Central lymphatic flow is often impaired in patients with right-sided congenital heart defects, tricuspid valve regurgitation, and/or right ventricular failure due to chronically elevated central venous pressures1, 2, 3. Similarly, patients that undergo functional single ventricle palliation with the Fontan procedure (i.e., total cavopulmonary anastomosis) have persistently elevated systemic venous pressures that are equal to or higher than pulmonary artery in the absence of a subpulmonic ventricle4, 5, 6. These chronically elevated central venous pressures increase lymphatic fluid production and retrograde pressure on the thoracic duct, which impedes lymphatic fluid drainage into the systemic venous circulation and leads to progressive overload and congestion of the lymphatic circulation that can ultimately result in lymphatic failure1,2,7, 8, 9, 10, 11, 12. When lymphatic failure occurs, the lymphatic circulation fails to adequately remove excess interstitial fluid from tissues, which is directly responsible for many of the clinical manifestations associated with heart failure (e.g., peripheral edema, pleural effusions, ascites, etc.) and other severe complications (i.e., chylothorax, protein-losing enteropathy, plastic bronchitis, etc.)1,3,6, 7, 8, 9, 10, 11, 12, 13, 14.

In recent years, the ability to diagnose and treat complications of lymphatic failure has improved vastly as advanced lymphatic imaging techniques have evolved alongside the development and application of novel percutaneous and surgical lymphatic interventions15, 16, 17, 18, 19, 20, 21. For example, selective embolization of abnormal lymphatic ducts or channels can provide immediate and lasting relief for some individuals with severe complications of lymphatic failure (e.g., protein-losing enteropathy, plastic bronchitis, etc.) by preventing pathologic lymphatic fluid flow22, 23, 24, 25. Meanwhile, other interventions have sought to decompress the lymphatic circulation, including the innominate vein turn-down procedure, thoracic duct externalization, and the surgical creation of a lymphocutaneous fistula or a lymphovenous anastomosis (LVA) between the thoracic duct and central venous circulation26, 27, 28, 29, 30, 31, 32, 33. While these interventions represent a paradigm shift in managing complications of lymphatic failure in patients with congenital heart disease and other lymphatic flow disorders, the long-term durability of these interventions remains unknown. Moreover, these complex procedures are not always possible, and have their own limitations. For example, although the surgical creation of a LVA between the thoracic duct and central venous circulation may improve lymphatic flow in some patients (i.e., thoracic duct obstruction, central venous thrombosis, etc.), this intervention is not able to decompress the lymphatic circulation in patients with elevated central venous pressures32,33.

Thus, there is consensus that further research efforts are needed to identify novel therapeutic targets and innovative procedures that can address the morbidity and mortality associated with lymphatic failure in patients with congenital heart disease, and particularly those with right-sided and single ventricle congenital heart defects34,35. Therefore, this investigation sought to develop an optimal surgical technique for creating a thoracic duct-to-pulmonary vein LVA in swine that could reroute lymphatic fluid flow into the lower-pressure, left-sided system regardless of central venous pressure. Our primary aim was to develop a reproducible technique for creating a thoracic duct-to-pulmonary vein LVA that would remain patent and preserve unidirectional lymphatic fluid flow for one week, which could be applied in future preclinical studies evaluating the potential safety and efficacy of this novel intervention in treating or preventing lymphatic failure in individuals that require congenital cardiac surgery.