with ductal dependent pulmonary blood flow (PBF) that can be used to assess outcomes. BACKGROUND: The impact of ductal morphology on outcomes following patent ductus arteriosus (PDA) stenting is not well defined. METHODS: Patients <1 year of age who underwent PDA stenting for ductal dependent PBF at the four centers comprising the Congenital Catheterization Research Collaborative (CCRC) were included. A classification scheme for PDA morphology was devised based on a tortuosity index (TI)-Type I (straight), Type II (one turn), and Type III (multiple turns). A subtype classification was used based upon the ductal origin. RESULTS: One hundred and five patients underwent PDA stenting. TI was Type I in 58, Type II in 24, and Type III in 23 PDAs, respectively. There was a significant association between ductal origin and vascular access site (p < 0.001). Procedure times and need for >1 stent did not differ based on TI. Greater TI was associated with pulmonary artery (PA) jailing (p = 0.003). Twelve (11.4%) patients underwent unplanned reintervention, more commonly with greater TI (p = 0.022) and PA jailing (p < 0.001). At the time of subsequent surgical repair/palliative staging, PA arterioplasty was performed in 32 patients, more commonly when a PA was jailed (p = 0.048). PA jailing did not affect PA size at follow up. CONCLUSIONS: The proposed qualitative and quantitative PDA morphology classification scheme may be helpful in anticipating outcomes in patients with ductal dependent PBF undergoing PDA stenting.