SUMMARY/ABSTRACT Heart Failure (HF) is a devastating epidemic affecting more than 23 million patients worldwide; in the U.S. alone, 1,000,000 new cases are reported each year. While heart transplantation provides the best treatment option for many patients, less than 6,000 procedures take place globally each year. Consequently, it is estimated that 50,000 – 100,000 patients could immediately benefit from mechanical circulatory support. Many circulatory support devices are available for patients who require left ventricular support, but few options exist for patients who would benefit from biventricular support. With the exception of transplantation, the optimal approach to biventricular failure is the replacement of the native heart with a Total Artificial Heart (TAH). Traditional approaches have used volume displacement pumps, which have inherent limitations due to their large size, flexing membranes, and valves that conspire to reduce the durability and lifetime of the device. The same limitations were observed throughout the early application of VAD technology, which prompted a transition to rotary blood pumps for size reduction and increased durability. Today, more than 60,000 patients are supported with rotary VADs. Capitalizing on the advantages of rotary blood pump technology, the BiVACOR TAH is small, reliable, blood-friendly and has inherently balanced blood flows. Under the previous SBIR grants, the system components of the BiVACOR TAH were significantly improved and validated on the benchtop and in-vivo. BiVACOR has entered the final product development and manufacturing phase and wishes to utilize the SBIR II scheme to use the BiVACOR TAH system for the first time clinically via an FDA-approved Early Feasibility Study (EFS). To achieve this goal, the following specific aims will be completed: 1) clinical study initiation; 2) evaluate the safety and performance of the BIVACOR TAH in a clinical study; and 3) evaluate the outcomes of the Early Feasibility Study and identify required device updates. The commercial application and viability of this product will be demonstrated and will encourage additional investment for full commercialization. The world-wide impact of a commercially viable, long-term mechanical replacement to the failing human heart will be tremendous. The wait for patients desperately requiring a heart transplant will go from years to off-the- shelf availability, thereby quickly providing a vastly improved quality of life. Leveraging the successful durability and small size of similar technologies used for ventricular assistance into the BiVACOR rotary TAH provides a promising pathway to finally achieve the goal of a reliable, biocompatible, physiological, and ultimately practical replacement to the failing human heart.

NARRATIVE Cardiovascular disease is the number one cause of death in the United States, and while heart transplantation is currently the most effective treatment, the number of patients needing a transplant is far greater than the number of available donor organs. The proposed project will progress the BiVACOR total artificial heart through the first clinical use of the device in an Early Feasibility Study approved by the FDA. Successful completion of this program will provide a viable alternative to donor heart transplantation therapy: improving clinical outcomes and increasing the quality of life for recipients of the device, thus reducing associated healthcare costs and thereby guiding future development and use of rotary blood pumps, including left ventricular assist devices and other total artificial hearts.