SUMMARY/ABSTRACT Heart Failure (HF) is a devastating disease affecting more than 20 million patients worldwide, with 5.7 million of these American at an incidence of 870,000 new cases each year. Whilst heart transplants provide the best treatment option for many of these patients, less than 4200 heart transplants take place globally each year. Furthermore, current growth rates predict a 25% increase in the incidence of HF by 2030 at an expected cost of USD$69.7 B per annum. The US National Institute of Health (NIH) estimated that 100,000 patients could immediately benefit from mechanical circulatory support (MCS). Patients with severe heart failure have a poor outlook without intervention. Drug therapy is not an effective option, and the limited availability of donor hearts suggests the only viable alternative at this point in time is MCS. Ventricular assist devices (VADs) and Total Artificial Hearts (TAHs) are mechanical pumps that are surgically implanted alongside or in replacement of the heart of patients with severe HF, to restore the adequate blood flow. Technological advances in the field have addressed many issues associated with isolated left ventricular HF resulting in the commercialization of a number of left ventricular assist devices (LVADs). However, up to 30% of HF patients have biventricular HF, or it develops after LVAD implantation. This necessitates the removal of the heart and implantation of a TAH, or the implantation of a second VAD alongside the right heart to provide biventricular assistance (BiVAD). However, there are no long-term biventricular devices that adequately meet the needs of this population due to concerns regarding durability and adverse events. The BiVACOR device is poised to take advantage of this market gap. The BiVACOR TAH utilizes the same approach as the modern successful LVADs which are based on rotary blood pump (RBP) technology with magnetically levitated rotors, and applies it to provide simultaneous, reliable and biocompatible support for both the systemic and pulmonary circulations. The device has progressed though concept and feasibility phase I via private funding sources, and is now entering the development phase II. Therefore, this SBIR proposal is targeting a direct to phase II application, with the following specific aims (1) Implement and refine speed control algorithms to restore pulsatility and outflow adaptation, (2) Refine the design of implantable components while achieving an optimized human anatomical fit, (3) Construct hermetically sealed devices under design controls, and (4) Verification of processes and validation of device function in vitro and chronic in vivo. Attainment of these milestones would lead to a design freeze whilst demonstrating the clinical utility of this product, raising the profile of the technology, and thus encouraging the additional investment needed to enter into Phase III commercialization. The impact of a long-term practical mechanical replacement to the failing human heart for men, women and children would be tremendous. Patients would no longer need to wait for a heart transplant to return to a vastly improved quality of life. Leveraging the successful durability and small size of similar VAD technologies into the BiVACOR TAH provides a clear pathway to achieve the goal of a practical replacement of the failing human heart.

NARRATIVE Cardiovascular disease is the number one cause of death in the United States and the need for heart transplants by far outweighs the number of available donor organs. Mechanical circulatory support devices are commonly used to support patients waiting for a transplant or as therapy to allow patients to return home. The proposed study will progress the BiVACOR total artificial heart through the research and development phase to achieve a mature design freeze, and verify performance in vitro and in vivo. Furthermore, the implementation of a speed control algorithm will attempt to recreate pulsatile outflow whilst adjusting total outflow in response to physiological demand. Successful development of this device will provide a viable alternative to donor heart transplantation therapy, ultimately improving heart failure patient’s outcomes and quality of life, reducing associated healthcare costs and guiding future development and use of rotary blood pumps, including left ventricular assist devices and total artificial hearts.