Exercise Training in Transthyretin Cardiac Amyloidosis

Eligibility Criteria

• * Diagnosis and typing of ATTR-CM by endomyocardial biopsy or by Grade 2 or Grade 3 pyrophosphate (PYP) positivity (exception: nonamyloid control arm in aim 1).
• * Diagnosis of heart failure, with prior or current need of diuretics and increased N-terminal prohormone B-natureitic peptide (BNP) (≥450 pg/ml).
• * Peak VO2 \<80% predicted, indicating impaired aerobic capacity (for aim 2 only).
• * Taking tafamidis (for aim 2 only)
• * Able to walk 4 meters (with or without the use of an assistive device) and independent with basic activities of daily living at the time of enrolment.
• * Adequate clinical stability has been achieved in the judgment of the investigator to allow participation in study assessments and the intervention.
• * Signed informed consent document indicating that the patient understands the purpose of and procedures required for the study and is willing to participate in the study.
• * Acute myocardial infarction (Note: given that cardiac biomarkers such as troponin are frequently elevated in ATTR-CM patients, the diagnosis of acute myocardial infarction should be based on clinical diagnosis, not biomarkers alone)
• * \>70% obstructive coronary artery disease
• * Severe aortic valve stenosis
• * Already actively participating in formal, facility-based cardiac exercise
• * Already engaging in regular moderate to vigorous exercise conditioning defined as \> 30 minutes per day, ≥ twice per week consistently during the previous 6 weeks
• * Ventricular assist device
• * Light chain amyloidosis or other form of non-ATTR amyloidosis
• * Advanced chronic kidney disease defined as estimated glomerular filtration rate \<20 mL/min/1.73m2
• * Any organ transplantation
• * Terminal illness other than HF with life expectancy \< 1 year
• * Pacemaker or implantable cardioverter-defibrillato (ICD) with heart rate limits \< expected heart rates for exercise and unable to be reprogrammed
• * Neuropathy due to transthyretin (TTR) mutation
• * Impairment from stroke, injury or other medical disorder that precludes participation in the intervention
• * Abnormal cardiopulmonary exercise testing (CPET) finding that requires further investigation and management
• * Dementia that precludes ability to participate in exercise and follow study protocols
• * High risk for non-adherence as determined by screening evaluation
• * Inability or unwillingness to comply with the study requirements