Cardiac amyloidosis (CA) represents an increasingly recognized but historically underdiagnosed cause of restrictive cardiomyopathy and heart failure. CA is now understood to be more prevalent, particularly in older adults, as advancements in imaging and biomarker technologies have improved detection. The disease results from the misfolding of precursor proteins, primarily immunoglobulin light chains (in light chain (AL) amyloidosis) or transthyretin (in transthyretin (ATTR) amyloidosis), into insoluble fibrils that deposit in myocardial tissue. These deposits cause structural and functional cardiac impairment through both physical infiltration and cytotoxic mechanisms, leading to diastolic dysfunction, arrhythmias, and progressive heart failure. Understanding the molecular basis of amyloid formation and deposition has revealed subtype-specific mechanisms of toxicity and tissue tropism, highlighting the central role of protein instability, proteolytic cleavage, and oxidative stress in disease progression.
