The treatment of coronary bifurcation lesions represents a challenge for the interventional cardiologists due to the lower rate of procedural success and the higher risk of restenosis. The advent of drug-eluting stents (DES) has dramatically reduced restenosis and consequently the request for re-intervention. The aim of the present work is to provide further insight about the effectiveness of DES by means of a computational study that combines virtual stent implantation, fluid dynamics and drug release for different stenting protocols currently used in the treatment of a coronary artery bifurcation. An explicit dynamic finite element model is developed in order to obtain realistic configurations of the implanted devices used to perform fluid dynamics analysis by means of a previously developed finite element method coupling the blood flow and the intramural plasma filtration in rigid arteries. To efficiently model the drug release, a multiscale strategy is adopted, ranging from lumped parameter model accounting for drug release to fully 3-D models for drug transport to the artery. Differences in drug delivery to the artery are evaluated with respect to local drug dosage. This model allowed to compare alternative stenting configurations (namely the Provisional Side Branch, the Culotte and the Inverted Culotte techniques), thus suggesting guidelines in the treatment of coronary bifurcation lesions and addressing clinical issues such as the effectiveness of drug delivery to lesions in the side branch, as well as the influence of incomplete strut apposition and overlapping stents.
#2Paolo Zunino(Polytechnic University of Milan)H-Index: 28
We consider a time dependent coupled Stokes/Darcy flow problem and study an approximation method based on a unified finite element scheme complemented with implicit time stepping. Our finite element formulation relies on a weighing strategy in which the physical and discretization parameters are taken into account to robustly enforce interface and boundary conditions by means of the Nitsche method. We study absolute stability and convergence of the scheme, and discuss the algebraic properties of...
The majority of heart attacks occur when there is a sudden rupture of atherosclerotic plaque, exposing prothrombotic emboli to coronary blood flow, forming clots that can cause blockages of the arterial lumen. Diseased arteries can be treated with drugs delivered locally to vulnerable plaques. The objective of this work was to develop a computational tool-set to support the design and analysis of a catheter-based nanoparticulate drug delivery system to treat vulnerable plaques and diffuse athero...
Medicated cardiovascular stents, also called drug eluting stents (DES), represent a relevant application of controlled drug release mechanisms. Modeling of drug release from DES also represents a challenging problem for theoretical and computational analysis. In particular, the study of drug release involves models with singular behavior, arising, for instance, in the analysis of drug release in the small diffusion regime. Moreover, the application to realistic stent configurations requires one ...
Abstract Despite their success, stenting procedures are still associated to some clinical problems like sub-acute thrombosis and in-stent restenosis. Several clinical studies associate these phenomena to a combination of both structural and hemodynamic alterations caused by stent implantation. Recently, numerical models have been widely used in the literature to investigate stenting procedures but always from either a purely structural or fluid dynamic point of view. The aim of this work is the ...
In vitro tissue engineering is investigated as a potential source of functional tissue constructs for cartilage repair, as well as a model system for controlled studies of cartilage development and function. Among the different kinds of devices for the cultivation of 3D cartilage cell colonies, we consider here polymeric scaffold-based perfusion bioreactors, where an interstitial fluid supplies nutrients and oxygen to the growing biomass. At the same time, the fluid-induced shear acts as a physi...
We consider a two-phase generalization of the classical Higuchi model for controlled drug release. The drug is assumed to be prepared in a stent in its solid phase by immersion in a polymeric matrix, which eventually delivers the drug when it reaches the free end. We derive a single effective evolution equation, which we prove to be equivalent to the original system of two coupled PDEs. We provide analytical estimates for the asymptotic regimes of large and small diffusion. Results from numerica...
#1Carlo D'Angelo(Polytechnic University of Milan)H-Index: 10
#2Paolo Zunino(Polytechnic University of Milan)H-Index: 28
The fully coupled description of blood flow and mass transport in blood vessels requires extremely robust numerical methods. In order to handle the heterogeneous coupling between blood flow and plasma filtration, addressed by means of Navier-Stokes and Darcy's equations, we need to develop a numerical scheme capable to deal with extremely variable parameters, such as the blood viscosity and Darcy's permeability of the arterial walls. In this paper, we describe a finite element method for the app...
Percutaneous treatment of bifurcations with conventional (straight) stents has been associated with complex procedures and poor clinical outcomes. Also, several limitations including side branch ostial gap, excessive metal density in the parent vessel, incomplete stent apposition, and stent distortion/disruption have been reported with current techniques. Dedicated bifurcation stents have been designed to simplify the procedure, even in complex and challenging anatomies, and to improve acute and...
For several decades, coronary-artery bypass grafting (CABG) has been regarded as the treatment of choice for patients with unprotected left main coronary artery (LMCA) disease. However, because of marked advancements in techniques of percutaneous coronary intervention (PCI) with stenting and CABG, as well as adjunctive pharmacologic therapy, a new evaluation and review of current indications for optimal revascularisation therapy for LMCA disease may be required to determine the standard of care ...
An analytical solution for solving the transient drug diffusion in adjoining porous wall layers faced with a drug-eluting stent is presented. The endothelium, intima, internal elastic lamina and media are all treated as homogeneous porous media and the drug transfer through them is modelled by a set of coupled partial differential equations. The classical separation of variables method for a multi-layer configuration is used. The model addresses the concept of penetration depth for multi-layer s...
In the last decade, many computational models have been developed to describe the transport of drug eluted from stents and the subsequent uptake into arterial tissue. Each of these models has its own set of limitations: for example, models typically employ simplified stent and arterial geometries, some models assume a homogeneous arterial wall, and others neglect the influence of blood flow and plasma filtration on the drug transport process. In this study, we focus on two common limitations. Sp...
Abstract Since theoretical models provide data that cannot be otherwise gathered, numerical methods applied to medical devices analysis have emerged as fundamental tool in preclinical development. Large efforts were done to study mechanical and drug-eluting properties in stents but often the coating modelling is neglected. This work presents a finite element framework to calculate mechanical loads and drug distribution in three commercial drug-eluting stents (Palmaz-Schatz, Palmaz Genesis and Mu...
Last. Hongyan Kang(Ministry of Education)H-Index: 10
view all 5 authors...
Objectives. The study investigates local hemodynamic environment changes caused by straightening phenomenon and the relationship between straightening phenomenon and in-stent restenosis. Background. Intravascular intervention is an effective treatment in restoring the normal flow conditions and vascular lumen. Unfortunately, in-stent restenosis often occurs in a subset of patients after stent implantation and limits the success of stent implantation outcomes. The implanted stent usually causes a...
Abstract Stents have become the most successful device to treat advanced atherosclerotic lesions. However, one of the main issues with these interventions is the development of restenosis. The coating of stents with antiproliferative substances to reduce this effect is now standard, although such drugs can also delay re-endothelialization of the intima. The drug release strategy is therefore a key determinant of drug-eluting stent efficacy. Many mathematical models describing drug transport in a...
Last. Lianglong Chen(Fujian Medical University)H-Index: 10
view all 3 authors...
AbstractBackground:In patients with complex true coronary bifurcation lesions (CBLs), Crush or Culotte stenting has been the commonest approaches of percutaneous coronary intervention (PCI). However, the optimal one remains in debate.Methods:A systematic review and meta-analysis of cohort studies se
#2John Reizes(UNSW: University of New South Wales)H-Index: 19
Last. Tracie Barber(UNSW: University of New South Wales)H-Index: 15
view all 3 authors...
Prior numerical studies have shown that the blood flow patterns surrounding drug-eluting stents can enhance drug uptake in stented arteries. However, these studies employed steady-state simulations, wherein flow and drug transport parameters remained constant with respect to time. In the present study, numerical simulations and in-vitro experiments were performed to determine whether luminal blood flow patterns can truly enhance drug uptake in stented arteries. Unlike the aforementioned studies,...
#2Arul K. Prakash(Indian Institute of Technology Madras)H-Index: 2
Last. Perumal Nithiarasu(Indian Institute of Technology Madras)H-Index: 35
view all 3 authors...
In this paper we introduce a novel method for prescribing terminal boundary conditions in one-dimensional arterial flow networks. This is carried out by coupling the terminal arterial vessel with a poro-elastic tube, representing the flow resistance offered by microcirculation. The performance of the proposed porous media-based model has been investigated through several different numerical examples. First, we investigate model parameters that have a profound influence on the flow and pressure d...
The present study is aimed to investigate the drug transport from a half-embedded drug-eluting stent in presence of atherosclerotic plaque. The luminal drug transport has been modelled by convection–diffusion process, whereas, the transport of free drug within the plaque and healthy tissue by reaction–diffusion process and that of bound drug by reaction process only. The time-dependent release of drug from embedded struts and pulsatile flow at the luminal inlet have been modelled in this study. ...
The present work is concerned with an investigation of the effect of flow pulsatility and time-dependent release kinetics on the transport and retention of drug in a stent-based delivery through atherosclerotic plaque. Keeping the relevance of the physiological situation in view, an axi-symmetric two-dimensional model of drug delivery from a strut has been developed in cylindrical polar coordinate system. Here, the luminal drug transport is considered as an unsteady convection–diffusion process,...