Effect of Mechanical Circulatory Support on Exercise Capacity in Heart Failure

机械循环支持对心力衰竭患者运动能力的影响

• 批准号: 9088687
• 负责人: William Cornwell
• 金额: $ 17.05万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9088687
• 关键词: Acetylene; Active Learning; Affect; Age; Artificial Heart; Autonomic nervous system; Award; Biological Neural Networks; Biomedical Engineering; Blood; Blood Pressure; Blood flow; Brain; Cardiac Output; Cardiopulmonary; Cardiovascular Physiology; Cardiovascular system; Cerebrovascular Physiology; Clinical Sciences; Control Groups; Data; Development; Development Plans; Devices; Disease; Ensure; Environment; Environmental Medicine; Exercise; Exercise Physiology; Exercise stress test; Funding; Future Generations; Goals; Heart; Heart Rate; Heart failure; Housing; Human body; Individual; Institutes; Institution; International; Intervention; Laboratory Research; Lead; Left ventricular structure; Life; Mechanics; Medical center; Mentored Patient-Oriented Research Career Development Award; Mentors; Metabolic; Methods; Morbidity - disease rate; Muscle; Nerve; Operative Surgical Procedures; Outcome; Oxygen; Patient Schedules; Patients; Performance; Physiology; Population; Positioning Attribute; Procedures; Process; Public Health; Publications; Publishing; Qi; Quality of life; Recovery; Reflex action; Reporting; Research; Research Personnel; Resources; Rest; Risk; Skeletal Muscle; Staging; Symptoms; Teacher Professional Development; Technology; Testing; Texas; Time; Training; Translational Research; United States; United States National Institutes of Health; Universities; Ventricular Function; Work; ascending aorta; base; career; career development; exercise capacity; exercise intervention; exercise rehabilitation; experience; functional disability; hemodynamics; implantation; improved; interest; left ventricular assist device; meetings; mortality; next generation; novel strategies; patient population; programs; public health relevance; reduce symptoms; relating to nervous system; response; skills; success; symposium; therapy design; uptake

 DESCRIPTION (provided by applicant): My career goal is to become an independent NIH-funded RO1 investigator contributing to advancements in mechanical circulatory support ("mechanical hearts") for patients with advanced heart failure. My work to date has focused on the impact of continuous-flow (CF) left ventricular assist devices (LVADs), a type of mechanical heart, on cerebrovascular physiology, sympathetic neural activity and blood pressure. This work has led to several presentations at national conferences, first-author publications that are either published or in review and research awards. However, there are two immediate research goals that are necessary for my own career development and to advance the field, including: 1) acquire new skills in the assessment of the cardiovascular and autonomic nervous system; and 2) extend my research program from the study of the cardiovascular system and CF-LVAD interactions under resting conditions, to dynamic conditions during exercise. To accomplish these goals, I have assembled a rigorous career development plan with experiential learning, opportunities to gain proficiency in procedures that I can incorporate into my research program, formal coursework to obtain a Master in Clinical Science degree, and oversight from mentors and advisors who are international experts in their respective fields. I will continue my successful mentored relationship with Dr. Benjamin Levine, who will serve as my primary mentor, Dr. Mark H. Drazner, who will serve as my co-mentor, as well as Drs Qi Fu and Jere Mitchell, who will continue to serve as research advisors. In addition, I will form a new collaborative relationship with Dr. Murray Esler, an international expert in cardiovascular and exercise physiology, with expertise in assessment of the autonomic nervous system. My long term goal is to understand how the cardiovascular system operates in the presence of a CF-LVAD. The objectives of this proposal are to determine how CF-LVADs impact exercise pressor reflexes and to identify the factor(s) which determine exercise capacity in advanced heart failure patients with these devices. Here, I will test the central hypothesis that exercise pressor reflexe improve following CF-LVAD implantation and that the primary determinant of exercise capacity is contractility of the left ventricle. The objectives of this proposal will be accomplished by pursuing two specific aims: 1) Determine the effect of a CF-LVAD on exercise pressor reflex in heart failure patients; and 2) Define the primary determinant(s) of exercise capacity in heart failure patients prior to and following CF-LVAD implantation. Results delivered from these specific aims will provide major contributions to the field and inform development of novel strategies to improve quality of life and survival in this unique patient population, and contribut to refinements in device technology, such that future-generation LVADs can modulate flow during exercise, similar to the normal heart. The proposed research will be conducted at the University of Texas Southwestern Medical Center (UTSW) and the Institute of Exercise and Environmental Medicine (IEEM) in Dallas, Texas. UTSW provides extraordinary translational research opportunities and faculty development programs, while the IEEM houses a world- renowned physiology research laboratory. I will have complete access to all resources available at these two institutions that will ensure my success during this K23 award period and that my career goals are achieved. Based on my training to date, mentored research experience and institutional environment, I believe that I am uniquely positioned to accomplish all objectives outlined in this career development project. This success will ensure that I transition into an independent RO1 funded investigator with expertise in cardiovascular and exercise physiology in patients with advanced heart failure, with a unique skillset in assessment of the autonomic nervous system, which few researchers possess.

 描述（由申请人提供）：我的职业目标是成为一名 NIH 资助的独立 RO1 研究者，为晚期心力衰竭患者的机械循环支持（“机械心脏”）的进步做出贡献。迄今为止，我的工作重点是连续流 (CF) 左心室辅助装置 (LVAD)（一种机械心脏）对脑血管生理、交感神经活动和血压的影响。这项工作已在国家会议上进行了多次演讲，第一作者出版物是 发表或获得评论和研究奖项。然而，有两个直接的研究目标对于我自己的职业发展和推进该领域是必要的，包括：1）获得评估心血管和自主神经系统的新技能； 2) 将我的研究项目从静息条件下的心血管系统和 CF-LVAD 相互作用的研究扩展到运动期间的动态条件。为了实现这些目标，我制定了严格的职业发展计划，包括体验式学习、熟练掌握程序的机会（可以将其纳入我的研究计划）、获得临床科学硕士学位的正式课程，以及来自各自领域国际专家的导师和顾问的监督。我将继续与 Benjamin Levine 博士（他将担任我的主要导师）、Mark H. Drazner 博士（他将担任我的共同导师）以及 Qi Fu 博士和 Jere Mitchell 博士（他们将继续担任研究顾问）保持成功的指导关系。此外，我将与 Murray Esler 博士建立新的合作关系，他是心血管和运动生理学方面的国际专家，在自主神经系统评估方面拥有专业知识。我的长期目标是了解心血管系统在 CF-LVAD 存在的情况下如何运作。该提案的目的是确定 CF-LVAD 如何影响运动加压反射，并确定决定使用这些设备的晚期心力衰竭患者运动能力的因素。在这里，我将检验中心假设，即 CF-LVAD 植入后运动加压反射得到改善，并且运动能力的主要决定因素是左心室的收缩力。该提案的目标将通过追求两个具体目标来实现：1）确定 CF-LVAD 对心力衰竭患者运动升压反射的影响； 2) 确定 CF-LVAD 植入前后心力衰竭患者运动能力的主要决定因素。这些具体目标所取得的结果将为该领域做出重大贡献，并为开发新策略提供信息，以提高这一独特患者群体的生活质量和生存率，并有助于设备技术的改进，使下一代 LVAD 可以在运动过程中调节流量，类似于正常心脏。拟议的研究将在德克萨斯大学西南医学中心 (UTSW) 和德克萨斯州达拉斯的运动与环境医学研究所 (IEEM) 进行。 UTSW 提供非凡的转化研究机会和教师发展计划，而 IEEM 则拥有世界著名的生理学研究实验室。我将可以完全使用这两个机构提供的所有资源，这将确保我在 K23 奖励期间取得成功并实现我的职业目标。根据我迄今为止的培训、指导研究经验和机构环境，我相信我具有独特的优势来实现这个职业发展项目中概述的所有目标。这一成功将确保我转变为一名独立的 RO1 资助的研究者，拥有晚期心力衰竭患者的心血管和运动生理学方面的专业知识，并在评估自主神经系统方面拥有独特的技能，而很少有研究人员拥有这些技能。