Protein losing enteropathy after the Fontan operation

Abstract

The Fontan or Fontan Kreutzer procedure is the culmination of staged, surgical palliation of functional single ventricle congenital heart disease, offering the potential for survival and good quality of life well into adulthood. As more patients with Fontan circulation age, a variety of complications involving almost every organ system may occur. Protein-losing enteropathy is a major cause of morbidity and mortality after the Fontan operation, occurring more often in patients with adverse hemodynamics and presenting weeks to years after Fontan surgery. The causes are not well understood, but likely include a combination of lymphatic insufficiency, high central venous pressure, loss of heparan sulfate from intestinal epithelial cells, abnormal mesenteric circulation, and intestinal inflammation. A comprehensive evaluation including multimodality imaging and cardiac catheterization is necessary to diagnose and treat any reversible causes. In advanced cases, early referral for heart transplantation evaluation or lymphatic decompression procedures (if the single ventricle function remains adequate) is indicated. Despite the improvement in detection and management options, the mortality remains high. Standardization of protein-losing enteropathy definition and management strategies will help facilitate interpretation of research and clinical experience, potentially fostering the identification of new therapies. Based on the published data, this review suggests a standardized approach to diagnosis and treatment.

Keywords: Fontan; Heart failure; Protein losing enteropathy; Single ventricle.

Fig. 1

The pathophysiology of protein losing enteropathy in Fontan circulation.

Fig. 2

A suggested stepwise approach to managing a symptomatic patient with new diagnosis of protein losing enteropathy. When a diagnosis of protein losing enteropathy is confirmed, our approach is to start with step 1 therapies. If albumin concentration does not normalize with these interventions in 1–2 months, then transition to step 2. In more severe cases without response to step 2, transition to step 3. This approach is usually individualized to each patient based on response to therapy. ACEi: Angiotensin converting enzymes inhibitor, ARB: Angiotensin II receptor blocker, MCT: medium chain triglycerides.

Fig. 3

Conceptual framework for the course of PLE. A: Some patients have subclinical PLE which may or may not progress to overt PLE. B: Transient PLE with one episode followed by long term remission without long-term medical therapy has been reported. C: Waxing and waning course is common with multiple episodes followed by long periods of remission on medical therapy has been described. D: Progressive PLE with a chronic course of PLE, multiple worsening episodes and steep clinical decline is also reported.