THE BRAIN-HEART AXIS: INVESTIGATION OF CARDIAC STRUCTURAL PATHOLOGY AND ASSOCIATION WITH STROKE SUBTYPE AND PATIENT OUTCOMES

Abstract

Ischemic stroke is a deadly disease, with cardioembolic stroke (CS) being particularly costly to patients and their families, due to both high rates of recurrence and the highest rate of mortality, compared to other stroke sub-types. CS composes about 30% of all ischemic strokes with higher incidence at older ages, and among those with cardiac risk factors. Particularly devastating is that most CS patients are left debilitated, placing a high burden on their caregiver. This disability is not only physical, but also cognitive, as over 2 million stroke survivors in the United States suffer from dementia. Diagnosing the primary stroke mechanism is important because it enables appropriate secondary stroke prevention. The most common cause of CS is atrial fibrillation (AF). Oral anticoagulation (AC) reduces the risk of ischemic stroke by 64% for those diagnosed with AF. However, CS is known to occur independently of AF, with all other embolic strokes currently treated with antiplatelet medications. There is increasing evidence of the need to redefine the existing paradigm between the heart, particularly the left atrium (LA), and the brain, specifically the cause of the embolic stroke. Are there cardiac anatomical features and functional parameters that would offer insight as to the origin of the embolus, and should these patients then be treated with AC? This dissertation seeks to address some of these questions. The introduction describes stroke etiology, its determination, the evidence-based treatment of AF stroke patients, evidence that patients without AF have CS, and finally, the tools available to move the field of CS diagnosis and treatment forward. Chapter 1 describes a cohort study using transthoracic echocardiography (TTE) to evaluate specific cardiac parameters of acute ischemic stroke patients, and their associations with CS. Chapter 2 builds upon the first and uses TTE with strain to focus on LA anatomy. Chapter 3 describes a large, population-based cohort study of participants with markers of LA cardiopathy and their associations with cerebral beta-amyloid, a pathology necessary in the development of Alzheimer’s disease. The conclusion describes the future of this exciting field, and the ongoing research efforts resulting from this dissertation.