Emotional Stress as a Risk Factor for Arrhythmia: Ischemic and Genetic Mechanisms

情绪压力作为心律失常的危险因素：缺血和遗传机制

• 批准号: 9205533
• 负责人: Amit Jasvant Shah
• 金额: $ 18.78万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-15 至 2019-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9205533
• 关键词: Acute; Adrenergic Agents; Adverse event; Advisory Committees; Affect; Anxiety; Arousal; Arrhythmia; Autonomic nervous system; Biofeedback; Biological Markers; Candidate Disease Gene; Cardiac; Cessation of life; Cholinergic Receptors; Clinical Research; Clinical Trials; Cognitive Therapy; Computer software; Coronary Arteriosclerosis; Coronary Stenosis; Coronary heart disease; Custom; Data; Development; Electrocardiogram; Electrophysiology (science); Emotional; Emotional Stress; Emotions; Epidemiology; Evaluation; Event; Exercise; Frequencies; Future; Genetic; Genetic Markers; Genetic Polymorphism; Genetic Predisposition to Disease; Genotype; Goals; Heart Diseases; Individual; Intervention; Investigation; Ischemia; K-Series Research Career Programs; Knowledge; Laboratories; Lead; Learning; Measures; Medical center; Medicine; Mental Depression; Mentors; Mentorship; Molecular Target; Myocardial Infarction; Myocardial Ischemia; Myocardial perfusion; Natural Disasters; Norepinephrine; Paper; Parents; Pathology; Patient risk; Patients; Perfusion; Peripheral; Phase; Phenotype; Physiological; Play; Populations at Risk; Predictive Value; Preventive; Psyche structure; Psychiatrist; Psychological Stress; Research; Research Personnel; Risk; Risk Factors; Scholarship; Serum; Stress; Stress Tests; Surrogate Markers; Testing; Training; Training Programs; United States National Institutes of Health; Universities; Ventricular Arrhythmia; Vertebral column; Viola; Withdrawal; arterial tonometry; base; beta-adrenergic receptor; biological adaptation to stress; career; cholinergic; clinically significant; cohort; diaries; digital; effective therapy; experience; fighting; follow-up; genome wide association study; genome-wide; genomic data; heart rate variability; high risk; novel; nuclear imaging; patient oriented; patient oriented research; perfusion imaging; personalized intervention; professor; prognostic significance; prognostic value; psychologic; public health relevance; radiologist; rare variant; receptor; response; signal processing; single photon emission computed tomography; skills; stress reactivity; vasoconstriction

 DESCRIPTION (provided by applicant): This is a revised application for a K23 Career Development award for Dr. Amit Shah, Assistant Professor of Epidemiology and Medicine at Emory University, and preventive cardiologist at the Atlanta VA Medical Center. Dr. Shah is establishing himself as a young investigator in patient-oriented clinical research. This K23 will provide Dr. Shah with support necessary to accomplish the following goals: (1) to become an expert in signal processing of electrocardiogram (ECG) data, including the use of custom and commercial software to derive heart rate variability (HRV), T-wave alternans (TWA), and spatial QRS-T angle (SA); (2) learn, through formal didactics and hands on experience, the necessary skills to evaluate genetic and ischemic determinants of arrhythmia risk due to acute emotional stress; and (3) learn core clinical research skills to plan and execute patient-oriented studies, including hands-on training with patients in the clinical research lab. Dr. Shah has assembled a mentoring team comprised of a primary mentor, Dr. Viola Vaccarino, Chair of Epidemiology, and renown expert on psychological risk factors of heart disease, and 2 co-mentors who are long-standing collaborators with Dr. Vaccarino, including Dr. Rachel Lampert, a Yale electrophysiologist who is an expert in emotional determinants of arrhythmia, and Dr. J Douglas Bremner (co-mentor), an Emory psychiatrist and radiologist with expertise in nuclear imaging and traumatic stress. The epidemiology, mechanisms, and therapies for emotionally-triggered arrhythmia are difficult to study because many ventricular arrhythmias are fatal. As a solution to this conundrum, Dr. Shah proposes to study surrogate ECG markers of arrhythmia during laboratory-induced acute mental stress in a large study of nearly 1,000 CHD patients led by his mentor, Dr. Vaccarino (R01 HL109413), and advisor, Dr. Quyyumi (P01 HL101398). In this well-characterized, genotyped and phenotyped cohort, he will study the relationships of autonomic modulation during stress and mental stress ischemia with arrhythmia risk during stress (T-wave alternans and spatial QRS-T angle) in Aim 1. Specifically, he will evaluate to what extent electrical instability may develop due to parasympathetic withdrawal (reduced HRV), and sympathetic activation (increased norepinephrine and vasoconstriction). To assess potential molecular targets and better risk stratify high-risk subjects, he will study select adrenergic/cholinergic genetic receptor polymorphisms that may influence electrical instability during mental stress (Aim 2). Finally, in aim 3, he will evaluate the prognostic value of stress reactivity based on autonomic and electrophysiologic measures under study towards major adverse cardiac events and death. Overall, this research will form the basis for larger studies that systematically evaluate risk prediction strategies and possible treatments such as cognitive therapy and biofeedback in CHD patients.

 描述（由申请人提供）：这是为 Amit Shah 博士申请 K23 职业发展奖的修订申请，Amit Shah 博士是埃默里大学流行病学和医学助理教授，也是亚特兰大 VA 医疗中心的预防心脏病专家。作为以患者为导向的临床研究的年轻研究者，该 K23 将为 Shah 博士提供实现以下目标所需的支持：(1) 成为心电图 (ECG) 数据信号处理（包括使用）的专家。使用定制和商业软件来导出心率变异性 (HRV)、T 波交替 (TWA) 和空间 QRS-T 角度 (SA)；(2) 通过正式教学和实践经验学习评估所需的必要技能；急性情绪压力导致心律失常风险的遗传和缺血性决定因素；(3) 学习核心临床研究技能，以计划和执行以患者为导向的研究，包括在临床研究实验室对患者进行实践培训。导师团队由一位主要导师 Viola Vaccarino 博士（流行病学主席、心脏病心理危险因素方面的著名专家）和 2 位共同导师组成，他们是 Vaccarino 博士的长期合作者，其中包括耶鲁大学的 Rachel Lampert 博士电生理学家，心律失常的情绪决定因素方面的专家，J Douglas Bremner 博士（共同导师），埃默里大学的精神病患者和放射科医生，在核成像和创伤应激方面具有专业知识。情绪引发的心律失常的流行病学、机制和治疗方法很难研究，因为许多室性心律失常是致命的。作为解决这一难题的方法，Shah 博士建议研究实验室诱发的急性精神应激期间心律失常的替代心电图标记。由他的导师 Vaccarino 博士 (R01 HL109413) 领导的针对近 1,000 名先心病患者的大型研究，以及顾问 Quyyumi 博士 (P01 HL101398) 在这个特征明确、基因分型和表型分型的队列中，他将研究压力和精神压力缺血期间的自主调节与压力期间心律失常风险的关系（T 波交替和空间 QRS-T）。目标 1 中的角度）。具体而言，他将评估由于副交感神经退缩（HRV 降低）和交感神经激活而导致电不稳定的程度（去甲肾上腺素和血管收缩增加）。为了评估潜在的分子目标并更好地对高危受试者进行风险分层，他将研究可能影响精神压力期间电不稳定的选定肾上腺素能/胆碱能遗传受体多态性（目标 2）。他将根据正在研究的自主神经和电生理测量来评估应激反应对主要不良心脏事件和死亡的预后价值。总体而言，这项研究将为更大规模的研究奠定基础。系统评估冠心病患者的风险预测策略和可能的治疗方法，例如认知疗法和生物反馈。