{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T23:49:58Z","timestamp":1785800998658,"version":"3.56.0"},"reference-count":122,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T00:00:00Z","timestamp":1728864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education, Science, and Technological Development of the Republic of Serbia","award":["415-03-65\/2024-03\/200122"],"award-info":[{"award-number":["415-03-65\/2024-03\/200122"]}]},{"name":"Ministry of Education, Science, and Technological Development of the Republic of Serbia","award":["415-03-65\/2024-03\/200111"],"award-info":[{"award-number":["415-03-65\/2024-03\/200111"]}]},{"name":"Ministry of Education, Science, and Technological Development of the Republic of Serbia","award":["JP05\/23"],"award-info":[{"award-number":["JP05\/23"]}]},{"name":"Ministry of Education, Science, and Technological Development of the Republic of Serbia","award":["JP06\/23"],"award-info":[{"award-number":["JP06\/23"]}]},{"name":"Ministry of Education, Science, and Technological Development of the Republic of Serbia","award":["JP17\/19"],"award-info":[{"award-number":["JP17\/19"]}]},{"name":"Junior Projects of the Faculty of Medical Sciences at the University of Kragujevac, Serbia","award":["415-03-65\/2024-03\/200122"],"award-info":[{"award-number":["415-03-65\/2024-03\/200122"]}]},{"name":"Junior Projects of the Faculty of Medical Sciences at the University of Kragujevac, Serbia","award":["415-03-65\/2024-03\/200111"],"award-info":[{"award-number":["415-03-65\/2024-03\/200111"]}]},{"name":"Junior Projects of the Faculty of Medical Sciences at the University of Kragujevac, Serbia","award":["JP05\/23"],"award-info":[{"award-number":["JP05\/23"]}]},{"name":"Junior Projects of the Faculty of Medical Sciences at the University of Kragujevac, Serbia","award":["JP06\/23"],"award-info":[{"award-number":["JP06\/23"]}]},{"name":"Junior Projects of the Faculty of Medical Sciences at the University of Kragujevac, Serbia","award":["JP17\/19"],"award-info":[{"award-number":["JP17\/19"]}]},{"name":"Senate of the University of Defense","award":["415-03-65\/2024-03\/200122"],"award-info":[{"award-number":["415-03-65\/2024-03\/200122"]}]},{"name":"Senate of the University of Defense","award":["415-03-65\/2024-03\/200111"],"award-info":[{"award-number":["415-03-65\/2024-03\/200111"]}]},{"name":"Senate of the University of Defense","award":["JP05\/23"],"award-info":[{"award-number":["JP05\/23"]}]},{"name":"Senate of the University of Defense","award":["JP06\/23"],"award-info":[{"award-number":["JP06\/23"]}]},{"name":"Senate of the University of Defense","award":["JP17\/19"],"award-info":[{"award-number":["JP17\/19"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Heyde syndrome, marked by aortic stenosis, gastrointestinal bleeding from angiodysplasia, and acquired von Willebrand syndrome, is often underreported. Shear stress from a narrowed aortic valve degrades von Willebrand factor multimers, leading to angiodysplasia formation and von Willebrand factor deficiency. This case report aims to raise clinician awareness of Heyde syndrome, its complexity, and the need for a multidisciplinary approach. We present a 75-year-old man with aortic stenosis, gastrointestinal bleeding from angiodysplasia, and acquired von Willebrand syndrome type 2A. The patient was successfully treated with argon plasma coagulation and blood transfusions. He declined further treatment for aortic stenosis but was in good overall health with improved laboratory results during follow-up. Additionally, we provide a comprehensive review of the molecular mechanisms involved in the development of this syndrome, discuss current diagnostic and treatment approaches, and offer future perspectives for further research on this topic.<\/jats:p>","DOI":"10.3390\/ijms252011041","type":"journal-article","created":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T12:44:31Z","timestamp":1728909871000},"page":"11041","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Heyde Syndrome Unveiled: A Case Report with Current Literature Review and Molecular Insights"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8259-6060","authenticated-orcid":false,"given":"Mladen","family":"Maksi\u0107","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4675-4344","authenticated-orcid":false,"given":"Irfan","family":"Corovi\u0107","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8308-8885","authenticated-orcid":false,"given":"Isidora","family":"Stanisavljevi\u0107","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9700-0215","authenticated-orcid":false,"given":"Du\u0161an","family":"Radojevi\u0107","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tijana","family":"Veljkovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9989-5921","authenticated-orcid":false,"given":"\u017deljko","family":"Todorovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7691-6133","authenticated-orcid":false,"given":"Marina","family":"Jovanovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia"},{"name":"Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nata\u0161a","family":"Zdravkovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6115-612X","authenticated-orcid":false,"given":"Bojan","family":"Stojanovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bojana Simovi\u0107","family":"Markovi\u0107","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1169-2378","authenticated-orcid":false,"given":"Ivan","family":"Jovanovi\u0107","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1056\/NEJM195807242590416","article-title":"Gastrointestinal bleeding in aortic stenosis","volume":"259","author":"Heyde","year":"1958","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2549","DOI":"10.3748\/wjg.v25.i21.2549","article-title":"Diagnostic and therapeutic challenges of gastrointestinal angiodysplasias: A critical review and view points","volume":"25","year":"2019","journal-title":"World J. Gastroenterol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"924","DOI":"10.12659\/AJCR.911298","article-title":"A Case of Heyde Syndrome with Resolution of Gastrointestinal Bleeding Two Weeks After Aortic Valve Replacement","volume":"19","author":"Alshuwaykh","year":"2018","journal-title":"Am. J. Case Rep."},{"key":"ref_4","first-page":"1939","article-title":"Heyde syndrome: Prevalence and outcomes in patients undergoing transcatheter aortic valve implantation","volume":"110","author":"Waldschmidt","year":"2021","journal-title":"Clin. Res. Cardiol. Off. J. Ger. Card. Soc."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.cger.2019.03.007","article-title":"Heyde Syndrome: Aortic Stenosis and Beyond","volume":"35","author":"Blackshear","year":"2019","journal-title":"Clin. Geriatr. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1111\/bjh.12272","article-title":"Von Willebrand disease-associated angiodysplasia: A few answers, still many questions","volume":"161","author":"Franchini","year":"2013","journal-title":"Br. J. Haematol."},{"key":"ref_7","first-page":"41","article-title":"Perils, problems, and progress in laboratory diagnosis of von Willebrand disease","volume":"40","author":"Flood","year":"2014","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1038\/ajg.2015.246","article-title":"ACG Clinical Guideline: Diagnosis and Management of Small Bowel Bleeding","volume":"110","author":"Gerson","year":"2015","journal-title":"Am. J. Gastroenterol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e000866","DOI":"10.1136\/bmjgast-2021-000866","article-title":"Heyde\u2019s syndrome: A systematic review of case reports","volume":"9","author":"Saha","year":"2022","journal-title":"BMJ Open Gastroenterol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1016\/j.jacc.2018.12.045","article-title":"von Willebrand Factor and Management of Heart Valve Disease: JACC Review Topic of the Week","volume":"73","author":"Vincent","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1182\/bloodadvances.2020003265","article-title":"ASH ISTH NHF WFH 2021 guidelines on the diagnosis of von Willebrand disease","volume":"5","author":"James","year":"2021","journal-title":"Blood Adv."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1111\/jth.13551","article-title":"Von Willebrand factor and angiogenesis: Basic and applied issues","volume":"15","author":"Randi","year":"2017","journal-title":"J. Thromb. Haemost."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1182\/blood-2012-01-405134","article-title":"Sequence and structure relationships within von Willebrand factor","volume":"120","author":"Zhou","year":"2012","journal-title":"Blood"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.bcmd.2017.04.006","article-title":"Platelet factor XI: Intracellular localization and mRNA splicing following platelet activation","volume":"69","author":"Zucker","year":"2018","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_15","first-page":"e177","article-title":"Effects of moderate-intensity physical exercise on pharmacokinetics of factor VIII and von Willebrand factor in young adults with severe haemophilia A: A pilot study","volume":"22","author":"Zourikian","year":"2016","journal-title":"Haemoph. Off. J. World Fed. Hemoph."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1111\/jth.13749","article-title":"Abnormal von Willebrand factor secretion, factor VIII stabilization and thrombus dynamics in type 2N von Willebrand disease mice","volume":"15","author":"Swystun","year":"2017","journal-title":"J. Thromb. Haemost."},{"key":"ref_17","first-page":"3177","article-title":"Hemostasis components in cerebral amyloid angiopathy and Alzheimer\u2019s disease","volume":"42","author":"Ziliotto","year":"2021","journal-title":"Neurol. Sci. Off. J. Ital. Neurol. Soc. Ital. Soc. Clin. Neurophysiol."},{"key":"ref_18","first-page":"338","article-title":"Monitoring Therapy during Treatment of von Willebrand Disease","volume":"43","author":"Favaloro","year":"2017","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_19","first-page":"e232","article-title":"Platelet Activation Pathways Controlling Reversible Integrin \u03b1IIb\u03b23 Activation","volume":"8","author":"Zou","year":"2024","journal-title":"TH Open Companion J. Thromb. Haemost."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1097\/MCG.0000000000000260","article-title":"Expression of Angiogenic Factors in Patients With Sporadic Small Bowel Angiodysplasia","volume":"49","author":"Holleran","year":"2015","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.bbrc.2014.08.078","article-title":"Structural insights into the interaction of blood coagulation co-factor VIIIa with factor IXa: A computational protein-protein docking and molecular dynamics refinement study","volume":"452","author":"Venkateswarlu","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1111\/bjh.12473","article-title":"Different factor VIII neutralizing effects on anti-factor VIII inhibitor antibodies associated with epitope specificity and von Willebrand factor","volume":"163","author":"Yada","year":"2013","journal-title":"Br. J. Haematol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1055\/s-0039-3402430","article-title":"Genetic Background of von Willebrand Disease: History, Current State, and Future Perspectives","volume":"46","author":"Zolkova","year":"2020","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_24","first-page":"e29733","article-title":"A Child With Hereditary Spherocytosis Associated With Von Willebrand\u2019s Disease: A Case Report From Saudi Arabia","volume":"14","author":"Zolaly","year":"2022","journal-title":"Cureus"},{"key":"ref_25","first-page":"445","article-title":"Diagnostic biologique de la maladie de Willebrand et ses difficultes [Biological diagnosis of Von Willebrand disease and its difficulties]","volume":"85","author":"Znazen","year":"2007","journal-title":"Tunis. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1055\/s-0031-1281037","article-title":"Management of inherited von Willebrand disease in Italy: Results from the retrospective study on 1234 patients","volume":"37","author":"Federici","year":"2011","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.thromres.2017.09.025","article-title":"Von Willebrand disease mutation spectrum and associated mutation mechanisms","volume":"159","author":"Eikenboom","year":"2017","journal-title":"Thromb. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e3038","DOI":"10.1097\/MD.0000000000003038","article-title":"A Laboratory Phenotype\/Genotype Correlation of 1167 French Patients From 670 Families With von Willebrand Disease: A New Epidemiologic Picture","volume":"95","author":"Veyradier","year":"2016","journal-title":"Medicine"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1111\/jth.13243","article-title":"Developments in the diagnostic procedures for von Willebrand disease","volume":"14","author":"Eikenboom","year":"2016","journal-title":"J. Thromb. Haemost."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1002\/jca.20202","article-title":"Effect of blood group on idiopathic thrombotic thrombocytopenic purpura","volume":"24","author":"Zuberi","year":"2009","journal-title":"J. Clin. Apher."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/jth.12221","article-title":"Structure-function and regulation of ADAMTS-13 protease","volume":"11","author":"Zheng","year":"2013","journal-title":"J. Thromb. Haemost."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4143","DOI":"10.1182\/blood-2013-07-517086","article-title":"Solution structure of the major factor VIII binding region on von Willebrand factor","volume":"123","author":"Shiltagh","year":"2014","journal-title":"Blood"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1007\/s11239-012-0719-5","article-title":"Relationship between ABO blood groups and von Willebrand factor, ADAMTS13 and factor VIII in patients undergoing hemodialysis","volume":"33","author":"Rios","year":"2012","journal-title":"J. Thromb. Thrombol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e257760","DOI":"10.1136\/bcr-2023-257760","article-title":"Surprise diagnosis of acquired von Willebrand syndrome in a patient previously thought to have type III von Willebrand disease: Evaluation and periprocedural management","volume":"16","author":"Zhou","year":"2023","journal-title":"BMJ Case Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3389\/fmed.2019.00007","article-title":"Acquired von Willebrand Syndrome in Patients With Ventricular Assist Device","volume":"6","author":"Rauch","year":"2019","journal-title":"Front. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1111\/j.1600-0609.2011.01636.x","article-title":"Pathophysiology of acquired von Willebrand disease: A concise review","volume":"87","author":"Shetty","year":"2011","journal-title":"Eur. J. Haematol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2646","DOI":"10.1007\/s10439-021-02845-5","article-title":"A Continuum Model for the Unfolding of von Willebrand Factor","volume":"49","author":"Zhussupbekov","year":"2021","journal-title":"Ann. Biomed. Eng."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1111\/j.1365-2516.2007.01642.x","article-title":"Hypothyroidism and acquired von Willebrand\u2019s syndrome: A systematic review","volume":"14","author":"Manfredi","year":"2008","journal-title":"Haemoph. Off. J. World Fed. Hemoph."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"S56","DOI":"10.1016\/S0049-3848(14)50010-2","article-title":"Supportive transfusion therapy in cancer patients with acquired defects of hemostasis","volume":"133","author":"Federici","year":"2014","journal-title":"Thromb. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1159\/000214858","article-title":"Causes, etiology and diagnosis of acquired von Willebrand disease: A prospective diagnostic workup to establish the most effective therapeutic strategies","volume":"121","author":"Sucker","year":"2009","journal-title":"Acta Haematol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"6777","DOI":"10.1182\/blood-2010-11-297580","article-title":"How I treat the acquired von Willebrand syndrome","volume":"117","author":"Tiede","year":"2011","journal-title":"Blood"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1111\/joic.12478","article-title":"Von Willebrand factor revisited","volume":"31","author":"Yasar","year":"2018","journal-title":"J. Interv. Cardiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"S11","DOI":"10.1097\/01.mbc.0000167657.85143.ad","article-title":"Shear stress and the role of high molecular weight von Willebrand factor multimers in thrombus formation","volume":"16","author":"Dong","year":"2005","journal-title":"Blood Coagul. Fibrinolysis Int. J. Haemost. Thromb."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1126\/science.1170905","article-title":"Mechanoenzymatic cleavage of the ultralarge vascular protein von Willebrand factor","volume":"324","author":"Zhang","year":"2009","journal-title":"Science"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4870","DOI":"10.1182\/blood-2009-11-254193","article-title":"Mutation and ADAMTS13-dependent modulation of disease severity in a mouse model for von Willebrand disease type 2B","volume":"115","author":"Rayes","year":"2010","journal-title":"Blood"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"303","DOI":"10.5551\/jat.RV17031","article-title":"Acquired von Willebrand Syndrome Associated with Cardiovascular Diseases","volume":"26","author":"Horiuchi","year":"2019","journal-title":"J. Atheroscler. Thromb."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e17952","DOI":"10.1016\/j.heliyon.2023.e17952","article-title":"Transcatheter aortic valve implantation for patients with heyde syndrome: A literature review of case reports","volume":"9","author":"Wang","year":"2023","journal-title":"Heliyon"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1056\/NEJMoa022831","article-title":"Acquired von Willebrand syndrome in aortic stenosis","volume":"349","author":"Vincentelli","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.5551\/jat.30809","article-title":"Unexpectedly High Prevalence of Acquired von Willebrand Syndrome in Patients with Severe Aortic Stenosis as Evaluated with a Novel Large Multimer Index","volume":"22","author":"Tamura","year":"2015","journal-title":"J. Atheroscler. Thromb."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1093\/ehjci\/jeaa056","article-title":"High-molecular-weight von Willebrand Factor multimer ratio differentiates true-severe from pseudo-severe classical low-flow, low-gradient aortic stenosis","volume":"21","author":"Kellermair","year":"2020","journal-title":"Eur. Heart J. Cardiovasc. Imaging"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jcin.2018.09.041","article-title":"Blood Disorders in Patients Undergoing Transcatheter Aortic Valve Replacement: A Review","volume":"12","author":"Puri","year":"2019","journal-title":"JACC Cardiovasc. Interv."},{"key":"ref_52","first-page":"2188","article-title":"Angiodysplasia in the renal patient: How to diagnose and how to treat?","volume":"13","author":"Poralla","year":"1998","journal-title":"Nephrol. Dial. Transplant. Off. Publ. Eur. Dial. Transpl. Assoc. \u2014Eur. Ren. Assoc."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1053\/bega.2000.0155","article-title":"Vascular malformations of the gastrointestinal tract","volume":"15","author":"Gordon","year":"2001","journal-title":"Best. Pract. Res. Clin. Gastroenterol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1111\/apt.12527","article-title":"Review article: Gastrointestinal angiodysplasia\u2014Pathogenesis, diagnosis and management","volume":"39","author":"Sami","year":"2014","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"6235","DOI":"10.3748\/wjg.v18.i43.6235","article-title":"Distribution of bleeding gastrointestinal angioectasias in a Western population","volume":"18","author":"Bollinger","year":"2012","journal-title":"World J. Gastroenterol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1001\/archinte.1985.00360030098019","article-title":"Angiodysplasia as a cause of upper gastrointestinal bleeding","volume":"145","author":"Clouse","year":"1985","journal-title":"Arch. Intern. Med."},{"key":"ref_57","first-page":"564","article-title":"Prevalence and natural history of colonic angiodysplasia among healthy asymptomatic people","volume":"90","author":"Foutch","year":"1995","journal-title":"Am. J. Gastroenterol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1159\/000524268","article-title":"Small-Bowel Angioectasias: Are They Responsible for a Real Impact on Survival?","volume":"30","author":"Correia","year":"2022","journal-title":"GE-Port. J. Gastroenterol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1055\/s-2007-1018385","article-title":"Vascular malformations of the stomach and duodenum: An endoscopic classification","volume":"18","author":"Figa","year":"1986","journal-title":"Endoscopy"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1111\/j.1365-2036.2005.02485.x","article-title":"Review article: The management of lower gastrointestinal bleeding","volume":"21","author":"Farrell","year":"2005","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1053\/j.gastro.2007.06.007","article-title":"American Gastroenterological Association American Gastroenterological Association (AGA) Institute technical review on obscure gastrointestinal bleeding","volume":"133","author":"Raju","year":"2007","journal-title":"Gastroenterology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3331","DOI":"10.1053\/j.jvca.2020.10.003","article-title":"Heyde Syndrome-Pathophysiology and Perioperative Implications","volume":"35","author":"Mondal","year":"2021","journal-title":"J. Cardiothorac. Vasc. Anesth."},{"key":"ref_63","first-page":"1110","article-title":"A review on angiogenesis and its assays","volume":"15","author":"Tahergorabi","year":"2012","journal-title":"Iran. J. Basic. Med. Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1038\/nm0603-653","article-title":"Angiogenesis in health and disease","volume":"9","author":"Carmeliet","year":"2003","journal-title":"Nat. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1055\/s-2004-835678","article-title":"Platelet dysfunction in renal failure","volume":"30","author":"Boccardo","year":"2004","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1046\/j.1365-2796.2000.00717-2.x","article-title":"Increased plasma vascular endothelial growth factor levels in patients with angiodysplasia","volume":"248","author":"Fujita","year":"2000","journal-title":"J. Intern. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1111\/j.1572-0241.1999.01017.x","article-title":"Increased expression of angiogenic factors in human colonic angiodysplasia","volume":"94","author":"Junquera","year":"1999","journal-title":"Am. J. Gastroenterol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.ijscr.2017.06.068","article-title":"Ileal angiodysplasia presentation as a bowel obstruction: A case report","volume":"39","author":"Ghdes","year":"2017","journal-title":"Int. J. Surg. Case Rep."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1016\/S0016-5085(77)80149-2","article-title":"On the nature and etiology of vascular ectasias of the colon. Degenerative lesions of aging","volume":"72","author":"Boley","year":"1977","journal-title":"Gastroenterology"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/S0003-4975(10)60563-2","article-title":"Resolution of Heyde\u2019s syndrome of aortic stenosis and gastrointestinal bleeding after aortic valve replacement","volume":"42","author":"Scheffer","year":"1986","journal-title":"Ann. Thorac. Surg."},{"key":"ref_71","first-page":"2329","article-title":"Upper gastrointestinal bleeding in patients with chronic renal failure: Role of vascular ectasia","volume":"91","author":"Chalasani","year":"1996","journal-title":"Am. J. Gastroenterol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1177\/1947601911423654","article-title":"Hypoxia-induced angiogenesis: Good and evil","volume":"2","author":"Krock","year":"2011","journal-title":"Genes Cancer"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1111\/j.1525-139X.2006.00179.x","article-title":"Platelet dysfunction and end-stage renal disease","volume":"19","author":"Kaw","year":"2006","journal-title":"Semin. Dial."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1111\/sdi.12301","article-title":"Evidence-based review of gastrointestinal bleeding in the chronic kidney disease patient","volume":"28","author":"Kalman","year":"2015","journal-title":"Semin. Dial."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1182\/blood.V76.7.1336.1336","article-title":"Uremic platelets have a functional defect affecting the interaction of von Willebrand factor with glycoprotein IIb-IIIa","volume":"76","author":"Escolar","year":"1990","journal-title":"Blood"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Chaudhary, P.K., Kim, S., and Kim, S. (2022). An Insight into Recent Advances on Platelet Function in Health and Disease. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23116022"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/S0016-5107(80)73303-5","article-title":"Endoscopic diagnosis and therapy of mucosal vascular abnormalities of the gastrointestinal tract occurring in elderly patients and associated with cardiac, vascular, and pulmonary disease","volume":"26","author":"Rogers","year":"1980","journal-title":"Gastrointest. Endosc."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1007\/BF01255601","article-title":"Idiopathic gastrointestinal bleeding and aortic stenosis","volume":"19","author":"Cody","year":"1974","journal-title":"Am. J. Dig. Dis."},{"key":"ref_79","first-page":"1623","article-title":"Aortic stenosis and unexplained gastrointestinal bleeding","volume":"50","author":"Nordstrom","year":"1967","journal-title":"Minn. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/j.lpm.2011.10.012","article-title":"Severe gastro-intestinal angiodysplasia in context of Heyde\u2019s syndrome durably cured after aortic valve replacement","volume":"41","author":"Michot","year":"2012","journal-title":"Presse Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"47","DOI":"10.2174\/157340311795677699","article-title":"Treatment of Heyde\u2019s Syndrome by Aortic Valve Replacement","volume":"7","author":"Karam","year":"2011","journal-title":"Curr. Cardiol. Rev."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1016\/S0016-5085(88)80095-7","article-title":"Aortic stenosis, idiopathic gastrointestinal bleeding, and angiodysplasia: Is there an association? A methodologic critique of the literature","volume":"95","author":"Imperiale","year":"1988","journal-title":"Gastroenterology"},{"key":"ref_83","first-page":"75","article-title":"Prevalence of aortic valve stenosis in patients affected by gastrointestinal angiodysplasia","volume":"2","author":"Oneglia","year":"1993","journal-title":"Eur. J. Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/0002-9343(89)90295-7","article-title":"Reassessment of the association between gastrointestinal arteriovenous malformations and aortic stenosis","volume":"86","author":"Mehta","year":"1989","journal-title":"Am. J. Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1001\/archinte.163.15.1821","article-title":"Increased prevalence of aortic stenosis in patients with arteriovenous malformations of the gastrointestinal tract in Heyde syndrome","volume":"163","author":"Batur","year":"2003","journal-title":"Arch. Intern. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/s10456-009-9141-9","article-title":"Cooperation between integrin alphavbeta3 and VEGFR2 in angiogenesis","volume":"12","author":"Somanath","year":"2009","journal-title":"Angiogenesis"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"6471","DOI":"10.1073\/pnas.84.18.6471","article-title":"Human endothelial cells synthesize and express an Arg-Gly-Asp-directed adhesion receptor involved in attachment to fibrinogen and von Willebrand factor","volume":"84","author":"Cheresh","year":"1987","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/nm.1941","article-title":"Stimulation of tumor growth and angiogenesis by low concentrations of RGD-mimetic integrin inhibitors","volume":"15","author":"Reynolds","year":"2009","journal-title":"Nat. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.gie.2014.03.040","article-title":"GI bleeding in patients with continuous-flow left ventricular assist devices: A systematic review and meta-analysis","volume":"80","author":"Draper","year":"2014","journal-title":"Gastrointest. Endosc."},{"key":"ref_90","first-page":"371","article-title":"Aortic Stenosis: Diagnosis and Treatment","volume":"93","author":"Grimard","year":"2016","journal-title":"Am. Fam. Physician"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"467","DOI":"10.4291\/wjgp.v5.i4.467","article-title":"Diagnosis of gastrointestinal bleeding: A practical guide for clinicians","volume":"5","author":"Kim","year":"2014","journal-title":"World J. Gastrointest. Pathophysiol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"7319","DOI":"10.12998\/wjcc.v9.i25.7319","article-title":"Aortic stenosis and Heyde\u2019s syndrome: A comprehensive review","volume":"9","author":"Lourdusamy","year":"2021","journal-title":"World J. Clin. Cases"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1111\/nyas.14092","article-title":"Anemia epidemiology, pathophysiology, and etiology in low- and middle-income countries","volume":"1450","author":"Chaparro","year":"2019","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_94","first-page":"98","article-title":"Iron deficiency anemia: Evaluation and management","volume":"87","author":"Short","year":"2013","journal-title":"Am. Fam. Physician"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"81","DOI":"10.36628\/ijhf.2020.0036","article-title":"Biomarkers in Acute Heart Failure: Diagnosis, Prognosis, and Treatment","volume":"3","author":"Wettersten","year":"2021","journal-title":"Int. J. Heart Fail."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"G19","DOI":"10.1530\/ERP-20-0035","article-title":"Echocardiographic assessment of aortic stenosis: A practical guideline from the British Society of Echocardiography","volume":"8","author":"Ring","year":"2021","journal-title":"Echo Res. Pract."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.giec.2016.08.012","article-title":"Gastrointestinal Angiodysplasia: Diagnosis and Management","volume":"27","author":"Jackson","year":"2017","journal-title":"Gastrointest. Endosc. Clin."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"3168","DOI":"10.1093\/eurheartj\/ehad340","article-title":"Effectiveness of aortic valve replacement in Heyde syndrome: A meta-analysis","volume":"44","author":"Goltstein","year":"2023","journal-title":"Eur. Heart J."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.jtcvs.2011.05.034","article-title":"Risk of recurrent gastrointestinal bleeding after aortic valve replacement in patients with Heyde syndrome","volume":"144","author":"Thompson","year":"2012","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"721","DOI":"10.4070\/kcj.2022.0234","article-title":"Aortic Stenosis: New Insights in Diagnosis, Treatment, and Prevention","volume":"52","author":"Ito","year":"2022","journal-title":"Korean Circ. J."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1016\/j.jtcvs.2024.01.020","article-title":"Outcomes following initial multicenter experience with robotic aortic valve replacement: Defining a path forward","volume":"167","author":"Badhwar","year":"2024","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2317","DOI":"10.1016\/S0140-6736(23)01518-0","article-title":"Treatment of severe symptomatic aortic valve stenosis using non-invasive ultrasound therapy: A cohort study","volume":"402","author":"Messas","year":"2023","journal-title":"Lancet"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1080\/17474124.2023.2214726","article-title":"Small bowel bleeding: Clinical diagnosis and management in the elderly","volume":"17","author":"Oka","year":"2023","journal-title":"Expert Rev. Gastroenterol. Hepatol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1016\/S2468-1253(21)00262-4","article-title":"Effectiveness and predictors of response to somatostatin analogues in patients with gastrointestinal angiodysplasias: A systematic review and individual patient data meta-analysis","volume":"6","author":"Goltstein","year":"2021","journal-title":"Lancet. Gastroenterol. Hepatol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1053\/j.gastro.2023.12.020","article-title":"Standard of Care Versus Octreotide in Angiodysplasia-Related Bleeding (the OCEAN Study): A Multicenter Randomized Controlled Trial","volume":"166","author":"Goltstein","year":"2024","journal-title":"Gastroenterology"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1080\/14656566.2024.2348091","article-title":"Pharmacotherapy for Gastrointestinal Angiodysplasia: Is it effective?","volume":"25","author":"Johnson","year":"2024","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1056\/NEJMoa2303706","article-title":"Thalidomide for Recurrent Bleeding Due to Small-Intestinal Angiodysplasia","volume":"389","author":"Chen","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_108","first-page":"194","article-title":"Management of thalidomide toxicity","volume":"1","author":"Ghobrial","year":"2003","journal-title":"J. Support. Oncol."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Becq, A., Sidhu, R., Goltstein, L.C.M.J., and Dray, X. (2024). Recent advances in the treatment of refractory gastrointestinal angiodysplasia. United Eur. Gastroenterol. J., Advance online publication.","DOI":"10.1002\/ueg2.12648"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1080\/17474086.2016.1214070","article-title":"Von Willebrand factor (Vonvendi\u00ae): The first recombinant product licensed for the treatment of von Willebrand disease","volume":"9","author":"Franchini","year":"2016","journal-title":"Expert Rev. Hematol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/S0003-4975(10)62112-1","article-title":"The association of unexplained gastrointestinal bleeding with calcific aortic stenosis","volume":"44","author":"King","year":"1987","journal-title":"Ann. Thorac. Surg."},{"key":"ref_112","first-page":"e25461","article-title":"Comparison Between Intravenous and Intramuscular Octreotide in the Management of Heyde\u2019s Syndrome","volume":"14","author":"Cheema","year":"2022","journal-title":"Cureus"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"907","DOI":"10.14740\/jocmr2321w","article-title":"Severe Gastrointestinal Bleeding in a Patient With Subvalvular Aortic Stenosis Treated With Thalidomide and Octreotide: Bridging to Transcoronary Ablation of Septal Hypertrophy","volume":"7","author":"Poulsen","year":"2015","journal-title":"J. Clin. Med. Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"3850","DOI":"10.1182\/bloodadvances.2021004810","article-title":"Systemic bevacizumab for refractory bleeding and transfusion-dependent anemia in Heyde syndrome","volume":"5","author":"Song","year":"2021","journal-title":"Blood Adv."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.healun.2020.02.012","article-title":"Intravenous bevacizumab as a novel treatment for refractory left ventricular assist device-related gastrointestinal bleeding","volume":"39","author":"Asleh","year":"2020","journal-title":"J. Heart Lung Transplant. Off. Publ. Int. Soc. Heart Transplant."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"bcr2017221832","DOI":"10.1136\/bcr-2017-221832","article-title":"Tranexamic acid in treatment-resistant chronic transfusion-dependent gastrointestinal angiodysplasia bleeding","volume":"2017","author":"Grooteman","year":"2017","journal-title":"BMJ Case Rep."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"127","DOI":"10.4291\/wjgp.v8.i3.127","article-title":"Assessment of serum angiogenic factors as a diagnostic aid for small bowel angiodysplasia in patients with obscure gastrointestinal bleeding and anaemia","volume":"8","author":"Holleran","year":"2017","journal-title":"World J. Gastrointest. Pathophysiol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"2885","DOI":"10.1093\/eurheartj\/ehab153","article-title":"Electrocardiogram screening for aortic valve stenosis using artificial intelligence","volume":"42","author":"Attia","year":"2021","journal-title":"Eur. Heart J."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"4592","DOI":"10.1093\/eurheartj\/ehad456","article-title":"Severe aortic stenosis detection by deep learning applied to echocardiography","volume":"44","author":"Holste","year":"2023","journal-title":"Eur. Heart J."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"31","DOI":"10.31083\/j.rcm2501031","article-title":"Artificial Intelligence in the Screening, Diagnosis, and Management of Aortic Stenosis","volume":"25","author":"Zhang","year":"2024","journal-title":"Rev. Cardiovasc. Med."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"879","DOI":"10.3748\/wjg.v29.i5.879","article-title":"Convolutional neural network-based segmentation network applied to image recognition of angiodysplasias lesion under capsule endoscopy","volume":"29","author":"Chu","year":"2023","journal-title":"World J. Gastroenterol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.thromres.2021.05.008","article-title":"Deciphered coagulation profile to diagnose the antiphospholipid syndrome using artificial intelligence","volume":"203","author":"Wahl","year":"2021","journal-title":"Thromb. Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/20\/11041\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:13:17Z","timestamp":1760112797000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/20\/11041"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,14]]},"references-count":122,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["ijms252011041"],"URL":"https:\/\/doi.org\/10.3390\/ijms252011041","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,14]]}}}