This document outlines a study to quantify hemodynamic changes caused by stenting of coronary artery bifurcation lesions using computational fluid dynamics (CFD) models. The study aims to: 1) Create idealized models to simulate blood flow through a left anterior descending/diagonal 1 bifurcation pre-stenting, post-stenting, and post-kissing stent; 2) Create patient-specific models to simulate blood flow pre- and post-stenting; and 3) Simulate stent expansion using finite element analysis. The results will provide insight into how stenting techniques, stent orientation, and post-implantation geometry affect local hemodynamics at bifurcations.

1. Quantifying Hemodynamic Changes Caused by Stenting
of Coronary Bifurcation Lesions Using Realistic
Computational Fluid Dynamics Models
November 14, 2008
By
Andrew R. Williams, B.S.
Committee:
John LaDisa, PhD
Said Audi, PhD
Bon-Kwon Koo, MD PhD
Lars Olson, PhD
1
1

2. Outline
• Introduction
• Methods
• Specific Aim 1
• Specific Aim 2
• Specific Aim 3
• Discussion
• Conclusions
• Next Steps
2
2

3. Introduction - Cardiovascular Disease
• 1 in 2.8 deaths in the United States is caused by
cardiovascular disease (CVD)
• 52% of those deaths are caused by coronary artery
disease (CAD) in which fatty deposits form and
occlude blood flow to the heart
• Risk factors manifest globally and include:
• High cholesterol
• High Blood pressure
• Diabetes mellitus
• Smoking
3 AHA Heart Disease and Stroke Statistics 2007 update
3

4. Introduction - Bifurcations
• Plaque tends to form
locally at
• Bends
• Branches
• Bifurcations
Fung Y. Biomechanics: Mech. Properties of Living Tissues. New York: Springer; 1993.
4
4

5. Introduction - Coronary Anatomy
2
1
Major coronary arteries
include the: 3
1. Right Coronary Artery
(RCA)
2. Left Circumflex (LCX)
3. Left Anterior
Descending (LAD)
The most common site of bifurcation plaque is the LAD/D1
From Wolf-Heidegger’s Atlas of Human Anatomy. 6th ed.
5
5

6. Introduction - Bifurcation Flow Profile
The flow profile after a bifurcation is skewed towards the
carina.
6 Courtesy of Eric Gross MD, PhD
6

7. Introduction - Important Indices
• Wall shear stress (WSS or τ):
The tangential stress imparted onto the walls of a
blood vessel as a result of moving fluid
• Oscillatory shear index (OSI):
OSI quantifies the deviation of WSS from the
primary flow direction during the cardiac cycle
OSI ranges between 0 (no change in direction) and
0.5 (complete reversal of direction)
7
7

8. Introduction - Coronary Artery Disease
Plaque forms at locations of low time averaged wall
shear stress (TAWSS) and high oscillatory shear
index (OSI)
8 www.nhlbi.nih.gov/health/dci/Diseases/Angioplasty
8

9. Introduction - Stenting
• Stenting is the most
common method to
treat CAD
• Procedure involves:
A. Position catheter
B. Expand the stent
C. Remove the catheter
• In 2005 in the US,
there were 1,265,000
PCI of which 620,000
were stent
implantations
9 www.nhlbi.nih.gov/health/dci/Diseases/Angioplasty
9

10. Introduction - Restenosis
Over the course of months, 15-20% of stented patients
have neointimal hyperplasia growth through and around
the stent potentially causing:
• redevelopment of the
stenosis
• an increase in resistance
• reduced blood flow
Stent geometry is an
important factor in
restenosis
10
Deplano et al. Med Biol Eng Comput. Sep 2004;42(5):650-659. www.nhlbi.nih.gov/health/dci/Diseases/Angioplasty
10

11. Introduction - Types of Stents
Taxus Express2 Taxus Liberte
(Boston Scientific) (Boston Scientific)
Cypher
(Cordis, J&J)
11
11

12. Introduction - Bifurcation Stents
MultiLink Frontier
(Abbott Vascular)
Axxess Plus
(Devax)
12
12

13. Introduction - Bifurcation Stenting
There are multiple methods to stent bifurcations
with traditional stents.
Single Stent Method Two Stent Method
Adapted from www.angioscore.com 13
13

14. Introduction - Difficulties studying blood flow in vivo
Blood flow is therefore important, but
• WSS measurement is not part of clinical practice
• devices do not have required resolution
Velocity and shear rate in a human common carotid artery with ultrasound
14 Katritsis et al. Prog Cardiovasc Dis. Mar-Apr 2007;49(5):307-329.
14

15. Introduction - CFD
Computational Fluid Dynamics (CFD) is an
advanced simulation tool ideal for studying the local
effects of blood flow.
Example Model Geometry
Requirements:
Inflow
• Model Geometry
• Computational Mesh
Wall properties
• Inflow Boundary
Conditions
• Outflow Boundary Outflow
Conditions
• Wall Properties
15
15

16. Introduction - Previous Work - CFD Stents
LaDisa et al. simulated blood flow through a stented model
to show that WSS correlated with neointimal hyperplasia in
rabit illiacs.
Deplano et al. simulated blood flow through a stented
bifurcation with zero pressure outlet boundary conditions.
16
LaDisa et al. AJP - Heart Circ Physiol 288: H2465-75, 2005 Deplano et al. Med Biol Eng Comput. Sep 2004;42(5):650-659.
16

17. Introduction - Previous Work (cont.)
• CFD bifurcation models with realistic
dimensions and physiologic boundary conditions
have not been created
• Previous CFD studies with stents have used
simplified geometries
• Treatment-specific changes in coronary
bifurcation blood flow have not been studied
• Patient-specific models have not included stents
previously
17
17

18. Hypothesis
Adverse hemodynamic changes are
introduced in bifurcation regions by
stenting and are influenced by
implantation technique, stent
orientation, and post-implantation
geometry
18
18

19. Specific Aims
1. Create idealized models and simulate
blood flow through the LAD/D1
bifurcation pre-stenting, post-stenting,
and post-kissing
2. Create patient-specific models and
simulate blood flow through the LAD/D1
bifurcation pre- and post-stenting
3. Simulate the expansion of a stent using
finite element analysis (FEA)
19
19

20. Outline
• Introduction
• Methods
• Specific Aim 1
• Specific Aim 2
• Specific Aim 3
• Discussion
• Conclusions
• Next Steps
20
20

21. Methods
• Meshing
• Inflow Boundary Conditions
• Outflow Boundary Conditions
• Vessel Wall Properties
21
21

22. Methods - Meshing
Meshing discretizes a model into millions of element
for which the mass and momentum balance
equations are solved
22
22

23. Methods - Inflow Boundary Conditions
• An inflow waveform must be defined for at least one face
• LaDisa et al. measured blood flow through a canine coronary
artery using an ultrasonic flow probe
• Resting and elevated blood flow conditions were applied
using a Womersley velocity profile
3.500
1.5
3.000
1.2
2.500
Blood Flow (cc/s)
0.9 2.000
Blood Flow (cc/s)
1.500
0.6
1.000
0.3
0.500
0.0 0.000
0.00 0.10 0.20 0.30 0.40 0.50 0.60 0.000 0.100 0.200 0.300 0.400 0.500 0.600
Time (s) Time (s)
Rest Elevated Blood Flow
23 LaDisa et al. JAP 2002; 93:1939-1946
23

24. Methods - Outlet Boundary Conditions
• Input impedance represents the contribution of all
vessels distal to an outlet
• Coronary input impedance increases during systole
constituting a non-linear, time-varying system for
which standard frequency analysis is invalid
• Van Huis et al. measured the impulse response in the
canine LAD under resting conditions circumventing
this limitation
• These methods neglect the time-varying resistance
caused by myocardial contraction
• The input impedance can be approximated by a three
element Windkessel model with limitations
24 From the SimVascular User Manual
24

25. Outlet Boundary Conditions (cont.)
• Rp is the characteristic impedance (Zc):
where Cph is wave speed, ρ is density, and r is radius
• Rp was calculated for each branch individually
25 Van Huis et al. Am J Physiol. Aug 1987;253(2 Pt 2):H317-324
25

26. Outlet Boundary Conditions (cont.)
• Van Huis et al. calculated Rd:
• Capacitance is found by using the pulse pressure
method of Stergiopulos et al. which iterates the
capacitance until the simulation pulse pressure
matches physiologic pulse pressure
• The mean flow was calculated as the fraction of the
total flow going to each branch, assuming WSS auto-
regulation or equal WSS at the outlets
26 Van Huis et al. Am J Physiol. Aug 1987;253(2 Pt 2):H317-324
26

27. Outlet Boundary Conditions (cont.)
• Elevated blood flow conditions (i.e. exercise or
hyperemia) representative of those achieved by
continuous intracoronary adenosine infusion were
applied
• Rp was calculated using a representative wave speed
for exercise
• Elevated blood flow conditions from LaDisa et al.
were imposed
• Rd and C were calculated with increased flow and
the same pressure
27 Koo et al. Circ. Aug. 2005; 69: 908-912
27

28. Methods - Vessel Wall Properties
• No slip assumed
• Rigid walls assumed
• Later simulations will include deformable
walls with different moduli for vessel and
stent surfaces
28
28

29. Outline
• Introduction
• Methods
• Specific Aim 1
• Specific Aim 2
• Specific Aim 3
• Discussion
• Conclusions
• Next Steps
29
29

30. Specific Aim 1
-Idealized models
• Motivation
• Model generation
• Stent Creation
• Design parameters
• Results
• Summary
30
30

31. Specific Aim 1- Motivation Carina Shift
Intravascular Ultrasound (IVUS) Data
Pre-Stent
Post-Stent
Post-Kiss
31 Images courtesy of Bon-Kwon Koo, MD, PhD
31

32. Specific Aim 1- Motivation (cont.)
• Finet’s Law
Empirically derived formula relating parent vessel
radius (rp) to the sum of the daughter vessels radii
(rdaughter1, rdaughter2)
32
Courtesy of Bon-Kwon Koo, MD PhD Finet et al. EuroInterv. 2007;3.
32

33. Specific Aim 1- Design Parameters
33 Ikeda et al. Jpn Heart J. Sep 1991;32(5):627-633
33

34. Specific Aim 1- Design Parameters (cont.)
Crimped Stent Sketch
34
34

35. Specific Aim 1 - Important Indices
• Fractional Flow Reserve (FFR) is clinical method to
quantify the severity of a stenosis
Where QSmax and QNmax are the maximum flows
through the stenosed and normal vessels
respectively
In practice FFR is approximated, where Pd and Pa are
the pressure distal and proximal to the stenosis,
respectively, during exercise
• % Stenosis is the percent change in area measured
by angiography
35 Adapted from Bon-Kwon Koo, MD PhD
35

36. Specific Aim 1 - Important Indices (cont.)
• Angiographic Severity vs. FFR Severity
• FFR Severity does not correlate well with %
Why discrepancy????
stenosis.
One explanation is that only the minor diameter of the side
branch is observed and the major diameter cannot be seen during
an angiographic assessment.
Why discrepancy????
MB
MB
MB SB
MB
SB
Major
SB
SB
Diameter
Minor
Diameter
36
Koo et al. JACC 2005, 46(4) 633-7 Adapted from Bon-Kwon Koo, MD PhD
36

37. Specific Aim 1- Model Generation
37
37

38. Specific Aim 1- Stent Creation
38
38

39. Specific Aim 1- Boolean Subtraction
39
39

40. Specific Aim 1- Resulting Models
IVUS Data Resulting Idealized Models
Pre-Stent
Post-Stent
Post-Kiss
40
40

41. Specific Aim 1- Side Branch Jailing
Post-Stent Best Case Post-Stent Worst Case
Post-Kiss
41
41

42. Specific Aim 1 - Mesh Independence
• CFD models were simulated with increasingly refined
element density using an adaptive meshing approach
• Results were assumed to be mesh independent when
TAWSS at 5 locations within the computational
domain changed less than 6% (< 0.09 dyn/cm2)
between two successive meshes
Figure showing faces where WSS was assessed
42
42

43. Specific Aim 1 - Mesh Independence (cont.)
Number of Elements In Successive Meshes
43
43

44. Specific Aim 1- Volume Rendered Velocity
Pre-Stent Pre-Stent
0 22.5 0 55
Rest (cm/s) Exercise (cm/s)
Post-Stent
Worst Post-Kiss
0 20 0 20
Rest (cm/s) Rest (cm/s)
44
44

45. Specific Aim 1- TAWSS Resting
Post-Stent Post-Stent
Pre-Stent Post-Kiss
Best Case Worst Case
0 20
Time-averaged WSS (dynes/cm2)
45
45

46. Specific Aim 1- TAWSS Exercise
Post-Stent Post-Stent
Pre-Stent Post-Kiss
Best Case Worst Case
0 30
Time-averaged WSS (dynes/cm2)
46
46

47. Specific Aim 1 - Area with Low WSS
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Stenting increases area of low WSS
Area of low WSS is reduced during exercise
47
47

48. Specific Aim 1- OSI Rest
Post-Stent Post-Stent
Pre-Stent Post-Kiss
Best Case Worst Case
0 0.5
Oscillatory Shear Index
48
48

49. Specific Aim 1- OSI Exercise
Post-Stent Post-Stent
Pre-Stent Post-Kiss
Best Case Worst Case
0 0.5
Oscillatory Shear Index
49
49

50. Specific Aim 1- Summary
• Idealized models show the effects of single
stent implantation on WSS, OSI and
velocity distribution
• Stenting causes a shift in the carina
towards the side branch, skewing the
velocity profile of the main branch
• Post-stenting dilation to shift the carina
back towards the main branch skews the
velocity profile away from the carina
50
50

51. Specific Aim 1- Summary (cont.)
• Velocity profiles near the bifurcation are
therefore influenced by the location of the
carina
• Stenting introduces areas of low WSS near
stent struts and opposite the carina that
are alleviated by exercise
• Stenting introduces areas of high OSI near
stent struts and opposite the carina that
are pronounced by exercise
51
51

52. Outline
• Introduction
• Methods
• Specific Aim 1
• Specific Aim 2
• Specific Aim 3
• Discussion
• Conclusions
• Next Steps
52
52

53. Specific Aim 2
- Patient Specific Models
• Motivation
• Model Generation
• Stent Creation
• Results
• Summary
53
53

54. Specific Aim 2
- Motivation
• Provide increased physiologic realism
• Support results from first specific aim
• Develop methods for subsequent studies
54 Image courtesy of Jon Freeman MD and Ray Migrino MD
54

55. Specific Aim 2 - Model Generation
A. 64 slice CT angiographic data taken for a human
B. Center paths are drawn through the bifurcated vessel
images and cross sections are segmented
C. CVSim lofts between the segments to created a geometric
model of the bifurcated vessel
D. Geometric model is meshed with >1.5 million elements
55
55

56. Specific Aim 2- Patient Specific Stent Creation
56
56

57. Specific Aim 2- Velocity Rest
Pre-Stent Post-Stent
20
Volume-rendered
Velocity (cm/s)
0
57
57

58. Specific Aim 2- Velocity Exercise
Pre-Stent Post-Stent
55
Volume-rendered
Velocity (cm/s)
0
58
58

59. Specific Aim 2- Patient Specific TAWSS Rest
Pre-Stent Post-Stent
20
Time-averaged WSS
(dynes/cm2)
0
59
59

60. Specific Aim 2- Patient Specific TAWSS Exercise
Pre-Stent Post-Stent
30
Time-averaged WSS
(dynes/cm2)
0
60
60

61. Specific Aim 2- Patient Specific OSI Rest
Pre-Stent Post-Stent
Oscillatory Shear Index
0.5
0
61
61

62. Specific Aim 2- Patient Specific OSI Exercise
Pre-Stent Post-Stent
Oscillatory Shear Index
0.5
0
62
62

63. Specific Aim 2 - Summary
• Similar to the idealized models, stenting
introduces areas of low WSS and high OSI
around stent struts that is similarly influenced
by exercise
• Regions of high OSI were less pronounced
compared to the idealized models
• Stent struts protruding into (i.e. jailing) the
side branch ostium cause vortices that are
pronounced during exercise
63
63

64. Outline
• Introduction
• Methods
• Specific Aim 1
• Specific Aim 2
• Specific Aim 3
• Discussion
• Conclusions
• Next Steps
64
64

65. Specific Aim 3
- Implantation Using FEA
• Motivation
• Model generation
• Results
• Summary
65
65

66. Specific Aim 3
- Motivation
Wu et al. simulated the
expansion of a stent in a
straight vessel (SV) and
curved vessel (CV)
model.
(Displacement (top) and stress (bottom))
Applying these methods
would allow simulation of
two stent bifurcation
approaches
66 Wu et al. J Biomech. 2007;40(11):2580-2585.
66

67. Specific Aim 3
- Model Generation
67
67

68. Specific Aim 3 - Simulation Parameters
Number of Elements 24,000
Element Type 8-node Solid 185
Stent Material 316L annealed stainless steal
Modulus 201 GPa
Poisons Ratio 0.3
Simulation Time 100 seconds
Number of Substeps 50
Pressure Applied to Inner
2.01*104 Pa
Surface of the Ring
68
68

69. Specific Aim 3
- Results
69
69

70. Specific Aim 3
- Results (cont.)
70
70

71. Specific Aim 3 - Summary
• Simulated expansion of one macro ring element of
the Taxus Express2 stent with FEA demonstrates
feasibility of these methods
• Expansion caused stress concentration in regions of
curvature within the macro ring element
• Expansion introduced modest “S” curve in straight
regions of the macro ring elements
• This progress reveals the geometric limitations of the
stent models used in specific aims 1 and 2
71
71

72. Outline
• Introduction
• Methods
• Specific Aim 1
• Specific Aim 2
• Specific Aim 3
• Discussion
• Conclusions
• Next Steps
72
72

73. Discussion
• Clinical Application to FFR
• Area of Low TAWSS and High OSI
• Limitations of Models
• Novelty of Current Work
73
73

74. Discussion - FFR
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Stenting reduces FFR but not to a clinically significant level (0.75)
The worst case orientation decreased FFR most
74
74

75. Discussion - TAWSS and OSI
• Low TAWSS and high OSI have been
correlated with restenosis
• Stenting introduces areas of low WSS and
high OSI near stent struts and near the
carina
• Therefore, we might expect restenosis to
occur in those areas
75
75

76. Discussion - Limitations
• Straight Vessels - Coronary arteries are located on
the curved surface of the heart
• Sharp Transitions - Sharp vascular transitions add
artifact to idealized models
• Simplified Stent Implantation - Some distortion of
strut length
• RCR Boundary Conditions - Time varying resistor
not included
• Rigid Walls - Future simulations will include
deformable walls
76
76

77. Discussion - Novelty of Current Work
• Idealized models reproduced clinical observations
with improved realism allowing for measurement of
hemodynamic and clinical parameters
• Results of patient-specific models built upon findings
of idealized models by adding increased physiologic
realism
• FEA simulations of stent expansion helped evaluate
geometric limitations of the stented models and
developed tools for future work with patient-
specific models
77
77

78. Conclusions
• Stenting causes geometric changes to the lumen of the
vessel which cause increased areas of low TAWSS and high
OSI
• Low TAWSS and high OSI have been shown to
correlate with restenosis
• Idealized and patient-specific CFD models of the LAD/D1
bifurcation site were developed with virtual implantation of
a common stent used in clinical practice
• Implantation technique, stent orientation in the side
branch ostium, and carina location affect WSS and OSI
• Methods were also developed to simulate the virtual
implantation of a stent with FEA
78
78

79. Next Steps
• Simulate with deformable walls
• Investigate different stent types and multiple
stent strategies
• Investigate the effect of strut orientation in the
ostium
• Apply current and future developments to next
generation bifurcation stent designs
79
79

80. Acknowledgements
John LaDisa, PhD
Bon-Kwon Koo, MD, PhD
Lars Olson, PhD
Said Audi, PhD
John Freeman, MD
Ray Migrino, MD
80
80

81. Questions?
• Thank You
81