Cardiac pathologies, blood flow abnormalities and haemostasis

Team 2 – INSERM U1011 – Lille University – CHU Lille – Institut Pasteur de Lille

Presentation

Highlights

• Constitution of a unique biobank of human aortic valvular tissue and cells was performed due to synergistic collaborations of the Lille University Hospital, Cardiac Surgery Department and the European Graft bank (to collect normal valves). These results have the potential for innovative approaches to reduce calcification of either native valves or bioprosthesis. Our results are leading to a pending patent (InsermTransfert).

• In 2018, we obtained a funding for “Appel à projet générique” by the international jury of the national application “Agence Nationale de la Recherche” (ANR) for the RETINAVs project.

• We successfully described and deciphered the biology and mechanisms of von Willebrand factor alterations in high shear cardiac disorders such as aortic stenosis. Based on these findings, we provided clinical evidence that changes in von Willebrand factor multimeric profile could be used as a biological tool to assess the flow-abnormalities and that, as such, von Willebrand factor functions as a dynamic marker of changes in blood flow and are applied in this concept in a large clinical trial demonstrating the usefulness of this marker in a clinical setting (Van Belle, JACC, 2016, Van Belle, JACC, 2019).

• Our know-how, the models that we have developed (dedicated animal models of high shear with controlled pulsatility and prototypes of ex-vivo mock circulatory loops) and our different cohorts have been the basis of collaborations with industries developing solutions for cardiac failure (Carmat, Abiomed, CorWave) and aiming to preserve haemostasis and von Willebrand factor to limit bleeding complications, identification of patients at high risk of bleeding (Stago, Siemens, Sebia) and treatment for bleeding associated with Von Willebrand alterations (acquired von Willebrand syndrome (AVWS)) (Shire, LFB) .

• S. Susen has been appointed as the French national coordinator for Von Willebrand Disease (VWD) network in 2017. This recognition reinforced the synergy between the research team and the French network of VWD.

• We obtained a PHRC-N grant for the PHAM (Prevention of Hemorrhage After Implantation of Mechanical Circulatory Support) This study was also supported by the Laboratoire Français du fractionnement et des Biotechnologies (LFB).

• We obtained an “Recherche Hospitalo-Universitaire en santé” (RHU) in 2017 (the WillAssistHeart proposal; 17-RHUS-0011) to develop diagnostic tools and new treatments targeting von Willebrand factor degradation. The consortium presented in the proposal by our group was made of our team, members of U1176 and 2 industrial partners (Stago and LFB).

• We also obtained a grant from the PHRC-N 2017 for the WITAVI-Real study, a national multicentric trial aiming, to evaluate the impact of monitoring von Willebrand factor by PFA measurement during transcatheter aortic valve replacement  in real life.

• In 2018, in association with the industrial Corwave, we obtained a PSPC (“programme de soutien aux pôles de compétitivité”) a funding from the BpiFrance for the Calypso (Connected Left Ventricular Assist Device respecting patient physiology for an optimized care) project.

Transversals projects

Study the potential of original pathway through identification of nuclear receptors as therapeutic targets to slow aortic valve stenosis and bioprosthetic degeneration

Collaboration : D Smadja, Inserm UMR1140, R Jashari, European Homograft Bank

Investigate the consequences of flow disturbances due to cardiac structural abnormalities on haemostasis

Collaboration : P Lenting, Inserm U1176; JP Collet, Ican; P Leprince, Pitié-Salpétrière; A Barakaht, LadHyx; CorWave , Stago, Abiomed (Industrials); S De Meyer, KU-Leuven, Belgium; E Gardiner, Australian National University, Canberra, Australia

Qualify von Willebrand factor as a biological marker of blood flow and investigate its role in the occurrence of bleeding

Collaboration : JP Collet, UPMC; O Morel, Inserm UMR1260; S De Meyer, KU-Leuven, Belgium; P Généreux, USA

Members

Annabelle DUPONT
PU-PH

Francis JUTHIER
PU-PH

Natacha ROUSSE
PH

Christophe ZAWADZKI
PH

Eric BOULLEAUX
Engineer, technician, administrative

Mélusine DIDELOT
Engineer, technician, administrative

Bénédicte PRADINES
Engineer, technician, administrative

Florence VAAST
Engineer, technician, administrative

Mouhamed MOUSSA
PhD Student

Publications

Van Belle E, Vincent F, Rauch A, Casari C, Jeanpierre E, Loobuyck V, Rosa M, Delhaye C, Spillemaeker H, Paris C, Debry N, Verdier B, Vincentelli A, Dupont A, Lenting PJ, Susen S.
von Willebrand Factor and Management of Heart Valve Disease: JACC Review Topic of the Week.
J Am Coll Cardiol. 2019 Mar 12;73(9):1078-1088.

Vincent F, Rauch A, Spillemaeker H, Vincentelli A, Paris C, Rosa M, Dupont A, Delhaye C, Verdier B, Robin E, Lenting PJ, Susen S, Van Belle E.
Real-Time Monitoring of von Willebrand Factor in the Catheterization Laboratory: The Seatbelt of Mini-Invasive Transcatheter Aortic Valve Replacement ?
JACC Cardiovasc Interv. 2018 Sep 10;11(17):1775-1778.

Vincent F, Rauch A, Loobuyck V, Moussa M, Juthier F, Debry N, Jeanpierre E, Lenting PJ, Susen S, Van Belle E.
von Willebrand Factor for Aortic Valve Intervention: From Bench to Real-Time Bedside Assessment.
Circ Res. 2018 May 25;122(11):1499-1500.

Vincent F, Rauch A, Loobuyck V, Robin E, Nix C, Vincentelli A, Smadja DM, Leprince P, Amour J, Lemesle G, Spillemaeker H, Debry N, Latremouille C, Jansen P, Capel A, Moussa M, Rousse N, Schurtz G, Delhaye C, Paris C, Jeanpierre E, Dupont A, Corseaux D, Rosa M, Sottejeau Y, Barth S, Mourran C, Gomane V, Coisne A, Richardson M, Caron C, Preda C, Ung A, Carpentier A, Hubert T, Denis C, Staels B, Lenting PJ, Van Belle E, Susen S.
Arterial Pulsatility and Circulating von Willebrand Factor in Patients on Mechanical Circulatory Support.
J Am Coll Cardiol. 2018 May 15;71(19):2106-2118.

Van Belle E, Rauch A, Vincent F, Robin E, Kibler M, Labreuche J, Jeanpierre E, Levade M, Hurt C, Rousse N, Dally JB, Debry N, Dallongeville J, Vincentelli A, Delhaye C, Auffray JL, Juthier F, Schurtz G, Lemesle G, Caspar T, Morel O, Dumonteil N, Duhamel A, Paris C, Dupont-Prado A, Legendre P, Mouquet F, Marchant B, Hermoire S, Corseaux D, Moussa K, Manchuelle A, Bauchart JJ, Loobuyck V, Caron C, Zawadzki C, Leroy F, Bodart JC, Staels B, Goudemand J, Lenting PJ, Susen S.
Von Willebrand Factor Multimers during Transcatheter Aortic-Valve Replacement.
N Engl J Med. 2016 Jul 28;375(4):335-44.

Keywords

Von Willebrand Factor (VWF) ; Von Willebrand Disease ; Haemostasis ; Bleeding ; Cardiovascular diseases ; LVAD ; Aortic Valve Stenosis ; Hemodynamic ; Heart Valve Disease ; Blood flow

Team contact

Sophie Susen
Medicine profesor

sophie.susen@inserm.fr