Heterogeneity and predictors of stress reactivity in takotsubo syndrome

takotsubo 综合征应激反应的异质性和预测因素

基本信息

批准号：
10117102
负责人：
Elena Salmoirago-Blotcher
金额：
$ 55.6万
依托单位：
MIRIAM HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-03-01 至 2025-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10117102
关键词：
Accounting Acute Address Admission activity Affect Area Arrhythmia Autonomic nervous system Cardiac Cardiovascular system Catecholamines Chronic Clinical Clinical Trials Consensus Diagnosis Disease Echocardiography Electrocardiogram Elements Emotional Enzymes Evaluation Event Exposure to Functional disorder Health Heart Atrium Heterogeneity Hospitals Impairment Individual Intervention Interview Knowledge Laboratories Left Ventricular Function Link Longevity Measures Medical Medical center Methods Modeling Morbidity - disease rate Myocardial Ischemia National Heart, Lung, and Blood Institute Outcome Participant Pathway interactions Patients Persons Physiological Physiology Play Prognosis Protocols documentation Psyche structure Questionnaires Recovery Research Methodology Research Priority Role Stress Stress cardiomyopathy Subgroup Survivors Sympathetic Nervous System Symptoms Syndrome Systolic heart failure Testing Ventricular Ventricular Function Visit acute coronary syndrome age group cerebrovascular clinically relevant coronary lesion data registry design follow-up functional disability heart function hemodynamics high risk improved indexing innovation mortality older women prevent psychologic psychosocial recruit response stress reactivity

项目摘要

PROJECT SUMMARY/ABSTRACT Takotsubo syndrome (TS) is an increasingly recognized condition characterized by acute, reversible systolic heart failure which uniquely affects older women (more than 90% of cases). Although most patients recover after an acute episode, survivors have a high risk of long-term major cerebrovascular events (MACCE) and of chronic impairments of the left ventricular (LV) function. Despite its clinical relevance, important knowledge gaps exist about this interesting and perhaps underappreciated condition. While there is a general consensus that an exaggerated sympathetic nervous system (SNS) discharge is the final common pathophysiologic event that underlies the onset of acute systolic heart failure in TS, this condition has considerable heterogeneity. First, exposure to an emotional trigger was thought to be a defining precipitant of TS, but recent registry data indicate instead that emotional triggers are present only in 1/3 of cases, with physical triggers (1/3) and no triggers (1/3) accounting for the remaining cases. Second, the pathophysiological pathway linking the precipitating trigger to the onset of TS remains to be articulated. Third, it is unclear why certain individuals develop an exaggerated SNS response when exposed to emotional triggers which sooner or later affect all individuals throughout the lifespan with no or limited health consequences. Finally, no study has rigorously tested the contribution of triggering event and mental stress responsiveness to the long-term prognosis of these patients. To address these key evidence gaps we will conduct a mechanistic clinical trial among 246 newly admitted patients with a validated diagnosis of TS from 3 large medical centers in the Providence, RI area. Participants will undergo a comprehensive interview to identify the events proximal to the onset of TS and complete a battery of psychosocial questionnaires 2 weeks after hospital discharge. Approximately 4 weeks after discharge they will undergo a laboratory mental stress protocol previously utilized by our group. Baseline and reactive changes in measures of autonomic nervous system activity (circulating catecholamines and cardiac vagal control), LV function (2D speckle tracking echocardiography (2D-STE)), and hemodynamic parameters will be assessed. LV function and MACCE will be assessed 12 months later. The proposed study will address the noted evidence gaps by a) Rigorously assessing the full range of circumstances proximal to TS onset, b) Assessing the constellation of physiological elements that define TS (autonomic nervous system activity and LV function) under controlled conditions, and c) Link the type of trigger to physiology. Furthermore, by using 2D-STE we will be able to capture both reactive and long-term subtle anomalies of LV function in these patients. This will be the first study to rigorously investigate the heterogeneity in clinical presentation, physiopathology, and prognosis in TS. The identification of distinct sub-groups in TS will provide the rationale for the design and testing of properly targeted interventions to improve the prognosis of these patients.

项目摘要/摘要 Takotsubo综合征（TS）是一种越来越公认的疾病，其特征是急性，可逆的收缩期心力衰竭会影响老年妇女（超过90％的病例）。尽管大多数患者康复急性发作后，幸存者的长期大脑血管事件（MACCE）和左心室（LV）功能的慢性障碍。尽管具有临床意义，但重要的知识关于这种有趣的且可能不足的状况存在差距。虽然有一般共识夸张的交感神经系统（SNS）排出是最终的常见病理生理事件这是TS中急性收缩性心力衰竭的发作，这种情况具有相当大的异质性。首先，被认为是TS的定义悬浮物，但最新的注册表数据被认为是一种定义的诱因。相反，表明情绪触发器仅在1/3的情况下出现，有物理触发器（1/3），没有触发器（1/3）考虑了其余案件。其次，联系了的病理生理途径将TS发作的引发触发尚待阐明。第三，目前尚不清楚为什么某些人当暴露于情感触发器时，会产生夸张的SNS响应，迟早会影响所有人在整个生命周期内没有健康后果的个人。最后，没有严格的研究测试了触发事件和心理压力反应性对长期预后的贡献这些患者。为了解决这些主要证据差距，我们将在246中进行机械临床试验新入院的患者在Providence的3个大型医疗中心对TS进行了验证，RI 区域。参与者将接受全面的采访，以确定接近TS发作的活动并在出院2周后完成一系列的社会心理问卷。大约4个出院几周后，他们将接受我们小组先前使用的实验室心理压力方案。自主神经系统活动量度的基线和反应性变化（循环儿茶酚胺 LV功能（2D斑点跟踪超声心动图（2D-STE））和血液动力学将评估参数。 LV功能和MACCE将在12个月后评估。拟议的研究将通过a）严格评估附近的各种情况来解决著名的证据差距 TS发作，b）评估定义TS的生理元素的星座（自主神经系统活动和LV功能）在受控条件下，c）将触发类型与生理学联系起来。此外，通过使用2D-Ste，我们将能够捕获LV功能的反应性和长期微妙异常这些患者。这将是第一个严格研究临床表现异质性的研究， TS的生理病理学和预后。 TS中不同子组的识别将提供理由为了设计和测试正确靶向的干预措施，以改善这些患者的预后。