Protein-losing enteropathy after the Fontan procedure – A cardiologist’s and gastroenterologist’s perspective

Protein-losing enteropathy (PLE) is a severe, multifactorial complication of Fontan circulation that affects approximately 12% of patients with single-ventricle physiology. Because no universal standard therapy exists, management is individualized and guided by the dominant hemodynamic and lymphatic drivers, clinical severity, and local expertise. Chronically elevated central venous pressure and impaired lymphatic drainage promote lymph congestion and leakage into the intestinal lumen, leading to hypoalbuminemia, edema, diarrhea, malnutrition, and immune dysfunction. Treatment is multimodal and includes optimization of Fontan hemodynamics, symptomatic and anti-inflammatory pharmacotherapy, and targeted nutritional strategies (high-protein diet, medium-chain triglycerides, and supplementation). Advances in lymphatic imaging have enabled phenotype-based, lymphatic-directed interventions such as lymphatic embolization and thoracic duct decompression, which can improve outcomes in selected patients. When conservative and interventional strategies fail, heart transplantation remains the definitive option. Emerging evidence also highlights the potential contribution of the gut-liver axis, including intestinal barrier dysfunction and alterations in the microbiome, which may influence inflammation and disease persistence. This review summarizes current concepts in PLE pathophysiology and therapeutic approaches, with emphasis on lymphatic dysfunction and evolving adjunctive targets.