There is increasing recognition that structural factors such as left atrial (LA) size, blood flow, fibrosis, and strain, are involved in the development and maintenance of AF and ischemic stroke, even in the absence of AF. Northwestern University plans to submit 3 synergistic projects that align with the AHA mission of building healthier lives free of cardiovascular disease and stroke. To contribute to this mission, our proposal will develop a comprehensive understanding of the role of the underlying atrial substrate in the pathogenesis of AF and its major morbidity - thromboembolic stroke. This application consists of three synergistic projects (along with a training program) that uses cutting-edge technologies and collaborations to comprehensively characterize the atrial myopathy underlying AF and related brain disease with a goal towards improving patient outcomes. The clinical project (Co-PIs: Rod S. Passman MD, MSCE and Daniel Kim, PhD) entitled 'ATRIAL MYOPATHY: STRUCTURE AND FUNCTION IN AF ABLATION' will use novel cardiac MRI indices of left atrial structure and function (CMR strain, dimensions, fibrosis and 4D-CMR flow/stasis of the left atrium and left atrial appendage) along with clinical variables and serum biomarkers (in collaboration with Drs. Yao and Elbayoumi ' Midwestern University) to assess predictors of successful ablation and reverse remodeling post-ablation. Novel targets for future AF therapies based on intracardiac AF electrogram responses to oxidative stress will also be evaluated. The basic science Project (Co-PIs: Rishi Arora, MD and Daniel Lee, MD) is entitled 'THE ROLE OF OXIDATIVE STRESS IN CREATING A VULNERABLE SUBSTRATE FOR AF IN THE INTACT ATRIUM' and will study the role of oxidative stress in the initiation and perpetuation of AF and the in vivo assessment of oxidative stress via defining characteristics on AF electrogram analysis and cardiac MR imaging. The epidemiology project: (Co-PIs: Philip Greenland, MD and Michael Markl, PhD in collaboration Dr. Susan Heckbert (University of Washington)), entitled 'EPIDEMIOLOGY OF SUBCLINICAL AF SUBSTRATE' will examine patients in the MESA cohort for AF and clinical/ subclinical brain infarcts and correlate these findings with left atrial flow and stasis on 4D CMR.
|Program type||Strategically Focused Research Network|
|Effective start/end date||07/01/2018 → 06/30/2022|