Abstract

Lipid-rich atheromas are linked to plaque rupture in stented atherosclerotic arteries. While fibrous cap thickness is acknowledged as a critical indicator of vulnerability, it is likely that other morphological features also exert influence. However, detailed quantifications of their contributions and intertwined effects in stenting are lacking. Therefore, our goal is to assess the impact of plaque characteristics on the fibrous cap stress and elucidate their underlying mechanisms. We analyzed the stent deployment in a three-dimensional patient-specific coronary artery reconstructed from intravascular optical coherence tomography (IVOCT) data using the finite element method. Additionally, we performed sensitivity analysis on 78,000 distinct plaque geometries of two-dimensional arterial cross section for verification. Results from the three-dimensional patient-specific model indicate strong correlations between maximum fibrous cap stress and lipid arc (r=0.769), area stenosis (r=0.550), and lumen curvature (r=0.642). Plaques with lipid arcs >60 deg, area stenosis >75%, and lumen curvatures >5 mm−1 are at rupture risk. While we observed a rise in stress with thicker lipid cores, it was less representative than other features. Fibrous cap thickness showed a poor correlation, with the sensitivity analysis revealing its significance only when high stretches are induced by other features, likely due to its J-shaped stress–stretch response. Contrary to physiological pressure, the stent expansion generates unique vulnerable features as the stent load-transferring characteristics modify the plaque's response. This study is expected to prompt further clinical investigations of other morphological features for predicting plaque rupture in stenting.

References

1.
Roth
,
G. A.
,
Johnson
,
C.
,
Abajobir
,
A.
,
Abd-Allah
,
F.
,
Abera
,
S. F.
,
Abyu
,
G.
,
Ahmed
,
M.
, et al.,
2017
, “
Global, Regional, and National Burden of Cardiovascular Diseases for 10 Causes, 1990 to 2015
,”
J. Am. Coll. Cardiol.
,
70
(
1
), pp.
1
25
.10.1016/j.jacc.2017.04.052
2.
Patel
,
V. G.
,
Brayton
,
K. M.
,
Mintz
,
G. S.
,
Maehara
,
A.
,
Banerjee
,
S.
, and
Brilakis
,
E. S.
,
2013
, “
Intracoronary and Noninvasive Imaging for Prediction of Distal Embolization and Periprocedural Myocardial Infarction During Native Coronary Artery Percutaneous Intervention
,”
Circ.: Cardiovasc. Imaging
,
6
(
6
), pp.
1102
1114
.10.1161/CIRCIMAGING.113.000448
3.
Virmani
,
R.
,
Kolodgie
,
F. D.
,
Burke
,
A. P.
,
Farb
,
A.
, and
Schwartz
,
S. M.
,
2000
, “
Lessons From Sudden Coronary Death: A Comprehensive Morphological Classification Scheme for Atherosclerotic Lesions
,”
Arterioscler., Thromb., Vasc. Biol.
,
20
(
5
), pp.
1262
1275
.10.1161/01.ATV.20.5.1262
4.
Kiousis
,
D. E.
,
Gasser
,
T. C.
, and
Holzapfel
,
G. A.
,
2007
, “
A Numerical Model to Study the Interaction of Vascular Stents With Human Atherosclerotic Lesions
,”
Ann. Biomed. Eng.
,
35
(
11
), pp.
1857
1869
.10.1007/s10439-007-9357-z
5.
Iannaccone
,
F.
,
Debusschere
,
N.
,
De Bock
,
S.
,
De Beule
,
M.
,
Van Loo
,
D.
,
Vermassen
,
F.
,
Segers
,
P.
, and
Verhegghe
,
B.
,
2014
, “
The Influence of Vascular Anatomy on Carotid Artery Stenting: A Parametric Study for Damage Assessment
,”
J. Biomech.
,
47
(
4
), pp.
890
898
.10.1016/j.jbiomech.2014.01.008
6.
Li
,
Z.-Y.
,
Tang
,
T.
,
U-King-Im
,
J.
,
Graves
,
M.
,
Sutcliffe
,
M.
, and
Gillard
,
J. H.
,
2008
, “
Assessment of Carotid Plaque Vulnerability Using Structural and Geometrical Determinants
,”
Circ. J.
,
72
(
7
), pp.
1092
1099
.10.1253/circj.72.1092
7.
Cilla
,
M.
,
Peña
,
E.
, and
Martínez
,
M. A.
,
2012
, “
3D Computational Parametric Analysis of Eccentric Atheroma Plaque: Influence of Axial and Circumferential Residual Stresses
,”
Biomech. Model. Mechanobiol.
,
11
(
7
), pp.
1001
1013
.10.1007/s10237-011-0369-0
8.
Balzani
,
D.
,
Brinkhues
,
S.
, and
Holzapfel
,
G. A.
,
2012
, “
Constitutive Framework for the Modeling of Damage in Collagenous Soft Tissues With Application to Arterial Walls
,”
Comput. Methods Appl. Mech. Eng.
,
213–216
, pp.
139
151
.10.1016/j.cma.2011.11.015
9.
Gasser
,
T. C.
, and
Holzapfel
,
G. A.
,
2007
, “
Modeling Plaque Fissuring and Dissection During Balloon Angioplasty Intervention
,”
Ann. Biomed. Eng.
,
35
(
5
), pp.
711
723
.10.1007/s10439-007-9258-1
10.
Ferrara
,
A.
, and
Pandolfi
,
A.
,
2008
, “
Numerical Modelling of Fracture in Human Arteries
,”
Comput. Methods Biomech. Biomed. Eng.
,
11
(
5
), pp.
553
567
.10.1080/10255840701771743
11.
Holzapfel
,
G. A.
,
Stadler
,
M.
, and
Gasser
,
T. C.
,
2005
, “
Changes in the Mechanical Environment of Stenotic Arteries During Interaction With Stents: Computational Assessment of Parametric Stent Designs
,”
ASME J. Biomech. Eng.
,
127
(
1
), pp.
166
180
.10.1115/1.1835362
12.
Noble
,
C.
,
Carlson
,
K. D.
,
Neumann
,
E.
,
Dragomir-Daescu
,
D.
,
Erdemir
,
A.
,
Lerman
,
A.
, and
Young
,
M.
,
2020
, “
Patient Specific Characterization of Artery and Plaque Material Properties in Peripheral Artery Disease
,”
J. Mech. Behav. Biomed. Mater.
,
101
, p.
103453
.10.1016/j.jmbbm.2019.103453
13.
Cheng
,
G. C.
,
Loree
,
H. M.
,
Kamm
,
R. D.
,
Fishbein
,
M. C.
, and
Lee
,
R. T.
,
1993
, “
Distribution of Circumferential Stress in Ruptured and Stable Atherosclerotic Lesions. A Structural Analysis With Histopathological Correlation
,”
Circulation
,
87
(
4
), pp.
1179
1187
.10.1161/01.CIR.87.4.1179
14.
Auer
,
M.
,
Regitnig
,
P.
,
Stollberger
,
R.
,
Ebner
,
F.
, and
Holzapfel
,
G. A.
,
2008
, “
A Methodology to Study the Morphologic Changes in Lesions During In Vitro Angioplasty Using MRI and Image Processing
,”
Med. Image Anal.
,
12
(
2
), pp.
163
173
.10.1016/j.media.2007.09.001
15.
Loree
,
H. M.
,
Kamm
,
R. D.
,
Stringfellow
,
R. G.
, and
Lee
,
R. T.
,
1992
, “
Effects of Fibrous Cap Thickness on Peak Circumferential Stress in Model Atherosclerotic Vessels
,”
Circ. Res.
,
71
(
4
), pp.
850
858
.10.1161/01.RES.71.4.850
16.
Gu
,
L.
,
Zhao
,
S.
, and
Froemming
,
S. R.
,
2012
, “
Arterial Wall Mechanics and Clinical Implications After Coronary Stenting: Comparisons of Three Stent Designs
,”
Int. J. Appl. Mech.
,
04
(
2
), p.
1250013
.10.1142/S1758825112500135
17.
Krishna Kumar
,
R.
,
2005
, “
Influence of Lumen Shape and Vessel Geometry on Plaque Stresses: Possible Role in the Increased Vulnerability of a Remodelled Vessel and the ‘Shoulder’ of a Plaque
,”
Heart
,
91
(
11
), pp.
1459
1465
.10.1136/hrt.2004.049072
18.
Conway
,
C.
,
McGarry
,
J. P.
, and
McHugh
,
P. E.
,
2014
, “
Modelling of Atherosclerotic Plaque for Use in a Computational Test-Bed for Stent Angioplasty
,”
Ann. Biomed. Eng.
,
42
(
12
), pp.
2425
2439
.10.1007/s10439-014-1107-4
19.
Polzer
,
S.
,
Polišenská
,
A.
,
Novák
,
K.
, and
Burša
,
J.
,
2019
, “
Moderate Thickness of Lipid Core in Shoulder Region of Atherosclerotic Plaque Determines Vulnerable Plaque a Parametric Study
,”
Med. Eng. Phys.
,
69
, pp.
140
146
.10.1016/j.medengphy.2019.04.011
20.
Imoto
,
K.
,
Hiro
,
T.
,
Fujii
,
T.
,
Murashige
,
A.
,
Fukumoto
,
Y.
,
Hashimoto
,
G.
,
Okamura
,
T.
,
Yamada
,
J.
,
Mori
,
K.
, and
Matsuzaki
,
M.
,
2005
, “
Longitudinal Structural Determinants of Atherosclerotic Plaque Vulnerability
,”
J. Am. Coll. Cardiol.
,
46
(
8
), pp.
1507
1515
.10.1016/j.jacc.2005.06.069
21.
Lee
,
J.
,
Kim
,
J. N.
,
Gharaibeh
,
Y.
,
Zimin
,
V. N.
,
Dallan
,
L. A. P.
,
Pereira
,
G. T. R.
,
Vergara-Martel
,
A.
,
Kolluru
,
C.
,
Hoori
,
A.
,
Bezerra
,
H. G.
, and
Wilson
,
D. L.
,
2023
, “
OCTOPUS—Optical Coherence Tomography Plaque and Stent Analysis Software
,”
Heliyon
,
9
(
2
), p.
e13396
.10.1016/j.heliyon.2023.e13396
22.
Tearney
,
G. J.
,
Regar
,
E.
,
Akasaka
,
T.
,
Adriaenssens
,
T.
,
Barlis
,
P.
,
Bezerra
,
H. G.
,
Bouma
,
B.
, et al.,
2012
, “
Consensus Standards for Acquisition, Measurement, and Reporting of Intravascular Optical Coherence Tomography Studies
,”
J. Am. Coll. Cardiol.
,
59
(
12
), pp.
1058
1072
.10.1016/j.jacc.2011.09.079
23.
Gasser
,
T. C.
,
Ogden
,
R. W.
, and
Holzapfel
,
G. A.
,
2006
, “
Hyperelastic Modelling of Arterial Layers With Distributed Collagen Fibre Orientations
,”
J. R. Soc. Interface
,
3
(
6
), pp.
15
35
.10.1098/rsif.2005.0073
24.
Holzapfel
,
G. A.
,
Sommer
,
G.
,
Gasser
,
C. T.
, and
Regitnig
,
P.
,
2005
, “
Determination of Layer-Specific Mechanical Properties of Human Coronary Arteries With Nonatherosclerotic Intimal Thickening and Related Constitutive Modeling
,”
Am. J. Physiol.: Heart Circ. Physiol.
,
289
(
5
), pp.
H2048
H2058
.10.1152/ajpheart.00934.2004
25.
Cilla
,
M.
,
Peña
,
E.
,
Martínez
,
M. A.
, and
Kelly
,
D. J.
,
2013
, “
Comparison of the Vulnerability Risk for Positive Versus Negative Atheroma Plaque Morphology
,”
J. Biomech.
,
46
(
7
), pp.
1248
1254
.10.1016/j.jbiomech.2013.02.012
26.
Gasser
,
T. C.
, and
Holzapfel
,
G. A.
,
2002
, “
A Rate-Independent Elastoplastic Constitutive Model for Biological Fiber-Reinforced Composites at Finite Strains: Continuum Basis, Algorithmic Formulation and Finite Element Implementation
,”
Comput. Mech.
,
29
(
4–5
), pp.
340
360
.10.1007/s00466-002-0347-6
27.
Colmenarez
,
J. A.
,
Zhai
,
Y.
,
Mendoza
,
V. O.
,
Dong
,
P.
,
Nunes
,
K.
,
Suh
,
D.
, and
Gu
,
L.
,
2024
, “
Damage-Induced Softening of the Sclera: A Pseudo-Elastic Modeling Approach
,”
ASME J. Eng. Sci. Med. Diagn. Ther.
,
7
(
3
), p.
031001
.10.1115/1.4063467
28.
Zhao
,
S.
,
Gu
,
L.
, and
Froemming
,
S. R.
,
2012
, “
Finite Element Analysis of the Implantation of a Self-Expanding Stent: Impact of Lesion Calcification
,”
ASME J. Med. Devices
,
6
(
2
), p.
021001
.10.1115/1.4006357
29.
Maher
,
E.
,
Creane
,
A.
,
Sultan
,
S.
,
Hynes
,
N.
,
Lally
,
C.
, and
Kelly
,
D. J.
,
2011
, “
Inelasticity of Human Carotid Atherosclerotic Plaque
,”
Ann. Biomed. Eng.
,
39
(
9
), pp.
2445
2455
.10.1007/s10439-011-0331-4
30.
Zhao
,
S.
,
Gu
,
L.
, and
Froemming
,
S. R.
,
2012
, “
On the Importance of Modeling Stent Procedure for Predicting Arterial Mechanics
,”
ASME J. Biomech. Eng.
,
134
(
12
), p.
121005
.10.1115/1.4023094
31.
Dong
,
P.
,
Colmenarez
,
J.
,
Lee
,
J.
,
Hassani
,
N. S.
,
Wilson
,
D. L.
,
Bezerra
,
H. G.
, and
Gu
,
L.
,
2023
, “
Load-Sharing Characteristics of Stenting and Post-Dilation in Heavily Calcified Coronary Artery
,”
Sci. Rep.
,
13
(
1
), p.
16878
.10.1038/s41598-023-43160-4
32.
Sobol′
,
I. M.
,
2001
, “
Global Sensitivity Indices for Nonlinear Mathematical Models and Their Monte Carlo Estimates
,”
Math. Comput. Simul.
,
55
(
1–3
), pp.
271
280
.10.1016/S0378-4754(00)00270-6
33.
Saltelli
,
A.
, ed.,
2008
,
Global Sensitivity Analysis: The Primer
,
Wiley
,
Chichester, UK
.
34.
Holzapfel
,
G. A.
,
Mulvihill
,
J. J.
,
Cunnane
,
E. M.
, and
Walsh
,
M. T.
,
2014
, “
Computational Approaches for Analyzing the Mechanics of Atherosclerotic Plaques: A Review
,”
J. Biomech.
,
47
(
4
), pp.
859
869
.10.1016/j.jbiomech.2014.01.011
35.
Räber
,
L.
,
Mintz
,
G. S.
,
Koskinas
,
K. C.
,
Johnson
,
T. W.
,
Holm
,
N. R.
,
Onuma
,
Y.
,
Radu
,
M. D.
, et al.,
2018
, “
Clinical Use of Intracoronary Imaging. Part 1: Guidance and Optimization of Coronary Interventions. An Expert Consensus Document of the European Association of Percutaneous Cardiovascular Interventions
,”
Eur. Heart J.
,
39
(
35
), pp.
3281
3300
.10.1093/eurheartj/ehy285
36.
Stone
,
G. W.
,
Maehara
,
A.
,
Ali
,
Z. A.
,
Held
,
C.
,
Matsumura
,
M.
,
Kjøller-Hansen
,
L.
,
Bøtker
,
H. E.
, et al.,
2020
, “
Percutaneous Coronary Intervention for Vulnerable Coronary Atherosclerotic Plaque
,”
J. Am. Coll. Cardiol.
,
76
(
20
), pp.
2289
2301
.10.1016/j.jacc.2020.09.547
37.
Kini
,
A. S.
,
Motoyama
,
S.
,
Vengrenyuk
,
Y.
,
Feig
,
J. E.
,
Pena
,
J.
,
Baber
,
U.
,
Bhat
,
A. M.
,
Moreno
,
P.
,
Kovacic
,
J. C.
,
Narula
,
J.
, and
Sharma
,
S. K.
,
2015
, “
Multimodality Intravascular Imaging to Predict Periprocedural Myocardial Infarction During Percutaneous Coronary Intervention
,”
JACC Cardiovasc. Intervention
,
8
(
7
), pp.
937
945
.10.1016/j.jcin.2015.03.016
38.
Soud
,
M.
,
Ho
,
G.
,
Hideo-Kajita
,
A.
,
Yacob
,
O.
,
Waksman
,
R.
,
McFadden
,
E. P.
, and
Garcia-Garcia
,
H. M.
,
2020
, “
Periprocedural Myocardial Injury: Pathophysiology, Prognosis, and Prevention
,”
Cardiovasc. Revasc. Med.
,
21
(
8
), pp.
1041
1052
.10.1016/j.carrev.2020.04.011
39.
Tanaka
,
A.
,
Imanishi
,
T.
,
Kitabata
,
H.
,
Kubo
,
T.
,
Takarada
,
S.
,
Tanimoto
,
T.
,
Kuroi
,
A.
, et al.,
2009
, “
Lipid-Rich Plaque and Myocardial Perfusion After Successful Stenting in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome: An Optical Coherence Tomography Study
,”
Eur. Heart J.
,
30
(
11
), pp.
1348
1355
.10.1093/eurheartj/ehp122
40.
Katayama
,
Y.
,
Taruya
,
A.
,
Kashiwagi
,
M.
,
Ozaki
,
Y.
,
Shiono
,
Y.
,
Tanimoto
,
T.
,
Yoshikawa
,
T.
,
Kondo
,
T.
, and
Tanaka
,
A.
,
2022
, “
No-Reflow Phenomenon and In Vivo Cholesterol Crystals Combined With Lipid Core in Acute Myocardial Infarction
,”
IJC Heart Vasculature
,
38
, p.
100953
.10.1016/j.ijcha.2022.100953
41.
Sekimoto
,
T.
,
Mori
,
H.
,
Koba
,
S.
,
Arai
,
T.
,
Matsukawa
,
N.
,
Sakai
,
R.
,
Yokota
,
Y.
, et al.,
2022
, “
Clinical Features and Lipid Profiles of Plaque Erosion Over Lipid-Rich Plaque Versus Fibrous Plaque in Patients With Acute Coronary Syndrome
,”
Atherosclerosis
,
360
, pp.
47
52
.10.1016/j.atherosclerosis.2022.07.008
42.
Sato
,
H.
,
Iida
,
H.
,
Tanaka
,
A.
,
Tanaka
,
H.
,
Shimodouzono
,
S.
,
Uchida
,
E.
,
Kawarabayashi
,
T.
, and
Yoshikawa
,
J.
,
2004
, “
The Decrease of Plaque Volume During Percutaneous Coronary Intervention Has a Negative Impact on Coronary Flow in Acute Myocardial Infarction
,”
J. Am. Coll. Cardiol.
,
44
(
2
), pp.
300
304
.10.1016/j.jacc.2004.04.036
43.
Higashikuni
,
Y.
,
Tanabe
,
K.
,
Tanimoto
,
S.
,
Aoki
,
J.
,
Yamamoto
,
H.
,
Nakazawa
,
G.
,
Chihara
,
R.
,
Onuma
,
Y.
,
Ohtsuki
,
S.
,
Yagishita
,
A.
,
Yachi
,
S.
,
Nakajima
,
H.
, and
Hara
,
K.
,
2008
, “
Impact of Culprit Plaque Composition on the No-Reflow Phenomenon in Patients With Acute Coronary Syndrome an Intravascular Ultrasound Radiofrequency Analysis: An Intravascular Ultrasound Radiofrequency Analysis
,”
Circ. J.
,
72
(
8
), pp.
1235
1241
.10.1253/circj.72.1235
44.
Bouki
,
K. P.
,
Sakkali
,
E.
,
Toutouzas
,
K.
,
Vlad
,
D.
,
Barmperis
,
D.
,
Phychari
,
S.
,
Riga
,
M.
,
Apostolou
,
T.
, and
Stefanadis
,
C.
,
2015
, “
Impact of Coronary Artery Stent Edge Dissections on Long‐Term Clinical Outcome in Patients With Acute Coronary Syndrome: An Optical Coherence Tomography Study
,”
Catheterization Cardiovasc. Interventions
,
86
(
2
), pp.
237
246
.10.1002/ccd.25855
45.
Zhao
,
S.
,
Gu
,
L.
, and
Froemming
,
S. R.
,
2012
, “
Effects of Arterial Strain and Stress in the Prediction of Restenosis Risk: Computer Modeling of Stent Trials
,”
Biomed. Eng. Lett.
,
2
(
3
), pp.
158
163
.10.1007/s13534-012-0067-6
46.
Gu
,
L.
,
Zhao
,
S.
,
Muttyam
,
A. K.
, and
Hammel
,
J. M.
,
2010
, “
The Relation Between the Arterial Stress and Restenosis Rate After Coronary Stenting
,”
ASME J. Med. Devices
,
4
(
3
), p.
031005
.10.1115/1.4002238
47.
Barlis
,
P.
,
Serruys
,
P. W.
,
DeVries
,
A.
, and
Regar
,
E.
,
2008
, “
Optical Coherence Tomography Assessment of Vulnerable Plaque Rupture: Predilection for the Plaque ‘Shoulder’
,”
Eur. Heart J.
,
29
(
16
), p.
2023
.10.1093/eurheartj/ehn085
48.
Akyildiz
,
A. C.
,
Speelman
,
L.
,
Nieuwstadt
,
H. A.
,
Van Brummelen
,
H.
,
Virmani
,
R.
,
Van Der Lugt
,
A.
,
Van Der Steen
,
A. F. W.
,
Wentzel
,
J. J.
, and
Gijsen
,
F. J. H.
,
2016
, “
The Effects of Plaque Morphology and Material Properties on Peak Cap Stress in Human Coronary Arteries
,”
Comput. Methods Biomech. Biomed. Eng.
,
19
(
7
), pp.
771
779
.10.1080/10255842.2015.1062091
49.
Finet
,
G.
,
Ohayon
,
J.
, and
Rioufol
,
G.
,
2004
, “
Biomechanical Interaction Between Cap Thickness, Lipid Core Composition and Blood Pressure in Vulnerable Coronary Plaque: Impact on Stability or Instability
,”
Coron. Artery Dis.
,
15
(
1
), pp.
13
20
.10.1097/00019501-200402000-00003
50.
Ohayon
,
J.
,
Finet
,
G.
,
Gharib
,
A. M.
,
Herzka
,
D. A.
,
Tracqui
,
P.
,
Heroux
,
J.
,
Rioufol
,
G.
,
Kotys
,
M. S.
,
Elagha
,
A.
, and
Pettigrew
,
R. I.
,
2008
, “
Necrotic Core Thickness and Positive Arterial Remodeling Index: Emergent Biomechanical Factors for Evaluating the Risk of Plaque Rupture
,”
Am. J. Physiol.: Heart Circ. Physiol.
,
295
(
2
), pp.
H717
H727
.10.1152/ajpheart.00005.2008
51.
Teng
,
Z.
,
Sadat
,
U.
,
Li
,
Z.
,
Huang
,
X.
,
Zhu
,
C.
,
Young
,
V. E.
,
Graves
,
M. J.
, and
Gillard
,
J. H.
,
2010
, “
Arterial Luminal Curvature and Fibrous-Cap Thickness Affect Critical Stress Conditions Within Atherosclerotic Plaque: An In Vivo MRI-Based 2D Finite-Element Study
,”
Ann. Biomed. Eng.
,
38
(
10
), pp.
3096
3101
.10.1007/s10439-010-0078-3
52.
Qiu
,
T. Y.
,
Song
,
M.
, and
Zhao
,
L. G.
,
2018
, “
A Computational Study of Crimping and Expansion of Bioresorbable Polymeric Stents
,”
Mech. Time-Depend. Mater.
,
22
(
2
), pp.
273
290
.10.1007/s11043-017-9371-y
53.
Hurtado
,
J. A.
, and
Govindarajan
,
S. M.
,
2007
, “
Simulation of Mullins Effect in Filled Elastomers Using Multiplicative Decomposition
,” Proceedings of the 5th
European Conference for Constitutive Models for Rubber, Balkema
, Paris, France, Sept. 4–7, pp.
249
254
.
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