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Kellermair, Jörg; Saeed, Sahrai; Ott, Helmut W.; Kammler, Jürgen; Blessberger, Hermann; Suppan, Markus; Grund, Michael; Kiblboeck, Daniel; Urheim, Stig; Chambers, John B.; Steinwender, Clemens (2020): High-molecular-weight von Willebrand Factor multimer ratio differentiates true-severe from pseudo-severe classical low-flow, low-gradient aortic stenosis. In: European Heart Journal-Cardiovascular Imaging, Vol. 21, No. 10: pp. 1123-1130
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Aims: Upon high wall shear stress, high-molecular-weight (HMW) von Willebrand Factor (VWF) multimers are degraded, thus, HMW VWF multimer deficiency mirrors haemodynamics at the site of aortic stenosis (AS). The aim of the present study was to analyse the role of HMW VWF multimer ratio for subcategorization of classical low-flow, low-gradient (LF/LG) AS. Methods and results Eighty-three patients with classical LF/LG AS were prospectively recruited and HMW VWF multimer pattern was analysed using a densitometric quantification of western blot bands. Patients were subclassified into true-severe (TS) and pseudo-severe (PS) classical LF/LG AS based on dobutamine stress echocardiography (DSE). Positive and negative predictive values (PPV/NPV) of HMW VWF multimer ratio for diagnosis of the TS subtype were calculated. HMW VWF multimer ratio in TS classical LF/LG AS was significantly decreased compared to PS classical LF/LG AS (0.86 +/- 0.27 vs. 1.06 +/- 0.09, P < 0.001). HMW VWF multimer deficiency occurred exclusively in the TS subtype with an optimal PPV of 1.000 and NPV of 0.379. HMW VWF multimer ratio showed a strong correlation with mean transvalvular pressure gradients during DSE (r = -0.616;P < 0.001). HMW VWF multimer ratio measured at baseline was higher compared to levels measured after DSE (0.87 +/- 0.27 vs. 0.84 +/- 0.31;P = 0.031) indicating DSE-induced increased proteolysis. Conclusion HMW VWF multimer ratio represents a valuable biomarker for classical LF/LG AS subclassification and mirrors haemodynamics during DSE. HMW VWF multimer ratio identifies the TS subtype without the use of other imaging techniques.