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: 10055092
• 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/10055092
• 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 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.

项目摘要 心脏符号中风（CES）不仅在财务上，而且对患者及其家人的成本高昂， 与其他亚型的中风相比，复发率高和死亡率最高。一个 该领域进步的关键障碍是，目前，CES的唯一基于证据的治疗策略是 当鉴定出心房心律失常（例如心房颤动（AF））时，抗凝（AC）的启动（AC）。 冲程后。但是，AF可能只是反映了基础左心房（LA）病理学的一个标记 证据表明心脏结构和功能的其他变化，例如发生在 内皮水平，负责血栓形成，而与AF的表现无关。目前，尚无已知 正确识别增加中风风险的其他心脏病理 心律不齐。一项正在进行的临床试验（Arcadia）提供了心房心理的一个定义，但是是否 定义就足够了。此外，这种标记曾经识别出影响患者护理和长期影响 术语结果也未知。该建议的目的是表征心脏结构和功能 在患有急性缺血性中风的患者中，通过（a）评估特定心脏解剖学之间的关联 标记和患者的长期功能结果（AIM 1）和（b）利用先进的成像技术 提高确定这种心脏解剖结构以实现CE的精度（AIM 2）。 在CE患者中定义这些目前未知的机制，但没有AF 制定旨在减轻复发性中风和患者结果差的有效策略。对于目标1， 我将遵循先前资助的，前瞻性地招收的急性缺血性中风患者 超声心动图（STTE）在击球后长达5年，以评估3种不同的措施 结果：90天修改后的Rankin量表（MRS），再入院率和经常性中风。我假设这一点 LA功能障碍的特定STTE标记将与较差的结果有关。对于AIM 2，我将招募一个 新的急性缺血性中风患者没有AF，并利用了更先进的成像技术 （计算机化冠状动脉层学血管造影，C-CTA）定义特定LA标记的关联 中风子类型，假设特定的C-CTA参数将与CES相关联，并且这些参数 标记将仅超出Stte，以及当前的试验定义，以改善中风子类型的预测 心房病（Arcadia）。了解LA功能和中风标记之间的关系 亚型以及对患者重要的势头结果将影响临床实践并帮助未来 研究。该科学将与高级心血管成像方法的重要培训配对，风险 预测和队列和临床试验方法。支持授予的研究，结合了拟议的 培训计划将使我能够成功地晋升为医生科学家的独立职业。