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Original research
Assessment of exercise-induced changes in von Willebrand factor as a marker of severity of aortic stenosis
  1. Jo M Zelis1,
  2. Frederik M Zimmermann1,
  3. Froukje P J Andriessen1,
  4. Patrick Houthuizen1,
  5. Jop Van de Ven2,
  6. Jolanda Leuverman2,
  7. Nils P Johnson3,
  8. Nico H J Pijls1,
  9. Volkher Scharnhorst2,
  10. Marcel Van 't Veer1 and
  11. Pim A L Tonino1
  1. 1Cardiology, Catharina Hospital, Eindhoven, The Netherlands
  2. 2Laboratory, Catharina Hospital, Eindhoven, The Netherlands
  3. 3Division of Cardiology Department of Medicine, Weatherhead Pet Center McGovern Medical School at UTHealth and Memorial Hermann Hospital, Houston, Texas, USA
  1. Correspondence to Dr Jo M Zelis; jo.zelis{at}


Background Loss of high-molecular-weight multimers (HMWMs) of von Willebrand factor (vWF) occurs due to high shear stress in patients with aortic stenosis. As symptoms of aortic stenosis occur during exercise, measurement of vWF during exercise might identify patients with aortic stenosis of clinical importance. The aim of this pilot study is to evaluate whether vWF changes over time as a result of exercise in patients with asymptomatic moderate or severe aortic stenosis.

Methods Ten subjects were analysed for changes in vWF by measuring HMWMs and closure time with adenosine diphosphate (CT-ADP). All subjects underwent a full stress test on a bicycle ergometer. At rest and at peak exercise, a transthoracic echocardiogram was performed. HMWMs and CT-ADP were assessed at baseline, during and after exercise.

Results HMWMs and CT-ADP did not change significantly during exercise, p=0.45 and p=0.65, respectively. HMWMs and CT-ADP correlated well, Spearman’s rho −0.621, p<0.001. HMWMs during peak exercise did not correlate with maximal velocity measured, p=0.21. CT-ADP during exercise correlated well with the maximal echocardiographic velocity over the aortic valve (AV), rho 0.82, p=0.04.

Conclusions In a cohort of 10 patients with moderate or severe aortic stenosis, we observed no significant change in vWF biomarkers during exercise. Peak CT-ADP during exercise showed a good correlation with peak AV velocity measured with echo. Although CT-ADP is an easy test to perform and could be an alternative for peak AV velocity measured during exercise, our results suggest that it can only detect large changes in shear stress.

  • aortic valve disease
  • von willebrand factor
  • exercise physiology

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  • Contributors All authors contributed significantly in this study and they have also read and approved the content of the manuscript. JMZ: design of the study, data acquisition and analyses and writing the paper. FMZ: design of the study and data acquisition and analyses. FPJA: data acquisition and analyses. PH: data acquisition and analyses. JVdV: data acquisition and analyses. JL: data acquisition and analyses. NJ: design of the study and verified the analytical methods. NHJP: funding and supervised the findings of this work. VS: supervised the data acquisition and analyses. MVV: design of the study data analyses and writing the article. PT: design of the study, funding and supervised the findings of this work.

  • Funding This investigator initiated study was supported by an unrestricted research grant from Medtronic Inc.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data may be obtained from a third party and are not publicly available. All data relevant to the study are included in the article or uploaded as supplementary information.

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