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IMPROVEMENT OF HAEMODYNAMIC STENT STRUT CONFIGURATIONFOR PATENT DUCTUS ARTERIOSUS THROUGH COMPUTATIONAL
MODELLING
ISHKRIZAT BIN TAIB
A thesis submitted in fulfilment of therequirements for the award of the degree of
Doctor of Philosophy (Mechanical Engineering)
Faculty of Mechanical EngineeringUniversiti Teknologi Malaysia
JANUARY 2016
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To my beloved Ayah, Mak, Abah, Mak Labu, my supportive wife Norsa’adah, mychildren Muhammad Hadif and Muhammad Hafiy and my siblings Mashitah, Aden,
Firdaus and Asma Husna and my family
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ACKNOWLEDGEMENT
Foremost, thanks to Almighty Allah, the Most Gracious the Most Merciful, forthe wisdom he bestowed upon me, the strength, knowledge and good health in order tofinish this research.
I wish to express my sincere appreciation and thanks to my Family for givingcontinuous support and encouragement in finishing my study. My beloved andsupportive wife, Norsa’adah Binti Abdul Kadir, and my lovable children, MuhammadHadif and Muhammad Hafiy who served as my inspiration to complete this research.
I would like to express my special gratitude to my supervisor, Assoc. Prof.Dr. Kahar bin Osman, and co-supervisors, Assoc. Prof. Dr. Takahisa Yamamoto andDr Ahmad Zahran Khudzari for imparting their knowledge, encouragement, guidance,critics and suggestions. Without their continuous support and interest, this thesis wouldnot have been the same as presented here.
My thanks and appreciations to Computational Fluid Mechanics Lab membersand Advanced Stent Group, Dr. Mohamed Ikhwan Kori and Dr. Fara LyanaJamalruhanordin. I will be forever grateful for their love and kindness.
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ABSTRACT
Currently, the treatment of Patent Ductus Arteriosus (PDA) by the implantationof coronary stent has resulted in severe hemodynamic complications. There isthus a need to customize and improve current stent geometry specific to PDA toovercome this problem. Computational Fluid Dynamics (CFD) approaches, verifiedby an experimental technique are used to analyze current stent strut configurations.Statistical analysis is used to rank the parameter performance and to obtain the beststent configuration. The most favorable configuration is then used to design newstent strut configuration specific for PDA. In the analysis of the new stent design,CFD results show low possibility of re-stenosis process due to thrombosis formation,inflammation, and neo-intimal hyperplasia. Furthermore, comprehensive CFD analysisby solving fluid-structure interaction (FSI) cases has produced an optimum stent strutconfiguration that is structurally sound. The strength of stent strut configuration dueto hemodynamic effect is analyzed through the Von Misses stress distribution. Theresults show that the new improved design of stent strut configuration has excellenthemodynamic performance. Finally, the new stent design is predicted to be ableto overcome hemodynamic complications and stent structural failure when appliedspecifically to PDA.
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ABSTRAK
Rawatan implantasi stent koronari pada Patent Ductus Arteriosus (PDA)
telah menyebabkan komplikasi hemodinamik yang ketara. Oleh yang demikian,penambahbaikan kepada bentuk stent sedia ada perlu dilaksanakan terutamanyauntuk kegunaan PDA. Dalam kajian ini, penambahbaikan reka bentuk stent koronarisedia ada untuk kesesuaian pemasangan di PDA telah dapat diimplementasikan.Dinamik Bendalir Perkomputeran (CFD) turut dibuktikan dengan menggunakanteknik eksperimen dengan menganalisis konfigurasi stent sedia ada. Analisisstatistik digunakan untuk menilai prestasi setiap parameter stent dan untuk mendapatkonfigurasi stent yang terbaik. Konfigurasi yang terbaik kemudiannya digunakanuntuk mereka bentuk konfigurasi stent yang baru khusus untuk kegunaan PDA.Dalam analisis reka bentuk stent yang baru, hasil analisis CFD menunjukkan prosesre-stenosis yang disebabkan oleh pembentukan trombosis, keradangan, dan neo-
intimal hyperplasia adalah rendah. Selain itu, hasil analisis CFD yang menyeluruhdengan menyelesaikan interaksi struktur-bendalir (FSI) telah membuktikan strukturkonfigurasi stent adalah kukuh. Kekuatan konfigurasi stent disebabkan oleh kesanhemodinamik telah dikenal pasti melalui analisis agihan tegasan von Misses. Hasilkajian menunjukkan bahawa reka bentuk stent yang diubah suai ini mempunyaiprestasi hemodinamik yang sangat baik. Akhir sekali, reka bentuk stent baru inidijangka dapat mengatasi komplikasi hemodinamik dan juga kegagalan struktur stent
apabila diguna pakai secara khusus dalam PDA.
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TABLE OF CONTENTS
CHAPTER TITLE PAGE
DECLARATION iiDEDICATION iiiACKNOWLEDGEMENT ivABSTRACT vABSTRAK viTABLE OF CONTENTS viiLIST OF TABLES xiLIST OF FIGURES xviLIST OF ABBREVIATIONS xxiiiLIST OF SYMBOLS xxiv
1 INTRODUCTION 11.1 Problem Statement 31.2 Significance of the Study 31.3 Objectives 31.4 Scope 4
2 LITERATURE REVIEW 52.1 The implantation of stent in Patent Ductus
Arteriosus 52.2 Treatment and complications in PDA 62.3 Effect of stent geometry design of hemodynamics 92.4 In-vivo and In-vitro testing on stenting arteries 112.5 The emerging challenges of stented arteries using
computational modelling 152.5.1 Stent geometry and strut pattern effects on
arterial hemodynamic 162.5.2 Single stent strut configurations effect on
arterial hemodynamic 19
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2.6 Variables predicting the progression of vasculardisease 23
2.7 Fluid structure interaction (FSI) in artery stenting 25
3 METHODOLOGY 273.1 Flow chart of the study 273.2 The simplified model of DA 30
3.2.1 The selections on commercial stent strutconfigurations 31
3.3 The geometry of the stent 323.4 The modified geometry for stent strut configuration 353.5 Parametric studies on stent strut configuration 353.6 Material properties for vessel and stent 373.7 Computational Methods 37
3.7.1 Governing equations 373.7.1.1 Conservation of Mass-The con-
tinuity equation 383.7.1.2 Linear Momentum equation-
The Cauchy’s equation 403.7.1.3 Navier-Stokes equation for In-
compressible 413.7.2 FSI simulation 433.7.3 Meshing of stented PDA models 453.7.4 Boundary conditions 46
3.8 Mathematical calculation on prediction of neointi-mal proliferation 483.8.1 Wall shear stress 483.8.2 Wall shear stress gradient 493.8.3 Wall shear stress angle gradient 493.8.4 Oscillatory shear index 503.8.5 Relative residence time 503.8.6 Statistical analysis on the results 513.8.7 Scoring system to evaluate stent perfor-
mance 523.9 Experimental set up for validation 53
3.9.1 Mock Loop Set up 563.9.2 Particle image velocimetry (PIV) data
acquisition 563.9.3 Experimental parameters 56
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4 STENT STRUT CONFIGURATION EFFECTS ONDUCTUS ARTERIOSUS HEMODYNAMICS 574.1 Validations on computational models 574.2 Cyclic convergences for pulsatile waveforms 624.3 Mesh convergences 624.4 Evaluating the hemodynamic performances of
commercial stents strut configurations 634.4.1 Prediction of thrombosis formation near
to stent strut configurations 644.4.2 Time averaged Wall Shear Stress Gradient
(TAWSSG) 704.4.3 Time-averaged Wall Shear Stress Angle
Gradient (TAWSSAG) 724.4.4 Oscillatory shear index (OSI) 744.4.5 Relative Residence Time (RRT) 76
4.5 Evaluation and ranking for commercial stentperformances 78
5 HEMODYNAMICALLY PARAMETRIC STENTSTRUT CONFIGURATIONS 815.1 Hemodynamic stent performance for modified stent
strut configurations 815.1.1 Hemodynamic TAWSS subjected to de-
velopment of thrombosis and artheroscle-rosis 82
5.1.2 Hemodynamic TAWSSG subjected toendothelial dysfunction 84
5.1.3 TAWSSAG analysis in predicting theendothelial permeability and risk ofinflammation 85
5.1.4 OSI in predicting atherosclerotic plaque 865.1.5 The prediction of flow stagnation through
RRT 885.1.6 The evaluation of hemodynamic stent
performances through the scoring system 895.2 Parametric study on modified stent strut configura-
tions 895.2.1 Comparison between proposed stents in
TAWSS 90
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5.2.2 Comparison between proposed stents inTAWSSG 91
5.2.3 Comparison between proposed stents inTAWSSAG 93
5.2.4 Comparison between proposed stents inOSI 94
5.2.5 Comparison between proposed stents inRRT 95
5.2.6 The scoring evaluation of hemodynamicstent performances 96
5.3 Parametric study on different strut thickness 975.3.1 The predictions of thrombosis and
arthrosclerosis formation 975.3.2 Comparison between proposed stents in
TAWSSG 995.3.3 Comparison between proposed stents in
TAWSSAG 1015.3.4 Comparison between proposed stents in
OSI 1025.3.5 Comparison between proposed stents in
RRT 104
6 FLUID STRUCTURE INTERACTION ON STENTEDPATENT DUCTUS ARTERIOSUS 1086.1 Validations of the models 1086.2 Comparison between FSI and rigid wall 1096.3 The effects on hemodynamic displacement of stent
strut configurations 1106.4 The analysis of stress distributions on stent strut
configurations 113
7 CONCLUSIONS 1187.1 Conclusions 1187.2 Recommendation for future work 119
REFERENCES 121Appendices A – C 134 – 153
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LIST OF TABLES
TABLE NO. TITLE PAGE
2.1 The chronology of clinical findings on PDA stenting andcomplications 8
2.2 The stent design effect on local hemodynamic divergence thatlead to re-stenosis process 10
2.3 The effect on stent strut design altered hemodynamic stentperformance for both in vitro and in silico studies 11
2.4 In vitro and in vivo findings on the effect of stent strutconfigurations on arterial walls that led to the developmentof re-stenosis process 14
2.5 Chronology studies on numerical modeling on stent designeffect on the arterial hemodynamic. 22
2.6 The prediction of re-stenosis growth through the computa-tional analysis 24
3.1 Specific information on selected commercial stents 333.2 Parametric study on different unit cell for both stent A and
stent B 363.3 The parametric study on the strut configurations thickness 363.4 Material properties selections 374.1 The area-averaged mean, standard deviation, kurtosis and
skewness of TAWSS ≤ 20 dyne/cm2 for bulging stented DAmodel 69
4.2 The area-averaged mean, standard deviation, kurtosis andskewness of TAWSS ≤ 20 dyne/cm2 for straight stented DAmodel 70
4.3 The area-averaged mean, standard deviation, kurtosis andskewness of TAWSSG ≤ 5000 N/m3 for bulging stented DAmodel 71
4.4 The area-averaged mean, standard deviation, kurtosis andskewness of TAWSSG ≤ 5000 N/m3 for straight stented DAmodel 72
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4.5 The area-averaged mean, standard deviation, kurtosis andskewness for TAWSSAG ≤ 300 rad/mm for bulging stentedDA model 73
4.6 The area-averaged mean, standard deviation, kurtosis andskewness for TAWSSAG ≤ 300 rad/mm for straight stentedDA model 74
4.7 The area-averaged mean, standard deviation, kurtosis andskewness for OSI ≤ 0.2 for bulging DA model 75
4.8 The area-averaged mean, standard deviation, kurtosis andskewness for OSI ≤ 0.2 for straight DA models 76
4.9 The area-averaged mean, standard deviation, kurtosis andskewness for RRT ≤ 10 Pa-1 for bulging stented DA model 77
4.10 The area-averaged mean, standard deviation, kurtosis andskewness for RRT ≤ 10 Pa-1for straight DA model 78
4.11 Ranking of hemodynamic stent performance based on area-averaged mean, standard deviation, and kurtosis analysis 79
4.12 Ranking of hemodynamic stent performance based onCohen’s d measurement 79
4.13 Ranking of hemodynamic stent performance based on totalscore between area-averaged mean, standard deviation andkurtosis and Cohen’s d measurement 80
5.1 The area-averaged mean, standard deviation, kurtosis andskewness for TAWSS ≤ 20 dyne/cm2 for modified stents 84
5.2 The area-averaged mean, standard deviation, kurtosis andskewness for TAWSSG ≤ 5000 N/m3 for modified stentedDA models 85
5.3 The area-averaged mean, standard deviation, kurtosis andskewness for TAWSSAG ≤ 300 rad/mm for modified stentedDA models 86
5.4 The area-averaged mean, standard deviation, kurtosis andskewness for OSI ≤ 0.2 for modified stented DA models 87
5.5 Time area weighted mean, standard deviation, kurtosis andskewness for RRT ≤ 10 Pa-1 for modified stented DA models 88
5.6 Ranking of hemodynamic stent performance between area-averaged mean, standard deviation, and kurtosis analysis andCohen’s d measurement 89
5.7 The area-averaged mean, standard deviation, kurtosis andskewness for TAWSS below 20 dyne/cm2 for different unitcell patterns 91
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5.8 The area-averaged mean, standard deviation, kurtosis andskewness for TAWSSG ≤ 5000 N/m3 for different unit cellspatterns 92
5.9 The area-averaged mean, standard deviation, kurtosis andskewness for TAWSSAG ≤ 300 rad/mm for different unitcells patterns 94
5.10 The area-averaged mean, standard deviation, kurtosis andskewness for OSI ≤ 0.2 for different unit cells patterns 95
5.11 The area-averaged mean, standard deviation, kurtosis andskewness for RRT ≤ 10 Pa-1 for different unit cells patterns 96
5.12 Ranking of hemodynamic stent performance between area-averaged mean, standard deviation, and kurtosis analysis andCohen’s d measurement 97
5.13 The area-averaged mean, standard deviation, kurtosis andskewness of TAWSS ≤ 20 dyne/cm2 for different stentsthickness. 99
5.14 The area-averaged mean, standard deviation, kurtosis andskewness of TAWSSG ≤ 5000 N/m3 for different of stentsthickness 101
5.15 The area-averaged mean, standard deviation, kurtosis andskewness of TAWSSAG ≤ 300 rad/mm for different of stentsthickness 102
5.16 The area-averaged mean, standard deviation, kurtosis andskewness of OSI ≤ 0.2 for different of stent thickness 104
5.17 The area-averaged mean, standard deviation, kurtosis andskewness of RRT ≤ 10 Pa-1 for different of stent thickness 105
5.18 Ranking of hemodynamic stent performance between area-averaged mean, standard deviation, and kurtosis analysis andCohen’s d measurement 106
5.19 Ranking of hemodynamic stent performance between area-averaged mean, standard deviation, and kurtosis analysis andCohen’s d measurement 107
6.1 The comparison between stented DA analyzed using FSI andrigid wall for both peak systole and early diastole time 109
6.2 The maximum and minimum displacement of the stent strutconfigurations for both peak systole and early systole time 113
6.3 The maximum and minimum value of von Misses stress onthe stent strut configurations for both peak systole and earlydiastole time with the percentage differences 117
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A.1 Patient specific data collected at National Heart National(IJN) Malaysia 134
B.1 Analysis on mean TAWSS data using Cohen’s d measurementfor bulging DA stented models 147
B.2 Analysis on mean TAWSSG data using Cohen’s d
measurement for bulging DA stented models 147B.3 Analysis on mean TAWSSAG data using Cohen’s d
measurement for bulging DA stented models 148B.4 Analysis on mean OSI data using Cohen’s d measurement for
bulging DA stented models 148B.5 Analysis on mean RRT data using Cohen’s d measurement
for bulging DA stented models 148B.6 Analysis on mean TAWSS data using Cohen’s d measurement
for straight DA stented models 148B.7 Analysis on mean TAWSSG data using Cohen’s d
measurement for straight DA stented models 149B.8 Analysis on mean TAWSSAG data using Cohen’s d
measurement for straight DA stented models 149B.9 Analysis on mean OSI data using Cohen’s d measurement for
straight DA stented models 149B.10 Analysis on mean RRT data using Cohen’s d measurement
for straight DA stented models 150B.11 Analysis on mean TAWSS data using Cohen’s d measurement
of stented models for different unit cells 150B.12 Analysis on mean TAWSSG data using Cohen’s d
measurement of stented models for different unit cells 150B.13 Analysis on mean TAWSSG data using Cohen’s d
measurement of stented models for different unit cells 150B.14 Analysis on mean OSI data using Cohen’s d measurement of
stented models for different unit cells 151B.15 Analysis on mean RRT data using Cohen’s d measurement of
stented models for different unit cells 151B.16 Analysis on mean TAWSS data using Cohen’s d measurement
of stented models for different stents thickness 151B.17 Analysis on mean TAWSSG data using Cohen’s d
measurement of stented models for different stents thickness 151B.18 Analysis on mean TAWSSAG data using Cohen’s d
measurement of stented models for different stents thickness 152
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B.19 Analysis on mean OSI data using Cohen’s d measurement ofstented models for different stents thickness 152
B.20 Analysis on mean RRT data using Cohen’s d measurement ofstented models for different stents thickness 152
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LIST OF FIGURES
FIGURE NO. TITLE PAGE
2.1 Illustration of patent ductus arteriosus stenting for neonatewith hypoplastic left heart syndrome 6
2.2 Definitive repair technique implemented on cyanotic CHD;(a) Blalock -Taussig (b) modified Blalock –Taussig (c) centralshunt (d) Right ventricle-pulmonary atresia shunt 6
2.3 Morphology of Congenital Heart Disease (a) PAIVS (b)Ebstein’s Anomaly (c) TOF 7
2.4 The illustration of the flow chamber with strut geometry forin vitro study conducted by Frank et al. 2002 13
2.5 The experimental model conducted by Pekkan et al. 2008on the embryonic aortic arch model and flow visualization onmean steady flow 13
2.6 The contour of WSS distribution in axial plane of coronaryartery conducted by Ladisa et al. 2003 17
2.7 The distribution of WSS for different design strut configura-tions with straight cylindrical coronary vessel conducted byLadisa et al. 2004 18
2.8 Parametric study on stent strut configurations conducted byHe at al. 2005, strut radius of r, axial distance between strutof h and axial strut length of f 20
2.9 Single strut configuration generated from realistic deformedCFD model on stented coronary vessel conducted byBolassino et al. 2008 20
2.10 Boundary condition of 3D model of single strut of BX-Velocity stent illustrated in axial plane presented byDuraiswamy et al. 2009 21
3.1 Visualization of the flow chart represents the sequence ofprocesses and steps implemented in obtaining the desiredmodified stent strut configurations for DA models 29
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3.2 Ilustrations for: (a) simplified bulged model of PDA, (b)patient specific PDA model with single tortuousity in bulgingshape taken from angiogram (c) simplified straight of PDA(d) patient specific PDA model in straight, short and conicalin shape taken from angiogram 30
3.3 The illustration of different types of stents; (a) Closed celldesign and (b) Opened cell stent design 31
3.4 The illustration of several types of commercial stentsestablished for DA model simulations 32
3.5 Three dimensional simplified model of the stented bulgingDA model; the length of L, normal diameter of d and bulgingdiameter of D 34
3.6 The geometry of the stents (a) The front view of stentgeometry before expansion (normal stent) (b) The top viewof stent geometry after expansion (c) The front view ofstent geometry before expansion (d) The stent angle afterexpansion 34
3.7 The illustration of modified stent strut configuration (a) StentA has developed similar O-ring shape and wave linkages (b)Stent B was similar to bone shape and wave connectors 35
3.8 Illustrations for PDA stenting technique imposed incomputational modelling; (a) 3D model simplified PDAstenting (b) Fill up the blood domain (c) Create the suitablemeshing quality 45
3.9 The discretization on simplified PDA; (a) the bulge simplifiedmodel discretized into tetrahedral shapes of meshes (b) thestraight simplified PDA model discretized locally near stentstrut configuration (c) The constraint of the structural modelof DA models 45
3.10 The schematic stented DA model of boundary conditions 473.11 Transient velocity waveform imposed to simulate the
pulsatile flow at patent ductus arteriosus 473.12 The outlet pressure waveforms employed at patent ductus
arteriosus 473.13 The flow loop model setting (a) Complete flow loop diagram
of DA model (b) The geometry of DA glass model (c) ThePIV system used in measuring velocity data at the horizontalplane. 55
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3.14 Schematic diagram of the PIV measures the velocity datafrom the top view 55
4.1 The velocity distributions of both numerical and experimentalresults at cross-sectional aneurysm models for Re of 300. (L/d= 4, D/d = 1.6) 58
4.2 The flow visualization of axial velocity distributions onluminal surface of coronary stented artery between presentstudy and the result conducted by Gundert et al. 2013 59
4.3 Comparison of velocity distributions at the cross sectionalhorizontal plane of straight stented DA models (a) Flowcharacteristics from the numerical modeling, (b) Flowcharacteristics from the experimental study 60
4.4 The velocity distributions on the straight stented DA modelsfor both numerical and experimental data 60
4.5 The velocity distributions at the cross sectional horizontalplane of bulging stented DA models (a) Flow characteristicson numerical modeling (b) Flow characteristics on experi-mental study 61
4.6 The velocity distributions on the bulging DA models for bothnumerical and experimental results 61
4.7 Cyclic convergence on pulsatile velocity distributions on thestented DA models (Type VI stent) 62
4.8 Mesh convergence results of straight stented DA model forthree different numbers of nodes 63
4.9 The percentages of areas exposed to WSS on luminal surfaceof commercial stents with the WSS ≤ 20 dyne/cm2 indifferent cardiac times 65
4.10 The distributions of time-averaged axial wall shear stress(TAAWSS) on the luminal surface of bulging stented DAmodels in predicting the formation of thrombosis 66
4.11 The distributions of TAWSS on luminal surface of straightstented DA models 67
4.12 Visualization of the TAWSS distribution near to stent strutconfigurations (a) The distribution of TAWSS at proximalarea (b) The visualized TAWSS at the ultimate stent strutconfiguration near to distal region 67
4.13 The percentages of areas exposed to TAWSS ≤ 20 dyne/cm2
for both stented DA models 68
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4.14 The percentages of areas exposed to TAWSSlow ≤ 5 dyne/cm2
for both stented DA models 694.15 The percentages of areas exposed to TAWSSG ≤ 5000
N/m3 for both stented DA model 714.16 The percentages of areas exposed to TAWSSAG ≤ 300
rad/mm for both stented DA model 734.17 The percentages of areas exposed to OSI ≤ 0.2 for both
stented DA model 754.18 The percentages of areas exposed to luminal surface of
stented DA models for RT ≤ 10 Pa-1 775.1 The percentages of areas exposed to TAWSSlow ≤ 5 dyne/cm2
for both commercial stents and modified stents 835.2 The percentages of areas exposed to TAWSS ≤ 20 dyne/cm2
for both commercial stents and modified stents 835.3 Comparison of percentages of areas exposed to TAWSSG ≤
5000 N/m3 between commercial stents and modified stents 855.4 The percentages of TAWSSAG between commercial stents
and modified stent A and B for the value ≤ 300 rad/mm 865.5 The percentages of areas exposed OSI ≤ 0.2 between
commercial stents and modified stent A and B 875.6 The percentages of areas exposed to RRT between
commercial stents and modified stent A and B 885.7 The percentages of areas exposed to TAWSSlow ≤ 5 dyne/cm2
between for different unit cell patterns 905.8 The percentages of areas exposed to TAWSS ≤ 20
dyne/cm2 for different unit cell patterns 915.9 The percentages of areas exposed to TAWSSG ≤ 5000
N/m3for different unit cells patterns 925.10 The percentages of areas exposed to TAWSSAG ≤ 300
rad/mm for modified patterns 935.11 The percentages of areas exposed to OSI ≤ 0.2 for different
unit cells stents 945.12 The percentages of areas exposed to RRT ≤ 10 Pa-1 for
different unit cell patterns 965.13 The percentages of areas exposed to TAWSSlow ≤ 5 dyne/cm2
on the luminal surface of DA models with the different ofstent thickness 98
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5.14 The percentages of areas exposed to TAWSS ≤ 20 dyne/cm2
on the luminal surface of DA models with the different ofstent thickness 99
5.15 The percentages of areas exposed to TAWSSG on the luminalsurface of DA models with the different stent thickness 100
5.16 The percentages of areas exposed to TAWSSAG ≤ 300rad/mm on the luminal surface of DA models with thedifferent stent thickness 102
5.17 The percentages of areas exposed to OSI≤ 0.2 on the luminalsurface of DA models with the different stent thickness 103
5.18 The percentages of areas exposed to RRT ≤ 10 Pa-1 onthe luminal surface of DA models with the different stentthickness 105
6.1 The displacement magnitude along fluid structure interactionof PDA at peak systole time (t = 0.37 s, P = 139.6 mmHg) 109
6.2 The hemodynamic effects on Type T1 stent displacementsat peak systole time (a) the maximum location of stentdisplacement (b) the minimum location of stent displacement 110
6.3 The hemodynamic effects of the stent displacement of threedifferent strut thicknesses during peak systole and earlydiastole time 111
6.4 The visualization of stent displacement due to hemodynamiceffects on different stents thickness for both peak systole andearly diastole times 111
6.5 The displacement of the stent strut configurations at curvesurface of single strut stent during peak systole time 112
6.6 The displacement of the stent strut configurations at curvesurface of single strut stent during early systole time 112
6.7 The von Misses stress distribution at peak systole time (a)the maximum location of von Misses stress (b) the minimumlocation of von Misses stress 114
6.8 The von Misses stress distributions on the arterial stentedDA model with three different strut thicknesses during peaksystole and early diastole time 114
6.9 The hemodynamic effects on the stent structure displacementfor three different stents 115
6.10 The distributions of von Misses stress along the stent strutconfigurations during peak systole time 116
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6.11 The distributions of von Misses stress along the stent strutconfigurations during early diastole time 116
A.1 Statistical data for PDA in tortuosity cases; More bending(MB), Not available (NA), straight (S) and Single bending(SB) of ductus arteriosus 135
A.2 The illustration of the dimension used in implementingtrapezoid method 135
A.3 Locations of Psystolic and Pdiastolic 136B.1 The distributions data of TAWSS ≤ 20 dyne/cm2 on the
luminal surface of the bulging stented DA model 137B.2 The distributions data of TAWSSG ≤ 5000 N/m3 on the
luminal surface of the bulging stented DA model 138B.3 The distributions data of TAWSSAG ≤ 300 rad/mm on the
luminal surface of the bulging stented DA model 138B.4 The distributions data of OSI ≤ 0.2 on the luminal surface of
the bulging stented DA model 139B.5 The distributions data of RRT ≤ 10 Pa-1 on the luminal
surface of the bulging stented DA model 139B.6 The distributions data of TAWSS ≤ 20 dyne/cm2 on the
luminal surface of the straight stented DA model 140B.7 The distributions data of TAWSSG ≤ 5000 N/m3 on the
luminal surface of the straight stented DA model 140B.8 The distributions data of TAWSSAG ≤ 300 rad/mm on the
luminal surface of the straight stented DA models 141B.9 The distributions data of OSI ≤ 0.2 on the luminal surface of
the straight stented DA model 141B.10 The distributions data of RRT≤ 10 Pa-1on the luminal surface
of the straight stented DA model 142B.11 The distributions data of TAWSS ≤ 20 dyne/cm2on the
luminal surface for Type A stent with the different unit cellof stented DA models 142
B.12 The distributions data of TAWSSG ≤ 5000 N/m3 on theluminal surfaces for Type A stent with the different unit cellof stented DA models 143
B.13 The distributions data of TAWSSAG ≤ 300 rad/mm on theluminal surfaces for the different unit cell of stented DAmodels 143
B.14 The distributions data of OSI ≤ 0.2 on the luminal surfacesfor the different unit cell of stented DA models 144
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B.15 The distributions data of RRT ≤ 10 Pa-1 on the luminalsurfaces for the different unit cell of stented DA models 144
B.16 The distributions data of TAWSS ≤ 20 dyne/cm2 on theluminal surfaces for Type A stent with the different thicknessof stented DA models 145
B.17 The distributions data of TAWSSG ≤ 5000 N/m3 on theluminal surfaces for Type A stent with the different thicknessof stented DA models 145
B.18 The distributions data of TAWSSAG ≤ 300 rad/mm on theluminal surfaces for Type A stent with the different thicknessof stented DA models 146
B.19 The distributions data of OSI ≤ 0.2 on the luminal surfacesfor Type A stent with the different thickness of stented DAmodels 146
B.20 The distributions data of RRT ≤ 10 Pa-1 on the luminalsurfaces for Type A stent with the different thickness ofstented DA models 147
C.1 The matlab program to calculate area-averaged mean,standard deviation, kurtosis and skewness 154
C.2 The matlab program to sort the data in hemodynamicvariables range 155
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LIST OF ABBREVIATIONS
BMS - Bare metallic stent
CFD - Computational Fluid Dynamics
CHD - Congenital Heart Disease
CCD - Charged couple device
CO - Cardiac ouput
DA - Ductus Arteriosus
DES - Drug Eluting Stent
FEM - Finite Element Method
FSI - Fluid Structure Interaction
FSP - Flow separation time
IJN - Institut Jantung Negara
LVOT - Left ventricular outflow tract
MAP - Mean arterial pressure
mBT - Modified Blalock-Taussig
MOSI - Modified oscillatory shear index
NIH - Neointimal hyperplasia
OSI - Oscillatory shear index
PAIVS - Pulmonary Atresia with intact ventricular septal
PDA - Patent Ductus Arteriosus
PGE1 - Prolonged prostaglandin E1
RRT - Relative residence time
RVOT - Right ventricular outflow tract
st - Stroke volume
TAWSS - Time-averaged wall shear stress
TAWSSG - Time-averaged wall shear stress gradient
TGA - Transposition of Great Arteries
TOF - Tetralogy of Fallot
xxiv
LIST OF SYMBOLS
E - Young modulus
Re - Reynolds number
I/Ds - Height of void area
V/Ls - Width of void area
α - Angle AB
β - Angle AC
v - Poisson’s ratio
ρ - Fluid density
τ - Wall shear stress
µ - Viscosity coefficient
φ - Faced-averaged variable
σy - Yield stress
∆ - Vector gradient operator
V F - Velocity vector
Γ - Boundary
üs - Local acceleration of the solid
fBF - body force per unit volume
σs - Solid stress
σF - Fluid stress
CHAPTER 1
INTRODUCTION
The implantation of thin wire meshes called stent in Ductus Arteriosus (DA)has become a viable alternative treatment for neonates who have been diagnosed withCyanotic Congenital Heart Disease. The stent is temporarily implanted in the DAregion the so-called patent ductus arteriosus (PDA) within 6 to 12 months or until theneonate has gained sufficient weight to undergo the surgical repair for palliative overconduit surgery or first stage cavopulmonary anastomosis. Between 2001 and 2003,approximately 8.9 percent all patients who underwent the PDA stenting procedureswere deemed unsuccessful as reported by the National Heart Institute of Malaysia(IJN) [1]. However, rapid advancement of interventional trans-catheter stentingtechnique is able to reduce mortality and morbidity in neonates [2]. From 2010 to 2011,PDA stenting procedure were successfully implemented on 29 neonates aged less thanthree months based on data reported by the Department of Pediatrics, National HeartInstitute (IJN) of Malaysia.
Maintaining the patency of DA with metallic-based coronary stent was appliedas a novel approach, but earlier results have been discouraging [1, 3, 4]. This is dueto the difficulty of pulmonary arterioplasty during definitive repairs with less thansatisfactory results when the metallic stent is densely embedded into the fibrotic tissue[5]. The complications after the PDA invasive technique such as re-stenosis, acutestent thrombosis, and stent embolization have inspired researchers to develop newand improved stent technology. Previous researchers had reported that the stent strutconfigurations had a major influence on the process of re-stenosis, especially on theformation of thrombosis [5, 6, 7, 8, 9]. Thus, the stent strut configurations are requiredto be studied, simulated, and analyzed in detail in order to find some degree of strutimprovement due to hemodynamic variables.
The hemodynamic stent performances are predicted based on the hemodynamicvariables via computational modeling. Recently, stented DA model can be simulated
2
near the vessel environment due to the advancement and improvement of computingability and performance. Both computational fluid dynamic (CFD) and fluid-structureinteraction (FSI) methods are used and proven by many researchers [5, 6, 8, 9, 10] topredict the hemodynamic stent performance of altered hemodynamic variables. Hence,computational modeling is suitable to be utilized to predict the risk of re-stenosis basedon the hemodynamic stent impact on the arterial PDA.
This study proposes a detailed analysis and assessment via statistical datadistributions to predict the favorable hemodynamic stents performances among thestents. Three different studies are conducted to pre-clinically assess the stent impacton the arterial PDA stenting. This study begins by comparing the hemodynamicvariable effects on eight different types of commercial stent strut configurations.The stents represent both open and closed cell stents implying different response inhemodynamic variables. The hemodynamic variables considered in this study includeTime-averaged Wall Shear Stress (TAWSS), Time-averaged low Wall Shear Stress(TAWSSlow), Time-averaged Wall Shear Stress gradient (TAWSSG), Time-averagedWall Shear Stress angle gradient (TAWSSAG), oscillating shear index (OSI), andrelative residence time (RRT). These hemodynamic variables are adopted to predict thebest hemodynamic stent performances through the implementation of scoring systems.The implementation of a scoring system to determine the favorable hemodynamic stentperformances is then discussed in detail.
In the second study, modified parametric stent strut configurations are modeledand simulated using CFD to predict the hemodynamic effects on the arterial stentedPDA. The stent modifications are made based on the hemodynamic results obtainedfrom the simulation of commercial stent strut configurations. The parametric stentmodels differ in the number of unit cell stents, thickness, and width of strutconfigurations. The hemodynamic performances of modified strut configuration arethen compared with the modified stents to find the best stent through the highest score.
In the third study, computational modelling via fluid-structure interactions(FSI) is performed to predict the hemodynamic effect on the stented PDA. TheFSI modeling gives important information related to the stent displacement and themaximum stress exerted on the luminal surfaces, which cannot be obtained fromrigid wall simulation. The distinctions of the luminal surface area between FSI andrigid wall imply that the FSI method has the ability to predict nearer to the realvessel environment as compared to rigid wall simulation. The analysis of stressexerted on the stent surfaces is calculated through the von Misses stress that can
3
predict structural stent failure due to hemodynamic effects. Thus, this study aims topredict the hemodynamic stents performances by means of CFD and FSI to reduce thedevelopment of re-stenosis.
1.1 Problem Statement
The increase in the rate of re-stenosis a few weeks after stent implantation wasof concern and normally depends on various factors including stent strut configurationswhich alter the hemodynamic variables [5]. Four key processes can explain the processof re-stenosis: thrombus formation, arterial inflammation, neo-intimal hyperplasia(NIH) and remodeling [11]. These processes are triggered by the stimulus from theinjury incurred after the stenting procedure. The excessive growth of cell proliferationfrom the NIH process caused blockage of the arterial wall, thus requiring anotherstenting procedure. However, this subsequent stent implantation may cause a moresevere complication called in-stent restenosis.
1.2 Significance of the Study
Changes of stent strut parameters such as increasing the spacing between strutand strut, decreasing the strut width, and sometimes fewer strut-strut intersections havea significant effect on reducing the re-stenosis rate [12]. This may be due to a differenthemodynamic effects on blood borne and arterial wall cells after the implantationof various stent configurations. Thus, stent geometry has become highly significantto be studied and investigated in detail in order to improve the hemodynamic stentsperformances.
1.3 Objectives
The objectives of this project are:
1. To establish the hemodynamic stent performances due to the effect of existingstrut configuration differences by altering hemodynamic variables.
4
2. To improve and modify stent strut configuration geometry parameterizations toobtain desired strut configuration
3. To quantify the hemodynamic effects on the stent structural in predicting thepossibility of structural failure.
1.4 Scope
1. Stents are selected among the commercially available coronary stents.
2. The effects of hemodynamic variables in stent geometry are obtained from theCFD and FSI only.
3. Data establishment on hemodynamic stents performances is based on simplifiedDA models.
4. The experimental work is validated with the results of numerical simulation.
CHAPTER 2
LITERATURE REVIEW
2.1 The implantation of stent in Patent Ductus Arteriosus
Patent Ductus Arteriosus (PDA) stenting for newborns with cyanotic congenitalheart disease (CHD) is a minimally invasive alternative technique to surgery as shownin Figure 2.1 [5]. This technique provides a first-stage palliation in cyanotic CHDwhereby the ductal patency becomes a sole source of pulmonary blood flow [5, 11, 12].This procedure required the stent to be temporarily implanted between 6 months to 12months before the patients underwent more surgical repair for palliative over conduitsurgery or first stage cavopulmonary anastomosis [2] as illustrated in Figure 2.2 [13].This temporizing time is important for babies to survive early infancy until attaining asufficient weight gain before any definitive surgical can be performed [5].
In the previous research, PDA stenting has been shown to be an effectivetreatment as it is performed in modified Blalock-Taussig (mBT) in promoting globalpulmonary artery growth as well as controlling the distribution of blood flow topulmonary artery [14]. However, keeping the ductal patency via stent until thetime of definitive repair has remained challenging in terms of long-term survival[5] even though advanced techniques on coronary intervention for adults have beenimplemented [10, 1, 15, 8]. Alwi et al, 2013 [5] reported that PDA stenting mayface a negative response from the pulmonary artery branches because of a significantproportion of cyanotic CHD, thus the patient’s long-term survival is still undermined.
6
Figure 2.1: Illustration of patent ductus arteriosus stenting for neonate with hypoplasticleft heart syndrome
Figure 2.2: Definitive repair technique implemented on cyanotic CHD; (a) Blalock -Taussig (b) modified Blalock –Taussig (c) central shunt (d) Right ventricle-pulmonaryatresia shunt
2.2 Treatment and complications in PDA
PDA stenting is a common treatment in cyanotic CHD that provides thebridging palliation as a first indication in order to maintain the PDA as a sole sourcefor pulmonary artery. The second treatment is to augment the pulmonary blood
7
flow to pulmonary atresia with intact ventricular septal (PAIVS) and tricuspid atresia.Ebstein’s anomaly is a third treatment to avoid prolonged prostaglandin E1 (PGE1)infusion. Fourth treatment is a simple transposition of great arteries (TGA) withinflated left ventricle. However, the American Heart Association reported PAIVS asa first indication for PDA stenting and categorized it in class IIa while temporarybridging palliation was categorized as class IIb, Ebstein anomaly as third indicationand finally TGA as fourth indication for PDA stenting as shown in Figure 2.3 [16].
Figure 2.3: Morphology of Congenital Heart Disease (a) PAIVS (b) Ebstein’s Anomaly(c) TOF
Many complications have been reported after the insertion of stent such asacute stent thrombosis, vascular injury, cardiac failure, PDA spasm, migration of thestent, and hemorrhage [5, 6]. The failure of the palliative procedure owing to stentstenosis from short term to medium term follow up observation has been reported[5, 6]. However, the advances in interventional trans-catheter stenting techniquesin congenital heart has reduced the rate of mortality and morbidity in neonates [2].Between 2001 and 2003, approximately 8.9% of patients who underwent the PDAstenting procedure were not successful as reported by the National Heart Institute(IJN) of Malaysia [2] because of tortuosity of PDA morphology. Previous findingson clinical PDA stenting had shown that design of stents has influenced the processof re-stenosis especially in formation of thrombosis [5, 6, 9, 10] as illustrated in Table2.1. Many researchers [8, 9, 17] have concluded that the structural failure of the stentis most apparent 2 to 5 years after clinical implantation in abdominal aortic aneurysmand coronary arteries. No findings have reported on PDA stenting structure failure,unless many complications are reported due to hemodynamic variables [6].
8
Table 2.1: The chronology of clinical findings on PDA stenting and complications
Aut
hors
/Yea
rs
Age
s
Type
sO
fSte
nts
Tota
lNum
berO
fSte
nt
Tota
lPat
ient
s
Tota
lSuc
cess
fulP
roce
dure
Tota
lUns
ucce
ssfu
lPro
cedu
re
Com
plic
atio
ns
Schneider
et al, [10]
1998
13.3
days (d)
(median)
Coronary
stent: Pal-
maz–Schatz
stents
32 21 21 - Arterial
damage, early
re-
interventional
Gibbs et
al, [9]
1999
4-78 d Coronary
stent: Pal-
maz–Schatz
stents
- 19 17 2 died
-tortuosity
Spasm (2), stent
thrombosis
Alwi et al,
[1]2004
2.3
months
(median)
Coronary
stent
56 61 56 5 -not done
because of
tortuosity)
Stent
embolization,
Cardiac failure
Hussain et
al, [18]
2008
24 d
(mean)
Coronary
stent
14 21 14 5 - not done
because of
tortuosity),
2 died
Alwi et
al,[6]
2011
10d
(median)
Coronary
stent
37 37 37 - Acute stent
thrombosis, loss
of femoral
artery pulse (5)
Odemis et
al, [19]
2012
10.5d
(median)
Coronary
stent
8 13 9 4 2 died with
pulmonary
haemorrhage
and
retroperitoneal
haemorrhage
9
Schranz et
al, [20]
2006
21 d Biodegradable
stent: (AMS,
Biotronik
TM,
Germany)
1 1 1 - -
Mc
Mahon et
al,[21]
2007
2 months Biodegradable
stent: (AMS,
Biotronik
TM,
Germany)
1 1 1 - -
2.3 Effect of stent geometry design of hemodynamics
Different designs of stents have induced the alteration of local hemodynamicnear to stent strut configurations leading to the development of re-stenosis process[22, 23]. Maintaining unobstructed ductus arteriosus with coronary stents have beenadopted before [1, 3, 4] but early results were discouraging due to the presence ofre-stenosis [24]. Many researchers have reported that the design of the stent hasa significant influence on growth of re-stenosis even though a different material ofthe stent has been used as seen in Table 2.1. Table 2.1 shows the previous studieson the impact of stent design on arterial hemodynamic that lead to re-stenosis. Re-stenosis is a process of re-narrowing of the stented segment of the artery because offour key processes including thrombosis formation, arterial inflammation, neointimalhyperplasia (NIH) and remodeling [25].
Re-stenosis in stented PDA is normally caused by divergence of localhemodynamic near stent strut configuration leading to excessive growth of cellproliferation associated with the embedded stent into fibrotic tissue [5]. Previousstudies reported that changes in stent design parameters such as increasing stentconnector spacing, decreasing the width of the stent strut and fewer inter-strutconnections resulted in a reduction of re-stenosis, but will increase the wall shear stressthat could cause adverse reactions to blood and arterial cells [22, 24, 25, 26, 27, 28].The divergences of the local hemodynamic near to stent strut lead to the deposition ofplatelets which finally accelerated the progression of late thrombosis [6, 22, 28, 29, 30,31].
10
Table 2.2: The stent design effect on local hemodynamic divergence that lead to re-stenosis process
Author/Years Types Of Stents Findings
Pache et al,2003, Mauri etal 2008[27, 28]
Bare Metallicstent (BMS)
Re-stenosis is the major clinical limitation forBMS. However, the changes in stent design:increasing the strut-strut spacing, strut widthand fewer strut-strut interaction will reducedthe degree of stenosis.
Mauri et al2008 [27]
Drug ElutingStent (DES)
Late thrombosis is the major limitation forDES design. Long term issue compared inBMS.
Wernick et al,2006 [30]
DES Late thrombosis the long issues in DESbecause of stent design.
Camenzind etal, 2007 [31]
DES Stent design increased risk of late thrombosisparticularly in complex lesion subsets.
Gundert et al2012 [22]
DES Stent strut can delayed the prosesRe-endothelialization increased the risk ofthrombosis which can lead to myocardialinfarction.
Alwi et al,2011 [6]
Biodegradablestent (clinicalstudy)
This stent has limited mechanical performanceand not strong as metallic stent which result inearly recoil and neointimal hyperplasia.
11
Table 2.3: The effect on stent strut design altered hemodynamic stent performance forboth in vitro and in silico studies
Author/years Method ofstudy
The study aims Hemodynamicanalysis
Kono et al(2013) [32]
Experimentaland CFD
To investigate the effect of 8different types of the stent at
bifurcation aneurysm
WSS,velocity, Flow
separation
Babiker etal, 2012
[33]
Experimentaland CFD
To investigate the flow studyelucidates the influence of stent
configuration on cerebral aneurysmfluid dynamics in an idealized
wide-neck basilar tip aneurysmmodel.
Velocitymagnitude,
flowdisturbance
Gundert etal, 2012
[22]
CFD To investigate the relationshipbetween vessel diameter and thehemodynamically optimal Nc.
The area oflow time
averaged WSS(TAWSS)
Duraiswamyet al, 2009
[24]
CFD To investigate the characterize theflow disturbance induced by
different commercially availablestents
WSS,Elevated
WSS, WSSG,Low WSS,
Flowseparation
2.4 In-vivo and In-vitro testing on stenting arteries
Clinical findings have reported that stent design plays an important role in theformation of in stent re-stenosis and has been regarded as second risk factor in re-stenosis process [34]. There have been reports on the different surgical outcomes interms of re-stenosis rate from various stent strut configurations, and these studies canbe categorized into two sections – those reporting clinical outcomes from surgery [34,35, 36, 37, 38, 39] and those predicting the outcome of surgery through computationalmeans [24, 25, 26, 40] These clinical trials compared 2 stent designs throughout thetrial period with a follow up between 6 to 12 months. The stents used in these trialswere GR-II, PS, NIR, ML, SES and Bx-Velocity. The parameters of the stent designvary and include stent strut connector spacing, opened and closed stent strut.
12
The re-stenosis rate varies 0 % for SES at 6 months follow-up [41], and highre-stenosis rate of 47.3 % was reported for GR-II at 12 months follow-up [35]. Oneof the reported works concluded that strut-junction on stent design should be reducedas the numbers contribute to stent re-stenosis [26, 39]. Kastrati et al. [34] conductedan in vivo study of 651 patients and concluded that a reduction in strut thickness cansignificantly reduce the process of re-stenosis. An in vitro study conducted by Franket al. [42] showed that the growth of cell and platelet adhesion was influenced by strutspacing. This result is in agreement with those results conducted by many researchers[37, 38, 39, 43] as illustrated in Table 2.4. Table 2.4 shows the findings on the stentstrut configurations affected the arterial hemodynamic that lead to the development ofre-stenosis process.
In 2002, Frank et al. conducted in vitro study on arterial stents [42]. Thepurpose of this study was to predict both platelet adhesion and ECs re-growth underphysiological flow conditions. The typical flow chamber was developed consisting offlat plate type, providing a varying stent strut geometry in terms of stent strut spacingand strut height as well as protrusion into the flow stream as seen in Figure 2.4. Atransient spatially uniform velocity was imposed as the boundary inlet while zeropressure was set up as a boundary outlet. The inlet and outlet were extended to morethan 10 times the height of the chamber to promote the developed flow. The steadystate under mean flow conditions was applied as an initial condition. Two completecycles of the transient flow were applied to ensure the periodicity. The results showthat the strut spacing and flow condition play important roles in the EC growth. Cellgrowth was seen to be greater near the strut spacing.
Pekkan et al. [44] conducted an in vitro study on the embryonic aortic archusing the physiological flow waveform. The aim of the study was to gain a betterbiophysical understanding of fetal flow loop for flow visualization to identify the CFDresults. Both steady and unsteady circulation pump were used in this study. Leftventricular outflow tract (LVOT) and right ventricular outflow tract (RVOT) wereinvestigated and measured using ultrasonic clamp-on flow probes (Model T 108,Transonic Inc., NY). The flow visualizations on cardiac gated were then conductedusing high density prylolite particles captured by charged couple device (CCD) cameraat 250 frames/s (Model T108, Transonic Inc., NY). The results showed that distinctswirling flow was observed for both CFD and in vitro results at pulmonary arteries(PA) as illustrated in Figure 2.5.
13
Figure 2.4: The illustration of the flow chamber with strut geometry for in vitro studyconducted by Frank et al. 2002
Figure 2.5: The experimental model conducted by Pekkan et al. 2008 on the embryonicaortic arch model and flow visualization on mean steady flow
14
Table 2.4: In vitro and in vivo findings on the effect of stent strut configurations onarterial walls that led to the development of re-stenosis process
Author/Years ModelType
Domain Problems Findings
Lansky etal, 2000[35]
Clinical Analyzed on 755 patientswith myocardial ischemiaand coronary stenoses withstent Palmaz-Schatz andGR-II stents
Patients treated with theGR-II stent had more earlycomplications (stentthrombosis and 30-daycomposite events) andhigher late angiographicand clinical re-stenosis ratesthan did the patients treatedwith the PS stent
Kastrati etal, 2001[34]
Clinical Analysed 4510 patientswith stent implantation
Re-stenosis appear aftercoronary placement ofvarious stent types
Frank et al,2002 [42]
In vitro In vitro experimentalstudies of platelet adhesionand endothelial cellre-growth
Results from the endothelialcell regrowth study showthat strut spacing and flowconditions also affect theway in which endothelialcells regrowth over asimulated stented artery(images taken for 96 H ofexposure to the high flowcondition)
Briguori etal, 2002[45]
Analysed 821 patientswhich are divided into thingroup included 400 patientswith 505 lesions and thickgroup included 421 patientswith 436 lesions
Results show that strutthickness give impact there-stenosis rate after stentimplantation in smallcoronary arteries
15
Ladisa etal, 2005
[43]
In vitro In vitro experimentalstudies of alterations in wallshear stress predict sites ofneointimal hyperplasia(NIH) after stentimplantation in rabbit iliacarteries
Results show thatneointimal hyperplasia, thespatial clustering of cells,and expression of severalmolecular mediators ofproliferation were observedat stagnation points and inregions of low WSS alongthe cylinder
Pekkan etal, 2008
[44]
In vitro In vitro hemodynamicinvestigation of theembryonic aortic arch atlate gestation
There were regions ofconstant flow separationdistal and proximal, andthese constant separationregions exhibited very lowplatelet deposition
Larrabideet al, 2010
[38]
In vitro Placement of a metal cliparound the neck of theaneurysm so as to isolatethe aneurysm from theparent vasculature and tore-establish physiologicalblood flow by method andin vitro evaluation
Virtual angiographies areused to compare in vitroexperiments and CFDanalysis and contrasttime-density curves for vitroand CFD data weregenerated and used tocompare them
2.5 The emerging challenges of stented arteries using computationalmodelling
In silico studies via computational means have been conducted by severalresearchers [23, 24, 25, 26] previously where prediction of potential re-stenosisprocess has been analyzed. The emerging advanced technology of computationalmodeling enable an implicit explanation of the mechanism of re-stenosis process[12, 24, 42, 32, 46, 47, 48, 49] which is extremely difficult to obtain throughthe experimental method in addition to its high cost [22, 32, 50]. Murphy et al.[25] reported that modern computational modeling enable the accurate simulationof models as well as the prediction of the stimuli process responsible for causingre-stenosis after stenting. Computational modeling via computational fluid dynamic
16
(CFD) method has been evaluated to identify the effect of different stent designconfigurations on the altered local hemodynamic. The hemodynamic parameters suchas velocity distribution, pressure distribution, wall shear stress (WSS) as well as wallshear stress gradient (WSSG), oscillatory shear indices (OSI) and low WSS weresusceptible to re-stenosis [51]. The region of flow recirculation with separation andattachment point is also susceptible to re-stenosis which is investigated with flowseparation parameter (FSP). However, Duraiswamy et al. [24] reported that the valuefrom FSP was too small and can be neglected.
Finite element method (FEM) is another method in computational modelingin predicting the distribution of stress exerted along the arterial hemodynamic. Thismethod is able to analyze the structure behavior on stent deployment in predicting thedevelopment of re-stenosis. Lally et al. [52] reported that the maximum principlestress above 4MPa for the stented artery was subjected due to re-stenosis.
Advanced computational modeling has coupled two different surfaces betweenintact fluid domains with elastic body to elucidate the response of stented arteries onthe compliance wall altered local hemodynamic [53, 54]. The compliance body mayinfluence the changes of the hemodynamic variables that represent a realistic arteryphysiologically similar to real arteries.
Re-stenosis has been reported to vary in rate subjected to different stentstrut configurations [34]. Many researchers reported that various stent designs weresusceptible for re-stenosis [26, 34, 55, 56]. The formation of re-stenosis was observedto be an obvious aggregation at a certain region in the stented artery [43]. Thus,comprehensive knowledge of re-stenosis mechanism process after stenting is beneficialfor the future design of stent. Both qualitative and quantitative study on stented arteriesare necessary in investigating the stimuli process of tissue for re-stenosis. The findingsin these studies also are divided into two different sections; first is a study on stentgeometry and the effect of strut patterns on arterial hemodynamic and second sectioninvestigates the effect of single stent strut configurations on arterial hemodynamic.
2.5.1 Stent geometry and strut pattern effects on arterial hemodynamic
The investigation on the impact of coronary stenting alters arterialhemodynamic was started by Ladisa et al. 2003 by [57] using computational
17
modeling via CFD method. The 3D model was modeled in straight cylindrical vesselwith commercial stent implantation resembling the Palmaz Schatz stent (Johnson &Johnson). The un-stented coronary artery was simulated as a basis comparison. Theresult findings were that WSS contributed to uniform distribution for un-stented arterywhile WSS on stented artery showed non-uniform distribution. The high WSS wasseen at the surface of the stent strut which attached to the arterial wall. However, thearea of low WSS was observed to be dominated at the region near the stent strut asillustrated in Figure 2.6. Ladisa et al. concluded that the geometry of the stent hasa significant alteration in hemodynamic especially in local WSS which increased therisk of re-stenosis.
Figure 2.6: The contour of WSS distribution in axial plane of coronary arteryconducted by Ladisa et al. 2003
In 2004, Ladisa et al. [58] studied CFD analysis on parametric on includingPalmaz Schatz stent with variation in longitudinal cell strut, strut width and thicknessstrut. The purpose of the study was to compare the hemodynamic performance of theparametric stent strut configurations. These parametric studies varied the longitudinalcells and strut thickness of the stent as a comparison which is illustrated in Figure 2.7.The hemodynamic performance of stent was measured in terms of WSS distributionexposed on the luminal surface of the stented artery. The results of the study showedthat the lower percentage of WSS distributions was exposed to the arterial wall for thestent in fewer longitudinal cells and thinner struts. The conclusion of the study wasthat the fewer the longitudinal cells and less thickness of the stent strut would reducethe susceptible growth of the re-stenosis.
18
Figure 2.7: The distribution of WSS for different design strut configurations withstraight cylindrical coronary vessel conducted by Ladisa et al. 2004
Pant et al. 2010 [26] have conducted a comparison study between five differentcommercial coronary stents using CFD method. This study investigated the stentresembling the Art stent, Bx VELOCITY stent, NIR stent, the MULTI_LINK Zetastent and the Biometrix stent with straight cylindrical vessel. The aim of the studywas to investigate the effect of different stent designs on the arterial hemodynamic.Pulsatile blood flow was applied on 3D models of coronary stenting. The resultsshowed that the connector length in both cross–flow direction and aligned with themain flow would affect the hemodynamic performance of stent. Design index also wasformulated in this study varying from 18.8 percent to 24.91 percent in order to quantifythe flow feature which could influence the growth of re-stenosis rates.
Similar studies by [23, 25, 32] have been reported and revealed a comparisonof the effect of various stent designs on the arterial hemodynamic. Murphy et al. [25]compared 3 different stent designs resembling BX –Velocity stent, Gianturco-RoubinII stent and Palmaz Schatz stent and compared re-stenosis rate from clinical outcomesof other reported works. The statistical analysis has been performed to investigate thehemodynamic performance of each simulated stent. Their results on coronary arterysimulation showed superior outcome for the Palmaz Schatz. In contrast, another studycompared 8 different stent designs resembling Carbosirius stent, BX-Velocity stent,
19
Closed Cell S stent, Closed Cell V stent, Genesis stent, Palmaz Schatz stent, Unit Cellstent and Type I stent on bulging shape in patent ductus arteriosus (PDA). Both closedand opened cell stent were carried out in this study. The pusatile blood flow withNewtonian and homogenous flow was imposed in 3D model. The aim of the study wasto compare the hemodynamic performance of the stents via hemodynamic variablessuch WSS and WSSG. The results of the finding were that the Carbo Sirius stent andBX- Velocity were found to have performed better than the rest [5]. The conclusion ofthe study was that the performance of the opened cell stent was observed to be betterthan closed cell stent.
2.5.2 Single stent strut configurations effect on arterial hemodynamic
Study of the impact of single stent strut configurations on the arterialhemodynamic can predict the susceptibility of re-stenosis. Many researchersproclaimed that the re-stenosis process was susceptible to growth near the stent strutconfigurations. Thus, the study on single strut configuration was only marginallyuseful in predicting the distribution of WSS in the inter strut-strut that influenced thegrowth of re-stenosis.
In 2005, He et al. studied the effect of the parametric strut design overhemodynamic variables [59]. Four different parametric models of stent strut designwere modeled in 3D as illustrated in Figure 2.8. The purpose of this study wasto compare the effect of parametric strut design on the distribution of WSS andflow separation parameter (FSP) near stent strut configurations. The pulsatile bloodflow was imposed as a boundary condition. The results showed that stagnation flowwas observed near the stent strut design. The restoration percentage of low flowcondition on mean axial WSS was slightly lower than high flow condition with adifference of about 10 – 12 percent. The restoration percentage of WSS for the stentwith longitudinal connectors was smaller at about 11 percent compared to withoutconnectors. The conclusions of the findings were that the strut design should be alignedto the flow direction to reduce the flow recirculation and the lesser strut connector wasrecommended to be parallel to the axis.
20
Figure 2.8: Parametric study on stent strut configurations conducted by He at al. 2005,strut radius of r, axial distance between strut of h and axial strut length of f
In 2008, Balossino et al. conducted study on four different stent strut designsincluding BX-Velocity stent, Jostent Flex stent, Sorin Carbostent stent and PalmazSchatz stent by using finite element method [60]. The expansion of each stent strutconfiguration associated with normalized plaque has been analyzed numerically asillustrated in Figure 2.9. Then, the expansion stent has been defined as a boundarycondition in CFD. The finding of the study showed the highest WSS was dominantnear the stent strut wall region throughout the cardiac cycle. The lesser stent strutwould also demonstrate the reduction in the percentages of WSSlow exposed on theluminal surface.
Figure 2.9: Single strut configuration generated from realistic deformed CFD modelon stented coronary vessel conducted by Bolassino et al. 2008
Further study on single strut design and its effect on the arterial hemodynamic
21
was conducted by Duraiswamy et al. [24] in 2009. Four different commercial designstent struts including BX-Velocity stent, NIR stent, Wallstent stent and Aurora stentwas simulated in axial plane as shown in Figure 2.10. The objective of the finding wasto compare the flow characteristic near the stent strut using CFD method. The result ofthe finding showed that the Wallstent has the worst performance of stent evaluated bylarger percentage of low mean WSS (5 dynes/cm2) and elevated WSS gradient (> 20dyne/cm2). This finding draws the conclusion that Bx-Velocity and NIR stents werepredicted to have a lower rate of re-stenosis [8]. These results are in agreement withthe conclusion made by Salehi et al. [61] that stent similar to BX-velocity indicatedthe lowest rate of re-stenosis compared to others.
Figure 2.10: Boundary condition of 3D model of single strut of BX-Velocity stentillustrated in axial plane presented by Duraiswamy et al. 2009
22
Table 2.5: Chronology studies on numerical modeling on stent design effect on thearterial hemodynamic.
Author/Year Vessel Geometry Type of stents ModellingMethod
HemodynamicVariableInvestigation
Ladisa etal, 2003
[57]
Straight cylindricalvessel on canine leftanterior descendingcoronary artery
Palmaz Schatzstent–slottedtube
CFD Velocitydistribution ,Max WSS forresting 18-65dyne/cm2
Ladisa etal, 2004
[58]
Straight cylindricalvessel on canine leftanterior descendingcoronary artery
Palmaz Schatz CFD WSSlow for ≤ 5dynes/cm2
,WSSG ≤ 300N/m3
He et al,2005 [62]
Straight cylindricalvessel in thenear-strut region ofstented arteriesunder pulsatile flowconditions
Palmaz Schatzstent–slottedtube
CFD WSSlow for ≤0.01 dynes/cm2 ,Mean TransverseShear Stress
Balossinoet al, 2008
[60]
Straight cylindricalvessel
PalmazSchatz,BX-Velocity,SorinCarbostent,and JostentFlex
FEMand
CFD
WSSlow for ≤ 5dynes/cm2
Jimenez etal, 2009
[49]
Straight cylindricalvessel of coronaryartery
Specificcommercialstent withaerodynami-cally inspireddesign
CFD Pressure field,Shear ratedistribution andWSS
23
Pant et al,2010 [26]
Straight cylindricalvessel at the centerof the artery with anaxial distance of twotimes arterydiameter
ART,BX-Velocity,NIR, MULTI-LINK, andBiomatrix
CFD WSSlow for ≤ 5dynes/cm2 ,Axial WSS for ≤0 dynes/cm2 ,ModifiedOscillatory ShearIndex (MOSI)
Duraiswamyet al, 2010[24]
Straight cylindricalvessel on stentedarteries underpulsatile flowconditions
Single Unitcell resembleWallstent,BX-Velovity,Aurora andNIR
CFD WSSlow for ≤5dynes/cm2 ,WSSG for≥ 200N/m3
Gundert etal, 2013[22]
Straight and rigidcylindrical vessel
Integrity,Driver,Multi-LinkVision, andBX-Velocity
CFD WSS for ≤ 4dynes/cm2 , Timeaverage WSS(TAWSS) ,Oscillatory ShearIndex (OSI) for >0.1
Taib et al,2013 [23]
Straight cylindricalPDA vessel
PalmazSchatz, TypeOne, Genesis,Unit cell,Closed Cell V,Closed Cell S,CordisBX-Velocity,andCarbostentSirius
CFD Max WSS,WSSlow ≤ 0.5dyne/cm2, WSSG≤ 200 N/m3
2.6 Variables predicting the progression of vascular disease
Analysis of WSS variables would also provide the qualitative and quantitativeassessment to accurately predict the hemodynamic stent performance [63]. Stent
24
strut configuration, stent geometry and stent deployment ratio were observed to havehigh impact on stent hemodynamic and tissue indicator [25]. The expansion of thestent into an intimal layer of arterial wall would influence tissue proliferation due tohemodynamic WSS [25, 64]. The extreme growth of tissue proliferation managedto drive the development of stenosis. Design of stent was found to have contributedto the development of re-stenosis as reported by Kastrati et al. clinically [34]. Theabnormal hemodynamic impact on the arterial luminal surfaces has stimulated thedevelopment of NIH through the exertion of abnormal stress on the endothelial cellas well as increased the platelet advection and white blood cells to the arterial wall[30]. The low WSS (WSSlow) experienced growth of thrombosis for WSS less than0.5 N/m2 and increased the uptake the blood borne particles at the arterial wall as wellas increased the permeability of the endothelial layer [22, 25]. WSS greater than 2N/m2 experienced reduced regulation of the molecular adhesion on the arterial wall[65] which could lead to the formation of atherosclerosis.
Table 2.6: The prediction of re-stenosis growth through the computational analysisAuthor/Years Hemodynamic variable investigation
Ladisa et al,2003 [57]
Velocity distribution , Max WSS for resting -18-65 dyne/cm2
Ladisa et al,2004 [58]
WSSlow for ≤ 5 dyne/cm2 ,8 dyne/cm2≤WSShigh ≤ 12dyne/cm2, 5 dyne/cm2≤WSSmoderate≤ 8 dyne/cm2, WSSG for ≤300 N/m3
He et al, 2005[59]
WSSlow for ≤ 0.01 dyne/cm2and negative , Nominal ShearStress for 10 ± 5 dyne/cm2
Balossino etal, 2008 [60]
WSSlow for ≤ 5 dyne/cm2
Jimenez et al,2009 [49]
WSSlow for ≤ 5 dyne/cm2, Mean Velocity for 0.38 m/s
Pant et al,2010 [26]
WSSlow for ≤ 5 dyne/cm2, Axial WSS for ≤ 0 dyne/cm2,Modified Oscillatory Shear Index (MOSI) for value ‘1’ or ‘-1’
Duraiswamyet al, 2010
[24]
WSSlow for ≤ 5 dyne/cm2, WSSG for ≥ 200 N/m3
Gundert et al,2013 [66]
WSS for ≤ 4 dyne/cm2, Oscillatory Shear Index (OSI) for ≥ 0.1 ,
Taib et al,2013 [23]
WSSmax for ≤ 20 dyne/cm2, WSSlow for ≤ 0.5 dyne/cm2,WSSG for ≤ 200 N/m3, Velocity distribution, Pressuredistribution
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