Amyloidosis as a Systemic Disease in Context

Abstract

The systemic amyloidoses are a group of diseases characterized by the deposition of amyloid, a material formed from misfolding of proteins, in one or more organs. The 2 commonest forms of amyloidosis are transthyretin amyloidosis (ATTR), derived from wild-type or mutant transthyretin, and light-chain (AL) amyloidosis, derived from abnormal circulating light chains produced by plasma cell dyscrasia. Both frequently involve the heart, producing an infiltrative cardiomyopathy with restrictive pathophysiology. Although advances in echocardiographic, magnetic resonance, and nuclear imaging have rendered diagnosis of cardiac amyloidosis easier, diagnosis is still often delayed. This review focuses on noncardiac manifestations of AL and TTR amyloidosis that may aid the cardiologist in making an earlier diagnosis of cardiac amyloidosis in a patient with cardiac symptoms (such as periorbital purpura in AL amyloidosis and a history of carpal tunnel syndrome and ruptured biceps tendon in ATTR). It also focuses on the unique challenges that treatment of cardiac amyloidosis poses owing to concomitant noncardiac disease, such as nephrotic syndrome-related edema and hypotension due to autonomic neuropathy, and stresses the importance of a precise typing of amyloidosis and a multidisciplinary approach to therapy.