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Principal Investigator: Sarah AM Cuddy
Organization: BRIGHAM AND WOMEN'S HOSPITAL
Fiscal Year: 2024
Award: $193,687
Funding agency: National Heart Lung and Blood Institute
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.
Terms: <21+ years old><65 and older><65 or older><65 years of age and older><65 years of age or more><65 years of age or older><65+ years><65+ years old><> 65 years><Activities of Daily Living><Activities of everyday life><Adult><Adult Human><Advisory Committees><Aerobic><Affect><Age><Aged 65 and Over><Aging><American><Amyloidosis><Award><Biology of Aging><Boston><Cardiac><Cardiomyopathies><Cardiopulmonary><Cities><Clinical><Control Groups><Data><Disease><Disease Progression><Disorder><Dysfunction><EFRAC><Ejection Fraction><Enrollment><Evaluation><Exercise Test><Extensor><Functional disorder><Future><Goals><Heart failure><Hospital Admission><Hospitalization><Hospitals><Image><Investigators><Investments><Kansas><Knowledge><Left><Leg><Life><Lower Extremity><Lower Limb><Measures><Medicine><Membrum inferius><Mentors><Mentorship><Morbidity><Morbidity - disease rate><Muscle><Muscle Tissue><Musculoskeletal><Myocardial Diseases><Myocardial Disorder><Myocardial depression><Myocardial dysfunction><Myocardiopathies><Patients><Performance><Persons><Physical Performance><Physicians><Physiopathology><Population><Prealbumin><Proalbumin><Program Development><Progressive Disease><Prospective Studies><Proteins><Protocol><Protocols documentation><Publications><QOL><Qualifying><Quality of life><Questionnaires><Randomized, Controlled Trials><Research><Research Personnel><Researchers><Scientific Publication><Scientist><Severities><Skeletal Muscle><Systemic disease><Task Forces><Therapeutic Intervention><Therapeutic Trials><Thick><Thickness><Training Programs><Transthyretin><Treatment Failure><VO2 max><VO2max><Ventricular><Voluntary Muscle><Woman><Work><above age 65><adulthood><advisory team><after age 65><age 65 and greater><age 65 and older><age 65 or older><age > 65><age of 65 years onward><aged 65 and greater><aged 65+><aged ≥65><ages><aging associated disease><aging related disease><amyloid disease><cardiac amyloidosis><cardiac dysfunction><cardiac failure><cardiac imaging><cardiac scanning><career><career development><cohort><cost><daily living function><daily living functionality><design><designing><develop therapy><disease of aging><disorder of aging><elderly patient><enroll><exercise intervention><exercise intolerance><exercise program><exercise training><fitness program><functional ability><functional capacity><heart dysfunction><heart imaging><heart scanning><human old age (65+)><imaging><improved><individualized strategies><instructor><intervention development><intervention therapy><maximal oxygen uptake><medical college><medical schools><mortality><muscular><myocardium disease><myocardium disorder><neuromuscular><novel><old age><older adult><older adulthood><older patient><optimal therapies><optimal treatments><over 65 years><pathophysiology><personalized strategies><physical activity intervention><preservation><randomized control trial><response><school of medicine><sex><skills><therapy development><therapy failure><treatment development><≥65 years>