Administraive Core

行政核心

• 批准号: 10551295
• 负责人: BENJAMIN D LEVINE
• 金额: $ 11.56万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-09 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10551295
• 关键词: Activities of Daily Living; Acute; Address; Advisory Committees; Cardiac; Cardiology; Cardiopulmonary; Cardiovascular Diseases; Cardiovascular system; Clinical; Clinical Trials Data Monitoring Committees; Collaborations; Communication; Communities; Complex; Creativeness; Data; Disease; Dyspnea; EFRAC; Ensure; Exercise; Exercise Test; Exertion; Functional disorder; Funding; Goals; Health Resources; Heart Diseases; Heart failure; Individual; Ingestion; Knowledge; Leg; Link; Morbidity - disease rate; Muscle; National Heart, Lung, and Blood Institute; Patients; Peripheral; Personnel Management; Phenotype; Physical activity; Physiological; Precision therapeutics; Prevalence; Prevention; Program Research Project Grants; Progress Reports; Quality of life; Randomized; Recommendation; Reporting; Research; Research Activity; Research Personnel; Resistance; Resolution; Resource Sharing; Resources; Safety; Scientific Advances and Accomplishments; Services; Suggestion; Symptoms; Testing; Texas; Time; Training; Vascular Diseases; Work; Workload; clinically relevant; cost; data acquisition; data repository; data sharing; deconditioning; design; exercise intervention; exercise intolerance; exercise training; improved; meetings; member; mortality; muscle form; novel; preservation; pressure; programs; recruit; standard care; therapy design; virtual; working group

Project Summary/Abstract Heart failure with preserved ejection fraction (HFpEF) is perhaps the most common “untreatable” disease in the world. It makes up more than 50% of all heart failure cases and in contrast to other cardiovascular diseases, its prevalence is increasingly resulting in substantial morbidity, mortality, and cost. HFpEF has been resistant to “one-size-fits-all” therapies that have become standard treatment of heart failure with a reduced ejection fraction (HFrEF); therefore there has been increasing pressure to better phenotype this complex and multifactorial disease in order to direct “personalized” pathophysiology based therapy. The dominant symptom of patients with HFpEF is exercise intolerance and dyspnea on exertion (DOE). Such dyspnea can be pro- found, occur at very low levels of external work, and thereby limits physical activity leading to a downward spiral of inactivity and deconditioning which compounds the underlying cardiac and vascular disease. In 2012 The National Heart, Lung, and Blood Institute convened a working group to identify the key knowledge gaps in this field and to suggest strategies for future research on exercise intolerance, and exercise training as a treat- ment for heart failure.(Fleg 2015) We propose to address each of the working group recommendations through a unique PPG that links 4 projects and 3 cores to address the global objective of determining the mechanisms of exercise intolerance and dyspnea in patients with HFpEF and based on this pathophysiology, designing cre- ative exercise interventions that improve quality of life. Although virtually all Program Project Grants are linked together by a common theme, this PPG will be unique in that the individual projects will be linked even more closely by working together on common patients. All patients will be recruited into the Program by a specializ- ed Recruitment Core; each patient will then undergo high resolution physiological phenotyping by all 4 projects followed by a tailored intervention designed to test the clinical relevance of the phenotyping strategy. This approach will allow us to accomplish the following specific aims: Specific Aim 1: To determine the mechan- ism(s) of exercise intolerance and dyspnea in patients with HFpEF using invasive and non-invasive cardio- pulmonary exercise testing. Patients will be divided into those with a primarily “central” limitation and those with a primarily “peripheral limitation” based on this initial assessment. Specific Aim #2: to determine whether a “precision” exercise intervention based on the high resolution phenotyping will lead to clinically meaningful improvements in functional capacity and reduction in dyspnea. All patients will be randomized to undergo one of two tailored exercise interventions for 16 weeks: a) small muscle mass, single leg kicking exercise to allow high intensity muscle exercise without challenging cardiovascular reserve; b) reduce cardiac filling pressure during exercise with acute ingestion of TNG to allow higher systemic workloads and improved training. By combining efforts into a PPG integrated by studying the same patients across multiple platforms, our team has the potential to make highly novel advances towards improving the quality of life for patients with HFpEF.

项目摘要/摘要 保留的射血分数（HFPEF）的心力衰竭可能是最常见的“不可治疗”疾病 世界。它占所有心力​​衰竭病例的50％以上，与其他心血管形成鲜明对比 疾病，其患病率越来越多，导致了大量的发病率，死亡率和成本。 hfpef曾经 耐药的“千篇一律”疗法，这些疗法已成为心力衰竭的标准疗法 射血分数（HFREF）;因此，有越来越多的压力以更好地表型这种复合物和 多因素疾病是为了指导基于“个性化”病理生理学的疗法。主要症状 HFPEF患者的锻炼是运动症和呼吸困难（DOE）。这样的呼吸困难可以促成 发现，外部工作水平非常低，从而限制了体育锻炼 无活动性和衰减的螺旋，使潜在的心脏和血管疾病更加复杂。 2012年 国家心脏，肺部和血液研究所召集了一个工作组，以确定关键知识差距 该领域并提出有关未来研究的策略，以及运动训练作为一种治疗 心力衰竭。（Fleg 2015）我们建议通过 链接4个项目和3个核心的独特PPG解决了确定机制的全球目标 HFPEF患者并基于该病理生理学的患者进行肠道摄入和呼吸困难，设计CRE- 改善生活质量的锻炼干预措施。尽管几乎所有计划项目赠款都链接 通过一个共同的主题，该PPG将是独一无二的 通过在普通患者身上共同努力密切。所有患者将被专门招募到该计划 ED招聘核心；然后，每个患者将接受所有4个项目的高分辨率生理表型 然后进行量身定制的干预措施，旨在测试表型策略的临床相关性。这 方法将使我们能够实现以下特定目标：具体目的1：确定机制 - HFPEF患者使用侵入性和非侵入性心脏的锻炼和呼吸困难的ISM（s） 肺运动测试。患者将被分为具有主要“中心”限制的患者 基于此初步评估，具有主要的“外围限制”。特定目标＃2：确定是否 基于高分辨率表型的“精度”运动干预将导致临床意义 呼吸困难的功能能力和降低的改善。所有患者将被随机进行一次 在两次量身定制的运动干预措施16周内：a）小肌肉质量，单腿踢运动以允许 高强度肌肉运动而无需挑战心血管储备； b）降低心脏填充压力 在急性摄入TNG的运动过程中，可以允许更高的系统性工作量和改进的培训。经过 通过在多个平台上研究同一患者，将努力合并为PPG，我们的团队拥有 提高HFPEF患者生活质量的高度新进展的潜力。