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

• 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
• 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

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。 在65岁的美国人中，心力衰竭(HF)是住院的主要原因，≥有570万 患者和每年约392亿美元的收入。心力衰竭患者出现呼吸急促、疲劳和运动。 不宽容。改善VO2峰值是治疗心力衰竭的一个重要临床目标，因为它与降低死亡率有关 并提高了生活质量。运动康复被认为是对心力衰竭患者的IA级推荐， 指南建议进行中等强度的有氧运动，通常与阻力相结合 训练(AT+RT)。这些指南的一个关键局限性是，它们主要来自涉及患者的数据 队列有时比诊断为心衰的中位年龄(77岁)年轻20岁(51-81岁)。 考虑到患有心力衰竭的老年人有很高的共病患病率，功能受损 能力、肌肉质量和力量减少，以及25%的5年存活率，目前尚不清楚 运动指南可以被大多数现实世界中的心衰患者所容忍并产生功能上的好处。 人们普遍认为，周围组织的损伤包括：肌肉血流量减少， 肌肉质量和肌肉代谢异常是运动能力下降的重要原因 在心力衰竭患者中。事实上，许多患有心力衰竭的老年患者表现出石棺减少的后遗症，这种后遗症是独立的 会带来不祥的预后。因此，我们开发并试行了“外围设备改造” 通过间歇性肌肉锻炼“(PRIME)方法。Prime提供低质量、高重复性、本地化的 刺激外周肌肉和组织，不会造成中枢性心肺压力。在探索性的 提供当前建议的研究表明，19名HFrEF受试者(65岁，VO2峰值=13.5ml/kg/min)增加 4周的Prime和AT+RT的VO2峰值、无氧阈值和最大强度。这个 对照组在整个8周进行AT+RT，仅增加最大力量。 我们建议对这一有希望的数据进行扩展，以最终确定在一项意向治疗试验中登记92人 患有HFrEF的患者被随机分为：(A)4周的PRIME+8周的AT+RT，或(B)12周 持续数周的AT+RT。将使用基线和12周干预后的数据来确定；(Aim1) 极量周期运动期间VO2峰值的组变化(次要临床结果为肌力和 日常生活活动能力)；(AIM2)组中枢和外周血流动力学及组织灌注量的变化。 探索性目标将检查充血性心力衰竭严重程度的血液标记物、生活质量问卷和骨骼 VO2峰值肌肉介质(Opt-in活检)。我们将进行为期6个月的耐用性培训后评估 体能和机能方面的任何变化。 这项研究是结束临床运动研究中出现的年龄偏见的重要一步。如果Prime是 研究表明，HFrEF对老年患者有益，可能会更好地为这些患者提供运动康复指南 个人。