Thoracic Stent Graft Numerical Models To Virtually Simulate Thoracic Endovascular Aortic Repair: A Scoping Review.

OBJECTIVE: Pre-procedural planning of thoracic endovascular aortic repair (TEVAR) may implement computational adjuncts to predict technical and clinical outcomes. The aim of this scoping review was to explore the currently available TEVAR procedure and stent graft modelling options. DATA SOURCES: PubMed (MEDLINE), Scopus, and Web of Science were systematically searched (English language, up to 9 December 2022) for studies presenting a virtual thoracic stent graft model or TEVAR simulation. REVIEW METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) was followed. Qualitative and quantitative data were extracted, compared, grouped, and described. Quality assessment was performed using a 16 item rating rubric. RESULTS: Fourteen studies were included. Among the currently available in silico simulations of TEVAR, severe heterogeneity exists in study characteristics, methodological details, and evaluated outcomes. Ten studies (71.4%) were published during the last five years. Eleven studies (78.6%) included heterogeneous clinical data to reconstruct patient specific aortic anatomy and disease (e.g., type B aortic dissection, thoracic aortic aneurysm) from computed tomography angiography imaging. Three studies (21.4%) constructed idealised aortic models with literature input. The applied numerical methods consisted of computational fluid dynamics analysing aortic haemodynamics in three studies (21.4%) and finite element analysis analysing structural mechanics in the others (78.6%), including or excluding aortic wall mechanical properties. The thoracic stent graft was modelled as two separate components (e.g., graft, nitinol) in 10 studies (71.4%), as a one component homogenised approximation (n = 3, 21.4%), or including nitinol rings only (n = 1, 7.1%). Other simulation components included the catheter for virtual TEVAR deployment and numerous outcomes (e.g., Von Mises stresses, stent graft apposition, drag forces) were evaluated. CONCLUSION: This scoping review identified 14 severely heterogeneous TEVAR simulation models, mostly of intermediate quality. The review concludes there is a need for continuous collaborative efforts to improve the homogeneity, credibility, and reliability of TEVAR simulations.

A numerical investigation to evaluate the washout of blood compartments in a total artificial heart.

Total artificial heart (TAH) represents the only valid alternative to heart transplantation, whose number is continuously increasing in recent years. The TAH used in this work, is a biventricular pulsatile, electrically powered, hydraulically actuated flow pump with all components embodied in a single device. One of the major issues for TAHs is the washout capability of the device, strictly correlated with the presence of blood stagnation sites. The aim of this work was to develop a numerical methodology to study the washout coupled with the fluid dynamics evaluation of a total artificial heart under nominal working conditions. The first part of this study focussed on the CT scan analysis of the hybrid membrane kinematics during TAH operation, which was replicated with a fluid-structure interaction simulation in the second part. The difference in percentage between the in vitro and in silico flow rates and stroke volume is 9.7% and 6.3%, respectively. An injection of contrast blood was simulated, and a good washout performance was observed and quantified with the volume fraction of the contrast blood still in the ventricle. The left chamber of the device showed a superior washout performance, with a contrast volume still inside the device after four washout cycles of 6.2%, with the right chamber showing 15%.

Simultaneous kissing stents to treat unprotected left main stem coronary artery bifurcation disease; stent expansion, vessel injury, hemodynamics, tissue healing, restenosis, and repeat revascularization.

OBJECTIVES: To perform detailed analysis of stent expansion, vessel wall stress, hemodynamics, re-endothelialization, restenosis, and repeat PCI in the simultaneous kissing stents (SKS) technique of bifurcation left main stem (LMS) stenting. BACKGROUND: The SKS technique is useful to treat patients with true bifurcation disease of the LMS but remains controversial. METHODS AND RESULTS: Computational structural analysis of SKS expansion demonstrated undistorted and evenly expanded stents. Computational fluid dynamics modelling revealed largely undisturbed blood flow. 239 PCI procedures were performed on 217 patients with unprotected bifurcation LMS disease with SKS using DES (2004-2017). We electively studied 13 stable patients from baseline to 10 years post-SKS with repeat angiography and optical coherence tomography, and demonstrated tissue coverage of the stent struts at the carina, with no evidence of lacunae behind the stents. We studied all patients with symptomatic recurrence. Target lesion revascularization rate was 3.2% at 1 year and 4.6% at 2 years. Of all 20 patients with restenosis, the site was the LMS-Cx stent in 7, the LMS-LAD stent in 2 and both in 11. Two-year recurrence rate was 7/32 (5.3%) for first, and 4/108 (3.7%) for second generation DES. Treatment with repeat kissing techniques was undertaken in 19/20, with sustained clinical results with re-SKS. CONCLUSION: The SKS technique for treating unprotected LMS bifurcation disease does not distort the stents, is associated with favorable hemodynamics, tissue coverage of the exposed struts, and a low restenosis rate when performed with contemporary stents. Re-PCI with repeat SKS appears feasible, safe, and durable.

Differences in rotational positioning and subsequent distal main branch rewiring of the Tryton stent: An optical coherence tomography and computational study.

OBJECTIVES: To evaluate the occurrence of rewiring through one of the panels of the Tryton stent (instead of the assumed re-wiring in-between the panels) and the influence on stent geometry and mechanics. BACKGROUND: Tryton is a side branch stent used in combination with a main branch device. It is placed without the need of rotational orientation. However, it is unknown whether main branch re-wiring accidentally may occur through a panel, instead of in-between the panels. METHODS: We used three-dimensional optical coherence tomography to evaluate the location of distal main branch re-wiring through Tryton. Furthermore, we used computer simulations to evaluate the influence on stent geometry and mechanics. RESULTS: Rewiring through a panel (instead of in-between two panels) occurred in 45% of the cases. By using virtual stent deployment, we found minimal differences in ostial side branch stenoses (44.8% in-between the panels and 39.0% through a panel). There were no differences in minimum stent areas of the distal main branch (6.38 mm2 vs. 6.39 mm2 ). In both scenarios, the re-wired Tryton cell was large enough for main branch stenting (expressed as the diameter of the largest possible circle that fits within the cells): 3.40 mm (in-between the panels) vs. 3.02 mm (through a panel). CONCLUSIONS: In 45% of the Tryton implantations, distal main branch rewiring (and subsequent main branch stenting) was performed through one Tryton panel, instead of the assumed rewiring in-between the panels. However, this did not result in unfavorable stent geometries or mechanics, as evaluated with computer simulations.

Numerical Approach to Study the Behavior of an Artificial Ventricle: Fluid-Structure Interaction Followed By Fluid Dynamics With Moving Boundaries.

Heart failure is a progressive and often fatal pathology among the main causes of death in the world. An implantable total artificial heart (TAH) is an alternative to heart transplantation. Blood damage quantification is imperative to assess the behavior of an artificial ventricle and is strictly related to the hemodynamics, which can be investigated through numerical simulations. The aim of this study is to develop a computational model that can accurately reproduce the hemodynamics inside the left pumping chamber of an existing TAH (Carmat-TAH) together with the displacement of the leaflets of the biological aortic and mitral valves and the displacement of the pericardium-made membrane. The proposed modeling workflow combines fluid-structure interaction (FSI) simulations based on a fixed grid method with computational fluid dynamics (CFD). In particular, the kinematics of the valves is accounted for by means of a dynamic mesh technique in the CFD. The comparison between FSI- and CFD-calculated velocity fields confirmed that the presence of the valves in the CFD model is essential for realistically mimicking blood dynamics, with a percentage difference of 2% during systole phase and 13% during the diastole. The percentage of blood volume in the CFD simulation with a shear stress above the threshold of 50 Pa is less than 0.001%. In conclusion, the application of this workflow to the Carmat-TAH provided consistent results with previous clinical studies demonstrating its utility in calculating local hemodynamic quantities in the presence of complex moving boundaries.

Numerical model of a valvuloplasty balloon: in vitro validation in a rapid-prototyped phantom.

BACKGROUND: Patient-specific simulations can provide insight into the mechanics of cardiovascular procedures. Amongst cardiovascular devices, non-compliant balloons are used in several minimally invasive procedures, such as balloon aortic valvuloplasty. Although these balloons are often included in the computer simulations of these procedures, validation of the balloon behaviour is often lacking. We therefore aim to create and validate a computational model of a valvuloplasty balloon. METHODS: A finite element (FE) model of a valvuloplasty balloon (Edwards 9350BC23) was designed, including balloon geometry and material properties from tensile testing. Young's Modulus and distensibility of different rapid prototyping (RP) rubber-like materials were evaluated to identify the most suitable compound to reproduce the mechanical properties of calcified arteries in which such balloons are likely to be employed clinically. A cylindrical, simplified implantation site was 3D printed using the selected material and the balloon was inflated inside it. The FE model of balloon inflation alone and its interaction with the cylinder were validated by comparison with experimental Pressure-Volume (P-V) and diameter-Volume (d-V) curves. RESULTS: Root mean square errors (RMSE) of pressure and diameter were RMSE P = 161.98 mmHg (3.8 % of the maximum pressure) and RMSE d = 0.12 mm (<0.5 mm, within the acquisition system resolution) for the balloon alone, and RMSE P = 94.87 mmHg (1.9 % of the maximum pressure) and RMSE d = 0.49 mm for the balloon inflated inside the simplified implantation site, respectively. CONCLUSIONS: This validated computational model could be used to virtually simulate more realistic valvuloplasty interventions.

Numerical blood flow simulation in surgical corrections: what do we need for an accurate analysis?

BACKGROUND: Computational fluid dynamics has been increasingly used in congenital heart surgery to simulate pathophysiological blood flow, investigate surgical options, or design medical devices. Several commercial and research computational or numerical codes have been developed. They present different approaches to numerically solve the blood flow equations, raising the question whether these numerical codes are equally reliable to achieve accurate simulation results. Accordingly, we sought to examine the influence of numerical code selection in several complex congenital cardiac operations. MATERIAL AND METHODS: The main steps of blood flow simulations are detailed (geometrical mesh, boundary conditions, and solver numerical methods) for congenital cardiac operations of increasing complexity. The first case tests different numerical solutions against an analytical, or exact, solution. In the second case, the three-dimensional domain is a patient-specific superior cavopulmonary anastomosis. As an analytical solution does not exist in such a complex geometry, different numerical solutions are compared. Finally, a realistic case of a systemic-to-pulmonary shunt is presented with both geometrically and physiologically challenging conditions. For all, solutions from a commercially available code and an open-source research code are compared. RESULTS: In the first case, as the mesh or solver numerical method is refined, the simulation results for both codes converged to the analytical solution. In the second example, velocity differences between the two codes are greater when the resolution of the mesh were lower and less refined. The third case with realistic anatomy reveals that the pulsatile complex flow is very similar for both codes. CONCLUSIONS: The precise setup of the numerical cases has more influence on the results than the choice of numerical codes. The need for detailed construction of the numerical model that requires high computational cost depends on the precision needed to answer the biomedical question at hand and should be assessed for each problem on a combination of clinically relevant patient-specific geometry and physiological conditions.

A simulation protocol for exercise physiology in Fontan patients using a closed loop lumped-parameter model.

BACKGROUND: Reduced exercise capacity is nearly universal among Fontan patients, though its etiology is not yet fully understood. While previous computational studies have attempted to model Fontan exercise, they did not fully account for global physiologic mechanisms nor directly compare results against clinical and physiologic data. METHODS: In this study, we developed a protocol to simulate Fontan lower-body exercise using a closed-loop lumped-parameter model describing the entire circulation. We analyzed clinical exercise data from a cohort of Fontan patients, incorporated previous clinical findings from literature, quantified a comprehensive list of physiological changes during exercise, translated them into a computational model of the Fontan circulation, and designed a general protocol to model Fontan exercise behavior. Using inputs of patient weight, height, and if available, patient-specific reference heart rate (HR) and oxygen consumption, this protocol enables the derivation of a full set of parameters necessary to model a typical Fontan patient of a given body-size over a range of physiologic exercise levels. RESULTS: In light of previous literature data and clinical knowledge, the model successfully produced realistic trends in physiological parameters with exercise level. Applying this method retrospectively to a set of clinical Fontan exercise data, direct comparison between simulation results and clinical data demonstrated that the model successfully reproduced the average exercise response of a cohort of typical Fontan patients. CONCLUSION: This work is intended to offer a foundation for future advances in modeling Fontan exercise, highlight the needs in clinical data collection, and provide clinicians with quantitative reference exercise physiologies for Fontan patients.

Shear Stress Quantification in Tissue Engineering Bioreactor Heart Valves: A Computational Approach.

Tissue-engineered heart valves can grow, repair, and remodel after implantation, presenting a more favorable long-term solution compared to mechanical and porcine valves. Achieving functional engineered valve tissue requires the maturation of human cells seeded onto valve scaffolds under favorable growth conditions in bioreactors. The mechanical stress and strain on developing valve tissue caused by different pressure and flow conditions in bioreactors are currently unknown. The aim of this study is to quantify the wall shear stress (WSS) magnitude in heart valve prostheses under different valve geometries and bioreactor flow rates. To achieve this, this study used fluid-structure interaction simulations to obtain the valve's opening geometries during the systolic phase. These geometries were then used in computational fluid dynamics simulations with refined near-wall mesh elements and ranges of prescribed inlet flow rates. The data obtained included histograms and regression curves that characterized the distribution, peak, and median WSS for various flow rates and valve opening configurations. This study also found that the upper region of the valve near the commissures experienced higher WSS magnitudes than the rest of the valve.

On the necessity to include arterial pre-stress in patient-specific simulations of minimally invasive procedures.

Transcatheter aortic valve implantation (TAVI) and thoracic endovascular aortic repair (TEVAR) are minimally invasive procedures for treating aortic valves and diseases. Finite element simulations have proven to be valuable tools in predicting device-related complications. In the literature, the inclusion of aortic pre-stress has not been widely investigated. It plays a crucial role in determining the biomechanical response of the vessel and the device-tissue interaction. This study aims at demonstrating how and when to include the aortic pre-stress in patient-specific TAVI and TEVAR simulations. A percutaneous aortic valve and a stent-graft were implanted in aortic models reconstructed from patient-specific CT scans. Two scenarios for each patient were compared, i.e., including and neglecting the wall pre-stress. The neglection of pre-stress underestimates the contact pressure of 48% and 55%, the aorta stresses of 162% and 157%, the aorta strains of 77% and 21% for TAVI and TEVAR models, respectively. The stent stresses are higher than 48% with the pre-stressed aorta in TAVI simulations; while, similar results are obtained in TEVAR cases. The distance between the device and the aorta is similar with and without pre-stress. The inclusion of the aortic wall pre-stress has the capability to give a better representation of the biomechanical behavior of the arterial tissues and the implanted device. It is suggested to include this effect in patient-specific simulations replicating the procedures.

Predicting 1-year in-stent restenosis in superficial femoral arteries through multiscale computational modelling.

In-stent restenosis in superficial femoral arteries (SFAs) is a complex, multi-factorial and multiscale vascular adaptation process whose thorough understanding is still lacking. Multiscale computational agent-based modelling has recently emerged as a promising approach to decipher mechanobiological mechanisms driving the arterial response to the endovascular intervention. However, the long-term arterial response has never been investigated with this approach, although being of fundamental relevance. In this context, this study investigates the 1-year post-operative arterial wall remodelling in three patient-specific stented SFA lesions through a fully coupled multiscale agent-based modelling framework. The framework integrates the effects of local haemodynamics and monocyte gene expression data on cellular dynamics through a bi-directional coupling of computational fluid dynamics simulations with an agent-based model of cellular activities. The framework was calibrated on the follow-up data at 1 month and 6 months of one stented SFA lesion and then applied to the other two lesions. The calibrated framework successfully captured (i) the high lumen area reduction occurring within the first post-operative month and (ii) the stabilization of the median lumen area from 1-month to 1-year follow-ups in all the stented lesions, demonstrating the potentialities of the proposed approach for investigating patient-specific short- and long-term responses to endovascular interventions.

Investigating the effect of drug release on in-stent restenosis: A hybrid continuum - agent-based modelling approach.

BACKGROUND AND OBJECTIVE: In-stent restenosis (ISR) following percutaneous coronary intervention with drug-eluting stent (DES) implantation remains an unresolved issue, with ISR rates up to 10%. The use of antiproliferative drugs on DESs has significantly reduced ISR. However, a complete knowledge of the mechanobiological processes underlying ISR is still lacking. Multiscale agent-based modelling frameworks, integrating continuum- and agent-based approaches, have recently emerged as promising tools to decipher the mechanobiological events driving ISR at different spatiotemporal scales. However, the integration of sophisticated drug models with an agent-based model (ABM) of ISR has been under-investigated. The aim of the present study was to develop a novel multiscale agent-based modelling framework of ISR following DES implantation. METHODS: The framework consisted of two bi-directionally coupled modules, namely (i) a drug transport module, simulating drug transport through a continuum-based approach, and (ii) a tissue remodelling module, simulating cellular dynamics through an ABM. Receptor saturation (RS), defined as the fraction of target receptors saturated with drug, is used to mediate cellular activities in the ABM, since RS is widely regarded as a measure of drug efficacy. Three studies were performed to investigate different scenarios in terms of drug mass (DM), drug release profiles (RP), coupling schemes and idealized vs. patient-specific artery geometries. RESULTS: The studies demonstrated the versatility of the framework and enabled exploration of the sensitivity to different settings, coupling modalities and geometries. As expected, changes in the DM, RP and coupling schemes illustrated a variation in RS over time, in turn affecting the ABM response. For example, combined small DM - fast RP led to similar ISR degrees as high DM - moderate RP (lumen area reduction of ∼13/17% vs. ∼30% without drug). The use of a patient-specific geometry with non-equally distributed struts resulted in a heterogeneous RS map, but did not remarkably impact the ABM response. CONCLUSION: The application to a patient-specific geometry highlights the potential of the framework to address complex realistic scenarios and lays the foundations for future research, including calibration and validation on patient datasets and the investigation of the effects of different plaque composition on the arterial response to DES.

A low dimensional surrogate model for a fast estimation of strain in the thrombus during a thrombectomy procedure.

BACKGROUND: Intra-arterial thrombectomy is the main treatment for acute ischemic stroke due to large vessel occlusions and can consist in mechanically removing the thrombus with a stent-retriever. A cause of failure of the procedure is the fragmentation of the thrombus and formation of micro-emboli, difficult to remove. This work proposes a methodology for the creation of a low-dimensional surrogate model of the mechanical thrombectomy procedure, trained on realizations from high-fidelity simulations, able to estimate the evolution of the maximum first principal strain in the thrombus. METHOD: A parametric finite-element model was created, composed of a tapered vessel, a thrombus, a stent-retriever and a catheter. A design of experiments was conducted to sample 100 combinations of the model parameters and the corresponding thrombectomy simulations were run and post-processed to extract the maximum first principal strain in the thrombus during the procedure. Then, a surrogate model was built with a combination of principal component analysis and Kriging. RESULTS: The surrogate model was chosen after a sensitivity analysis on the number of principal components and was tested with 10 additional cases. The model provided predictions of the strain curves with correlation above 0.9 and a maximum error of 28%, with an error below 20% in 60% of the test cases. CONCLUSIONS: The surrogate model provides nearly instantaneous estimates and constitutes a valuable tool for evaluating the risk of thrombus rupture during pre-operative planning for the treatment of acute ischemic stroke.

Utilizing numerical simulations to prevent stent graft kinking during thoracic endovascular aortic repair.

Numerical simulations of thoracic endovascular aortic repair (TEVAR) may be implemented in the preoperative workflow if credible and reliable. We present the application of a TEVAR simulation methodology to an 82-year-old woman with a penetrating atherosclerotic ulcer in the left hemiarch, that underwent a left common carotid artery to left subclavian artery bypass and consequent TEVAR in zone 2. During the intervention, kinking of the distal thoracic stent graft occurred and the simulation was able to reproduce this event. This report highlights the potential and reliability of TEVAR simulations to predict perioperative adverse events and short-term postoperative technical results.

Applicability assessment for in-silico patient-specific TEVAR procedures.

Thoracic Endovascular Aortic Repair (TEVAR) is a minimally invasive technique to treat thoracic aorta pathologies and consists of placing a self-expandable stent-graft into the pathological region to restore the vessel lumen and recreate a more physiological condition. Exhaustive computational models, namely the finite element analysis, can be implemented to reproduce the clinical procedure. In this context, numerical models, if used for clinical applications, must be reliable and the simulation credibility should be proved to predict clinical procedure outcomes or to build in-silico clinical trials. This work aims first at applying a previously validated TEVAR methodology to a patient-specific case. Then, defining the TEVAR procedure performed on a patient population as the context of use, the overall applicability of the TEVAR modeling is assessed to demonstrate the reliability of the model itself following a step-by-step method based on the ASME V&V40 protocol. Validation evidence sources are identified for the specific context of use and adopted to demonstrate the applicability of the numerical procedure, thereby answering a question of interest that evaluates the deployed stent-graft configuration in the vessel.

In silico thrombectomy trials for acute ischemic stroke.

BACKGROUND AND OBJECTIVE: In silico trials aim to speed up the introduction of new devices in clinical practice by testing device design and performance in different patient scenarios and improving patient stratification for optimizing clinical trials. In this paper, we demonstrate an in silico trial framework for thrombectomy treatment of acute ischemic stroke and apply this framework to compare treatment outcomes in different subpopulations and with different thrombectomy stent-retriever devices. We employ a novel surrogate thrombectomy model to evaluate the thrombectomy success in the in silico trial. METHODS: The surrogate thrombectomy model, built using data from a fine-grained finite-element model, is a device-specific binary classifier (logistic regression), to estimate the probability of successful recanalization, the outcome of interest. We incorporate this surrogate model within our previously developed in silico trial framework and demonstrate its use with three examples of in silico clinical trials. The first trial is a validation trial for the surrogate thrombectomy model. We then present two exploratory trials: one evaluating the performance of a commercially available device based on the fibrin composition in the occluding thrombus and one comparing the performance of two commercially available stent retrievers. RESULTS: The Validation Trial showed the surrogate thrombectomy model was able to reproduce a similar recanalization rate as the real-life MR CLEAN trial (p=0.6). Results from the first exploratory trial showed that the chance of successful thrombectomy increases with higher blood cell concentrations in the thrombi, which is in line with observations from clinical data. The second exploratory trial showed improved recanalization success with a newer stent retriever device; however, these results require further investigation as the surrogate model for the newer stent retriever device has not yet been validated. CONCLUSIONS: In this novel study, we have shown that in silico trials have the potential to help inform medical device developers on the performance of a new device and may also be used to select populations of interest for a clinical trial. This would reduce the time and costs involved in device development and traditional clinical trials.

Microcatheter tracking in thrombectomy procedures: A finite-element simulation study.

BACKGROUND AND OBJECTIVE: Mechanical thrombectomy is a minimally invasive procedure that aims at removing the occluding thrombus from the vasculature of acute ischemic stroke patients. Thrombectomy success and failure can be studied using in-silico thrombectomy models. Such models require realistic modeling steps to be effective. We here present a new approach to model microcatheter tracking during thrombectomy. METHODS: For 3 patient-specific vessel geometries, we performed finite-element simulations of the microcatheter tracking (1) following the vessel centerline (centerline method) and (2) as a one-step insertion simulation, where the microcatheter tip was advanced along the vessel centerline while its body was free to interact with the vessel wall (tip-dragging method). Qualitative validation of the two tracking methods was performed with the patient's digital subtraction angiography (DSA) images. In addition, we compared simulated thrombectomy outcomes (successful vs unsuccessful thrombus retrieval) and maximum principal stresses on the thrombus between the centerline and tip-dragging method. RESULTS: Qualitative comparison with the DSA images showed that the tip-dragging method more realistically resembles the patient-specific microcatheter-tracking scenario, where the microcatheter approaches the vessel walls. Although the simulated thrombectomy outcomes were similar in terms of thrombus retrieval, the thrombus stress fields (and the associated fragmentation of the thrombus) were strongly different between the two methods, with local differences in the maximum principal stress curves up to 84%. CONCLUSIONS: Microcatheter positioning with respect to the vessel affects the stress fields of the thrombus during retrieval, and therefore, may influence thrombus fragmentation and retrieval in-silico thrombectomy.

Coronary artery plaque rupture and erosion: Role of wall shear stress profiling and biological patterns in acute coronary syndromes.

AIMS: Wall shear stress (WSS) is involved in coronary artery plaque pathological mechanisms and modulation of gene expression. This study aims to provide a comprehensive haemodynamic and biological description of unstable (intact-fibrous-cap, IFC, and ruptured-fibrous-cap, RFC) and stable (chronic coronary syndrome, CCS) plaques and investigate any correlation between WSS and molecular pathways. METHODS AND RESULTS: We enrolled 24 CCS and 25 Non-ST Elevation Myocardial Infarction-ACS patients with IFC (n = 11) and RFC (n = 14) culprit lesions according to optical coherence tomography analysis. A real-time PCR primer array was performed on peripheral blood mononuclear cells for 17 different molecules whose expression is linked to WSS. Computational fluid dynamics simulations were performed in high-fidelity 3D-coronary artery anatomical models for three patients per group. A total of nine genes were significantly overexpressed in the unstable patients as compared to CCS patients, with no differences between IFC and RFC groups (GPX1, MMP1, MMP9, NOS3, PLA2G7, PI16, SOD1, TIMP1, and TFRC) while four displayed different levels between IFC and RFC groups (TNFα, ADAMTS13, EDN1, and LGALS8). A significantly higher WSS was observed in the RFC group (p < 0.001) compared to the two other groups. A significant correlation was observed between TNFα (p < 0.001), EDN1 (p = 0.036), and MMP9 (p = 0.005) and WSS values in the RFC group. CONCLUSIONS: Our data demonstrate that IFC and RFC plaques are subject to different WSS conditions and gene expressions, suggesting that WSS profiling may play an essential role in the plaque instability characterization with relevant diagnostic and therapeutic implications in the era of precision medicine.