Abstract

Intracoronary thrombus from plaque erosion could cause fatal acute coronary syndrome (ACS). A conservative antithrombotic therapy has been proposed to treat ACS patients in lieu of stenting. It is speculated that the residual thrombus after aspiration thrombectomy would influence the prognosis of this treatment. However, biomechanical mechanisms affecting intracoronary thrombus remodeling and clinical outcome remain largely unknown. in vivo optical coherence tomography (OCT) data of a coronary plaque with two residual thrombi after antithrombotic therapy were acquired from an ACS patient with consent obtained. Three OCT-based fluid–structure interaction (FSI) models with different thrombus volumes, fluid-only, and structure-only models were constructed to simulate and compare the biomechanical interplay among blood flow, residual thrombus, and vessel wall mimicking different clinical situations. Our results showed that residual thrombus would decrease coronary volumetric flow rate by 9.3%, but elevate wall shear stress (WSS) by 29.4% and 75.5% at thrombi 1 and 2, respectively. WSS variations in a cardiac cycle from structure-only model were 12.1% and 13.5% higher at the two thrombus surfaces than those from FSI model. Intracoronary thrombi were subjected to compressive forces indicated by negative thrombus stress. Tandem intracoronary thrombus might influence coronary hemodynamics and solid mechanics differently. Computational modeling could be used to quantify biomechanical conditions under which patients could receive patient-specific treatment plan with optimized outcome after antithrombotic therapy. More patient studies with follow-up data are needed to continue the investigation and better understand mechanisms governing thrombus remodeling process.

References

1.
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
2.
Kanwar
,
S. S.
,
Stone
,
G. W.
,
Singh
,
M.
,
Virmani
,
R.
,
Olin
,
J.
,
Akasaka
,
T.
, and
Narula
,
J.
,
2016
, “
Acute Coronary Syndromes Without Coronary Plaque Rupture
,”
Nat. Rev. Cardiol.
,
13
(
5
), pp.
257
265
.10.1038/nrcardio.2016.19
3.
Jia
,
H.
,
Dai
,
J.
,
Hou
,
J.
,
Xing
,
L.
,
Ma
,
L.
,
Liu
,
H.
,
Xu
,
M.
,
Yao
,
Y.
,
Hu
,
S.
,
Yamamoto
,
E.
,
Lee
,
H.
,
Zhang
,
S.
,
Yu
,
B.
, and
Jang
,
I.
,
2017
, “
Effective Anti-Thrombotic Therapy Without Stenting: Intravascular Optical Coherence Tomography-Based Management in Plaque Erosion (the EROSION Study)
,”
Eur. Heart J.
,
38
, pp.
792
800
. 10.1093/eurheartj/ehw381
4.
Furie
,
B.
, and
Furie
,
B. C.
,
2008
, “
Mechanisms of Thrombus Formation
,”
N. Engl. J. Med.
,
359
(
9)
, pp.
938
949
.10.1056/NEJMra0801082
5.
Jolly
,
S. S.
,
James
,
S.
,
Džavík
,
V.
,
Cairns
,
J. A.
,
Mahmoud
,
K. D.
,
Zijlstra
,
F.
,
Yusuf
,
S.
,
Olivecrona
,
G. K.
,
Renlund
,
H.
,
Gao
,
P.
,
Lagerqvist
,
B.
,
Alazzoni
,
A.
,
Kedev
,
S.
,
Stankovic
,
G.
,
Meeks
,
B.
, and
Frøbert
,
O.
,
2017
, “
Thrombus Aspiration in ST-Segment-Elevation Myocardial Infarction: An Individual Patient Meta-Analysis: Thrombectomy Trialists Collaboration
,”
Circulation
,
135
(
2
), pp.
143
152
.10.1161/CIRCULATIONAHA.116.025371
6.
Johnson
,
T. W.
,
Räber
,
L.
,
di Mario
,
C.
,
Bourantas
,
C.
,
Jia
,
H.
,
Mattesini
,
C.
,
Gonzalo
,
N.
,
de la Torre Hernandez
,
J. M.
,
Prati
,
F.
,
Koskinas
,
K.
,
Joner
,
M.
,
Radu
,
M. D.
,
Erlinge
,
D.
,
Regar
,
E.
,
Kunadian
,
V.
,
Maehara
,
A.
,
Byrne
,
R. A.
,
Capodanno
,
D.
,
Akasaka
,
T.
,
Wijns
,
W.
,
Mintz
,
G. S.
, and
Guagliumi
,
G.
,
2019
, “
Clinical Use of Intracoronary Imaging. Part 2: Acute Coronary Syndromes, Ambiguous Coronary Angiography Findings, and Guiding Interventional Decision-Making: An Expert Consensus Document of the European Association of Percutaneous Cardiovascular Interventions
,”
Eur. Heart J.
,
40
(
31
), pp.
2566
2584
.10.1093/eurheartj/ehz332
7.
Higuma
,
T.
,
Soeda
,
T.
,
Yamada
,
M.
,
Yokota
,
T.
,
Yokoyama
,
H.
,
Izumiyama
,
K.
,
Nishizaki
,
F.
,
Minami
,
Y.
,
Xing
,
L.
,
Yamamoto
,
E.
,
Lee
,
H.
,
Okumura
,
K.
, and
Jang
,
I.
,
2016
, “
Does Residual Thrombus After Aspiration Thrombectomy Affect the Outcome of Primary PCI in Patients With ST-Segment Elevation Myocardial Infarction? An Optical Coherence Tomography Study
,”
J. Am. Coll. Cardiol.
,
9
(
19)
, pp.
2002
2011
.10.1016/j.jcin.2016.06.050
8.
Jia
,
H.
,
Abtahian
,
F.
,
Aguirre
,
A. D.
,
Lee
,
S.
,
Chia
,
S.
,
Lowe
,
H.
,
Kato
,
K.
,
Yonetsu
,
T.
,
Vergallo
,
R.
,
Hu
,
S.
,
Tian
,
J.
,
Lee
,
H.
,
Park
,
S.
,
Jang
,
Y.
,
Raffel
,
O. C.
,
Mizuno
,
K.
,
Uemura
,
S.
,
Itoh
,
T.
,
Kakuta
,
T.
,
Choi
,
S.
,
Dauerman
,
H. L.
,
Prasad
,
A.
,
Toma
,
C.
,
McNulty
,
I.
,
Zhang
,
S.
,
Yu
,
B.
,
Fuster
,
V.
,
Narula
,
J.
,
Virmani
,
R.
, and
Jang
,
I.
,
2013
, “
In Vivo Diagnosis of Plaque Erosion and Calcified Nodule in Patients With Acute Coronary Syndrome by Intravascular Optical Coherence Tomography
,”
J. Am. Coll. Cardiol.
,
62
(
19
), pp.
1748
1758
.10.1016/j.jacc.2013.05.071
9.
Guo
,
X.
,
Giddens
,
D. P.
,
Molony
,
D.
,
Yang
,
C.
,
Samady
,
H.
,
Zheng
,
J.
,
Mintz
,
G. S.
,
Maehara
,
A.
,
Wang
,
L.
,
Pei
,
X.
,
Li
,
Z.
, and
Tang
,
D.
,
2018
, “
Combining IVUS and OCT for More Accurate Coronary Cap Thickness Quantification and Stress/Strain Calculations: A Patient-Specific 3D FSI Modeling Approach
,”
ASME J. Biomech. Eng.
,
140
(
4
), p.
041005
.10.1115/1.4038263
10.
Tricot
,
O.
,
Mallat
,
Z.
,
Heymes
,
C.
,
Belmin
,
J.
,
Lesèche
,
G.
, and
Tedgui
,
A.
,
2000
, “
Relation Between Endothelial Cell Apoptosis and Blood Flow Direction in Human Atherosclerotic Plaques
,”
Circulation
,
101
(
21
), pp.
2450
2453
.10.1161/01.CIR.101.21.2450
11.
Durand
,
E.
,
Scoazec
,
A.
,
Lafont
,
A.
,
Boddaert
,
J.
,
Al Hajzen
,
A.
,
Addad
,
F.
,
Mirshahi
,
M.
,
Desnos
,
M.
,
Tedgui
,
A.
, and
Mallat
,
Z.
,
2004
, “
In Vivo Induction of Endothelial Apoptosis Leads to Vessel Thrombosis and Endothelial Denudation: A Clue to the Understanding of the Mechanisms of Thrombotic Plaque Erosion
,”
Circulation
,
109
(
21
), pp.
2503
2506
.10.1161/01.CIR.0000130172.62481.90
12.
Sumi
,
T.
,
Yamashita
,
A.
,
Matsuda
,
S.
,
Goto
,
S.
,
Nishihira
,
K.
,
Furukoji
,
E.
,
Sugimura
,
H.
,
Kawahara
,
H.
,
Imamura
,
T.
,
Kitamura
,
K.
,
Tamura
,
S.
, and
Asada
,
Y.
,
2010
, “
Disturbed Blood Flow Induces Erosive Injury to Smooth Muscle Cell-Rich Neointima and Promotes Thrombus Formation in Rabbit Femoral Arteries
,”
J. Thromb. Haemostasis
,
8
(
6
), pp.
1394
1402
.10.1111/j.1538-7836.2010.03843.x
13.
Vergallo
,
R.
,
Papafaklis
,
M. I.
,
D'Amario
,
D.
,
Michalis
,
L. K.
,
Crea
,
F.
, and
Porto
,
I.
,
2019
, “
Coronary Plaque Erosion Developing in an Area of High Endothelial Shear Stress: Insights From Serial Optical Coherence Tomography Imaging
,”
Coron. Artery Dis.
,
30
(
1)
, pp.
74
75
.10.1097/MCA.0000000000000673
14.
Johnson
,
S.
,
Duffy
,
S.
,
Gunning
,
G.
,
Gilvarry
,
M.
,
McGarry
,
J. P.
, and
McHugh
,
P. E.
,
2017
, “
Review of Mechanical Testing and Modeling of Thrombus Material for Vascular Implant and Device Design
,”
Ann. Biomed. Eng.
,
45
(
11
), pp.
2494
2508
.10.1007/s10439-017-1906-5
15.
Ward
,
M. R.
,
Pasterkamp
,
G.
,
Yeung
,
A. C.
, and
Borst
,
C.
,
2000
, “
Arterial Remodeling. Mechanisms and Clinical Implications
,”
Circulation
,
102
(
10
), pp.
1186
1191
.10.1161/01.CIR.102.10.1186
16.
Kok
,
A. M.
,
Speelman
,
L.
,
Virmani
,
R.
,
van der Steen
,
A. F. W.
,
Gijsen
,
F. J. H.
, and
Wentzel
,
J. J.
,
2016
, “
Peak Cap Stress Calculations in Coronary Atherosclerotic Plaques With an Incomplete Necrotic Core Geometry
,”
BioMed. Eng. OnLine
,
15
, p.
48
.10.1186/s12938-016-0162-5
17.
Yang
,
C.
,
Bach
,
R.
,
Zheng
,
J.
,
El Naqa
,
I.
,
Woodard
,
P. K.
,
Teng
,
Z.
,
Billiar
,
K. L.
, and
Tang
,
D.
,
2009
, “
In Vivo IVUS-Based 3D Fluid Structure Interaction Models With Cyclic Bending and Anisotropic Vessel Properties for Human Atherosclerotic Coronary Plaque Mechanical Analysis
,”
IEEE Trans. Biomed. Eng.
,
56
(
10
), pp.
2420
2428
.10.1109/TBME.2009.2025658
18.
Holzapfel
,
G. A.
,
Gasser
,
T. C.
, and
Ogden
,
R. W.
,
2000
, “
A New Constitutive Framework for Arterial Wall Mechanics and a Comparative Study of Material Models
,”
J. Elast. Phys. Sci. Solids
,
61
(
1
), pp.
1
48
.10.1023/A:1010835316564
19.
Guo
,
X.
,
Zhu
,
J.
,
Maehara
,
A.
,
Monoly
,
D.
,
Samady
,
H.
,
Wang
,
L.
,
Billiar
,
K. L.
,
Zheng
,
J.
,
Yang
,
C.
,
Mintz
,
G. S.
,
Giddens
,
D. P.
, and
Tang
,
D.
,
2017
, “
Quantify Patient-Specific Coronary Vessel Material Property and Its Impact on Plaque Stress/Strain Calculations Using In Vivo IVUS Data and 3D FSI Models: A Pilot Study
,”
Biomech. Model. Mechanobiol.
,
16
(
1
), pp.
333
344
.10.1007/s10237-016-0820-3
20.
Di Martino
,
E.
,
Mantero
,
S.
,
Inzoli
,
F.
,
Melissano
,
G.
,
Astore
,
D.
,
Chiesa
,
R.
, and
Fumero
,
R.
,
1998
, “
Biomechanics of Abdominal Aortic Aneurysm in the Presence of Endolumial Thrombus: Experimental Characterisation and Structural Static Computational Analysis
,”
Eur. J. Vasc. Endovasc. Surg.
,
15
(
4)
, pp.
290
299
.10.1016/S1078-5884(98)80031-2
21.
Chueh
,
J. Y.
,
Wakhloo
,
A. K.
,
Hendricks
,
G. H.
,
Silva
,
C. F.
,
Weaver
,
J. P.
, and
Gounis
,
M. J.
,
2011
, “
Mechanical Characterization of Thromboemboli in Acute Ischemic Stroke and Laboratory Embolus Analogs
,”
AJNR Am. J. Neuroradiol.
,
32
(
7
), pp.
1237
1244
.10.3174/ajnr.A2485
22.
Tang
,
D.
,
Kamm
,
R. D.
,
Yang
,
C.
,
Zheng
,
J.
,
Canton
,
G.
,
Bach
,
R.
,
Huang
,
X.
,
Hatsukami
,
T. S.
,
Zhu
,
J.
,
Ma
,
G.
,
Maehara
,
A.
,
Mintz
,
G. S.
, and
Yuan
,
C.
,
2014
, “
Image-Based Modeling for Better Understanding and Assessment of Atherosclerotic Plaque Progression and Vulnerability: Data, Modeling, Validation, Uncertainty and Predictions
,”
J. Biomech.
,
47
(
4
), pp.
834
846
.10.1016/j.jbiomech.2014.01.012
23.
Tu
,
S.
,
Barbato
,
E.
,
Köszegi
,
Z.
,
Yang
,
J.
,
Sun
,
Z.
,
Holm
,
N. R.
,
Tar
,
B.
,
Li
,
Y.
,
Rusinaru
,
D.
,
Wijns
,
W.
, and
Reiber
,
J. H. C.
,
2014
, “
Fractional Flow Reserve Calculation From 3-Dimensional Quantitative Coronary Angiography and TIMI Frame Count: A Fast Computer Model to Quantify the Functional Significance of Moderately Obstructed Coronary Arteries
,”
J. Am. Coll. Cardiol.
,
7
(
7)
, pp.
768
777
.10.1016/j.jcin.2014.03.004
24.
Bathe
,
K. J.
,
2007
, “
Theory and Modeling Guide. Vol. I and II: ADINA and ADINA-F
,”
ADINA R&D, Inc
.,
Watertown, MA
.
25.
Wang
,
L.
,
Tang
,
D.
,
Maehara
,
A.
,
Wu
,
Z.
,
Yang
,
C.
,
Muccigrosso
,
D.
,
Zheng
,
J.
,
Bach
,
R.
,
Billiar
,
K. L.
, and
Mintz
,
G. S.
,
2018
, “
Fluid-Structure Interaction Models Based on Patient-Specific IVUS at Baseline and Follow-Up for Prediction of Coronary Plaque Progression by Morphological and Biomechanical Factors: A Preliminary Study
,”
J. Biomech.
,
68
, pp.
43
50
.10.1016/j.jbiomech.2017.12.007
26.
Chen
,
C. Y.
,
Antón
,
R.
,
Hung
,
M. Y.
,
Menon
,
P.
,
Finol
,
E. A.
, and
Pekkan
,
K.
,
2014
, “
Effects of Intraluminal Thrombus on Patient-Specific Abdominal Aortic Aneurysm Hemodynamics Via Stereoscopic Particle Image Velocity and Computational Fluid Dynamics Modeling
,”
ASME J. Biomech. Eng.
,
136
(
3
), p.
031001
.10.1115/1.4026160
27.
Raptis
,
A.
,
Xenos
,
M.
,
Dimas
,
S.
,
Giannoukas
,
A.
,
Labropoulos
,
N.
,
Bluestein
,
D.
, and
Matsagkas
,
M. I.
,
2016
, “
Effect of Macroscale Formation of Intraluminal Thrombus on Blood Flow in Abdominal Aortic Aneurysms
,”
Comput. Methods Biomech.
,
19
(
1
), pp.
84
92
.10.1080/10255842.2014.989389
28.
Leach
,
J.
,
Kao
,
E.
,
Zhu
,
C.
,
Saloner
,
D.
, and
Hope
,
M. D.
,
2019
, “
On the Relative Impact of Intraluminal Thrombus Heterogeneity on Abdominal Aortic Aneurysm Mechanics
,”
ASME J. Biomech. Eng.
,
141
(
11
), p.
111010
.10.1115/1.4044143
29.
Fröbert
,
O.
,
Lagerqvist
,
B.
,
Olivecrona
,
G. K.
,
Omerovic
,
E.
,
Gudnason
,
T.
,
Maeng
,
M.
,
Aasa
,
M.
,
Angerås
,
O.
,
Calais
,
F.
,
Danielewicz
,
M.
,
Erlinge
,
D.
,
Hellsten
,
L.
,
Jensen
,
U.
,
Johansson
,
A. C.
,
Kåregren
,
A.
,
Nilsson
,
J.
,
Robertson
,
L.
,
Sandhall
,
L.
,
Sjögren
,
I.
,
Ostlund
,
O.
,
Harnek
,
J.
, and
James
,
S. K.
,
2013
, “
TASTE Trial. Thrombus Aspiration During ST-Segment Elevation Myocardial Infarction
,”
N. Engl. J. Med.
,
369
(
17
), pp.
1587
1597
.10.1056/NEJMoa1308789
30.
Casa
,
L. D. C.
, and
Ku
,
D. N.
,
2017
, “
Thrombus Formation at High Shear Rates
,”
Annu. Rev. Biomed. Eng.
,
19
(
1)
, pp.
415
433
.10.1146/annurev-bioeng-071516-044539
31.
Vlaar
,
P. J.
,
Svilaas
,
T.
,
van der Horst
,
I. C.
,
Diercks
,
G. F. H.
,
Fokkema
,
M. L.
,
de Smet
,
B. J. G. L.
,
van den Heuvel
,
A. F. M.
,
Anthonio
,
R. L.
,
Jessurun
,
G. A.
,
Tan
,
E.
,
Suurmeijer
,
A. J. H.
, and
Zijlstra
,
F.
,
2008
, “
Cardiac Death and Reinfarction After 1 Year in the Thrombus Aspiration During Percutaneous Coronary Intervention in Acute Myocardial Infarction Study (TAPAS): A 1-Year Follow-Up Study
,”
Lancet
,
371
(
9628
), pp.
1915
1920
.10.1016/S0140-6736(08)60833-8
32.
Young
,
L.
,
Ockelford
,
P.
,
Milne
,
D.
,
Rolfe-Vyson
,
V.
,
Mckelvie
,
S.
, and
Harper
,
P.
,
2006
, “
Post-Treatment Residual Thrombus Increases the Risk of Recurrent Deep Vein Thrombosis and Mortality
,”
J. Thromb. Haemostasis
,
4
(
9
), pp.
1919
1924
.10.1111/j.1538-7836.2006.02120.x
33.
Kim
,
H. J.
,
Vignon-Clementel
,
I. E.
,
Coogan
,
J. S.
,
Figueroa
,
C. A.
,
Jansen
,
K. E.
, and
Taylor
,
C. A.
,
2010
, “
Patient Specific Modeling of Blood Flow and Pressure in Human Coronary Arteries
,”
Ann. Biomed. Eng.
,
38
(
10
), pp.
3195
3209
.10.1007/s10439-010-0083-6
34.
Ohayon
,
J.
,
Dubreuil
,
O.
,
Tracqui
,
P.
,
Le Floc'h
,
S.
,
Rioufol
,
G.
,
Chalabreysse
,
L.
,
Thivolet
,
F.
,
Pettigrew
,
R. I.
, and
Finet
,
G.
,
2007
, “
Influence of Residual Stress/Strain on the Biomechanical Stability of Vulnerable Coronary Plaques: Potential Impact for Evaluating the Risk of Plaque Rupture
,”
Am. J. Physiol.: Heart Circ. Physiol.
,
293
(
3
), pp.
H1987
H1996
.10.1152/ajpheart.00018.2007
35.
Fung
,
Y. C.
, and
Liu
,
S. Q.
,
1992
, “
Strain Distribution in Small Blood Vessel With Zero-Stress State Taken Into Consideration
,”
Am. J. Physiol.
,
262
(
2
), pp.
H544
H552
.10.1152/ajpheart.1992.262.2.H544
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