Exercise Training in Transthyretin Cardiac Amyloidosis

Prior treatment

• 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

• 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.