Personalized Exercise Training to Improve Functional Capacity in Transthyretin Cardiac Amyloidosis

个性化运动训练可提高甲状腺素运载蛋白心脏淀粉样变性的功能能力

• 批准号: 10570629
• 负责人: Sarah AM Cuddy
• 金额: $ 19.37万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-05 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10570629
• 关键词: Activities of Daily Living; Adult; Advisory Committees; Aerobic; Affect; Age; Aging; American; Amyloidosis; Award; Biology of Aging; Boston; Cardiac; Cardiomyopathies; Cardiopulmonary; Cities; Clinical; Control Groups; Data; Disease; Disease Progression; EFRAC; Elderly; Enrollment; Evaluation; Exercise Test; Extensor; Functional disorder; Future; Goals; Heart failure; Hospitalization; Hospitals; Image; Investments; Kansas; Knowledge; Left; Leg; Life; Lower Extremity; Measures; Medicine; Mentors; Mentorship; Morbidity - disease rate; Muscle; Musculoskeletal; Myocardial dysfunction; Patients; Performance; Persons; Physical Performance; Physicians; Population; Prealbumin; Program Development; Progressive Disease; Prospective Studies; Proteins; Protocols documentation; Publications; Qualifying; Quality of life; Questionnaires; Randomized, Controlled Trials; Research; Research Personnel; Scientist; Severities; Skeletal Muscle; Systemic disease; Therapeutic Intervention; Therapeutic Trials; Thick; Training Programs; Treatment Failure; VO2max; Ventricular; Woman; Work; cardiac amyloidosis; career; career development; cohort; cost; design; exercise intervention; exercise intolerance; exercise program; exercise training; heart imaging; human old age (65+); improved; instructor; medical schools; mortality; neuromuscular; novel; older patient; optimal treatments; personalized strategies; preservation; response; sex; skills; therapy development

Project Summary Heart failure (HF) affects over 5 million adults over the age of 65. Cardiac transthyretin amyloidosis (ATTR-CM) is a cause of HF in ~10% of older adults and leads to significant morbidity and mortality. Musculoskeletal manifestations are common in ATTR-CM and occur 5-10 years prior to onset of HF. Exercise intolerance, a cardinal feature, is traditionally attributed to cardiac dysfunction but contributing systemic mechanisms have not been evaluated. Tafamidis, a transthyretin stabilizer, is the only approved therapy for ATTR-CM. It slows disease progression, prolongs life, and reduces HF hospitalizations. However, it does not improve functional capacity- no therapeutic intervention has been shown to do so in ATTR-CM. The central premise of this proposal is that skeletal muscle dysfunction from amyloidosis and HF severely limits aerobic capacity and, thus, quality of life in ATTR-CM, and that targeted exercise training will improve quality of life by improving skeletal muscle performance and aerobic capacity. Cardiopulmonary exercise testing (CPET) and the short physical performance battery (SBBP), including a leg extensor muscle power assessment will be used to achieve the following specific aims; 1) to compare skeletal muscle performance in ATTR-CM and non-amyloid HF; and 2) to determine improvements in aerobic capacity and quality of life due to 12 weeks of supervised exercise training in patients with ATTR-CM. To achieve the second aim, we use a personalized exercise intervention developed and led by Dr Bhasin’s team at the Boston Older Americans Independence Center (Boston OAIC) at BWH. Dr. Cuddy is an Instructor of Medicine at Harvard Medical School and Brigham and Women’s Hospital (BWH) who is highly qualified and invested in leading this study. She is a cardiologist and an expert in cardiac amyloidosis with a track record of successful research, including publications and awards. Her long-term career goal is to be become a clinician-scientist at the forefront of optimizing quality of life in adults with ATTR-CM. This research will be accomplished in the setting of a comprehensive career development program designed to provide the candidate with the skills needed to become an independent physician-scientist in CV medicine, with a well-qualified mentorship team led by Dr. Sharmila Dorbala. Data collected in this proposal on systemic dysfunction and the efficacy of exercise training in this population will ultimately inform future therapeutic trials. An outstanding mentoring team and advisory committee of established scientists in the fields of CV medicine, CV imaging, Aging, and Function-promoting therapies, will guide the candidate in her transition to scientific independence over the course of the award period.

项目概要 心力衰竭 (HF) 影响超过 500 万 65 岁以上的成年人。心脏运甲状腺素蛋白淀粉样变性 (ATTR-CM) 是约 10% 老年人发生心力衰竭的原因，并导致显着的发病率和死亡率。肌肉骨骼 这些症状在 ATTR-CM 中很常见，并且发生在 HF 发病前 5-10 年。运动不耐受， 主要特征，传统上归因于心脏功能障碍，但贡献的系统机制并没有 被评估。 Tafamidis 是一种转甲状腺素蛋白稳定剂，是唯一获批的 ATTR-CM 疗法。它可以减缓疾病 病进展、延长生命并减少心衰住院率。然而，它并不能提高功能能力—— 目前尚无任何治疗干预措施可以在 ATTR-CM 中显示出这种效果。该提案的中心前提是 淀粉样变性和心力衰竭导致的骨骼肌功能障碍严重限制了有氧能力，从而影响了人们的生活质量 ATTR-CM，有针对性的运动训练将通过改善骨骼肌来提高生活质量 表现和有氧能力。心肺运动试验（CPET）和短期体能测试 性能电池 (SBBP)，包括腿部伸肌力量评估，将用于实现 遵循具体目标； 1) 比较 ATTR-CM 和非淀粉样蛋白 HF 中的骨骼肌性能； 2) 到 确定 12 周监督运动训练带来的有氧能力和生活质量的改善 ATTR-CM 患者。为了实现第二个目标，我们使用开发的个性化运动干预措施 由 BWH 波士顿美国老年人独立中心 (Boston OAIC) 的 Bhasin 博士团队领导。 Cuddy 博士是哈佛医学院和布莱根妇女医院 (BWH) 的医学讲师 他具有高素质并投资于领导这项研究。她是一位心脏病专家，也是心脏病方面的专家 淀粉样变性具有成功研究的记录，包括出版物和奖项。她的长期职业生涯 目标是成为一名站在优化 ATTR-CM 成人生活质量最前沿的临床医生科学家。这 研究将在制定综合职业发展计划的过程中完成，该计划旨在 为候选人提供成为心血管医学领域独立医师科学家所需的技能， 由 Sharmila Dorbala 博士领导的高素质导师团队。本提案中收集的有关系统性的数据 该人群的功能障碍和运动训练的效果最终将为未来的治疗试验提供信息。 由CV医学领域知名科学家组成的杰出导师团队和顾问委员会， CV 成像、衰老和功能促进疗法将指导候选人向科学过渡 奖励期间的独立性。