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High-molecular-weight von Willebrand factor multimer ratio for the differentiation between true-severe and pseudo-severe low-flow, low-gradient aortic stenosis

Session Poster Session 5

Speaker Joerg Kellermair

Event : ESC Congress 2018

  • Topic : valvular, myocardial, pericardial, pulmonary, congenital heart disease
  • Sub-topic : Valvular Heart Disease – Diagnostic Methods
  • Session type : Poster Session

Authors : J Kellermair (Linz,AT), H Ott (Munich,DE), D Kiblboeck (Linz,AT), H Blessberger (Linz,AT), J Kammler (Linz,AT), C Reiter (Linz,AT), T Lambert (Linz,AT), M Grund (Linz,AT), C Steinwender (Linz,AT)

J. Kellermair1 , H. Ott2 , D. Kiblboeck1 , H. Blessberger1 , J. Kammler1 , C. Reiter1 , T. Lambert1 , M. Grund1 , C. Steinwender1 , 1Kepler University Hospital, Department of Cardiology and Internal Intensive Medicine - Linz - Austria , 2Ludwig-Maximilians University, Department of Hemostasis and Transfusion Medicine - Munich - Germany ,

European Heart Journal ( 2018 ) 39 ( Supplement ), 915-916

Background: Subclassification of low-flow, low-gradient (LF/LG) aortic stenosis (AS) into a true-severe (TS) and a pseudo-severe (PS) subform bases on dobutamine stress echocardiography (DSE) and multi-detector computed tomography (MDCT). Uncertainty about stenosis severity frequently persists even after DSE and MDCT, therefore, there is a need for a biomarker-based discrimination to expand the diagnostic portfolio.

Sheer-stress induced degradation of high-molecular-weight (HMW) von Willebrand factor (VWF) multimers is a frequent phenomenon at the site of AS, thus, it might represent a valueable biomarker. The present study analysed the value of HMW VWF multimer ratio for LF/LG AS subcategorization.

Methods: Sixty consecutive patients with diagnosis of LF/LG AS were prospectively recruited and subclassified using DSE and/or MDCT. HMW VWF multimers of all patients were analysed using a densitometric quantification of Western Blot bands and HMW VWF multimer ratio was calculated.

Results: Patients were subclassified into TS LF/LG AS (n=36) and PS LF/LG AS (n=24) using DSE and MDCT. Patients with PS LF/LG AS showed a mean HMW VWF multimer ratio of 1.07±0.09 while in patients with TS LF/LG AS the mean ratio was 0.82±0.28 (p<0.001). HMW VWF ratio presented a ROC-AUC of 0.780 (95% CI: 0.667–0.894; p<0.001) with a calculated sensitivity of 0.47 (95% CI: 0.30–0.65) and a specificity of 1.00 (95% CI: 0.86–1.00) at the optimal cut-off <0.905 for diagnosis of the TS subform.

Conclusion: The present study introduces HMW VWF multimer ratio as a novel biomarker for LF/LG AS subclassification that may be integrated at an early stage of the diagnostic work-up of patients with LF/LG AS.

Comparison of baseline data of patients with TS LF/LG AS and PS LF/LG AS
LF/LG ASp-value
Baseline patient characteristics(n=36)(n=24)
  Age (mean years ± SD)81±1079±70.088
  Male Gender (%)29/36 (80.6%)18/24 (75%)0.751
  BMI (mean kg/m2± SD)26±430±6<0.001
Baseline echocardiographic data
  Indexed stroke volume (mean ml/m2 ± SD)28±431±50.450
  Mean aortic gradient (mean mmHg ± SD)29±625±60.002
  AVA (mean cm2± SD)0.73±0.100.84±0.13<0.001
Baseline laboratory characteristics
  proBNP (mean pg/mL ± SD)10951±109907873±137560.039
  HMW VWF multimer ratio (mean ± SD)0.82±0.281.07±0.09<0.001
HMW multimer ratio in PS and TS LF/LG AS

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