Bioenergetics and Rehabilitation in Older Patients with Acute Heart Failure

 描述(由申请人提供)：老年人表现出较差的恢复，在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只显示了不大的好处，因为导致不良结果的机制仍然没有得到承认，因此没有得到缓解。这项拟议的研究将通过检查系统性线粒体生物能量能力作为住院急性失代偿性心力衰竭患者身体功能低下的根本因素、康复的成功以及患者住院后的预后来解决这一关键知识差距。这将作为Rehab-HF(R01AG045551；PI：Kitzman)的一项辅助研究，以高度翻译和成本效益的方式实现。Rehab-HF是一项由NIA资助的多中心临床试验，测试身体功能受损是老年ADHF患者不良后果的假设，并采用一种新的康复计划，从住院期间开始，针对多个身体功能领域，持续12周。康复-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作用机制。线粒体功能可能是 调节康复心力衰竭参与者的生理衰退，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 失败和住院。跨多个组织的线粒体功能障碍与心力衰竭相关的生理性衰退有关，并被认为是由影响全身生物能量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图谱可以用来报告全身性生物能量下降。 在心力衰竭患者中，并将与身体功能和长期结果相关--包括再住院率。我们将确定与对照组相比，康复-HF康复计划是否增加了生物能量能力，从而改善了功能结果。多个血细胞群体的生物能量图谱将使我们能够识别特定的细胞类型和生物能量参数，或由多个变量组成的模式，这些与康复-HF结果最密切相关的结果，如身体功能和生活质量。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。缓解身体机能不良和改善长期结果的成功战略取决于确定导致患者出院后脆弱性的机制。生物能量分析可能能够识别需要更密集的治疗和有针对性的康复的患者。基于血液的生物能量分析的进展将在未来的试验中加强这一有前景的测试的使用，并有可能在与身体残疾和不良临床结果相关的各种慢性疾病的老年患者的临床护理中使用。

 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.