Cardiogenic shock (CS) is a serious clinical condition of reduced cardiac output (CO) with end organ hypoperfusion. In severe CS, end organ hypoperfusion leads to multi-organ failure, and elevated left ventricle (LV) preload increases LV wall stress, exacerbating myocardial injury. Venoarterial extracorporeal membrane oxygenation (VA ECMO) has been increasingly used to support severe CS patients due to its high efficiency, cost effectiveness, wide availability, and minimally invasive capability. VA ECMO pumps almost total CO to normalize end organ perfusion. However, VA ECMO is unable to unload the LV in severe CS patients with more than 50% of these patients developing LV distension, which further damages the myocardium and prevents myocardial recovery. In VA ECMO, some blood still goes to the left heart, but the compromised LV fails to pump this blood out, resulting in LV blood accumulation (LV distension). Currently, there is no minimally invasive device specifically designed for LV unloading during VA ECMO. Our ultimate goal is to develop a percutaneous device to unload the LV during VA ECMO, facilitating myocardial recovery. The enabling technology is a percutaneous pulmonary artery (PA) drainage device that keeps the PA/tricuspid valves persistently open, allowing blood flow from the PA toward the right atrium for ECMO drainage. This results in a lower PA pressure (PAP) which decreases blood flow toward the left heart and enables retrograde blood flow from the left atrium to PA to efficiently unload the LV. Our percutaneous PA drainage device: 1) is minimally invasive to eliminate complicated surgery, 2) decreases PAP to decompress the heart, 3) prevents drainage- induced low central venous pressure to enhance VA ECMO drainage, and 4) monitors PAP to confirm/evaluate LV unloading. In our LV distension sheep model with massive myocardial infarction (MI)-induced severe CS and VA ECMO support, our first percutaneous PA drainage device prototype was properly deployed and efficiently unloaded the LV (n=2), demonstrating the LV unloading feasibility of our device. Our objective in this Phase I SBIR is to develop/fabricate a new percutaneous PA drainage device prototype for in vitro testing and in vivo testing in our LV distension sheep model. Specific Aim 1: To design, fabricate, and bench-test a percutaneous PA drainage device prototype. The prototype will be a 7 Fr triple lumen catheter-based memory alloy wire cage. This cage will be close to the catheter for easy installation/removal and will open inside the PA/tricuspid valves to create valve regurgitation. Back flow efficiency and valve opening reliability will be tested in a simulation mock loop. Specific Aim 2: To test a percutaneous PA drainage device prototype in a LV distension sheep model. Our established LV distension sheep model with massive MI- induced severe CS and VA ECMO support will be used to test our percutaneous PA drainage device prototype for ease of deployment, LV unloading efficiency, and 6 hour reliability (n=5). W-Z Biotech will design, fabricate, and perform in vitro testing while the University of Kentucky will conduct the in vivo animal studies.
Public Health Relevance Statement: We are proposing to develop a percutaneous pulmonary artery drainage device to address the critical problem of left ventricular distension in VA ECMO-supported severe cardiogenic shock patients. The enabling technology is a 7 Fr triple lumen catheter-based memory alloy wire cage that keeps the pulmonary and tricuspid valves persistently open to efficiently unload the left ventricle. Our percutaneous pulmonary artery drainage device will facilitate myocardial recovery in severe cardiogenic shock patients, significantly impacting their outcomes.
Project Terms: Acute myocardial infarction; Address; Alloys; Animals; Aorta; Arrhythmia; artificial lung; Back; base; Biotechnology; Blood; Blood Circulation; Blood flow; blood pump; Cannulas; Carbon Dioxide; Cardiac; Cardiac Output; Cardiogenic Shock; Catheters; Central venous pressure; Cessation of life; Clinical; Complex; cost effectiveness; design; Development; Devices; Drainage procedure; Drug toxicity; Engineering; Equipment; Excision; experience; Extracorporeal Membrane Oxygenation; Failure; Goals; Heart; Heart Atrium; Heart Transplantation; Heart Valve Diseases; Hour; Human Resources; hypoperfusion; In Vitro; in vitro testing; in vivo; in vivo evaluation; Injury; Kentucky; Label; Laboratory Animal Production and Facilities; Lead; Left; Left atrial structure; Left ventricular structure; Low Cardiac Output; Lung; Mechanics; Memory; minimally invasive; Modeling; Monitor; mortality; multidisciplinary; Myocardial; Myocardial Infarction; Myocarditis; Myocardium; Operative Surgical Procedures; Organ; Outcome; Patients; performance tests; Perfusion; Phase; Polyurethanes; pressure; prevent; prototype; Publications; Pulmonary artery structure; Pulmonary valve structure; Pump; Recovery; research and development; Research Support; Right atrial structure; Risk; Scientist; Sheep; simulation; Small Business Innovation Research Grant; Stress; Surgeon; Techniques; Technology; Testing; Tricuspid Valve Insufficiency; Tricuspid valve structure; Universities; Venous; Ventricular; ventricular assist device
