EXPLANATION


The Fontan physiology has a significant adverse impact on the lymphatic system. Chronic venous hypertension characterizing the Fontan circulation causes a shift in Starling forces, which favors fluid accumulation in the interstitial tissue. Additional demand for lymphatic fluid clearance may be due to the following: 1) hypoalbuminemia; 2) increased lymph production due to elevated inferior vena cava pressure and hepatic congestion; 3) diaphragmatic dysfunction leading to flow reversal in the portal vein; 4) direct capillary leak due to endothelial dysfunction; 5) low cardiac output and, 6) direct injury to lymphatic structures, such as the thoracic duct, during surgical procedures. Lymphatic vessels become tortuous, dilated, and develop collaterals to accommodate the increased volume and abnormal flow of lymphatic fluid. Inadequate lymph drainage leads to the development of pleural effusions, chylothorax, ascites, protein losing enteropathy and plastic bronchitis. These are all components of a “failed Fontan circulation” and lead to increased morbidity and mortality.


Plastic bronchitis has a prevalence of approximately 4-5% in Fontan patients and is associated with a 5-year mortality of up to 50%. The exudation of proteinaceous material into the airways can lead to cast formation, potentially resulting in significant respiratory symptoms and total airway obstruction. Medical management includes airway clearance, bronchodilators, aggressive chest physiotherapy, mucolytic therapy with N-acetylcysteine and/or dornase-alpha, diuretics, pulmonary vasodilators, aerosolized tissue plasminogen activator, aldosterone inhibitors and a low-fat diet to decrease lymphatic fluid production and flow.


Following failure of medical therapy and after fully addressing reversible causes of lymphatic failure, interventions to decompress the lymphatic system or to occlude abnormal lymphatic vessels are the next options. There are several interventions for lymphatic decompression including surgical decompression, percutaneous thoracic duct decompression, thoracic duct stenting, and creation of a lymphovenous anastomosis. Occlusion techniques include lymphatic embolization, thoracic duct embolization, selective lymphatic duct embolization and thoracic duct ligation. Thoracic duct decompression is surgically accomplished with anastomosis of the left innominate vein to the common atrium. The major disadvantages of this procedure include the need for cardiopulmonary bypass, creation of a right-to-left shunting with resultant cyanosis, and the unknown long-term consequences of lymphatic return directly to the systemic circulation that bypasses the pulmonary circulation. Perhaps the most efficacious option is orthotopic heart transplantation, which is typically reserved for end-stage “failing Fontan” physiology. However, in recent years, the central role of the lymphatic system in the pathophysiology of plastic bronchitis has been recognized, and percutaneous lymphatic intervention has emerged as an additional therapeutic approach for plastic bronchitis prior to heart transplantation.


Dori et al reported the results of selective lymphatic embolization using Dynamic Contrast-enhanced Magnetic Resonance Lymphangiography (DCMRL) and T2-weighted MRI in 17 of 18 total patients with plastic bronchitis. They were followed for a median of 315 days, with 88% experiencing significant symptomatic improvement, including temporary resolution of cast formation. The procedure involved identifying a target lymphatic vessel by injecting contrast into the inguinal lymph nodes followed by MR imaging to illustrate the passage of contrast through the lymphatic system in real time, allowing for identification of lymphatic leakage and flow disturbances. MRI or lymphangiogram or both illustrated retrograde lymphatic flow toward the lung parenchyma in 16 patients. Of the 18 patients, 17 underwent either embolization or thoracic duct stenting, thereby rerouting lymphatic flow to provide a measure of symptomatic relief and improvement in quality of life. Clearly however, these procedures do not address the root cause of elevated central venous pressures and continued attention to optimization of the Fontan physiology/pathway is imperative.


The patient in the stem has an open fenestration and Fontan hemodynamics that are within the expected range. There is also normal pulmonary vascular resistance, and the transpulmonary gradient is not elevated. Thus, balloon dilation of the fenestration and treatment with bosentan will be of minimal benefit. Given the failure of maximal medical therapy, selective lymphatic embolization should be considered as the next treatment modality and prior to orthotopic heart transplantation, though often a curative treatment for plastic bronchitis. Unfortunately, selective lymphatic embolization is performed at very few centers currently, which may necessitate the use of other treatment modalities mentioned earlier in the explanation (i.e. thoracic duct ligation).


REFERENCES


Rychik J, Atz AM, Celermajer DS, et al. Evaluation and management of the child and adult with Fontan circulation: A scientific statement from the American Heart Association. Circulation. 2019;140(6):e234-e284.


RochéRodríguez M, DiNardo JA. The lymphatic system in the Fontan patient-pathophysiology, imaging, and interventions: what the anesthesiologist should know. J Cardiothorac Vasc Anesth. 2022;36(8 Pt A):2669-2678.


Dori Y, Keller M, Rome J, et al. Percutaneous lymphatic embolization of abnormal pulmonary lymphatic flow as treatment of plastic bronchitis in patients with congenital heart disease. Circulation. 2016;133:1160-1170.