Amyloid fibril (AL and ATTR types) (AL/ATTR amyloid)

Amyloid deposits in cardiac tissue represent the pathological accumulation of insoluble, misfolded protein fibrils within the myocardial extracellular space, primarily occurring in Amyloid Light-chain (AL) and Amyloid Transthyretin (ATTR) amyloidosis (StatPearls, 2023). In AL amyloidosis, these deposits are formed from monoclonal immunoglobulin light chains produced by aberrant plasma cells, while in ATTR amyloidosis, they result from the dissociation and misfolding of the transthyretin transport protein (NIH, 2022). The infiltration of these fibrils disrupts the normal cardiac architecture, leading to increased ventricular wall thickness, restrictive physiology, and progressive heart failure (Circulation, 2020). Modern therapeutic strategies target these deposits by either stabilizing the precursor proteins (e.g., Tafamidis) to prevent new fibril formation or utilizing monoclonal antibodies (e.g., Birtamimab, NI006) designed to specifically bind misfolded epitopes and facilitate the clearance of existing fibrils via phagocytosis (NEJM, 2018; NEJM, 2023). Effective management of cardiac amyloidosis relies on early detection through biomarkers and advanced imaging, as the accumulation of these deposits is strongly associated with poor clinical outcomes and high mortality.

Other names

Cardiac amyloid depositsAmyloid light-chain fibrilsTransthyretin amyloid fibrilsMisfolded protein aggregatesCardiac amyloidosis

Kinetic stabilization of precursor protein tetramers to prevent dissociation and subsequent aggregation, or monoclonal antibody-mediated binding to misfolded epitopes to promote immune-mediated clearance of existing tissue fibrils.