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.

项目摘要（30 行） Jarett Berry 博士是 UT 西南医学中心心脏病科的医学教授。 在过去 13 年多的时间里，他领导了一项成功的研究计划，该计划得到了持续的支持 来自 NIH 和/或美国心脏协会的资助。他建立了一个成功的研究计划 描述运动对射血分数保留的心力衰竭风险的影响。他曾举办过 在德州大学西南分校和全国范围内担任领导职务。此外，他还指导过无数的学员 水平，促进他们向独立的过渡，这一点可以从他们自己的独立研究生涯中得到证明。 从 2019 年开始，他被任命为达拉斯心脏研究的新 PI，领导一个多学科研究 努力描述一个大型多种族队列中健康衰老的生物学特征。他还开发并服务 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 关于国土安全部参与者。他目前的研究是由支持第三次研究的大型机构承诺资助的 国土安全部的检查。他的研究还得到了美国国立卫生研究院额外资助的支持。因此他是 他有能力领导扩展他的指导计划，该计划将得到 K24 机制的支持，并且 支持他的长期职业目标：(1) 领导一项专注于预防心力衰竭的重大研究项目 射血分数保留 (HFpEF)； (2) 提高对导致低水平的机制的认识 中年时期的锻炼能力并确定有针对性的治疗策略； (3) 发展新一代 具备知识和技能的临床研究人员能够进行高质量、以患者为导向的研究 心血管研究。在此奖励期内，PI 将接受额外的领导力培训并获得 通过参加集中培训接触使用高场 7T MRI 的先进成像技术 与他的高级成像同事一起积累经验和实践工作。根据之前的研究 PI，本申请的中心假设是老年 HFpEF 患者的运动不耐受反映了 中年运动能力低下的自然史。该提案的具体目标如下： 具体 目标#1：描述健康中年人运动能力下降的外围机制 以及 HFpEF 风险增加的老年人。 DHS 参与者将完成 (1) 功能测量 [VO2 次最大运动时的动力学和氧提取（AVO2 差异）]； (2) 结构测量（骨骼 肌肉体积、肌肉脂肪渗透）。国土安全部的一部分参与者还将接受额外的体内功能治疗 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 已确诊 HFpEF 的患者与其他健康成人的 EI 外周机制 使用与目标 1 中相同的测量来获得相似/匹配的峰值 V02。学员将获得患者的经验 定向研究并参加由 PI 领导的非正式和正式研究培训经验，作为 他在 CTSA 指导学员方面发挥的机构作用。