The long term goal of the proposal is to determine the role of aging-associated platelet hyperreactivity for increasing stroke risk after transcatheter aortic valve replacement in older adults. More than 60,000 people undergo cardiac surgery in the United States each year which allows them to live longer and more fulfilling lives, but if the procedure is complicated by stroke mortality increases up to 10-fold. Dr. Clendenen is a Cardiothoracic Anesthesiologist dedicated to improving clinical outcomes after cardiac procedures for older adults and this NIA GEMSSTAR proposal is designed to provide him with the structured mentorship and training necessary to become a leader in perioperative aging research. He has developed a collaborative mentorship team led by Dr. Adit Ginde who is an Emergency Medicine Physician and national PI for a large PETAL network clinical trial with 3,000 participants, with co-mentorship provided by Dr. Robert Schwartz, , a recognized leader in aging research. Methodological advisors include Dr. Alex Kaizer (Biostatistics) and Dr. Kirk Hansen (Thrombosis). This proposal leverages the collective expertise of an established mentorship team and the unique environment at the University of Colorado Anschutz Medical Center that incorporates a tertiary referral center for cardiac procedures in the setting of a large public research University. These ample resources will allow Dr. Clendenen to address key barriers to reducing stroke risk after transcatheter aortic valve replacement with a large retrospective cohort study collecting data from 50 institutions across 19 states (Multicenter Perioperative Outcomes Group, MPOG, n >14,000) and a prospective observational cohort with in depth platelet hyperreactivity analysis (n = 100). He will accomplish this by determining the association between aging associated platelet hyperreactivity and in-hospital stroke after TAVR with MPOG (Aim 1) and determining the detrimental effect of TAVR on aging-associated platelet hyperreactivity with the prospective cohort (Aim 2). These specific aims require Dr. Clendenen to develop expertise in analyzing large datasets and aging research. He will accomplish this with a focused Professional Development Plan including coursework on biostatistics, clinical study design, and aging research. Completion of the proposed project will provide the necessary mentorship, training, and experience required to allow Dr. Clendenen to become a leader in perioperative aging research to improve outcomes after transcatheter aortic valve replacement.

PROJECT NARRATIVE Transcatheter aortic valve replacement is effective for improving the health of older adults with aortic stenosis disease, but many patients experience complications such as stroke that result in an increased risk of death and disability. Platelet hyperreactivity is common in older adults and increases the risk of stroke after transcatheter aortic valve replacement. The proposed research will identify to the best way to reduce platelet hyperreactivity before transcatheter aortic valve replacement to reduce the risk of stroke in older adults after the procedure.