Managing Iatrogenic Aortic Dissection: Insight from 3D-holographic Imaging and CT Computational Fluid Dynamic Simulations.

Iatrogenic aortic dissection is a rare but life-threatening complication of coronary artery bypass surgery. We report a case with incidentally detected iatrogenic aortic dissection related to aorta cross-clamping successfully managed with watchful follow-up. The decision-making was based on 3D hologram and fluid dynamic analysis guidance.

Point-of-care detection of fibrosis in liver transplant surgery using near-infrared spectroscopy and machine learning.

Introduction: Visual assessment and imaging of the donor liver are inaccurate in predicting fibrosis and remain surrogates for histopathology. We demonstrate that 3-s scans using a handheld near-infrared-spectroscopy (NIRS) instrument can identify and quantify fibrosis in fresh human liver samples. Methods: We undertook NIRS scans on 107 samples from 27 patients, 88 from 23 patients with liver disease, and 19 from four organ donors. Results: Liver disease patients had a median immature fibrosis of 40% (interquartile range [IQR] 20-60) and mature fibrosis of 30% (10%-50%) on histopathology. The organ donor livers had a median fibrosis (both mature and immature) of 10% (IQR 5%-15%). Using machine learning, this study detected presence of cirrhosis and METAVIR grade of fibrosis with a classification accuracy of 96.3% and 97.2%, precision of 96.3% and 97.0%, recall of 96.3% and 97.2%, specificity of 95.4% and 98.0% and area under receiver operator curve of 0.977 and 0.999, respectively. Using partial-least square regression machine learning, this study predicted the percentage of both immature (R 2 = 0.842) and mature (R 2 = 0.837) with a low margin of error (root mean square of error of 9.76% and 7.96%, respectively). Conclusion: This study demonstrates that a point-of-care NIRS instrument can accurately detect, quantify and classify liver fibrosis using machine learning.

Angiography and optical coherence tomography derived shear stress: are they equivalent in my opinion?

Advances in image reconstruction using either single or multimodality imaging data provide increasingly accurate three-dimensional (3D) patient's arterial models for shear stress evaluation using computational fluid dynamics (CFD). We aim to evaluate the impacts on endothelial shear stress (ESS) derived from a simple image reconstruction using 3D-quantitative coronary angiography (3D-QCA) versus a multimodality reconstruction method using optical coherence tomography (OCT) in patients' vessels treated with bioresorbable scaffolds. Seven vessels at baseline and five-year follow-up of seven patients from a previous CFD investigation were retrospectively selected for a head-to-head comparison of angiography-derived versus OCT-derived ESS. 3D-QCA significantly underestimated the minimum stent area [MSA] (-2.38mm2) and the stent length (-1.46 mm) compared to OCT-fusion method reconstructions. After carefully co-registering the region of interest for all cases with a sophisticated statistical method, the difference in MSA measurements as well as the inability of angiography to visualise the strut footprint in the lumen surface have translated to higher angiography-derived ESS than OCT-derived ESS (1.76 Pa or 1.52 times for the overlapping segment). The difference in ESS widened with a more restricted region of interest (1.97 Pa or 1.63 times within the scaffold segment). Angiography and OCT offer two distinctive methods of ESS calculation. Angiography-derived ESS tends to overestimate the ESS compared to OCT-derived ESS. Further investigations into ESS analysis resolution play a vital role in adopting OCT-derived ESS.

Merging virtual and physical experiences: extended realities in cardiovascular medicine.

Technological advancement and the COVID-19 pandemic have brought virtual learning and working into our daily lives. Extended realities (XR), an umbrella term for all the immersive technologies that merge virtual and physical experiences, will undoubtedly be an indispensable part of future clinical practice. The intuitive and three-dimensional nature of XR has great potential to benefit healthcare providers and empower patients and physicians. In the past decade, the implementation of XR into cardiovascular medicine has flourished such that it is now integrated into medical training, patient education, pre-procedural planning, intra-procedural visualization, and post-procedural care. This review article discussed how XR could provide innovative care and complement traditional practice, as well as addressing its limitations and considering its future perspectives.

Agreement of wall shear stress distribution between two core laboratories using three-dimensional quantitative coronary angiography.

Wall shear stress (WSS) estimated in models reconstructed from intravascular imaging and 3-dimensional-quantitative coronary angiography (3D-QCA) data provides important prognostic information and enables identification of high-risk lesions. However, these analyses are time-consuming and require expertise, limiting WSS adoption in clinical practice. Recently, a novel software has been developed for real-time computation of time-averaged WSS (TAWSS) and multidirectional WSS distribution. This study aims to examine its inter-corelab reproducibility. Sixty lesions (20 coronary bifurcations) with a borderline negative fractional flow reserve were processed using the CAAS Workstation WSS prototype to estimate WSS and multi-directional WSS values. Analysis was performed by two corelabs and their estimations for the WSS in 3 mm segments across each reconstructed vessel was extracted and compared. In total 700 segments (256 located in bifurcated vessels) were included in the analysis. A high intra-class correlation was noted for all the 3D-QCA and TAWSS metrics between the estimations of the two corelabs irrespective of the presence (range: 0.90-0.92) or absence (range: 0.89-0.90) of a coronary bifurcation, while the ICC was good-moderate for the multidirectional WSS (range: 0.72-0.86). Lesion level analysis demonstrated a high agreement of the two corelabls for detecting lesions exposed to an unfavourable haemodynamic environment (WSS > 8.24 Pa, κ = 0.77) that had a high-risk morphology (area stenosis > 61.3%, κ = 0.71) and were prone to progress and cause events. The CAAS Workstation WSS enables reproducible 3D-QCA reconstruction and computation of WSS metrics. Further research is needed to explore its value in detecting high-risk lesions.

An optical coherence tomography and endothelial shear stress study of a novel bioresorbable bypass graft.

Endothelial shear stress (ESS) plays a key role in the clinical outcomes in native and stented segments; however, their implications in bypass grafts and especially in a synthetic biorestorative coronary artery bypass graft are yet unclear. This report aims to examine the interplay between ESS and the morphological alterations of a biorestorative coronary bypass graft in an animal model. Computational fluid dynamics (CFD) simulation derived from the fusion of angiography and optical coherence tomography (OCT) imaging was used to reconstruct data on the luminal anatomy of a bioresorbable coronary bypass graft with an endoluminal "flap" identified during OCT acquisition. The "flap" compromised the smooth lumen surface and considerably disturbed the local flow, leading to abnormally low ESS and high oscillatory shear stress (OSI) in the vicinity of the "flap". In the presence of the catheter, the flow is more stable (median OSI 0.02384 versus 0.02635, p < 0.0001; maximum OSI 0.4612 versus 0.4837). Conversely, OSI increased as the catheter was withdrawn which can potentially cause back-and-forth motions of the "flap", triggering tissue fatigue failure. CFD analysis in this report provided sophisticated physiological information that complements the anatomic assessment from imaging enabling a complete understanding of biorestorative graft pathophysiology.

Projecting Future Climate Impact on National Australian Respiratory-Related Intensive Care Unit Demand.

BACKGROUND AND AIMS: A robust climate-health projection model has the potential to improve health care resource allocation. We aim to explore the relationship between Australian intensive care unit (ICU) demand and various measures of the long-lived large-scale climate and to develop a future nationwide climate-health projection model. METHODS: We investigated patients admitted to ICUs in Australia between January 2003 and December 2019 who were exposed to long-lived large-scale combined climatic measures of temperature and humidity. We analysed the projected demand for respiratory-related ICU average length of stay (in days) per capita (ICUD/C) with four historical and one future projection dataset. These datasets included: i) Australian and New Zealand Intensive Care Society adult patient database, ii) Socioeconomic Data and Applications Center gridded global historical population, iii) Australian Bureau of Statistics national historical population, iv) Japanese 55-year Reanalysis historical climate (JRA55), and v) the fifth Coupled Model Inter-comparison Project future climate projections. RESULTS: 148,638 patients with respiratory issues required intensive care between 2003 and 2019. The annual growth in the population density-weighted wet-bulb-globe temperature-a combined measure of temperature and humidity-is strongly correlated with the annual per capita growth ICUD/C for respiratory-related conditions (r=0.771; p<0.001). This relationship was applied to develop a model projecting future respiratory-related ICU demand with three possible future Representative Concentration Pathways (RCP). RCP2.6 (lowest carbon emission climate scenario) showed only a 33.4% increase in Australian ICUD/C demand by 2090, while the RCP8.5 (highest carbon emission climate scenario) demonstrated almost two-fold higher demand (66.1%) than RCP2.6 by 2090. CONCLUSIONS: The annual growth in population density-weighted wet-bulb-globe temperature correlates with the annual growth in Australian ICUD/C for respiratory-related conditions. A model based on possible future climate scenarios can be developed to predict changes in ICU demand in response to CO2 changes over the coming decades.

MRI in CFD for chronic type B aortic dissection: Ready for prime time?

OBJECTIVES: Better tools are needed for risk assessment of Type B aortic dissection (TBAD) to determine optimal treatment for patients with uncomplicated disease. Magnetic resonance imaging (MRI) has the potential to inform computational fluid dynamics (CFD) simulations for TBAD by providing individualised quantification of haemodynamic parameters, for assessment of complication risks. This systematic review aims to present an overview of MRI applications for CFD studies of TBAD. METHODS: Following PRISMA guidelines, a search in Medline, Embase, and the Scopus Library identified 136 potentially relevant articles. Studies were included if they used MRI to inform CFD simulation in TBAD. RESULTS: There were 20 articles meeting the inclusion criteria. 19 studies used phase contrast MRI (PC-MRI) to provide data for CFD flow boundary conditions. In 12 studies, CFD haemodynamic parameter results were validated against PC-MRI. In eight studies, geometric models were developed from MR angiography. In three studies, aortic wall or intimal flap motion data were derived from PC/cine MRI. CONCLUSIONS: MRI provides complementary patient-specific information in CFD haemodynamic studies for TBAD that can be used for personalised care. MRI provides structural, dynamic and flow data to inform CFD for pre-treatment planning, potentially advancing its integration into clinical decision-making. The use of MRI to inform CFD in TBAD surgical planning is promising, however further validation and larger cohort studies are required.

Numerical simulation of the blood flow through the coronary artery stenosis: Effects of varying eccentricity.

Blockages within arteries, called stenoses, are a common cause of coronary artery disease (CAD). Stenosis is a result of atherosclerotic plaque build-up limits blood flow and hence oxygen and nutrient supplies. Past studies on stenosed arterial flows often assumed stenosis to be axisymmetric in shape. However, medical imaging modalities have shown that stenoses in the coronary arteries are often asymmetric. To address it, an asymmetric stenosis is considered in the model which is based on common dimensions of the left anterior descending artery (LAD). The hemodynamic impacts are studied over a range of degrees of eccentricity (DoE) and degree of stenosis (DoS). Blood flow within the artery is analyzed by solving the incompressible Navier-Stokes equations with both resting and hyperemic flow rates. The wall shear stress (WSS), oscillatory shear index (OSI) and fractional flow reserve (FFR) are calculated. The eccentricity makes the flow deflect away from the model's centerline. Behavior of the deflected flow is significantly altered downstream of the stenosis. Transverse dimension of the recirculation zone grows with increasing DoE, while its longitudinal dimension mainly depends on DoS. Eccentricity also contributes to the development of secondary flow distal to the stenosis. Such complex flow behavior contributes to a further pressure loss and hence a significant change in FFR (<0.8). Calculated WSS and OSI indicate that in actual eccentric stenotic LAD the asymmetric remodeling is anticipated. Thus, consideration of the DoE, along with the DoS, could lead to better patient stratification.

Non-Newtonian Endothelial Shear Stress Simulation: Does It Matter?

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.

High endothelial shear stress and stress gradient at plaque erosion persist up to 12 months.

BACKGROUND: Local hemodynamics are known to play an important role in the development of plaque erosion. Recent studies showed that erosion patients might be treated conservatively without stent implantation. We investigated evolution of hemodynamic parameters on the plaque erosion site in conservatively treated patients. METHODS: Computational fluid dynamics (CFD) simulations were performed using the coronary angiogram and optical coherence tomography (OCT) images of non-stent treated erosion patients who had serial OCT studies. Calculated CFD parameters included endothelial shear stress (ESS), ESS gradient (ESSG), and oscillatory shear index (OSI). RESULTS: The CFD parameters at the erosion and non-erosion sites were compared among baseline (n = 23), and 1-month (n = 20) and 12-month (n = 16) follow-ups. The erosion site had higher ESS and ESSG values than the non-erosion sites at baseline (mean ESS: 3.00 vs 1.36 Pa, p < 0.01; mean ESSG: 1.71 vs. 0.65 Pa/mm, p = 0.01), 1-month (mean ESS: 2.89 vs 1.19 Pa, p < 0.01; mean ESSG: 1.71 vs. 0.60 Pa/mm, p < 0.01), and 12-month (mean ESS: 3.26 vs 1.59 Pa, p < 0.01; mean ESSG: 1.87 vs. 0.78 Pa/mm, p < 0.01). OSI was not different between erosion and and non-erosion sites. CONCLUSIONS: ESS and ESSG values were higher at the plaque erosion sites compared to non-erosion sites. Elevated ESS and ESSG at the erosion site persisted up to 12 months. These data indicate that a local thrombogenic milieu related to hemodynamic perturbation persists up to 12 months at the plaque erosion sites following conservative treatment. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov: NCT02041650.

An extensional strain sensing mechanosome drives adhesion-independent platelet activation at supraphysiological hemodynamic gradients.

BACKGROUND: Supraphysiological hemodynamics are a recognized driver of platelet activation and thrombosis at high-grade stenosis and in blood contacting circulatory support devices. However, whether platelets mechano-sense hemodynamic parameters directly in free flow (in the absence of adhesion receptor engagement), the specific hemodynamic parameters at play, the precise timing of activation, and the signaling mechanism(s) involved remain poorly elucidated. RESULTS: Using a generalized Newtonian computational model in combination with microfluidic models of flow acceleration and quasi-homogenous extensional strain, we demonstrate that platelets directly mechano-sense acute changes in free-flow extensional strain independent of shear strain, platelet amplification loops, von Willebrand factor, and canonical adhesion receptor engagement. We define an extensional strain sensing "mechanosome" in platelets involving cooperative Ca2+ signaling driven by the mechanosensitive channel Piezo1 (as the primary strain sensor) and the fast ATP gated channel P2X1 (as the secondary signal amplifier). We demonstrate that type II PI3 kinase C2α activity (acting as a "clutch") couples extensional strain to the mechanosome. CONCLUSIONS: Our findings suggest that platelets are adapted to rapidly respond to supraphysiological extensional strain dynamics, rather than the peak magnitude of imposed wall shear stress. In the context of overall platelet activation and thrombosis, we posit that "extensional strain sensing" acts as a priming mechanism in response to threshold levels of extensional strain allowing platelets to form downstream adhesive interactions more rapidly under the limiting effects of supraphysiological hemodynamics.

One-year performance of biorestorative polymeric coronary bypass grafts in an ovine model: correlation between early biomechanics and late serial Quantitative Flow Ratio.

OBJECTIVES: This study aimed to investigate the impact of mechanical factors at baseline on the patency of a restorative conduit for coronary bypass grafts in an ovine model at serial follow-up up to 1 year. METHODS: The analyses of 4 mechanical factors [i.e. bending angle, superficial wall strain and minimum and maximum endothelial shear stress (ESS)] were performed in 3D graft models reconstructed on baseline (1-month) angiograms frame by frame by a core laboratory blinded for the late follow-up. The late patency was documented by Quantitative Flow Ratio (QFR®) that reflects the physiological status of the graft. The correlation between 4 mechanical factors and segmental QFR (△QFR) were analysed on 10 equal-length segments of each graft. RESULTS: A total of 69 graft geometries of 7 animals were performed in the study. The highest △QFR at 12 months was colocalized in segments of the grafts with the largest bending angles at baseline. Higher △QFR at 3 months were both at the anastomotic ends and were colocalized with the highest superficial wall strain at baseline. High baseline ESS was topographically associated with higher △QFR at the latest follow-up. Correlations of minimum and maximum ESS with △QFR at 3 months were the strongest among these parameters (ρ = 0.30, 95% CI [-0.05 to 0.56] and ρ = 0.27, 95% CI [-0.05 to 0.54], respectively). CONCLUSIONS: Despite the limited number of grafts, this study suggests an association between early abnormal mechanical factors and late flow metrics of the grafts. The understanding of the mechanical characteristics could help to improve this novel conduit.

Optical Coherence Tomography of Coronary Plaque Progression and Destabilization: JACC Focus Seminar Part 3/3.

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.

Angiography-Based 4-Dimensional Superficial Wall Strain and Stress: A New Diagnostic Tool in the Catheterization Laboratory.

A novel method for four-dimensional superficial wall strain and stress (4D-SWS) is derived from the arterial motion as pictured by invasive coronary angiography. Compared with the conventional finite element analysis of cardiovascular biomechanics using the estimated pulsatile pressure, the 4D-SWS approach can calculate the dynamic mechanical state of the superficial wall in vivo, which could be directly linked with plaque rupture or stent fracture. The validation of this approach using in silico models showed that the distribution and maximum values of superficial wall stress were similar to those calculated by conventional finite element analysis. The in vivo deformation was validated on 16 coronary arteries, from the comparison of centerlines predicted by the 4D-SWS approach against the actual centerlines reconstructed from angiograms at a randomly selected time-point, which demonstrated a good agreement of the centerline morphology between both approaches (scaling: 0.995 ± 0.018 and dissimilarity: 0.007 ± 0.014). The in silico vessel models with softer plaque and larger plaque burden presented more variation in mean lumen diameter and resulted in higher superficial wall stress. In more than half of the patients (n = 16), the maximum superficial wall stress was found at the proximal lesion shoulder. Additionally, in three patients who later suffered from acute coronary syndrome, the culprit plaque rupture sites co-localized with the site of highest superficial wall stress on their baseline angiography. These representative cases suggest that angiography-based superficial wall dynamics have the potential to identify coronary segments at high-risk of plaque rupture and fracture sites of implanted stents. Ongoing studies are focusing on identifying weak spots in coronary bypass grafts, and on exploring the biomechanical mechanisms of coronary arterial remodeling and aneurysm formation. Future developments involve integration of fast computational techniques to allow online availability of superficial wall strain and stress in the catheterization laboratory.

High spatial endothelial shear stress gradient independently predicts site of acute coronary plaque rupture and erosion.

AIMS: To investigate local haemodynamics in the setting of acute coronary plaque rupture and erosion. METHODS AND RESULTS: Intracoronary optical coherence tomography performed in 37 patients with acute coronary syndromes caused by plaque rupture (n = 19) or plaque erosion (n = 18) was used for three-dimensional reconstruction and computational fluid dynamics simulation. Endothelial shear stress (ESS), spatial ESS gradient (ESSG), and oscillatory shear index (OSI) were compared between plaque rupture and erosion through mixed-effects logistic regression. Lipid, calcium, macrophages, layered plaque, and cholesterol crystals were also analysed. By multivariable analysis, only high ESSG [odds ratio (OR) 5.29, 95% confidence interval (CI) 2.57-10.89, P < 0.001], lipid (OR 12.98, 95% CI 6.57-25.67, P < 0.001), and layered plaque (OR 3.17, 95% CI 1.82-5.50, P < 0.001) were independently associated with plaque rupture. High ESSG (OR 13.28, 95% CI 6.88-25.64, P < 0.001), ESS (OR 2.70, 95% CI 1.34-5.42, P = 0.005), and OSI (OR 2.18, 95% CI 1.33-3.54, P = 0.002) independently associated with plaque erosion. ESSG was higher at rupture sites than erosion sites [median (interquartile range): 5.78 (2.47-21.15) vs. 2.62 (1.44-6.18) Pa/mm, P = 0.009], OSI was higher at erosion sites than rupture sites [1.04 × 10-2 (2.3 × 10-3-4.74 × 10-2) vs. 1.29 × 10-3 (9.39 × 10-5-3.0 × 10-2), P < 0.001], but ESS was similar (P = 0.29). CONCLUSIONS: High ESSG is independently associated with plaque rupture while high ESSG, ESS, and OSI associate with plaque erosion. While ESSG is higher at rupture sites than erosion sites, OSI is higher at erosion sites and ESS was similar. These results suggest that ESSG and OSI may play critical roles in acute plaque rupture and erosion, respectively.

Preclinical evaluation of a thin-strut bioresorbable scaffold (ArterioSorb): acute-phase invasive imaging assessment and hemodynamic implication.

AIMS: The aim of this study was to assess the acute performance of the 95 µm ArterioSorb oriented poly L-lactic acid (PLLA) scaffold in comparison with the XIENCE metallic drug-eluting stent (DES) in porcine coronary arteries. METHODS AND RESULTS: In 15 non-atherosclerotic Yucatan mini pigs, the ArterioSorb (3.0/14 mm) and XIENCE (3.0/15 mm) were implanted in 25 and 15 vessels, respectively. Acute performance was evaluated by using quantitative coronary angiography (QCA) and optical coherence tomography (OCT). Following three-dimensional reconstruction of the coronary arteries, endothelial shear stress (ESS) was quantified using non-Newtonian steady-flow simulation. Acute recoil measured by QCA was comparable in the two arms. Post-procedural flow and scaffold/stent area by OCT did not differ between the two devices. ESS post procedure was comparable between ArterioSorb and XIENCE (2.21±1.97 vs 2.25±1.71 Pa, p=0.314). CONCLUSIONS: Acute recoil, luminal dimensions and ESS in the ArterioSorb oriented PLLA scaffold with thin struts of 95 µm were comparable to those in the XIENCE metallic DES.

Numerical Study of Incomplete Stent Apposition Caused by Deploying Undersized Stent in Arteries With Elliptical Cross Sections.

Incomplete stent apposition (ISA) is one of the causes leading to poststent complications, which can be found when an undersized or an underexpanded stent is deployed at lesions. The previous research efforts have focused on ISA in idealized coronary arterial geometry with circular cross section. However, arterial cross section eccentricity plays an important role in both location and severity of ISA. Computational fluid dynamics (CFD) simulations are carried out to systematically study the effects of ISA in arteries with elliptical cross section, as such stents are partially embedded on the minor axis sides of the ellipse and malapposed elsewhere. Overall, ISA leads to high time-averaged wall shear stress (TAWSS) at the proximal end of the stent and low TAWSS at the ISA transition region and the distal end. Shear rate depends on both malapposition distance and blood stream locations, which is found to be significantly higher at the inner stent surface than the outer surface. The proximal high shear rate signifies increasing possibility in platelet activation, when coupled with low TAWSS at the transition and distal regions which may indicate a nidus for in-stent thrombosis.