title: Drug deposition in coronary arteries with overlapping drug-eluting stents.
abstract: Drug-eluting stents are accepted as mainstream endovascular therapy, yet concerns for their safety may be under-appreciated. While failure from restenosis has dropped to below 5%, the risk of stent thrombosis and associated mortality remain relatively high. Further optimization of drug release is required to minimize thrombosis risk while maintaining therapeutic dose. The complex three-dimensional geometry of deployed stents together with the combination of diffusive and advective drug transport render an intuitive understanding of the situation exceedingly difficult. In situations such as this, computational modeling has proven essential, helping define the limits of efficacy, determine the mode and mechanism of drug release, and identify alternatives to avoid toxicity. A particularly challenging conformation is encountered in coronary arteries with overlapping stents. To study hemodynamics and drug deposition in such vessels we combined high-resolution, multi-scale ex vivo computed tomography with a flow and mass transfer computational model. This approach ensures high geometric fidelity and precise, simultaneous calculation of blood flow velocity, shear stress and drug distribution. Our calculations show that drug uptake by the arterial tissue is dependent both on the patterns of flow disruption near the wall, as well as on the relative positioning of drug-eluting struts. Overlapping stent struts lead to localized peaks of drug concentration that may increase the risk of thrombosis. Such peaks could be avoided by anisotropic stent structure or asymmetric drug release designed to yield homogeneous drug distribution along the coronary artery and, at the least, suggest that these issues need to remain in the forefront of consideration in clinical practice.
authors.affiliation: Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA. Electronic address: farhadr@mit.edu.
authors.forename: Farhad
authors.initials: F
authors.lastname: Rikhtegar
authors.affiliation: Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA; Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Elazer R
authors.initials: ER
authors.lastname: Edelman
authors.affiliation: The Interface Group, Institute of Physiology, University of Zurich, Zurich, Switzerland.
authors.forename: Ufuk
authors.initials: U
authors.lastname: Olgac
authors.affiliation: Laboratory of Thermodynamics in Emerging Technologies, Department of Mechanical and Process Engineering, ETH Zurich, Zurich, Switzerland.
authors.forename: Dimos
authors.initials: D
authors.lastname: Poulikakos
authors.affiliation: The Interface Group, Institute of Physiology, University of Zurich, Zurich, Switzerland; Zurich Center for Integrative Human Physiology and National Center of Competence 'Kidney.CH', University of Zurich, Zurich, Switzerland.
authors.forename: Vartan
authors.initials: V
authors.lastname: Kurtcuoglu
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D003198:Computer Simulation; D003331:Coronary Vessels / Q000502:physiology*; D054855:Drug-Eluting Stents / Q000009:adverse effects; D008955:Models, Cardiovascular; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000097:blood*; D011474:Prosthesis Design; D013314:Stress, Mechanical; D013552:Swine; D013927:Thrombosis / Q000209:etiology
chemical_list: D004364:Pharmaceutical Preparations
keywords: Arterial drug uptake; Drug-eluting stent; Hemodynamics; Overlap