Atrial Fibrillation Precursors May Be Novel Stroke Risk Factors

心房颤动前兆可能是新的中风危险因素

• 批准号: 9334941
• 负责人: Hooman Kamel
• 金额: $ 18.75万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9334941
• 关键词: Accident and Emergency department; Address; Affect; Age-Years; Anticoagulant therapy; Anticoagulants; Anticoagulation; Area; Arrhythmia; Arteries; Atherosclerosis; Atrial Fibrillation; Biological Markers; California; Cardiac; Cardiology; Clinical; Clinical Investigator; Clinical Research; Clinical Trials; Clinical Trials Design; Code; Comorbidity; Data; Databases; Development; Diagnosis; Diagnostic Procedure; Disease; EKG P Wave; Embolism; Enrollment; Epidemiology; Fibrosis; Fostering; Functional disorder; Goals; Heart; Heart Atrium; Heart Diseases; Holter Electrocardiography; Hour; ICD-9-CM; Incidence; Inpatients; Ischemic Brain Injury; Ischemic Stroke; Knowledge; Label; Link; Medical Records; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Mission; Monitor; National Institute of Neurological Disorders and Stroke; Neurologist; Neurology; Outcome Study; Paroxysmal supraventricular tachycardia; Patients; Population Study; Predisposition; Public Health; Recruitment Activity; Research; Research Personnel; Risk; Risk Factors; Series; Severities; Source; Stroke; Stroke prevention; Supraventricular Arrhythmia; Testing; Time; Training; Transient Ischemic Attack; Validation; Wolves; Work; adjudicate; base; biomarker development; cardiovascular disorder epidemiology; career; career development; clinical Diagnosis; clinical practice; cohort; epidemiology study; follow-up; high risk; improved; innovation; multidisciplinary; nervous system disorder; novel; patient oriented; population based; prospective; public health relevance; screening; secondary analysis; skills; stomach cardia; technique development; tool

DESCRIPTION (provided by applicant): Atrial Fibrillation Precursors May Be Novel Stroke Risk Factors. This is a K23 resubmission application for Dr. Hooman Kamel, a neurologist and young investigator pursuing patient-oriented clinical research on ischemic stroke caused by cardiac arrhythmias. A K23 award will provide him with the means to acquire critical skills in three key career development areas: 1) epidemiology and clinical trial design, 2) cardiac diagnostic techniques, and 3) biomarker development and assessment. By acquiring these skills, Dr. Kamel will fulfill his long-term career goal of becoming an independent clinical investigator. To pursue this goal, Dr. Kamel has recruited a primary mentor, Dr. Richard Devereux, a cardiologist with expertise in cardiovascular epidemiology and cardiac diagnostic techniques, and two co- mentors, Dr. Mitchell Elkind, a neurologist with expertise in stroke epidemiology and clinical trial design, and Dr. Costantino Iadecola, a neurologist with expertise in ischemic brain injury and biomarkers. Based on recent evidence and his own preliminary data, Dr. Kamel's central hypothesis is that supraventricular arrhythmias increase stroke risk even before the development of atrial fibrillation/flutter (AF), which is currently the only cardia arrhythmia thought to cause stroke. Testing this hypothesis will address a fundamental gap in knowledge about which supraventricular arrhythmias cause stroke. Until this knowledge gap is filled, optimal strategies for preventing stroke from cardiac disease cannot be fully determined. By pursuing the following specific aims, the applicant will test his hypothesis and gather data for a population- based study of stroke risk from supraventricular arrhythmias (to be proposed in an R01 application during the K23 award period). Specific Aim 1 will test the hypothesis that electrocardiographic P-wave dispersion, an early marker of atrial electrical dysfunction and predisposition to supraventricular arrhythmias, is associated with an increased risk of stroke. This aim will be pursued by analyzing a cohort without AF enrolled in the Strong Heart Study, a population-based epidemiological study with baseline electrocardiographic data and >375 adjudicated and classified cases of stroke. Specific Aim 2 will test the hypothesis that supraventricular ectopy is associated with cryptogenic stroke. In a prospectively enrolled series of patients, rates of supraventricular ectopy during cardiac monitoring will be compared between 75 patients with cryptogenic stroke and 75 patients with stroke from small-vessel occlusion or large-artery atherosclerosis. Secondary analyses will compare biomarkers of cardiac embolism between the two groups, and correlate rates of supraventricular ectopy with these biomarkers. Specific Aim 3 will test the hypothesis that clinical diagnoses of paroxysmal supraventricular tachycardia are associated with the risk of stroke after transient ischemic attack. This aim will b pursued using a validated ICD-9-CM code for paroxysmal supraventricular tachycardia and linked medical records from the California State Inpatient Database and Emergency Department Database. The proposed research is significant because positive results will uncover novel stroke risk factors, while negative results will counter the increasing off-label use of unproven anticoagulant therapy for nonspecific supraventricular arrhythmias after cryptogenic stroke. The proposed research is innovative because it seeks to shift current research and clinical practice paradigms by identifying a large new class of patients who are at high risk for stroke and may benefit from existing anticoagulant drugs, and also seeks to bridge cardiology and neurology via the new application of cardiology tools to stroke research.

说明(申请人提供)：房颤前兆可能是新的卒中危险因素。这是胡曼·卡迈勒博士的K23重新提交申请，他是一位神经学家和年轻的研究员，致力于以患者为导向的心律失常引起的缺血性中风的临床研究。K23奖项将为他提供在三个关键职业发展领域获得关键技能的手段：1)流行病学和临床试验设计，2)心脏诊断技术，3)生物标记物开发和评估。通过掌握这些技能，卡迈勒博士将实现他成为一名独立临床研究员的长期职业目标。为了实现这一目标，Kamel博士聘请了一位主要导师Richard Devereux博士，他是一位在心血管流行病学和心脏诊断技术方面有专长的心脏病专家，以及两位共同导师，一位是在中风流行病学和临床试验设计方面有专长的神经科医生Mitchell Elkind，另一位是在缺血性脑损伤和生物标记物方面有专长的神经学家Costantino Iadecola博士。根据最近的证据和他自己的初步数据，Kamel博士的中心假设是，在发生房颤/扑动(AF)之前，室上性心律失常就会增加中风的风险，房颤是目前唯一被认为会导致中风的心脏性心律失常。验证这一假说将解决关于哪些室上性心律失常导致中风的基本知识空白。在填补这一知识空白之前，无法完全确定预防心脏病导致中风的最佳策略。通过追求以下具体目标，申请者将检验他的假设并收集数据以 一项基于人群的室上性心律失常的中风风险研究(将在K23获奖期间的R01申请中提出)。具体目标1将检验这样一种假设，即心电P波离散度是房电功能障碍和室上性心律失常的早期标志，与中风风险增加有关。为了达到这一目的，我们将分析一个没有房颤的队列，该队列没有纳入强心研究，这是一项以人群为基础的流行病学研究，有基线的心电数据，以及375例被判定和分类的中风病例。《特定目标2》将验证室上性异位与隐源性中风相关的假设。在一组前瞻性登记的患者中，将比较75名不明原因中风患者和75名小血管闭塞或大动脉粥样硬化患者在心脏监测期间的室上性异位发生率。二次分析将比较两组之间心脏栓塞的生物标志物，并将室上性异位的发生率与这些生物标志物相关联。具体目标3将验证阵发性室上性心动过速的临床诊断与短暂性脑缺血发作后中风风险相关的假设。这一目标将使用阵发性室上性心动过速的有效ICD-9-CM代码和加利福尼亚州住院患者数据库和急诊科数据库的相关医疗记录来实现。这项拟议的研究具有重要意义，因为阳性结果将揭示新的中风危险因素，而阴性结果将抵消越来越多的未经证实的抗凝剂治疗隐源性中风后非特异性室上性心律失常的标签外使用。这项拟议的研究具有创新性，因为它试图通过确定一大批新的中风高危患者并可能受益于现有的抗凝药物来改变当前的研究和临床实践范式，并寻求通过将心脏病学工具应用于中风研究来架起心脏病学和神经学的桥梁。

项目成果

Stratifying Stroke Risk in Atrial Fibrillation: Beyond Clinical Risk Scores.

• DOI: 10.1161/strokeaha.117.017084
• 发表时间: 2017-10
• 期刊: Stroke
• 影响因子: 8.3
• 作者: Yaghi S;Kamel H
• 通讯作者: Kamel H

Risk of Ischemic Stroke after Intracranial Hemorrhage in Patients with Atrial Fibrillation.

• DOI: 10.1371/journal.pone.0145579
• 发表时间: 2015
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Lerario MP;Gialdini G;Lapidus DM;Shaw MM;Navi BB;Merkler AE;Lip GY;Healey JS;Kamel H
• 通讯作者: Kamel H

Atrial cardiopathy: a broadened concept of left atrial thromboembolism beyond atrial fibrillation.

• DOI: 10.2217/fca.15.22
• 发表时间: 2015-05
• 期刊: Future cardiology
• 影响因子: 1.7
• 作者: Kamel H;Okin PM;Longstreth WT Jr;Elkind MS;Soliman EZ
• 通讯作者: Soliman EZ

Demographic Differences in Catheter Ablation After Hospital Presentation With Symptomatic Atrial Fibrillation.

• DOI: 10.1161/jaha.115.002097
• 发表时间: 2015-09-22
• 期刊: Journal of the American Heart Association
• 影响因子: 5.4
• 作者: Kummer BR;Bhave PD;Merkler AE;Gialdini G;Okin PM;Kamel H
• 通讯作者: Kamel H

Left Atrial Appendage Function and Stroke Risk.

• DOI: 10.1161/strokeaha.115.011273
• 发表时间: 2015-12
• 期刊: Stroke
• 影响因子: 8.3
• 作者: Yaghi S;Song C;Gray WA;Furie KL;Elkind MS;Kamel H
• 通讯作者: Kamel H