What is the term for anemia in severe aortic stenosis?

Heyde Syndrome: Anemia in Severe Aortic Stenosis

The phenomenon of low hemoglobin with severe aortic stenosis is called Heyde syndrome, characterized by the triad of aortic stenosis, acquired von Willebrand syndrome, and gastrointestinal angiodysplasia leading to iron deficiency anemia.

Pathophysiology

Heyde syndrome involves several interconnected mechanisms:

1. Acquired von Willebrand Factor Deficiency

   • High shear stress across the stenotic aortic valve causes degradation of von Willebrand factor (vWF) multimers
   • Loss of large vWF multimers impairs platelet adhesion and normal hemostasis

2. Gastrointestinal Angiodysplasia

   • Vascular malformations in the GI tract, particularly in the small intestine
   • These malformations are prone to bleeding, especially with the acquired coagulopathy

3. Iron Deficiency Anemia

   • Results from chronic, often occult GI bleeding
   • May be refractory to oral iron supplementation

Clinical Presentation

• Anemia (often severe and refractory to oral iron therapy)
• Symptoms of aortic stenosis (dyspnea, angina, syncope)
• Possible melena or occult GI bleeding
• Fatigue and reduced exercise tolerance (may be attributed to both anemia and cardiac condition)

Diagnostic Approach

1. Confirm Severe Aortic Stenosis

   • Echocardiography showing aortic valve area <1 cm², mean gradient ≥40 mmHg, or peak velocity ≥4 m/s 1

2. Evaluate Anemia

   • Complete blood count showing hemoglobin <12 g/dL in women or <13 g/dL in men
   • Iron studies (ferritin, transferrin saturation) to confirm iron deficiency

3. Assess for GI Bleeding

   • Upper and lower endoscopy
   • Capsule endoscopy of small intestine if conventional endoscopy is negative
   • Look for angiodysplasia or vascular malformations 2

4. Specialized Testing

   • von Willebrand factor multimer analysis to detect deficiency of large vWF multimers
   • Elevated erythropoietin levels may have prognostic significance 3

Management

1. Definitive Treatment

   • Aortic valve replacement (surgical or transcatheter) is the definitive treatment
   • Correction of aortic stenosis typically resolves the vWF abnormality and reduces GI bleeding 2
   • Recent evidence shows significant increase in hemoglobin levels 5-12 months after TAVR 4

2. Anemia Management

   • Iron supplementation (IV iron may be preferred if oral iron fails)
   • Blood transfusion for symptomatic anemia with restrictive strategy (Hb threshold 7-8 g/dL) 5
   • Avoid erythropoiesis-stimulating agents as they increase thrombotic risk 5

3. Anticoagulation Considerations

   • Careful risk-benefit assessment if anticoagulation is required
   • Consider temporary interruption of anticoagulation if active bleeding or severe anemia
   • Resume when hemoglobin stabilizes >10 g/dL 5

Prognosis

• Anemia is associated with increased mortality in patients with severe aortic stenosis 3, 6
• Aortic valve replacement significantly improves outcomes and often resolves the anemia 4, 2
• Higher erythropoietin levels are associated with worse mid-term mortality after TAVR, independent of anemia status 3

Clinical Pearls

• Always consider Heyde syndrome in elderly patients with unexplained iron deficiency anemia and aortic stenosis
• The absence of visible GI bleeding does not exclude the diagnosis
• Aortic valve replacement should be prioritized over repeated endoscopic interventions or long-term iron supplementation
• The resolution of anemia after valve replacement confirms the diagnosis and mechanism