Heyde Syndrome

Dr. Marong treated us to the case of an elderly male with a history of chronic GI bleeding secondary to AVMs who was admitted to the hospital with two days of increasing dyspnea and fatigue: the patient was ultimately diagnosed with Heyde Syndrome.

What is Heyde Syndrome?

Heyde syndrome is the triad of aortic stenosis, acquired Von Willebrand syndrome type 2A (vWS-2A) and anemia due to bleeding intestinal arteriovenous malformation (AVM).

There are two leading theories to as how this develops:

1. Chronic Hypoxia & Altered Pulse Wave Theory- This theory states that the presence of aortic stenosis results in chronic low-grade hypoxia, which results in reflex sympathetic vasodilation & smooth muscle relaxation, which ultimately results in GI vessel wall ectasia.

2. Acquired Von Willebrand syndrome theory: this is the more accepted & clinically proven theory

J.Loscalzo. From Clinical observation to Mechanism. NEJM (2012);367:1954-1956

This theory states that von Willebrand multimer is sheared by the stenotic aortic valve, ultimately resulting in this chronic bleeding.

This theory is cool, but how does this apply to clinical practice?

First, both aortic stenosis and GI bleeding are common conditions in elderly patients. The prevalence of critical aortic stenosis is 1-2 % at age 75; 6% at 85.

Additionally, angiodysplasia is not an uncommon cause of inpatient GI bleeds, estimated to account for up to 3% of admissions for GI bleeding. It is also incidentally found in 3% of non-bleeding patients greater than age 65.

Furthermore, aortic valve replacement cures patients of Heyde syndrome. In a retrospective study: 91 patients with chronic unexplained GIB and aortic stenosis, bleeding ceased in 93% treated with valvular replacement!

References

1. Heyde EC. Gastrointestinal bleeding in aortic stenosis (Letter).N Engl J Med 1958; 259: 196

2. Warkentin TE, Moore JC, Anand SS et al. Gastrointestinal bleeding, angiodysplasia, cardiovascular disease, and acquired von Willebrand syndrome. Transfus Med Rev 2003; 17: 272–86.

3. Pate GE, ChandavimolM,Naiman SC et al. Heyde’s syndrome:a review. J Heart Valve Dis 2004; 13: 701–12.

4. 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: 1821–4.

5. Luckraz H, Hashim S, Ashraf S. Aortic stenosis and angiodysplasia in the elderly: common things occur commonly? Interactive Cardiovasc Thorac Surg 2003; 2: 526–8.

6. Pareti FI, Lattuada A, Bressi C et al. Proteolysis of von Willebrand factor and shear stress-induced platelet aggregation in patients with aortic valve stenosis. Circulation 2000; 102: 1290–5.

7. Warkentin TE, Moore JC, Morgan DG. Aortic stenosis and bleeding gastrointestinal angiodysplasia: is acquired von Willebrand’s disease the link? Lancet 1992; 340: 35-7.

8. King RM, Pluth JR, Giuliani ER. The association of unexplained gastrointestinal bleeding with calcific aortic stenosis. Am Thorac Surg 1987; 44: 514–6.

9. Mack et al for the PARTNER3 trial. NEJM (2019); 380:1695-1705

10. Popma et al for the Evolut trial. NEJM (2019); 380:1706-1715

11. Schwaiger et al.Vicious Circle: Heyde Syndrome in Mild Aortic Stenosis, CASE, Volume 3, Issue 4, 2019,Pages 171-176,ISSN 2468-6441.