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Bioenergetics and Rehabilitation in Older Patients with Acute Heart Failure

老年急性心力衰竭患者的生物能学和康复

基本信息

批准号：
9267094
负责人：
ANTHONY J MOLINA
金额：
$ 22.93万
依托单位：
WAKE FOREST UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-05-01 至 2019-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9267094
关键词：
Acute Address Affect Aging Ancillary Study Bioenergetics Blood Blood Cells Blood Platelets Cardiac Caring Cells Chronic Clinical Clinical Management Clinical Trials Comorbidity Coupled Data Diagnosis Elderly Environment Event Exercise Exercise stress test Exhibits Fatigue Funding Future Genetic Heart failure Hormones Hospitalization Impairment Inflammation Inflammatory Intervention Intervention Trial Knowledge Lymphocyte Machine Learning Measures Mediating Medical Medicare Mitochondria Modeling Monitor Multi-Institutional Clinical Trial Myocardium Organelles Outcome Oxidation-Reduction Oxygen Consumption Parents Participant Patient-Focused Outcomes Patients Pattern Physical Function Physically Handicapped Physiological Population Protons Quality of life Recovery Recruitment Activity Rehabilitation therapy Reporting Respiration Role Sampling Signal Transduction Skeletal Muscle Stress Syndrome Testing Time Tissues adverse outcome age effect age related base cell type clinical practice cost cost effective cytokine exercise intolerance follow-up functional outcomes high risk improved indexing individual patient insight long-term rehabilitation mitochondrial dysfunction monocyte novel older patient outcome forecast primary outcome programs public health relevance rehabilitation management respiratory success treatment strategy

项目摘要

DESCRIPTION (provided by applicant): Older adults exhibit poor recovery and are at high risk for rehospitalization after acute heart failure. Current rehabilitation and clinical management strategies have shown only modest benefits because the mechanisms underlying poor outcomes remain under recognized and therefore unmitigated. The proposed study will address this critical knowledge gap by examining the role of systemic mitochondrial bioenergetic capacity as a fundamental factor underlying poor physical function in hospitalized acute decompensated heart failure, the success of rehabilitation, and the prognosis of patients following hospitalization. This will be accomplished in a highly translational and cost-effective manner as an ancillary study to REHAB-HF (R01AG045551; PI: Kitzman), a multi-center clinical trial funded by the NIA that tests the hypothesis that impaired physical function underlies adverse outcomes in older hospitalized ADHF patients and employs a novel rehabilitation program that targets multiple domains of physical function for 12 weeks beginning during hospitalization. The results of REHAB-HF can impact clinical practice; however, its outcomes do not directly address potential mechanisms of action. Mitochondrial function is likely candidate for mediating physiological decline in REHAB-HF participants, because these organelles are sensitive to a myriad of intrinsic and extrinsic factors related to aging, physical function, heart failure, and hospitalization. Mitochondrial dysfunction across multiple tissues has been implicated in physiological decline associated with heart failure and is thought to be mediated by circulating factors that affect systemic bioenergetic capacity. Therefore, we propose that respirometric profiling of circulating cells can be used to report on systemic bioenergetic decline in heart failure patients and will be associated with physical function and long term outcomes - including rehospitalization rate. We will determine whether the REHAB-HF rehabilitation program increases bioenergetic capacity, compared to control, thereby improving functional outcomes. Bioenergetic profiling of multiple blood cell populations will enable us to identify the specific cell types and bioenergetic parameters, or patterns comprised of multiple variables, that are most closely associated with REHAB-HF outcomes such as physical function and quality of life. We will also determine the ability of blood cells to report on systemic bioenergetic decline y examining relationships with mitochondrial function measured in skeletal muscle. Successful strategies for mitigating poor physical function and improving long-term outcomes rely on the identification of mechanisms that contribute to the vulnerability of patients after discharge. Bioenergetic profiling may enable the identification of patients in need of more intensive management and targeted rehabilitation. The advancement of blood-based bioenergetic profiling will enhance the use of this promising test in future trials, and potentially, in the cliical care of older patients with the wide range of chronic medical conditions associated with physical disability and poor clinical outcomes.

描述（由申请人提供）：老年人恢复不良，急性心力衰竭后再次住院的风险很高。目前的康复和临床管理策略仅显示出有限的益处，因为不良结果背后的机制仍未得到认识，因此未得到缓解。拟议的研究将通过检查全身线粒体生物能能力作为住院急性失代偿性心力衰竭身体功能不良的基本因素的作用、康复的成功以及住院后患者的预后来解决这一关键的知识差距。这将以高度转化和具有成本效益的方式完成，作为 REHAB-HF（R01AG045551；PI：Kitzman）的辅助研究，REHAB-HF 是一项由 NIA 资助的多中心临床试验，该试验测试了老年住院 ADHF 患者不良后果的基础是身体功能受损的假设，并采用了一种新颖的康复计划，该计划从 12 周开始针对身体功能的多个领域。住院治疗。 REHAB-HF 的结果可以影响临床实践；然而，其结果并不直接涉及潜在的行动机制。线粒体功能可能是介导 REHAB-HF 参与者的生理衰退，因为这些细胞器对与衰老、身体功能、心脏相关的无数内在和外在因素敏感失败并住院。跨多个组织的线粒体功能障碍与心力衰竭相关的生理衰退有关，并且被认为是由影响全身生物能能力的循环因素介导的。因此，我们建议循环细胞的呼吸测量分析可用于报告全身生物能下降在心力衰竭患者中，这与身体功能和长期结果（包括再住院率）相关。我们将确定与对照相比，REHAB-HF 康复计划是否可以提高生物能量能力，从而改善功能结果。多个血细胞群的生物能分析将使我们能够识别与 REHAB-HF 结果（例如身体功能和生活质量）最密切相关的特定细胞类型和生物能参数或由多个变量组成的模式。我们还将通过检查与骨骼肌中测量的线粒体功能的关系来确定血细胞报告全身生物能量下降的能力。减轻身体功能不良和改善长期结果的成功策略依赖于确定导致患者出院后脆弱性的机制。生物能量分析可以识别需要更强化管理和有针对性康复的患者。基于血液的生物能量分析的进步将增强这种有前途的测试在未来试验中的使用，并有可能在老年患者的临床护理中得到应用，这些患者患有与身体残疾和临床结果不佳相关的各种慢性疾病。