What is the management of Heyde syndrome?

Management of Heyde Syndrome

The definitive treatment for Heyde syndrome is aortic valve replacement (AVR), which resolves both the gastrointestinal bleeding from angiodysplasia and the acquired von Willebrand syndrome by eliminating the pathologic shear stress that degrades von Willebrand factor multimers. 1, 2, 3

Understanding the Pathophysiology

Heyde syndrome represents a triad of aortic stenosis, gastrointestinal bleeding from angiodysplasia, and acquired von Willebrand syndrome type 2A. 1, 2 The narrowed aortic valve creates abnormal shear stress that cleaves high molecular weight von Willebrand factor multimers, leading to both bleeding diathesis and angiodysplasia formation through angiogenic dysregulation. 1, 3

Diagnostic Workup

When evaluating suspected Heyde syndrome, obtain:

• Echocardiography to document aortic stenosis severity and valve area 2, 3
• Platelet function assay and von Willebrand factor multimer analysis to confirm acquired von Willebrand syndrome type 2A 2, 3
• Capsule endoscopy followed by double balloon endoscopy if standard upper and lower endoscopy are unremarkable, as angiodysplasias are typically located in the small intestine 2, 3
• Complete blood count to assess severity of anemia and transfusion requirements 1, 2

Treatment Algorithm

First-Line: Aortic Valve Replacement

Proceed with AVR as the primary therapeutic intervention, as this addresses the underlying pathophysiology. 3, 4 Both surgical AVR and transcatheter aortic valve replacement (TAVR) are effective options. 5, 2

• Bioprosthetic valves are strongly preferred over mechanical valves to avoid mandatory anticoagulation, which would exacerbate gastrointestinal bleeding. 4
• Resolution of gastrointestinal bleeding typically occurs within 12-20 months post-AVR as angiodysplasias regress and von Willebrand factor multimers normalize. 3
• Transfusion requirements cease after successful valve replacement. 3, 4

Bridging Therapy for Severe Bleeding

When severe bleeding or transfusion dependence precludes safe antiplatelet therapy required for AVR:

• Argon plasma coagulation (APC) can provide temporary hemostasis for accessible angiodysplasias. 1
• Blood transfusions and iron supplementation to maintain hemoglobin while preparing for definitive treatment. 1, 2
• Systemic bevacizumab (antiangiogenic therapy) represents a novel approach for refractory bleeding that cannot be controlled with endoscopic therapy, allowing stabilization for subsequent AVR. 5 This targeted therapy inhibits the angiogenic dysregulation characteristic of Heyde syndrome and can achieve durable hemostasis, normalize hemoglobin, and eliminate transfusion dependence. 5

Management Sequence

1. Stabilize acute bleeding with endoscopic therapy (APC) and transfusions as needed 1
2. Consider bevacizumab if bleeding is refractory and prevents safe initiation of antiplatelet therapy 5
3. Initiate aspirin therapy once hemostasis is achieved 5
4. Proceed with AVR (TAVR or surgical) using bioprosthetic valve 5, 2, 4
5. Monitor for resolution of bleeding over 12-20 months post-procedure 3

Critical Pitfalls to Avoid

Do not perform intestinal resection before addressing the aortic stenosis, as the underlying pathophysiology will persist and bleeding will recur from remaining or new angiodysplasias. 4 AVR must precede any consideration of bowel resection. 4

Avoid mechanical valve prostheses that require anticoagulation, as this will worsen gastrointestinal bleeding in patients with persistent angiodysplasias and coagulopathy. 4

Do not dismiss the diagnosis in elderly patients with recurrent gastrointestinal bleeding and a systolic murmur—actively evaluate for this triad. 3 Standard endoscopy may be negative, requiring capsule endoscopy for diagnosis. 2, 3

Long-Term Outcomes

Following successful AVR, patients experience cessation of gastrointestinal bleeding, normalization of von Willebrand factor multimers, elimination of transfusion requirements, and improvement in both cardiac and general health status. 3, 4 The multisystem benefits underscore that AVR is not merely treating the valve disease but resolving the entire syndrome. 4