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Second Meeting of the (EBC) European Bifurcation Club Friday 29 – Saturday 30 September 2006. GRAND HOTEL Palazzo Carpegna. Laboratoire d’Etudes Aérodynamiques Bld Marie et Pierre Curie, Téléport 2 86962 Futuroscope Chasseneuil France.
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Second Meeting of the (EBC) European Bifurcation ClubFriday 29 – Saturday 30 September 2006 GRAND HOTEL Palazzo Carpegna
Laboratoire d’Etudes Aérodynamiques Bld Marie et Pierre Curie, Téléport 2 86962 Futuroscope Chasseneuil France Why a so high restenosis rate even with DES ?Hemodynamics perturbations insights Dr N.BENARD (PhD), Dr D. COISNE (MD, PhD) Nicolas.benard@lea.univ-poitiers.fr
Why study blood flow perturbationsin biomedical engineering ? 2
I-1 Stent design and restenosis rate 3 The stent design acts on the restenosis rate and the TLR rate via: • Heterogeneous vascular injuries • Local blood flow perturbations Kastrati A, Mehilli J, Dirschinger J, Pache J, Ulm K, Schuhlen H, Seyfarth M, Schmitt C, Blasini R, Neumann FJ, Schomig A, 2001. Restenosis after coronary placement of various stent types. Am J Cardiol.87:34-39.
I-2 Blood flow perturbations outcome 4 Intra-stent blood flow involves: • Stagnation regions (V~0 mm.s-1) • Low recirculating areas (V<2 mm.s-1, shear rate<10 s-1) • Shear stresses alterations: • Low shear stresses in the stagnation and recirculating regions • Low wall shear stresses close to the vascular wall • High wall shear stresses over the strut edges • Oscillatory wall shear stresses around the stent struts All of these flow features appear close to the wall and the stent struts (h<0.2 mm) The central flow is generally not affected by the stent design.
Clot formation, platelet adhesion Blood hemolysis Restenosis I-3 Physiological consequences 5 • Blood stagnation Increase of the blood residence time Lipidic mass transfert in the parietal wall thrombus formation Low shear rates (<50 s-1) • Low recirculating flow High shear stress (>2000 dyn/cm²) • Shear stress alterations Low wall shear stress (<10 dyn/cm²)
I-4 WSS and cellular responses 6 As the vascular wall is partly denuded after the stent deployment, both endothelial and smooth muscular cell undergo a local shear stress stimulation. An healthy coronary artery experienced a wss mean value about 18-22 dyn/cm². For WSS<10dyn/cm² • Proliferation • Aggregation • Migration • Growth factors release Endothelial and smooth muscular cells responses to wall shear stress stimulation participate to the restenosis process during the acute stage of stent implantation.
II Methodologies for intra-stent flow analysis 7 Blood flow analysis involves qualitative and quantitative investigations Aim: obtain the velocity fields I- Experimental investigations Methods: Laser measurements (Particle Image Velocimetry). Advantages: High temporal and spatial resolution, accurate method. Inconvenient: Require a transparent scaled model. II- Numerical investigations Methods: Computational Fluid Dynamics Advantages: Modelling of complex geometries and physiological environment Inconvenient: Require experimental validation.
II-1 Case of a single stented coronary artery 8 Application of the intra-stent flow analysis: Influence of the wire height or impact rate on 2D flow perturbations Qualitative and quantitative numerical results (Benard etal.) Qualitative experimental results (Benard et al.) This study highlights that wire height is a preponderent factor of 2D flow perturbations Thinner stent struts induce less stagnation regions and smaller parietal surface submitted to low wss. In vivo studies confirms a low restenosis rate for stent design using thinner struts.
Application of the intra-stent flow analysis: Influence of the stent pattern on wss repartition II-1 Case of a single stented coronary artery 9 Velocity and temporal wss evolution (numerical results Benard et al.) Fully deployed Helistent model Lower wss<2 dyn/cm² Higher wss>30 dyn/cm² Velocity and wss distribution at mean flow rate (experimental results Benard et al.)
II-1 Case of a single stented coronary artery 10 Application of the intra-stent flow analysis: Temporal and spatial wall shear stress evolution for flow through Helistent model WSS Evolution at 2.8 µm (numerical results Benard et al.)
Application of fluid dynamics analysis: Blood flow at bifurcation site A A III Bifurcations 11 CFD results (Tada, 2005, Ann. of Biomed. Eng.33) Qualitative experimental visualization (Fabregues, 1998, J. of Biomechanics 31) Large recirculations (A) are observed at the bifurcation apex or in the daughter branches
Application of fluid dynamics analysis: Macroscopic flow perturbations at stented bifurcation site A A B B B III Bifurcations 12 Physiological flow through a bifurcation model with palmaz stent (Fabregues, 1998, J. of Biomech.31) A stagnation zone (A) appear if the stent does not conform to the artery. The stent implantation in a daughter branch induces recirculation zones in the healthy artery branch (B) due to the protruding part of the stent. The flow perturbations at the wire scale are actually not investigated.
Intuitive consequence of 4 stenting techniques on local hemodynamics 2 Important flow separation 1 Large recirculation at the daughter entrance Large recirculation at the bifurcation apex 3 IV Influence of 4 stenting techniques on hemodynamic 13 High wire density (1) I Kissing Stenting Stagnation area between the struts Large area of low wss High flow obstruction (1) High flow obstruction (2) Ormiston II Provitional ‘T’ Stenting High flow obstruction (3) Ormiston
Potentially increase restenosis risk Stagnation area Important flow separation → low wss Can act like a flow divider1 and increase the wss IV Influence of 4 stenting techniques on hemodynamic 14 III ‘Culotte’ Stenting High wire density (4) 4 High flow obstacle (2 layers of strut) (5) 5 Ormiston IV ‘V’ Stenting High stented surface 6 High wire density in the central flow (6) 1 S. Carlier, 2003, Circulation 107 Ormiston
Conclusion 15 • Flow disturbances induced by a stent could be microscopic (between the strut pattern) or macroscopic. • The flow disturbances are significant and participate to the restenosis process in the acute stage of the stent implantation. • The enhancement of blood flow dynamics can decrease the restenosis rate (Pache, 2003, J. Am. Coll. of Cardiol. 41 and Kastrati, 2003, Circulation 103). • Stenting of bifurcation site requires blood flow analysis to fully understand the in vivo investigations and to provide accurate recommendations for future developments.
Laboratoire d’Etudes Aérodynamiques Bld Marie et Pierre Curie, Téléport 2 86962 Futuroscope Chasseneuil France Why a so high restenosis rate even with DES ?Hemodynamics perturbations insights Dr N.BENARD (PhD), Dr D. COISNE (MD, PhD) Nicolas.benard@lea.univ-poitiers.fr