Hemodynamics of Stent Implantation Procedures in Coronary Bifurcations: an in vitro study

Stent implantation in coronary bifurcations presents unique challenges and currently there is no universally accepted stent deployment approach. Despite clinical and computational studies, to date, the effect of each stent implantation method on the coronary artery hemodynamics is not well understood. In this study the hemodynamics of stented coronary bifurcations under pulsatile flow conditions were investigated experimentally. Three implantation methods, provisional side branch (PSB), culotte (CUL), and crush (CRU), were investigated using time-resolved particle image velocimetry (PIV) to measure the velocity fields. Subsequently, hemodynamic parameters including wall shear stress (WSS), oscillatory shear index (OSI), and relative residence time (RRT) were calculated and the pressure field through the vessel was non-invasively quantified. The effects of each stented case were evaluated and compared against an un-stented case. CRU provided the lowest compliance mismatch, but demonstrated detrimental stent interactions. PSB, the clinically preferred method, and CUL maintained many normal flow conditions. However, PSB provided about a 300% increase in both OSI and RRT. CUL yielded a 10% and 85% increase in OSI and RRT, respectively. The results of this study support the concept that different bifurcation stenting techniques result in hemodynamic environments that deviate from that of un-stented bifurcations, to varying degrees.Comment: 33 pages, 8 figures, 3 table

Optimal Site for Proximal Optimization Technique in Complex Coronary Bifurcation Stenting: A Computational Fluid Dynamics Study

Background/purpose: The optimal position of the balloon distal radio-opaque marker during the post optimization technique (POT) remains debated. We analyzed three potential different balloon positions for the final POT in two different two-stenting techniques, to compare the hemodynamic effects in terms of wall shear stress (WSS) in patients with complex left main (LM) coronary bifurcation. Methods/materials: We reconstructed the patient-specific coronary bifurcation anatomy using the coronary computed tomography angiography (CCTA) data of 8 consecutive patients (6 males, mean age 68.2± 18.6 years) affected by complex LM bifurcation disease. Subsequently a virtual bench test was performed in each patient using two different double stenting techniques represented by the DK and Nano crush using the reconstruction of Orsiro stents (Biotronik IC, Bulack, Switzerland). Results: A significant reduction in the mean WSS values in all the lesion's sites was observed when the final POT was performed 1 mm distally the carina cut plane in both techniques. Moreover, a significant improvement in the mean WSS values of the entire SB (e.g. LCX) was obtained performing the POT 1 mm distally to the carina cut plane. The proximal POT resulted in larger area of lower WSS values at the carina using both the Nano crush and the DK crush techniques. Conclusions: In patients with complex LM bifurcation disease the use of a final POT performed 1 mm distally to the carina cut plane might results in more favorable WSS patterns (i.e. higher WSS values) along all stented segments and, especially, along the entire LCX lesions

Biomechanical Evaluation of Different Balloon Positions for Proximal Optimization Technique in Left Main Bifurcation Stenting

Background: Proximal optimization technique (POT) is a key step during left main (LM) bifurcation stenting. However, after crossover stenting, the ideal position of POT balloon is unclear. We sought to evaluate the biomechanical impact of different POT balloon positions during LM cross-over stenting procedure. Methods: We reconstructed the patient-specific LM bifurcation anatomy, using coronary computed tomography angiography data of 5 consecutive patients (3 males, mean age 66.3 ± 21.6 years) with complex LM bifurcation disease, defined as Medina 1,1,1, evaluated between 1st January 2018 to 1st June 2018 at our center. Finite element analyses were carried out to virtually perform the stenting procedure. POT was virtually performed in a mid (marker just at the carina cut plane), proximal (distal marker 1 mm before the carina) and distal (distal marker 1 mm after the carina) position in each investigated case. Final left circumflex obstruction (SBO%), strut malapposition, elliptical ratio and stent malapposition were evaluated. Results: The use of both proximal and distal POT resulted in a smaller LM diameter compared to the mid POT. SBO was significantly higher in both proximal and distal configurations compared to mid POT: 38.3 ± 5.1 and 29.3 ± 3.1 versus 18.3 ± 3.6%, respectively. Similarly stent malapposition was higher in both proximal and distal configurations compared to mid POT: 1.3 ± 0.4 and 0.82 ± 1.8 versus 0.78 ± 1.2, respectively. Conclusions: Mid POT offers the best results in terms of LCx opening maintaining slightly smaller but still acceptable LM and LAD diameters compared to alternative POT configuration

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

In silico biomechanical design of the metal frame of transcatheter aortic valves: multi-objective shape and cross-sectional size optimization

Transcatheter aortic valve (TAV) implantation has become an established alternative to open-hearth surgical valve replacement. Current research aims to improve the treatment safety and extend the range of eligible patients. In this regard, computational modeling is a valuable tool to address these challenges, supporting the design phase by evaluating and optimizing the mechanical performance of the implanted device. In this study, a computational framework is presented for the shape and cross-sectional size optimization of TAV frames. Finite element analyses of TAV implantation were performed in idealized aortic root models with and without calcifications, implementing a mesh-morphing procedure to parametrize the TAV frame. The pullout force magnitude, peak maximum principal stress within the aortic wall, and contact pressure in the left ventricular outflow tract were defined as objectives of the optimization problem to evaluate the device mechanical performance. Design of experiment coupled with surrogate modeling was used to define an approximate relationship between the objectives and the TAV frame parameters. Surrogate models were interrogated within a fixed design space and multi-objective design optimization was conducted. The investigation of the parameter combinations within the design space allowed the successful identification of optimized TAV frame geometries, suited to either a single or groups of aortic root anatomies. The optimization framework was efficient, resulting in TAV frame designs with improvedmechanical performance, ultimately leading to enhanced procedural outcomes and reduced costs associated with the device iterative development cycle

3D modelling of drug-coated balloons for the treatment of calcified superficial femoral arteries

Background/Objectives Drug-coated balloon therapy for diseased superficial femoral arteries remains controversial. Despite its clinical relevance, only a few computational studies based on simplistic two-dimensional models have been proposed to investigate this endovascular therapy to date. This work addresses the aforementioned limitation by analyzing the drug transport and kinetics occurring during drug-coated balloon deployment in a three-dimensional geometry. Methods An idealized three-dimensional model of a superficial femoral artery presenting with a calcific plaque and treated with a drug-coated balloon was created to perform transient mass transport simulations. To account for the transport of drug (i.e. paclitaxel) released by the device, a diffusion-reaction equation was implemented by describing the drug bound to specific intracellular receptors through a non-linear, reversible reaction. The following features concerning procedural aspects, pathologies and modelling assumptions were investigated: (i) balloon application time (60–180 seconds); (ii) vessel wall composition (healthy vs. calcified wall); (iii) sequential balloon application; and (iv) drug wash-out by the blood stream vs. coating retention, modeled as exponential decay. Results The balloon inflation time impacted both the free and specifically-bound drug concentrations in the vessel wall. The vessel wall composition highly affected the drug concentrations. In particular, the specifically-bound drug concentration was four orders of magnitude lower in the calcific compared with healthy vessel wall portions, primarily as a result of reduced drug diffusion. The sequential application of two drug-coated balloons led to modest differences (~15%) in drug concentration immediately after inflation, which became negligible within 10 minutes. The retention of the balloon coating increased the drug concentration in the vessel wall fourfold. Conclusions The overall findings suggest that paclitaxel kinetics may be affected not only by the geometrical and compositional features of the vessel treated with the drug-coated balloon, but also by balloon design characteristics and procedural aspects that should be carefully considered

Does the shape of inflow velocity profiles affect hemodynamics in computational coronary artery models?

In this study, the impact of velocity inflow profiles shape on computational hemodynamic models of coronary arteries was investigated. To this purpose, 3D realistic velocity profiles were generated analytically and prescribed as inflow boundary condition and the impact on near-wall and intravascular flow was assessed. The results suggest that the impact of the shape of inflow velocity profiles on simulated coronary hemodynamics is limited to the proximal segment, while the global hemodynamics is poorly affected