{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T10:59:50Z","timestamp":1785149990467,"version":"3.55.0"},"reference-count":33,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T00:00:00Z","timestamp":1784937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>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 \u201camyloidosis\u201d, \u201cthoracic aorta\u201d, \u201cthoracic aortic aneurysm\u201d, \u201caortic dissection\u201d, and \u201caortopathy\u201d 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\u2013dexamethasone (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.<\/jats:p>","DOI":"10.3390\/jcm15155817","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T09:47:41Z","timestamp":1785145661000},"page":"5817","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Amyloidosis and Thoracic Aortic Disease: A Scoping Review"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-2445-0879","authenticated-orcid":false,"given":"Vasiliki","family":"Androutsopoulou","sequence":"first","affiliation":[{"name":"Department of Cardiothoracic Surgery, University Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41222 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2891-777X","authenticated-orcid":false,"given":"Konstantinos","family":"Spanos","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, University Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41222 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioanna","family":"Giannouka","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, General Hospital of Larissa, 41222 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4872-1811","authenticated-orcid":false,"given":"Konstantinos","family":"Tzimkas-Dakis","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, University Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41222 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Karakoussis","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, General Hospital of Larissa, 41222 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3323-6995","authenticated-orcid":false,"given":"Athanasios D.","family":"Giannoukas","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, University Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41222 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1002\/ejhf.2589","article-title":"Prevalence and clinical outcomes of transthyretin amyloidosis: A systematic review and meta-analysis","volume":"24","author":"Antonopoulos","year":"2022","journal-title":"Eur. J. Heart Fail."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1080\/13506129.2022.2159369","article-title":"Cardiac amyloidosis remains significantly underdiagnosed in patients undergoing TAVR: Analysis of National Inpatient Sample","volume":"30","author":"Antonopoulos","year":"2023","journal-title":"Amyloid"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1016\/j.jacc.2016.06.053","article-title":"AL (Light-Chain) Cardiac Amyloidosis: A Review of Diagnosis and Therapy","volume":"68","author":"Falk","year":"2016","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.carpath.2015.07.008","article-title":"Cardiac amyloidosis: Pathology, nomenclature, and typing","volume":"24","author":"Maleszewski","year":"2015","journal-title":"Cardiovasc. Pathol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1080\/13506129.2025.2554880","article-title":"Medin and transthyretin: A new amyloid double act in the aortic wall and valves","volume":"33","author":"Maerivoet","year":"2025","journal-title":"Amyloid"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"ytaf393","DOI":"10.1093\/ehjcr\/ytaf393","article-title":"Case report of isolated aortic valve AL-amyloidosis following aortic valve replacement","volume":"9","author":"Choudhury","year":"2025","journal-title":"Eur. Heart J. Case Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1038\/labinvest.3700679","article-title":"Role of aggregated medin in the pathogenesis of thoracic aortic aneurysm and dissection","volume":"87","author":"Peng","year":"2007","journal-title":"Lab. Investig."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"467","DOI":"10.7326\/M18-0850","article-title":"PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation","volume":"169","author":"Tricco","year":"2018","journal-title":"Ann. Intern. Med."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Schardt, C., Adams, M.B., Owens, T., Keitz, S., and Fontelo, P. (2007). Utilization of the PICO framework to improve searching PubMed for clinical questions. BMC Med. Inf. Decis. Mak., 7.","DOI":"10.1186\/1472-6947-7-16"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Wang, M., McGraw, K.R., and Monticone, R.E. (2023). Milk Fat Globule Epidermal Growth Factor VIII Fragment Medin in Age-Associated Arterial Adverse Remodeling and Arterial Disease. Cells, 12.","DOI":"10.3390\/cells12020253"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1080\/13506129.2019.1625323","article-title":"Idiopathic degenerative thoracic aneurysms are associated with increased aortic medial amyloid","volume":"26","author":"Davies","year":"2019","journal-title":"Amyloid"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Okada, A., Kakuta, T., Tadokoro, N., Tateishi, E., Morita, Y., Kitai, T., Amaki, M., Kanzaki, H., Ohta-Ogo, K., and Ikeda, Y. (2023). Transthyretin derived amyloid deposits in the atrium and the aortic valve: Insights from multimodality evaluations and mid-term follow up. BMC Cardiovasc. Disord., 23.","DOI":"10.1186\/s12872-023-03319-3"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"102311","DOI":"10.1016\/j.jaccas.2024.102311","article-title":"Wild-type Transthyretin Amyloid Deposition in an Ascending Aortic Aneurysm","volume":"29","author":"Hoteit","year":"2024","journal-title":"JACC Case Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1002\/jcu.22547","article-title":"Cardiac amyloidosis is associated with increased aortic stiffness","volume":"46","author":"Nemes","year":"2018","journal-title":"J. Clin. Ultrasound"},{"key":"ref_15","first-page":"555885","article-title":"Degenerative thoracic and peripheral arterial aneurysms: The amyloidosis connection, case report and overview","volume":"14","author":"Ibrahimi","year":"2025","journal-title":"J. Anesth. Intensive Care Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"ehaf784.2954","DOI":"10.1093\/eurheartj\/ehaf784.2954","article-title":"Exploring the burden of amyloidosis in patients with aortic disease: Insights from the national inpatient sample (2015 to 2021)","volume":"46","author":"Ersoezlue","year":"2025","journal-title":"Eur. Heart J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4957","DOI":"10.1182\/blood-2009-07-230722","article-title":"Classification of amyloidosis by laser microdissection and mass spectrometry-based proteomic analysis","volume":"114","author":"Vrana","year":"2009","journal-title":"Blood"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1080\/13506129.2016.1257986","article-title":"Amyloid fibril proteins and amyloidosis: Chemical identification and clinical classification International Society of Amyloidosis 2016 Nomenclature Guidelines","volume":"23","author":"Sipe","year":"2016","journal-title":"Amyloid"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2440","DOI":"10.1161\/01.CIR.0000068314.02595.B2","article-title":"Serum N-terminal pro-brain natriuretic peptide is a sensitive marker of myocardial dysfunction in AL amyloidosis","volume":"107","author":"Palladini","year":"2003","journal-title":"Circulation"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2325","DOI":"10.1182\/blood-2014-04-570010","article-title":"A staging system for renal outcome and early markers of renal response to chemotherapy in AL amyloidosis","volume":"124","author":"Palladini","year":"2014","journal-title":"Blood"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.1093\/eurheartj\/ehab072","article-title":"Diagnosis and treatment of cardiac amyloidosis: A position statement of the ESC","volume":"42","author":"Rapezzi","year":"2021","journal-title":"Eur. Heart J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1182\/blood-2007-02-076034","article-title":"Treatment with oral melphalan plus dexamethasone produces long-term remissions in AL amyloidosis","volume":"110","author":"Palladini","year":"2007","journal-title":"Blood"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2311","DOI":"10.1038\/leu.2014.227","article-title":"Melphalan and dexamethasone with or without bortezomib in newly diagnosed AL amyloidosis: A matched case-control study on 174 patients","volume":"28","author":"Palladini","year":"2014","journal-title":"Leukemia"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1182\/blood-2015-06-648113","article-title":"Upfront CyBorD in AL amyloidosis","volume":"126","author":"Cibeira","year":"2015","journal-title":"Blood"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1182\/blood-2017-01-763599","article-title":"Daratumumab yields rapid and deep hematologic responses in patients with heavily pretreated AL amyloidosis","volume":"130","author":"Kaufman","year":"2017","journal-title":"Blood"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6610","DOI":"10.1182\/blood-2011-04-351643","article-title":"Doxycycline reduces fibril formation in a transgenic mouse model of AL amyloidosis","volume":"118","author":"Ward","year":"2011","journal-title":"Blood"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e546","DOI":"10.1038\/bcj.2017.26","article-title":"Encouraging impact of doxycycline on early mortality in cardiac light chain (AL) amyloidosis","volume":"7","author":"Wechalekar","year":"2017","journal-title":"Blood Cancer J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1007\/s00392-010-0142-x","article-title":"Effects of the main green tea polyphenol epigallocatechin-3-gallate on cardiac involvement in patients with AL amyloidosis","volume":"99","author":"Mereles","year":"2010","journal-title":"Clin. Res. Cardiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1200\/JCO.2015.63.6530","article-title":"First-in-Human Phase I\/II Study of NEOD001 in Patients with Light Chain Amyloidosis and Persistent Organ Dysfunction","volume":"34","author":"Gertz","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1080\/13506129.2017.1292900","article-title":"Interim analysis of the phase 1a\/b study of chimeric fibril-reactive monoclonal antibody 11-1F4 in patients with AL amyloidosis","volume":"24","author":"Edwards","year":"2017","journal-title":"Amyloid"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1161\/ATVBAHA.118.310956","article-title":"Therapies for thoracic aortic aneurysms and acute aortic dissections","volume":"39","author":"Milewicz","year":"2019","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_32","first-page":"886","article-title":"Impact of amyloidosis on outcomes after transcatheter aortic valve implantation","volume":"78","author":"Gerra","year":"2025","journal-title":"Cardiologia"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.amjcard.2025.12.018","article-title":"Artificial Intelligence as a Prognostic Tool in Cardiac Amyloidosis: A Review","volume":"262","author":"Kong","year":"2025","journal-title":"Am. J. Cardiol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/15\/5817\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T10:06:10Z","timestamp":1785146770000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/15\/5817"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,25]]},"references-count":33,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["jcm15155817"],"URL":"https:\/\/doi.org\/10.3390\/jcm15155817","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,25]]}}}