A relationship between aortic valve stenosis (AS) and intestinal bleeding of unknown origin is observed in 3% of patients with severe AS. It was first suggested by Edward J. Heyde in 1958 and corroborated in 1971 by Boss and Rosenblum who demonstrated the co-existance of gastrointestinal (GI) bleeding angiodysplasia and AS in autopsy.The hypothesis of association between the two pathologies was confirmed by further studies, though several questions related to the pathogenesis and optimal management remain unanswered.
Angiodysplasias are the most common sources of bleeding from the small intestine in patients older than 50–60 years; they are often encountered in the large bowel and upper gastrointestinal tract. Up to 5–6% of gastrointestinal bleeding is caused by angiodysplasia in the upper or lower gastrointestinal tract. Asymptomatic colonic angiodysplasia is found in about 1% of patients undergoing colonoscopy. Angiodysplasia can cause both acute gastrointestinal bleeding or chronic iron deficiency anaemia. Histologically, angiodysplasias are lesions present only in the superficial layers of the bowel wall (mucosa and submucosa). Vessels – small veins, capillaries and arteries – are dilated, tortuous, and very thin-walled, lined by endothelium with only a little smooth muscle, with no inflammation or fibrosis. Diagnosis may be difficult: high-quality standard endoscopy, capsule endoscopy, and double-balloon enteroscopy are most efficacious.. Pharmacological therapy with blood transfusions and supplementation of iron has been employed, but a final conclusion about its efficacy cannot yet be drawn. Favorable but temporary results were obtained with octreotide, or it could be possible to performed an electrocoagulation or injection sclerosing substances (vasoconstrictors and / or embolization). Therapy using argon plasma coagulation is currently preferred.
In the picture endoscopic treatment using argon plasma coagulation.
More about: Fouch PG, Angiodysplasia of the gastrointestinal tract. Am J Gastroenterol 1993; 88; 807-818
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Severe aortic valve stenosis, remains the main cause of morbidity and mortality in the elderly, reaching a prevalence of 2-7% above the age of 65years old. But the prevalence of AS in patients with bleeding from colonic angiodysplasia is still undefined and controversial. The incidence of GI bleeding in the general population is about 0.9 . According to different sources, between 7-29 of patients with diagnosed GI bleeding angiodysplasia suffer from AS or aortic sclerosis and 3% of advanced AS patients have GI bleeding
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The evidence of a link between angiodysplasia has been known since 1958. Since then many aspects have been valuated to explain the link between the two pathologies. A common trigger should be identified in age-dependent tissue degeneration that could lead to both aortic valve stenosis and GI angiodysplasia and, thus explain this concomitance in elderly patients. In 1992, Warketin et al. observed a loss of highest molecular weight (HMW) multimers von Willebrand factor in patients suffering aortic valve stenosis and elucidated the pathogenesis of the Heyde’s syndrome. According to this pathogenic concept, high shear stress induced by the stenotic valve orifice leads to a conformational change in the structure of the large multimers of von Willebrand factor making it more prone to proteolysis by ADAMTS 13. The HMW multimers induce platelet aggregation and hemostasis in areas of high shear stress such as in angiodysplasia, so HMW multimers are required to maintain the homeostasis in these vessels. In conclusion the reduced number of HMW multimers impairs platelet-mediated hemostasis and predisposes the patient to bleeding.
HOW TO TEST vW FACTOR:
There are many methods that could be used to evaluate large von Willebrand factor multimers. the gold standard is gel electrophoresis that is able to visualize the absence of large von Willebrand multimers. Other tests that could be used are Platelet Functional Analyzer-100, closure time, von Willebrand factor risocetin cofactor activity, skin bleeding time and von Willebrand factor antigen level, thus less sensitive. However the evidence of other cases of Heyde’s syndrome without the decrease in large von Willebrand factor multimers suggests the need of further studies to elucidate which abnormalities are responsible for bleeding tendency in AS patients.
Patients’ VWF multimer patterns (1–5) before surgery comparedwith normal plasma (NP) and a type 2A VWD patient.
Samples were run in non-reducing conditions using high-gelling-temperature agarose(1.4%). VWF multimers were detected by autoradiography using 125I-labelledanti-VWF antibody. Large VWF multimers are at the top, small forms at the bottom. See the variable shortage of large VWF multimers, which was more pronounced in patients 1, 4 and 5; no increase in low and intermediateVWF multimers was observed, in contrast to type 2A VWD.
(Casonato et. All von Willebrand factor abnormalities in aortic valve stenosis:Pathophysiology and impact on bleeding Thromb Haemost 2011; 106: 58–66)
Management of this syndrome is complex and often requires help from cardiologists, gastroenterologists, surgeons and hematologists. There are many methods of therapy, however aortic valve replacement (AVR) should be recommended as “gold standard”. This should act in reducing the shear stress caused by a narrowed aortic valve orifice, preventing the reduction of HMW multimers and so GI bleeding. Treating the GI bleeding first showed disappointing results: only 5% of patients had a durable remission against 93% of patients undergoing AVR .
Performing only an endoscopic treatment is often ineffective because of the multifocal pattern of angiodysplasia in Heyde’s syndrome. Super-selective embolization of the feeding artery at the bleeding site stops colonic hemorrhage but is a technically difficult procedure with a risk of bowel infarction. Colectomy might serve as a therapeutic option for Heyde’s syndrome after the precise site of angiodysplasia is detected by angiography . Another minimal invasive approach that has been suggested is an endoscopic clipping of the bleeding lesions followed by a AVR.
In conclusion aortic valve replacement seems to decrease the risk of gastrointestinal bleeding in patients with Heyde syndrome and is curative in approximately 80% even though at subsequent colonscopies the angiodysplastic vessels remained visible.
More about: : Anderson PP, McGranth K, Street A. Reversal of aortic atenosis bleeding gastrointestinal angiodysplasia and von Willebrand syndrome by aortic valve replacement. Lancet, 1996; 347: 689-890