Fontan-related protein-losing enteropathy: A comprehensive review of pathophysiology and current therapies

Figure 1 Pathophysiology of Fontan-associated protein-losing enteropathy. A: Fontan hemodynamics; B: Lymphatic dysfunction; C: Intestinal barrier injury; D: Inflammation and immune dysregulation. Chronically elevated systemic venous pressure and reduced cardiac output increase intestinal filtration and impair mesenteric perfusion, leading to lymphatic hypertension and abnormal enteric lymphatic flow. Lymphatic congestion and mucosal edema disrupt epithelial barrier integrity, including glycocalyx and tight junction alterations. Inflammatory and immune dysregulation further amplifies permeability and endothelial dysfunction. These interconnected processes form a self-reinforcing cycle that culminates in enteric protein loss. DCMRL: Dynamic contrast-enhanced magnetic resonance lymphangiography; IL-6: Interleukin-6; QOL: Quality of life; TNF-α: Tumor necrosis factor alpha.