Cardiac amyloidosis in 2023: A review of pathophysiology, diagnosis, and treatment

Cardiac amyloidosis is caused by the extracellular, interstitial deposition of misfolded protein deposits or amyloid fibrils that result in a restrictive cardiomyopathy with associated conduction system and rhythm disturbances. This family of diseases has distinct prognoses and treatment options depending on the precursor protein that misfolds into amyloid fibrils. The two most commonly encountered types of amyloidosis that involve the heart are as follows: (a) light chain amyloidosis (AL amyloidosis), produced by an underlying plasma cell dyscrasia; and (b) transthyretin (TTR) amyloidosis. Amyloidogenic TTR (ATTR) amyloidosis can exist in a genetically normal (wild-type) or hereditary (variant) form. With recent advances in noninvasive imaging modalities, ATTR cardiac amyloidosis, in particular, has emerged as a common subtype of heart failure with preserved ejection fraction in older individuals. The last decade has witnessed paradigm-shifting advancements in the effective treatment of AL and ATTR cardiac amyloidosis, thereby transforming this frequently encountered cardiomyopathy from an almost universally fatal disease to one that can be managed successfully, resulting in meaningful long-term survival.