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Shah I, Molony D, Lefieux A, Crawford K, Piccinelli M, Sun H, Giddens D, Samady H, Veneziani A. Impact of the stent footprint on endothelial wall shear stress in patient-specific coronary arteries: A computational analysis from the SHEAR-STENT trial. COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE 2025; 266:108762. [PMID: 40245606 DOI: 10.1016/j.cmpb.2025.108762] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/20/2024] [Revised: 03/07/2025] [Accepted: 03/31/2025] [Indexed: 04/19/2025]
Abstract
BACKGROUND AND OBJECTIVE Wall shear stress (WSS) has been known to play a critical role in the development of several complications following coronary artery stenting, including in-stent restenosis and thrombosis. Computational fluid dynamics is often used to quantify the post-stenting WSS, which may potentially be used as a predictive metric. However, large-scale studies for WSS-based risk stratification often neglect the footprint of the stent due to reconstruction challenges. The primary objective of this study is to statistically evaluate the impact of the stent footprints (Xience and Resolute stents) on the computed endothelial WSS and quantitatively identify the relationship between these local hemodynamic alterations and the global properties of the vessel, such as curvature, on WSS. The ultimate goal is to evaluate whether and when it is worth including the footprint of the stent in an in-silico study to compute the WSS reliably. METHODS A previously developed semi-automated reconstruction approach for patient-specific coronaries was employed as a part of the SHEAR-STENT trial. A subset of patients was analyzed (N=30), and CFD simulations were performed with and without the stent to evaluate the impact of the stent footprint on WSS. Due to the computationally expensive nature of transient analyses, a sub-cohort of ten patients were used to assess the reliability of WSS obtained from steady computations as a surrogate for the time-averaged results. Global and local vessel curvature data were extracted for all cases and evaluated against stent-induced alterations in the WSS. The differences between the Xience and Resolute stent platforms were also examined to quantify each stent's unique WSS footprint. RESULTS Results from the surrogate analysis indicate that steady WSS serves as an excellent approximation of the time-averaged computations. The presence of either stent footprint causes a statistically significant decrease in the space-averaged WSS, and a significant increase in the endothelial regions exposed to very low WSS as well (<0.5 Pa). Negative correlations were observed between vessel curvature and WSS differences, indicating that macroscopic vessel characteristics play a more prominent role in determining endothelial WSS at higher curvature values. In our pool of cases, comparison of Xience and Resolute stents revealed that the Resolute platform seems to lead to lower space-averaged WSS and an increase in areas of very low WSS. CONCLUSION These results outline (1) the necessity of including the stent footprint for accurate in-silico WSS analysis; (2) the global features of stented arteries serving as the dominant determinant of WSS past a certain curvature threshold; and (3) the Xience stent resulting in a milder presence of hemodynamically unfavorable WSS regions compared to the Resolute stent.
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Affiliation(s)
- Imran Shah
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology & Emory University, 387 Nerem Street NW, Atlanta, GA 30313, USA; Department of Mathematics, Emory University, 400 Dowman Drive, Atlanta, GA 30322, USA.
| | - David Molony
- Georgia Heart Institute, Northeast Georgia Medical Center, 200 South Enota Drive, Gainseville, GA 30501, USA
| | - Adrien Lefieux
- Georgia Heart Institute, Northeast Georgia Medical Center, 200 South Enota Drive, Gainseville, GA 30501, USA
| | - Kaylyn Crawford
- Georgia Heart Institute, Northeast Georgia Medical Center, 200 South Enota Drive, Gainseville, GA 30501, USA
| | - Marina Piccinelli
- Department of Radiology and Imaging Sciences, Emory University School of Medicine, 100 Woodruff Circle, Atlanta, GA 30322, USA
| | - Hanyao Sun
- AU/UGA Medical Partnership, Medical College of Georgia, Prince Avenue, Athens, GA 30602, USA
| | - Don Giddens
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology & Emory University, 387 Nerem Street NW, Atlanta, GA 30313, USA; Department of Medicine, Emory University School of Medicine, 100 Woodruff Circle, Atlanta, GA 30322, USA
| | - Habib Samady
- Georgia Heart Institute, Northeast Georgia Medical Center, 200 South Enota Drive, Gainseville, GA 30501, USA; Department of Medicine, Emory University School of Medicine, 100 Woodruff Circle, Atlanta, GA 30322, USA
| | - Alessandro Veneziani
- Department of Mathematics, Emory University, 400 Dowman Drive, Atlanta, GA 30322, USA; Department of Computer Science, Emory University, 400 Dowman Drive, Atlanta, GA 30322, USA
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Chan WX, Ding W, Li B, Wong HS, Yap CH. Role of physics-informed constraints in real-time estimation of 3D vascular fluid dynamics using multi-case neural network. Comput Biol Med 2025; 190:110074. [PMID: 40147188 DOI: 10.1016/j.compbiomed.2025.110074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Revised: 02/04/2025] [Accepted: 03/21/2025] [Indexed: 03/29/2025]
Abstract
Numerical simulations of fluid dynamics in tube-like structures are important to biomedical research to model flow in blood vessels and airways. It is further useful to some clinical applications, such as predicting arterial fractional flow reserves, and assessing vascular flow wall shear stresses to predict atherosclerosis disease progression. Traditionally, they are conducted via computational fluid dynamics (CFD) simulations, which, despite optimization, still take substantial time, limiting clinical adoption. To improve efficiency, we investigate the use of the multi-case Neural Network (NN) to enable real-time predictions of fluid dynamics (both steady and pulsatile flows) in a 3D curved tube (with a narrowing in the middle mimicking a stenosis) of any shape within a geometric range, using only geometric parameters and boundary conditions. We compare the unsupervised approach guided by physics governing equations (physics informed neural network or PINN) to the supervised approach of using mass CFD simulations to train the network (supervised network or SN). We find that multi-case PINN can generate accurate velocity, pressure and wall shear stress (WSS) results under steady flow (spatially maximum error < 2-5 %), but this requires a specific enhancement strategies: (1) estimating the curvilinear coordinate parameters via a secondary NN to use as inputs into PINN, (2) imposing no-slip wall boundary condition as a hard constraint, and (3) advanced strategy to better spatially propagate effects of boundary conditions. However, we cannot achieve reasonable accuracy for pulsatile flow with PINN. Conversely, SN provides very accurate velocity, pressure, and WSS predictions under both steady and pulsatile flow scenarios (spatially and/or temporally maximum error averaged over all geometries <1 %), and is much less computationally expensive to train. To achieve this, strategies (1) and (2) above and a spectral encoding strategy for pulsatile flow are necessary. Thus, interestingly, the use of physics constraints is not effective in our application.
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Affiliation(s)
- Wei Xuan Chan
- Department of Bioengineering, Imperial College London, Exhibition Road, London, SW7 2AZ, United Kingdom
| | - Wenhao Ding
- Department of Bioengineering, Imperial College London, Exhibition Road, London, SW7 2AZ, United Kingdom
| | - Binghuan Li
- Department of Chemical Engineering, Imperial College London, Exhibition Road, London, SW7 2AZ, United Kingdom
| | - Hong Shen Wong
- Department of Bioengineering, Imperial College London, Exhibition Road, London, SW7 2AZ, United Kingdom
| | - Choon Hwai Yap
- Department of Bioengineering, Imperial College London, Exhibition Road, London, SW7 2AZ, United Kingdom.
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Zhang M, Keramati H, Gharleghi R, Beier S. Reliability of characterising coronary artery flow with the flow-split outflow strategy: Comparison against the multiscale approach. COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE 2025; 263:108669. [PMID: 39956049 DOI: 10.1016/j.cmpb.2025.108669] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Revised: 12/18/2024] [Accepted: 02/11/2025] [Indexed: 02/18/2025]
Abstract
BACKGROUND In computational modelling of coronary haemodynamics, imposing patient-specific flow conditions is paramount, yet often impractical due to resource and time constraints, limiting the ability to perform a large number of simulations particularly for diseased cases. OBJECTIVE To compare coronary haemodynamics quantified using a simplified flow-split strategy with varying exponents against the clinically verified but computationally intensive multiscale simulations under both resting and hyperaemic conditions in arteries with varying degrees of stenosis. METHODS Six patient-specific left coronary artery trees were segmented and reconstructed, including three with severe (>70 %) and three with mild (<50 %) focal stenoses. Simulations were performed for the entire coronary tree to account for the flow-limiting effects from epicardial artery stenoses. Both a 0D-3D coupled multiscale model and a flow-split approach with four different exponents (2.0, 2.27, 2.33, and 3.0) were used. The resulting prominent haemodynamic metrics were statistically compared between the two methods. RESULTS Flow-split and multiscale simulations did not significantly differ under resting conditions regardless of the stenosis severity. However, under hyperaemic conditions, the flow-split method significantly overestimated the time-averaged wall shear stress by up to 16.8 Pa (p = 0.031) and underestimate the fractional flow reserve by 0.327 (p = 0.043), with larger discrepancies observed in severe stenoses than in mild ones. Varying the exponent from 2.0 to 3.0 within the flow-split methods did not significantly affect the haemodynamic results (p > 0.141). CONCLUSIONS Flow-split strategies with exponents between 2.0 and 3.0 are appropriate for modelling stenosed coronaries under resting conditions. Multiscale simulations are recommended for accurate modelling of hyperaemic conditions, especially in severely stenosed arteries.(247/250 words).
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Affiliation(s)
- Mingzi Zhang
- Sydney Vascular Modelling Group, School of Mechanical and Manufacturing Engineering, University of New South Wales, Sydney, NSW 2052, Australia.
| | - Hamed Keramati
- Sydney Vascular Modelling Group, School of Mechanical and Manufacturing Engineering, University of New South Wales, Sydney, NSW 2052, Australia
| | - Ramtin Gharleghi
- Sydney Vascular Modelling Group, School of Mechanical and Manufacturing Engineering, University of New South Wales, Sydney, NSW 2052, Australia
| | - Susann Beier
- Sydney Vascular Modelling Group, School of Mechanical and Manufacturing Engineering, University of New South Wales, Sydney, NSW 2052, Australia
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Bingyu W, Jun Q, Bingyang L, Xi Y, Jianqing Z, Jiangfang L. Trimethylamine N-oxide promotes PERK-mediated endothelial-mesenchymal transition and apoptosis thereby aggravates atherosclerosis. Int Immunopharmacol 2024; 142:113209. [PMID: 39340998 DOI: 10.1016/j.intimp.2024.113209] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Revised: 09/16/2024] [Accepted: 09/17/2024] [Indexed: 09/30/2024]
Abstract
The endothelial-mesenchymal transition (EndMT) is involved in the development of atherosclerosis (AS) and is a key process in vascular endothelial injury. Oxidative stress, inflammation, and apoptosis are common causes of EndMT, and EndMT progression can further accelerate the development of AS. The metabolite trimethylamine N-oxide (TMAO) is produced by the gut microbiome and is implicated in the development of several diseases, including diabetes and chronic kidney disease. However, the impact of TMAO on transforming growth factor β1(TGF-β1)-induced EndMT remains unclear. We hypothesize that TMAO exacerbates plaque formation and cardiac function impairment by promoting EndMT. Herein, we showed that high serum TMAO levels caused plaque formation, cardiac function damage and haemodynamic changes in ApoE-/- mice. In vitro, TMAO upregulated mesenchymal markers and downregulated endothelial markers in HAECs. Furthermore, TMAO increased the migratory capacity of EndMT cells. Mechanistically, we found that PERK downregulation could alleviate TMAO-induced oxidative stress, EndMT, plaque formation and cardiac function damage. Further study showed that activated transcription factor 3 (ATF3), the downstream molecule of protein kinase RNA-like endoplasmic reticulum kinase (PERK), could bind with TGF-β1/2 and affect EndMT. Overall, TMAO promotes EndMT, possibly through the PERK-eIF2α-ATF4-CHOP or the PERk-eIF2α-ATF3-TGF-β signalling pathways.
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Affiliation(s)
- Wang Bingyu
- Department of Cardiovascular, Ningbo Medical Center Lihuili Hospital, Ningbo University, Ningbo, China
| | - Qiu Jun
- Department of Cardiovascular, Ningbo Medical Center Lihuili Hospital, Ningbo University, Ningbo, China
| | - Liu Bingyang
- Department of Cardiovascular, Ningbo Medical Center Lihuili Hospital, Ningbo University, Ningbo, China
| | - Yang Xi
- Ningbo Institute of Innovation for Combined Medicine and Engineering, Ningbo, China.
| | - Zhou Jianqing
- Department of Cardiovascular, Ningbo Medical Center Lihuili Hospital, Ningbo University, Ningbo, China; Ningbo Institute of Innovation for Combined Medicine and Engineering, Ningbo, China.
| | - Lian Jiangfang
- Department of Cardiovascular, Ningbo Medical Center Lihuili Hospital, Ningbo University, Ningbo, China; Ningbo Institute of Innovation for Combined Medicine and Engineering, Ningbo, China.
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5
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Martín Tempestti J, Kim S, Lindsey BD, Veneziani A. A Pseudo-Spectral Method for Wall Shear Stress Estimation from Doppler Ultrasound Imaging in Coronary Arteries. Cardiovasc Eng Technol 2024; 15:647-666. [PMID: 39103664 DOI: 10.1007/s13239-024-00741-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2023] [Accepted: 06/24/2024] [Indexed: 08/07/2024]
Abstract
PURPOSE The Wall Shear Stress (WSS) is the component tangential to the boundary of the normal stress tensor in an incompressible fluid, and it has been recognized as a quantity of primary importance in predicting possible adverse events in cardiovascular diseases, in general, and in coronary diseases, in particular. The quantification of the WSS in patient-specific settings can be achieved by performing a Computational Fluid Dynamics (CFD) analysis based on patient geometry, or it can be retrieved by a numerical approximation based on blood flow velocity data, e.g., ultrasound (US) Doppler measurements. This paper presents a novel method for WSS quantification from 2D vector Doppler measurements. METHODS Images were obtained through unfocused plane waves and transverse oscillation to acquire both in-plane velocity components. These velocity components were processed using pseudo-spectral differentiation techniques based on Fourier approximations of the derivatives to compute the WSS. RESULTS Our Pseudo-Spectral Method (PSM) is tested in two vessel phantoms, straight and stenotic, where a steady flow of 15 mL/min is applied. The method is successfully validated against CFD simulations and compared against current techniques based on the assumption of a parabolic velocity profile. The PSM accurately detected Wall Shear Stress (WSS) variations in geometries differing from straight cylinders, and is less sensitive to measurement noise. In particular, when using synthetic data (noise free, e.g., generated by CFD) on cylindrical geometries, the Poiseuille-based methods and PSM have comparable accuracy; on the contrary, when using the data retrieved from US measures, the average error of the WSS obtained with the PSM turned out to be 3 to 9 times smaller than that obtained by state-of-the-art methods. CONCLUSION The pseudo-spectral approach allows controlling the approximation errors in the presence of noisy data. This gives a more accurate alternative to the present standard and a less computationally expensive choice compared to CFD, which also requires high-quality data to reconstruct the vessel geometry.
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Affiliation(s)
| | - Saeyoung Kim
- George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, 801 Ferst Dr., Atlanta, GA, 30332, USA
- Interdisciplinary BioEngineering Graduate Program, Georgia Institute of Technology, 315 Ferst Dr., Atlanta, GA, 30332, USA
| | - Brooks D Lindsey
- George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, 801 Ferst Dr., Atlanta, GA, 30332, USA
- Interdisciplinary BioEngineering Graduate Program, Georgia Institute of Technology, 315 Ferst Dr., Atlanta, GA, 30332, USA
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 313 Ferst Dr NW, Atlanta, GA, 30332, USA
| | - Alessandro Veneziani
- Department of Mathematics, Emory University, 400 Dowman Dr, Atlanta, 30322, GA, USA
- Department of Computer Science, Emory University, 400 Dowman Dr, Atlanta, GA, 30322, USA
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6
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Liu Y, Wu B, Wu S, Liu Z, Wang P, Lv Y, Wu R, Ji B, Peng Z, Lu C, Wei D, Li G, Liu J, Wu G. Comparison of stable carotid plaques in patients with mild-to-moderate carotid stenosis with vulnerable plaques in patients with significant carotid stenosis. Medicine (Baltimore) 2024; 103:e40613. [PMID: 39612378 PMCID: PMC11608718 DOI: 10.1097/md.0000000000040613] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Accepted: 11/01/2024] [Indexed: 12/01/2024] Open
Abstract
To compare the characteristics of stable and vulnerable carotid plaques, and investigate the diagnostic performance of wall shear stress (WSS) based on magnetic resonance plaque imaging in carotid plaques. Retrospectively analyzed and divided 64 atherosclerotic plaques into stable carotid plaque groups with mild-to-moderate stenosis and vulnerable carotid plaque groups with significant stenosis. Computational fluid dynamics simulations were performed to calculate WSS parameters by using three-dimensional wall geometry based on high-resolution magnetic resonance plaque imaging of carotid bifurcation and patient specific boundary conditions obtained through color Doppler ultrasound. WSS parameters including upstream (WSSup), downstream (WSSdown), and core (WSScore) of plaque. The WSS parameters values were compared between the stable and vulnerable carotid plaque groups. Receiver operating characteristic curves and area under the curve (ROC-AUC) and Python were used to evaluate discriminative efficacy of WSS. WSSdown exhibited significant decrease in the vulnerable carotid plaque group (2.88 ± 0.41 Pa) compared to the stable carotid plaque group (4.47 ± 0.84 Pa) (P = .003). The difference of WSSup (3.28 ± 0.85 Pa vs 4.02 ± 0.74 Pa) and WSScore (1.12 ± 0.18 Pa vs 1.38 ± 0.38 Pa) between the two groups were also pronounced (P = .02, 0.01, respectively). The ROC-AUC values for WSSup, WSSdown, WSScore were 0.75 (95% CI, 0.58-0.93), 0.96 (95% CI, 0.79-1.14), 0.69 (95% CI, 0.56-0.83) respectively. When the value of WSSdown was 3.5 Pa, the sensitivity was 93.7% (95% CI, 76.1-111), specificity and accuracy was 87.5% (95% CI, 70.0-105), 88.4% (95% CI, 70.6-105) respectively. Notably, among these parameters, WSSdown demonstrated the highest discriminative efficiency with a F1 Score of 0.90, Diagnostic Odds Ratio of 105.0 and Matthews Correlation Coefficient of 0.81. Vulnerable carotid plaques with significant stenosis have lower WSS compared to stable plaques with mild-to-moderate stenosis, and downstream WSS showing the highest diagnostic efficacy.
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Affiliation(s)
- Yumeng Liu
- Department of Radiology, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen, China
| | - Bokai Wu
- Laboratory for Engineering and Scientific Computing, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
| | - Songxiong Wu
- Department of Radiology, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen, China
| | - Zhenyu Liu
- Department of Radiology, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen, China
| | - Panying Wang
- Department of Radiology, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen, China
| | - Yungang Lv
- Department of Radiology, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen, China
| | - Ruodai Wu
- Department of Radiology, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen, China
| | - Bin Ji
- Department of Radiology, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen, China
| | - Zhengkun Peng
- Department of Radiology, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen, China
| | - Chao Lu
- Department of Radiology, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen, China
| | - Dazhong Wei
- Department of Radiology, Luocheng People Hospital, Luocheng, China
| | - Guangyao Li
- Department of Radiology, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen, China
| | - Jia Liu
- Laboratory for Engineering and Scientific Computing, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
| | - Guangyao Wu
- Department of Radiology, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen, China
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Chamié D, Pfau S. Following the Dynamic Changes of Coronary Atherosclerosis: An Uphill Battle. J Am Heart Assoc 2024; 13:e037395. [PMID: 39435716 PMCID: PMC11935670 DOI: 10.1161/jaha.124.037395] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Accepted: 09/03/2024] [Indexed: 10/23/2024]
Affiliation(s)
- Daniel Chamié
- Section of Cardiovascular Medicine, Yale School of MedicineYale UniversityNew HavenCT
| | - Steven Pfau
- Section of Cardiovascular Medicine, Yale School of MedicineYale UniversityNew HavenCT
- VA ConnecticutWest HavenCT
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Zhang Y, Dai D, Geng S, Rong C, Zou R, Leng X, Xiang J, Liu J, Ding J. PCSK9 expression in fibrous cap possesses a marker for rupture in advanced plaque. Vasc Med 2024; 29:483-495. [PMID: 38860436 DOI: 10.1177/1358863x241252370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/12/2024]
Abstract
BACKGROUND To date, PCSK9 inhibitors are well known for eliminating cardiac and cerebral artery ischemia events by lowering the serum lipid level. However, the pathophysiological value of in-plaque PCSK9 expression is still unclear. METHODS Advanced plaques removed by carotid endarterectomy were sectioned and stained to identify the PCSK9 expression pattern and its co-expression with rupture-relevant markers. To investigate the correlation of PCSK9 expression with regional blood shear flow, hemodynamic characteristics were analyzed using computational fluid dynamics, and representative parameters were compared between PCSK9 positive and negative staining plaques. To explore this phenomenon in vitro, human aortic vascular smooth muscle cells were used to overexpress and knock down PCSK9. The impacts of PCSK9 modulations on mechanical sensor activity were testified by western blot and immunofluorescence. Real-time polymerase chain reaction was used to evaluate the transcription levels of downstream rupture-prone effectors. RESULTS PCSK9 distribution in plaque preferred cap and shoulder regions, residing predominantly in smooth muscle actin-positive cells. Cap PCSK9 expression correlated with fibrous cap thickness negatively and co-expressed with MMP-9, both pointing to the direction of plaque rupture. A hemodynamic profile indicated a rupture-prone feature of cap PCSK9 expression. In vitro, overexpression and knockdown of PCSK9 in human aortic vascular smooth muscle cells has positive modulation on mechanical sensor Yes-associated protein 1 (YAP) activity and transcription levels of its downstream rupture-prone effectors. Serial section staining verified in situ colocalization among PCSK9, YAP, and downstream effectors. CONCLUSIONS Cap PCSK9 possesses a biomarker for rupture risk, and its modulation may lead to a novel biomechanical angle for plaque interventions.
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MESH Headings
- Humans
- Plaque, Atherosclerotic
- Proprotein Convertase 9/genetics
- Proprotein Convertase 9/metabolism
- Rupture, Spontaneous
- Myocytes, Smooth Muscle/pathology
- Myocytes, Smooth Muscle/enzymology
- Myocytes, Smooth Muscle/metabolism
- Muscle, Smooth, Vascular/pathology
- Muscle, Smooth, Vascular/metabolism
- Muscle, Smooth, Vascular/enzymology
- Fibrosis
- Cells, Cultured
- Matrix Metalloproteinase 9/genetics
- Matrix Metalloproteinase 9/metabolism
- Male
- Endarterectomy, Carotid
- Carotid Arteries/pathology
- Carotid Arteries/surgery
- Carotid Arteries/enzymology
- Carotid Arteries/metabolism
- Aged
- Mechanotransduction, Cellular
- Female
- Regional Blood Flow
- Carotid Stenosis/pathology
- Carotid Stenosis/genetics
- Carotid Stenosis/surgery
- Carotid Stenosis/metabolism
- Carotid Stenosis/enzymology
- Carotid Artery Diseases/genetics
- Carotid Artery Diseases/enzymology
- Carotid Artery Diseases/pathology
- Carotid Artery Diseases/metabolism
- Carotid Artery Diseases/surgery
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Affiliation(s)
- Yingying Zhang
- Department of Neurology, Fudan University Zhongshan Hospital, Shanghai, China
| | - Dongwei Dai
- Department of Neurovascular Center, Naval Medical University Changhai Hospital, Shanghai, China
- Department of Neurosurgery, Fudan University Huadong Hospital, Shanghai, China
| | | | | | - Rong Zou
- ArteryFlow Technology Co., Ltd, Hangzhou, China
| | | | | | - Jianmin Liu
- Department of Neurovascular Center, Naval Medical University Changhai Hospital, Shanghai, China
| | - Jing Ding
- Department of Neurology, Fudan University Zhongshan Hospital, Shanghai, China
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9
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Zhang M, Gharleghi R, Shen C, Beier S. A new understanding of coronary curvature and haemodynamic impact on the course of plaque onset and progression. ROYAL SOCIETY OPEN SCIENCE 2024; 11:241267. [PMID: 39309260 PMCID: PMC11416812 DOI: 10.1098/rsos.241267] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Accepted: 08/01/2024] [Indexed: 09/25/2024]
Abstract
The strong link between atherosclerosis and luminal biomechanical stresses is well established. Yet, this understanding has not translated into preventative coronary diagnostic imaging, particularly due to the under-explored role of coronary anatomy and haemodynamics in plaque onset, which we aim to address with this work. The left coronary trees of 20 non-stenosed (%diameter stenosis [%DS] = 0), 12 moderately (0 < %DS < 70) and 7 severely (%DS ≥ 70) stenosed cases were dissected into bifurcating and non-bifurcating segments for whole-tree and segment-specific comparisons, correlating nine three-dimensional coronary anatomical features, topological shear variation index (TSVI) and luminal areas subject to low time-average endothelial shear stress (%LowTAESS), high oscillatory shear index (%HighOSI) and high relative residence time (%HighRRT). We found that TSVI is the only metric consistently differing between non-stenosed and stenosed cases across the whole tree, bifurcating and non-bifurcating segments (p < 0.002, AUC = 0.876), whereas average curvature and %HighOSI differed only for the whole trees (p < 0.024) and non-bifurcating segments (p < 0.027), with AUC > 0.711. Coronary trees with moderate or severe stenoses differed only in %LowTAESS (p = 0.009) and %HighRRT (p = 0.012). This suggests TSVI, curvature and %HighOSI are potential factors driving plaque onset, with greater predictive performance than the previously recognized %LowTAESS and %HighRRT, which appears to play a role in plaque progression.
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Affiliation(s)
- Mingzi Zhang
- School of Mechanical and Manufacturing Engineering, University of New South Wales, Sydney, New South Wales2052, Australia
| | - Ramtin Gharleghi
- School of Mechanical and Manufacturing Engineering, University of New South Wales, Sydney, New South Wales2052, Australia
| | - Chi Shen
- School of Mechanical and Manufacturing Engineering, University of New South Wales, Sydney, New South Wales2052, Australia
| | - Susann Beier
- School of Mechanical and Manufacturing Engineering, University of New South Wales, Sydney, New South Wales2052, Australia
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Zhao C, Lv R, Maehara A, Wang L, Gao Z, Xu Y, Guo X, Zhu Y, Huang M, Zhang X, Zhu J, Yu B, Jia H, Mintz GS, Tang D. Plaque Ruptures Are Related to High Plaque Stress and Strain Conditions: Direct Verification by Using In Vivo OCT Rupture Data and FSI Models. Arterioscler Thromb Vasc Biol 2024; 44:1617-1627. [PMID: 38721707 PMCID: PMC11208065 DOI: 10.1161/atvbaha.124.320764] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Accepted: 04/24/2024] [Indexed: 06/28/2024]
Abstract
BACKGROUND While it has been hypothesized that high plaque stress and strain may be related to plaque rupture, its direct verification using in vivo coronary plaque rupture data and full 3-dimensional fluid-structure interaction models is lacking in the current literature due to difficulty in obtaining in vivo plaque rupture imaging data from patients with acute coronary syndrome. This case-control study aims to use high-resolution optical coherence tomography-verified in vivo plaque rupture data and 3-dimensional fluid-structure interaction models to seek direct evidence for the high plaque stress/strain hypothesis. METHODS In vivo coronary plaque optical coherence tomography data (5 ruptured plaques, 5 no-rupture plaques) were acquired from patients using a protocol approved by the local institutional review board with informed consent obtained. The ruptured caps were reconstructed to their prerupture morphology using neighboring plaque cap and vessel geometries. Optical coherence tomography-based 3-dimensional fluid-structure interaction models were constructed to obtain plaque stress, strain, and flow shear stress data for comparative analysis. The rank-sum test in the nonparametric test was used for statistical analysis. RESULTS Our results showed that the average maximum cap stress and strain values of ruptured plaques were 142% (457.70 versus 189.22 kPa; P=0.0278) and 48% (0.2267 versus 0.1527 kPa; P=0.0476) higher than that for no-rupture plaques, respectively. The mean values of maximum flow shear stresses for ruptured and no-rupture plaques were 145.02 dyn/cm2 and 81.92 dyn/cm2 (P=0.1111), respectively. However, the flow shear stress difference was not statistically significant. CONCLUSIONS This preliminary case-control study showed that the ruptured plaque group had higher mean maximum stress and strain values. Due to our small study size, larger scale studies are needed to further validate our findings.
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Affiliation(s)
- Chen Zhao
- Department of Cardiology, Second Affiliated Hospital of Harbin Medical University, China (C.Z., Z.G., Y.X., B.Y., H.J.)
- National Key Laboratory of Frigid Zone Cardiovascular Diseases, Harbin, China (C.Z., Z.G., Y.X., B.Y., H.J.)
- The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China (C.Z., Z.G., Y.X., B.Y., H.J.)
| | - Rui Lv
- Department of Cardiac Surgery, Shandong Second Provincial General Hospital, Jinan, China (R.L.)
- School of Biological Science and Medical Engineering, Southeast University, Nanjing, China (R.L., L.W., Y.Z., M.H., D.T.)
| | - Akiko Maehara
- The Cardiovascular Research Foundation, Columbia University, New York, NY (A.M., G.S.M.)
| | - Liang Wang
- School of Biological Science and Medical Engineering, Southeast University, Nanjing, China (R.L., L.W., Y.Z., M.H., D.T.)
| | - Zhanqun Gao
- Department of Cardiology, Second Affiliated Hospital of Harbin Medical University, China (C.Z., Z.G., Y.X., B.Y., H.J.)
- National Key Laboratory of Frigid Zone Cardiovascular Diseases, Harbin, China (C.Z., Z.G., Y.X., B.Y., H.J.)
| | - Yishuo Xu
- Department of Cardiology, Second Affiliated Hospital of Harbin Medical University, China (C.Z., Z.G., Y.X., B.Y., H.J.)
- National Key Laboratory of Frigid Zone Cardiovascular Diseases, Harbin, China (C.Z., Z.G., Y.X., B.Y., H.J.)
- The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China (C.Z., Z.G., Y.X., B.Y., H.J.)
| | - Xiaoya Guo
- School of Science, Nanjing University of Posts and Telecommunications, China (X.G.)
| | - Yanwen Zhu
- School of Biological Science and Medical Engineering, Southeast University, Nanjing, China (R.L., L.W., Y.Z., M.H., D.T.)
| | - Mengde Huang
- School of Biological Science and Medical Engineering, Southeast University, Nanjing, China (R.L., L.W., Y.Z., M.H., D.T.)
| | - Xiaoguo Zhang
- Department of Cardiology, Zhongda Hospital, Southeast University, China (X.Z., J.Z.)
| | - Jian Zhu
- Department of Cardiology, Zhongda Hospital, Southeast University, China (X.Z., J.Z.)
| | - Bo Yu
- Department of Cardiology, Second Affiliated Hospital of Harbin Medical University, China (C.Z., Z.G., Y.X., B.Y., H.J.)
- National Key Laboratory of Frigid Zone Cardiovascular Diseases, Harbin, China (C.Z., Z.G., Y.X., B.Y., H.J.)
- The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China (C.Z., Z.G., Y.X., B.Y., H.J.)
| | - Haibo Jia
- Department of Cardiology, Second Affiliated Hospital of Harbin Medical University, China (C.Z., Z.G., Y.X., B.Y., H.J.)
- National Key Laboratory of Frigid Zone Cardiovascular Diseases, Harbin, China (C.Z., Z.G., Y.X., B.Y., H.J.)
- The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China (C.Z., Z.G., Y.X., B.Y., H.J.)
| | - Gary S. Mintz
- The Cardiovascular Research Foundation, Columbia University, New York, NY (A.M., G.S.M.)
| | - Dalin Tang
- School of Biological Science and Medical Engineering, Southeast University, Nanjing, China (R.L., L.W., Y.Z., M.H., D.T.)
- Mathematical Sciences Department, Worcester Polytechnic Institute, MA (D.T.)
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11
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Jiang S, Dong D, Chen K, Zhang C, Dou W, Wang X. Assessment of paclitaxel drug-coated balloon angioplasty for intracranial atherosclerotic disease based on high-resolution vessel wall magnetic resonance imaging. Interv Neuroradiol 2024:15910199241239718. [PMID: 38539050 PMCID: PMC11571170 DOI: 10.1177/15910199241239718] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Accepted: 02/27/2024] [Indexed: 11/20/2024] Open
Abstract
BACKGROUND To accurately assess the treatment effect of paclitaxel drug-coated balloon (DCB) angioplasty is essential for intracranial atherosclerotic disease (ICAD) patients. This study aimed to investigate the clinical feasibility of high-resolution vessel wall MRI (HR-VWI) in assessing ICAD with DCB angioplasty. METHODS Forty-five patients with intracranial atherosclerotic stenosis ≥ 70% confirmed by digital subtraction angiography (DSA) underwent HR-VWI before and after DCB angioplasty. Postoperative follow-up was performed after 6 months (±1 month). The differences of pre- and postoperative HR-VWI characteristics, including vessel and lumen area at maximal lumen narrowing (MLN), plaque area and length, degree of stenosis, plaque burden (PB), remodeling index, and plaque enhancement amplitude (PEA) were compared. The relationship between stenotic rate obtained using HR-VWI and DSA was evaluated. Each HR-VWI characteristic and clinical factor before DCB angioplasty was separately evaluated for the association with postoperative restenosis. RESULTS After six months, lumen area of MLN, plaque length and area, degree of stenosis, PB, and PEA showed a significantly difference relative to the value before DCB angioplasty (all P < 0.05). Spearman correlation coefficients of 0.865 and 0.932 were revealed between DSA and HR-VWI regarding the stenotic rate analysis pre- and post-operation (both P < 0.05). ROC analysis showed PEA, plaque length, and PB before DCB angioplasty separately provided robust prediction of postoperative restenosis (area under the curve = 0.909, 0.814 and 0.743; all P < 0.05). Multivariable analysis revealed that PEA was an independent predictor of prognosis. CONCLUSIONS The HR-VWI can accurately assess the treatment effect of DCB and robustly predict prognosis.
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Affiliation(s)
- Shu Jiang
- Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong Province, China
| | - Dong Dong
- Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong Province, China
| | - Kunjian Chen
- Department of Radiology, Weifang People's Hospital, Weifang, Shandong Province, China
| | - Chao Zhang
- Department of Radiology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong Province, China
| | | | - Xinyi Wang
- Department of Radiology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong Province, China
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12
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Gao W, Dong Y, Dong F, Hong S, Song D, Liu M, Wei Z, Du Y, Li S, Xu J. Feasibility study of combining wall shear stress and elastography to assess the vascular status of carotid artery. Curr Med Imaging 2024; 20:e270323214999. [PMID: 37018521 DOI: 10.2174/1573405620666230327125840] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2022] [Revised: 01/17/2023] [Accepted: 02/02/2023] [Indexed: 04/07/2023]
Abstract
INTRODUCTION At present, early detection of the potential risk of atherosclerosis and prevention is of great significance to reduce the occurrence of stroke. AIM This study aims to explore the value of combining the wall shear stress measured by ultrasound vector flow imaging technique and sound touch elastography of common carotid artery in normal adults using the Mindray Resona 7 ultrasound system. METHODS Forty volunteers (mean age 39.5 y, 23 females, 17 males) were divided into four groups according to their age. All volunteers underwent ultrasound carotid artery examination, and the values of wall shear stress and elasticity on the posterior wall of the common carotid artery were measured using advanced imaging functions, vector flow imaging technique, and sound touch elastography. RESULTS Different cut-off values of wall shear stress were used to investigate the significance between two groups with corresponding sound touch elastography values. It can be seen that the statistical difference could be found when the mean wall shear stress was larger than 1.5 Pa approximately (statistical significance was defined when P < 0.05), and the sound touch elastography value was positively correlated with the wall shear stress value. CONCLUSION This study reveals that the combination of wall shear stress and sound touch elastography is an effective and feasible method for assessing carotid artery health. When the mean wall shear stress value is over 1.5 Pa, the corresponding sound touch elastography value increases significantly. The risk of atherosclerosis increases with the stiffness of blood vessel walls.
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Affiliation(s)
- Wenjing Gao
- Department of Ultrasound, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong, China
| | - Yinghui Dong
- Department of Ultrasound, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong, China
| | - Fajin Dong
- Department of Ultrasound, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong, China
| | - Shaofu Hong
- Department of Ultrasound, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong, China
| | - Di Song
- Department of Ultrasound, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong, China
| | - Mengmeng Liu
- Department of Ultrasound, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong, China
| | - Zhanghong Wei
- ShenZhen People's Hospital Department of Ultrasound Shenzhen China
| | - Yigang Du
- Shenzhen Mindray Bio-Medical Electronics Co., Ltd., Shenzhen 518057, Guangdong, China
| | - Shuangshuang Li
- Shenzhen Mindray Bio-Medical Electronics Co., Ltd., Shenzhen 518057, Guangdong, China
| | - Jinfeng Xu
- Department of Ultrasound, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong, China
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Tziotziou A, Hartman E, Korteland SA, van der Lugt A, van der Steen AFW, Daemen J, Bos D, Wentzel J, Akyildiz AC. Mechanical wall stress and wall shear stress are associated with atherosclerosis development in non-calcified coronary segments. Atherosclerosis 2023; 387:117387. [PMID: 38029610 DOI: 10.1016/j.atherosclerosis.2023.117387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Revised: 11/09/2023] [Accepted: 11/10/2023] [Indexed: 12/01/2023]
Abstract
BACKGROUND AND AIMS Atherosclerotic plaque onset and progression are known to be affected by local biomechanical factors. While the role of wall shear stress (WSS) has been studied, the impact of another biomechanical factor, namely mechanical wall stress (MWS), remains poorly understood. In this study, we investigated the association of MWS, independently and combined with WSS, towards atherosclerosis in coronary arteries. METHODS Thirty-four human coronary arteries were analyzed using near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) and optical coherence tomography (OCT) at baseline and after 12 months. Baseline WSS and MWS were calculated using computational models, and wall thickness (ΔWT) and lipid-rich necrotic core size (ΔLRNC) change were measured in non-calcified coronary segments. The arteries were further divided into 1.5 mm/45° sectors and categorized as plaque-free or plaque sectors. For each category, associations between biomechanical factors (WSS & MWS) and changes in coronary wall (ΔWT & ΔLRNC) were studied using linear mixed models. RESULTS In plaque-free sectors, higher MWS (p < 0.001) was associated with greater vessel wall growth. Plaque sectors demonstrated wall thickness reduction over time, likely due to medical therapy, where higher levels of WSS and WMS, individually and combined, (p < 0.05) were associated with a greater reduction. Sectors with low MWS combined with high WSS demonstrated the highest LRNC increase (p < 0.01). CONCLUSIONS In this study, we investigated the association of the (largely-overlooked) biomechanical factor MWS with coronary atherosclerosis, individually and combined with WSS. Our results demonstrated that both MWS and WSS significantly correlate with atherosclerotic plaque initiation and development.
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Affiliation(s)
- Aikaterini Tziotziou
- Department of Biomedical Engineering, Erasmus Medical Center, Rotterdam, the Netherlands
| | - Eline Hartman
- Department of Biomedical Engineering, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Cardiology, Erasmus Medical Center, Rotterdam, the Netherlands
| | - Suze-Anne Korteland
- Department of Biomedical Engineering, Erasmus Medical Center, Rotterdam, the Netherlands
| | - Aad van der Lugt
- Department of Radiology & Nuclear Medicine, Erasmus Medical Center, Rotterdam, the Netherlands
| | | | - Joost Daemen
- Department of Cardiology, Erasmus Medical Center, Rotterdam, the Netherlands
| | - Daniel Bos
- Department of Radiology & Nuclear Medicine, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands
| | - Jolanda Wentzel
- Department of Biomedical Engineering, Erasmus Medical Center, Rotterdam, the Netherlands
| | - Ali C Akyildiz
- Department of Biomedical Engineering, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Biomechanical Engineering, Delft University of Technology, Delft, the Netherlands.
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14
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Yang S, Koo BK. Coronary Physiology-Based Approaches for Plaque Vulnerability: Implications for Risk Prediction and Treatment Strategies. Korean Circ J 2023; 53:581-593. [PMID: 37653694 PMCID: PMC10475684 DOI: 10.4070/kcj.2023.0117] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Accepted: 05/19/2023] [Indexed: 09/02/2023] Open
Abstract
In the catheterization laboratory, the measurement of physiological indexes can help identify functionally significant lesions and has become one of the standard methods to guide treatment decision-making. Plaque vulnerability refers to a coronary plaque susceptible to rupture, enabling risk prediction before coronary events, and it can be detected by defining a certain type of plaque morphology on coronary imaging modalities. Although coronary physiology and plaque vulnerability have been considered different attributes of coronary artery disease, the underlying pathophysiological basis and clinical data indicate a strong correlation between coronary hemodynamic properties and vulnerable plaque. In prediction of coronary events, emerging data have suggested independent and additional implications of a physiology-based approach to a plaque-based approach. This review covers the fundamental interplay between coronary physiology and plaque morphology during disease progression with clinical data supporting this relationship and examines the clinical relevance of physiological indexes in prediction of clinical outcomes and therapeutic decision-making along with plaque vulnerability.
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Affiliation(s)
- Seokhun Yang
- Department of Internal Medicine and Cardiovascular Center, Seoul National University Hospital, Seoul National University of College Medicine, Seoul, Korea
| | - Bon-Kwon Koo
- Department of Internal Medicine and Cardiovascular Center, Seoul National University Hospital, Seoul National University of College Medicine, Seoul, Korea.
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15
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Pan J, Cai Y, Wu J, Lu Y, Li Z. Shear stress and plaque microenvironment induce heterogeneity: A multiscale microenvironment evolution model. COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE 2023; 235:107514. [PMID: 37037161 DOI: 10.1016/j.cmpb.2023.107514] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 03/19/2023] [Accepted: 03/27/2023] [Indexed: 05/08/2023]
Abstract
BACKGROUND Both clinical images and in vivo observations have demonstrated the heterogeneity in atherosclerotic plaque composition. However, the quantitative mechanisms that contribute to the heterogeneity, such as the wall shear stress (WSS) and the interplays among microenvironmental factors are still unclear. METHODS We develop a multiscale model coupling computational fluid dynamics, interactions of microenvironmental factors and evolutions of cellular behaviors to investigate the formation of plaque heterogeneity in a three-dimensional vessel segment. The model involves WSS, lipid deposition and inflammatory response to reveal the dynamic balance existed between the lipid metabolism and the phagocytosis of macrophages. RESULTS The dynamic balance in microenvironment is influenced by both the WSS and the interactions with microenvironmental factors, and consequently results in the longitudinal heterogeneity observed in plaque pathology. In addition, plaque heterogeneity can be reduced by decreasing low WSS area at downstream, as well as by altering the phagocytic abilities of macrophage on lipoproteins, which may be used to develop future plaque regression strategies. CONCLUSIONS This multiscale modeling provides a framework to understand the mechanisms in dynamics of plaque composition and also provides quantitative information to better risk stratification of plaque vulnerability in future clinical practice.
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Affiliation(s)
- Jichao Pan
- School of Biological Sciences and Medical Engineering, Southeast University, Nanjing 210096, China
| | - Yan Cai
- School of Biological Sciences and Medical Engineering, Southeast University, Nanjing 210096, China
| | - Jie Wu
- Key Laboratory of Hydrodynamics (Ministry of Education), School of Naval Architecture, Ocean and Civil Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Yunhao Lu
- School of Biological Sciences and Medical Engineering, Southeast University, Nanjing 210096, China
| | - Zhiyong Li
- School of Biological Sciences and Medical Engineering, Southeast University, Nanjing 210096, China; School of Mechanical, Medical and Process Engineering, Queensland University of Technology, Brisbane, QLD 4001, Australia.
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16
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Khil J, Kim SM, Chang J, Choi S, Lee G, Son JS, Park SM, Keum N. Changes in total cholesterol level and cardiovascular disease risk among type 2 diabetes patients. Sci Rep 2023; 13:8342. [PMID: 37221278 DOI: 10.1038/s41598-023-33743-6] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Accepted: 04/18/2023] [Indexed: 05/25/2023] Open
Abstract
Despite many diabetic patients having hypercholesterolemia, the association of total cholesterol (TC) levels with CVD risk in type 2 diabetes (T2D) patients is unclear. Diagnosis of type 2 diabetes often leads to changes in total cholesterol (TC) levels. Thus, we examined whether changes in TC levels from pre- to post-diagnosis of T2D were associated with CVD risk. From the National Health Insurance Service Cohort, 23,821 individuals diagnosed with T2D from 2003 to 2012 were followed-up for non-fatal CVD incidence through 2015. Two measurements of TC, 2 years before and after T2D diagnosis, were classified into 3 levels (low, middle, high) to define changes in cholesterol levels. Cox proportional hazards regression was performed to estimate adjusted hazards ratios (aHRs) and 95% confidence intervals (CIs) for the associations between changes in cholesterol levels and CVD risk. Subgroup analyses were performed by use of lipid-lowering drugs. Compared with low-low, aHR of CVD was 1.31 [1.10-1.56] for low-middle and 1.80 [1.15-2.83] for low-high. Compared with middle-middle, aHR of CVD was 1.10 [0.92-1.31] for middle-high but 0.83 [0.73-0.94] for middle-low. Compared with high-high, aHR of CVD was 0.68 [0.56-0.83] for high-middle and 0.65 [0.49-0.86] for high-low. The associations were observed regardless of use of lipid-lowering drugs. For diabetic patients, management of TC levels may be important to lower CVD risk.
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Affiliation(s)
- Jaewon Khil
- Department of Food Science and Biotechnology, Dongguk University Graduate School, Seoul, Korea
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Sung Min Kim
- Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea
| | - Jooyoung Chang
- Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea
| | - Seulggie Choi
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | | | - Joung Sik Son
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea
| | - Sang Min Park
- Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea.
- Department of Family Medicine, Seoul National University Hospital, Seoul, Korea.
| | - NaNa Keum
- Department of Food Science and Biotechnology, Dongguk University Graduate School, Seoul, Korea.
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
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17
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Zhou M, Yu Y, Chen R, Liu X, Hu Y, Ma Z, Gao L, Jian W, Wang L. Wall shear stress and its role in atherosclerosis. Front Cardiovasc Med 2023; 10:1083547. [PMID: 37077735 PMCID: PMC10106633 DOI: 10.3389/fcvm.2023.1083547] [Citation(s) in RCA: 74] [Impact Index Per Article: 37.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2022] [Accepted: 03/09/2023] [Indexed: 04/05/2023] Open
Abstract
Atherosclerosis (AS) is the major form of cardiovascular disease and the leading cause of morbidity and mortality in countries around the world. Atherosclerosis combines the interactions of systemic risk factors, haemodynamic factors, and biological factors, in which biomechanical and biochemical cues strongly regulate the process of atherosclerosis. The development of atherosclerosis is directly related to hemodynamic disorders and is the most important parameter in the biomechanics of atherosclerosis. The complex blood flow in arteries forms rich WSS vectorial features, including the newly proposed WSS topological skeleton to identify and classify the WSS fixed points and manifolds in complex vascular geometries. The onset of plaque usually occurs in the low WSS area, and the plaque development alters the local WSS topography. low WSS promotes atherosclerosis, while high WSS prevents atherosclerosis. Upon further progression of plaques, high WSS is associated with the formation of vulnerable plaque phenotype. Different types of shear stress can lead to focal differences in plaque composition and to spatial variations in the susceptibility to plaque rupture, atherosclerosis progression and thrombus formation. WSS can potentially gain insight into the initial lesions of AS and the vulnerable phenotype that gradually develops over time. The characteristics of WSS are studied through computational fluid dynamics (CFD) modeling. With the continuous improvement of computer performance-cost ratio, WSS as one of the effective parameters for early diagnosis of atherosclerosis has become a reality and will be worth actively promoting in clinical practice. The research on the pathogenesis of atherosclerosis based on WSS is gradually an academic consensus. This article will comprehensively review the systemic risk factors, hemodynamics and biological factors involved in the formation of atherosclerosis, and combine the application of CFD in hemodynamics, focusing on the mechanism of WSS and the complex interactions between WSS and plaque biological factors. It is expected to lay a foundation for revealing the pathophysiological mechanisms related to abnormal WSS in the progression and transformation of human atherosclerotic plaques.
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Affiliation(s)
- Manli Zhou
- College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
| | - Yunfeng Yu
- College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
- The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, China
| | - Ruiyi Chen
- The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, China
| | - Xingci Liu
- College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
- The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, China
| | - Yilei Hu
- College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
| | - Zhiyan Ma
- College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
| | - Lingwei Gao
- College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
| | - Weixiong Jian
- College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
- National Key Discipline of Traditional Chinese Medicine Diagnostics, Hunan Provincial Key Laboratory, Hunan University of Chinese Medicine, Changsha, China
- Correspondence: Weixiong Jian Liping Wang
| | - Liping Wang
- College of Rehabilitation Medicine and Health Care, Hunan University of Medicine, Huaihua, China
- Correspondence: Weixiong Jian Liping Wang
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Karageorgos GM, Kemper P, Lee C, Weber R, Kwon N, Meshram N, Mobadersany N, Grondin J, Marshall RS, Miller EC, Konofagou EE. Adaptive Wall Shear Stress Imaging in Phantoms, Simulations and In Vivo. IEEE Trans Biomed Eng 2023; 70:154-165. [PMID: 35776824 PMCID: PMC10103592 DOI: 10.1109/tbme.2022.3186854] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
WSS measurement is challenging since it requires sensitive flow measurements at a distance close to the wall. The aim of this study is to develop an ultrasound imaging technique which combines vector flow imaging with an unsupervised data clustering approach that automatically detects the region close to the wall with optimally linear flow profile, to provide direct and robust WSS estimation. The proposed technique was evaluated in phantoms, mimicking normal and atherosclerotic vessels, and spatially registered Fluid Structure Interaction (FSI) simulations. A relative error of 6.7% and 19.8% was obtained for peak systolic (WSSPS) and end diastolic (WSSED) WSS in the straight phantom, while in the stenotic phantom, a good similarity was found between measured and simulated WSS distribution, with a correlation coefficient, R, of 0.89 and 0.85 for WSSPS and WSSED, respectively. Moreover, the feasibility of the technique to detect pre-clinical atherosclerosis was tested in an atherosclerotic swine model. Six swines were fed atherogenic diet, while their left carotid artery was ligated in order to disturb flow patterns. Ligated arterial segments that were exposed to low WSSPS and WSS characterized by high frequency oscillations at baseline, developed either moderately or highly stenotic plaques (p < 0.05). Finally, feasibility of the technique was demonstrated in normal and atherosclerotic human subjects. Atherosclerotic carotid arteries with low stenosis had lower WSSPS as compared to control subjects (p < 0.01), while in one subject with high stenosis, elevated WSS was found on an arterial segment, which coincided with plaque rupture site, as determined through histological examination.
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Woo HG, Kim HG, Lee KM, Ha SH, Jo H, Heo SH, Chang DI, Liebeskind DS, Kim BJ. Wall Shear Stress Associated with Stroke Occurrence and Mechanisms in Middle Cerebral Artery Atherosclerosis. J Stroke 2023; 25:132-140. [PMID: 36746383 PMCID: PMC9911838 DOI: 10.5853/jos.2022.02754] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Revised: 11/27/2022] [Accepted: 12/08/2022] [Indexed: 02/03/2023] Open
Abstract
BACKGROUND AND PURPOSE Various mechanisms are involved in the etiology of stroke caused by atherosclerosis of the middle cerebral artery (MCA). Here, we compared differences in plaque nature and hemodynamic parameters according to stroke mechanism in patients with MCA atherosclerosis. METHODS Consecutive patients with asymptomatic and symptomatic MCA atherosclerosis (≥50% stenosis) were enrolled. MCA plaque characteristics (location and plaque enhancement) and wall shear stress (WSS) were measured using high-resolution vessel wall and four-dimensional flow magnetic resonance imaging, respectively, at five points (initial, upstream, minimal lumen, downstream, and terminal). These parameters were compared between patients with asymptomatic and symptomatic MCA atherosclerosis with infarctions of different mechanisms (artery-to-artery embolism vs. local branch occlusion). RESULTS In total, 110 patients (46 asymptomatic, 32 artery-to-artery embolisms, and 32 local branch occlusions) were investigated. Plaques were evenly distributed in the MCA of patients with asymptomatic MCA atherosclerosis, more commonly observed in the distal MCA of patients with artery-to-artery embolism, and in the middle MCA of patients with local branch occlusion. Maximum WSS and plaque enhancement were more prominent in the minimum lumen area of patients with asymptomatic MCA atherosclerosis or those with local branch occlusion, and were more prominent in the upstream area in those with artery-to-artery embolism. The elevated variability in the maximum WSS was related to stroke caused by artery-to-artery embolism. CONCLUSION Stroke caused by artery-to-artery embolism was related to plaque enhancement and the highest maximum WSS at the upstream point of the plaque, and was associated with elevated variability of maximum WSS.
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Affiliation(s)
- Ho Geol Woo
- Department of Neurology, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul, Korea
| | - Hyug-Gi Kim
- Department of Radiology, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul, Korea
| | - Kyung Mi Lee
- Department of Radiology, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul, Korea
| | - Sang Hee Ha
- Department of Neurology, Asan Medical Center, Seoul, Korea
| | - HangJin Jo
- Department of Mechanical Engineering & Division of Advanced Nuclear Engineering, POSTECH, Pohang, Korea
| | - Sung Hyuk Heo
- Department of Neurology, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul, Korea
| | - Dae-il Chang
- Department of Neurology, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul, Korea
| | - David S. Liebeskind
- Department of Neurology, University of California in Los Angeles, Los Angeles, CA, USA
| | - Bum Joon Kim
- Department of Neurology, Asan Medical Center, Seoul, Korea
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20
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Warren JL, Yoo JE, Meyer CA, Molony DS, Samady H, Hayenga HN. Automated finite element approach to generate anatomical patient-specific biomechanical models of atherosclerotic arteries from virtual histology-intravascular ultrasound. FRONTIERS IN MEDICAL TECHNOLOGY 2022; 4:1008540. [PMID: 36523426 PMCID: PMC9745200 DOI: 10.3389/fmedt.2022.1008540] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Accepted: 11/07/2022] [Indexed: 11/16/2023] Open
Abstract
Despite advancements in early detection and treatment, atherosclerosis remains the leading cause of death across all cardiovascular diseases (CVD). Biomechanical analysis of atherosclerotic lesions has the potential to reveal biomechanically instable or rupture-prone regions. Treatment decisions rarely consider the biomechanics of the stenosed lesion due in-part to difficulties in obtaining this information in a clinical setting. Previous 3D FEA approaches have incompletely incorporated the complex curvature of arterial geometry, material heterogeneity, and use of patient-specific data. To address these limitations and clinical need, herein we present a user-friendly fully automated program to reconstruct and simulate the wall mechanics of patient-specific atherosclerotic coronary arteries. The program enables 3D reconstruction from patient-specific data with heterogenous tissue assignment and complex arterial curvature. Eleven arteries with coronary artery disease (CAD) underwent baseline and 6-month follow-up angiographic and virtual histology-intravascular ultrasound (VH-IVUS) imaging. VH-IVUS images were processed to remove background noise, extract VH plaque material data, and luminal and outer contours. Angiography data was used to orient the artery profiles along the 3D centerlines. The resulting surface mesh is then resampled for uniformity and tetrahedralized to generate the volumetric mesh using TetGen. A mesh convergence study revealed edge lengths between 0.04 mm and 0.2 mm produced constituent volumes that were largely unchanged, hence, to save computational resources, a value of 0.2 mm was used throughout. Materials are assigned and finite element analysis (FEA) is then performed to determine stresses and strains across the artery wall. In a representative artery, the highest average effective stress was in calcium elements with 235 kPa while necrotic elements had the lowest average stress, reaching as low as 0.79 kPa. After applying nodal smoothening, the maximum effective stress across 11 arteries remained below 288 kPa, implying biomechanically stable plaques. Indeed, all atherosclerotic plaques remained unruptured at the 6-month longitudinal follow up diagnosis. These results suggest our automated analysis may facilitate assessment of atherosclerotic plaque stability.
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Affiliation(s)
- Jeremy L. Warren
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, United States
| | - John E. Yoo
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, United States
| | - Clark A. Meyer
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, United States
| | - David S. Molony
- Northeast Georgia Health System, Georgia Heart Institute, Gainesville, GA, United States
| | - Habib Samady
- Northeast Georgia Health System, Georgia Heart Institute, Gainesville, GA, United States
| | - Heather N. Hayenga
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, United States
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21
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Avtaar Singh SS, Nappi F. Pathophysiology and Outcomes of Endothelium Function in Coronary Microvascular Diseases: A Systematic Review of Randomized Controlled Trials and Multicenter Study. Biomedicines 2022; 10:3010. [PMID: 36551766 PMCID: PMC9775403 DOI: 10.3390/biomedicines10123010] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Revised: 11/17/2022] [Accepted: 11/18/2022] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND Coronary macrovascular disease is a concept that has been well-studied within the literature and has long been the subject of debates surrounding coronary artery bypass grafting (CABG) vs. Percutaneous Coronary Intervention (PCI). ISCHEMIA trial reported no statistical difference in the primary clinical endpoint between initial invasive management and initial conservative management, while in the ORBITA trial PCI did not improve angina frequency score significantly more than placebo, albeit PCI resulted in more patient-reported freedom from angina than placebo. However, these results did not prove the superiority of the PCI against OMT, therefore do not indicate the benefit of PCI vs. the OMT. Please rephrase the sentence. We reviewed the role of different factors responsible for endothelial dysfunction from recent randomized clinical trials (RCTs) and multicentre studies. METHODS A detailed search strategy was performed using a dataset that has previously been published. Data of pooled analysis include research articles (human and animal models), CABG, and PCI randomized controlled trials (RCTs). Details of the search strategy and the methods used for data pooling have been published previously and registered with Open-Source Framework. RESULTS The roles of nitric oxide (NO), endothelium-derived contracting factors (EDCFs), and vasodilator prostaglandins (e.g., prostacyclin), as well as endothelium-dependent hyperpolarization (EDH) factors, are crucial for the maintenance of vasomotor tone within the coronary vasculature. These homeostatic mechanisms are affected by sheer forces and other several factors that are currently being studied, such as vaping. The role of intracoronary testing is crucial when determining the effects of therapeutic medications with further studies on the horizon. CONCLUSION The true impact of coronary microvascular dysfunction (CMD) is perhaps underappreciated, which supports the role of medical therapy in determining outcomes. Ongoing trials are underway to further investigate the role of therapeutic agents in secondary prevention.
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Affiliation(s)
| | - Francesco Nappi
- Department of Cardiac Surgery, Centre Cardiologique du Nord of Saint-Denis, 93200 Saint-Denis, France
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22
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Vesterbekkmo EK, Madssen E, Aamot Aksetøy I, Follestad T, Nilsen HO, Hegbom K, Wisløff U, Wiseth R. CENIT (Impact of Cardiac Exercise Training on Lipid Content in Coronary Atheromatous Plaques Evaluated by Near‐Infrared Spectroscopy): A Randomized Trial. J Am Heart Assoc 2022; 11:e024705. [PMID: 35574968 PMCID: PMC9238565 DOI: 10.1161/jaha.121.024705] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Background The effect of physical exercise on lipid content of coronary artery plaques is unknown. With near infrared spectroscopy we measured the effect of high intensity interval training (HIIT) on lipid content in coronary plaques in patients with stable coronary artery disease following percutaneous coronary intervention. Methods and Results In CENIT (Impact of Cardiac Exercise Training on Lipid Content in Coronary Atheromatous Plaques Evaluated by Near‐Infrared Spectroscopy) 60 patients were randomized to 6 months supervised HIIT or to a control group. The primary end point was change in lipid content measured as maximum lipid core burden index at 4 mm (maxLCBI4mm). A predefined cutoff of maxLCBI4mm >100 was required for inclusion in the analysis. Forty‐nine patients (HIIT=20, usual care=29) had maxLCBI4mm >100 at baseline. Change in maxLCBI4mm did not differ between groups (−1.2, 95% CI, −65.8 to 63.4, P=0.97). The estimated reduction in maxLCBI4mm was −47.7 (95% CI, −100.3 to 5.0, P=0.075) and −46.5 (95% CI, −87.5 to −5.4, P=0.027) after HIIT and in controls, respectively. A negative correlation was observed between change in peak oxygen uptake (VO2peak) and change in lipid content (Spearman’s correlation −0.44, P=0.009). With an increase in VO2peak above 1 metabolic equivalent task, maxLCBI4mm was on average reduced by 142 (−8 to −262), whereas the change was −3.2 (154 to −255) with increased VO2peak below 1 metabolic equivalent task. Conclusions Six months of HIIT following percutaneous coronary intervention did not reduce lipid content in coronary plaques compared with usual care. A moderate negative correlation between increase in VO2peak and change in lipid content generates the hypothesis that exercise with a subsequent increase in fitness may reduce lipid content in coronary atheromatous plaques. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02494947.
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Affiliation(s)
- Elisabeth Kleivhaug Vesterbekkmo
- Clinic of Cardiology St. Olavs University Hospital Trondheim Norway
- Department of Circulation and Medical Imaging Norwegian University of Science and Technology Trondheim Norway
- National Advisory Unit on Exercise Training as Medicine for Cardiopulmonary Conditions Trondheim Norway
| | - Erik Madssen
- Clinic of Cardiology St. Olavs University Hospital Trondheim Norway
- Department of Circulation and Medical Imaging Norwegian University of Science and Technology Trondheim Norway
| | - Inger‐Lise Aamot Aksetøy
- Clinic of Cardiology St. Olavs University Hospital Trondheim Norway
- Department of Circulation and Medical Imaging Norwegian University of Science and Technology Trondheim Norway
- National Advisory Unit on Exercise Training as Medicine for Cardiopulmonary Conditions Trondheim Norway
| | - Turid Follestad
- Department of Clinical and Molecular Medicine Norwegian University of Science and Technology Trondheim Norway
| | - Hans Olav Nilsen
- Clinic of Cardiology St. Olavs University Hospital Trondheim Norway
- Department of Circulation and Medical Imaging Norwegian University of Science and Technology Trondheim Norway
| | - Knut Hegbom
- Clinic of Cardiology St. Olavs University Hospital Trondheim Norway
| | - Ulrik Wisløff
- Department of Circulation and Medical Imaging Norwegian University of Science and Technology Trondheim Norway
- School of Human Movement and Nutrition Science University of Queensland Australia
| | - Rune Wiseth
- Clinic of Cardiology St. Olavs University Hospital Trondheim Norway
- Department of Circulation and Medical Imaging Norwegian University of Science and Technology Trondheim Norway
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23
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Guo X, Maehara A, Yang M, Wang L, Zheng J, Samady H, Mintz GS, Giddens DP, Tang D. Predicting Coronary Stenosis Progression Using Plaque Fatigue From IVUS-Based Thin-Slice Models: A Machine Learning Random Forest Approach. Front Physiol 2022; 13:912447. [PMID: 35620594 PMCID: PMC9127388 DOI: 10.3389/fphys.2022.912447] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Accepted: 04/22/2022] [Indexed: 11/22/2022] Open
Abstract
Introduction: Coronary stenosis due to atherosclerosis restricts blood flow. Stenosis progression would lead to increased clinical risk such as heart attack. Although many risk factors were found to contribute to atherosclerosis progression, factors associated with fatigue is underemphasized. Our goal is to investigate the relationship between fatigue and stenosis progression based on in vivo intravascular ultrasound (IVUS) images and finite element models. Methods: Baseline and follow-up in vivo IVUS and angiography data were acquired from seven patients using Institutional Review Board approved protocols with informed consent obtained. Three hundred and five paired slices at baseline and follow-up were matched and used for plaque modeling and analysis. IVUS-based thin-slice models were constructed to obtain the coronary biomechanics and stress/strain amplitudes (stress/strain variations in one cardiac cycle) were used as the measurement of fatigue. The change of lumen area (DLA) from baseline to follow-up were calculated to measure stenosis progression. Nineteen morphological and biomechanical factors were extracted from 305 slices at baseline. Correlation analyses of these factors with DLA were performed. Random forest (RF) method was used to fit morphological and biomechanical factors at baseline to predict stenosis progression during follow-up. Results: Significant correlations were found between stenosis progression and maximum stress amplitude, average stress amplitude and average strain amplitude (p < 0.05). After factors selection implemented by random forest (RF) method, eight morphological and biomechanical factors were selected for classification prediction of stenosis progression. Using eight factors including fatigue, the overall classification accuracy, sensitivity and specificity of stenosis progression prediction with RF method were 83.61%, 86.25% and 80.69%, respectively. Conclusion: Fatigue correlated positively with stenosis progression. Factors associated with fatigue could contribute to better prediction for atherosclerosis progression.
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Affiliation(s)
- Xiaoya Guo
- School of Science, Nanjing University of Posts and Telecommunications, Nanjing, China
| | - Akiko Maehara
- The Cardiovascular Research Foundation, Columbia University, New York, NY, United States
| | - Mingming Yang
- Department of Cardiology, Zhongda Hospital, Southeast University, Nanjing, China
| | - Liang Wang
- School of Biological Science and Medical Engineering, Southeast University, Nanjing, China
| | - Jie Zheng
- Mallinckrodt Institute of Radiology, Washington University, St. Louis, MO, United States
| | - Habib Samady
- Department of Medicine, Emory University School of Medicine, Atlanta, GA, United States
| | - Gary S. Mintz
- The Cardiovascular Research Foundation, Columbia University, New York, NY, United States
| | - Don P. Giddens
- Department of Medicine, Emory University School of Medicine, Atlanta, GA, United States
- The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, United States
| | - Dalin Tang
- School of Biological Science and Medical Engineering, Southeast University, Nanjing, China
- Mathematical Sciences Department, Worcester Polytechnic Institute, Worcester, MA, United States
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24
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Milewski M, Ng CKJ, Gąsior P, Lian SS, Qian SX, Lu S, Foin N, Kedhi E, Wojakowski W, Ang HY. Polymer Coating Integrity, Thrombogenicity and Computational Fluid Dynamics Analysis of Provisional Stenting Technique in the Left Main Bifurcation Setting: Insights from an In-Vitro Model. Polymers (Basel) 2022; 14:polym14091715. [PMID: 35566886 PMCID: PMC9099851 DOI: 10.3390/polym14091715] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Revised: 04/19/2022] [Accepted: 04/20/2022] [Indexed: 02/04/2023] Open
Abstract
Currently, the provisional stenting technique is the gold standard in revascularization of lesions located in the left main (LM) bifurcation. The benefit of the routine kissing balloon technique (KBI) in bifurcation lesions is still debated, particularly following the single stent treatment. We compared the latest-generation drug-eluting stent (DES) with no side branch (SB) dilatation “keep it open” technique (KIO) vs. KBI technique vs. bifurcation dedicated drug-eluting stent (BD-DES) implantation. In vitro testing was performed under a static condition in bifurcation silicone vessel models. All the devices were implanted in accordance with the manufacturers’ recommendations. As a result, computational fluid dynamics (CFD) analysis demonstrated a statistically higher area of high shear rate in the KIO group when compared to KBI. Likewise, the maximal shear rate was higher in number in the KIO group. Floating strut count based on the OCT imaging was significantly higher in KIO than in KBI and BD-DES. Furthermore, according to OTC analysis, the thrombus area was numerically higher in both KIO and KBI than in the BD-DES. Scanning electron microscopy (SEM) analysis shows the highest degree of strut coating damage in the KBI group. This model demonstrated significant differences in CFD analysis at SB ostia with and without KBI optimization in the LM setting. The adoption of KBI was related to a meaningful reduction of flow disturbances in conventional DES and achieved results similar to BD-DES.
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Affiliation(s)
- Marek Milewski
- Division of Cardiology and Structural Heart Diseases, Medical University of Silesia in Katowice, 40-635 Katowice, Poland; (M.M.); (P.G.); (E.K.); (W.W.)
| | - Chen Koon Jaryl Ng
- National Heart Research Institute Singapore, National Heart Centre Singapore, 5 Hospital Drive, Singapore 169609, Singapore; (C.K.J.N.); (S.L.); (N.F.)
| | - Pawel Gąsior
- Division of Cardiology and Structural Heart Diseases, Medical University of Silesia in Katowice, 40-635 Katowice, Poland; (M.M.); (P.G.); (E.K.); (W.W.)
| | - Shaoliang Shawn Lian
- Department of Biomedical Engineering, National University of Singapore, Singapore 119077, Singapore;
| | - Su Xiao Qian
- Division of Chemical and Biomolecular Engineering, Nanyang Technological University, Singapore 637459, Singapore;
| | - Shengjie Lu
- National Heart Research Institute Singapore, National Heart Centre Singapore, 5 Hospital Drive, Singapore 169609, Singapore; (C.K.J.N.); (S.L.); (N.F.)
| | - Nicolas Foin
- National Heart Research Institute Singapore, National Heart Centre Singapore, 5 Hospital Drive, Singapore 169609, Singapore; (C.K.J.N.); (S.L.); (N.F.)
- Duke-NUS Medical School, Singapore 169857, Singapore
| | - Elvin Kedhi
- Division of Cardiology and Structural Heart Diseases, Medical University of Silesia in Katowice, 40-635 Katowice, Poland; (M.M.); (P.G.); (E.K.); (W.W.)
- Erasmus Hospital, Université libre de Bruxelles (ULB), 1070 Brussels, Belgium
| | - Wojciech Wojakowski
- Division of Cardiology and Structural Heart Diseases, Medical University of Silesia in Katowice, 40-635 Katowice, Poland; (M.M.); (P.G.); (E.K.); (W.W.)
| | - Hui Ying Ang
- National Heart Research Institute Singapore, National Heart Centre Singapore, 5 Hospital Drive, Singapore 169609, Singapore; (C.K.J.N.); (S.L.); (N.F.)
- Department of Biomedical Engineering, National University of Singapore, Singapore 119077, Singapore;
- Duke-NUS Medical School, Singapore 169857, Singapore
- Correspondence: ; Tel.: +65-6704-2343; Fax: +65-6704-2210
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25
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Thondapu V, Shishikura D, Dijkstra J, Zhu SJ, Revalor E, Serruys PW, van Gaal WJ, Poon EKW, Ooi A, Barlis P. Non-Newtonian Endothelial Shear Stress Simulation: Does It Matter? Front Cardiovasc Med 2022; 9:835270. [PMID: 35497989 PMCID: PMC9046559 DOI: 10.3389/fcvm.2022.835270] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Accepted: 03/09/2022] [Indexed: 12/05/2022] Open
Abstract
Patient-specific coronary endothelial shear stress (ESS) calculations using Newtonian and non-Newtonian rheological models were performed to assess whether the common assumption of Newtonian blood behavior offers similar results to a more realistic but computationally expensive non-Newtonian model. 16 coronary arteries (from 16 patients) were reconstructed from optical coherence tomographic (OCT) imaging. Pulsatile CFD simulations using Newtonian and the Quemada non-Newtonian model were performed. Endothelial shear stress (ESS) and other indices were compared. Exploratory indices including local blood viscosity (LBV) were calculated from non-Newtonian simulation data. Compared to the Newtonian results, the non-Newtonian model estimates significantly higher time-averaged ESS (1.69 (IQR 1.36)Pa versus 1.28 (1.16)Pa, p < 0.001) and ESS gradient (0.90 (1.20)Pa/mm versus 0.74 (1.03)Pa/mm, p < 0.001) throughout the cardiac cycle, under-estimating the low ESS (<1Pa) area (37.20 ± 13.57% versus 50.43 ± 14.16%, 95% CI 11.28-15.18, p < 0.001). Similar results were also found in the idealized artery simulations with non-Newtonian median ESS being higher than the Newtonian median ESS (healthy segments: 0.8238Pa versus 0.6618Pa, p < 0.001 proximal; 0.8179Pa versus 0.6610Pa, p < 0.001 distal; stenotic segments: 0.8196Pa versus 0.6611Pa, p < 0.001 proximal; 0.2546Pa versus 0.2245Pa, p < 0.001 distal) On average, the non-Newtonian model has a LBV of 1.45 times above the Newtonian model with an average peak LBV of 40-fold. Non-Newtonian blood model estimates higher quantitative ESS values than the Newtonian model. Incorporation of non-Newtonian blood behavior may improve the accuracy of ESS measurements. The non-Newtonian model also allows calculation of exploratory viscosity-based hemodynamic indices, such as local blood viscosity, which may offer additional information to detect underlying atherosclerosis.
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Affiliation(s)
- Vikas Thondapu
- Department of Medicine, Faculty of Medicine, Melbourne Medical School, Dentistry and Health Sciences, University of Melbourne, Parkville, VIC, Australia
- Department of Mechanical Engineering, Melbourne School of Engineering, University of Melbourne, Parkville, VIC, Australia
- Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT, United States
| | - Daisuke Shishikura
- Department of Cardiology, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Jouke Dijkstra
- Department of Radiology, Division of Image Processing, Leiden University Medical Center, Leiden, Netherlands
| | - Shuang J. Zhu
- Department of Mechanical Engineering, Melbourne School of Engineering, University of Melbourne, Parkville, VIC, Australia
| | - Eve Revalor
- Department of Medicine, Faculty of Medicine, Melbourne Medical School, Dentistry and Health Sciences, University of Melbourne, Parkville, VIC, Australia
- Department of Biomedical Engineering, Melbourne School of Engineering, University of Melbourne, Parkville, VIC, Australia
| | - Patrick W. Serruys
- Department of Cardiology, National University of Ireland Galway (NUIG), Galway, Ireland
- National Heart and Lung Institute, Imperial College London, London, United Kingdom
| | - William J. van Gaal
- Department of Medicine, Faculty of Medicine, Melbourne Medical School, Dentistry and Health Sciences, University of Melbourne, Parkville, VIC, Australia
- Department of Cardiology, Northern Hospital, Epping, NSW, Australia
| | - Eric K. W. Poon
- Department of Medicine, Faculty of Medicine, Melbourne Medical School, Dentistry and Health Sciences, University of Melbourne, Parkville, VIC, Australia
| | - Andrew Ooi
- Department of Mechanical Engineering, Melbourne School of Engineering, University of Melbourne, Parkville, VIC, Australia
| | - Peter Barlis
- Department of Medicine, Faculty of Medicine, Melbourne Medical School, Dentistry and Health Sciences, University of Melbourne, Parkville, VIC, Australia
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26
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Lv R, Wang L, Maehara A, Guo X, Zheng J, Samady H, Giddens DP, Mintz GS, Stone GW, Tang D. Image-based biomechanical modeling for coronary atherosclerotic plaque progression and vulnerability prediction. Int J Cardiol 2022; 352:1-8. [PMID: 35149139 DOI: 10.1016/j.ijcard.2022.02.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Revised: 02/04/2022] [Accepted: 02/07/2022] [Indexed: 01/01/2023]
Abstract
Atherosclerotic plaque progression and rupture play an important role in cardiovascular disease development and the final drastic events such as heart attack and stroke. Medical imaging and image-based computational modeling methods advanced considerably in recent years to quantify plaque morphology and biomechanical conditions and gain a better understanding of plaque evolution and rupture process. This article first briefly reviewed clinical imaging techniques for coronary thin-cap fibroatheroma (TCFA) plaques used in image-based computational modeling. This was followed by a summary of different types of biomechanical models for coronary plaques. Plaque progression and vulnerability prediction studies based on image-based computational modeling were reviewed and compared. Much progress has been made and a reasonable high prediction accuracy has been achieved. However, there are still some inconsistencies in existing literature on the impact of biomechanical and morphological factors on future plaque behavior, and it is very difficult to perform direct comparison analysis as differences like image modality, biomechanical factors selection, predictive models, and progression/vulnerability measures exist among these studies. Encouraging data and model sharing across the research community would partially resolve these differences, and possibly lead to clearer assertive conclusions. In vivo image-based computational modeling could be used as a powerful tool for quantitative assessment of coronary plaque vulnerability for potential clinical applications.
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Affiliation(s)
- Rui Lv
- School of Biological Science & Medical Engineering, Southeast University, Nanjing, China
| | - Liang Wang
- School of Biological Science & Medical Engineering, Southeast University, Nanjing, China.
| | - Akiko Maehara
- The Cardiovascular Research Foundation, Columbia University, New York, USA.
| | - Xiaoya Guo
- School of Science, Nanjing University of Posts and Telecommunications, Nanjing 210023, China
| | - Jie Zheng
- Mallinckrodt Institute of Radiology, Washington University, St. Louis, MO, USA.
| | - Habib Samady
- School of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
| | - Don P Giddens
- The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
| | - Gary S Mintz
- The Cardiovascular Research Foundation, Columbia University, New York, USA
| | - Gregg W Stone
- The Cardiovascular Research Foundation, Columbia University, New York, USA; The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, NY, New York, USA.
| | - Dalin Tang
- School of Biological Science & Medical Engineering, Southeast University, Nanjing, China; Mathematical Sciences Department, Worcester Polytechnic Institute, Worcester, USA.
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27
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Godo S, Takahashi J, Yasuda S, Shimokawa H. Endothelium in Coronary Macrovascular and Microvascular Diseases. J Cardiovasc Pharmacol 2021; 78:S19-S29. [PMID: 34840261 PMCID: PMC8647695 DOI: 10.1097/fjc.0000000000001089] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Accepted: 06/05/2021] [Indexed: 01/09/2023]
Abstract
ABSTRACT The endothelium plays a pivotal role in the regulation of vascular tone by synthesizing and liberating endothelium-derived relaxing factors inclusive of vasodilator prostaglandins (eg, prostacyclin), nitric oxide (NO), and endothelium-dependent hyperpolarization factors in a distinct blood vessel size-dependent manner. Large conduit arteries are predominantly regulated by NO and small resistance arteries by endothelium-dependent hyperpolarization factors. Accumulating evidence over the past few decades has demonstrated that endothelial dysfunction and coronary vasomotion abnormalities play crucial roles in the pathogenesis of various cardiovascular diseases. Structural and functional alterations of the coronary microvasculature have been coined as coronary microvascular dysfunction (CMD), which is highly prevalent and associated with adverse clinical outcomes in many clinical settings. The major mechanisms of coronary vasomotion abnormalities include enhanced coronary vasoconstrictive reactivity at epicardial and microvascular levels, impaired endothelium-dependent and endothelium-independent coronary vasodilator capacities, and elevated coronary microvascular resistance caused by structural factors. Recent experimental and clinical research has highlighted CMD as the systemic small artery disease beyond the heart, emerging modulators of vascular functions, novel insights into the pathogenesis of cardiovascular diseases associated with CMD, and potential therapeutic interventions to CMD with major clinical implications. In this article, we will summarize the current knowledge on the endothelial modulation of vascular tone and the pathogenesis of coronary macrovascular and microvascular diseases from bench to bedside, with a special emphasis placed on the mechanisms and clinical implications of CMD.
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Affiliation(s)
- Shigeo Godo
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; and
| | - Jun Takahashi
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; and
| | - Satoshi Yasuda
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; and
| | - Hiroaki Shimokawa
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; and
- Graduate School, International University of Health and Welfare, Narita, Japan
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28
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Adriaenssens T, Allard-Ratick MP, Thondapu V, Sugiyama T, Raffel OC, Barlis P, Poon EKW, Araki M, Nakajima A, Minami Y, Takano M, Kurihara O, Fuster V, Kakuta T, Jang IK. Optical Coherence Tomography of Coronary Plaque Progression and Destabilization: JACC Focus Seminar Part 3/3. J Am Coll Cardiol 2021; 78:1275-1287. [PMID: 34531029 DOI: 10.1016/j.jacc.2021.07.032] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Revised: 07/07/2021] [Accepted: 07/13/2021] [Indexed: 10/20/2022]
Abstract
The development of optical coherence tomography (OCT) has revolutionized our understanding of coronary artery disease. In vivo OCT research has paralleled with advances in computational fluid dynamics, providing additional insights in the various hemodynamic factors influencing plaque growth and stability. Recent OCT studies introduced a new concept of plaque healing in relation to clinical presentation. In addition to known mechanisms of acute coronary syndromes such as plaque rupture and plaque erosion, a new classification of calcified plaque was recently reported. This review will focus on important new insights that OCT has provided in recent years into coronary plaque development, progression, and destabilization, with a focus on the role of local hemodynamics and endothelial shear stress, the layered plaque (signature of previous subclinical plaque destabilization and healing), and the calcified culprit plaque.
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Affiliation(s)
- Tom Adriaenssens
- Department of Cardiovascular Medicine, University Hospitals Leuven, Leuven, Belgium
| | - Marc P Allard-Ratick
- Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Vikas Thondapu
- Cardiovascular Imaging Research Center, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Tomoyo Sugiyama
- Department of Cardiology, Tsuchiura Kyodo General Hospital, Tsuchiura, Ibaraki, Japan
| | | | - Peter Barlis
- Department of Medicine, St Vincent's Hospital, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Australia
| | - Eric K W Poon
- Department of Medicine, St Vincent's Hospital, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Australia
| | - Makoto Araki
- Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Akihiro Nakajima
- Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Yoshiyasu Minami
- Department of Cardiovascular Medicine, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
| | - Masamichi Takano
- Cardiovascular Center, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Chiba, Japan
| | - Osamu Kurihara
- Cardiovascular Center, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Chiba, Japan
| | - Valentin Fuster
- Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York City, New York, USA; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
| | - Tsunekazu Kakuta
- Department of Cardiology, Tsuchiura Kyodo General Hospital, Tsuchiura, Ibaraki, Japan
| | - Ik-Kyung Jang
- Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA; Cardiology Division, Kyung Hee University Hospital, Seoul, South Korea.
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29
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Lv R, Maehara A, Matsumura M, Wang L, Zhang C, Huang M, Guo X, Samady H, Giddens DP, Zheng J, Mintz GS, Tang D. Using Optical Coherence Tomography and Intravascular Ultrasound Imaging to Quantify Coronary Plaque Cap Stress/Strain and Progression: A Follow-Up Study Using 3D Thin-Layer Models. Front Bioeng Biotechnol 2021; 9:713525. [PMID: 34497800 PMCID: PMC8419245 DOI: 10.3389/fbioe.2021.713525] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2021] [Accepted: 07/20/2021] [Indexed: 11/13/2022] Open
Abstract
Accurate plaque cap thickness quantification and cap stress/strain calculations are of fundamental importance for vulnerable plaque research. To overcome uncertainties due to intravascular ultrasound (IVUS) resolution limitation, IVUS and optical coherence tomography (OCT) coronary plaque image data were combined together to obtain accurate and reliable cap thickness data, stress/strain calculations, and reliable plaque progression predictions. IVUS, OCT, and angiography baseline and follow-up data were collected from nine patients (mean age: 69; m: 5) at Cardiovascular Research Foundation with informed consent obtained. IVUS and OCT slices were coregistered and merged to form IVUS + OCT (IO) slices. A total of 114 matched slices (IVUS and OCT, baseline and follow-up) were obtained, and 3D thin-layer models were constructed to obtain stress and strain values. A generalized linear mixed model (GLMM) and least squares support vector machine (LSSVM) method were used to predict cap thickness change using nine morphological and mechanical risk factors. Prediction accuracies by all combinations (511) of those predictors with both IVUS and IO data were compared to identify optimal predictor(s) with their best accuracies. For the nine patients, the average of minimum cap thickness from IVUS was 0.17 mm, which was 26.08% lower than that from IO data (average = 0.23 mm). Patient variations of the individual errors ranged from ‒58.11 to 20.37%. For maximum cap stress between IO and IVUS, patient variations of the individual errors ranged from ‒30.40 to 46.17%. Patient variations of the individual errors of maximum cap strain values ranged from ‒19.90 to 17.65%. For the GLMM method, the optimal combination predictor using IO data had AUC (area under the ROC curve) = 0.926 and highest accuracy = 90.8%, vs. AUC = 0.783 and accuracy = 74.6% using IVUS data. For the LSSVM method, the best combination predictor using IO data had AUC = 0.838 and accuracy = 75.7%, vs. AUC = 0.780 and accuracy = 69.6% using IVUS data. This preliminary study demonstrated improved plaque cap progression prediction accuracy using accurate cap thickness data from IO slices and the differences in cap thickness, stress/strain values, and prediction results between IVUS and IO data. Large-scale studies are needed to verify our findings.
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Affiliation(s)
- Rui Lv
- School of Biological Science and Medical Engineering, Southeast University, Nanjing, China
| | - Akiko Maehara
- The Cardiovascular Research Foundation, Columbia University, New York, NY, United States
| | - Mitsuaki Matsumura
- The Cardiovascular Research Foundation, Columbia University, New York, NY, United States
| | - Liang Wang
- School of Biological Science and Medical Engineering, Southeast University, Nanjing, China
| | - Caining Zhang
- School of Biological Science and Medical Engineering, Southeast University, Nanjing, China
| | - Mengde Huang
- School of Biological Science and Medical Engineering, Southeast University, Nanjing, China
| | - Xiaoya Guo
- School of Science, Nanjing University of Posts and Telecommunications, Nanjing, China
| | - Habib Samady
- Department of Medicine, Emory University School of Medicine, Atlanta, GA, United States
| | - Don. P. Giddens
- Department of Medicine, Emory University School of Medicine, Atlanta, GA, United States
- The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, United States
| | - Jie Zheng
- Mallinckrodt Institute of Radiology, Washington University, St. Louis, MO, United States
| | - Gary S. Mintz
- The Cardiovascular Research Foundation, Columbia University, New York, NY, United States
| | - Dalin Tang
- School of Biological Science and Medical Engineering, Southeast University, Nanjing, China
- Mathematical Sciences Department, Worcester Polytechnic Institute, Worcester, MA, United States
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30
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Boussoussou M, Vattay B, Szilveszter B, Kolossváry M, Simon J, Vecsey-Nagy M, Merkely B, Maurovich-Horvat P. Functional assessment of coronary plaques using CT based hemodynamic simulations: Current status, technical principles and clinical value. IMAGING 2021. [DOI: 10.1556/1647.2020.00011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
AbstractIn recent years, coronary computed tomography angiography (CCTA) has emerged as an accurate and safe non-invasive imaging modality in terms of detecting and excluding coronary artery disease (CAD). In the latest European Society of Cardiology Guidelines CCTA received Class I recommendation for the evaluation of patients with stable chest pain with low to intermediate clinical likelihood of CAD. Despite its high negative predictive value, the diagnostic performance of CCTA is limited by the relatively low specificity, especially in patients with heavily calcified lesions. The discrepancy between the degree of stenosis and ischemia is well established based on both invasive and non-invasive tests. The rapid evolution of computational flow dynamics has allowed the simulation of CCTA derived fractional flow reserve (FFR-CT), which improves specificity by combining anatomic and functional information regarding coronary atherosclerosis. FFR-CT has been extensively validated against invasively measured FFR as the reference standard. Due to recent technological advancements FFR-CT values can also be calculated locally, without offsite processing. Wall shear stress (WSS) and axial plaque stress (APS) are additional key hemodynamic elements of atherosclerotic plaque characteristics, which can also be measured using CCTA images. Current evidence suggests that WSS and APS are important hemodynamic features of adverse coronary plaques. CCTA based hemodynamic calculations could therefore improve prognostication and the management of patients with stable CAD.
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Affiliation(s)
- Melinda Boussoussou
- MTA-SE Cardiovascular Imaging Research Group, Heart and Vascular Center, Semmelweis University, Budapest, Hungary
| | - Borbála Vattay
- MTA-SE Cardiovascular Imaging Research Group, Heart and Vascular Center, Semmelweis University, Budapest, Hungary
| | - Bálint Szilveszter
- MTA-SE Cardiovascular Imaging Research Group, Heart and Vascular Center, Semmelweis University, Budapest, Hungary
| | - Márton Kolossváry
- MTA-SE Cardiovascular Imaging Research Group, Heart and Vascular Center, Semmelweis University, Budapest, Hungary
| | - Judit Simon
- MTA-SE Cardiovascular Imaging Research Group, Heart and Vascular Center, Semmelweis University, Budapest, Hungary
| | - Milán Vecsey-Nagy
- MTA-SE Cardiovascular Imaging Research Group, Heart and Vascular Center, Semmelweis University, Budapest, Hungary
| | - Béla Merkely
- MTA-SE Cardiovascular Imaging Research Group, Heart and Vascular Center, Semmelweis University, Budapest, Hungary
| | - Pál Maurovich-Horvat
- MTA-SE Cardiovascular Imaging Research Group, Heart and Vascular Center, Semmelweis University, Budapest, Hungary
- Department of Radiology, Medical Imaging Centre, Semmelweis University, Budapest, Hungary
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31
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Assessment with clinical data of a coupled bio-hemodynamics numerical model to predict leukocyte adhesion in coronary arteries. Sci Rep 2021; 11:12680. [PMID: 34135399 PMCID: PMC8208986 DOI: 10.1038/s41598-021-92084-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 05/28/2021] [Indexed: 11/30/2022] Open
Abstract
Numerical simulations of coupled hemodynamics and leukocyte transport and adhesion inside coronary arteries have been performed. Realistic artery geometries have been obtained for a set of four patients from intravascular ultrasound and angiography images. The numerical model computes unsteady three-dimensional blood hemodynamics and leukocyte concentration in the blood. Wall-shear stress dependent leukocyte adhesion is also computed through agent-based modeling rules, fully coupled to the hemodynamics and leukocyte transport. Numerical results have a good correlation with clinical data. Regions where high adhesion is predicted by the simulations coincide to a good approximation with artery segments presenting plaque increase, as documented by clinical data from baseline and six-month follow-up exam of the same artery. In addition, it is observed that the artery geometry and, in particular, the tortuosity of the centerline are a primary factor in determining the spatial distribution of wall-shear stress, and of the resulting leukocyte adhesion patterns. Although further work is required to overcome the limitations of the present model and ultimately quantify plaque growth in the simulations, these results are encouraging towards establishing a predictive methodology for atherosclerosis progress.
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32
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Godo S, Suda A, Takahashi J, Yasuda S, Shimokawa H. Coronary Microvascular Dysfunction. Arterioscler Thromb Vasc Biol 2021; 41:1625-1637. [PMID: 33761763 DOI: 10.1161/atvbaha.121.316025] [Citation(s) in RCA: 70] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
[Figure: see text].
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Affiliation(s)
- Shigeo Godo
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan (S.G., A.S., J.T., S.Y., H.S.)
| | - Akira Suda
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan (S.G., A.S., J.T., S.Y., H.S.)
| | - Jun Takahashi
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan (S.G., A.S., J.T., S.Y., H.S.)
| | - Satoshi Yasuda
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan (S.G., A.S., J.T., S.Y., H.S.)
| | - Hiroaki Shimokawa
- Graduate School, International University of Health and Welfare, Narita, Japan (H.S.)
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33
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El Zayat A, Eldeeb M, Gad M, Ibrahim IM. Effect of Presence of Ramus Intermedius Artery on Location of Culprit Lesions in Acute Left Circumflex Coronary Artery Occlusion. J Saudi Heart Assoc 2021; 33:35-40. [PMID: 33936939 PMCID: PMC8084308 DOI: 10.37616/2212-5043.1238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Revised: 01/18/2021] [Accepted: 01/27/2021] [Indexed: 11/20/2022] Open
Abstract
BACKGROUND AND AIM Coronary artery anatomy frequently affects location of atherosclerotic plaques and subsequent culprit lesions. We sought to clarify whether presence or absence of Ramus Intermedius coronary artery (RI) would affect location of culprit lesions in acute left circumflex (LCX) coronary artery occlusion. METHODS The study included 180 patients, 100 with a diagnosis of non-ST elevation myocardial infarction (NSTEMI) and 80 with ST elevation myocardial infarction (STEMI). All culprit lesions were located in the LCX coronary artery. RI group included 45 patients and the No RI group included 135 patients. RESULTS Culprit LCX lesions were similarly located at a comparable distance from LCX ostium in both groups and the presence of RI was not associated with significantly more proximally located culprit LCX lesions (34.7 ± 15.2 mm compared to 30.8 ± 17.9 mm respectively, p > 0.05). The frequency distribution of culprit lesions' distance from LCX ostium showed no significant difference between both groups in any of the segments studied (10 mm each). There was no significant difference between both groups regarding markers of myocardial necrosis size as cardiac biomarkers (peak cardiac troponin-T 1077.4 ± 361.2 pg/dl vs 926 ± 462.2 pg/dl respectively, p = 0.13), (peak creatine kinase-MB 232.2 ± 81 ng/dl vs 194.7 ± 99.2 ng/dl respectively, p = 0.07) or left ventricular ejection fraction (EF 46.3 ± 6.3% vs 48.3 ± 8.3% respectively, p = 0.76). CONCLUSION Presence of RI coronary artery, as an additional flow divider, may not be associated with more proximal culprit lesions, compared to its absence, in cases of acute LCX coronary artery occlusion. Possible underlying pathophysiologic mechanisms remain to be clarified.
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Affiliation(s)
- Ahmed El Zayat
- Cardiology Department, Faculty of Medicine, Zagazig University,
Egypt
| | - Mohey Eldeeb
- Cardiology Department, Faculty of Medicine, Zagazig University,
Egypt
| | - Marwa Gad
- Cardiology Department, Faculty of Medicine, Zagazig University,
Egypt
| | - Ismail M. Ibrahim
- Cardiology Department, Faculty of Medicine, Zagazig University,
Egypt
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34
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Guo X, Maehara A, Matsumura M, Wang L, Zheng J, Samady H, Mintz GS, Giddens DP, Tang D. Predicting plaque vulnerability change using intravascular ultrasound + optical coherence tomography image-based fluid-structure interaction models and machine learning methods with patient follow-up data: a feasibility study. Biomed Eng Online 2021; 20:34. [PMID: 33823858 PMCID: PMC8025351 DOI: 10.1186/s12938-021-00868-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Accepted: 03/13/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Coronary plaque vulnerability prediction is difficult because plaque vulnerability is non-trivial to quantify, clinically available medical image modality is not enough to quantify thin cap thickness, prediction methods with high accuracies still need to be developed, and gold-standard data to validate vulnerability prediction are often not available. Patient follow-up intravascular ultrasound (IVUS), optical coherence tomography (OCT) and angiography data were acquired to construct 3D fluid-structure interaction (FSI) coronary models and four machine-learning methods were compared to identify optimal method to predict future plaque vulnerability. METHODS Baseline and 10-month follow-up in vivo IVUS and OCT coronary plaque data were acquired from two arteries of one patient using IRB approved protocols with informed consent obtained. IVUS and OCT-based FSI models were constructed to obtain plaque wall stress/strain and wall shear stress. Forty-five slices were selected as machine learning sample database for vulnerability prediction study. Thirteen key morphological factors from IVUS and OCT images and biomechanical factors from FSI model were extracted from 45 slices at baseline for analysis. Lipid percentage index (LPI), cap thickness index (CTI) and morphological plaque vulnerability index (MPVI) were quantified to measure plaque vulnerability. Four machine learning methods (least square support vector machine, discriminant analysis, random forest and ensemble learning) were employed to predict the changes of three indices using all combinations of 13 factors. A standard fivefold cross-validation procedure was used to evaluate prediction results. RESULTS For LPI change prediction using support vector machine, wall thickness was the optimal single-factor predictor with area under curve (AUC) 0.883 and the AUC of optimal combinational-factor predictor achieved 0.963. For CTI change prediction using discriminant analysis, minimum cap thickness was the optimal single-factor predictor with AUC 0.818 while optimal combinational-factor predictor achieved an AUC 0.836. Using random forest for predicting MPVI change, minimum cap thickness was the optimal single-factor predictor with AUC 0.785 and the AUC of optimal combinational-factor predictor achieved 0.847. CONCLUSION This feasibility study demonstrated that machine learning methods could be used to accurately predict plaque vulnerability change based on morphological and biomechanical factors from multi-modality image-based FSI models. Large-scale studies are needed to verify our findings.
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Affiliation(s)
- Xiaoya Guo
- School of Science, Nanjing University of Posts and Telecommunications, Nanjing, 210023, China.
- Department of Mathematics, Southeast University, Nanjing, 210096, China.
| | - Akiko Maehara
- The Cardiovascular Research Foundation, Columbia University, New York, NY, 10022, USA
| | - Mitsuaki Matsumura
- The Cardiovascular Research Foundation, Columbia University, New York, NY, 10022, USA
| | - Liang Wang
- School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China
| | - Jie Zheng
- Mallinckrodt Institute of Radiology, Washington University, St. Louis, MO, 63110, USA
| | - Habib Samady
- Department of Medicine, Emory University School of Medicine, Atlanta, GA, 30307, USA
| | - Gary S Mintz
- The Cardiovascular Research Foundation, Columbia University, New York, NY, 10022, USA
| | - Don P Giddens
- Department of Medicine, Emory University School of Medicine, Atlanta, GA, 30307, USA
- The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, 30332, USA
| | - Dalin Tang
- Department of Mathematics, Southeast University, Nanjing, 210096, China.
- Mathematical Sciences Department, Worcester Polytechnic Institute, Worcester, MA, 01609, USA.
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35
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Zuin M, Rigatelli G, Zuliani G, Roncon L. New prediction tools for coronary plaque erosion: Don't forget computational fluid dynamic analysis. Atherosclerosis 2021; 323:54-55. [PMID: 33762115 DOI: 10.1016/j.atherosclerosis.2021.03.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Revised: 02/19/2021] [Accepted: 03/04/2021] [Indexed: 11/19/2022]
Affiliation(s)
- Marco Zuin
- Department of Morphology, Surgery & Experimental Medicine, University of Ferrara, Ferrara, Italy
| | - Gianluca Rigatelli
- Department of Specialistic Medicine, Division of Cardiology, Rovigo General Hospital, Rovigo, Italy.
| | - Giovanni Zuliani
- Department of Morphology, Surgery & Experimental Medicine, University of Ferrara, Ferrara, Italy
| | - Loris Roncon
- Department of Specialistic Medicine, Division of Cardiology, Rovigo General Hospital, Rovigo, Italy
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36
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Pan J, Cai Y, Wang L, Maehara A, Mintz GS, Tang D, Li Z. A prediction tool for plaque progression based on patient-specific multi-physical modeling. PLoS Comput Biol 2021; 17:e1008344. [PMID: 33780445 PMCID: PMC8057612 DOI: 10.1371/journal.pcbi.1008344] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Revised: 04/20/2021] [Accepted: 03/10/2021] [Indexed: 11/19/2022] Open
Abstract
Atherosclerotic plaque rupture is responsible for a majority of acute vascular syndromes and this study aims to develop a prediction tool for plaque progression and rupture. Based on the follow-up coronary intravascular ultrasound imaging data, we performed patient-specific multi-physical modeling study on four patients to obtain the evolutional processes of the microenvironment during plaque progression. Four main pathophysiological processes, i.e., lipid deposition, inflammatory response, migration and proliferation of smooth muscle cells (SMCs), and neovascularization were coupled based on the interactions demonstrated by experimental and clinical observations. A scoring table integrating the dynamic microenvironmental indicators with the classical risk index was proposed to differentiate their progression to stable and unstable plaques. The heterogeneity of plaque microenvironment for each patient was demonstrated by the growth curves of the main microenvironmental factors. The possible plaque developments were predicted by incorporating the systematic index with microenvironmental indicators. Five microenvironmental factors (LDL, ox-LDL, MCP-1, SMC, and foam cell) showed significant differences between stable and unstable group (p < 0.01). The inflammatory microenvironments (monocyte and macrophage) had negative correlations with the necrotic core (NC) expansion in the stable group, while very strong positive correlations in unstable group. The inflammatory microenvironment is strongly correlated to the NC expansion in unstable plaques, suggesting that the inflammatory factors may play an important role in the formation of a vulnerable plaque. This prediction tool will improve our understanding of the mechanism of plaque progression and provide a new strategy for early detection and prediction of high-risk plaques. Besides the traditional systematic factors, the influences of the local microenvironmental factors on atherosclerotic plaque progression have been demonstrated. Mathematical and computational modeling is an important tool to investigate the complex interplay between plaque progression and the microenvironment, and provides a potential way toward the prediction of plaque vulnerability according to the comprehensive evaluation of both morphological and/or biochemical factors in tissue level with microenvironmental factors in cellular level. We performed patient-specific multi-physical modeling study on four patients to obtain the evolutional processes of the microenvironment during plaque progression and predicted the possible plaque developments. A scoring table integrating the dynamic microenvironmental indicators with the classical risk index was proposed to differentiate their progression to stable and unstable plaques. Based on patient-specific imaging data, the mathematical model will provide a novel method to predict the changes of plaque microenvironment and improve ability to access the personal therapeutic strategy for atherosclerotic plaque.
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Affiliation(s)
- Jichao Pan
- School of Biological Sciences and Medical Engineering, Southeast University, Nanjing Jiangsu, China
| | - Yan Cai
- School of Biological Sciences and Medical Engineering, Southeast University, Nanjing Jiangsu, China
| | - Liang Wang
- School of Biological Sciences and Medical Engineering, Southeast University, Nanjing Jiangsu, China
| | - Akiko Maehara
- The Cardiovascular Research Foundation, New York, New York, United States of America
| | - Gary S Mintz
- The Cardiovascular Research Foundation, New York, New York, United States of America
| | - Dalin Tang
- School of Biological Sciences and Medical Engineering, Southeast University, Nanjing Jiangsu, China
- Mathematical Sciences Department, Worcester Polytechnic Institute, Massachusetts, United States of America
| | - Zhiyong Li
- School of Biological Sciences and Medical Engineering, Southeast University, Nanjing Jiangsu, China
- School of Mechanical, Medical and Process Engineering, Queensland University of Technology, Brisbane, Queensland, Australia
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37
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Hoogendoorn A, Kok AM, Hartman EMJ, de Nisco G, Casadonte L, Chiastra C, Coenen A, Korteland SA, Van der Heiden K, Gijsen FJH, Duncker DJ, van der Steen AFW, Wentzel JJ. Multidirectional wall shear stress promotes advanced coronary plaque development: comparing five shear stress metrics. Cardiovasc Res 2021; 116:1136-1146. [PMID: 31504238 PMCID: PMC7177495 DOI: 10.1093/cvr/cvz212] [Citation(s) in RCA: 72] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2019] [Revised: 07/15/2019] [Accepted: 08/20/2019] [Indexed: 01/02/2023] Open
Abstract
Aims Atherosclerotic plaque development has been associated with wall shear stress (WSS). However, the multidirectionality of blood flow, and thus of WSS, is rarely taken into account. The purpose of this study was to comprehensively compare five metrics that describe (multidirectional) WSS behaviour and assess how WSS multidirectionality affects coronary plaque initiation and progression. Methods and results Adult familial hypercholesterolaemic pigs (n = 10) that were fed a high-fat diet, underwent imaging of the three main coronary arteries at three-time points [3 (T1), 9 (T2), and 10–12 (T3) months]. Three-dimensional geometry of the arterial lumen, in combination with local flow velocity measurements, was used to calculate WSS at T1 and T2. For analysis, arteries were divided into 3 mm/45° sectors (n = 3648). Changes in wall thickness and final plaque composition were assessed with near-infrared spectroscopy–intravascular ultrasound, optical coherence tomography imaging, and histology. Both in pigs with advanced and mild disease, the highest plaque progression rate was exclusively found at low time-averaged WSS (TAWSS) or high multidirectional WSS regions at both T1 and T2. However, the eventually largest plaque growth was located in regions with initial low TAWSS or high multidirectional WSS that, over time, became exposed to high TAWSS or low multidirectional WSS at T2. Besides plaque size, also the presence of vulnerable plaque components at the last time point was related to low and multidirectional WSS. Almost all WSS metrics had good predictive values for the development of plaque (47–50%) and advanced fibrous cap atheroma (FCA) development (59–61%). Conclusion This study demonstrates that low and multidirectional WSS promote both initiation and progression of coronary atherosclerotic plaques. The high-predictive values of the multidirectional WSS metrics for FCA development indicate their potential as an additional clinical marker for the vulnerable disease.
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Affiliation(s)
- Ayla Hoogendoorn
- Department of Cardiology, Biomedical Engineering, Erasmus MC, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands
| | - Annette M Kok
- Department of Cardiology, Biomedical Engineering, Erasmus MC, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands
| | - Eline M J Hartman
- Department of Cardiology, Biomedical Engineering, Erasmus MC, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands
| | - Giuseppe de Nisco
- PoliToMed Lab, Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Turin, Italy
| | - Lorena Casadonte
- Department of Biomedical Engineering and Physics, Amsterdam UMC, Amsterdam, The Netherlands
| | - Claudio Chiastra
- PoliToMed Lab, Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Turin, Italy
| | - Adriaan Coenen
- Department of Cardiology, Biomedical Engineering, Erasmus MC, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands
- Department of Radiology, Erasmus MC, Rotterdam, The Netherlands
| | - Suze-Anne Korteland
- Department of Cardiology, Biomedical Engineering, Erasmus MC, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands
| | - Kim Van der Heiden
- Department of Cardiology, Biomedical Engineering, Erasmus MC, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands
| | - Frank J H Gijsen
- Department of Cardiology, Biomedical Engineering, Erasmus MC, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands
| | - Dirk J Duncker
- Department of Cardiology, Experimental Cardiology, Erasmus MC, Rotterdam, The Netherlands
| | - Antonius F W van der Steen
- Department of Cardiology, Biomedical Engineering, Erasmus MC, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands
| | - Jolanda J Wentzel
- Department of Cardiology, Biomedical Engineering, Erasmus MC, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands
- Corresponding author. Tel: +31 10 7044 044; fax: +31 10 7044 720, E-mail:
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Bajraktari A, Bytyçi I, Henein MY. High Coronary Wall Shear Stress Worsens Plaque Vulnerability: A Systematic Review and Meta-Analysis. Angiology 2021; 72:706-714. [PMID: 33535802 PMCID: PMC8326896 DOI: 10.1177/0003319721991722] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Aim: The aim of this meta-analysis is to assess the impact of wall shear stress (WSS) severity on arterial plaque vulnerability. Methods: We systematically searched electronic databases and selected studies which assessed the relationship between WSS measured by intravascular ultrasound and coronary artery plaque features. In 7 studies, a total of 615 patients with 28 276 arterial segments (median follow-up: 7.71 months) were identified. At follow-up, the pooled analysis showed high WSS to be associated with regression of plaque fibrous area, weighted mean difference (WMD) −0.11 (95% CI: −0.20 to −0.02, P = .02) and fibrofatty area, WMD −0.09 (95% CI: −0.17 to −0.01, P = .02), reduction in plaque total area, WMD −0.09 (95% CI: −0.14 to −0.04, P = .007) and increased necrotic core area, and WMD 0.04 (95% CI: 0.01-0.09, P = .03) compared with low WSS. Dense calcium deposits remained unchanged in high and low WSS (0.01 vs 0.02 mm2; P > .05). High WSS resulted in profound remodeling (40% vs 18%, P < .05) and with more constructive remodeling than low WSS (78% vs 40%, P < .01). Conclusions: High WSS in coronary arteries is associated with worsening plaque vulnerability and more profound arterial wall remodeling compared with low WSS.
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Affiliation(s)
- Artan Bajraktari
- Institute of Public Health and Clinical Medicine, Umea University, Sweden
| | - Ibadete Bytyçi
- Institute of Public Health and Clinical Medicine, Umea University, Sweden.,University College, Bardhosh, Kosovo.,Clinic of Cardiology, University Clinical Centre of Kosovo, Prishtina, Kosovo
| | - Michael Y Henein
- Institute of Public Health and Clinical Medicine, Umea University, Sweden.,Molecular and Clinic Research Institute, St George University, London, and Brunel University, United Kingdom
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39
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Okamoto N, Vengrenyuk Y, Fuster V, Samady H, Yasumura K, Baber U, Barman N, Suleman J, Sweeny J, Krishnan P, Mehran R, Sharma SK, Narula J, Kini AS. Relationship between high shear stress and OCT-verified thin-cap fibroatheroma in patients with coronary artery disease. PLoS One 2020; 15:e0244015. [PMID: 33332434 PMCID: PMC7746187 DOI: 10.1371/journal.pone.0244015] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Accepted: 12/01/2020] [Indexed: 12/16/2022] Open
Abstract
High-risk coronary plaques have been considered predictive of adverse cardiac events. Both wall shear stress (WSS) in patients with hemodynamically significant lesions and optical coherence tomography (OCT) -verified thin-cap fibroatheroma (TCFA) are associated with plaque rupture, the most common underlying mechanism of acute coronary syndrome. The aim of the study was to test the hypothesis that invasive coronary angiography-based high WSS is associated with the presence of TCFA detected by OCT in obstructive lesions. From a prospective study of patients who underwent OCT examination for angiographically obstructive lesions (Yellow II), we selected patients who had two angiographic projections to create a 3-dimensional reconstruction model to allow assessment of WSS. The patients were divided into 2 groups according to the presence and absence of TCFA. Mean WSS was assessed in the whole lesion and in the proximal, middle and distal segments. Of 70 patients, TCFA was observed in 13 (19%) patients. WSS in the proximal segment (WSSproximal) (10.20 [5.01, 16.93Pa]) and the whole lesion (WSSlesion) (12.37 [6.36, 14.55Pa]) were significantly higher in lesions with TCFA compared to WSSproximal (5.84 [3.74, 8.29Pa], p = 0.02) and WSSlesion (6.95 [4.41, 11.60], p = 0.04) in lesions without TCFA. After multivariate analysis, WSSproximal was independently associated with the presence of TCFA (Odds ratio 1.105; 95%CI 1.007-1.213, p = 0.04). The optimal cutoff value of WSSproximal to predict TCFA was 6.79 Pa (AUC: 0.71; sensitivity: 0.77; specificity: 0.63 p = 0.02). Our results demonstrate that high WSS in the proximal segments of obstructive lesions is an independent predictor of OCT-verified TCFA.
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Affiliation(s)
- Naotaka Okamoto
- Division of Cardiology, Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai, New York, NY, United States of America
| | - Yuliya Vengrenyuk
- Division of Cardiology, Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai, New York, NY, United States of America
| | - Valentin Fuster
- Division of Cardiology, Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai, New York, NY, United States of America
| | - Habib Samady
- Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, United States of America
| | - Keisuke Yasumura
- Division of Cardiology, Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai, New York, NY, United States of America
| | - Usman Baber
- Division of Cardiology, Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai, New York, NY, United States of America
| | - Nitin Barman
- Division of Cardiology, Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai, New York, NY, United States of America
| | - Javed Suleman
- Division of Cardiology, Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai, New York, NY, United States of America
| | - Joseph Sweeny
- Division of Cardiology, Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai, New York, NY, United States of America
| | - Prakash Krishnan
- Division of Cardiology, Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai, New York, NY, United States of America
| | - Roxana Mehran
- Division of Cardiology, Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai, New York, NY, United States of America
| | - Samin K. Sharma
- Division of Cardiology, Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai, New York, NY, United States of America
| | - Jagat Narula
- Division of Cardiology, Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai, New York, NY, United States of America
| | - Annapoorna S. Kini
- Division of Cardiology, Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai, New York, NY, United States of America
- * E-mail:
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40
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McCallinhart PE, Scandling BW, Trask AJ. Coronary remodeling and biomechanics: Are we going with the flow in 2020? Am J Physiol Heart Circ Physiol 2020; 320:H584-H592. [PMID: 33185115 DOI: 10.1152/ajpheart.00634.2020] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Under normal conditions, coronary blood flow (CBF) provides critical blood supply to the myocardium so that it can appropriately meet the metabolic demands of the body. Dogmatically, there exist several known regulators and modulators of CBF that include local metabolites and neurohormonal factors that can influence the function of the coronary circulation. In disease states such as diabetes and myocardial ischemia, these regulators are impaired or shifted such that CBF is reduced. Although functional considerations have been and continued to be well studied, more recent evidence builds upon established studies that collectively suggest that the relative roles of coronary structure, biomechanics, and the influence of cardiac biomechanics via extravascular compression may also play a significant role in dictating CBF. In this mini review, we discuss these regulators of CBF under normal and pathophysiological conditions and their potential influence on the control of CBF.
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Affiliation(s)
- Patricia E McCallinhart
- Center for Cardiovascular Research, The Heart Center, The Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, Ohio
| | - Benjamin W Scandling
- Department of Biomedical Engineering, College of Engineering, The Ohio State University, Columbus, Ohio.,Frick Center for Heart Failure and Arrhythmia, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Aaron J Trask
- Center for Cardiovascular Research, The Heart Center, The Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, Ohio.,Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio
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41
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Gijsen F, Katagiri Y, Barlis P, Bourantas C, Collet C, Coskun U, Daemen J, Dijkstra J, Edelman E, Evans P, van der Heiden K, Hose R, Koo BK, Krams R, Marsden A, Migliavacca F, Onuma Y, Ooi A, Poon E, Samady H, Stone P, Takahashi K, Tang D, Thondapu V, Tenekecioglu E, Timmins L, Torii R, Wentzel J, Serruys P. Expert recommendations on the assessment of wall shear stress in human coronary arteries: existing methodologies, technical considerations, and clinical applications. Eur Heart J 2020; 40:3421-3433. [PMID: 31566246 PMCID: PMC6823616 DOI: 10.1093/eurheartj/ehz551] [Citation(s) in RCA: 200] [Impact Index Per Article: 40.0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2018] [Revised: 04/09/2019] [Accepted: 09/23/2019] [Indexed: 01/09/2023] Open
Affiliation(s)
- Frank Gijsen
- Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Yuki Katagiri
- Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, the Netherlands
| | - Peter Barlis
- Department of Medicine and Radiology, Melbourne Medical School, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, VIC, Australia.,Department of Cardiology, Northern Hospital, 185 Cooper Street, Epping, Australia.,St Vincent's Heart Centre, Building C, 41 Victoria Parade, Fitzroy, Australia
| | - Christos Bourantas
- Institute of Cardiovascular Sciences, University College of London, London, UK.,Department of Cardiology, Barts Heart Centre, London, UK.,School of Medicine and Dentistry, Queen Mary University London, London, UK
| | - Carlos Collet
- Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, the Netherlands
| | - Umit Coskun
- Division of Cardiovascular Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Joost Daemen
- Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Jouke Dijkstra
- LKEB-Division of Image Processing, Department of Radiology, Leiden University Medical Centre, Leiden, the Netherlands
| | - Elazer Edelman
- Division of Cardiovascular Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA.,Institute for Medical Engineering and Science, MIT, Cambridge, MA, USA
| | - Paul Evans
- Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, UK
| | - Kim van der Heiden
- Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Rod Hose
- Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, UK.,Department of Circulation and Imaging, NTNU, Trondheim, Norway
| | - Bon-Kwon Koo
- Department of Internal Medicine and Cardiovascular Center, Seoul National University Hospital, Seoul, Korea.,Institute of Aging, Seoul National University, Seoul, Korea
| | - Rob Krams
- School of Engineering and Materials Science Queen Mary University of London, London, UK
| | - Alison Marsden
- Departments of Bioengineering and Pediatrics, Institute of Computational and Mathematical Engineering, Stanford University, Stanford, CA, USA
| | - Francesco Migliavacca
- Laboratory of Biological Structure Mechanics (LaBS), Department of Chemistry, Materials and Chemical Engineering "Giulio Natta", Politecnico di Milano, Milan, Italy
| | - Yoshinobu Onuma
- Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Andrew Ooi
- Department of Mechanical Engineering, Melbourne School of Engineering, The University of Melbourne, Melbourne, VIC, Australia
| | - Eric Poon
- Department of Mechanical Engineering, Melbourne School of Engineering, The University of Melbourne, Melbourne, VIC, Australia
| | - Habib Samady
- Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - Peter Stone
- Division of Cardiovascular Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Kuniaki Takahashi
- Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, the Netherlands
| | - Dalin Tang
- Department of Mathematics, Southeast University, Nanjing, China; Mathematical Sciences Department, Worcester Polytechnic Institute, Worcester, MA, USA
| | - Vikas Thondapu
- Department of Medicine and Radiology, Melbourne Medical School, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, VIC, Australia.,Department of Mechanical Engineering, Melbourne School of Engineering, The University of Melbourne, Melbourne, VIC, Australia.,Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Erhan Tenekecioglu
- Department of Interventional Cardiology, Thoraxcentre, Erasmus Medical Centre, Rotterdam, the Netherlands
| | - Lucas Timmins
- Department of Biomedical Engineering, University of Utah, Salt Lake City, UT.,Scientific Computing and Imaging Institute, University of Utah, Salt Lake City, UT
| | - Ryo Torii
- Department of Mechanical Engineering, University College London, UK
| | - Jolanda Wentzel
- Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Patrick Serruys
- Erasmus University Medical Center, Rotterdam, the Netherlands.,Imperial College London, London, UK.,Melbourne School of Engineering, University of Melbourne, Melbourne, Australia
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Sechtem U, Brown D, Godo S, Lanza GA, Shimokawa H, Sidik N. Coronary microvascular dysfunction in stable ischaemic heart disease (non-obstructive coronary artery disease and obstructive coronary artery disease). Cardiovasc Res 2020; 116:771-786. [PMID: 31958128 DOI: 10.1093/cvr/cvaa005] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2019] [Revised: 12/09/2019] [Accepted: 01/15/2020] [Indexed: 01/12/2023] Open
Abstract
Diffuse and focal epicardial coronary disease and coronary microvascular abnormalities may exist side-by-side. Identifying the contributions of each of these three players in the coronary circulation is a difficult task. Yet identifying coronary microvascular dysfunction (CMD) as an additional player in patients with coronary artery disease (CAD) may provide explanations of why symptoms may persist frequently following and why global coronary flow reserve may be more prognostically important than fractional flow reserve measured in a single vessel before percutaneous coronary intervention. This review focuses on the challenges of identifying the presence of CMD in the context of diffuse non-obstructive CAD and obstructive CAD. Furthermore, it is going to discuss the pathophysiology in this complex situation, examine the clinical context in which the interaction of the three components of disease takes place and finally look at non-invasive diagnostic methods relevant for addressing this question.
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Affiliation(s)
- Udo Sechtem
- Department of Cardiology, Robert Bosch Krankenhaus, Auerbachstr. 110, D-70376 Stuttgart, Germany
| | - David Brown
- Cardiovascular Division, Washington University School of Medicine, St Louis, MO, USA
| | - Shigeo Godo
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Gaetano Antonio Lanza
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Cardiology Institute, Roma, Italy
| | - Hiro Shimokawa
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Novalia Sidik
- University of Glasgow, Golden Jubilee National Hospital, Glasgow, UK
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43
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Lin GH, Song JX, Fu NX, Huang X, Lu HX. Quantitative and Qualitative Analysis of Atherosclerotic Stenosis in the Middle Cerebral Artery Using High-Resolution Magnetic Resonance Imaging. Can Assoc Radiol J 2020; 72:783-788. [PMID: 33023323 DOI: 10.1177/0846537120961312] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
PURPOSE We analyzed and compared the imaging characteristics of the vessel wall of the middle cerebral artery (MCA) in symptomatic and asymptomatic patients using a 3.0-T high-resolution magnetic resonance imaging (HR-MRI) protocol, including a 3-dimensional T1-sampling perfection with application-optimized contrasts using different flip angle evolutions sequence. METHODS Fifty-three patients with atherosclerotic stenosis of the MCA underwent 3.0-T HR-MRI examinations. The characteristics of atherosclerotic plaques in 53 patients (28 symptomatic, 25 asymptomatic) were analyzed, including plaque distribution and signal intensity. Plaque burden (PB), stenosis degree, and the remodeling index were measured and compared between symptomatic and asymptomatic patients. RESULTS The PB of the symptomatic group was significantly higher than that of the asymptomatic group (P = .006), and moderate-severe stenosis was more common (P = .01). The remodeling index of the symptomatic group was also lower (P = .015) and negative remodeling (NR) was more common (P = .043). Binary logistic regression analysis showed that stenosis degree was a risk factor in symptomatic patients (odds ratio = 135, P = .023). CONCLUSION There is a trend that some characteristics of plaques and vessels, including the moderate-severe stenosis, larger PB, and NR, were observed more frequently among patients with symptomatic atherosclerotic stenosis of the MCA than among asymptomatic patients.
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Affiliation(s)
- Guo-Hui Lin
- Department of Radiology, Shenzhen Bao'an People's Hospital, Shenzhen, Guangdong, China
| | - Jian-Xun Song
- Department of Radiology, Shenzhen Bao'an People's Hospital, Shenzhen, Guangdong, China.,Guangdong Medical University, Guangdong, China
| | - Nian-Xia Fu
- Department of Radiology, Shenzhen Bao'an People's Hospital, Shenzhen, Guangdong, China
| | - Xu Huang
- Department of Radiology, Shenzhen Bao'an People's Hospital, Shenzhen, Guangdong, China
| | - Hong-Xia Lu
- Department of Radiology, Shenzhen Bao'an People's Hospital, Shenzhen, Guangdong, China
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44
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Lan L, Liu H, Ip V, Soo Y, Abrigo J, Fan F, Ma SH, Ma K, Ip B, Liu J, Fan Y, Zeng J, Mok V, Wong L, Liebeskind D, Leung T, Leng X. Regional High Wall Shear Stress Associated With Stenosis Regression in Symptomatic Intracranial Atherosclerotic Disease. Stroke 2020; 51:3064-3073. [PMID: 32883193 DOI: 10.1161/strokeaha.120.030615] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Background and Purpose:
Understanding the mechanisms underlying progression/regression of symptomatic intracranial atherosclerotic stenosis (sICAS) will inform secondary prevention of the patients. Focal wall shear stress (WSS) may play an important role, which, however, had seldom been investigated.
Methods:
Patients with acute ischemic stroke or transient ischemic attack (TIA) attributed to 50% to 99% intracranial atherosclerotic stenosis were recruited. All patients underwent cerebral computed tomography angiography at baseline, and a computational fluid dynamics model was built based on computed tomography angiography to simulate blood flow and quantify WSS in the vicinity of the sICAS lesion. All patients received optimal medical treatment and a second computed tomography angiography at 1 year. The change in the luminal stenosis from baseline to 1 year in sICAS was defined as progression (increased >10%), quiescence (±10%), or regression (decreased >10%). Associations between baseline WSS metrics and sICAS regression were analyzed.
Results:
Among 39 patients (median age 62 years; 27 males), sICAS luminal stenosis progressed, remained quiescent and regressed in 6 (15.4%), 15 (38.5%), and 18 (46.2%) cases, respectively. A higher maximum WSS and larger high-WSS area, throughout the sICAS lesion or obtained separately in the proximal and distal parts of the lesion, were independently associated with regression of luminal stenosis in sICAS over 1 year.
Conclusions:
A majority of sICAS lesions regress or stay quiescent in the luminal stenosis over 1 year after stroke under optimal medical treatment, when higher focal WSS may facilitate stenosis regression. Further studies of the effects of hemodynamics including WSS in altering plaque vulnerability and stroke risks are needed.
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Affiliation(s)
- Linfang Lan
- Department of Medicine and Therapeutics (L.L., H.L., V.I., Y.S., F.F., S.H.M., K.M., B.I., V.M., L.W., T.L., X.L.), The Chinese University of Hong Kong, Prince of Wales Hospital, China
- Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University (L.L., Y.F., J.Z.)
- Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China (L.L., Y.F., J.Z.)
| | - Haipeng Liu
- Department of Medicine and Therapeutics (L.L., H.L., V.I., Y.S., F.F., S.H.M., K.M., B.I., V.M., L.W., T.L., X.L.), The Chinese University of Hong Kong, Prince of Wales Hospital, China
- Department of Imaging and Interventional Radiology (H.L., J.A.), The Chinese University of Hong Kong, Prince of Wales Hospital, China
- Research Centre of Intelligent Healthcare, Faculty of Health and Life Science, Coventry University, United Kingdom (H.L.)
| | - Vincent Ip
- Department of Medicine and Therapeutics (L.L., H.L., V.I., Y.S., F.F., S.H.M., K.M., B.I., V.M., L.W., T.L., X.L.), The Chinese University of Hong Kong, Prince of Wales Hospital, China
| | - Yannie Soo
- Department of Medicine and Therapeutics (L.L., H.L., V.I., Y.S., F.F., S.H.M., K.M., B.I., V.M., L.W., T.L., X.L.), The Chinese University of Hong Kong, Prince of Wales Hospital, China
| | - Jill Abrigo
- Department of Imaging and Interventional Radiology (H.L., J.A.), The Chinese University of Hong Kong, Prince of Wales Hospital, China
| | - Florence Fan
- Department of Medicine and Therapeutics (L.L., H.L., V.I., Y.S., F.F., S.H.M., K.M., B.I., V.M., L.W., T.L., X.L.), The Chinese University of Hong Kong, Prince of Wales Hospital, China
| | - Sze Ho Ma
- Department of Medicine and Therapeutics (L.L., H.L., V.I., Y.S., F.F., S.H.M., K.M., B.I., V.M., L.W., T.L., X.L.), The Chinese University of Hong Kong, Prince of Wales Hospital, China
| | - Karen Ma
- Department of Medicine and Therapeutics (L.L., H.L., V.I., Y.S., F.F., S.H.M., K.M., B.I., V.M., L.W., T.L., X.L.), The Chinese University of Hong Kong, Prince of Wales Hospital, China
| | - Bonaventure Ip
- Department of Medicine and Therapeutics (L.L., H.L., V.I., Y.S., F.F., S.H.M., K.M., B.I., V.M., L.W., T.L., X.L.), The Chinese University of Hong Kong, Prince of Wales Hospital, China
| | - Jia Liu
- Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, China (J.L.)
| | - Yuhua Fan
- Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University (L.L., Y.F., J.Z.)
- Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China (L.L., Y.F., J.Z.)
| | - Jinsheng Zeng
- Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University (L.L., Y.F., J.Z.)
- Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China (L.L., Y.F., J.Z.)
| | - Vincent Mok
- Department of Medicine and Therapeutics (L.L., H.L., V.I., Y.S., F.F., S.H.M., K.M., B.I., V.M., L.W., T.L., X.L.), The Chinese University of Hong Kong, Prince of Wales Hospital, China
| | - Lawrence Wong
- Department of Medicine and Therapeutics (L.L., H.L., V.I., Y.S., F.F., S.H.M., K.M., B.I., V.M., L.W., T.L., X.L.), The Chinese University of Hong Kong, Prince of Wales Hospital, China
| | - David Liebeskind
- Department of Neurology, Neurovascular Imaging Research Core and UCLA Stroke Center, University of California Los Angeles (D.L.)
| | | | - Xinyi Leng
- Shenzhen Research Institute, The Chinese University of Hong Kong, China (X.L.)
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45
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Tenekecioglu E, Katagiri Y, Takahashi K, Tomaniak M, Dudek D, Cequier A, Carrié D, Iñiguez A, Johannes van der Schaaf R, Dominici M, Boven AJV, Helqvist S, Sabaté M, Baumbach A, Piek JJ, Wykrzykowska JJ, Kitslaar P, Dijkstra J, Reiber JHC, Chevalier B, Ural D, Pekkan K, Bourantas CV, Gijsen F, Onuma Y, Torii R, Serruys PW. Endothelial shear stress and vascular remodeling in bioresorbable scaffold and metallic stent. Atherosclerosis 2020; 312:79-89. [PMID: 32979635 DOI: 10.1016/j.atherosclerosis.2020.08.031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2019] [Revised: 08/12/2020] [Accepted: 08/13/2020] [Indexed: 10/23/2022]
Abstract
BACKGROUND AND AIMS The impact of endothelial shear stress (ESS) on vessel remodeling in vessels implanted with bioresorbable scaffold (BRS) as compared to metallic drug-eluting stent (DES) remains elusive. The aim of this study was to determine whether the relationship between ESS and remodeling patterns differs in BRS from those seen in metallic DES at 3-year follow-up. METHODS In the ABSORB II randomized trial, lesions were investigated by serial coronary angiography and intravascular ultrasound (IVUS). Three-dimensional reconstructions of coronary arteries post-procedure and at 3 years were performed. ESS was quantified using non-Newtonian steady flow simulation. IVUS cross-sections in device segment were matched using identical landmarks. RESULTS Paired ESS calculations post-procedure and at 3 years were feasible in 57 lesions in 56 patients. Post-procedure, median ESS at frame level was higher in BRS than in DES, with marginal statistical significance (0.97 ± 0.48 vs. 0.75 ± 0.39 Pa, p = 0.063). In the BRS arm, vessel area and lumen area showed larger increases in the highest tercile of median ESS post-procedure as compared to the lowest tercile. In contrast, in DES, no significant relationship between median ESS post-procedure and remodeling was observed. In multivariate analysis, smaller vessel area, larger lumen area, higher plaque burden post-procedure, and higher median ESS post-procedure were independently associated with expansive remodeling in matched frames. Only in BRS, younger age was an additional significant predictor of expansive remodeling. CONCLUSIONS In a subset of lesions with large plaque burden, shear stress could be associated with expansive remodeling and late lumen enlargement in BRS, while ESS had no impact on vessel dimension in metallic DES.
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Affiliation(s)
- Erhan Tenekecioglu
- Department of Interventional Cardiology, Erasmus University Medical Center. Thoraxcenter, Rotterdam, the Netherlands
| | - Yuki Katagiri
- Department of Cardiology Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
| | - Kuniaki Takahashi
- Department of Cardiology Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
| | - Mariusz Tomaniak
- Department of Interventional Cardiology, Erasmus University Medical Center. Thoraxcenter, Rotterdam, the Netherlands; First Department of Cardiology, Medical University of Warsaw, Warsaw, Poland
| | - Dariusz Dudek
- Department of Interventional Cardiology, Jagiellonian University, Krakow, Poland
| | | | | | - Andrés Iñiguez
- Interventional Cardiology Unit, Cardiology Department, Hospital Alvaro Cunqueiro, University Hospital of Vigo, Vigo, Spain
| | | | | | | | | | - Manel Sabaté
- Biomédiques August Pi I Sunyer, University of Barcelona, Barcelona, Spain
| | | | - Jan J Piek
- Department of Cardiology Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
| | - Joanna J Wykrzykowska
- Department of Cardiology Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
| | - Pieter Kitslaar
- LKEB-Division of Image Processing, Department of Radiology, Leiden University Medical Centre, Leiden, the Netherlands
| | - Jouke Dijkstra
- LKEB-Division of Image Processing, Department of Radiology, Leiden University Medical Centre, Leiden, the Netherlands
| | - Johan H C Reiber
- LKEB-Division of Image Processing, Department of Radiology, Leiden University Medical Centre, Leiden, the Netherlands
| | - Bernard Chevalier
- Ramsay Générale de Santé, Institut Cardiovasculaire Paris Sud, Massy, France
| | - Dilek Ural
- Department of Cardiology, Koç University, Istanbul, Turkey
| | - Kerem Pekkan
- Department of Mechanical Engineering, Koç University, Istanbul, Turkey
| | - Christos V Bourantas
- Department of Cardiology, University College of London Hospitals, London, United Kingdom; Department of Cardiology, Barts Heart Centre, London, United Kingdom
| | - Frank Gijsen
- Department of Biomedical Engineering, Erasmus University Medical Center, Thoraxcenter, Rotterdam, the Netherlands
| | - Yoshinobu Onuma
- Department of Interventional Cardiology, Erasmus University Medical Center. Thoraxcenter, Rotterdam, the Netherlands
| | - Ryo Torii
- Department of Mechanical Engineering, University College London, United Kingdom
| | - Patrick W Serruys
- Imperial College London, London, United Kingdom; Department of cardiology, National University of Ireland, Galway (NUIG), Galway, Ireland.
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Samady H, Molony DS, Coskun AU, Varshney AS, De Bruyne B, Stone PH. Risk stratification of coronary plaques using physiologic characteristics by CCTA: Focus on shear stress. J Cardiovasc Comput Tomogr 2020; 14:386-393. [DOI: 10.1016/j.jcct.2019.11.012] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Revised: 08/15/2019] [Accepted: 11/24/2019] [Indexed: 01/09/2023]
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Godo S, Corban MT, Toya T, Gulati R, Lerman LO, Lerman A. Association of coronary microvascular endothelial dysfunction with vulnerable plaque characteristics in early coronary atherosclerosis. EUROINTERVENTION 2020; 16:387-394. [DOI: 10.4244/eij-d-19-00265] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
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48
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Wang L, Tang D, Maehara A, Wu Z, Yang C, Muccigrosso D, Matsumura M, Zheng J, Bach R, Billiar KL, Stone GW, Mintz GS. Using intravascular ultrasound image-based fluid-structure interaction models and machine learning methods to predict human coronary plaque vulnerability change. Comput Methods Biomech Biomed Engin 2020; 23:1267-1276. [PMID: 32696674 DOI: 10.1080/10255842.2020.1795838] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
Plaque vulnerability prediction is of great importance in cardiovascular research. In vivo follow-up intravascular ultrasound (IVUS) coronary plaque data were acquired from nine patients to construct fluid-structure interaction models to obtain plaque biomechanical conditions. Morphological plaque vulnerability index (MPVI) was defined to measure plaque vulnerability. The generalized linear mixed regression model (GLMM), support vector machine (SVM) and random forest (RF) were introduced to predict MPVI change (ΔMPVI = MPVIfollow-up‒MPVIbaseline) using ten risk factors at baseline. The combination of mean wall thickness, lumen area, plaque area, critical plaque wall stress, and MPVI was the best predictor using RF with the highest prediction accuracy 91.47%, compared to 90.78% from SVM, and 85.56% from GLMM. Machine learning method (RF) improved the prediction accuracy by 5.91% over that from GLMM. MPVI was the best single risk factor using both GLMM (82.09%) and RF (78.53%) while plaque area was the best using SVM (81.29%).
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Affiliation(s)
- Liang Wang
- School of Biological Science and Medical Engineering, Southeast University, Nanjing, China.,Mathematical Sciences Department, Worcester Polytechnic Institute, Worcester, MA, USA
| | - Dalin Tang
- School of Biological Science and Medical Engineering, Southeast University, Nanjing, China.,Mathematical Sciences Department, Worcester Polytechnic Institute, Worcester, MA, USA
| | - Akiko Maehara
- The Cardiovascular Research Foundation, Columbia University, New York, NY, USA
| | - Zheyang Wu
- Mathematical Sciences Department, Worcester Polytechnic Institute, Worcester, MA, USA
| | - Chun Yang
- Mathematical Sciences Department, Worcester Polytechnic Institute, Worcester, MA, USA
| | - David Muccigrosso
- Mallinckrodt Institute of Radiology, Washington University, St. Louis, MO, USA
| | - Mitsuaki Matsumura
- The Cardiovascular Research Foundation, Columbia University, New York, NY, USA
| | - Jie Zheng
- Mallinckrodt Institute of Radiology, Washington University, St. Louis, MO, USA
| | - Richard Bach
- Cardiovascular Division, Washington University School of Medicine, St. Louis, MO, USA
| | - Kristen L Billiar
- Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA, USA
| | - Gregg W Stone
- The Cardiovascular Research Foundation, Columbia University, New York, NY, USA
| | - Gary S Mintz
- The Cardiovascular Research Foundation, Columbia University, New York, NY, USA
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Cameron JN, Mehta OH, Michail M, Chan J, Nicholls SJ, Bennett MR, Brown AJ. Exploring the relationship between biomechanical stresses and coronary atherosclerosis. Atherosclerosis 2020; 302:43-51. [PMID: 32438198 DOI: 10.1016/j.atherosclerosis.2020.04.011] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2019] [Revised: 04/05/2020] [Accepted: 04/22/2020] [Indexed: 10/24/2022]
Abstract
The pathophysiology of coronary atherosclerosis is multifaceted. Plaque initiation and progression are governed by a complex interplay between genetic and environmental factors acting through processes such as lipid accumulation, altered haemodynamics and inflammation. There is increasing recognition that biomechanical stresses play an important role in atherogenesis, and integration of these metrics with clinical imaging has potential to significantly improve cardiovascular risk prediction. In this review, we present the calculation of coronary biomechanical stresses from first principles and computational methods, including endothelial shear stress (ESS), plaque structural stress (PSS) and axial plaque stress (APS). We discuss the current experimental and human data linking these stresses to the natural history of coronary artery disease and explore the future potential for refining treatment options and predicting future ischaemic events.
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Affiliation(s)
- James N Cameron
- Monash Cardiovascular Research Centre and MonashHeart, Monash Health, Melbourne, Australia
| | - Ojas H Mehta
- Monash Cardiovascular Research Centre and MonashHeart, Monash Health, Melbourne, Australia
| | - Michael Michail
- Monash Cardiovascular Research Centre and MonashHeart, Monash Health, Melbourne, Australia; Institute of Cardiovascular Science, University College London, London, United Kingdom
| | - Jasmine Chan
- Monash Cardiovascular Research Centre and MonashHeart, Monash Health, Melbourne, Australia
| | - Stephen J Nicholls
- Monash Cardiovascular Research Centre and MonashHeart, Monash Health, Melbourne, Australia
| | - Martin R Bennett
- Division of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom
| | - Adam J Brown
- Monash Cardiovascular Research Centre and MonashHeart, Monash Health, Melbourne, Australia.
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Computational fluid dynamic study of multiple sequential coronary artery bypass anastomoses in a native coronary stenosis model. Coron Artery Dis 2020; 31:458-463. [PMID: 32271246 DOI: 10.1097/mca.0000000000000864] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND The objective of this study was to evaluate the hemodynamic characteristics of multiple sequential coronary artery bypass grafting using a computational fluid dynamics study. METHODS First anastomosis was configured into parallel and diamond anastomoses, and the second anastomosis was set as end-side anastomosis. The anastomosis incision lengths were fixed at 2 mm. Various combinations of the degree of first and second stenoses were studied. The diameter of both the native and graft vessels was set at 2 mm. The inlet boundary condition was set by a sample of the transient time flow measurement, which was measured intraoperatively. RESULTS Both swirl and stagnation were observed at the outlets of the stenosis and the anastomosis sites. When the severity of the second stenosis was larger than that of the first, the flow at the outlet of the second stenosis was more unstable. Higher wall shear stress and larger oscillatory shear index regions were observed when the severe stenosis was bypassed by the first anastomosis, especially with diamond anastomoses. Less energy loss and higher energy efficiency were present when the vessel with more severe stenosis was bypassed as the second anastomosis. Energy loss was lower and energy efficiency was higher with parallel anastomosis than diamond anastomosis when the severity of the two stenoses was the same. CONCLUSIONS It is ideal to bypass the less severe stenosis vessel first with a parallel anastomosis method when employing multiple sequential bypass grafting. This improves hemodynamic stability and energy efficiency, according to a computational fluid dynamics model.
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