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.

项目概要（30行） 博士Jarett Berry是UT西南医学中心心脏病科的医学教授。 在过去的13年多里，他领导了一个成功的研究计划，该计划得到了持续的支持。 由NIH和/或美国心脏协会资助。他建立了一个成功的研究项目 描述运动对射血分数正常的心力衰竭风险的影响。他曾担任 在UT西南和全国的领导角色。此外，他还指导了许多学员 水平，促进他们过渡到独立，证明了他们自己的独立研究生涯。 从2019年开始，他被任命为达拉斯心脏研究的新PI，在那里他领导了一项多学科的研究。 努力在一个大的，多种族的队列中描述健康老龄化的生物学特征。他还开发并服务于 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 国土安全部的参与者他目前的研究是由一个大的倡议承诺，支持第三次 检查DHS。他的研究也得到了NIH的额外资助。所以他是 能够很好地领导他的辅导计划的扩展，该计划将得到K24机制的支持， 支持他的长期职业目标：（1）领导一个主要的研究项目，重点是预防心力衰竭 射血分数保留（HFpEF）;（2）提高对导致低射血分数的机制的理解 锻炼中年人的能力，并确定有针对性的治疗策略;（3）培养新一代 临床研究者的知识和技能，以进行高质量的，以病人为导向的 心血管研究在此奖励期间，PI将获得额外的领导力培训， 通过参加重点培训，接触使用高场、7 T MRI的先进成像技术 经验和实践工作与他的先进的成像同事。根据先前的研究， PI，本申请的中心假设是，老年HFpEF患者的运动不耐受反映了 中年运动能力低的自然史。该提案的具体目标如下： 目的#1：描述健康中年人运动能力降低的外周机制 和老年人HFpEF的风险增加。DHS参与者将完成（1）功能测量[VO 2 亚极量运动时的动力学和氧提取（AVO 2差异）];和（2）结构测量（骨骼 肌肉体积、肌肉脂肪浸润）。DHS参与者子集还将接受额外的体内功能性检查 使用我们建立的7 T MRI/MRS平台测量线粒体功能。具体目标#2：比较 已确定HFpEF患者与其他健康成人中EI的外周机制， 使用与目标1中相同的测量值，获得相似/匹配的峰值V02。实习生将获得经验，在病人- 以研究为导向，并参与PI领导的非正式和正式的研究培训经验， 他在指导CTSA学员方面的机构角色。