Author + information
- Received July 30, 2017
- Revision received January 25, 2018
- Accepted February 25, 2018
- Published online May 7, 2018.
- Flavien Vincent, MDa,b,c,∗,
- Antoine Rauch, MD, PhDb,c,d,∗,
- Valentin Loobuyck, MDb,c,e,
- Emmanuel Robin, MD, PhDb,c,f,
- Christoph Nix, MScg,
- André Vincentelli, MD, PhDb,c,e,
- David M. Smadja, PharmD, PhDh,i,
- Pascal Leprince, MD, PhDj,
- Julien Amour, MD, PhDk,
- Gilles Lemesle, MD, PhDa,b,c,
- Hugues Spillemaeker, MDa,b,c,
- Nicolas Debry, MDa,
- Christian Latremouille, MD, PhDl,
- Piet Jansen, MD, PhDm,
- Antoine Capel, PhDm,
- Mouhamed Moussa, MDb,c,f,
- Natacha Rousse, MDe,
- Guillaume Schurtz, MDa,
- Cédric Delhaye, MDa,
- Camille Paris, MDd,
- Emmanuelle Jeanpierre, PharmDd,
- Annabelle Dupont, PharmD, PhDb,c,d,
- Delphine Corseaux, PhDb,c,
- Mickaël Rosa, PhDb,c,
- Yoann Sottejeau, PhDb,c,
- Svenja Barth, MScg,
- Claudia Mourran, PhDg,
- Valérie Gomane, BScd,
- Augustin Coisne, MDa,b,c,
- Marjorie Richardson, MDa,
- Claudine Caron, MD, PhDd,
- Cristian Preda, PhDn,
- Alexandre Ung, BScb,c,d,
- Alain Carpentier, MDl,m,
- Thomas Hubert, DVM, PhDo,
- Cécile Denis, PhDp,
- Bart Staels, PhDb,c,
- Peter J. Lenting, PhDp,
- Eric Van Belle, MD, PhDa,b,c,∗∗ ( and )
- Sophie Susen, MD, PhDb,c,d,∗∗∗ ()
- aCHU Lille, Cardiology, Lille, France
- bUniversity of Lille, INSERM U1011-EGID, Lille, France
- cInstitut Pasteur de Lille, Lille, France
- dCHU Lille, Hematology Transfusion, Lille, France
- eCHU Lille, Cardiac Surgery, Lille, France
- fCHU Lille, Department of Anesthesia and Intensive Care, Lille, France
- gAbiomed Europe GmbH, Aachen, Germany
- hHematology Department, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, University Paris Descartes, Sorbonne Paris Cité, Paris, France
- iInserm UMR-S1140, Paris, France
- jSorbonne Université, UMR INSERM 1166, IHU ICAN, Assistance Publique-Hôpitaux de Paris (AP-HP), Department of Thoracic and Cardiovascular Surgery, Pitié-Salpêtrière Hospital, Paris, France
- kSorbonne Université, UMR INSERM 1166, IHU ICAN, Assistance Publique-Hôpitaux de Paris (AP-HP), Department of Anesthesiology and Critical Care Medicine, Pitié-Salpêtrière Hospital, Paris, France
- lDepartment of Cardiovascular Surgery, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, University Paris Descartes-Sorbonne Paris Cité, Paris, France
- mCarmat SA, Vélizy-Villacoublay, France
- nLaboratoire de Mathématiques, Paul Painlévé, UMR CNRS 8524, Université de Sciences et Technologies de Lille, Lille, France
- oINSERM U1190-EGID, Lille, France
- pINSERM U1176, University Paris-Sud, University Paris-Saclay, Le Kremlin-Bicêtre, France
- ↵∗Address for correspondence:
Dr. Eric Van Belle, Department of Cardiology, Institut Cœur Poumon, Centre Hospitalier Universitaire de Lille, Boulevard du Pr. Jules Leclercq, 59037 Lille Cedex, France.
- ↵∗∗Dr. Sophie Susen, Centre Hospitalier Universitaire de Lille, Département d’hématologie et transfusion, Boulevard du Pr. Jules Leclercq, 59037 Lille Cedex, France.
Background The main risk factor for bleeding in patients with continuous-flow mechanical circulatory support (CF-MCS) is the acquired von Willebrand factor (VWF) defect related to the high shear-stress forces developed by these devices. Although a higher bleeding rate has been reported in CF-MCS recipients who had reduced pulsatility, the relation between pulsatility and the VWF defect has never been studied.
Objectives The purpose of this study was to investigate the relation between pulsatility and VWF under CF-MCS.
Methods We assessed the effect of 2 CF-MCS on VWF multimer degradation in a mock circulatory loop (model 1). Using these devices, we investigated in a dose-effect model (model 2) 3 levels of pulsatility in 3 groups of swine. In a cross-over model (model 3), we studied the effects of sequential changes of pulsatility on VWF. We reported the evolution of VWF multimerization in a patient undergoing serial CF-MCS and/or pulsatile-MCS.
Results We demonstrated the proteolytic degradation of VWF multimers by high shear CF-MCS in a circulatory loop without pulsatility. We observed both in swine models and in a patient that the magnitude of the VWF degradation is modulated by the pulsatility level in the high shear-stress level condition, and that the restoration of pulsatility is a trigger for the endothelial release of VWF.
Conclusions We demonstrated that the VWF defect reflects the balance between degradation induced by the shear stress and the endothelial release of new VWF triggered by the pulsatility. This modulation of VWF levels could explain the relationship between pulsatility and bleeding observed in CF-MCS recipients. Preservation of pulsatility may be a new target to improve clinical outcomes of patients.
- arterial pulsatility
- blood flow
- extracorporeal membrane oxygenation
- mechanical circulatory support
- von Willebrand factor
↵∗ Drs. Vincent, Rauch, Van Belle, and Susen contributed equally to the study.
This work was supported by Lille-II University and by the National Research Agency (Programme d’Investissement d’Avenir), ANR-17-RHUS-0011. The clinical study of feasibility and safety of CARMAT pulsatile total artificial heart implantation is registered to French government health authorities with number 2001-A00972-39 and financed by Carmat. Dr. Vincent has received a research grant from the Fédération Française de Cardiologie. Drs. Nix, Barth, and Mourran are full-time employees of Abiomed. Dr. Carpentier is cofounder and shareholder of Carmat. Drs. Smadja, Latremouille, Leprince, and Susen have received consulting fees from Carmat. Dr. Leprince has served as a proctor for St. Jude/Abbott, Medtronic, and Syncardia. Dr. Lemesle has received fees for lectures or consulting from Amgen, AstraZeneca, Bayer, Biopharma, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi-Sankyo, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Sanofi, Servier, and The Medicines Company. Drs. Jansen and Capel are employed by Carmat. Dr. Susen has received consulting fees from LFB, HemaBiologics, Roche, Shire, Sobi, and Carmat; has received research support from CSL-Behring, LFB, Stago, and Carmat; and has received travel fees from CSL-Behring, LFB, Bayer, Novo, Shire, Siemens, Sobi, Stago, and Bristol-Myers Squibb-Pfizer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received July 30, 2017.
- Revision received January 25, 2018.
- Accepted February 25, 2018.
- 2018 American College of Cardiology Foundation
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