Abstract
BACKGROUND: The mechanisms contributing to impaired neurocognitive performance in adults born with congenital heart disease (ACHD) are incompletely defined. OBJECTIVES: The authors performed a pilot study measuring novel biomarkers of blood-brain barrier integrity, angiogenesis, and endothelial function in patients with ACHD. METHODS: Adults with congenital heart disease underwent biomarker assessment. Plasma levels of asymmetric dimethyl arginine, as a marker of endothelial dysfunction, vascular endothelial growth factor A, as a measure of angiogenesis, and S100B, as a biomarker of the integrity of the blood-brain barrier, were assayed. RESULTS: A total of 70 patients were recruited with the average age of 43.6 years with 54% patients female. The majority of patients were considered to have moderate severity ACHD (43/70). S100B levels were undetectable in patients with mild ACHD and highest in the cohort with severe ACHD (4,551.9 pg/mL; P = 0.24). Patients with Fontan palliation (1,383.89 pg/mL) and those having undergone atrial switch repair (14,845.78 pg/mL) had the highest mean levels of S100B. Mean asymmetric dimethyl arginine levels were particularly elevated in patients with aortic coarctation surgery (358.10 ng/UL). Mean vascular endothelial growth factor levels were elevated across the spectrum of patients with ACHD, most notably in patients with moderate severity ACHD incorporating repaired tetralogy of Fallot (306.2 pg/mL vs 177.9 pg/mL [severe] and 145.0 pg/mL [mild]; P = 0.01). CONCLUSIONS: In a pilot study across the spectrum of ACHD, we note elevated levels of biomarkers that may improve the ability to more accurately identify neurological injury and impaired vascular function, which in turn may have implications with respect to cognitive function and cardiovascular sequelae.