Individualized Exercise Training in Cardiac Amyloidosis

Habitual exercise has been shown to improve longevity and reduce overall mortality. Patients with ATTR-CM routinely experience reduced exercise tolerance and functional capacity as the disease progresses. Cardiopulmonary exercise testing (CPET) is the gold standard for assessing quantitative exercise capacity and cardiorespiratory fitness in clinical testing, and peak oxygen consumption (peak VO2) serves as one of the most powerful prognostic markers in cardiovascular health. Lower peak VO2 values are strongly correlated with adverse cardiac events and mortality in individuals with ATTR-CM, including those on contemporary therapies. While major RCTs assessing TTR silencers and stabilizers have shown a reduction in the rate of decline of functional capacity compared to placebo, patients on active therapy still experience an overall decline in functional status. Existing clinical trials have not investigated the effects of a structured exercise training protocol on preventing this functional decline in patients with ATTR-CM. This study aims to evaluate whether an individualized exercise regimen provides additive improvements in exercise capacity and quality of life for patients with ATTR-CM who are receiving background TTR-directed therapy.

Inclusion criteria

• Clinical diagnosis of ATTR-cardiac amyloidosis
• Able to perform endurance and resistance exercise
• Currently on stable dose of TTR-directed therapy, if on therapy
• Adequate clinical stability has been achieved (in the judgment of the investigator) to allow participation in study assessments and intervention.
• Signed informed consent indicating that the patient understands the purpose of the study, the procedures required and is willing to participate

Exclusion criteria

• Sustained ventricular arrhythmias or ICD shock within 6 months
• Severe valvular stenosis
• Pregnancy
• Recent acute coronary syndrome or coronary artery bypass < 6 months
• Large pericardial effusion
• Recent acute myocarditis (< 3 months)
• Recent cardiac medication changes for management of cardiomyopathy
• Patients with investigational intracardiac devices