Heyde's Syndrome - a comprehensive review
DOI:
https://doi.org/10.12775/QS.2025.45.66474Keywords
Heyde’s syndrome, acquired von Willebrand disease, aortic stenosis, gastrointestinal bleeding, ADAMTS13Abstract
Introduction: The objective of this review is to provide a comprehensive overview of the current state of knowledge about Heyde’s syndrome, including its etiology, clinical symptoms, imaging and laboratory findings. The issue of potential complications is raised. Moreover, treatment strategies are introduced.
Materials and methods: A review of the literature was conducted through PubMed database to identify articles related to Heyde’s Syndrome using following keywords: “Heyde’s syndrome’’, “acquired von Willebrand disease”, “aortic stenosis”, “gastrointestinal bleeding”.
Summary: Heyde’s syndrome is a rare disorder characterized by the triad of aortic stenosis, acquired coagulopathy, and anemia due to recurrent bleeding from gastrointestinal dysplasia. Diagnosis is based on positive results in combined tests such as colonoscopy with the presence of angiodysplasia, echocardiogram showing aortic stenosis, and screening tests for von Willebrand syndrome type 2A. The main treatment is the replacement of the aortic valve, either by surgery or by TAVI.
Conclusions: Awareness of Heyde's syndrome is important for its proper identification and treatment. The management of this disease requires the teamwork of physicians from different specialties.
References
1. Heyde EC: Gastrointestinal bleeding in aortic stenosis. N Engl J Med. 1958, 259:196-8. 10.1056/NEJM195807242590416
2. Mondal S, Hollander KN, Ibekwe SO, Williams B, Tanaka K. Heyde Syndrome- Pathophysiology and Perioperative Implications. J Cardiothorac Vasc Anesth. 2021 Nov;35(11):3331-3339. doi: 10.1053/j.jvca.2020.10.003. Epub 2020 Oct 8. PMID: 33132021.
3. Suárez EU, Vidal-Laso R. Heyde syndrome. Ann Hematol. 2023 Sep;102(9):2617-2618. doi: 10.1007/s00277-023-05299-y. Epub 2023 May 29 PMID: 37246201.
4. Goltstein LCMJ, Rooijakkers MJP, Hoeks M, Li WWL, van Wely MH, Rodwell L, van Royen N, Drenth JPH, van Geenen EM. Effectiveness of aortic valve replacement in Heyde syndrome: a meta-analysis. Eur Heart J. 2023 Sep 1;44(33):3168-3177. doi: 10.1093/eurheartj/ehad340. PMID: 37555393; PMCID: PMC10471563.
5. Waldschmidt L, Seiffert M. Heyde syndrome: treat aortic valve disease to stop gastrointestinal bleeding? Eur Heart J. 2023 Sep 1;44(33):3178-3180. doi: 10.1093/eurheartj/ehad277. PMID: 37403478.
6. Saha B, Wien E, Fancher N, Kahili-Heede M, Enriquez N, Velasco-Hughes A. Heyde's syndrome: a systematic review of case reports. BMJ Open Gastroenterol. 2022 May;9(1):e000866. doi: 10.1136/bmjgast-2021-000866. PMID: 35534046; PMCID: PMC9086603.
7. Abdelmaseih R, Thakker R, Abdelmasih R, Ali A, Hasan M. Perspectives on Heyde's Syndrome and Calcific Aortic Valve Disease. Curr Probl Cardiol. 2022 Oct;47(10):100930. doi: 10.1016/j.cpcardiol.2021.100930. Epub 2021 Jul 10. PMID: 34384616.
8. İlkeli E, Albeyoğlu Ş, Çiloğlu U, Sabri D. Heyde's syndrome. Asian Cardiovasc Thorac Ann. 2014 Jun;22(5):592-4. doi: 10.1177/0218492313478433. Epub 2013 Aug 27. PMID: 24867036.
9. Maksić M, Corović I, Stanisavljević I, Radojević D, Veljković T, Todorović Ž, Jovanović M, Zdravković N, Stojanović B, Marković BS, Jovanović I. Heyde Syndrome Unveiled: A Case Report with Current Literature Review and Molecular Insights. Int J Mol Sci. 2024 Oct 14;25(20):11041. doi: 10.3390/ijms252011041. PMID: 39456826; PMCID: PMC11507012.
10. Waldschmidt L, Drolz A, Heimburg P, Goßling A, Ludwig S, Voigtländer L, Linder M, Schofer N, Reichenspurner H, Blankenberg S, Westermann D, Conradi L, Kluwe J, Seiffert M. Heyde syndrome: prevalence and outcomes in patients undergoing transcatheter aortic valve implantation. Clin Res Cardiol. 2021 Dec;110(12):1939-1946. doi: 10.1007/s00392-021-01905-z. Epub 2021 Jul 23. PMID: 34302190; PMCID: PMC8639542.
11. Massyn MW, Khan SA. Heyde syndrome: a common diagnosis in older patients with severe aortic stenosis. Age Ageing. 2009 May;38(3):267-70; discussion 251. doi: 10.1093/ageing/afp019. Epub 2009 Mar 10. PMID: 19276092.
12. Dahiya DS, Kichloo A, Zain EA, Singh J, Wani F, Mehboob A. Heyde Syndrome: An Unusual Cause of Gastrointestinal Bleeding. J Investig Med High Impact Case Rep. 2021 Jan-Dec;9:2324709621997279. doi: 10.1177/2324709621997279. PMID: 33629596; PMCID: PMC7919197.
13. Tjahjadi C, Wee Y, Hay K, Tesar P, Clarke A, Walters DL, Bett N. Heyde syndrome revisited: anaemia and aortic stenosis. Intern Med J. 2017 Jul;47(7):814-818. doi: 10.1111/imj.13419. PMID: 28276127.
14. Ramachandran R, Uqdah H, Jani N. A case of recurrent obscure gastrointestinal bleeding: Heyde's syndrome - case report and review. J Community Hosp Intern Med Perspect. 2018 Jun 12;8(3):127-129. doi: 10.1080/20009666.2018.1470441. PMID: 29915650; PMCID: PMC5998287.
15. Iijima M, Itoh N, Murase R, Makino Y. A surgical case of aortic stenosis with recurrent gastrointestinal bleeding: Heyde syndrome. Int J Surg Case Rep. 2018;53:281-284. doi: 10.1016/j.ijscr.2018.10.078. Epub 2018 Nov 10. PMID: 30448636; PMCID: PMC6240727.
16. Schwaiger JP, Ludwiczek O, Graziadei I, Grander W. A Vicious Circle: Heyde Syndrome in Mild Aortic Stenosis. CASE (Phila). 2019 May 31;3(4):171-176. doi: 10.1016/j.case.2019.04.005. PMID: 31468021; PMCID: PMC6710854.
17. Vincentelli A, Susen S, Le Tourneau T, Six I, Fabre O, Juthier F, Bauters A, Decoene C, Goudemand J, Prat A, Jude B. Acquired von Willebrand syndrome in aortic stenosis. N Engl J Med. 2003 Jul 24;349(4):343-9. doi: 10.1056/NEJMoa022831. PMID: 12878741.
18. Desai R, Parekh T, Singh S, Patel U, Fong HK, Zalavadia D, Savani S, Doshi R, Sachdeva R, Kumar G. Alarming Increasing Trends in Hospitalizations and Mortality With Heyde's Syndrome: A Nationwide Inpatient Perspective (2007 to 2014). Am J Cardiol. 2019 Apr 1;123(7):1149-1155. doi: 10.1016/j.amjcard.2018.12.043. Epub 2019 Jan 7. PMID: 30660352.
19. Lourdusamy D, Mupparaju VK, Sharif NF, Ibebuogu UN. Aortic stenosis and Heyde's syndrome: A comprehensive review. World J Clin Cases. 2021 Sep 6;9(25):7319-7329. doi: 10.12998/wjcc.v9.i25.7319. PMID: 34616798; PMCID: PMC8464459.
20. Oommen A, Gautam K, Kumar A. Beyond Acquired Von Willebrand Deficiency: Exploring Alternative Mechanisms of Heyde's Syndrome. Cureus. 2023 Jul 7;15(7):e41494. doi: 10.7759/cureus.41494. PMID: 37551240; PMCID: PMC10404466.
21. Tsuchiya S, Matsumoto Y, Doman T, Fujiya T, Sugisawa J, Suda A, Sato K, Ikeda S, Shindo T, Kikuchi Y, Hao K, Takahashi J, Hatta W, Koike T, Masamune A, Saiki Y, Horiuchi H, Shimokawa H. Disappearance of Angiodysplasia Following Transcatheter Aortic Valve Implantation in a Patient with Heyde's Syndrome: A Case Report and Review of the Literature. J Atheroscler Thromb. 2020 Mar 1;27(3):271-277. doi: 10.5551/jat.49239. Epub 2019 Aug 3. PMID: 31378751; PMCID: PMC7113142.
22. Loscalzo J. From clinical observation to mechanism--Heyde's syndrome. N Engl J Med. 2012 Nov 15;367(20):1954-6. doi: 10.1056/NEJMcibr1205363. PMID: 23150964.
23. De Carlini CC, Cantù E, Erba N, Maggiolini S. Gastrointestinal bleeding associated to aortic valve stenosis (Heyde's syndrome): a case series and literature review. Eur Heart J Case Rep. 2023 Aug 18;7(8):ytad412. doi: 10.1093/ehjcr/ytad412. PMID: 37650079; PMCID: PMC10464592.
24. Hudzik B, Wilczek K, Gasior M. Heyde syndrome: gastrointestinal bleeding and aortic stenosis. CMAJ. 2016 Feb 2;188(2):135-138. doi: 10.1503/cmaj.150194. Epub 2015 Jun 29. PMID: 26124230; PMCID: PMC4732965.
25. Chukwudum CA, Vera S, Sharma M, Varon J, Surani S. Heyde Syndrome: A Case Report and Literature Review. Cureus. 2020 Apr 30;12(4):e7896. doi: 10.7759/cureus.7896. PMID: 32494511; PMCID: PMC7263001.
26. Notoya G, Niikura R, Yamada A, Ochi M, Kawai T, Koike K. Long Survival after Gastrointestinal Bleeding in a New-Onset Heyde's Syndrome Patient Treated with Multiple Endoscopic Hemostatic Procedures and Repeated Transfusions after Aortic Valve Replacement. Case Rep Gastroenterol. 2021 Sep 23;15(3):819-824. doi: 10.1159/000519004. PMID: 34720829; PMCID: PMC8543306.
27. Jamil D, Tran HH, Mansoor M, Bbutt SR, Satnarine T, Ratna P, Sarker A, Ramesh AS, Munoz Tello C, Mohammed L. Multimodal Treatment and Diagnostic Modalities in the Setting of Heyde's Syndrome: A Systematic Review. Cureus. 2022 Aug 16;14(8):e28080. doi: 10.7759/cureus.28080. PMID: 36127959; PMCID: PMC9477546.
28. Thompson JL 3rd, Schaff HV, Dearani JA, Park SJ, Sundt TM 3rd, Suri RM, Blackshear JL, Daly RC. Risk of recurrent gastrointestinal bleeding after aortic valve replacement in patients with Heyde syndrome. J Thorac Cardiovasc Surg. 2012 Jul;144(1):112-6. doi: 10.1016/j.jtcvs.2011.05.034. Epub 2011 Aug 23. PMID: 21864855.
29. Wang L, Wu K, Ou W, Su X, Sun G, Wang W, Xu Q, Wang B. Transcatheter aortic valve implantation for patients with heyde syndrome: A literature review of case reports. Heliyon. 2023 Jul 5;9(7):e17952. doi: 10.1016/j.heliyon.2023.e17952. PMID: 37539190; PMCID: PMC10395290.
30. Crawley JT, de Groot R, Xiang Y, Luken BM, Lane DA. Unraveling the scissile bond: how ADAMTS13 recognizes and cleaves von Willebrand factor. Blood. 2011 Sep 22;118(12):3212-21. doi: 10.1182/blood-2011-02-306597. Epub 2011 Jun 29. PMID: 21715306; PMCID: PMC3179391.
31. Ahmed T, Haque R. Heyde's Syndrome Complicating Management in a Patient With High Bleeding and Thrombotic Risks. Cureus. 2020 May 25;12(5):e8280. doi: 10.7759/cureus.8280. PMID: 32601556; PMCID: PMC7317131.
32. Khazi FM, Siddiqi NR, Karaly YM, Aljassim O, Al-Halees ZY. Heyde's Syndrome - An Enigma. J Saudi Heart Assoc. 2020 Dec 14;33(2):95-100. doi: 10.37616/2212-5043.1237. PMID: 34183904; PMCID: PMC8143720.
33. Eveborn GW, Schirmer H, Heggelund G, Lunde P, Rasmussen K. The evolving epidemiology of valvular aortic stenosis. the Tromsø study. Heart. 2013 Mar;99(6):396-400. doi: 10.1136/heartjnl-2012-302265. Epub 2012 Sep 2. PMID: 22942293.
34. Bhatia N, Basra SS, Skolnick AH, Wenger NK. Aortic valve disease in the older adult. J Geriatr Cardiol. 2016 Dec;13(12):941-944. doi: 10.11909/j.issn.1671-5411.2016.12.004. PMID: 28321235; PMCID: PMC5351823.
35. Batur P, Stewart WJ, Isaacson JH. Increased prevalence of aortic stenosis in patients with arteriovenous malformations of the gastrointestinal tract in Heyde syndrome. Arch Intern Med. 2003 Aug 11-25;163(15):1821-4. doi: 10.1001/archinte.163.15.1821. PMID: 12912718.
36. Ring L, Shah BN, Bhattacharyya S, Harkness A, Belham M, Oxborough D, Pearce K, Rana BS, Augustine DX, Robinson S, Tribouilloy C. Echocardiographic assessment of aortic stenosis: a practical guideline from the British Society of Echocardiography. Echo Res Pract. 2021 Apr 28;8(1):G19-G59. doi: 10.1530/ERP-20-0035. PMID: 33709955; PMCID: PMC8115410.
37. Badhwar V, Pereda D, Khaliel FH, Poffo R, Darehzereshki A, Mehaffey JH, Yan TD, Melnitchouk S, Geirsson A, Arghami A, Navia JL, Raikar GV, Weber AC, Ramzy D, Černý Š, Vojáček J, Smith RL, Bonatti J, Thourani VH, Wei LM. Outcomes following initial multicenter experience with robotic aortic valve replacement: Defining a path forward. J Thorac Cardiovasc Surg. 2024 Apr;167(4):1244-1250. doi: 10.1016/j.jtcvs.2024.01.020. Epub 2024 Jan 19. PMID: 38246340.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Grzegorz Adaśko, Michał Świda, Jakub Bazarewicz, Cezary Kubuj, Urszula Mazur, Daniel Dmowski, Anna Teresa Michalska, Paulina Ogonowska, Julia Waszak, Marcin Siwik

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Stats
Number of views and downloads: 92
Number of citations: 0