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ObjectiveTo determine whether prenatal diagnosis lowers the risk of preoperative brain injury by assessing differences in the incidence of preoperative brain injury across centers.Study designFrom 2 prospective cohorts of newborns with complex congenital heart disease studied by preoperative cerebral magnetic resonance imaging, one cohort from the University Medical Center Utrecht (UMCU) and a combined cohort from the University of California San Francisco (UCSF) and University of British Columbia (UBC), patients with aortic arch obstruction were selected and their imaging and clinical course reviewed.ResultsBirth characteristics were comparable between UMCU (n = 33) and UCSF/UBC (n = 54). Patients had a hypoplastic aortic arch with either coarctation/interruption or hypoplastic left heart syndrome. In subjects with prenatal diagnosis, there was a significant difference in the prevalence of white matter injury (WMI) between centers (11 of 22 [50%] at UMCU vs 4 of 30 [13%] at UCSF/UBC; P < .01). Prenatal diagnosis was protective for WMI at UCSF/UBC (13% prenatal diagnoses vs 50% postnatal diagnoses; P < .01), but not at UMCU (50% vs 46%, respectively; P > .99). Differences in clinical practice between prenatally diagnosed subjects at UMCU vs UCSF/UBC included older age at surgery, less time spent in the intensive care unit, greater use of diuretics, less use of total parenteral nutrition (P < .01), and a greater incidence of infections (P = .01). In patients diagnosed postnatally, the prevalence of WMI was similar in the 2 centers (46% at UMCU vs 50% at UCSF/UBC; P > .99). Stroke prevalence was similar in the 2 centers regardless of prenatal diagnosis (prenatal diagnosis: 4.5% at Utrecht vs 6.7% at UCSF/UBC, P = .75; postnatal diagnosis: 9.1% vs 13%, respectively, P > .99).ConclusionPrenatal diagnosis can be protective for WMI, but this protection may be dependent on specific clinical management practices that differ across centers.

ObjectiveThe study objective was to determine the association between preoperative B-type natriuretic peptide levels and outcome after total cavopulmonary connection. Surgical palliation of univentricular cardiac defects requires a series of staged operations, ending in a total cavopulmonary connection. Although outcomes have improved, there remains an unpredictable risk of early total cavopulmonary connection takedown. The prediction of adverse postoperative outcomes is imprecise, despite an extensive preoperative evaluation.MethodsWe prospectively enrolled 50 patients undergoing total cavopulmonary connection. We collected preoperative clinical data, preoperative plasma B-type natriuretic peptide levels, and postoperative outcomes, including the incidence of an adverse outcome within 1 year of surgery (defined as death, total cavopulmonary connection takedown, or the need for cardiac transplantation).ResultsThe mean age of patients was 4.7 years (standard deviation, 2.1 years). The median (interquartile range) preoperative B-type natriuretic peptide levels were higher in patients who required total cavopulmonary connection takedown and early postoperative mechanical cardiac support (n = 3; median, 55; interquartile range, 42-121) compared with those with a good outcome (n = 47; median, 11; interquartile range, 5-17) (P

ObjectiveThe objective of this study was to determine the association between preoperative nutritional status and postoperative outcomes in children undergoing surgery for congenital heart defects (CHD).MethodsSeventy-one patients with CHD were enrolled in a prospective, 2-center cohort study. We adjusted for baseline risk differences using a standardized risk adjustment score for surgery for CHD. We assigned a World Health Organization z score for each subject's preoperative triceps skin-fold measurement, an assessment of total body fat mass. We obtained preoperative plasma concentrations of markers of nutritional status (prealbumin, albumin) and myocardial stress (B-type natriuretic peptide [BNP]). Associations between indices of preoperative nutritional status and clinical outcomes were sought.ResultsSubjects had a median (interquartile range [IQR]) age of 10.2 (33) months. In the University of California at San Francisco (UCSF) cohort, duration of mechanical ventilation (median, 19 hours; IQR, 29 hours), length of intensive care unit stay (median, 5 days; IQR 5 days), duration of any continuous inotropic infusion (median, 66 hours; IQR 72 hours), and preoperative BNP levels (median, 30 pg/mL; IQR, 75 pg/mL) were associated with a lower preoperative triceps skin-fold z score (P

ObjectiveTo determine the relationship between radiologically identifiable brain injuries and delayed brain development as reflected by brain metabolic and microstructural integrity.MethodsTerm newborns with congenital heart disease (CHD) (120 preoperatively and 104 postoperatively) were studied with MRI to determine brain injury severity (BIS), microstructure reflected by fractional anisotropy (FA) and average diffusivity (Dav), and metabolism reflected by N-acetylaspartate (NAA)/choline (Cho) and lactate/Cho. Brain development is characterized by increasing NAA/Cho and white matter FA, and by decreasing Dav and lactate/Cho.ResultsNewly acquired brain injury was common (41% preoperative, 30% postoperative). Lower white matter FA (p = 0.005) and lower NAA/Cho (p = 0.01) were associated with increasing preoperative BIS. Higher neonatal illness severity scores (p = 0.03), lower preoperative oxygen saturation (p = 0.002), hypotension (p < 0.001), and septostomy (p = 0.002) were also predictive of higher preoperative BIS. Preoperative FA, Dav, and NAA/Cho did not predict new postoperative BIS. Increasing preoperative BIS predicted higher postoperative Dav (p = 0.002) and lactate/Cho (p = 0.008). Within the postoperative scan, new brain injuries were associated with lower white matter FA (p = 0.04). Postoperative BIS (new lesions) was associated with lower postoperative systolic (p = 0.03) and mean (p = 0.05) blood pressures.ConclusionsBrain injuries in newborns with CHD are strongly related to abnormalities of brain microstructural and metabolic brain development, especially preoperatively. Both newly acquired preoperative and postoperative brain injuries are related to potentially modifiable clinical risk factors.

BackgroundPulmonary interstitial glycogenosis (PIG) arises from a developmental disorder of the pulmonary mesenchyme and presents clinically with reversible neonatal respiratory distress and/or persistent pulmonary hypertension of the newborn (PPHN).ObjectiveWe report two cases of PIG in patients with congenital heart disease (CHD) and evidence of PPHN.ResultsBoth cases demonstrated the hallmark PIG histologic finding of diffuse, uniform interstitial thickening due to the presence of immature interstitial cells containing abundant cytoplasmic glycogen.ConclusionsWe report the second and third patients with PIG associated with CHD. Because histologic examination is required to establish the diagnosis, we speculate that PIG, although rare, may be underrecognized in neonates presenting with PPHN in the setting of CHD.

Background: Pulmonary interstitial glycogenosis (PIG) arises from a developmental disorder of the pulmonary mesenchyme and presents clinically with reversible neonatal respiratory distress and/or persistent pulmonary hypertension of the newborn (PPHN). Obj

Background: Term newborns with congenital heart disease (CHD) show delayed brain development as early as the third trimester, especially in single-ventricle physiology (SVP). Mechanisms causing delayed brain development in CHD are uncertain but may include

We have previously shown that acute increases in pulmonary blood flow (PBF) are limited by a compensatory increase in pulmonary vascular resistance (PVR) via an endothelin-1 (ET-1) dependent decrease in nitric oxide synthase (NOS) activity. The mechanisms underlying the reduction in NO signaling are unresolved. Thus, the purpose of this study was to elucidate mechanisms of this ET-1-NO interaction. Pulmonary arterial endothelial cells were acutely exposed to shear stress in the presence or absence of tezosentan, a combined ET(A) /ET(B) receptor antagonist. Shear increased NO(x) , eNOS phospho-Ser1177, and H(2) O(2) and decreased catalase activity; tezosentan enhanced, while ET-1 attenuated all of these changes. In addition, ET-1 increased eNOS phospho-Thr495 levels. In lambs, 4 h of increased PBF decreased H(2) O(2) , eNOS phospho-Ser1177, and NO(X) levels, and increased eNOS phospho-Thr495, phospho-catalase, and catalase activity. These changes were reversed by tezosentan. PEG-catalase reversed the positive effects of tezosentan on NO signaling. In all groups, opening the shunt resulted in a rapid increase in PBF by 30 min. In vehicle- and tezosentan/PEG-catalase lambs, PBF did not change further over the 4 h study period. PVR fell by 30 min in vehicle- and tezosentan-treated lambs, and by 60 min in tezosentan/PEG-catalase-treated lambs. In vehicle- and tezosentan/PEG-catalase lambs, PVR did not change further over the 4 h study period. In tezosentan-treated lambs, PBF continued to increase and LPVR to decrease over the 4 h study period. We conclude that acute increases in PBF are limited by an ET-1 dependent decrease in NO production via alterations in catalase activity, H(2) O(2) levels, and eNOS phosphorylation.

BackgroundPulmonary vascular function is impaired with increased pulmonary blood flow (PBF). We hypothesized that a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist would mitigate this effect.MethodsAn aorta-to-pulmonary-artery shunt was placed in 11 fetal lambs. Lambs received the PPAR-γ agonist rosiglitazone (RG, 3 mg/kg/d, n = 6) or vehicle (n = 5) for 4 wk. Lung tissue from five normal 4-wk-old lambs was used for comparisons.ResultsAt 4 wk, pulmonary artery pressure (PAP) and vascular resistance (PVR) decreased with inhaled nitric oxide (NO) in RG- and vehicle-treated shunt lambs. PAP and PVR decreased with acetylcholine (Ach) in RG-treated, but not vehicle-treated, shunt lambs. In vehicle-treated shunt lambs, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, rac1, superoxide, and 3-nitrotyrosine (3-NT) levels were increased, and Ser1177 endothelial NO synthase (eNOS) protein was decreased as compared with normal lambs. In RG-treated shunt lambs, NOx, Ser1177 eNOS protein, and eNOS activity were increased, and NADPH activity, rac1, superoxide levels, and 3-NT levels were decreased, as compared with vehicle-treated shunt lambs. PPAR-γ protein expression was lower in vehicle-treated shunt lambs than in normal and RG-treated shunt lambs.ConclusionThe PPAR-γ agonist RG prevents the loss of agonist-induced endothelium-dependent pulmonary vascular relaxation in lambs with increased PBF, in part, due to decreased oxidative stress and/or increased NO production.

Pulmonary vascular function is impaired with increased pulmonary blood flow (PBF). We hypothesized that a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist would mitigate this effect.Methods:An aorta-to-pulmonary-artery shunt was placed in 11 f

We report a patient who presented during fetal life with severe aortic stenosis, left-ventricular dysfunction, and endocardial fibroelastosis (evolving hypoplastic left heart syndrome). Management involved in utero and postnatal balloon aortic valvuloplasty for partial relief of obstruction and early postnatal hybrid stage I palliation until recovery of left-ventricular systolic function had occurred. The infant subsequently had successful conversion to a biventricular circulation by combining resection of endocardial fibroelastosis with single-stage Ross-Konno, aortic arch reconstruction, hybrid takedown, and pulmonary artery reconstruction.