Stress and Congestive Heart Failure: A mechanistic clinical trial

项目摘要/摘要 心力衰竭(HF)严重损害了生活质量，每年导致100多万人住院 年。心脏失代偿仍然是住院的最常见原因。医疗保险中心 因此，医疗补助服务将减少心力衰竭住院人数确定为关键优先事项。识别 心力衰竭恶化的沉淀物可以为减少心力衰竭的入院和改善病情提供可行的目标 生活质量。心理应激可诱发心肌缺血、心律失常和左心室 功能障碍--即使在心力衰竭患者中也是如此，我们已经确定了高危人群。此外，针对这个 临床试验中的概况降低了事件风险。研究还表明，慢性心理压力可能会 增加心力衰竭住院的总体风险。缺乏一种非侵入性测量来捕捉心脏 然而，心力衰竭患者的失代偿阻碍了对心理体验的识别 作为急性沉淀物，导致心衰失代偿和住院。当务之急 减少心力衰竭的住院率刺激了技术创新，以捕捉早期代偿阶段 以及更快速的门诊干预。无线血流动力学监测器(例如，心脏微机械系统)就是这样的一种 创新。这些监护仪被植入肺动脉，直接测量肺动脉 压力(PAP)，提供失代偿和住院风险的衡量标准。我们的初步数据显示 PAP在交感神经高度活跃的情况下更高，焦虑和压力也是相关的 具有较高的PAP。因此，越来越多地使用这些监视器提供了一个独特的机会来确定 并对应激可能导致心力衰竭恶化的心力衰竭患者进行风险分层。我们建议利用 这项机械性临床试验中的新技术：(目标1a)确定急性实验室应激对 和(目标1b)确定日常压力和负面情绪与日常PAP的关系 由生态瞬时评估(EMA)捕获。对于目标2，我们将确定压力的关系- 诱导PAP增加导致心力衰竭加重；对于目标3，我们将探索PAP中的异质性标志 对压力的反应，包括疾病严重性、睡眠质量和心理社会因素的标记物，以确定 风险概况。植入心脏MEMS的心衰患者将在实验室应激方案内随机进行 我们已经开发了，在此期间将连续测量PAP。然后患者将完成我们的 基于智能手机应用程序的每日EMA，用于六个月内的压力暴露和负面体验 在临床规定的每日PAP测量期间。患者还将完成对 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 心脏综合征在减少发病率和死亡率方面显示出了希望。这项研究将展示如何 新的心脏微机械系统技术可以帮助确定沉淀剂作为特定患者的可行目标， 从而有助于减少住院，并以患者为中心的更好的结果。

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.