A Comprehensive Review of the Management of Light-Chain (AL) and Transthyretin (ATTR) Cardiac Amyloidosis

Cardiac amyloidosis, once considered a rare and untreatable disorder, is now increasingly recognized as a significant cause of heart failure, particularly in older adults. The two most clinically relevant subtypes of cardiac amyloidosis-immunoglobulin light-chain amyloidosis (AL) and transthyretin-related amyloidosis (ATTR)-differ in pathogenesis, natural history, and management strategies, thereby necessitating a tailored approach to diagnosis and therapy. Advances in multimodality cardiac imaging, including echocardiography, cardiac magnetic resonance, and nuclear scintigraphy, have enabled earlier detection and improved differentiation between subtypes. Management of AL centers on rapid initiation of plasma cell-directed therapies to suppress light-chain production, with autologous stem cell transplantation and novel chemotherapeutic regimens improving survival. In contrast, ATTR management focuses on stabilizing or reducing transthyretin deposition through disease-modifying agents, such as stabilizers, gene-silencing therapies, and emerging fibril-disrupting approaches. Supportive care, including guideline-directed heart failure therapies and arrhythmia management, as well as advanced therapies such as transplantation, remains essential across both subtypes, albeit with unique considerations due to amyloid-related hemodynamics. This review synthesizes current evidence on the diagnosis and treatment of AL and ATTR, highlights recent therapeutic breakthroughs, and discusses ongoing challenges in optimizing patient outcomes, from equitable access to therapies to the integration of multidisciplinary care.