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。

• 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
• 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

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。衰老和 HFrEF 的独特之处在于它们具有共同的病理学特征，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。衰老是不良反应的主要危险因素 与 HFrEF 相关的结果。尽管接受治疗，大多数 HFrEF 患者仍继续 经历运动能力下降和生活质量 (QoL) 差。最近的研究有 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，支持减弱这些作用的观点 异常可能有助于改善 HFrEF 的临床结果。我们之前已经演示过 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 失衡、炎症和内皮功能障碍。我们的具体目标包括： 1. 检验 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（通过心率变异性评估）和炎症的影响 HFrEF 患者和 3. 确定中期 LLTS 对内皮功能的影响 HFrEF 患者。拟议的概念验证人类可行性研究将提供 在较大的 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- 相关的紊乱和临床结果。鉴于老年人口数量不断增加 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 改善 HFrEF 健康结果的潜力。预计这些调查将 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。