Hemodynamics in coronary arteries with overlapping stents
Introduction
About 30% of patients undergoing percutaneous coronary intervention (PCI) with stent placement are treated with overlapping stents (Holmes et al., 2004, Räber et al., 2010). Stent overlap is associated with increased risk of adverse clinical outcome for both bare metal stents (BMS) and drug eluting stents (DES) (Ellis et al., 1992, Räber et al., 2010). Various studies have investigated clinical results and biological aspects of stent overlap, but the hemodynamics inside arteries with overlapping stents and the associated wall shear stress (WSS) parameters have received much less attention (Balakrishnan et al., 2005, Charonko et al., 2010, Peacock et al., 1995). This can be in part attributed to the lack of suitable methods for acquiring the geometry of arteries containing overlapping stents with sufficient accuracy.
Stent overlap is associated with increased in-stent restenosis and lumen loss due to delayed healing and increased inflammation regardless of stent type (Räber et al., 2010, Wang et al., 2000). While DES may reduce neointimal hyperplasia and restenosis in single stent cases (Moses et al., 2003, Tsagalou et al., 2005), their performance (Finn et al., 2005, Matsumoto et al., 2007) and safety (Moreno et al., 2005) in regions of overlap are a case of debate. Overlapping BMS are associated with worse clinical outcome compared to single BMS (Kastrati et al., 1999, Kereiakes et al., 2006, Serruys et al., 2002). This is attributed primarily to more pronounced arterial injury caused by the expansion of two stents at the same location, leading to increased inflammation. However, the poorer outcome may also be related to severe hemodynamic disturbances introduced by stent malapposition (Charonko et al., 2010) that are inherent in stent overlap but occur infrequently in single stents (Matsumoto et al., 2007).
It is generally accepted that hemodynamics influences vascular health and pathogenesis. WSS as one of the manifestations of blood flow has been shown to be an important factor in atherogenesis (Chatzizisis et al., 2007, Cheng et al., 2006) and in the pathobiology of neointimal hyperplasia, thrombosis and in-stent restenosis (Papafaklis et al., 2010, Wentzel et al., 2008). These latter processes are a concern in percutaneous vascular intervention in general and in stent placement in particular. For example, stent malapposition has been shown to increase thrombogenicity. It is hypothesized that hemodynamics plays a role therein, as adjacent high shear stress areas and recirculation zones caused by malapposed stents may activate platelets and increase local residence times of these thrombocytes (Hathcock, 2006, Kolandaivelu et al., 2011, Peacock et al., 1995). Kolandaivelu and co-workers showed in vitro and in a 2D computational model with idealized domain geometry that flow recirculation between malapposed and overlapping stent struts may modulate stent thrombogenicity (Kolandaivelu et al., 2011).
Computational fluid dynamics (CFD) is the method of choice for assessing shear stress and local hemodynamics in stented arteries. The precise acquisition of the stent struts and arterial geometry is a prerequisite for accurate CFD analysis, but no clinical imaging modality exists that could yield such data with sufficient resolution. Several approaches have been reported in the literature to circumvent this limitation: simulations may be conducted on idealized geometries based on stent CAD data (Gundert et al., 2011), on hybrid domains where the stent free geometry is obtained by CT, digital angiography or MRI and a stent is virtually implanted (De Santis et al., 2010, LaDisa et al., 2006), on ex vivo micro-computed tomography (µCT) data of explanted, stented arteries (Morlacchi et al., 2011) or µCT images of stented in vitro artery models (Benndorf et al., 2009, Connolley et al., 2007). While these methods have their undisputed respective strengths, they have either limited geometric accuracy, limited treatable vascular domain size or incomplete representation of the mechanical interaction between stent and arterial wall.
We have recently introduced a method that allows for precise ex vivo acquisition of arteries stented in vivo or ex vivo, yielding both the macroscopic arterial tree geometry as well as the configuration and morphology of individual stent struts (Rikhtegar et al., 2013). Here we make use of this method to investigate the shear stress distribution and hemodynamics of porcine coronary arteries with overlapping stents. Our goal is to evaluate flow disturbances and consequent shear stress alterations introduced by stent overlap which may contribute to the reported clinical problems associated with overlapping stents.
Section snippets
Methods
A concise description of the utilized methods is given here. We refer the reader to the Supplemental material and Rikhtegar et al. (2013) for a more detailed explanation of the individual process steps.
Results
It has been shown previously that the acquisition method used here can capture single stented arteries accurately at high resolution (Rikhtegar et al., 2013). Fig. 1 illustrates that this method also ensures anatomic fidelity in the case of overlapping stents, showing that it captures regions of prolapse between stent struts (Panel A), axial arterial deformation caused by the stent implantation (Panel B), strut overlap and relative positioning (Panel C), radial arterial deformation (Panel D)
Discussion
It is known that hemodynamics influences atherogenesis (Chatzizisis et al., 2007, Samady et al., 2011), thrombogenesis (Hathcock, 2006), vascular remodeling (Stone et al., 2003), neointimal hyperplasia (Wentzel et al., 2001) and endothelial healing (Franco et al., 2013). It is further known that stent overlap, compared to single stents, increases thrombogenicity (Kolandaivelu et al., 2011, Rogers and Edelman, 1995), may delay the re-endothelization and enhance platelet deposition and thrombus
Conclusion
We have shown that the relative size of low WSS areas is increased significantly in regions of stent overlap compared to non-overlapped regions. Since low WSS is generally accepted as a factor in atherogenesis and thrombogenesis, we conclude that the adverse hemodynamics caused by stent overlap may be responsible in part for the adverse clinical outcome in patients that are treated with overlapping stents. In cases where stent overlap cannot be avoided, new deployment strategies or stent
Conflict of interest statement
We have no conflicts of interest to report.
Acknowledgments
We thank Ryan J. Choo and Gian N. Schädli of ETH Zurich for help with the micro-computed tomography and image segmentation, respectively. This work was partially funded by the Swiss Federal Commission for Technology and Innovation through EnOp, grant 9921.1, and the Swiss National Science Foundation through NCCR Kidney.CH.
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