Von willebrand factor abnormalities and heyde syndrome in dysfunctional heart valve prostheses

IMPORTANCE: Limited data suggest that von Willebrand factor (VWF) abnormalities may accompany the high-shear state associated with prosthetic valve dysfunction. If true, laboratory testing could add value in quantifying prosthesis dysfunction and could suggest a pathophysiological explanation for acquired bleeding in some patients. OBJECTIVES: To determine whether dysfunctional valve prostheses are associated with VWF abnormalities compared with normally functioning valve prostheses, to identify the severity of the VWF abnormality relative to other conditions, and to describe associated bleeding and the occurrence of gastrointestinal angiodysplasia. DESIGN, SETTING, AND PARTICIPANTS: Cohort study in a multispecialty practice setting from August 2010 through November 2015. To assess the severity of VWF dysfunction, data were compared with those from previously reported healthy controls and patients with aortic stenosis, mitral regurgitation, and left ventricular assist devices. Patients underwent assessment of multiple VWF laboratory tests and echocardiography. MAIN OUTCOMES AND MEASURES: Loss of high-molecular-weight multimers of VWF. RESULTS: A total of 136 patients were included in this study. During the study period, we assessed 26 patients with normally functioning surgical or transcatheter aortic valve replacement, 24 patients with dysfunctional aortic valve replacement, 36 patients with normally functioning mitral valve replacement or repair, 19 patients with dysfunctional mitral valve replacement or repair, and 31 patients with native aortic regurgitation without coexisting aortic stenosis. Von Willebrand factor multimers were abnormal in 1 of 26 normal aortic valve replacements and in 2 of 36 normal mitral valve replacements or repairs but were abnormal in 20 of 24 dysfunctional aortic valve replacements and in 14 of 19 dysfunctional mitral valve replacements or repairs (P < .001 for both). Normal aortic valve replacement also had a higher VWF activity to antigen ratio, mean (range) 0.94 (0.84-0.99) compared to dysfunctional aortic valve replacement, 0.78 (0.73-0.87), P < .001, as did normal mitral valve replacement or repair, 0.90 (0.86-0.93) compared to dysfunctional mitral valve replacement or repair, 0.78 (0.70-0.90), P = .005. Platelet function analyzer closure times were lower with normal aortic valve replacement, mean (range) 92 (82-112) seconds compared to dysfunctional aortic valve replacement, 139 (122-177) seconds, P < .001, and also in normally functioning mitral valve replacement or repair, 85 (74-96) seconds compared to dysfunctional mitral valve replacement or repair, 143 (128-192) seconds, P < .001. Gastrointestinal bleeding was noted in 6 of 24 patients with aortic prosthesis dysfunction and in 5 of 19 patients with mitral prosthesis/repair dysfunction and was associated with a lower normalized VWF multimer ratio than in patients without bleeding. Gastrointestinal angiodysplasia was noted in 5 of 6 bleeding patients with dysfunctional aortic prostheses and in 3 of 5 bleeding patients with dysfunctional mitral prostheses/repair. CONCLUSIONS AND RELEVANCE: Acquired abnormalities of VWF multimers are associated with aortic and mitral prosthesis dysfunction, with occasional gastrointestinal bleeding and gastrointestinal angiodysplasia. Quantitative VWF tests may provide adjunctive value in the difficult assessment of prosthetic valve dysfunction.