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

定义心房性心脏病和亚临床心脏病在急性缺血性中风中的作用

• 批准号: 10468078
• 负责人: Michelle C. Johansen
• 金额: $ 19.93万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-15 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10468078
• 关键词: Acute; Address; Anatomy; Angiography; Anticoagulation; Arrhythmia; Atherosclerosis; Atrial Fibrillation; Cardiac; Cauliflower; Cessation of life; Clinical; Clinical Trials; Coronary; Data; Development; Diagnosis; Disease; Echocardiography; Electrocardiogram; Endothelium; Enrollment; Evaluation; Evidence based treatment; Family; Functional disorder; Funding; Future; Grant; Heart Atrium; Heart Diseases; Imaging Techniques; Individual; Ischemic Stroke; Lead; Left; Left Atrial Function; Left atrial structure; Link; Longterm Follow-up; Measures; Mechanics; Methodology; Monitor; Outcome; Pathology; Patient Care; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Physicians; Prevention; Preventive therapy; Recurrence; Research; Research Personnel; Risk; Risk Factors; Role; Science; Scientist; Secondary to; Shapes; Source; Stroke; Structure; Tachyarrhythmias; Testing; Therapeutic; Thrombosis; Training; Work; X-Ray Computed Tomography; adjudicate; anatomic imaging; aortic arch; appendage; auricular appendage; cardiovascular imaging; career; clinical practice; cohort; computerized; cost; disability; embolic stroke; functional outcomes; heart function; heart imaging; high risk; hospital readmission; imaging biomarker; imaging modality; improved; indexing; insight; mortality; patient subsets; post stroke; prevent; prospective; readmission rates; recruit; risk prediction; risk prediction model; skills; stroke outcome; stroke patient; stroke risk; stroke therapy; tomography; treatment strategy

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.

项目概要 心源性卒中（CES）不仅在经济上，而且对患者及其家人而言，都造成高昂的代价， 与其他亚型的中风相比，复发率高，死亡率最高。一个 该领域取得进展的关键障碍是，目前 CES 唯一基于证据的治疗策略是 当发现房性快速心律失常（例如房颤（AF））时开始抗凝（AC） 中风后。然而，房颤可能只是反映了潜在左心房 (LA) 病理的一种标志物，并且随着时间的推移， 有证据表明心脏结构和功能的其他变化，例如发生在 无论 AF 的表现如何，内皮水平都会导致血栓形成。目前，尚无已知的 是指除了识别中风之外，正确识别其他会增加中风风险的心脏病。 心律失常。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 定义是否充分尚不清楚。此外，这些标记物一旦被识别，将如何影响患者护理和长期治疗 期限结果也未知。该提案的目的是表征心脏结构和功能 在急性缺血性中风患者中，通过 (A) 评估特定心脏解剖结构之间的关联 标记物和患者长期功能结果（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度，以实现 CES 的预测（目标 2）。 在患有 CES 但没有 AF 的患者中定义这些目前未知的机制将允许 制定旨在减轻中风复发和患者不良预后的有效策略。对于目标 1， 我将跟踪一个先前资助的、前瞻性招募的急性缺血性中风患者队列 中风后长达 5 年的应变超声心动图 (sTTE)，用于评估患者的 3 种不同指标 结果：90 天改良 Rankin 量表 (mRS)、再入院率和复发性卒中。我假设 LA 功能障碍的特定 sTTE 标记将与更差的结果相关。对于目标 2，我将招募一名 新一批无房颤的急性缺血性中风患者并利用更先进的成像技术 （计算机冠状动脉断层扫描血管造影，C-CTA）来定义特定 LA 标记物与 中风亚型，假设特定的 C-CTA 参数将与 CES 相关，并且这些 标记物将改善中风亚型的预测，超越单独的 sTTE 和当前的试验定义 心房性心脏病（ARCADIA）。了解 LA 功能标志物与卒中之间的关系 对患者重要的亚型以及中风后结果将影响临床实践并帮助未来 研究。这门科学将与先进心血管成像方法、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晋升为一名医生科学家的独立职业。