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: 9893892
• 负责人: William Cornwell
• 金额: $ 13.82万
• 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 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9893892
• 关键词: Acetylene; Active Learning; Affect; Age; Artificial Heart; Autonomic nervous system; Award; Biomedical Engineering; Blood; Blood Pressure; Blood flow; Brain; Cardiac Output; Cardiopulmonary; Cardiovascular Physiology; Cardiovascular system; Cerebrovascular Physiology; Clinical; Clinical Sciences; Control Groups; Data; Development; Development Plans; Devices; Disease; Ensure; Environment; Environmental Medicine; Exercise; Exercise Physiology; Exercise Test; Funding; Future Generations; Goals; Heart; Heart Rate; Heart failure; Human body; Individual; Institutes; Institution; International; Intervention; Laboratory Research; Left ventricular structure; Life; Mechanics; Medical center; Mentored Patient-Oriented Research Career Development Award; Mentors; Metabolic; Methods; Morbidity - disease rate; Muscle; Nerve; Operating System; Operative Surgical Procedures; Outcome; Oxygen; Patient Schedules; Patients; Performance; Physiology; Population; Positioning Attribute; Procedures; Process; Program Development; Public Health; Publications; Publishing; Qi; Quality of life; Recovery; Reflex action; Reporting; Research; Research Personnel; Resources; Rest; Risk; Savings; Skeletal Muscle; 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; mortality; neural network; 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（由适用提供）：我的职业目标是成为一名独立的NIH资助的RO1调查员，为高级心力衰竭的患者提供了为机械电路支持（“机械心脏”）进步的贡献。迄今为止，我的工作集中在连续流（CF）左心室辅助设备（LVADS）（一种机械心脏）对脑血管生理学，交感神经元活性和血压的影响上。这项工作导致在国家会议上进行了几次演讲 发布或在审查和研究奖中。但是，对于我自己的职业发展并推进该领域，有两个即时的研究目标，包括：1）在评估心血管和自主神经系统时获得新技能； 2）将我的研究计划从对心血管系统和CF-LVAD相互作用的研究扩展到静止条件下的CF-LVAD相互作用，再到运动过程中的动态条件。为了实现这些目标，我通过专家学习，熟练地融入了我可以纳入我的研究计划中的程序，正式课程以获得临床科学学位的硕士学位以及来自各自领域的国际专家的指导者和顾问的监督的机会。我将继续与本杰明·莱文（Benjamin Levine）博士的成功建立关系，后者将担任我的主要导师马克·H·德拉兹纳（Mark H. Drazner）博士，他将担任我的联合学，以及Qi Fu博士和Jere Mitchell博士，后者将继续担任研究顾问。此外，我将与心血管和运动生理学的国际专家Murray Esler博士建立新的合作关系，并在评估自主神经系统方面具有专业知识。我的长期目标是了解心血管系统在CF-LVAD存在下的运作方式。该提案的目标是确定CF-LVAD如何影响运动训练反射，并确定确定这些设备晚期心力衰竭患者运动能力的因素。在这里，我将测试中心假设，即CF-LVAD植入后运动施加反射会得到改善，而运动能力的主要决定因素是左通气的收缩力。该提案的目标将通过追求两个具体的目的来实现：1）确定CF-LVAD对心力衰竭患者运动施加反射的影响； 2）在CF-LVAD植入之前和之后，定义心力衰竭患者运动能力的主要决定性。从这些特定目标带来的结果将为该领域提供重大贡献，并为这项独特的患者人群的生活质量和生存提供新的策略的发展，并为设备技术的改进做出贡献，从而使未来的生成LVAD可以在运动过程中调节流动，类似于正常的心脏。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提供了非凡的翻译研究机会和教师发展计划，而IEEM则拥有世界知名的生理学研究实验室。我将完全访问这两个机构可用的所有资源，这些资源将确保我在这个K23奖励期间取得成功，并实现我的职业目标。根据迄今为止的培训，我认为我相信我在实现此职业发展项目中概述的所有目标方面拥有独特的位置。这一成功将确保我转变为具有晚期心力衰竭患者心血管和运动生理学专业知识的独立RO1资助的研究者，并且在评估自主神经系统方面具有独特的技能，很少有研究人员所拥有的自主神经系统。

项目成果

Characteristics and Treatment of Exercise Intolerance in Patients With Long COVID.

长期新冠肺炎患者运动不耐受的特点及治疗。

• DOI: 10.1097/hcr.0000000000000821
• 发表时间: 2023
• 期刊: Journal of cardiopulmonary rehabilitation and prevention
• 影响因子: 3.8
• 作者: Edward,JustinA;Peruri,Adithya;Rudofker,Eric;Shamapant,Nikhil;Parker,Hugh;Cotter,Ryan;Sabin,Katherine;Lawley,Justin;Cornwell3rd,WilliamK
• 通讯作者: Cornwell3rd,WilliamK

Impact of Exercise on Cerebrovascular Physiology and Risk of Stroke.

• DOI: 10.1161/strokeaha.121.037343
• 发表时间: 2022-07
• 期刊: Stroke
• 影响因子: 8.3

Impact of Mechanical Circulatory Support on Exercise Capacity in Patients With Advanced Heart Failure.

• DOI: 10.1249/jes.0000000000000303
• 发表时间: 2022-10-01
• 期刊: EXERCISE AND SPORT SCIENCES REVIEWS
• 影响因子: 5.7
• 作者: Huang, Janice;McDonnell, Barry J.;Lawley, Justin S.;Byrd, Jessica;Stohr, Eric J.;Cornwell, William K., III
• 通讯作者: Cornwell, William K., III

Bionic women and men - Part 1: Cardiovascular lessons from heart failure patients implanted with left ventricular assist devices.

• DOI: 10.1113/ep088323
• 发表时间: 2020-05
• 期刊: EXPERIMENTAL PHYSIOLOGY
• 影响因子: 2.7
• 作者: Stohr, Eric J.;Cornwell, William K.;Kanwar, Manreet;Cockcroft, John R.;McDonnell, Barry J.
• 通讯作者: McDonnell, Barry J.

Bionic women and men - Part 4: Cardiovascular, cerebrovascular and exercise responses among patients supported with left ventricular assist devices.

仿生女性和男性 - 第 4 部分：左心室辅助装置支持的患者的心血管、脑血管和运动反应。

• DOI: 10.1113/ep088325
• 发表时间: 2020
• 期刊: Experimental physiology
• 影响因子: 2.7
• 作者: Buchanan,Cullen;Kanwar,Manreet;Cockcroft,JohnR;McDonnell,Barry;Stöhr,EricJ;Cornwell3rd,WilliamK
• 通讯作者: Cornwell3rd,WilliamK