Project Summary The objective of this career development plan and proposed research is to support my development into an independent investigator focused on resuscitation science, who can successfully conduct mechanism-driven and patient-oriented research for the development of novel clinical therapies in resuscitation and cardiovascular critical care. Out-of-hospital cardiac arrest (OHCA) is a leading cause of death in the U.S. and worldwide with less than 20% of patients surviving to hospital discharge and many survivors experiencing neurologic injuries. Resuscitation guidelines have espoused treatment recommendations in the delivery of high-quality cardiopulmonary resuscitation (CPR) and the evaluation for underlying causes of OHCA. However, despite these approaches, a substantial number of patients do not survive, suggesting a crucial need to seek new strategies in resuscitation care. Obstruction of the left ventricular outflow tract (LVOT) by chest compressions has been identified as an important factor causing ineffective CPR, but neither the hemodynamic nor the clinical impact of this has been well-established. Due to its endoscopic location, transesophageal echocardiography (TEE) can visualize the heart during the delivery of CPR, conveying unique real-time and actionable data. This K23 resubmission proposal builds upon prior work by our team demonstrating that TEE can be deployed rapidly and safely during resuscitation of OHCA patients, providing high-quality dynamic imaging of the heart and major vascular structures during CPR. Furthermore, since the original submission our team has successfully implemented a multi-center registry with 25 centers currently participating, and demonstrated the feasibility to obtain clinical, hemodynamic, and TEE data in patients with OHCA and in-hospital cardiac arrest. Leveraging this unique experience and infrastructure, as well as a multidisciplinary team of content-specific mentors, the objectives of this proposal are to perform focused clinical investigations, aimed to quantify the hemodynamic and clinical effects of TEE-guided CPR, and to elucidate the barriers to successful implementation of this intervention in acute care settings. In Aim1, I will leverage the existing infrastructure of our ongoing research network to conduct a multicenter observational cohort study of adults with atraumatic SCA, aimed to evaluate the impact of TEE guidance of CC location on hemodynamic endpoints and survival to hospital discharge. In Aim 2, using a mixed methods approach, I will characterize the implementation determinants, barriers, and facilitators of TEE-informed resuscitation. The results of this research could enhance the effectiveness of CPR, provide the basis for a novel patient-centric approach with the potential to impact over 400,000 patients with cardiac arrest annually in the U.S. The proposed activities will provide the PI with unique skills in the areas of pragmatic clinical trials, cardiovascular p...