Development of a Percutaneous Double Lumen Cannula-Based Cavopulmonary Assist System Toward Clinical Application

The standard palliative surgery for a single ventricle defect is a total cavopulmonary connection (TCPC), which separates the pulmonary and systemic circulations. This Fontan circulation eventually fails with severe end-organ dysfunction and high long-term mortality. A failing Fontan includes cavopulmonary failure (CPF) and/or ventricular failure. Unfortunately, no cavopulmonary assist (CPA) device is available for CPF. Our ultimate goal is to develop a percutaneous CPA system for total ambulatory support of CPF patients. Our enabling technology is a CPA dual lumen cannula (DLC) with paired membrane umbrellas. Through only one venous cannulation, this DLC connects the TCPC to an external pump without major surgery. This DLC-based system provided total CPA and reversed CPF hemodynamics/renal dysfunction in our lethal CPF sheep model, enabling 96 hr survival. To move our CPA DLC toward clinical application, the following specific aims were developed: Specific Aim 1: To design, optimize, and fabricate a new CPA DLC for least thrombogenic/ hemolytic potential and smooth installation/deployment. Specific Aim 1A: To design and optimize a CPA DLC. Paired membrane umbrellas ensure efficient/reliable performance. Slipknots smooth DLC installation and umbrella deployment. Validated computational fluid dynamics will be used for design optimization. Specific Aim 1B: To fabricate CPA DLC prototypes. The CPA DLC body will be made of ultrathin reinforced polyurethane (PU), and the infusion lumen is a PU membrane sleeve for maximal lumen area/low resistance. Two reinforced membrane umbrellas will be molded onto DLC. Specific Aim 2: To assess the in vitro and in silico patient efficacy of the DLC-based CPA system. Specific Aim 2A: To evaluate the performance of new CPA DLC in patient-specific TCPCs (PS-TCPCs). Silicone 3D PS-TCPC models will be made from our Fontan database patient MRIs. These models will be used in a mock loop to assess the CPA DLC for: 1) ability to fit/function well in PS-TCPCs and 2) potential flow stasis/high shear stress areas. Specific Aim 2B: To determine the CPA capacity required to reverse CPF patient pathothophysiology in silico. Our validated patient-specific Fontan simulation platform will be used to quantify the optimal CPA flow rates that mitigate liver congestion (n=33). Specific Aim 3: To evaluate the final CPA DLC prototype in a PS-TCPC mock loop for performance, reliability, and 30 day durability. A PS-TCPC mock loop with 37% glycerin will test flow efficiency/reliability with CPA DLC rotation/dislocation and 30-day durability at 4 L/min flow. Specific Aim 4: To evaluate the CPA DLC prototype for in vivo performance, reliability, and ease of installation/ deployment in a CPF sheep model. Specific Aim 4A: To perform acute testing of the CPA DLC prototype in CPF sheep (n=15). Ease of installation/deployment, performance, and reliability will be assessed in these 6 hr studies. Specific Aim 4B: To perform preclinical, 2-week testing of the final CPA DLC prototype in CPF sheep (n=15). This 2-week study will confirm full reversal of CPF hemodynamics/end-organ dysfunction and will assess biocompatibility.