Impact of Protein-Losing Enteropathy on Inflammatory Biomarkers and Vascular Dysfunction in Fontan Circulation

• Published in: The American journal of cardiology 2021-09, Vol.155, p.128-134
• Main Authors: Manning, Lauren N., Schumacher, Kurt R., Friedland-Little, Joshua M., Yu, Sunkyung, Lowery, Ray, Goldstein, Bryan H., Charpie, John R.
• Format: Article
• Language: English
• Subjects: Abnormalities; Ascites; Asymptomatic; Biomarkers; Blood pressure; Cells (biology); Complications; Creatinine; Cytokines; Edema; Endothelium; Feces; Heart failure; Heart surgery; Hyperemia; Inflammation; Laboratories; Morbidity; Palliation; Patients; Permeability; Phosphatase; Progenitor cells; Proteins; Stem cells; Stiffness; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Ventricle; Ventricles (cerebral); γ-Interferon
• ISSN: 0002-9149; 1879-1913
• DOI: 10.1016/j.amjcard.2021.06.022

Fontan palliation has improved survival for single ventricle patients, but long-term complications persist including cardiovascular dysfunction, neurohormonal abnormalities, and protein-losing enteropathy (PLE). Although chronic inflammation contributes to morbidity, an association between inflammation and vascular dysfunction has not been studied. We assessed inflammation and vascular function in 31 Fontan-palliated patients (52% male, median age 14.3 years), including 10 PLE+. Fontan circulation was associated with altered inflammatory cytokines (TNF-α: mean 2.5 ± 1.4 vs. 0.7 ± 0.2 pg/ml, p < 0.0001; sTNFR2: 371 ± 108 vs. 2694 ± 884 pg/ml, p < 0.0001) and vascular dysfunction [log-transformed reactive hyperemia index (lnRHI) 0.28 ± 0.19 vs. 0.47 ± 0.26, p < 0.01; augmentation index (AI) -2.9 ± 13.8 vs. -16.3 ± 12.0, p = 0.001; circulating endothelial progenitor cells (cEPCs) 5.0 ± 8.1 vs. 22.8 ± 15.9, p = 0.0002)]. Furthermore, PLE+ patients showed greater inflammation (IFN-γ 6.3 ± 2.2 vs. 11.5 ± 7.9 pg/ml, p = 0.01; sTNFR1: 1181 ± 420 vs. 771 ± 350 pg/ml, p = 0.01) and decreased arterial compliance (AI: 5.4 ± 17.1 vs. -6.8 ± 10.2, p = 0.02) than PLE- patients. Circulating EPCs, but not inflammatory cytokines, were inversely associated with arterial stiffness in Fontan patients. In conclusion, chronic inflammation and vascular dysfunction are observed after Fontan operation, with greater inflammation and arterial stiffness in Fontan patients with active PLE. However, there is no clear association between inflammatory cytokines and vascular dysfunction, suggesting these pathophysiologic processes are not mechanistically linked.