Flavien Vincent1, Antoine Rauch2, Valentin Loobuyck3, Emmanuel Robin4, Christoph Nix5, André Vincentelli3, David M Smadja6, Pascal Leprince7, Julien Amour8, Gilles Lemesle1, Hugues Spillemaeker1, Nicolas Debry9, Christian Latremouille10, Piet Jansen11, Antoine Capel11, Mouhamed Moussa4, Natacha Rousse12, Guillaume Schurtz9, Cédric Delhaye9, Camille Paris13, Emmanuelle Jeanpierre13, Annabelle Dupont2, Delphine Corseaux14, Mickaël Rosa14, Yoann Sottejeau14, Svenja Barth5, Claudia Mourran5, Valérie Gomane13, Augustin Coisne1, Marjorie Richardson9, Claudine Caron13, Cristian Preda15, Alexandre Ung2, Alain Carpentier16, Thomas Hubert17, Cécile Denis18, Bart Staels14, Peter J Lenting18, Eric Van Belle19, Sophie Susen20. 1. CHU Lille, Cardiology, Lille, France; University of Lille, INSERM U1011-EGID, Lille, France; Institut Pasteur de Lille, Lille, France. 2. University of Lille, INSERM U1011-EGID, Lille, France; Institut Pasteur de Lille, Lille, France; CHU Lille, Hematology Transfusion, Lille, France. 3. University of Lille, INSERM U1011-EGID, Lille, France; Institut Pasteur de Lille, Lille, France; CHU Lille, Cardiac Surgery, Lille, France. 4. University of Lille, INSERM U1011-EGID, Lille, France; Institut Pasteur de Lille, Lille, France; CHU Lille, Department of Anesthesia and Intensive Care, Lille, France. 5. Abiomed Europe GmbH, Aachen, Germany. 6. Hematology Department, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, University Paris Descartes, Sorbonne Paris Cité, Paris, France; Inserm UMR-S1140, Paris, France. 7. Sorbonne Université, UMR INSERM 1166, IHU ICAN, Assistance Publique-Hôpitaux de Paris (AP-HP), Department of Thoracic and Cardiovascular Surgery, Pitié-Salpêtrière Hospital, Paris, France. 8. Sorbonne 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. 9. CHU Lille, Cardiology, Lille, France. 10. Department of Cardiovascular Surgery, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, University Paris Descartes-Sorbonne Paris Cité, Paris, France. 11. Carmat SA, Vélizy-Villacoublay, France. 12. CHU Lille, Cardiac Surgery, Lille, France. 13. CHU Lille, Hematology Transfusion, Lille, France. 14. University of Lille, INSERM U1011-EGID, Lille, France; Institut Pasteur de Lille, Lille, France. 15. Laboratoire de Mathématiques, Paul Painlévé, UMR CNRS 8524, Université de Sciences et Technologies de Lille, Lille, France. 16. Department of Cardiovascular Surgery, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, University Paris Descartes-Sorbonne Paris Cité, Paris, France; Carmat SA, Vélizy-Villacoublay, France. 17. INSERM U1190-EGID, Lille, France. 18. INSERM U1176, University Paris-Sud, University Paris-Saclay, Le Kremlin-Bicêtre, France. 19. CHU Lille, Cardiology, Lille, France; University of Lille, INSERM U1011-EGID, Lille, France; Institut Pasteur de Lille, Lille, France. Electronic address: ericvanbelle@aol.com. 20. University of Lille, INSERM U1011-EGID, Lille, France; Institut Pasteur de Lille, Lille, France; CHU Lille, Hematology Transfusion, Lille, France. Electronic address: sophiesusen@aol.com.
Abstract
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.
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.
Authors: Ozair Rahman; Michael Scott; Emilie Bollache; Kenichiro Suwa; Jeremy Collins; James Carr; Paul Fedak; Patrick McCarthy; Chris Malaisrie; Alex J Barker; Michael Markl Journal: Int J Cardiovasc Imaging Date: 2019-05-29 Impact factor: 2.357
Authors: Eric J Stöhr; William K Cornwell; Manreet Kanwar; John R Cockcroft; Barry J McDonnell Journal: Exp Physiol Date: 2020-04-03 Impact factor: 2.858
Authors: Alexander A Pugovkin; Aleksandr G Markov; Sergey V Selishchev; Leonie Korn; Marian Walter; Steffen Leonhardt; Leo A Bockeria; Olga L Bockeria; Dmitry V Telyshev Journal: Cardiol Res Pract Date: 2019-11-15 Impact factor: 1.866