Indexes of von Willebrand Factor as Biomarkers of Aortic Stenosis Severity (From the Biomarkers of Aortic Stenosis Severity [BASS] Study)

Study Questions:

Do indices of von Willebrand Factor (VWF) predict severity of aortic stenosis (AS) and outcomes?


Patients with AS (n = 66 [16 mild, 20 moderate, and 30 severe]) and aortic valve (AV) replacement (n = 21) were assessed with VWF antigen, VWF activity, platelet function analyzer collagen plus adenosine diphosphate (PFA-CADP), VWF multimer ratio, and B-type natriuretic peptide (BNP) level after echocardiography.


In patients with AS, the mean gradient correlated with BNP, VWF activity/antigen ratio, PFA-CADP, and VWF multimer ratio. For the VWF multimer ratio, a threshold of 0.15 yielded a sensitivity and specificity for severe AS of 77% and positive predictive value of 74%. Bleeding (in 14%) was associated with a prolonged PFA-CADP time and reduced VWF activity/antigen ratio. Symptoms were associated with elevated BNP and low Duke Activity Status Index score. In 66 patients with AS, freedom from death (n = 4) or AV replacement (n = 22) was associated with PFA-CADP (p = 0.003), VWF high-molecular-weight multimers (p = 0.009), and VWF activity/antigen ratio (p < 0.001), but not BNP (p = 0.32). In severe AS versus AV replacement, the PFA-CADP and VWF multimer ratio differed (p < 0.001), but BNP and the VWF activity/VWF antigen ratio did not.


The authors concluded that VWF activity indexes are associated with AS severity and bleeding, and were predictive of cardiovascular outcomes.


Deciding when to refer a patient with moderate-severe AS for further invasive testing and/or valve replacement may be difficult, as confounding symptoms due to coexisting conditions are often present. Additional biomarkers reflective of truly critical AS and predictive of outcomes would be helpful. Previous studies have indicated that VWD (with bleeding), may be acquired in patients with severe AS due to valve-related shear stress. This study demonstrates that abnormalities in VWF may be useful in determining severity of AS and outcomes. The clinical utility of these measures will require further study.

Clinical Topics: Noninvasive Imaging, Echocardiography/Ultrasound

Keywords: Antipsychotic Agents, Platelet Function Tests, Sensitivity and Specificity, Blood Platelets, Clozapine, von Willebrand Factor, Biological Markers, Platelet Activation, Collagen, Hemorrhage, Natriuretic Peptide, Brain, Echocardiography

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