When to Suspect and How to Approach a Diagnosis of Amyloidosis

Diagnoses of amyloidosis, particularly transthyretin amyloid cardiomyopathy (ATTR-CM), are steadily increasing throughout the world, but the condition remains underdiagnosed. Patients with amyloidosis may present to a range of medical and surgical specialties, often with multisystemic disease, and a high index of clinical suspicion is required for diagnosis. Bone scintigraphy and cardiovascular magnetic resonance (CMR) imaging offer highly sensitive and specific imaging modalities for cardiac amyloidosis. Histological confirmation of amyloid deposition and amyloid type remains the cornerstone of diagnosis for most amyloid types, with transthyretin amyloid cardiomyopathy the exception, which may be diagnosed by validated nonbiopsy diagnostic criteria in the majority. Histological diagnosis of amyloid has been enhanced by laser capture microdissection and tandem mass spectrometry. Early diagnosis and treatment prior to the development of end-organ damage remains essential to improving morbidity and mortality for patients with amyloidosis.