Influence of Elevated Central Venous Pressure on Brain Development and Neurocognitive Outcome in Children before Fontan Procedure at 2 Years of Age

Objectives: Chronic increased central venous pressure (CVP) may influence brain growth in children with single ventricle after bidirectional cavopulmonary anastomosis. We analyzed hemodynamic impact on brain development at two years of age before Fontan procedure.

Methods: In a prospective two-center study we analyzed 32 children with univentricular CHD (59.4% male, 25 with Hybrid approach, seven with classical Norwood approach) at a mean age of 27.4 ± 4.0 months. Children with genetic comorbidities were excluded. We evaluated hemodynamic values before stage III during routine cardiac catheterization and used semi-automated segmentation of cerebral MRI scans and neurodevelopmental outcome by Bayley-III Scales.

Results: Patients with elevated CVP (measured in SVC, range 5–18 mm Hg, mean 10.7 mm Hg) and pulmonary artery pressure (PAP, range 6–16 mm Hg, mean 10.4 mm Hg) had significantly lower deep gray matter volumes (CVP: r = −0.40, p = 0.03; PAP: r = −0.38, p = 0.04). Elevated pulmonary capillary wedge pressure (PCWP, range 3–14 mm Hg, mean 6.6 mm Hg) was associated with both, smaller gray matter (r = −0.42, p = 0.03) and white matter (r = −0.42, p = 0.03) volumes. Increased CVP, PAP and PCWP were associated with higher cerebrospinal fluid volumes (CVP: r = 0.59, p = 0.001; PAP: r = 0.43, p = 0.02; PCWP: r = 0.43, p = 0.03). Larger cerebrospinal fluid volumes correlated negatively with Bayley III Scores: Cognitive Composite Scale (r = −0.45, p < 0.001), and Language Composite Scale (r = −0.46, p < 0.001), whereas total brain volumes did not. Subcortical gray matter volumes were smaller in Norwood patients (p = 0.02). However, these patients did not show significantly lower Bayley scores (p > 0.79).

Conclusion: Hemodynamics of bidirectional cavopulmonary anastomosis may influence brain growth and cerebrospinal fluid volume, measured in children at 2 years of age prior Fontan completion. Of note, these MRI findings are correlated with adverse neurodevelopmental outcome. Further studies are needed to identify the underlying pathomechanisms of these findings.