Atrial Fibrillation Precursors May Be Novel Stroke Risk Factors

标题：房颤先兆可能是新的卒中危险因素 项目摘要/摘要 这是一份K23重新提交给胡曼·卡迈勒博士的申请，他是一名神经学家和年轻的研究员 开展以患者为中心的心律失常所致缺血性卒中的临床研究。一个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)生物标记物的开发和评估。通过 掌握了这些技能，卡迈勒博士将实现他成为一名独立临床医生的长期职业目标 调查员。为了实现这一目标，卡迈勒博士聘请了一位主要导师理查德·德弗罗博士，他是一名 具有心血管流行病学和心脏诊断技术专业知识的心脏病专家，以及两名共同 导师，米切尔·埃尔金德博士，一位在中风流行病学和临床试验设计方面具有专业知识的神经学家，以及 Costantino Iadecola博士是一位神经学家，在缺血性脑损伤和生物标记物方面拥有专业知识。 根据最近的证据和他自己的初步数据，卡迈勒博士的中心假设是 甚至在房颤/扑动(AF)发展之前，室上性心律失常就增加了中风的风险。 这是目前唯一被认为会导致中风的心律失常。检验这一假说将解决 对哪些室上性心律失常导致中风的认识存在根本差距。直到这一知识 尽管这方面的空白已经填补，但预防心脏病导致中风的最佳战略还不能完全确定。通过 为了实现以下具体目标，申请者将检验他的假设并收集总体数据- 基于室上性心律失常的卒中风险研究(将在R01应用中建议在 K23奖励期)。特殊目标1将检验这样一个假设，即心电图P波离散度和 房电功能障碍的早期标志与室上性心律失常的易感性有关 中风的风险也会增加。这一目标将通过分析没有AF登记在 强心研究，一项以人群为基础的流行病学研究，具有基线心电数据和 &gt；375个已判决和分类的中风病例。《特定目标2》将检验室上性心动过速的假设 异位与隐源性中风有关。在一系列前瞻性登记的患者中， 心脏监测室上性异位在75例不明原因患者中的对比研究 卒中患者75例为卒中小血管闭塞或大动脉粥样硬化。次要的 分析将比较两组之间心脏栓塞的生物标志物，并与 使用这些生物标记物的室上性异位。具体目标3将检验这样的假设：临床诊断 短暂性脑缺血发作后，阵发性室上性心动过速与卒中风险相关。 将使用经验证的ICD-9-CM代码来实现这一目标，用于阵发性室上性心动过速和 来自加利福尼亚州住院病人数据库和急诊科数据库的相关医疗记录。 这项拟议的研究意义重大，因为积极的结果将揭示新的中风风险因素， 虽然阴性结果将抵消越来越多的未经证实的抗凝剂治疗在标签外的使用 不明原因卒中后非特异性室上性心律失常。建议的研究具有创新性。 因为它寻求通过确定一大类新的 中风的高危患者，可能从现有的抗凝药物中受益，并寻求 通过心脏病学工具在中风研究中的新应用，在心脏病学和神经学之间架起桥梁。

TITLE: Atrial Fibrillation Precursors May Be Novel Stroke Risk Factors PROJECT SUMMARY/ABSTRACT 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 cardiac 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 be 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.