Skip to main content
SpringerLink
Log in

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

  • Original Paper
  • Published:
Biomechanics and Modeling in Mechanobiology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Adriaenssens T, Byrne RA, Dibra A, Iijima R, Mehilli J, Bruskina O, Schömig A, Kastrati A (2008) Culotte stenting technique in coronary bifurcation disease: Angiographic follow-up using dedicated quantitative coronary angiographic analysis and 12-month clinical outcomes. Eur Heart J 29: 2868–2876

    Article  Google Scholar 

  • Assali AR, Assa HV, Ben-Dor I, Teplitsky I, Solodky A, Brosh D, Fuchs S, Kornowski R (2006) Drug-eluting stents in bifurcation lesions: to stent one branch or both. Catheter Cardiovasc Interv 68: 891–896

    Article  Google Scholar 

  • Balakrishnan B, Dooley J, Kopia G, Edelman ER (2008) Thrombus causes fluctuations in arterial drug delivery from intravascular stents. J Controlled Release 131: 173–180

    Article  Google Scholar 

  • Balakrishnan B, Dooley JF, Kopia G, Edelman ER (2007) Intravascular drug release kinetics dictate arterial drug deposition, retention, and distribution. J Controlled Release 123: 100–108

    Article  Google Scholar 

  • Balakrishnan B, Tzafriri AR, Seifert P, Groothuis A, Rogers C, Edelman BR (2005) Strut position, blood flow, and drug deposition: Implications for single and overlapping drug-eluting stents. Circulation 111: 2958–2965

    Article  Google Scholar 

  • Biscari P, Minisini S, Pierotti D, Verzini G, Zunino P (2011) Controlled release with finite dissolution rate. SIAM J Appl Math 71: 731–752

    Article  MathSciNet  Google Scholar 

  • Borghi A, Foa E, Balossino R, Migliavacca F, Dubini G (2008) Modelling drug elution from stents: effects of reversible binding in the vascular wall and degradable polymeric matrix. Comput Methods Biomech Biomed Eng 11: 367–377

    Article  Google Scholar 

  • Chevalier B, Glatt B, Royer T, Guyon P (1998) Placement of coronary stents in bifurcation lesions by the “Culotte” technique. Am J Cardiol 82: 943–949

    Article  Google Scholar 

  • Collet C, Costa RA, Abizaid A (2011) Dedicated bifurcation analysis: dedicated devices. Int J Cardiovasc Imaging 27: 181–188

    Article  Google Scholar 

  • D’Angelo C, Zunino P (2011) Robust numerical approximation of coupled Stokes’ and Darcy’s flows applied to vascular hemodynamics and biochemical transport. ESAIM Math Model Numer Anal 45: 447–476

    Article  MathSciNet  Google Scholar 

  • D’Angelo C, Zunino P, Porpora A, Morlacchi S, Migliavacca F (2011) Model reduction strategies enable computational analysis of controlled drug release from cardiovascular stents. SIAM J Appl Math 71: 2312–2333

    Article  MathSciNet  Google Scholar 

  • D’Angelo C, Zunino P (2012) Numerical approximation with Nitsche’s coupling of transient Stokes’/Darcy’s flow problems applied to hemodynamics. Appl Numer Math 62(4): 378–395

    Article  MathSciNet  Google Scholar 

  • Formaggia L, Quarteroni A, Veneziani A (2009) Cardiovascular mathematics modeling and simulation of the circulatory system. Springer, Milano

    Google Scholar 

  • Frenning G (2003) Theoretical investigation of drug release from planar matrix systems: effects of a finite dissolution rate. J Controlled Release 92: 331–339

    Article  Google Scholar 

  • Gastaldi D, Morlacchi S, Nichetti R, Capelli C, Dubini G, Petrini L, Migliavacca F (2010) Modelling of the provisional side-branch stenting approach for the treatment of atherosclerotic coronary bifurcations: effects of stent positioning. Biomech Model Mechanobiol 9: 551–561

    Article  Google Scholar 

  • Grassi M, Pontrelli G, Teresi L, Grassi G, Comel L, Ferluga A, Galasso L (2009) Novel design of drug delivery in stented arteries: a numerical comparative study. Math Biosci Eng 6: 493–508

    Article  MathSciNet  Google Scholar 

  • Gonzalo N, Garcia-Garcia HM, Regar E, Barlis P, Wentzel J, Onuma Y, Ligthart J, Serruys PW (2009) In vivo assessment of high-risk coronary plaques at bifurcations with combined intravascular ultrasound and optical coherence tomography. JACC Cardiovasc Imaging 2: 473–482

    Article  Google Scholar 

  • Higuchi T (1961) Rate of release of medicaments from ointment bases containing drugs in suspension. J Pharm Sci 50: 874–875

    Article  Google Scholar 

  • Holzapfel GA, Sommer G, Gasser CT, Regitnig P (2005) Determination of layer-specific mechanical properties of human coronary arteries with nonatherosclerotic intimal thickening and related constitutive modeling. Am J Physiol Heart Circ Physiol 289: H2048–H2058

    Article  Google Scholar 

  • Hose DR, Narracott AJ, Griffiths B, Mahmood S, Gunn J, Sweeney D, Lawford PV (2004) A thermal analogy for modelling drug elution from cardiovascular stents. Comput Methods Biomech Biomed Eng 7: 257–264

    Article  Google Scholar 

  • Hossain SS, Hossainy SFA, Bazilevs Y, Calo VM, Hughes TJR (2012) Mathematical modeling of coupled drug and drug-encapsulated nanoparticle transport in patient-specific coronary artery walls. Comput Mech 49: 213–242

    Article  MathSciNet  Google Scholar 

  • Hoye A (2006) Contemporary percutaneous coronary intervention for complex lesions: the treatment of chronic total occlusions and bifurcations in the drug-eluting stent era. Ph.D. thesis. http://repub.eur.nl/res/pub/7642/

  • Hwang C-, Wu D, Edelman ER (2001) Physiological transport forces govern drug distribution for stent-based delivery. Circulation 104: 600–605

    Article  Google Scholar 

  • Iakovou I, Ge L, Colombo A (2005) Contemporary stent treatment of coronary bifurcations. J Am Coll Cardiol 46: 1446–1455

    Article  Google Scholar 

  • Kolachalama VB, Levine EG, Edelman ER (2009a) Luminal flow amplifies stent-based drug deposition in arterial bifurcations. PLoS ONE 4

  • Kolachalama VB, Tzafriri AR, Arifin DY, Edelman ER (2009b) Luminal flow patterns dictate arterial drug deposition in stent-based delivery. J Controlled Release 133: 24–30

    Article  Google Scholar 

  • Lanzer P, Gijsen FJH, Topoleski LDT, Holzapfel GA (2010) Call for standards in technical documentation of intracoronary stents. Herz 35: 27–33

    Article  Google Scholar 

  • Lefèvre T, Louvard Y, Morice M, Dumas P, Loubeyre C, Benslimane A, Premchand RK, Guillard N, Piéchaud J (2000) Stenting of bifurcation lesions: classification, treatments, and results. Catheter Cardiovasc Interv 49: 274–283

    Article  Google Scholar 

  • Lovich MA, Edelman ER (1996) Computational simulations of local vascular heparin deposition and distribution. Am J Physiol Heart Circ Physiol 271: H2014–H2024

    Google Scholar 

  • Migliavacca F, Gervaso F, Prosi M, Zunino P, Minisini S, Formaggia L, Dubini G (2007) Expansion and drug elution model of a coronary stent. Comput Methods Biomech Biomed Eng 10: 63–73

    Article  Google Scholar 

  • Mongrain R, Faik I, Leask RL, Rodés-Cabau J, Bertrand OF, Bertrand OF (2007) Effects of diffusion coefficients and struts apposition using numerical simulations for drug eluting coronary stents. J Biomech Eng 129: 733–742

    Article  Google Scholar 

  • Morice M-, Serruys PW, Eduardo Sousa J, Fajadet J, Hayashi EB, Perin M, Colombo A, Schuler G, Barragan P, Guagliumi G, Molnà àr F, Falotico R (2002) A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization. N Engl J Med 346: 1773–1780

    Article  Google Scholar 

  • Morlacchi S, Chiastra C, Gastaldi D, Pennati G, Dubini G, Migliavacca F (2011) Sequential structural and fluid dynamic numerical simulations of a stented bifurcated coronary artery. J Biomech Eng 133(12)

  • Mortier P, Holzapfel GA, De Beule M, Van Loo D, Taeymans Y, Segers P, Verdonck P, Verhegghe B (2010) A novel simulation strategy for stent insertion and deployment in curved coronary bifurcations: comparison of three drug-eluting stents. Ann Biomed Eng 38: 88–99

    Article  Google Scholar 

  • Pan M, SuárezDe Lezo J, Medina A, Romero M, Segura J, Ramírez A, Pavlovic D, Hernández E, Ojeda S, Adamuz C (2002) A stepwise strategy for the stent treatment of bifurcated coronary lesions. Catheter Cardiovasc Interv 55: 50–57

    Article  Google Scholar 

  • Park S, Park D (2010) Left main stenting: is it a different animal. EuroIntervention 6: J112–J117

    Article  Google Scholar 

  • Perktold K, Hofer M, Rappitsch G, Loew M, Kuban BD, Friedman MH (1998) Validated computation of physiologic flow in a realistic coronary artery branch. J Biomech 31: 217–228

    Article  Google Scholar 

  • Pontrelli G, de Monte F (2010) A multi-layer porous wall model for coronary drug-eluting stents. Int J Heat Mass Transfer 53: 3629–3637

    Article  Google Scholar 

  • Sacco R, Causin P, Zunino P, Raimondi MT (2011) A multiphysics/multiscale 2D numerical simulation of scaffold-based cartilage regeneration under interstitial perfusion in a bioreactor. Biomech Model Mechanobiol 10: 577–589

    Article  Google Scholar 

  • Sakharov DV, Kalachev LV, Rijken DC (2002) Numerical simulation of local pharmacokinetics of a drug after intravascular delivery with an eluting stent. J Drug Target 10: 507–513

    Article  Google Scholar 

  • Sheiban I, Villata G, Bollati M, Sillano D, Lotrionte M, Biondi-Zoccai G (2008) Next-generation drug-eluting stents in coronary artery disease: Focus on everolimus-eluting stent (Xience V). Vasc Health Risk Manage 4: 31–38

    Article  Google Scholar 

  • Stankovic G, Mehmedbegovic Z, Zivkovic M (2010) Bifurcation coronary lesions—approaches to bifurcation management. J Interv Cardiol 5: 53–57

    Google Scholar 

  • Tzafriri AR, Levin AD, Edelman ER (2009) Diffusion-limited binding explains binary dose response for local arterial and tumour drug delivery. Cell Prolif 42: 348–363

    Article  Google Scholar 

  • Vairo G, Cioffi M, Cottone R, Dubini G, Migliavacca F (2010) Drug release from coronary eluting stents: a multidomain approach. J Biomech 43: 1580–1589

    Article  Google Scholar 

  • Zunino P, D’Angelo C, Petrini L, Vergara C, Capelli C, Migliavacca F (2009) Numerical simulation of drug eluting coronary stents: mechanics, fluid dynamics and drug release. Comput Methods Appl Mech Eng 198: 3633–3644

    Article  MathSciNet  Google Scholar 

  • Zunino P (2004) Multidimensional pharmacokinetic models applied to the design of drug-eluting stents. Cardiovasc Eng 4: 181–191

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Mathematics, Modelling and Scientific Computing (MOX), Politecnico di Milano, Milan, Italy

    Elena Cutrì & Paolo Zunino

  2. Department of Mechanical Engineering and Materials Science, University of Pittsburgh, Pittsburgh, PA, USA

    Paolo Zunino

  3. Laboratory of Biological Structure Mechanics (LaBS), Structural Engineering Department, Politecnico di Milano, Milan, Italy

    Stefano Morlacchi, Claudio Chiastra & Francesco Migliavacca

  4. Bioengineering Department, Politecnico di Milano, Milan, Italy

    Stefano Morlacchi & Claudio Chiastra

Authors
  1. Elena Cutrì
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paolo Zunino
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stefano Morlacchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Claudio Chiastra
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Francesco Migliavacca
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Paolo Zunino.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cutrì, E., Zunino, P., Morlacchi, S. et al. Drug delivery patterns for different stenting techniques in coronary bifurcations: a comparative computational study. Biomech Model Mechanobiol 12, 657–669 (2013). https://doi.org/10.1007/s10237-012-0432-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10237-012-0432-5

Keywords

Search

Navigation