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Personalized Exercise Training to Improve Functional Capacity in Transthyretin Cardiac Amyloidosis

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
依托单位国家:
美国
项目类别:
财政年份:
2023
资助国家:
美国
项目状态:
未结题
起止时间:
2023-05-05 至 2028-04-30

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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.
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