PRIME HRrEF: Novel Exercise for Older Patients with Heart Failure with Reduced Ejection Fraction

PRIME HRrEF：针对射血分数降低的老年心力衰竭患者的新型运动

基本信息

批准号：
10521639
负责人：
Jason David Allen
金额：
$ 62.2万
依托单位：
UNIVERSITY OF VIRGINIA
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：
2022-08-01 至 2027-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10521639
关键词：
Activities of Daily Living Address Adherence Adult Aerobic Age Aging American Anaerobic Threshold Beds Biogenesis Biopsy Blood Blood Pressure Blood flow Bone Density Bone Mineral Contents Cardiac Cardiovascular system Cessation of life Clinical Clinical Trials Design Control Groups Data Diagnosis Direct Costs EFRAC Elderly Enrollment Ergometry Exercise Exercise Test Exhibits Facilities and Administrative Costs Failure Fatigue Fiber Functional disorder Goals Guidelines Health Health Professional Heart failure High Prevalence Hospitalization Hybrids Impairment Individual Intervention Mediator of activation protein Mind Mitochondria Modality Muscle Muscular Atrophy Musculoskeletal Near-Infrared Spectroscopy Outcome Outcome Measure Participant Patients Perfusion Peripheral Persons Physical Fitness Physical Function Physical activity Population Procedures Prognosis Publications Quality of life Questionnaires Randomized Randomized Controlled Trials Recommendation Resistance Rest Risk Serum Markers Severities Shortness of Breath Skeletal Muscle Stimulus Stress Supervision Therapeutic Tissues Training Treatment Cost Walking Woman Workload actigraphy bone cohort comorbidity design exercise capacity exercise intolerance exercise program exercise rehabilitation exercise training experience fiber cell fitness fitness test follow-up functional disability functional independence hemodynamics human old age (65+)improved indexing insight interest men mortality muscle metabolism muscle strength myogenesis novel older patient pilot test primary outcome prognosis biomarker programs reduced muscle mass sarcopenia satellite cell strength training tonometry

项目摘要

Abstract. Heart failure (HF) is the leading cause of hospitalization among Americans ≥65 years old with 5.7 million sufferers and an annual of ~$39.2 billion. Patients with HF suffer from shortness of breath, fatigue and exercise intolerance. Improving VO2peak is an important clinical goal in HF as it is correlated with reduced mortality rate and increased quality of life. Exercise rehabilitation is considered class IA recommendation for people with HF, with guidelines recommending moderate-intensity aerobic modalities, often in conjunction with resistance training (AT+RT). A key limitation of these guidelines is that they arise largely from data involving a patient cohort sometimes two decades younger (range 51-81 yrs) than the median age of diagnosis for HF (77 yrs). Considering that older adults with HF experience a high prevalence of co-morbidities, impaired functional capacity, reduced muscle mass and strength, and a 5-year survival of 25%, it is unclear whether the current exercise guidelines can be tolerated by and generate functional benefits by a majority real-world HF patients. It is well accepted that impairments in peripheral tissues including; decreased muscle blood flow, decreased muscle mass, and abnormal muscle metabolism have a significant contribution to the reduced exercise capacity in patients with HF. In fact, many older patients with HF exhibit the sequelae of sarcopenia, which independently carries an ominous prognosis. Accordingly, we have developed and pilot tested the “Peripheral Remodelling via Intermitted Muscular Exercise” (PRIME) approach. PRIME offers a low mass, high repetition, localised stimulus to peripheral muscles and tissues, without imposing central cardiorespiratory strain. In an exploratory study which informed the current proposal, 19 subjects with HFrEF (>65yr, VO2peak=13.5ml/kg/min) increased VO2peak, anaerobic threshold and maximal strength with 4 weeks of PRIME followed by 4 weeks of AT+RT. The “control” group performed AT+RT for the whole 8 weeks and only increased maximal strength. We propose to expand on this promising data to definitively determine in an intent-to-treat trial enrolling 92 patients with HFrEF randomized to either: (A) 4 weeks of PRIME followed by 8 weeks of AT+RT, or: (B) 12 weeks of AT+RT. Data at baseline and following the 12-week interventions will be used to determine; (Aim1) group changes in VO2peak during maximal cycle exercise (secondary clinical outcomes of muscle strength and activities of daily living); (Aim2) group changes in central and peripheral hemodynamics and tissue perfusion. Exploratory aims will examine blood markers of CHF severity, questionnaires for quality of life and skeletal muscle mediators of VO2peak (opt-in biopsy). We will perform a 6-month post training assessment for durability of any changes in fitness and function. This study represents an important step in closing the age-bias seen in clinical exercise studies. If PRIME is shown to benefit elderly patients with HFrEF it may better inform exercise rehabilitation guidelines for these individuals.

抽象的。心力衰竭 (HF) 是 65 岁以上美国人住院的主要原因，有 570 万人每年约有 392 亿美元的心力衰竭患者遭受呼吸急促、疲劳和运动的困扰。改善 VO2peak 是心力衰竭的一个重要临床目标，因为它与降低死亡率相关。运动康复被认为是心力衰竭患者的 IA 级建议，指南建议中等强度的有氧运动，通常与阻力结合使用这些指南的一个关键限制是它们主要来自涉及患者的数据。有时队列比心力衰竭诊断中位年龄（77 岁）年轻 20 岁（范围 51-81 岁）。考虑到患有心力衰竭的老年人普遍存在合并症、功能障碍能力、肌肉质量和力量减少，以及 25% 的 5 年生存率，目前尚不清楚当前是否运动指南可以被大多数现实世界的心力衰竭患者所耐受并产生功能益处。人们普遍认为，外周组织的损伤包括：肌肉血流量减少，肌肉质量和肌肉代谢异常对运动能力下降有显着影响事实上，许多老年心力衰竭患者都表现出肌肉减少症的后遗症，这些后遗症是独立的。因此，我们开发并试点了“外围重塑”。通过间歇性肌肉锻炼”（PRIME）方法提供低质量、高重复、局部的锻炼。刺激周围肌肉和组织，而不施加中枢心肺压力。为当前提案提供信息的研究显示，19 名 HFrEF 受试者（>65 岁，VO2peak=13.5ml/kg/min）增加 4 周 PRIME，随后 4 周 AT+RT 的 VO2peak、无氧阈值和最大强度。 “对照组”进行了整整8周的AT+RT，仅增加了最大强度。我们建议扩展这一有希望的数据，以最终确定意向治疗试验的入组情况 92 HFrEF 患者随机接受：(A) 4 周 PRIME，随后 8 周 AT+RT，或：(B) 12 基线和 12 周干预后的数据将用于确定（目标 1）；最大周期运动期间摄氧量峰值的组变化（肌肉力量和肌肉力量的次要临床结果）（目标2）组中枢和外周血流动力学和组织灌注的变化。探索性目标将检查CHF严重程度的血液标志物、生活质量和骨骼的调查问卷 VO2peak 的肌肉调节剂（选择加入活检）我们将进行 6 个月的训练后耐久性评估。健康和功能的任何变化。这项研究代表了消除临床运动研究中年龄偏见的重要一步。研究表明对患有 HFrEF 的老年患者有益，它可以更好地为这些患者提供运动康复指南个人。