Early Tissue Clues of Transthyretin Cardiac Amyloidosis: Musculoskeletal Manifestations as Preclinical Indicators

Transthyretin cardiac amyloidosis is an important cause of chronic heart failure with preserved ejection fraction in the adult population; however, it remains underdiagnosed due to a lack of clinical suspicion, and current diagnostic screening methods identify cardiac involvement at stages in which structural and functional myocardial changes have already been established. Therefore, the identification of extracardiac manifestations that precede cardiac amyloid deposition is of particular importance. We review the main musculoskeletal clinical manifestations associated with cardiac amyloidosis, such as bilateral carpal tunnel syndrome, spinal stenosis, biceps tendon rupture, and a history of orthopedic surgeries, addressing the prevalence of amyloid deposits identified in biopsies of these tissues and their temporal relationship with the diagnosis of cardiac involvement. We conclude that these musculoskeletal manifestations constitute early tissue clues of an evolving systemic disease and represent warning signs that may facilitate the timely recognition of transthyretin cardiac amyloidosis, allowing therapeutic intervention at earlier stages of the disease.