Heydeʼs Syndrome: An Integrative Disease

Abstract

Heyde's syndrome is an integrative disease process that involves gastrointestinal bleeding, von-Willebrand's factor, and aortic stenosis. First described in 1958 through simple observations from an internist, its etiological description has since evolved, with clinical and bench research now indicating quite elegant pathophysiological underpinnings. We here present a case of Heyde's syndrome resulting in recurrent gastrointestinal bleeding. A 68-year-old Caucasian woman with medical comorbidities of coronary artery disease, severe aortic stenosis, hypertension, hyperlipidemia, and diabetes mellitus type 2 presented with 2 day onset of worsening chest pain and exertional dyspnea. On further inquiry, the patient also reported multiple dark bowel movements over the preceding three days. Initial laboratory values were significant for severe anemia (Hemoglobin of 7.1gm/dL). The patient was admitted for severe symptomatic anemia. A transthoracic echocardiogram revealed severe aortic stenosis (Figure 1). The patient underwent bidirectional endoscopy which demonstrated multiple arteriovenous malformations (AVMs) requiring the use of argon plasma coagulation and injection of epinephrine to achieve hemostasis. The patient was subsequently referred for expedited aortic valve replacement. It is quite infrequent that the disciplines of gastroenterology, hematology and cardiology intersect with each other in regards to forming pathophysiological basis of a disease. Heyde's syndrome represents one such example. Loss of Von-Willebrand factor (a high molecular weight protein multimer that is involved in primary hemostasis) in patients with severe aortic stenosis, is implicated in the pathogenesis. It is now believed that high-velocity flow through a stenotic aortic valve causes conformational change in the configuration of large molecular weight von-Willebrand factor, making it vulnerable to cleavage by the plasma protein ADATS13 and subsequently rendering it hemostatically inferior to the normal high molecular weight multimers. Von-Willebrand factor may have also an essential role in maintaining vascular integrity which could explain the development of angiodysplasias in patients with deficiency of this factor. Aortic valve replacement was shown to improve the levels of Von-Willebrand factor significantly and is considered the definitive treatment for Heyde's syndrome.Figure 1