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

项目总结 心栓性中风(CES)代价高昂，不仅在经济上，而且对患者及其家人个人也是如此， 与其他亚型中风相比，复发率和死亡率最高。一个 在这一领域取得进展的关键障碍是，目前CES唯一的循证治疗策略是 房性快速性心律失常，如房颤时，开始抗凝(AC) 中风后。然而，房颤可能只是反映了一个潜在的左房(LA)病理标记物。 有证据表明心脏结构和功能的其他变化，如发生在心脏 无论房颤的表现如何，血管内皮细胞水平都是血栓形成的原因。目前，尚无已知的 正确识别其他增加中风风险的心脏病理的手段，而不是识别 心律不齐。一项正在进行的临床试验(阿卡迪亚)提供了房性心脏病的一种定义，但这是否 定义是否足够是未知的。此外，一旦确定了这些标志物，将如何影响患者的护理和长期 任期结果也是未知的。这项建议的目的是描述心脏的结构和功能 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 标记物和患者的长期功能结果(目标1)和(B)利用先进的成像技术 提高识别此类心脏解剖结构的精确度，从而能够预测CES(目标2)。 在CES患者中明确这些目前未知的机制，但没有房颤将允许 制定有效的策略，旨在减轻中风复发和患者预后不良的风险。对于目标1， 我将跟踪先前资助的、预期登记的急性缺血性中风患者队列，这些患者患有 卒中后长达5年的负荷超声心动图(STTE)评估3种不同指标的患者 结果：90天改良Rankin评分(MRS)、再住院率和中风复发。我假设 LA功能障碍的特定sTTE标志物将与更差的结果相关。对于目标2，我将招募一名 无房颤的急性缺血性卒中患者的新队列，并利用更先进的成像技术 (计算机化冠状动脉断层血管造影术，C-CTA)以确定特定的LA标志物与 卒中子类型，假设特定的C-CTA参数将与CES相关联，并且这些 标记物将改善对卒中亚型的预测，而不仅仅是sTTE，而且超过目前的试验定义 房性心脏病(阿卡迪亚)。对LA功能标志物与卒中关系的认识 对患者重要的亚型和卒中后结果将影响临床实践并有助于未来 研究。这门科学将与先进的心血管成像方法、风险 预测和队列及临床试验方法学。赠款支持的研究，与拟议的 培训计划，将使我能够成功地进入独立的职业生涯，成为一名内科科学家。

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.