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

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

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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（由适用提供）：老年人暴露于恢复不良，并且在急性心力衰竭后处于重新宿舍的高风险。当前的康复和临床管理策略仅显示出适度的益处，因为较差结果的机制仍然被认识到，因此无法避免。拟议的研究将通过研究系统性线粒体生物能力作为住院治疗急性失败的心力衰竭，康复的成功和住院后患者预后的身体机能不佳的基本因素来解决这一关键知识差距。这将以高度翻译和具有成本效益的方式作为辅助研究（R01AG045551; PI：Kitzman），这是一项由NIA资助的多中心临床试验，该试验测试了该假设，该假设损害了年龄较大的ADHF患者的身体功能，该假设损害了较老的ADHF患者的广告，该功能是针对多个小型造成的，该功能是针对多个小型造成的，该功能是针对多重造成的，该功能是针对多重造成的，该功能是针对多重造成的。康复-HF的结果会影响临床实践；但是，其结果并不能直接解决潜在的作用机理。线粒体功能可能是候选的介导康复参与者的身体下降，因为这些细胞器对与衰老，身体机能，心脏有关的无数内在和外在因素敏感失败和住院。在与心力衰竭相关的身体下降方面已经实施了多个时机的线粒体功能障碍，并被认为是由影响全身生物能力的循环因素介导的。因此，我们提出，循环细胞的呼吸测量值可用于报告全身生物能下降在心力衰竭患者中，将与身体机能和长期结局有关 - 包括重新宿主率。我们将确定与对照相比，康复康复计划是否会增加生物能力，从而提高功能结果。多个血细胞群体的生物能分析将使我们能够识别特定的细胞类型和生物能参数，或包括多个变量的模式，这些变量与康复-HF结果（例如身体功能和生活质量）最紧密相关。我们还将确定血细胞报告有关系统性生物能下降的能力y检查与骨骼肌中线粒体功能的关系。减轻身体机能不佳和改善长期结局的成功策略取决于鉴定出院后患者脆弱性的机制。生物能分析可以使需要更密集管理和有针对性康复的患者鉴定。基于血液的生物能分析的进步将增强在未来的试验中使用该有前途的测试，并且可能在具有与身体残疾和临床不良结局相关的慢性病范围广泛的老年患者的克利克护理中。