Von Willebrand factor as a biological sensor of blood flow to monitor percutaneous aortic valve interventions

Eric Van Belle; Antoine Rauch; André Vincentelli; Emmanuelle Jeanpierre; Paulette Legendre; Francis Juthier; Christopher Hurt; Carlo Banfi; Natacha Rousse; Anne Godier; Claudine Caron; Ahmed Elkalioubie; Delphine Corseaux; Annabelle Dupont; Christophe Zawadzki; Cédric Delhaye; Frédéric Mouquet; Guillaume Schurtz; Dominique Deplanque; Giulia Chinetti; Bart Staels; Jenny Goudemand; Brigitte Jude; Peter J Lenting; Sophie Susen

doi:10.1161/CIRCRESAHA.116.305046

Von Willebrand factor as a biological sensor of blood flow to monitor percutaneous aortic valve interventions

Circ Res. 2015 Mar 27;116(7):1193-201. doi: 10.1161/CIRCRESAHA.116.305046. Epub 2015 Feb 10.

Authors

Eric Van Belle¹, Antoine Rauch¹, André Vincentelli¹, Emmanuelle Jeanpierre¹, Paulette Legendre¹, Francis Juthier¹, Christopher Hurt¹, Carlo Banfi¹, Natacha Rousse¹, Anne Godier¹, Claudine Caron¹, Ahmed Elkalioubie¹, Delphine Corseaux¹, Annabelle Dupont¹, Christophe Zawadzki¹, Cédric Delhaye¹, Frédéric Mouquet¹, Guillaume Schurtz¹, Dominique Deplanque¹, Giulia Chinetti¹, Bart Staels¹, Jenny Goudemand¹, Brigitte Jude¹, Peter J Lenting¹, Sophie Susen²

Affiliations

¹ From the Department of Cardiology, Lille University Hospital, Lille, France (E.V.B., A.V., F.J., C.H., C.B., N.R., C.D., G.S., D.D.); INSERM UMR 1011, Univ Lille 2, Institut Pasteur de Lille, EGID, Lille, France (E.V.B., A.R., A.V., E.J., F.J., C.B., N.R., C.C., A.E., D.C., A.D., C.Z., G.C., B.S., J.G., B.J., S.S.); Department of Hematology, Transfusion Lille University Hospital, Lille, France (A.R., E.J., C.C., A.E., C.Z., F.M., J.G., B.J., S.S.); INSERM U1176 and UMR_S1176, Univ Paris-Sud, Le Kremlin Bicêtre, France (P.L., P.J.L.); and INSERM UMR 1140, Paris, France (A.G.).
² From the Department of Cardiology, Lille University Hospital, Lille, France (E.V.B., A.V., F.J., C.H., C.B., N.R., C.D., G.S., D.D.); INSERM UMR 1011, Univ Lille 2, Institut Pasteur de Lille, EGID, Lille, France (E.V.B., A.R., A.V., E.J., F.J., C.B., N.R., C.C., A.E., D.C., A.D., C.Z., G.C., B.S., J.G., B.J., S.S.); Department of Hematology, Transfusion Lille University Hospital, Lille, France (A.R., E.J., C.C., A.E., C.Z., F.M., J.G., B.J., S.S.); INSERM U1176 and UMR_S1176, Univ Paris-Sud, Le Kremlin Bicêtre, France (P.L., P.J.L.); and INSERM UMR 1140, Paris, France (A.G.). sophiesusen@aol.com.

PMID: 25670067
DOI: 10.1161/CIRCRESAHA.116.305046

Abstract

Rationale: Percutaneous aortic valve procedures are a major breakthrough in the management of patients with aortic stenosis. Residual gradient and residual aortic regurgitation are major predictors of midterm and long-term outcome after percutaneous aortic valve procedures. We hypothesized that (1) induction/recovery of high molecular weight (HMW) multimers of von Willebrand factor defect could be instantaneous after acute changes in blood flow, (2) a bedside point-of-care assay (platelet function analyzer-closure time adenine DI-phosphate [PFA-CADP]), reflecting HMW multimers changes, could be used to monitor in real-time percutaneous aortic valve procedures.

Objective: To investigate the time course of HMW multimers changes in models and patients with instantaneous induction/reversal of pathological high shear and its related bedside assessment.

Methods and results: We investigated the time course of the induction/recovery of HMW multimers defects under instantaneous changes in shear stress in an aortic stenosis rabbit model and in patients undergoing implantation of a continuous flow left ventricular assist device. We further investigated the recovery of HMW multimers and monitored these changes with PFA-CADP in aortic stenosis patients undergoing transcatheter aortic valve implantation or balloon valvuloplasty. Experiments in the aortic stenosis rabbit model and in left ventricular assist device patients demonstrated that induction/recovery of HMW multimers occurs within 5 minutes. Transcatheter aortic valve implantation patients experienced an acute decrease in shear stress and a recovery of HMW multimers within minutes of implantation which was sustained overtime. In patients with residual high shear or with residual aortic regurgitation, no recovery of HMW multimers was observed. PFA-CADP profiles mimicked HMW multimers recovery both in transcatheter aortic valve implantation patients without aortic regurgitation (correction) and transcatheter aortic valve implantation patients with aortic regurgitation or balloon valvuloplasty patients (no correction).

Conclusions: These results demonstrate that variations in von Willebrand factor multimeric pattern are highly dynamic, occurring within minutes after changes in blood flow. It also demonstrates that PFA-CADP can evaluate in real time the results of transcatheter aortic valve procedures.

Keywords: aortic valve stenosis; blood flow velocity; von Willebrand factor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Angioplasty, Balloon
Animals
Aortic Valve / surgery*
Aortic Valve Insufficiency / blood
Aortic Valve Insufficiency / physiopathology
Aortic Valve Insufficiency / surgery
Aortic Valve Stenosis / blood
Aortic Valve Stenosis / physiopathology
Aortic Valve Stenosis / surgery
Biomarkers
Blood Flow Velocity
Computer Systems
Disease Models, Animal
Female
Heart-Assist Devices*
Hemorheology*
Humans
Male
Platelet Function Tests / methods
Prospective Studies
Protein Multimerization*
Rabbits
Transcatheter Aortic Valve Replacement*
von Willebrand Factor / chemistry*

Substances

Biomarkers
von Willebrand Factor