Gastric Antral Vascular Ectasia (GAVE) in Heyde Syndrome

Jay Bapaye, MD and Klaus Mönkemüller, MD, PhD, FASGE, FJGES

Department of Gastroenterology, Carilion Memorial Hospital, Virginia Tech Carilion School of Medicine, Roanoke, USA

An 80-year-old female with past medical history of chronic kidney disease stage IV, type 2 diabetes mellitus, quadruple coronary artery bypass, aortic and mitral stenosis treated with bioprosthetic aortic and mitral valves, pacemaker and defibrillator presented with recurrent occult gastrointestinal bleeding and iron deficiency anemia (hemoglobin 6.1 gr/dl). The patient had undergone multiple upper endoscopies and colonoscopies without significant findings except for small colon adenomas and “gastritis” and duodenal “polyps”. On EGD we found a linear, nodular antral gastritis, suspicious for nodular gastric antral vascular ectasia (GAVE) (Figure 1). Biopsies were obtained, confirming the endoscopic suspicion of GAVE. The GAVE was treated with multiple band ligations.

Figure 1. Gastric antra vascular ectasia (GAVE) of nodular type. A. “Nodular gastritis” in reality GAVE. B. Notice the characteristic edematous, erythematous, nodular, pseudo-polypoid linear appearance of nodular GAVE. C. Endoscopic band ligation of nodular GAVE.

The classic teaching refers to Heyde’s syndrome as “the association of aortic stenosis and cecal angiodysplasias” (1-3). Whereas this is partially true, here you will learn that Heyde syndrome is a type of hemophilia (acquired von Willebrand disease) leading to GI bleeding from various types of gastrointestinal angiodysplasias (2-5). Most often the angiodysplasias are in the small bowel and colon, but they can be located anywhere. Moreover, GAVE is also a form of deranged angioneogenesis (angiodysplasia), which may occur in the setting of Heyde syndrome (6). Now we know that Heyde syndrome is primarily a hemophilia, namely a form of acquired von Willebrand syndrome (2-4). There is a malfunction of von Willebrand factor, leading to gastrointestinal hemorrhage. In addition, deranged von Willebrand activity leads to angioneogenesis and occurrence of angiodysplasias and GAVE in the GI tract (2-4, 6). Many patients with aortic stenosis stop bleeding and develop angiodysplasias after receiving a new aortic valve (7). However, there are reports showing that Heyde syndrome may persist or develop despite aortic valve replacement (8, 9).

This case has several important take home messages. First, careful inspection of the stomach may uncover conditions such as nodular GAVE (Figure 2). Second, GAVE should be added to the spectrum of angiodysplasias occurring in Heyde syndrome. And finally, endoscopic band ligation is an alternative treatment of nodular GAVE.

Figure 2. Classification of GAVE. GAVE is characterized by a “characteristic” endoscopic pattern, mainly represented by red spots either organized in stripes radially departing from pylorus (“watermelon stomach” or arranged in a diffused-way or “honeycomb stomach”). In addition, there is a nodular variety, where there are multiple enlarged and nodular folds in the antrum (2, 3). Despite this, GAVE is often misclassified or mis-diagnosed.

References:

1. Heyde, E.C. Gastrointestinal Bleeding in Aortic Stenosis. N. Engl. J. Med. 1958, 259, 196.

2. Warkentin, T.; Morgan, D.G.; Moore, J.C. Aortic stenosis and bleeding gastrointestinal angiodysplasia: Is acquired von Willebrand’s disease the link? Lancet 1992, 340, 35–37.

3. 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;163(15):1821–1824. doi:10.1001/archinte.163.15.1821

4. Vincentelli A et al. Acquired von Willebrand in Aortic Stenosis. New Engl J Med. 2003

5. Okhota S, et el. Int. J. Mol. Sci. 2020, 21, 7804;

6. Dosi RV, Ambaliya AP, Patell RD, Sonune NN. Gastric antral vascular ectasia with aortic stenosis: Heydes syndrome. Indian J Med Sci. 2012 Mar-Apr;66(3-4):86-9. PMID: 23603627.

7. 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.

8. Akutagawa T, Shindo T, Yamanouchi K, Hayakawa M, Ureshino H, Tsuruoka N, Sakata Y, Shimoda R, Noguchi R, Furukawa K, Morita S, Iwakiri R, Kimura S, Matsumoto M, Fujimoto K. Persistent Gastrointestinal Angiodysplasia in Heyde's Syndrome after Aortic Valve Replacement. Intern Med. 2017 Sep 15;56(18):2431-2433. doi: 10.2169/internalmedicine.8603-16. Epub 2017 Aug 21. PMID: 28824071; PMCID: PMC5643169.

9. Oda, T., Kanamoto, R., Miyawaki, M. et al. Heyde-like syndrome occurring for the first time following aortic valve replacement with a bioprosthesis: a case report. Gen Thorac Cardiovasc Surg Cases 2, 52 (2023). https://doi.org/10.1186/s44215-023-00066-x