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：
10673759
负责人：
Jason David Allen
金额：
$ 61.19万
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/10673759
关键词：
Activities of Daily Living Address Adherence Adult Aerobic Aerobic Exercise Age Aging American Anaerobic Threshold Aorta Beds Biogenesis Biopsy Blood Blood Pressure Blood flow Bone Density Bone Mineral Contents Capillarity Cardiac Cardiovascular system Cessation of life Classification Clinical Clinical Trials Design Control Groups Data Diagnosis Direct Costs EFRAC Elderly Ergometry Exercise Exercise Test Exhibits Facilities and Administrative Costs Fatigue Fiber Functional disorder Goals Guidelines Health Health Professional Heart failure High Prevalence Hospitalization Hybrids Impairment Individual Intervention Mediator 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 Therapeutic Tissues Training Treatment Cost Walking Woman Workload actigraphy bone cohort comorbidity design exercise capacity exercise intolerance exercise prescription exercise program exercise rehabilitation exercise training experience 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 resistance exercise sarcopenia satellite cell tonometry trial enrollment

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岁的美国人住院的主要原因，570万患者，年度约392亿美元。 HF患者呼吸急促，疲劳和运动不宽容。改善VO2PEAK是HF的重要临床目标，因为它与死亡率降低相关并提高生活质量。运动康复被认为是针对HF患者的IA类建议有了建议现代强度有氧方式的指南，通常与阻力结合使用培训（在+RT）。这些准则的关键限制是它们主要来自涉及患者的数据队列有时比HF的诊断中位年龄（77岁）年轻二十年（范围51 - 81年）。考虑到HF患有HF的老年人的合并症患病率很高，功能受损容量，肌肉质量和力量降低，5年生存率为25％，目前尚不清楚大多数现实世界中的HF患者可以忍受运动指南并产生功能益处。公认的是外周组织中的损害，包括：减少肌肉血流，减少肌肉质量和异常肌肉代谢对降低运动能力有很大的贡献在HF患者中。实际上，许多HF患者表现出肌肉减少症的后遗症具有可观的预后。根据，我们已经开发并试点测试了“外围重塑通过互动的肌肉运动”（PRIME）方法。Prime提供低质量，高度重复，本地化刺激周围肌肉和组织，而不施加中央心脏呼吸菌株。在探索性中告知当前建议的研究，有19名HFREF的受试者（> 65yr，vo2peak = 13.5ml/kg/min）增加 VO2PEAK，厌氧阈值和最大强度为4周，然后为4周+RT。这 “控制”组在整个8周内进行+RT进行，仅提高了最大强度。我们建议扩展此承诺数据，以在注册的意图对治疗试验中明确确定92 HFREF的患者随机分配给：（a）4周的素数，然后是8周的+rt，或：（b）12 AT+RT的几周。基线和12周的干预措施的数据将用于确定；（AIM1）在最大周期运动中VO2PEAK的群体变化（肌肉力量的继发临床结果和日常生活的活动）；（AIM2）中央血流动力学和组织灌注的组变化。探索目的将检查CHF严重性的血液标记，生活质量和骨骼的问卷调查 VO2PEAK的肌肉介体（选择加入活检）。我们将对耐用性进行6个月的培训后6个月健身和功能的任何变化。这项研究代表了结束临床运动研究中看到的年龄偏见的重要一步。如果是Prime 证明有益于老年患者患有HFREF的患者，可以更好地告知锻炼康复指南个人。