Amyloidosis and Thoracic Aortic Disease: A Scoping Review.

Background and

Objectives

Amyloidosis is a systemic disorder characterized by extracellular deposition of misfolded protein fibrils, most commonly light-chain (AL) or transthyretin-derived (ATTR) ones. Cardiac involvement is well recognized, but large-vessel complications, including thoracic aortic aneurysms (TAA) and dissections, are rare and under-reported. The aim of this review article is to provide insights into pathophysiology, clinical diagnosis and the therapeutic opportunities in amyloidosis-related thoracic aortic diseases. Methods and Materials: The PRISMA Extension for Scoping Reviews (PRISMA-ScR) Guidelines were followed. An extensive search of the available literature in the English language, published between 1 January 2000, and 31 December 2025, in three large-scale scientific databases was undertaken by two independent reviewers. The terms "amyloidosis", "thoracic aorta", "thoracic aortic aneurysm", "aortic dissection", and "aortopathy" were used both as specific items, as well as in MeSH Terms. Studies reporting on the pathophysiology, diagnosis, clinical manifestations, treatment options and prognosis of amyloid deposition on the thoracic aorta were included in the review. Because of the nature of the existing literature, only a narrative review was possible.

Results

Twenty-nine studies were included. Owing to the rarity of reporting, data was derived mainly from case reports and series, as well as autopsy studies. Amyloid infiltration of the aortic wall has been associated with medial architectural disruption, degeneration of elastic fibers, impairment of vasa vasorum perfusion, and arterial stiffness, all of which could contribute to aneurysmal dilation and aortic lesions. Amyloidosis management combines targeted anti-plasma cell therapy with supportive care. In AL amyloidosis, melphalan-dexamethasone (MDex) was historically standard, but regimens such as cyclophosphamide, bortezomib, and dexamethasone (CyBorD) and bortezomib, melphalan, and dexamethasone (BMDex) achieve higher complete response rates. Immunotherapy with Daratumumab has shown high overall and complete response rates. Fibril-directed approaches, including doxycycline and epigallocatechin gallate, and monoclonal antibodies, are under evaluation. Acute management of large-vessel manifestations follows conventional protocols, but prognosis is often dominated by underlying cardiac and systemic involvement.

Conclusions

Management of thoracic aortic involvement follows standard imaging surveillance and surgical criteria, though operative risk is increased. Multidisciplinary care, early recognition, and individualized risk stratification are essential to improve outcomes, particularly given frequent cardiac involvement.