Neuromodulation of inflammation and endothelial function to treat elderly patients with systolic heart failure.

炎症和内皮功能的神经调节治疗老年收缩性心力衰竭患者。

基本信息

批准号：
10353835
负责人：
TARUN DASARI
金额：
$ 17.9万
依托单位：
UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-03-01 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10353835
关键词：
Activities of Daily Living Acute Affect Age Aging Anti-Cholinergics Anti-Inflammatory Agents Atrial Fibrillation Attenuated Autonomic nervous system Blood Vessels Brain Cervical Chronic Clinical Complement Data Dose Double-Blind Method Dyspnea EFRAC Endothelium Equilibrium Face Failure Fatigue Feasibility Studies Female Financial Hardship Frequencies Functional disorder Funding Mechanisms Guidelines Health Heart Heart Rate Heart failure Hospitalization Hour Human IL6 gene Impairment Inflammaging Inflammation Interleukin-18 Interleukin-6 Investigation Lead Light Limb structure Measures Mediating Medical Medical Device Minnesota Modality Morbidity - disease rate Nerve Nitric Oxide Operative Surgical Procedures Outcome Painless Pathologic Pathology Pathway interactions Patients Pharmaceutical Preparations Pharmacotherapy Pilot Projects Play Polypharmacy Population Pressoreceptors Process Property Publishing Quality of life Questionnaires Randomized Risk Factors Role Serum Symptoms Systolic heart failure TNF gene Techniques Testing Therapeutic Effect Time Tragus United States Vagus nerve structure Vasodilation Walking Withdrawal adverse outcome age related antagonist base brachial artery carotid sinus clinical biomarkers comorbidity endothelial dysfunction exercise capacity experience feasibility trial follow-up health related quality of life heart rate variability implantable device improved inflammatory marker interest male mortality neuroregulation non-compliance novel novel strategies novel therapeutics older patient recruit sex side effect symptomatic improvement therapeutic target vagus nerve stimulation valsartan

项目摘要

Heart failure with reduced ejection fraction (HFrEF) is a major cause of morbidity and mortality in United States. Aging and HFrEF are unique in that they share common pathologies, such as autonomic imbalance (increased sympathetic and reduced parasympathetic tone), inflammation (termed “inflammaging”) and endothelial dysfunction. Aging is a major risk factor for adverse outcomes associated with HFrEF. Despite treatment, majority of HFrEF patients continue to experience reduced exercise capacity and poor quality of life (QoL). Recent studies have suggested that age-associated autonomic imbalance, inflammation and endothelial dysfunction may play a central role in the progression of HFrEF, supporting the notion that attenuating these abnormalities may help improve clinical outcomes in HFrEF. We have previously demonstrated that low level transcutaneous tragus stimulation (LLTS) improves autonomic imbalance and suppresses inflammation in patients with atrial fibrillation and diastolic dysfunction and improved endothelial dysfunction in patients with HFrEF. The overall objective of this proposal is to examine the effects of LLTS on exercise capacity and QoL in patients with HFrEF and simultaneously determine its impact on the core age-related pathologic axes, autonomic imbalance, inflammation and endothelial dysfunction. Our specific aims include: 1. To examine the medium-term effect of intermittent (1-hour daily for 3 months) LLTS on exercise capacity and QoL, relative to sham stimulation, in patients with HFrEF, 2. To determine the effects of medium- term LLTS on autonomic imbalance (assessed by heart rate variability) and inflammation in patients with HFrEF and 3. To determine the effects of medium-term LLTS on endothelial function in patients with HFrEF. The proposed proof-of-concept human feasibility study will provide the basis for using LLTS among larger HFrEF populations. This proposal intends to a) elucidate the effects of LLTS on age-related abnormalities (autonomic imbalance, inflammation and endothelial dysfunction) and progression of HFrEF outcomes (exercise capacity and QoL) and b) develop and further refine novel therapies, such as LLTS, to ameliorate the underlying age- associated derangements and clinical outcomes. In light of the increasing number of elderly patients who, despite treatment, continue to experience HFrEF symptoms, recognized is a key point of interest in this funding mechanism, an alternative novel approach such as LLTS has the potential to improve health outcomes in HFrEF. It is anticipated that these investigations will contribute to a broader understanding of age-associated autonomic imbalance, inflammation and endothelial dysfunction in HFrEF and how its inhibition can be used to provide therapeutic effects.

射血分数降低的心力衰竭（HFrEF）是导致患者发病和死亡的主要原因美国的老龄化和 HFrEF 的独特之处在于它们具有共同的病理特征，例如自主神经失衡（交感神经增加和副交感神经紧张减少）、炎症（称为“炎症”）和内皮功能障碍是不良反应的主要危险因素。尽管接受了治疗，大多数 HFrEF 患者仍然存在与 HFrEF 相关的结果。最近的研究表明，运动能力下降和生活质量 (QoL) 较差。表明与年龄相关的自主神经失衡、炎症和内皮功能障碍可能在 HFrEF 的进展中发挥核心作用，支持减弱这些我们之前已经证明，异常可能有助于改善 HFrEF 的临床结果。低水平经皮耳屏刺激 (LLTS) 可改善自主神经失衡抑制房颤和舒张功能障碍患者的炎症并改善 HFrEF 患者的内皮功能障碍该提案的总体目标是检查 LLTS 对 HFrEF 患者运动能力和生活质量的影响同时确定其对与年龄相关的核心病理轴、自主神经轴的影响我们的具体目标包括： 1. 检查。间歇性（每天 1 小时，持续 3 个月）LLTS 对运动能力的中期影响相对于假刺激，HFrEF 患者的生活质量，2. 确定中度刺激的效果术语 LLTS 对自主神经失衡（通过心率失衡变异性进行评估）和炎症的影响 HFrEF 患者和 3. 确定中期 LLTS 对内皮功能的影响拟议的概念验证人体可行性研究将提供在较大 HFrEF 人群中使用 LLTS 的基础该提案旨在 a) 阐明。 LLTS 对年龄相关异常（自主神经失衡、炎症和内皮功能障碍）和 HFrEF 结果的进展（运动能力和生活质量）和 b) 开发并进一步完善新疗法，例如 LLTS，以改善潜在的年龄- 鉴于老年人数量不断增加，相关的紊乱和临床结果。对于尽管接受治疗但仍持续出现 HFrEF 症状的患者，认识到这一点是关键这种融资机制的兴趣点是，另一种新颖的方法（例如 LLTS）具有预计这些研究将改善 HFrEF 的健康结果。有助于更广泛地了解与年龄相关的自主神经失衡、炎症和 HFrEF 中的内皮功能障碍以及如何通过抑制其来提供治疗效果。