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: 10576358
• 负责人: TARUN DASARI
• 金额: $ 21.75万
• 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 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10576358
• 关键词: Activities of Daily Living; Acute; Affect; Age; Aging; Anti-Inflammatory Agents; Atrial Fibrillation; Autonomic nervous system; Blood Vessels; Brain; Cervical; Chronic; Clinical; Complement; Congestive Heart Failure; Data; Devices; Dose; Double-Blind Method; Dyspnea; EFRAC; Endothelium; Equilibrium; Face; Fatigue; Feasibility Studies; Female; Financial Hardship; Frequencies; Functional disorder; Funding Mechanisms; Guidelines; Health; Heart; Heart Rate; Heart failure; Hospitalization; Hour; Human; IL18 gene; IL6 gene; Impairment; Inflammaging; Inflammation; Interleukin-6; Investigation; Light; Limb structure; Measures; Mediating; Medical; 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; Recommendation; 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; brachial artery; carotid sinus; cholinergic; 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.

减少射血分数（HFREF）的心力衰竭是发病率和死亡率的主要原因 美国。衰老和HFREF的独特之处在于它们共同的病理，例如 自主不平衡（同情和副交感降低），炎症 （称为“炎症”）和内皮功能障碍。衰老是敌对的主要危险因素 与HFREF相关的结果。尽管有治疗，大多数HFREF患者仍在继续 经历降低运动能力和生活质量差（QOL）。最近的研究 建议与年龄相关的自主性失衡，创新和内皮功能障碍 可能在HFREF的进展中起着核心作用，支持削弱这些的观念 异常可能有助于改善HFREF的临床结果。我们以前已经证明了 低水平的经特拉格斯刺激（LLTS）改善了自主性失衡和 抑制心房颤动和舒张功能障碍患者的注射并改善 HFREF患者的内皮功能障碍。该提议的总体目的是 检查LLT对锻炼能力和QOL的影响对HFREF患者和 类似地确定了其对核心年龄相关的病理轴的影响 失衡，炎症和内皮功能障碍。我们的具体目的包括：1。检查 间歇性（每天1小时3个月）LLT对运动能力和 与假刺激相对于假刺激的QOL，在HFREF患者中，2。 术语LLT关于自主不平衡（根据心率变异性评估）和炎症 HFREF和3。确定中期LLT对内皮功能的影响 HFREF患者。拟议的概念证明人类可行性研究将提供 在较大的HFREF种群中使用LLT的基础。该提案旨在a）阐明 LLT对年龄相关异常的影响（自主性失衡，炎症和 内皮功能障碍）和HFREF结果的进展（运动能力和QOL）和B） 开发并进一步完善新的疗法，例如LLT，以改善潜在的年龄 相关的演变和临床结果。鉴于较长的数量 目的地治疗继续经历HFREF症状的患者认识到是关键 对这种融资机制的兴趣点，诸如LLT之类的替代新颖方法具有 改善HFREF健康状况的潜力。预计这些调查将 有助于更广泛地了解与年龄相关的自主性失衡，创新和 HFREF中的内皮功能障碍以及如何使用其抑制作用来提供治疗作用。