Characterization of Mechanisms of Exercise Intolerance in Patients at Risk for Heart Failure with Preserved Ejection Fraction

射血分数保留的心力衰竭风险患者运动不耐受机制的特征

• 批准号: 10570802
• 负责人: Jarett D Berry
• 金额: $ 11.43万
• 依托单位: UNIVERSITY OF TEXAS HLTH CTR AT TYLER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-06 至 2028-02-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10570802
• 关键词: ATP Synthesis Pathway; Accounting; Activities of Daily Living; Adult; Age; American; Anaerobic Threshold; Award; Berry; Biology; Cardiology; Cardiovascular system; Clinical; Clinical Investigator; Collaborations; Data; Databases; Diagnosis; EFRAC; Elderly; Enrollment; Environment; Exercise; Exercise Test; Exposure to; Faculty; Fatty acid glycerol esters; Funding; Generations; Goals; Heart; Heart failure; Hospitalization; Image; Imaging Techniques; Impairment; Individual; Infiltration; Infrastructure; Institution; Intake; Kinetics; Knowledge; Laboratories; Lead; Leadership; Magnetic Resonance Imaging; Measurement; Measures; Medical center; Medicine; Mentors; Midcareer Investigator Award in Patient-Oriented Research; Mitochondria; Muscle; Names; National Institute on Aging; Natural History; Oxygen; Participant; Patients; Peripheral; Phenotype; Physical activity; Physiology; Positioning Attribute; Prevention; Process; Protocols documentation; Recurrence; Reporting; Research; Research Personnel; Research Priority; Research Training; Rest; Risk; Role; Skeletal Muscle; Testing; Training; United States National Institutes of Health; Work; age related; career; cohort; dietary; effective therapy; exercise capacity; exercise intolerance; experience; healthy aging; high risk; improved; in vivo; inorganic phosphate; member; middle age; mitochondrial dysfunction; mortality risk; multi-ethnic; multidisciplinary; patient oriented; patient oriented research; preservation; professor; programs; sarcopenia; skills; support network; treatment strategy

PROJECT SUMMARY (30 lines) Dr. Jarett Berry is a Professor of Medicine in the Division of Cardiology at UT Southwestern Medical Center. Over the last 13+ years, he has led a successful program of research that has been supported through sustained funding from the NIH and/or the American Heart Assocation. He has established a successful research program characterizing the impact of exercise on the risk for heart failure with preserved ejection fraction. He has held leadership roles at UT Southwestern and nationally. Furthermore, he has mentored numerous trainees at all levels, facilitating their transition to indepdnence as evidenced by their own independent research careers. Beginning in 2019, he was named the new PI of the Dallas Heart Study, where he is leading a multidisciplinary effort to characterize the biology of healthy aging in a large, multiethnic cohort. He also developed and serves as the director of the DHS Exercise Testing Laboratory where his lab performs comprehensive exercise testing on DHS participants. His current research is funded by a large institional commitment that supports the 3rd examination of the DHS. His research is also supported by additional funding from the NIH. Therefore he is well positioned to lead an expansion of his mentoring program that will be supported by this K24 mechanism and support his long-term career goals: (1) Lead a major research program focused on the prevention of heart failure with preserved ejection fraction (HFpEF); (2) Improve the understanding of the mechanisms contributing to low exercise capacity in middle age and identify targeted strategies for treatment; and (3) Develop a new generation of clinical investigators equipped with knowledge and skill set to conduct high-quality, patient oriented cardiovascular research. During this award period, the PI will acquire additional leadership training and gain exposure to advanced imaging techniques using high-field, 7T MRI through attending focused training experiences and hands-on work with his advanced imaging colleagues. Based on prior research established by the PI, the central hypothesis of this application is that exercise intolerance in older HFpEF patients reflects the natural history of low exercise capacity in midlife. The Specific Aims of the proposal are the following: Specific Aim #1: Characterize peripheral mechanisms of reduced exercise capacity in otherwise healthy middle-aged and older adults at increased risk for HFpEF. DHS participants will complete (1) functional measurements [VO2 kinetics and oxygen extraction (AVO2 difference) at submax exercise]; and (2) structural measurements (skeletal muscle volume, muscle fat infiltration). A subset DHS participants will also undergo additional functional in vivo measurements of mitochondrial function using our established 7T MRI/MRS platform. Specific Aim #2: Compare the peripheral mechanisms of EI in patients with established HFpEF with otherwise healthy adults with similar/matched peak V02 using the same measurements as in Aim 1. Trainees will gain experience in patient- oriented research and participate in informal and formal research training experiences led by the PI as part of his institutional role in mentoring trainees in the CTSA.

项目总结(30行) Jarett Berry博士是德克萨斯大学西南医学中心心脏病科的医学教授。 在过去的13年里，他领导了一个成功的研究项目，该项目得到了持续不断的支持 资金来自美国国立卫生研究院和/或美国心脏协会。他已经建立了一个成功的研究项目 研究运动对射血分数保持不变的心力衰竭风险的影响。他已经举行了 在德克萨斯大学西南分校和全国担任领导职务。此外，他还指导过许多实习生 从他们自己的独立研究生涯可以看出，这有助于他们向独立的方向过渡。 从2019年开始，他被任命为达拉斯心脏研究的新PI，在那里他领导着一个多学科的 努力在一个大的、多民族的队列中描述健康老龄化的生物学特征。他还开发和服务于 作为国土安全部运动测试实验室的主任，他的实验室进行全面的运动测试 关于国土安全部的参与者。他目前的研究是由一个大的机构承诺资助的，该机构支持第三个 国土安全部的审查。他的研究还得到了美国国立卫生研究院额外资金的支持。因此，他是 能够很好地领导他的指导计划的扩展，该计划将得到K24机制的支持和 支持他的长期职业目标：(1)领导一个以预防心力衰竭为重点的重大研究项目 保留射血分数(HFpEF)；(2)提高对低血症发病机制的认识 中年的运动能力和确定有针对性的治疗策略；以及(3)培养新一代 具备知识和技能的临床研究人员进行高质量的、以患者为中心的 心血管研究。在此授勋期间，PI将获得额外的领导力培训并获得 通过参加集中培训，接触到使用高场7T磁共振成像的先进成像技术 与他的高级成像同事的经验和实践工作。基于之前由 PI，这一应用的中心假设是，老年HFpEF患者的运动耐量反映了 中年运动能力低的自然病史。该建议的具体目标如下： 目标1：描述健康中年人运动量减少的外周机制 以及患HFpEF风险增加的老年人。国土安全部参与者将完成(1)功能测量[VO2 动力学和亚极限运动时的氧摄取(AVO2差值)]；和(2)结构测量(骨骼 肌肉体积、肌肉脂肪渗透)。DHS参与者的子集也将在体内接受额外的功能 使用我们建立的7T MRI/MRS平台测量线粒体功能。具体目标2：比较 高血压性充血性心力衰竭患者EI的外周机制研究 使用与目标1相同的测量方法获得相似/匹配的峰V02。学员将获得患者- 以研究为导向，参加由PI领导的非正式和正式研究培训经验，作为 他在指导CTSA实习生方面的机构作用。