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Abstract 107: Increased Peak Wall Stress in Women With Abdominal Aortic Aneurysms
- Eric Shang,
- Grace Wang,
- Ronald Fairman and
- Benjamin Jackson
Arteriosclerosis, Thrombosis, and Vascular Biology Volume 37, Issue suppl_11 May 2017

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Objective: Women with abdominal aortic aneurysms (AAA) exhibit more rapid aneurysm growth and greater rupture risk at equivalent diameters relative to men. Evidence suggests that biomechanical peak wall stress (PWS) derived from finite element analysis of AAAs is a superior predictor of rupture compared to maximum transverse diameter (MTD). This study aimed to investigate differences in the calculated PWS of AAAs between men and women.Method: Men (n=35) and women (n=35) with infrarenal AAAs with 45-55mm MTD undergoing CTA were identified. Customized image processing algorithms extracted patient-specific AAA geometries from raw DICOM images. The resulting aortic reconstructions incorporated patient-specific and regionally resolved aortic wall thickness, intraluminal thrombus, and wall calcifications. Aortic models were loaded with 120mmHg blood pressure using commercially available FEA solvers.Results: Peak wall stress was found to be significantly higher in women (299±51 vs 257±53 kPA, P=0.001, see Figure). Neither MTD (50.5±3.1 vs 49.8±2.9 mm, P=0.34), mean aortic wall thickness (2.38±0.52 vs 2.34±0.50 mm, P=0.69), nor wall thickness at location of PWS (2.36±0.60 vs 2.20±0.46 mm, P=0.20) varied by sex. While there were no sex-associated differences in aneurysm volume (86.6±27.0 vs 94.8±25.5 cm³, P=0.76) or intraluminal thrombus volume (14.2±11.7 vs 16.3±13.4 mm, P=0.33), women’s AAAs had significantly increased maximum Gaussian curvature (0.032±0.011 vs 0.025±0.015 mm^-2, P=0.03).Conclusion: Comparably sized AAAs in women were shown to have significantly higher peak wall stress. Maximum gaussian curvature, a measure of aneurysm morphology, was significantly different between the two groups. These results suggest that men and women possess distinct aneurysm geometries, and that PWS-derived rupture risk prediction may provide a more reliable estimator of rupture risk in all patients.
Abstract 179: Computational Modelling Of Early Atherosclerotic Plaque Structure Reveals The Role Of The Rate Of Lipid Deposition On Plaque Structure And Growth Rate
- Ishraq Uddin and
- Mary R Myerscough
Arteriosclerosis, Thrombosis, and Vascular Biology Volume 37, Issue suppl_11 May 2017

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Much current research on inflammation in atherosclerosis focuses on specific cellular and biochemical processes as isolated phenomena. There is scope, therefore, for an integrated approach that examines the interactions between the various mechanisms involved in early plaque growth. An in silico modelling approach is promising in this regard as multiple biological processes can easily be incorporated into the model and used to simulate early plaque growth under a variety of conditions. We present a computational model to simulate early plaque growth and test the hypothesis that higher rates of lipid deposition in the artery wall will cause accelerated plaque growth and influence the plaque’s morphology and composition.We formulate a mathematical model based on the observed interactions between macrophages, pro-atherogenic extracellular lipid, lipid accumulated by macrophages, and apoptotic cells/cellular debris. This basic model incorporates several key processes including monocyte recruitment, phagocytosis, proliferation, apoptosis, lipid cytotoxicity, and cell migration. The model is used to computationally simulate how the early development of the plaque is influenced by its physiological environment, focusing in particular on the rate of lipid influx into the artery wall. Individual simulations yield a profile of how cells and lipids are spatially distributed over the plaque, and how this distribution and the total plaque size evolve in time.The model qualitatively suggests that the rate of lipid deposition has a key influence on early plaque morphology and behaviour. Specifically, increasing the rate of lipid deposition (simulating higher fat diets) accelerates the rate of plaque growth. The ratio of apoptotic cells to active macrophages also increases with distance from the endothelium, with the ratio becoming more pronounced in older plaques. The computational model provides a novel methodology with which to capture the dynamics and structure of early atherosclerotic plaques, and provides a foundation on which to build models that can account for further aspects of the relevant biology, including plaque regression and necrotic core formation.
Abstract 485: On the Relative Effectiveness of Machine Learning and Statistical Methods in Predicting Abdominal Aortic Aneurysm Rupture in the Asian Population
- Tejas Canchi,
- Sourav S Patnaik,
- E Y Ng,
- Dinesh K Srinivasan,
- Sriram Narayanan and
- Ender A Finol
Arteriosclerosis, Thrombosis, and Vascular Biology Volume 37, Issue suppl_11 May 2017

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Background: Abdominal Aortic Aneurysms (AAA) have a high risk of mortality if they rupture, making it one of the leading causes of death in elderly men. Hence, a better prediction method is necessary to identify high rupture risk patients.Methods: Retrospective data (clinical and AAA geometric parameters) were collected of 114 Asian AAA patients from an IRB approved database. We applied a novel machine learning algorithm (MLA) to predict AAA rupture by generating a decision tree of rupture risk predictors. For comparative analysis, a binary logistic regression (backward stepwise Wald) was also performed. The rupture status was the dependent variable for both methods; each method provided the highest weighted risk factors and effectiveness of classification as assessed by Receiver Operating Characteristic (ROC) curves.Results: For the MLA, the most significant risk factors were DAAA (maximum diameter) (> 57 mm), presence of hypertension, D4 (diameter at the iliac bifurcation) (> 23.7 mm), age (> 79 years), and D3 (right common iliac artery diameter) (> 14 mm), as seen in Fig. 1a. Similarly, the backward stepwise logistic regression analysis showed a strong association for rupture with DAAA (O.R. 2.635), L1 (distance between the lowest renal artery and the iliac bifurcation) (O.R. 1.658), D3 (O.R. 1.876), NL (AAA neck length) (O.R. 0.294), and age (O.R. 0.681). The MLA exhibited a lower classification accuracy (80.7% vs. 99.2%) and area under the curve (ROC analysis) (56.3% vs. 98.2%) when compared to the regression analysis, as seen in Fig. 1b.Conclusions: This is the first known report of predictive rupture risk in the Asian AAA patient population using MLA and statistical methods. Although the MLA did not provide improved classification accuracy compared to a standard statistical method, the risk factors obtained from both methods were similar. Future studies will aim at improving the prediction ability of MLA in a racially diverse AAA patient population.
Abstract 562: Human Carotid Atherosclerosis Plaque Progression and Vessel Material Stiffness at Follow Up Had Positive Correlation: An in vivo Vessel Stiffness MRI Follow Up Study
- Qingyu Wang,
- Dalin Tang,
- Gador Canton,
- Jian Guo,
- Xiaoya Guo,
- Thomas S Hatsukami,
- Kristen L Billiar,
- Zheyang Wu and
- Chun Yuan
Arteriosclerosis, Thrombosis, and Vascular Biology Volume 37, Issue suppl_11 May 2017

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It is hypothesized that artery stiffness may be associated with plaque progression. However, in vivo vessel material stiffness follow-up data is lacking in the literature.In vivo 3D multi-contrast and Cine magnetic resonance imaging (MRI) carotid plaque data were acquired from 8 patients with follow-up (18 months) with written informed consent obtained. Cine MRI and 3D thin-layer models were used to determine parameter values of the Mooney-Rivlin models for the 81slices from 16 plaques (2 scans/patient) using our established iterative procedures. Effective Young’s Modulus (YM) values for stretch ratio [1.0,1.3] were calculated for each slice for analysis.Stress-stretch ratio curves from Mooney-Rivlin models for the 16 plaques and 81 slices are given in Fig. 1. Average YM value of the 81 slices was 411kPa. Slice YM values varied from 70 kPa (softest) to 1284 kPa (stiffest), a 1734% difference. Average slice YM values by vessel varied from 109 kPa (softest) to 922 kPa (stiffest), a 746% difference. Location-wise, the maximum slice YM variation rate within a vessel was 306% (139 kPa vs. 564 kPa). Average slice YM variation rate within a vessel for the 16 vessels was 134%. Average variation of YM values from baseline (T1) to follow up (T2) for all patients was 61.0%. The range of the variation of YM values was [-28.4%, 215%]. For progression study, YM increase (YMI=YM_T2-TM_T1) showed negative correlation with plaque progression measured by wall thickness increase (WTI), (r= -0.6802, p=0.0634). YM_T2 showed strong negative correlation with WTI (r= -0.7764, p=0.0235). Correlation between YM_T1 and WTI was not significant (r= -0.4353, p= 0.2811).Conclusion In vivo carotid vessel material properties have large variations from patient to patient, along the vessel segment within a patient, and from baseline to follow up. Use of patient-specific, location specific and time-specific material properties could potentially improve the accuracy of model stress/strain calculations.
Abstract 345: Combining Morphological and Mechanical Risk Factors May Improve Carotid Plaque Progression Prediction: an Magnetic Resonance Image-Based Follow-Up Study
- Dalin Tang,
- Qingyu Wang,
- Gador Canton,
- Thomas S Hatsukami,
- Kristen L Billiar,
- Zheyang Wu and
- Chun Yuan
Arteriosclerosis, Thrombosis, and Vascular Biology Volume 38, Issue Suppl_11 May 2018

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It has been hypothesized that combining morphological and mechanical risk factors may improve plaque progression prediction. In this paper, plaque burden (PB), cap thickness (CT), lipid percent (LP), plaque wall stress (PWS), plaque wall strain (PWSn) and their combinations were used as predictors to identify the best predictor(s) for plaque progression measured by plaque area increase (PAI) from baseline (T1) and follow-up (T2).In vivo magnetic resonance image (MRI) carotid plaque data were acquired from 8 patients (5 m, mean age 71) with follow-up (18 months) with informed consent obtained. We built 3D thin-layer models for the 41 matched slices to obtain plaque stress/strain data using patient-specific material properties determined from Cine MRI and patient arm blood pressure. The mean values of the 5 predictors from all lumen points of each slice were obtained for analysis. For each predictor Y, a threshold value Yc was determined so that optimal agreement rate was obtained (agreement cases are either {(Y>Yc) and (PAI >0)} or {(Y≤Yc) and (PAI ≤0)}). For PWS and PWSn, we used (either {(Y<Yc) and (PAI >0)} or {(Y≥Yc) and (PAI ≤0)}). Two combinations of predictorsCOM1=a1*PB+a2*CT+a3*LP,COM2=b1*PB+b2*CT+b3*LP+b4*PWS+b5*PWSnwere considered, where COM1 combines PB with morphological features, and COM2 combines all 5 predictors. The coefficients in these formulas were determined by using iterative linearly fitting method and initial guess of threshold values from single predictor results.The optimal threshold values for the 5 single predictors and 2 combination predictors are given in Table 1. PWSn was the best single predictor and COM2 was the best combination predictor.The threshold value-based method is simple and easy for clinical implementation. Our preliminary results indicate that combining PB, CT, LP, PWS, and PWSn could improve the agreement rate by nearly 10%, compared to using PB alone. Large-scale patient studies are needed to confirm our findings.
Abstract 363: Platelet Mass Retraction is a Negative Feedback Regulator of Thrombin Generation and Activity
- Timothy J Stalker,
- Leonard Nettey,
- Chelsea Matzko,
- Izmarie Poventud-Fuentes,
- Talid Sinno,
- Lawrence F Brass and
- Maurizio Tomaiuolo
Arteriosclerosis, Thrombosis, and Vascular Biology Volume 38, Issue Suppl_11 May 2018

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Endogenous anticoagulants, including antithrombin III, tissue factor pathway inhibitor, and activated protein C (aPC) provide a biochemical means to inhibit thrombin generation and/or activity. In addition, we have previously shown that platelet mass retraction prevents the escape and exchange of solutes, thereby providing a biophysical mechanism to limit thrombin generation and activity. The relative contribution of each of these biochemical and biophysical mechanisms to the termination of thrombin activity during the hemostatic response in vivo remains poorly understood. Here, using computational simulations coupled with in vivo experimental models, we tested the hypotheses that 1) platelet mass retraction itself is physiologically relevant to inhibit thrombin generation; and 2) that given the spatial localization of protein C activation on the endothelial cell surface, aPC mediated thrombin inhibition has negligible effects on the hemostatic response. Our computational model has several innovative aspects, including 3D representations of the vessel, extravascular space, and injury, blood flow, and a simplified but anatomically correct model of coagulation. Our simulations show that tissue factor localization combined with flow exiting the injury limit thrombin generation/activity to the extravascular space. Our experiments using a mouse jugular puncture injury model show rich deposition of fibrin in the extravascular space and little to no fibrin in the luminal side. Additionally, our simulations illustrate how platelet mass retraction inhibits thrombin generation by decreasing the delivery of substrates, such as prothrombin and factor X, and at the same time it limits thrombin activity by constraining its movement. These effects are mediated by physical forces only and are independent of the biochemical inhibitory pathways. Our in vivo experiments using aPC inhibitory antibodies show that lack of aPC mediated thrombin inhibition has negligible effects on the hemostatic response. In conclusion, this study suggests that platelet mass retraction is an underappreciated mechanism that negatively regulates thrombin generation, while aPC mediated inhibition of thrombin generation plays a minor role in hemostasis.
Abstract 709: Computational Seal Zone Mechanics - Predicting EVAR Failures
- Luka Pocivavsek,
- Christopher Skelly and
- Ross Milner
Arteriosclerosis, Thrombosis, and Vascular Biology Volume 38, Issue Suppl_11 May 2018

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Introduction: Endovascular aortic stent-graft technology (EVAR) radically altered aortic aneurysm repair from a maximally invasive procedure to a minimally invasive approach. While the overall principle of the repair remained the same, the surgeon ceded control of graft/aorta coupling with EVAR from the time-honored surgical approach of suturing, which creates a mechanical kinematic coupling constraint at the graft/aorta interface. In EVAR, the coupling condition is replaced by contact mechanics between the outer graft surface and the aorta. We hypothesize that proximal endograft failure is linked to the complex contact mechanics occurring at the graft/aorta interface.Methods: We performed a detailed geometric/finite element analysis (FEA) of an abdominal aortic aneurysm in a patient who presented with a ruptured juxta-renal AAA. We used the pre and post-operative CTA imaging to perform FEA and defined the stent graft (SG)/aortic wall interactions using a fully integrated cohesive zone model (CZM) (see figure 1).Results: Three degrees of adhesion strength were studied, corresponding to F~0.1, 10, and 1000 Newton. In the case of the two weaker adhesion strengths, the SG and neck separated at local points along the interface. These areas of separation (interfacial failure) corresponded to zones of high stress (~ 10MPa) within the aortic wall. This points to a new physical model of aortic/SG stability, where local elastic deformation energy in the neck (G) competes with aortic/SG adhesion energy (gamma~Gc) giving rise to the criterion for seal failure: G>Gc .Conclusions: The energy balance of deformation of the aortic neck with stent graft adhesion strength provides a key new parameter in evaluating future EVAR repairs. Non-linear neck geometries give rise to complex non-linear stress distributions that can greatly impact the stability of a repair. We provide a computational methodology in which this can be systematically studied for any given patient anatomy.
Abstract 240: The Peak Systolic Velocity Ratio May Underestimate Internal Carotid Stenosis in the Presence of a Common Carotid Tandem Lesion
- Joe L Pantoja,
- Esteban Aguayo,
- Peter A Pellionisz,
- Erik Dutson,
- Peter F Lawrence and
- David A Rigberg
Arteriosclerosis, Thrombosis, and Vascular Biology Volume 39, Issue Suppl_11 May 2019

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Objectives: The consequences of a tandem common carotid artery (CCA) stenosis on standard sonographic criteria for grading internal carotid artery (ICA) stenoses are uncertain. This study aims to evaluate the use of sonographic parameters to grade ICA stenoses in the presence of a tandem CCA stenosis.Methods: A three-dimensional computational fluid dynamics model of the carotid artery was created from published geometry and flow characteristics. Next, a series of stenotic lesions (25-75% stenosis) were created in the proximal ICA with tandem lesions (25-75% stenosis) at the distal CCA. Two cardiac cycles were simulated and velocities at end diastole and peak systole (PSV) were measured at the ICA stenosis and the CCA stenosis (distal and proximal). CCA velocities both proximal and distal to the stenosis were then used to calculate ICA:CCA PSV ratios.Results: Without a tandem CCA stenosis, PSV and end diastolic velocity for a 75% ICA stenosis were 271.5 and 123.9 cm/s and 82.7 and 31.8 cm/s for a 50% ICA stenosis. With a tandem 75% CCA stenosis, velocities for a 75% ICA stenosis were 272.2 and 120.2 cm/s and 110.5 and 36.2 cm/s for a 50% ICA stenosis. However, a 75% CCA lesion decreased the ICA:CCA PSV ratio for a 75% ICA stenosis from 12.9 to 2.7 when CCA PSV was measured distal to the CCA stenosis. There was a three-fold increase in PSV across the 75% CCA stenosis (32.3 to 101.9 cm/s) effectively reducing the ratio. If the CCA PSV is measured proximal to the stenosis, then the ICA: CCA PSV ratio is unaffected.Conclusion: In the presence of a proximal tandem stenosis in the CCA, PSV and end diastolic velocity continue to distinguish between severe and moderate ICA stenoses. In the presence of a flow restricting tandem lesion, the PSV ratio is an unreliable measure of ICA stenosis unless CCA velocity is measured proximal to the tandem lesion. We recommend measuring CCA velocities proximal to any tandem lesions when possible. Furthermore, a discordance between ICA velocities and ratios may indicate the presence of a proximal tandem lesion otherwise missed on ultrasound.
Abstract 370: Machine Learning Powered High Resolution Identification of Monocyte Predictor Genes for Residual Cardiovascular Risk
- Chuan Li,
- Lili Qu,
- Yongmei Liu,
- Anthony Vella,
- Patrick Murphy,
- Annabelle Rodriguez and
- Beiyan Zhou
Arteriosclerosis, Thrombosis, and Vascular Biology Volume 40, Issue Suppl_11 May 2020

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Despite lipid-control therapies, substantial risk of major cardiovascular event remains. New approaches are needed to define and mitigate residual risks in a patient specific manner.Monocytes, critical player in CVD, transcriptionally respond to metabolic and inflammatory cues in the circulation and contribute to atherogenesis. However, previous studies of monocytes only found moderate associations to CVD events and with limited predictive power. Here we developed a novel computational approach from our macrophage characterization platform MacSpectrum, which effectively depicted heterogeneity of foam cells. Our algorithms revealed distinct separation by inflammatory features: foam cells with or without inflammatory programs. Whole-transcriptome analyses for these newly defined subpopulations identified a set of signature genes that depict inflammatory foam cell states significantly associated with severity of atherosclerosis in patients (gtexportal.org), including NR1H3, CLEC4E, and ACAT1.Next, we performed feature-based machine learning to characterize physiological parameters (BMI, lipid profiles, sex, etc) and monocyte transcriptome profiles of 1202 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). Consistently, our innovative inflammatory indices successfully identified subjects with CVD events by the transcriptome of their circulating monocytes independent of lipid profiles. We further created a recursive machine learning pipeline and developed a prognostic model that achieved high predicting power of AUC up to 0.97 in the MESA dataset (using 80% and 20% random subsets for training and testing), and 0.9 AUC in a different cohort (GSE129935) not included in training, despite their distinct background from MESA cohort.In summary, we successfully identified pathogenic foam cell subpopulations with active inflammatory and lipid metabolic programs. Characterization of these subsets revealed novel feature-based key genes directly contributing to CVD residual risks and endowed creation of a CVD prediction model with high accuracy. Further optimizing this model will facilitate both mechanistic investigations and development of therapeutic and prognosis strategies of CVD residual risk.
Abstract 431: MaxSpliZer: A Tool To Predict Effects Of LDLR Splice Variants Based On The Maximum Entropy Model
- Seyedmohammad Saadatagah,
- Reza Shahnazar,
- Alborz Sherafati,
- Lubna Alhalabi,
- Alexandra A Miller,
- Hamed Marwan and
- Iftikhar J Kullo
Arteriosclerosis, Thrombosis, and Vascular Biology Volume 42, Issue Suppl_11 May 2022

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Background: The Clinical Genome Resource Consortium (ClinGen) recommends MaxEntScan (MES) model to predict the effects of LDLR splice variants. We developed “MaxSpliZer”, a software tool to automate the implementation of MES, and validated it using ClinVar and UK-Biobank (UKBB) data.Method: We tested concordance of MaxSpliZer predictions with ClinVar classifications of benign/likely benign (B/LB) and pathogenic/likely pathogenic (P/LP) for LDLR variants with potential effect on splicing. We also annotated LDLR splice variants in 200,618 UKBB participants, categorizing them using MaxSpliZer as deleterious (n=90) and non-deleterious (n=7,404). Low-density lipoprotein cholesterol (LDL-C) levels were compared in these two groups after adjustment for lipid-lowering medication use.Results: MaxSpliZer prediction was concordant with the ClinVar classification in 128 of 138 P/LP variants (sensitivity 93%) and 432 of 436 B/LB variants (specificity 99%). In the UKBB, splice variants predicted as deleterious by MaxSpliZer had higher LDL-C than non-deleterious splice variants (158.7±47.4 vs. 146.0±34.8mg/dL, p-value = 0.014). Compared to manual curation time of 12±7 min per variant, MaxSpliZer took 0.52±0.11 min for single entries and 1.5 s per variant for biobank-scale data.Conclusion: MaxSpliZer, a software tool that implements MES based on the ClinGen guideline, can accurately classify LDLR splice variants in a rapid automated fashion.
Abstract 522: Computational Fluid Dynamics Analyses Of Geometric Incompatibility And Seal Zone Stability In Endovascular Aneurysm Repair
- Willa Li,
- Žiga Donik,
- Kayla Polcari,
- Seth Sankary,
- Sanjeev Dhara,
- Kathleen Cao,
- Nhung Nguyen,
- Janez Kramberger and
- Luka Pocivavsek
Arteriosclerosis, Thrombosis, and Vascular Biology Volume 43, Issue Suppl_11 May 2023

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Introduction: Long-term durability of endovascular aneurysm repair (EVAR) is often compromised due to inadequate sealing of the endograft to the aorta. We hypothesize that geometric mismatch between the aorta and endograft can lead to the development of bird-beak regions, type Ia endoleaks, and endograft migration. Our novel computational model shows how geometric incompatibility at the seal zone contributes to endoleak formation and propagation.Methods: Using finite-element modeling, we simulated endograft crimping and deployment in pressurized aortic models with different degrees of curvature (0°, 30°, 60°) and oversizing (0%, 20%, 25%). We then performed computational fluid dynamics (CFD) modeling with a detailed pressure analysis of various regions along the length of each model.Results: Across our models, pressure gradients developed between the bulk flow and endoleak regions. For all degrees of curvature, the average total pressure in the endoleak region was higher than that of the bulk flow in the 20% and 25% oversized models. While oversizing decreased the aorta-endograft geometric mismatch in the 60° model and mitigated the volume of endoleak, too much oversizing in the 0° models worsened endoleak.Conclusions: We present one of the first computational models to study the sensitivity of seal zone mechanics to the degree of aorta-endograft mismatch. Our finding of pressure gradients that exist between the endoleak and bulk flow may represent regions of high mechanical instability that may further propagate the endoleak. Our results highlight the importance of shape and oversizing considerations when selecting the appropriate endovascular therapy for EVAR patients.Figure 1: CFD simulations of aorta-endograft models with different degrees of curvature and oversizing show endoleak formation as a function of geometric incompatibility.
Abstract 622: Automated Platform For Large Scale Structural Simulations Of Atherosclerotic Lesions
- Ross Straughan,
- Karim Kadry,
- Elazer R Edelman and
- Farhad R Nezami
Arteriosclerosis, Thrombosis, and Vascular Biology Volume 43, Issue Suppl_11 May 2023

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Coronary artery disease persists as the world’s leading cause of death and often associated with atherosclerotic plaque disruption in the face of excessive plaque structure stress (PSS). Lesion tolerance of PSS correlates with the material and morphological properties of the arterial constituents. 2D-Finite Element Analysis (FEA) performed on models generated from arterial images (e.g. optical coherence tomography (OCT)) has procured a deeper understanding of lesion biomechanics but not the full complex 3D morphological-mechanical response. OCT frame sparsity and manual burden associated with 3D model generation have continuously plagued 3D simulations and automated large-scale studies. We present a fully automated software platform to determine 3D arterial stress distributions from deep-learning labeled OCT images of complex lesions by interpolating labeled frames. A preliminary study showed that frames with a high PSS (over 150 kPa) had significantly larger lipid arc angles, lumen-plaque eccentricity, lipid area, and calcium area, mirroring clinical observations. Such promising results validate the potential for the platform to be utilized for plethora of applications from unprecedented large scale in-silico studies to enhance clinical metrics, optimization of patient-specific angiography operations, and training data for emerging AI simulations.
Abstract 685: A New Volumetric Quantification Method For Atherosclerosis Using Histological Sections
- David B Graf,
- Hisashi Sawada,
- Alan Daugherty and
- Hong S Lu
Arteriosclerosis, Thrombosis, and Vascular Biology Volume 43, Issue Suppl_11 May 2023

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Background and Objective: Commonly used quantification methods of atherosclerosis in mouse models include en face analysis of lesions in the aorta and lesion area measurements in the aortic roots using cross-sections. The major shortcoming of these methods is that they quantify surface area, which does not reflect the total volume of atherosclerosis. The purpose of this study is to develop a method to measure atherosclerosis lesion volume.Methods and Results: Male LDL receptor -/- mice were fed a Western diet for 12 weeks, and then euthanized to collect aortic roots. Serial cross-sections of mouse aortic roots were obtained through a distance of 1 mm that included both the aortic sinus and a small portion of the ascending aorta. The interval between each two serial sections on a same slide were 100 μm. The cross-sections from one slide were stained with hematoxylin and eosin, then digitized using a robotic slide scanner. Lesion areas were captured using a post-processing stage to output accurate areas of lesions. This algorithm used linear regression combined with integration to give a volumetric approximation. This process acquired area of atherosclerosis in each section without bias, and created a regression line between sections from the area data, then integrated those functions over the distance between sections. Each integral region was aggregated to yield the total volume of atherosclerotic plaques.Conclusion: The volumetric approximation using a linear regression combined with integration is a simple and useful method for the quantification of atherosclerosis via histological sectioning.
Abstract 15816: Normal Distribution of Wall Shear Stress in the Coronary Arteries
- Anna Starikov,
- Guanglei Xiong and
- James K Min
Circulation Volume 132, Issue suppl_310 November 2015

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Introduction: The ability to detect hemodynamically significant coronary artery disease non-invasively has been a goal that has the potential to improve patient care significantly. New non-invasive approaches using coronary CT angiograms (CCTAs) have been proposed and appear to show some promise.Hypothesis: One such method is the measurement of measuring wall shear stress (WSS), the tangential force of flowing blood against the artery wall, using computational fluid dynamics (CFD). However, in order to deem this technique useful in clinical practice, the normal values must first be defined. These values have been minimally reported and are limited to the left coronary tree.Methods: We ran a CFD simulation of WSS on 3-D reconstructions of the coronary arteries derived from the CCTAs of 35 patients with either no disease or non-obstructive (< 50%) stenosis from the DeFACTO trial, a multi-center study. The resulting model was segmented according to the Society of Cardiovascular CT guidelines, separating the proximal and distal parts of each artery as well as the major side branches. The segments were composed of WSS values at hundreds of points along the vessel wall. The median value was taken as a representative of each segment.Results: The average values were calculated and varied significantly from one another, especially the proximal and distal parts of the same artery, as showing in Figure 1.Conclusions: These results establish the first known WSS distribution within all of the coronary arteries and serve as a foundation for defining a cut-off for abnormal values. Importantly, they also illuminate the variability of WSS that occurs even throughout a single artery and suggests that perhaps multiple abnormal cutoffs need to be established to evaluate WSS based on the location of the stenosis.
Abstract 17888: A Dynamically Updated Cardiac Transplant Waitlist Mortality Score
- Vincent B Cruz,
- Robert Steffen,
- Randall Starling,
- David O Taylor,
- Kathy Hoercher,
- Jeevanantham Rajeswaran,
- Nicholas Smedira,
- Edward Soltesz,
- Eugene H Blackstone and
- Nader Moazami
Circulation Volume 132, Issue suppl_310 November 2015

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Introduction: U.S. heart allocation policies are currently under review. However, investigations into prioritization schemes for patients waiting for transplantation are hampered by the paucity of post-listing event data and complicated by widespread Mechanical Circulatory Support (MCS) usage.Hypothesis: A dynamic score can predict mortality and inform prioritization of patients awaiting heart transplant or considered for listing at time of MCS implant using clinical data, time-varying exposures, and laboratory values during listing.Methods: From 1/2008 to 6/2013, patients listed for transplant (n=314, 76%) or implanted with a MCS device with intention to list (n=101, 24%) were identified. Factors for a predictive, time-varying hazard model were selected from 74 pre-listing variables, 8 events and complications, and routine laboratory results after listing.Results: Seventy-eight deaths and 381 adverse events occurred during listing. A score based on 17 variables was developed, including black race, actual listing (vs. MCS), pulmonary artery pressure, history of coronary artery disease, diabetes, and ventricular tachycardia at listing, MCS implant and complications, dialysis, respiratory events, and neurologic events on the waitlist, and time-varying serum total bilirubin and creatinine. The figure shows a sample of predicted mortality scores varying over time as events and changes in biomarkers occur.Conclusions: We demonstrated a dynamic, updatable mortality risk score that predicts urgency among patients waiting for hearts independent of most demographics, heart failure etiology, symptoms, and cardiac function. This score tracks dynamic changes with time as biomarkers change and adverse events occur. MCS-related complications, neurologic events, and kidney failure significantly affect mortality. Future changes to U.S. heart transplant policies could use this newly developed tool as part of a larger allocation system.
Abstract 18045: Mild Coarctation of the Aorta: To Touch or Not to Touch the Patient? Looking at Left Ventricular Function and Hemodynamics
- Zahra Keshavarz Motamed,
- Amanda Randles,
- Farhad Rikhtegar Nezami,
- Ramon Partida,
- Kenta Nakamura,
- Pedro V Staziaki,
- Brian Ghoshhajra,
- Ami Bhatt and
- Elazer R Edelman
Circulation Volume 132, Issue suppl_310 November 2015

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Introduction: Coarctation of the aorta (COA) is an obstruction of the aorta distal to the left subclavian artery. A peak-to-peak trans-coarctation pressure gradient (P_KdP) of greater than 20 mmHg warns of severe COA and the need for interventional/surgical repair. The optimal method and timing of the intervention remain uncertain especially when the severity of COA is mild (P_KdP < 20 mmHg) and it is unclear if mild COA should be treated at all. Rosenthal (2001; J Am Coll Cardiol) suggested that treatment strategies for patients with mild COA may need to be redefined as transcatheter interventions emerge, and yet the risks and benefits of such interventions in patients with mild COA are unclear. The aim of this study is to investigate the effects of transcatheter intervention on hemodynamics of the aorta and left ventricle (LV) in eleven patients with mild COA.Methods. We used specially developed computational fluid dynamics and lumped parameter modeling framework along with highly-resolved particle image velocimetry data and clinical measurements (Doppler-echocardiography, cardiac catheterization, CT and MRI) in this study.Results. COA intervention can improve aortic hemodynamics to some extent (i.e., time-averaged wall shear stress, oscillating shear index, peak jet velocity and kinetic energy [all averaged in the descending aorta] were reduced by 20%, 13.3%, 26.7% and 25%, respectively). However there is no concomitant effect on the LV hemodynamics (i.e., stroke work, normalized stroke work and peak LV pressure were reduced by only 3.8%, 3.7% and 3.2%, respectively; arterial systemic compliance was also reduced by 17%; N=11; p < 0.05).Conclusion. Our computational approach can effectively model and predict clinical conditions. Herein one must question intervention for mild COA, as it has limited utility in reducing myocardial strain.Figure 1. Catheter data and results of lumped parameter modeling in patient No. 1.
Abstract 11277: Computational Fluid Dynamics Characterization of Pulsatile Flow in Patient Specific Central and Sano Shunts: Relevance to Shear-Stress Induced, Platelet-Mediated Thrombosis
- Robert Ascuitto,
- Nancy Ross-Ascuitto,
- Carey Celestin and
- Martin Guillot
Circulation Volume 134, Issue suppl_111 November 2016

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Introduction: Central shunts (aorta) and Sano shunts (right ventricle) connected to the pulmonary arteries (PAs) are vital operations for infants with complex heart defects. However, they can become thrombosed.Hypothesis: At sites of prominent angulation, flow augments wall shear stress (WSS), a determinate of platelet-mediated thrombosis.Methods: We employed a patient-based computational model (Fluent) of pulsatile flow (viscosity 5 cPa-s), using a finite volume method and cardiac catheterization data, and geometric simulations (Autodesk Inventor), using angiography, to study flow behavior and WSS. Two central (4.0 and 3.5 mm) and Sano (5 and 6 mm) shunts were assessed. At the inlet to the central and Sano shunts, ascending aorta (AAo, 87/40 and 93/35 mmHg) and right ventricle (RV, 99/10 and 84/10 mmHg) pressures were used, respectively. At the outlets, measured PA pressures were used.Results: For central shunts, Fig 1, WSS reached 245 Pa and 123 Pa, peak systole. For Sano shunts, Fig 2, WSS attained 203 Pa and 133 Pa, peak systole. At sites of angulation, we identified flow vortices augmenting WSS (>100 Pa), and downstream regions of flow stagnation and recirculation, which are conducive to platelet aggregation and thrombus formation. Shunt burden, assessed by averaging WSS over the luminal surface of the shunts and the cardiac cycle, was 73.0 Pa and 67.2 Pa for central shunts, and 34.9 Pa and 19.6 Pa for Sano shunts.Conclusions: Our results indicate central shunts present a higher risk for thrombosis than Sano shunts. Importantly, WSS induced, platelet-mediated thrombosis is insensitive to aspirin, as the process does not involve the cyclooxygenase pathway.
Abstract 11921: Risk Stratification for Ventricular Arrhythmia in Patients With Repaired Tetralogy of Fallot (TOF) via Image-Based Computational Simulations: A Pilot Study
- Mark J Cartoski,
- Adityo Prakosa,
- Plamen Nikolov,
- Patrick M Boyle,
- Philip J Spevak and
- Natalia Trayanova
Circulation Volume 134, Issue suppl_111 November 2016

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Introduction: Patients with repaired TOF have increased arrhythmia risk due to myocardial fibrosis, scar and right ventricular dilation. Current risk stratification lacks consistent predictive value and clinical practicality. We surmised that personalized models developed from cardiac late gadolinium enhancement MRI (LGE-MRI) could correctly assess risk of arrhythmia in patients with repaired TOF using our previously-validated Virtual Arrhythmia Risk Prediction (VARP) protocol.Methods: As a proof-of-concept retrospective study, we developed personalized 3D computational models of TOF hearts from LGE-MRI scans. Three patients with clinically disparate arrhythmia status were included: patient 1 (P1) had clinical episodes of sustained ventricular tachycardia (VT) and inducibility in electrophysiologic study (EPS); patient 2 (P2) had negative EPS despite documented runs of non-sustained VT; patient 3 (P3) had no clinical evidence of VT. Then, for each heart, we applied our VARP protocol to generate a computational model, including personalized representations of scar and fibrosis. We then assessed the inducibility of reentrant arrhythmia from 26 pacing sites.Results: For all three cases, VARP outcomes correlated with clinical observations. In the P1 model sustained VT was induced with rapid ventricular pacing, while only non-sustained VT was induced in the P2 model (Fig 1). No arrhythmia was induced in the P3 model. Reentrant wavefronts in P1 and P2 occurred near the right ventricular outflow tract (RVOT) or ventricular septal defect patch, common sites of reentry observed in EPS in patients with TOF (Fig 1).Conclusion: Application of the VARP approach in repaired TOF patients is feasible and has the potential to correctly identify patients with a high risk of developing arrhythmia. With additional validation this non-invasive technique could serve as an effective tool for longitudinal risk assessment and help guide clinical decision making.
Abstract 14705: Quantitative Assessment of Residual Coronary Dissections Six Months After Balloon Angioplasty: A Novel Approach Using Optical Coherence Tomography
- Tudor C Poerner,
- Sylvia Otto,
- Corinna Duderstadt,
- Hans R Figulla and
- Christian Schulze
Circulation Volume 134, Issue suppl_111 November 2016

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Introduction: The feasibility of fractional flow reserve (FFR)-guided angioplasty using paclitaxel-coated balloons without stent implantation (DCB-only PCI) has been investigated in the OCTOPUS-2 trial (NCT02120859). According to the study protocol, dissections classified as NHLBI types A and B were not stented, if FFR > 0.8 and residual stenosis < 40%.Hypothesis: We evaluated the extent of residual dissections using the optical coherence tomography (OCT) recordings obtained at 6-month follow-up (f/u).Methods: A number of 41 pt with 45 lesions were successfully treated by FFR-guided DCB-only PCI and underwent 6-month angiographic and OCT f/u. OCT analysis included manual tracing of dissections and plaques, which were entered into a dedicated software program. The algorithm enabled beyond the spread-out vessel reconstruction ("carpet view" of inner vessel surface: Fig. 1) also the computation of volume, luminal surface area and length of dissections and plaques.Results: As shown in Table 1, no correlation was found between angiography and OCT at f/u regarding the presence or the extension of dissections. Angiographic dissection type, vessel diameter, lesion length, plaque burden or balloon to artery ratio were not predictive for the presence of dissection at OCT f/u.Conclusions: Clinically silent residual dissections after balloon angioplasty are largely misdiagnosed by angiography. Intracoronary imaging and FFR proved useful to guide the procedure and avoid unnecessary stenting. OCT using this novel algorithm for spread-out vessel reconstruction enables a comprehensive quantitative analysis of coronary artery dissections and plaque burden.
Abstract 16160: Using Computational Fluid Dynamics and Imaging Registration Techniques to Identify Predictive Hemodynamic Factors of Aneurysmal Degeneration in Type B Aortic Dissection
- Huijuan Xu,
- Bradley G Leshnower,
- Marina Piccinelli and
- Alessandro Veneziani
Circulation Volume 134, Issue suppl_111 November 2016

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Introduction: Progressive false lumen aneurysmal degeneration in type B aortic dissection (TBAD) is a complex process that is multi-factorial in etiology. Patient-specific computational fluid dynamics (CFD) simulations provide spatial and temporal hemodynamic quantities which facilitate the understanding of this disease progression.Hypothesis: By combining comprehensive morphological changes obtained using the image registration (IR) method, correlations between hemodynamic factors and changes in the false lumen may be established.Methods: Patient-specific CFD simulations were performed for the initial and four-year follow-up CT scans of a TBAD patient. Hemodynamic quantities, including wall shear stress and its gradient, time averaged wall shear stress and oscillatory shear index (OSI) were extracted from CFD simulations while a 3D deformation map between the initial and follow-up geometries was obtained using IR. Correlations between hemodynamic factors and the deformation map were analyzed.Results: Deformation contours obtained by registering the follow-up false lumen to initial presentation are shown in Figure A. Maximum deformation was observed in the anterior region while maximum wall shear stress in both stages appeared at the entry tear (15.57 v.s. 15.08 Pa). The aorta on the initial scan had higher wall shear stress (at peak systole), wall shear stress gradient and time average wall shear stress on the false lumen (0.41 vs 0.07 Pa, 3.32 vs 0.18 Pa and 0.21 vs 0.08 Pa). In contrast, the averaged OSI was lower as compared to the follow up (0.12 vs 0.18), as shown in Figure B. Moreover, as shown in Figure A and B, a close correlation between OSI and deformation contours was observed.Conclusions: OSI appears closely associated with false lumen degeneration in this patient. Further testing of this methodology may enable the use of CFD to predict which patients with complicated TBAD will develop late complication requiring surgical intervention.

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