DESCRIPTION (provided by applicant): My career goal is to become an independent NIH-funded RO1 investigator contributing to advancements in mechanical circulatory support ("mechanical hearts") for patients with advanced heart failure. My work to date has focused on the impact of continuous-flow (CF) left ventricular assist devices (LVADs), a type of mechanical heart, on cerebrovascular physiology, sympathetic neural activity and blood pressure. This work has led to several presentations at national conferences, first-author publications that are either published or in review and research awards. However, there are two immediate research goals that are necessary for my own career development and to advance the field, including: 1) acquire new skills in the assessment of the cardiovascular and autonomic nervous system; and 2) extend my research program from the study of the cardiovascular system and CF-LVAD interactions under resting conditions, to dynamic conditions during exercise. To accomplish these goals, I have assembled a rigorous career development plan with experiential learning, opportunities to gain proficiency in procedures that I can incorporate into my research program, formal coursework to obtain a Master in Clinical Science degree, and oversight from mentors and advisors who are international experts in their respective fields. I will continue my successful mentored relationship with Dr. Benjamin Levine, who will serve as my primary mentor, Dr. Mark H. Drazner, who will serve as my co-mentor, as well as Drs Qi Fu and Jere Mitchell, who will continue to serve as research advisors. In addition, I will form a new collaborative relationship with Dr. Murray Esler, an international expert in cardiovascular and exercise physiology, with expertise in assessment of the autonomic nervous system. My long term goal is to understand how the cardiovascular system operates in the presence of a CF-LVAD. The objectives of this proposal are to determine how CF-LVADs impact exercise pressor reflexes and to identify the factor(s) which determine exercise capacity in advanced heart failure patients with these devices. Here, I will test the central hypothesis that exercise pressor reflexe improve following CF-LVAD implantation and that the primary determinant of exercise capacity is contractility of the left ventricle. The objectives of this proposal will be accomplished by pursuing two specific aims: 1) Determine the effect of a CF-LVAD on exercise pressor reflex in heart failure patients; and 2) Define the primary determinant(s) of exercise capacity in heart failure patients prior to and following CF-LVAD implantation. Results delivered from these specific aims will provide major contributions to the field and inform development of novel strategies to improve quality of life and survival in this unique patient population, and contribut to refinements in device technology, such that future-generation LVADs can modulate flow during exercise, similar to the normal heart. The proposed research will be conducted at the University of Texas Southwestern Medical Center (UTSW) and the Institute of Exercise and Environmental Medicine (IEEM) in Dallas, Texas. UTSW provides extraordinary translational research opportunities and faculty development programs, while the IEEM houses a world- renowned physiology research laboratory. I will have complete access to all resources available at these two institutions that will ensure my success during this K23 award period and that my career goals are achieved. Based on my training to date, mentored research experience and institutional environment, I believe that I am uniquely positioned to accomplish all objectives outlined in this career development project. This success will ensure that I transition into an independent RO1 funded investigator with expertise in cardiovascular and exercise physiology in patients with advanced heart failure, with a unique skillset in assessment of the autonomic nervous system, which few researchers possess.

PUBLIC HEALTH RELEVANCE: This project will evaluate how the cardiovascular system interacts with mechanical hearts to provide blood flow to the body during exercise. Two aims are proposed: 1) to determine the impact of a mechanical heart on exercise pressor reflexes in heart failure patients; and 2) to define the primary determinant(s) of exercise capacity in heart failure patients before and after device implantation. This project is relevant to public health because results will lead to implementation of new strategies to improve quality of life and survival in this population and inform development of next-generation devices that can function similar to the normal heart.