Stress and Congestive Heart Failure: A mechanistic clinical trial

压力和充血性心力衰竭：机械临床试验

• 批准号: 10200143
• 负责人: Matthew M Burg
• 金额: $ 72.76万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10200143
• 关键词: Acute; Admission activity; Anger; Anxiety; Arrhythmia; Biological Markers; Cardiac; Cardiovascular system; Chronic; Chronic stress; Clinical; Clinical Trials; Congestive Heart Failure; Data; Devices; Disease Marker; EFRAC; Ecological momentary assessment; Emotions; Event; Heart failure; Heterogeneity; Hospital Costs; Hospitalization; Hostility; Impairment; Implant; Intervention; Laboratories; Left Ventricular Dysfunction; Life; Measurement; Measures; Medical; Mental Depression; Monitor; Morbidity - disease rate; Myocardial Ischemia; Outpatients; Patient-Focused Outcomes; Patients; Pharmacology; Physiological; Predisposition; Protocols documentation; Psyche structure; Psychological Stress; Psychosocial Assessment and Care; Psychosocial Factor; Pulmonary artery structure; Quality of life; Randomized; Research; Risk; Severity of illness; Signal Transduction; Stress; Syndrome; Technology; United States Centers for Medicare and Medicaid Services; Wireless Technology; acute stress; base; clinically significant; experience; hemodynamics; high risk; improved; innovation; mortality; new technology; preservation; pressure; prevent; psychologic; response; risk stratification; sleep quality; smartphone Application; technological innovation

Project Summary/Abstract Heart failure (HF) significantly impairs quality of life and contributes to over 1 million hospital admissions per year. Cardiac decompensation remains the most frequent cause of hospitalization. The Centers for Medicare and Medicaid Services has thus identified decreasing heart failure hospitalizations as a key priority. Identifying precipitants of HF exacerbation could provide actionable targets for reducing HF admissions and improving QOL. Psychological stress can precipitate myocardial ischemia, cardiac arrhythmia, and left ventricular dysfunction - even in patients with HF, and we have identified a high-risk profile. Furthermore, targeting this profile in clinical trials has reduced event risk. Studies also show that chronic psychological stress may increase overall risk for HF hospitalization. The absence of a non-invasive metric that captures cardiac decompensation in HF patients has however, impeded the identification of psychological experiences as acute precipitants that contribute to HF decompensation and hospitalization. The imperative to reduce HF hospitalizations has spurred technological innovations to capture early stages of decompensation and more rapid outpatient interventions. The wireless hemodynamic monitor (e.g., CardioMEMS,) is one such innovation. These monitors are implanted in the pulmonary artery and directly measure pulmonary artery pressure (PAP), providing a metric of decompensation and hospitalization risk. Our preliminary data suggest that PAP is higher in situations of high sympathetic activity, and that anxiety and stress are also associated with higher PAP. The increasing use of these monitors thus provides a unique opportunity to identify and risk stratify HF patients for whom stress may contribute to HF exacerbation. We propose to leverage this new technology in a mechanistic clinical trial to: (Aim 1a) determine the effect of acute laboratory stress on momentary PAP, and (Aim 1b) determine the relationship of daily stress and negative emotion to daily PAP as captured by ecological momentary assessment (EMA). For Aim 2 we will determine the relationship of stress- induced PAP increase to HF exacerbation; and for Aim 3 we will explore markers of heterogeneity in the PAP response to stress, including markers of disease severity, sleep quality, and psychosocial factors to identify a risk profile. CardioMEMS-implanted HF patients will be randomized within the laboratory stress protocol that we have developed, during which PAP will be measured continuously. Patients will then complete our smartphone 'app' based, daily EMA for stress exposures and negative experiences over a six-month period during clinically prescribed daily measurement of PAP. Patients will also complete assessment of psychosocial factors and related biomarkers of stress susceptibility. Clinical trials targeting stress induced cardiac syndromes have shown promise for reducing morbidity and mortality. This study will demonstrate how the new CardioMEMS technology can help identify precipitants as actionable targets for specific patients, thereby contributing to reduced hospitalization, and better patient centered outcomes.

项目总结/摘要 心力衰竭（HF）严重损害生活质量，每年导致超过100万例住院。 年心脏失代偿仍然是最常见的住院原因。医疗保险中心 因此，Medicaid Services已经将减少心力衰竭住院确定为关键优先事项。识别 HF恶化的促发因素可以为减少HF入院和改善 生活质量。心理应激可诱发心肌缺血、心律失常和左心室肥厚。 功能障碍-即使在HF患者中，我们已经确定了高风险特征。此外，针对这一 在临床试验中的特征降低了事件风险。研究还表明，长期的心理压力可能 增加HF住院的总体风险。缺乏一个非侵入性的指标，捕捉心脏 然而，HF患者的失代偿阻碍了对心理经历的识别， 作为导致HF失代偿和住院的急性沉淀物。的必要性 减少HF住院刺激了技术创新，以捕获失代偿的早期阶段 以及更快速的门诊干预。无线血液动力学监测器（例如，MEMS）就是这样一种 创新这些监测器植入肺动脉，直接测量肺动脉 压力（PAP），提供失代偿和住院风险的度量。我们的初步数据显示 PAP在交感神经活性高的情况下更高，焦虑和压力也与之相关， 更高的PAP因此，越来越多地使用这些监测器提供了一个独特的机会， 和风险分层的HF患者的压力可能会导致HF恶化。我们建议利用 这项新技术在一项机械临床试验中：（目的1a）确定急性实验室应激对 瞬时PAP，（目的1b）确定日常压力和负面情绪与日常PAP的关系， 生态瞬时评估（EMA）。对于目标2，我们将确定应力的关系- 诱导PAP升高至HF加重;对于目标3，我们将探索PAP异质性的标志物 对压力的反应，包括疾病严重程度、睡眠质量和心理社会因素的标志，以确定 风险概况。植入MEMS的HF患者将在实验室应激方案中随机分组， 在此期间，PAP将被连续测量。患者将完成我们的 基于智能手机“应用程序”的每日EMA，针对六个月期间的压力暴露和负面体验 在临床规定的PAP每日测量期间。患者还将完成以下评估： 心理社会因素和应激易感性的相关生物标志物。针对应激诱导的临床试验 心脏综合征显示出降低发病率和死亡率的希望。这项研究将展示如何 新的MEMS技术可以帮助识别沉淀物作为特定患者的可操作目标， 从而有助于减少住院和更好的以患者为中心的结果。