Defining the role of Atrial Cardiopathy and Subclinical Cardiac Disease in Acute Ischemic Stroke

项目摘要 脑栓塞性卒中（CES）不仅经济上昂贵，而且对患者及其家属来说也是昂贵的， 与其他亚型的中风相比，复发率高，死亡率最高。一 该领域进展的关键障碍是，目前，CES的唯一循证治疗策略是 当识别出房性快速性心律失常（如房颤（AF））时，开始抗凝治疗（AC） 中风后然而，房颤可能只是反映了潜在的左心房（LA）病理学的一个标志， 有证据表明，心脏结构和功能的其他变化，如发生在心脏 内皮水平，是血栓形成的原因，无论AF的表现如何。 是指正确识别其他心脏病，增加中风的风险，以外的识别， 心律不齐一项正在进行的临床试验（ARCADIA）提供了心房性心脏病的一个定义，但这是否 定义是未知的。此外，这些标志物一旦被识别，如何影响患者护理和长期- 长期结果也是未知的。该提案的目的是表征心脏结构和功能 在急性缺血性卒中患者中，通过（A）评估特定心脏解剖结构与 标记物和患者长期功能结局（目标1）和（B），利用先进的成像技术， 提高识别这种心脏解剖结构的精度，以实现CES的预测（目标2）。 在CES患者中定义这些目前未知的机制，但没有AF将允许 制定有效的策略，旨在减轻复发性卒中和不良患者结局。对于目标1， 我将跟踪一个先前资助的前瞻性入组的急性缺血性卒中患者队列， 卒中后长达5年的应变超声心动图（sTTE），以评估患者的3种不同指标 结果：90天改良兰金量表（mRS）、再入院率和复发性卒中。我假设 左心房功能障碍的特异性sTTE标志物与更差的结局相关。对于目标2，我将招募一名 无AF的急性缺血性卒中患者的新队列，并使用更先进的成像技术 （计算机冠状动脉断层扫描血管造影术，C-CTA），以确定特定LA标志物与 中风亚型，假设特定的C-CTA参数将与CES相关，并且这些 标志物将改善卒中亚型的预测，超过单独的sTTE，并超过目前的试验定义， 心房性心脏病（ARCADIA）。了解左心房功能标志物与卒中的关系 亚型以及对患者重要的卒中后结局将影响临床实践， research.这项科学将与先进的心血管成像方法，风险， 预测、队列和临床试验方法。资助的研究，结合拟议的 培训计划，将使我能够成功地推进到一个独立的职业生涯作为一个物理学家，科学家。

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.