PROJECT SUMMARY/ABSTRACTAdvanced heart diseases lead to a reduced blood supply from the heart and consequently fatigue and deficits inperforming physical activity. In the proposed research we will assess the lack of physiological reserve in olderadults with advanced heart disease focusing on motor and cardiac function to develop a novel objective quickand accurate frailty score. We designed this approach to enhance candidate selection of older adults goingthrough invasive therapies for advanced heart diseases. Although our approach is generic to reduce between-subject variability we focus on transcatheter aortic valve replacement (TAVR) for older adult with aortic stenosis.Therapeutic options continue to grow for TAVR; however it can be difficult to identify candidates with frailty levelthat prohibit them from tolerating the stress from aggressive therapy and those with potential reversible frailty. Itis thus critically important to introduce meaningful routine objective frailty assessment into clinical care of cardiacpatients. Frailty assessment is however not common in cardiology because current assessment tools areburdensome for older adults with advanced heart disease and impractical to implement in busy clinicalenvironments. More importantly no disease-specific tool is available to identify heart disease-related frailty.In continuation of our research program in the field of sensor-based frailty assessment within ourmultidisciplinary team of engineers cardiologists and geriatricians we propose the multimodal upper-extremityfunction (UEF) test for identifying frailty among older adults with advanced heart disease. UEF incorporates asynchronized system of motion sensors and electrocardiography (ECG) to measure motor performance andheart rate (HR) during a rapid 20-second elbow flexion task. Using our previously established UEF motiontracking component we can precisely measure the level of deficits in motor performance (slowness weaknessinflexibility and fatigue) which are not detectable using eyeball assessment. Using the ECG setup minimizingthe motion artifact using this localized task we accurately track HR response to the physical demand as well asrecovery behavior after the task. HR behavior during the task and recovery (HR dynamics) provide a measureof cardiac reserve associated with frailty in heart disease. We will further quantify dysregulation between HRresponse and motor demand as a novel measure of resilience. Based on our preliminary data we expect aweaker and delayed HR response to physical activity as well as an impaired motor function due to frailty.The proposed research will be a four-year study at the University of Arizona Cardiovascular program. In the firstarm we will establish a new HR score and merge it with our previously validated UEF motor score to develop amultimodal frailty score among older adults with advanced heart disease (n=120). In the second arm in alongitudinally setting we will validate the UEF multimodal frailty score for predicting TAVR complications foradvanced heart disease (n=75). Accomplishing these aims we will promote HR dynamic assessment for riskstratification of older adults with advanced heart disease with huge potentials for other comorbid conditions.