Case Description

A 77-year-old man presented to Vanderbilt University Medical Center for evaluation of presyncope, progressive orthopnea, and weight gain. The patient had been previously diagnosed with severe aortic valve stenosis (peak velocity 5.74 m/s, mean gradient 62 mm Hg, peak gradient 132 mm Hg, left ventricular ejection fraction 55%). He had severe chronic obstructive pulmonary disease, atrial fibrillation, hypertension, hyperlipidemia, and diabetes mellitus. His medical regimen included a daily aspirin, diltiazem, hydrochlorothiazide, glimeperide, metformin, and warfarin.

On presentation, he had an irregularly irregular rhythm, a late-peaking systolic murmur, diminished second heart sound, delayed carotid upstroke, elevated jugular venous pulsation >20 cm of water, faint inspiratory crackles over the left lung base, diminished breath sounds over the right lung base, and pitting edema of the lower extremities. Chest x-ray demonstrated an enlarged cardiac silhouette with bibasilar atelectasis and a right basilar effusion. Electrocardiography disclosed atrial fibrillation, left ventricular hypertrophy, and left atrial enlargement. The hematocrit was 26. An arteriovenous malformation was noted in the ascending colon, which was ablated with Erbe argon plasma coagulation therapy. One unit of packed red blood cells was transfused, and the patient was discharged.

The patient was readmitted to the medical intensive care unit 5 days after initial discharge with hemorrhagic shock from gastrointestinal bleeding necessitating aggressive resuscitation with blood products and international normalized ration reversal with vitamin K. Repeat endoscopy revealed fresh bleeding from the previously treated ascending colonic arteriovenous malformation. Immediate hemostasis was achieved with epinephrine injections and cauterization of the bleeding vessel during endoscopy. The patient continued to have bright red blood per rectum thereafter.

Given the severity of the patient’s bleeding and concomitant aortic stenosis, transcutaneous aortic valve implantation was expedited. A serum von Willebrand multimer profile demonstrated loss of the HMW von Willebrand factor (vWF) multimers. A 26-mm Edwards SAPIEN (Edwards Lifesciences Corporation) bioprosthetic aortic valve was implanted by way of a transfemoral approach without complications. A postoperative transthoracic echocardiography confirmed the bioprosthetic aortic valve was well seated without significant central or perivalvular aortic insufficiency. The mean gradient was 23 mm Hg; however, the dimensionless orifice index was 0.4, suggesting no significant prosthetic stenosis. These findings were confirmed with repeat echocardiography at 1 month (mean gradient 19 mm Hg, dimensionless orifice index 0.37). Repeat von Willebrand factor multimer testing on postoperative days 1 and 2 demonstrated normalization of the HMW multimers. The patient recovered well and has been free of gastrointestinal bleeding 10 months postoperatively.

Comment

The association between aortic stenosis and gastrointestinal bleeding was first described by Edward Heyde in a letter written to The New England Journal of Medicine in 1958. His observation of occult gastrointestinal bleeding in 10 patients with concomitant calcific aortic stenosis prompted Goldman, and later Williams, to review large cohorts of patients and establish a statistically significant association between the conditions by the late 1960s. Boss and Rosenbaum, Galloway et al, and Treweeke and Michelbach contributed to a growing body of evidence supporting intestinal tortuous vascular lesions (angiodysplasias) as the source of gastrointestinal bleeding associated with aortic stenosis. This association has since been termed “Heyde’s syndrome.”

There have been much interest and debate over the pathogenesis of mucosal bleeding and aortic stenosis. Indeed, it was not until 1979 that the causal relation between the aforementioned conditions was further supported by Bourdette and Greenburg who described resolution of gastrointestinal bleeding in a patient after surgical aortic valve replacement. By 1987, King et al published a cohort of 14 patients, the largest study at the time, undergoing surgical aortic valve replacement with clinically significant gastrointestinal bleeding. Complete resolution of hemorrhage was reported in all 14 patients, including those receiving long-term oral anticoagulation for mechanical aortic valve placement.

In 2003, Warkentin et al published a report of 2 patients with severe aortic stenosis and bleeding from intestinal angiodysplastic lesions visualized on preoperative endoscopy. Serum platelet counts, factor VIII levels, vWF antigen levels, and vWF ristocetin cofactor assay levels were normal in these patients. Preoperative serum gel electrophoreses documented the absence of HMW vWF multimers. Both patients were followed postoperatively and found to have resolution of their bleeding diathesis and normalization of their vWF profile at 10 years after valve replacement. In the same year, Vincentelli et al published a series of 42 patients with aortic stenosis and a history of bleeding undergoing surgical aortic valve replacement in The New England Journal of Medicine . Platelet function, vWF collagen-binding activity, vWF antigen levels, and vWF multimeric structure were evaluated preoperatively. All metrics were reassessed at postoperative days 1 and 7 and at 6 months. Severe aortic stenosis was associated with clinically relevant mucosal bleeding in 21% of their cohort, correlating strongly with severity of the valvular lesion. Loss of vWF collagen-binding activity and loss of HMW vWF multimers were observed in up to 92% of their cohort, and correction of the hematologic abnormalities was observed after valve replacement in the absence of a mismatch between patient and prosthesis.