Defining the role of Atrial Cardiopathy and Subclinical Cardiac Disease in Acute Ischemic Stroke: Critical Life Event Supplement

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PROJECT SUMMARY Cardioembolic stroke (CES) is costly, not only financially, but also personally to patients and their families, with high rates of recurrence and the highest rate of mortality when compared to strokes of other subtypes. A critical barrier to progress in the field is that currently, the only evidence-based treatment strategy for CES is initiation of anticoagulation (AC) when an atrial tachyarrhythmia, such as atrial fibrillation (AF), is identified post-stroke. However, AF may simply reflect one marker of underlying left atrial (LA) pathology with accruing evidence suggesting that other changes in cardiac structure and function, such as that which occurs at the endothelial level, is responsible for thrombosis irrespective of manifestation of AF. Currently, there is no known means to correctly identity other cardiac pathologies that increase risk for stroke, outside of identification of an arrhythmia. An ongoing clinical trial (ARCADIA) has offered one definition of atrial cardiopathy, but whether this definition is sufficient is unknown. Additionally, how such markers once identified impact patient care and long- term outcomes is also unknown. The purpose of this proposal is to characterize cardiac structure and function in patients with acute ischemic stroke, by (A) evaluating associations between specific cardiac anatomical markers and patient long-term functional outcomes (Aim 1) and (B) utilizing advanced imaging techniques to increase the precision by which such cardiac anatomy is identified to enable prediction of CES (Aim 2). Defining these currently unknown mechanisms in patients with CES, but without AF will allow for the development of effective strategies aimed at mitigating recurrent stroke and poor patient outcomes. For Aim 1, I will follow a previously funded, prospectively enrolled cohort of acute ischemic stroke patients with echocardiography with strain (sTTE) for up to 5 years post-stroke to assess 3 different measures of patient outcome: 90-day modified Rankin Scale (mRS), readmission rates and recurrent stroke. I hypothesize that specific sTTE markers of LA dysfunction will be associated with worse outcomes. For Aim 2, I will then recruit a new cohort of acute ischemic stroke patients without AF and utilize more advanced imaging techniques (computerized coronary tomography angiography, C-CTA) to define the association of specific LA markers with stroke subtype, hypothesizing that particular C-CTA parameters will be associated with CES and that these markers will improve prediction of stroke subtype beyond sTTE alone, and beyond a current trial definition of atrial cardiopathy (ARCADIA). Understanding the relationship between markers of LA function and stroke subtype as well as post-stroke outcomes important to the patient will impact clinical practice and aid future research. This science will be paired with critical training in advanced cardiovascular imaging methods, risk prediction and cohort and clinical trial methodology. The grant-enabled research, combined with the proposed training plan, will enable me to successfully advance to an independent career as a physician-scientist.