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Stent malapposition generates stent thrombosis: Insights from a thrombosis model

https://doi.org/10.1016/j.ijcard.2022.02.003Get rights and content

Highlights

  • Under-expansion alone did not result cause significant thrombosis in this in vitro model.

  • Under-expansion with malapposition resulted in more thrombus formation.

  • There is a positive correlation between length of malapposition and thrombus volume.

  • The longer malapposition segments generated larger measured thrombus volume.

Abstract

Background

Currently, there exists differing conclusions on the role of acute stent malapposition and its role in stent thrombosis (ST). The European Association of Percutaneous Cardiovascular Interventions (EAPCI) consensus recommends that acute malapposition <0.4 mm with longitudinal extension <1 mm need not be corrected since there is no clear correlation of malapposition with adverse clinical outcomes. However, malapposition was identified as the main mechanism of ST in the Bern and PESTO registries, and one of the three leading mechanism in the PRESTIGE study.

Methods

In this study, a validated perfused benchtop thrombosis model was deployed to evaluate the role of both stent under-expansion (UE) and acute stent malapposition (MA) on thrombus formation in vitro in a controlled reproducible environment.

Results

The results showed that UE alone did not result in acute thrombus formation, but UE together with MA did. The data suggested that a MA distance of 0.25 mm led to significant thrombus formation; and a positive correlation exists between the longitudinal extension of the MA and the thrombus volume formed.

Conclusion

Experiments in this in vitro model demonstrated that platelets and a thrombosis cascade were activated and developed around large segments of malapposed stent. This was significantly more thrombus formation than in the under-expanded stent region.

Introduction

Stent thrombosis (ST) is a rare but serious complication of percutaneous coronary interventions (PCI), and is typically associated with high rates of morbidity and mortality [1]. A plethora of factors contributes to the development of ST: patient-related, lesion-related, procedural and post procedural factors. Pathophysiological mechanisms involving adverse rheological features associated with the presence of thick struts and prothrombotic materials (e.g. uncovered stent struts and certain polymers) can initiate the extrinsic pathway of the coagulation cascade. Previously, we have shown how malapposed struts disrupt the laminar flow [2], creating larger regions of high shear rate compared to well-apposed struts. This observation has also been corroborated by other reports and in vivo imaging studies have shown some correlation between incomplete stent apposition and late stent thrombosis [3]. Clinical studies have associated stent under-expansion with acute/early ST and malapposition with late/very late ST. [[4], [5], [6]] These studies have suggested the importance of malapposition length (>1 mm) but not malapposition distance or area in predicting the risk of very late ST. Regions containing thrombus often have consecutive malapposed and uncovered struts [[4], [5], [6]].

However, other studies have challenged the role of acute stent malapposition on adverse clinical outcomes [7]. In a recent analysis of 356 lesions, Im et al. found no ST in patients with OCT-detected stent malapposition. Moreover, patients with and without stent malapposition had similar rate of adverse events at 5 years follow-up [7]. In the HORIZON-AMI sub-study, authors also concluded that malapposition did not correlate with early ST. These studies reduced the attention for aiming at achieving complete stent apposition to avoid ST. [8] The CLI-OPCI LATE study also showed in 1211 patients, acute stent malapposition (detected in 50% of stents) was not significantly related to worst outcomes [9]. Finally, in a recent review of various clinical studies, Ali et al. concluded that until data are available, attention should be focused on optimizing stent expansion and adequate lesion coverage rather than correcting acute malapposition [7].

These conflicting results have created confusion in the interventional community concerning how to approach acute stent malapposition. Several authors advocate now for a threshold of 0.4 mm of strut malapposition to justify the need for acute correction [10]. A recent position paper published by European Association of Percutaneous Cardiovascular Interventions (EAPCI), recommends that acute malapposition <0.4 mm with longitudinal extension <1 mm should not be corrected since this portends no clear clinical value, though the consensus document highlights that additional prospective validation are still required [11].

Section snippets

Stent deployment

Drug Eluting Stents (DES) were deployed in an in vitro model with a reference diameter of 2.75 mm and a minimum lumen diameter of 1.6 mm at the middle (~40% diameter stenosis). These lesion models were made from silicone (MED-4735 with 35 Shore hardness; NuSil Technology LLC, Carpinteria, CA, USA). The model had a 0.45 mm wall with isotropic-elastic material properties (density 1110 kg/m3; Young's modulus 1.2 MPa; Poisson's ratio 0.48). A sirolimus-eluting stent (Orsiro, Biotronik, Germany) was

Results and discussion

Based on our findings, under-expansion alone did not result in significant thrombus formation as compared to samples that had under-expansion with malapposition (0.03mm2 vs 3.05mm2 and 2.74mm2, p = 0.001 as seen in Fig. 1a). The results showed that in such perfusion in-vitro model, a malapposition distance of 0.25 mm caused significant thrombus formation but under-expansion alone did not. The length of the malapposition segment played a role on the total thrombus volume (8.99mm3 vs 4.69mm3, p

Conclusion

While it is largely recognized that mild acute stent malapposition, over a limited length (<1 mm), does not represent a major clinical concern and does not warrant correction with further expansion, the impact of larger acute malapposition remains controversial. Experiments in this in vitro model demonstrated that platelets and a thrombosis cascade were activated and developed around large segments of malapposed stent. This was significantly more thrombus formation than in the under-expanded

Declaration of Competing Interest

CC reports receiving research grants from Biosensor, Heart Flow Inc., Abbott Vascular, ShockWave Medical, Pie Medical Imaging, GE Healthcare, Siemens, Medis Medical Imaging, and consultancy fees from Heart Flow Inc., Boston Scientific, Siemens, Pfizer, and Philips Volcano. The rest of the authors have no relevant conflict of interest to declare.

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