Computer modelling of stent implantation: expansion and fluidynamics

1. Computer modelling of stent implantation: expansion and fluidynamics Francesca Gervaso Stents a Rilascio di farmaco. Aspetti clinici e tecnologici, Milano, 9 Maggio 2007

2. Introduction Arterial diseases like atherosclerosis are the leading causes of death in the industrialised world A reduction of the blood flow occurs because of the narrowing or occlusion of the affected arteries Stent implantationis a common procedure with a high rate of success when compared with angioplasty alone The purpose of a stent is to maintain the arterial lumen open by a scaffolding action that provides radial support Restenosisis a re-narrowing or blockage of an artery at the same site where treatment (such as a balloon angioplasty or stent procedure) has already taken place However, some limitations are still present and the major ones are those associated with the ‘in-stent restenosis’ process

3. Introduction Clinical trials showed the reduction of restenosis using a Drug Eluting Stent In fact… it is difficult to evaluate the effective release of the drug in the vascular tissue • stent design(i.e. strut thickness and shape) • drug(i.e. hydrophilic/hydrophobic) • coating type(i.e. pore size, continuous/reservoir) Moreover… • the expansion of the struts and the interaction with the vascularwallinfluences the outcome of the stenting procedure (Grenacher et al. 2006, Rogers and Edelman 1995) • fluidynamics is strongly influenced by the presence of the stent and correlations between wall shear stresses and restenosis exist (LaDisa et al., 2004)

4. Introduction FEMs are a useful tool to assess the influence of the factors affecting the drug release Finite Element (FE) models allow to stent-arterial wall interaction • predict phenomena fluidynamics drug release • interpret the available clinical data

5. Introduction Stent-arterial wall interaction 1) Coated vs. Reservoir stent 2) Balloon expandable stent stent expansion drug elution a stent is expanded inside an atherosclerotic coronary artery by means of the commercial finite element code ABAQUS (Abaqus Inc, RI, USA). the deformed coronary artery and stent are used as input geometries on which the drug eluting model analysis is carried out

6. Coated vs. Reservoir stent To analyse the drug release of two different DES resembling commercial products by means of numerical models based on the Finite Element Method Reservoir stent (Medsystem – Conor) Coated stent (Cordis – Cypher)

7. Coated vs. Reservoir stent: aim of the study • Quantitative evaluation of the mechanical interaction between the two stents and an atherosclerotic artery in terms of: • stressesinduced in the vascular wall • tissue prolapse within the stent cells • radial stretch ratioof the vascular tissue Rationale: • non physiological stress state field • tissue prolapse Restenosis 1) variation in tissue permeability due to the radial stretch ratio 2) Influence on the drug release

8. Coated vs. Reservoir stent: Materials & Methods CAD models • balloon expandable • AISI 316L Coated stent Reservoir stent Medsystem Conor Cordis Cypher

9. Coated vs. Reservoir stent: Materials & Methods Geometry Cordis Cypher Medsystem Conor = 1.2 mm Thickness = 0.1 mm 3.7 mm 3.68 mm Mesh shell elements number: 1400 ÷ 2100 Young modulus 193 GPa Poisson ratio 0.3 Material model: elasto-plastic

10. Coated vs. Reservoir stent: Materials & Methods Stent expansion: boundary conditions experimentaltests: At the end of the balloon inflation process the stent is UNIFORMLY EXPANDED in the radial direction a radial displacement up to 3 mm in diameter is imposed

11. Coated vs. Reservoir stent: Materials & Methods Coronary artery Realisticgeometryobtained from medical images Simplified symmetric geometry  influenced by simplified hypotheses  models and results near reality  reduced computational costs  high computational costs  utility for comparative analyses difficulties for comparative analyses 

12. Coated vs. Reservoir stent: Materials & Methods Material model: Artery • homogeneous • isotropic • incompressible (Hayashi and Imai, 1997) • hyperelastic Artery and plaque Geometry: • two hollow co-axial cylinders (no sliding) • artery internal diameter: 2.15 mm; thickness: 0.5 mm • plaque internal diameter: 1.25 mm; thickness: 0.45 mm • stenosis: 66% Plaque Mesh • 9230 Hexahedral elements (C3D8H)

13. Coated vs. Reservoir stent: Materials & Methods Simulations: STEP1: PRETENSIONING of 4% (Holtzapfel, 2005) axial stress equal to 0.006 MPa STEP2: PRESSURIZATION internal pressure of 100 mmHg STEP3: STENT EXPANSION up to 3 mm

14. Coated vs. Reservoir stent: Results • von Mises • triaxial plaque and artery MPa 0.35 0.29 0.23 0.17 0.11 0.06 0.00 MPa 4.52 3.67 2.62 1.81 0.97 0.53 0.00 Stresses 0.35 4.52 splaque~ 10 sartery Cordis Cypher Medsystem Conor scordis~ 3 sconor

15. Coated vs. Reservoir stent: Results • von Mises • triaxial plaque and artery MPa MPa MPa 0.20 -0.07 -0.34 -0.61 -0.87 -1.14 -1.41 2.26 1.90 1.54 1.19 0.83 0.47 0.11 0.40 0.21 0.01 -0.18 -0.38 -0.57 -0.76 Stresses Radial stress Medsystem Conor Circumferential stress Axial stress Cordis Cypher

16. Coated vs. Reservoir stent: Results MPa 0.27 0.20 0.13 0.06 0.00 -0.07 -0.14 • von Mises • triaxial plaque and artery Stresses Circumferential stress Axial stress Radial stress scordisslightly higher thensconor Cordis Cypher Medsystem Conor

17. Coated vs. Reservoir stent: Results • tissue prolapse (tp) • radial stretch ratio (lr) ln lr -0.09 -0.19 -0.28 -0.37 -0.46 -0.55 -0.65 lr increase of Deformed configuration Medsystem Conor Cordis Cypher 3.00 2.90 2.94 3.00 tp = 0.1 mm tp = 0.06 mm Influence on the drug release decrease of tissue permeability

18. Coated vs. Reservoir stent: Conclusions • It is difficult to find a strict correlation between prolapse, the in-stent restenosis and the geometrical design. The FEM of the stent expansion developed allowed:  to mechanically evaluate two stent designs in terms of effects on the arterial wall  to provide the initial geometry for the Drug Elution model A similar study could be useful when joined with a clinical trial aimed at comparing the influence of the stent design on the degree of restenosis. Clinical trials are present in the literature, but results are hardly comparable to those from previous trials, even for the same stent design, because of the different methods adopted (patient recruitment, primary or secondary endpoints, …).

19. Coated vs. Reservoir stent: limitations and future work Arterial wall • only one vessel layer considered • absence of plaque fracture • absence of vessel curvature Methodology • absence of the inflation/deflation of the balloon • only one stent unit analyzed • New material model: 3 layers (Holtzapfel et al.,2005) • Stent expansion by balloon inflation

20. Balloon expandable stent: Introduction Stent-arterial wall interaction 1) Coated vs. Reservoir stent 2) Balloon expandable stent Stent expansion Fluidynamics Two distinct computational models related to the implantation of balloon-expandable stent and the subsequent fluidynamics generated by stent presence were built

21. Balloon expandable stent: Materials and Methods FE models of balloon, stent and coronary artery were created using the commercial code ABAQUS/Explicit 6.5 Balloon Material 7.8 mm 3.2 mm linear-elastic Young modulus 1.4 GPa Poisson coefficient 0.3 Mesh 11762 M3D4R/M3D3R membrane elements 11872 nodes No radial and tangential displacements No axial and tangential displacements P<0

22. Balloon expandable stent: Materials and Methods FE models of balloon, stent and coronary artery were created using the commercial code ABAQUS/Explicit v.6.5 Stent Material elasto-plastic Young modulus 193 GPa Poisson coefficient 0.3 3.68 mm Mesh 14951 C3D8R solid elements 25724 nodes 1.2 mm 0.14 mm No axial and tangential displacements

23. Balloon expandable stent: Materials and Methods FEMs of balloon, stent and coronary artery were created using the commercial code ABAQUS (Abaqus Inc, RI, USA) Coronary artery Mesh Material 39420 C3D8R solid elements Cauchy Stresss (KPa) Three hyperelastic and isotropic layers Experimental data from tensile test on intima, media and adventitia (Holzapfel et al., 2005) Reduced Polynomial n=5

24. Balloon expandable stent: Materials and Methods The whole model – Simulations Step 2: Balloon pressurization (0.7 MPa) Step 1: Coronary pressurization (100 mmHg) Step 3: Balloon deflation (P=0 MPa)

25. Balloon expandable stent: Results I phase: balloon’s inflation II phase: dogboning effect IV phase: deflation of the balloon III phase: fully inflation of the balloon

26. Balloon expandable stent: Results [MPa] [MPa] 500 0.9 250 0.45 0 0 Von Mises stresses II phase:dogboning effect

27. Balloon expandable stent: Results [MPa] 0.9 [MPa] 0.45 500 0 250 0 Von Mises stresses Von Mises stresses IV phase:deflation of the balloon

28. Balloon expandable stent: Fluidynamics Outlet Inlet Velocity profile: parabolic and transient Constant fixed pressure 4 cardiac cycles pulse period = 0.54 s [ La Disa et al., 2004 ] Assumptions • rigid vessel wall • Newtonian fluid (Viscosity = 0.0035 kg/(m∙s), Density = 1060 kg/m3)

29. Balloon expandable stent: Fluidynamics 0.65 0.52 0.39 0.26 0.13 0 2.0 1.6 1.2 0.8 0.4 0 [Pa] 1.1 0.88 0.66 0.44 0.22 0 WSS values alternate across the vessel during the cardiac cycle [Pa] [Pa]

30. Balloon expandable stent: Conclusions This study presents an approach to simulate the interaction of a coronary stent with the vascular wall and the Fluidynamics into the arterial wall The stent expansion model allows: • to mechanically evaluate the stress effect generated by the stent on the arterial wall • to provide the initial geometry for the Fluidynamics The fluidynamics model allows • to evaluate the fluidynamic changes following a stent procedure

31. A B C D E G high F low Balloon expandable stent: limitations and future work Limitations • absence of vessel curvature • absence of plaque • only one unit analysed In collaboration with the Erasmus Centre - Rotterdam Future works • correlation between the structural and fluidynamics results, analyzing different stent designs jostent multilink cordis carbostent

32. Acknowledgements THANKS Rossella Balossino Claudio Capelli Francesco MigliavaccaLorenza Petrini Gabriele Dubini This work has been supported by the Fondazione Cariplo, Milan, Italy, under the project “Modellistica Matematica di Materiali Microstrutturati per Dispositivi a Rilascio di Farmaco” francesca.gervaso@polimi.it LABORATORY OF BIOLOGICAL STRUCTURE MECHANICS www.labsmech.polimi.it