DESCRIPTION (provided by applicant): Many Aortic valve disease (AVD) such as stenosis, insufficiency, or congenital defect can severely disrupt normal function of the left ventricle (LV) and aorta. However, the role of AVD and the development of concomitant myocardial dysfunction and aortopathy are not fully understood nor sufficiently characterized. Paradoxically, it is well known that similarly classified AVD patients under the ACC/AHA guidelines can have radically divergent outcomes - implying an incomplete characterization of the disease. To address these limitations, this career development award (CDA) is designed to leverage the PI's quantitative background in fluid dynamics, imaging physics, and cardiovascular imaging in order to further understand the mechanisms leading to LV dysfunction and aortopathy with the ultimate goal to improve AVD risk stratification. The CDA will be used to further the PI's trainin in translational clinical science through formal training in Clinical Investigation and specialized mentor oversight of the research plan, specifically in the areas of cardiology, cardiac surgery, tissue characterization and cardiac standard-of-care imaging. These training activities play into the PI's career goal to become a cross-disciplinary independent investigator at the intersection of cardiovascular hemodynamics, imaging physics, and cardiovascular outcomes research. The research project proposes the development of a comprehensive MRI exam to integrate valve geometry and function with the resulting aortic hemodynamics and energetics. It will be executed according to specific aims tailored to: (1) develop and optimize a MRI protocol designed to obtain aortic valve dynamics, aortic 3D blood flow, blood acceleration fields, and thus high SNR regional wall shear stress (WSS) and energy loss measures; (2) characterize the sensitivity of the measurements in healthy and disease states using physiologic flow phantoms and in-vivo test-retest reliability; (3) perform a longitudinal patient study aimed to correlate energy loss and WSS to outcomes and disease progression in a patient population consisting of moderate to severe aortic valve stenosis subjects. These development activities form a basis for the PI to translate his fluid dynamics and cardiovascular imaging research portfolio into an independent program focusing on the need for better risk-stratification and interventional timing in AVD patients. Additionally, novel insights into the mechanistic role of flow conditions on aortopathy and LV dysfunction will be investigated.

PUBLIC HEALTH RELEVANCE: It is our goal to determine which patients are most at-risk for severe complications related to the malfunctioning aortic valve. It is crucial to intervene before the patient suffers permanent damage or even death; however, the current recommended AHA standards are vague in defining exactly when, why, or if this intervention should happen. Therefore we are investigating: 1) is there a mechanistic or biophysical role for altered blood flow to influence cardiovascular dysfunction, and, 2) which measures most accurately represent the excess load placed on the heart and vessels for prognostic purposes.