Drug delivery patterns for different stenting techniques in coronary bifurcations: a comparative computational study

Abstract

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.

Computational fluid dynamic simulations of image-based stented coronary bifurcation models

“…A virtual model that takes into account the haemodynamics, and the drug release would be useful in order to better predict the instent restenosis regions. In the literature, some works on the study of the fluid dynamics coupled with drug transport have been already proposed but they consider simplified vessel geometries [49] or they approximate the stent as a line and not as a rsif.royalsocietypublishing.org J R Soc Interface 10: 20130193 complex three-dimensional structure [50,51]. Clinical followups of the studied cases will help in a better understanding of the link between haemodynamics and in-stent restenosis.…”

A combined numerical and experimental framework for determining permeability properties of the arterial media

“…This restriction may inhibit transport across the layer, leading to accumulation of macromolecules in the inner wall. Transport properties of the medial layer are also important in understanding the transport of drugs from stents (Vairo et al, 2010, Denny et al, 2012, Cutri et al, 2013, Bozsak et al, 2014.…”

Analytical modeling of drug dynamics induced by eluting stents in the coronary multi-layered curved domain

“…Therefore, proposed results clearly highlight that the variation of β and of the coating thickness produce some counteracting effects on the DES therapeutic effectiveness: when the therapeutic window (i.e., the duration of the therapeutic action) increases then the reacting drug fraction (i.e., the antiproliferative effectiveness) reduces, and viceversa. Accordingly, fully in agreement with clinical evidence (e.g., [6][7][8][9]12,31,32,55]) and other modeling approaches (e.g., [18][19][20][21][22][23][24][25][26][27][28][29][30][34][35][36]), applicative examples herein discussed suggest that a suitable therapeutic effectiveness can be obtained by choosing coating material and drug type such that drug diffusivity D 1 and topcoat permeability P 1 are small enough, as well as by prescribing values for coating thickness and drug reaction rate within certain optimal ranges.…”

“…In some cases drug transport due to the plasma filtration through the tissue (activated by physiological transmural pressure gradients) and chemical binding of drug with tissue proteins are also accounted for. Several computational approaches refer to simple one-dimensional formulations [18,19], as well as to more refined bi-dimensional [20][21][22][23][24][25] and threedimensional [26][27][28][29][30] models. In the context of one-dimensional models, a multi-layered computational approach has been proposed by Lovich and Edelman [18], with the aim of investigating the propagation of a hydrophilic drug, such as heparin.…”

“…In that work an advection-diffusion model was formulated and implemented by using a finite-element technique, highlighting the influence of both atherosclerotic plaque and strut pattern. More refined computational approaches were conceived by accounting for three-dimensional domains, either based on simplified geometry [26] or derived from the simulation of the stent expansion [27][28][29][30].…”