• GI Bleeding Linked to Dysfunctional Prosthetic Valves Catch-22 for valve repair in patients with high bleeding risk

    Abnormal von Willebrand factor (VWF) levels can indicate the dysfunction of prosthetic heart valves, according to a study, and that condition has in turn been tied to gastrointestinal bleeding acquired from a surgery or transcatheter procedure.

    While patients with working aortic and mitral valve prostheses rarely had low levels of VWF multimers, deficiencies were more common in those with dysfunctional valve implants (P<0.001).

    Functional aortic valves were associated with a higher VWF-to-antigen ratio (mean 0.95 versus 0.78 for dysfunctional, P<0.001). Similarly, patients with normal mitral valve implants also had higher VWF-to-antigen ratios (0.90 versus 0.78, P=0.005).

    Gastrointestinal bleeding was recorded in 25.0% of patients with aortic prosthesis dysfunction and 26.3% with mitral prosthesis/repair dysfunction.

    Indeed, gastrointestinal bleeding was also associated with a lower normalized VWF multimer ratio (P<0.001), reported Joseph L. Blackshear, MD, of Mayo Clinic in Jacksonville, Fla., and colleagues.

    The study seems to confirm that “aortic regurgitation and prosthetic valve dysfunction are associated with impairment of VWF function” and that “bleeding in the setting of dysfunctional left heart prosthesis could be due to acquired von Willebrand syndrome,” they reported online in JAMA Cardiology.

    William B. Hillegass, MD, MPH, and Nita A. Limdi, PharmD, PhD, MSPH, both of University of Alabama at Birmingham, noted in an accompanying editorial that “acquired type 2a von Willebrand syndrome is a relatively common and typically unrecognized life-threatening condition.”

    Heyde’s syndrome — gastrointestinal bleeding due to the loss of VWF multimers in high shear stress lesions seen in aortic stenosis — is now known to be caused by acquired von Willebrand syndrome, the duo wrote in accompanying editorial.

    “Recognition of the hemostatic defect of the acquired von Willebrand syndrome may itself provide a new avenue to help diagnose significant prosthetic valve dysfunction. A biomarker of valve dysfunction would assist in the often-difficult clinical determination of when prosthetic valve dysfunction is present and justifies repeat intervention,” they wrote.

    Tests of VWF activity can measure prosthetic function and severity of aortic regurgitation, Blackshear’s group agreed, adding that abnormal VWF results in a symptomatic patient “might provide an impetus for additional workup.”

    The prospective study included 136 patients who underwent surgical aortic valve replacement, mitral valve replacement or repair, or transcatheter aortic valve replacement (TAVR) from 2010 to 2015.

    It remains to be seen “whether percutaneous approaches, such as valve-in-valve replacement for late prosthesis failure, plugging to correct paravalvular leak, and percutaneous clipping of severe organic mitral regurgitation” are sufficient to correct loss of VWF activity, the study authors wrote.

    Blackshear and colleagues acknowledged that in their study, only four patients had truly severe aortic regurgitation. Furthermore, “the number of patients with severe bleeding who underwent intervention is insufficient to provide clear guidance on when intervention is clearly indicated,” they added.

    Hillegass and Limdi argued that it’s not just aortic stenosis that can induce VWF loss and the resulting gastrointestinal bleeding, listing “severe aortic regurgitation, severe mitral regurgitation, hypertrophic obstructive cardiomyopathy, congenital heart diseases, left ventricular assist devices, and other vascular lesions.”

    They emphasized that for patients on oral anticoagulation, it may turn out that their prosthetic valve dysfunction — and not the oral anticoagulant itself — is the “culprit” for their bleeding.

    Yet managing valve dysfunction and bleeding at the same time will be a challenge.

    Paradoxically, a high bleeding-risk patient ill-suited for valve replacement can only rely on another valve procedure to mediate a high shear stress lesion causing their VWF deficiency. If such a procedure is successful, however, VSF multimers may return to normal levels within hours or days, the editorialists suggested.

    “With the dramatically expanding capabilities for surgical and transcatheter treatment of valvular disease, we must routinely consider the possibility of acquired type 2A von Willebrand syndrome in every cardiac patient with blood flow exposed to a high shear stress lesion,” they concluded.


    The study was supported by the Mayo Foundation for Medical Research, the Center for Translational Science Activities, and the Michael S. Gordon Charitable Foundation.

    Blackshear disclosed serving on an advisory board for Baxalta.

    Hillegass and Limdi reported no relevant relationships with industry.




    JAMA Cardiology


    Blackshear JL, et al “Von Willebrand factor abnormalities and Heyde Syndrome in dysfunctional heart valve prostheses” JAMA Cardiol 2016; DOI: 10.1001/jamacardio.2016.0075.


    JAMA Cardiology


    Hillegass WB and Limdi NA “Valvular heart disease and acquired type 2A von Willebrand Syndrome: the ‘hemostatic’ waring blender syndrome” JAMA Cardiol 2016; DOI: 10.1001/jamacardio.2016.0182.

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