Thrombus Contribution to Very Late Restenosis of Bare-Metal Stent Treated by Excimer Laser Angioplasty: In Vivo Assessment with Optical Coherence Tomography

A 75-year-old, male ex-smoker with hypertension and family history of ischemic heart disease, previous anterior myocardial infarction, and angioplasty with bare-metal stent implantation to the left anterior descending artery 4 years earlier, developed effort angina. A nuclear myocardial scan documented a stress-inducible perfusion defect in the left ventricular anterior wall. The patient was taking 100 mg aspirin daily and a 300 mg loading dose of clopidogrel was administered the day before coronary angiography.

Coronary angiography showed focal proximal in-stent restenosis (Figure 1, Panel A). Optical coherence tomography (OCT) (ImageWire and Imaging System M2, LightLab Imaging, Westford, Massachusetts) was performed using a non-occlusive technique with automated pump injection of iso-osmolar contrast (Visipaque, GE Healthcare, Cork, Ireland) with a pullback speed of 2 mm/second, after intracoronary administration of 400 µg nitroglycerin and intravenous injection of 5,000 IU heparin. The stent was imaged for its entire length. OCT showed restenotic tissue with asymmetric thickness and heterogenous backscattering signal: low on the abluminal site close to the stent struts, and high toward the lumen, at 7 to 12 o’clock, from mid to proximal stent segment, with a minimal luminal area of 2.6 mm² (Figure 1, Panels IA and IB). At 1 to 6 o’clock, the restenotic tissue showed a uniform lower thickness with homogenous high backscattering signal, typical of neointimal hyperplasia (Figure 1, Panels IA and IB). At the proximal stent edge, an intraluminal protruding thrombotic mass was detected (Figure 1, Panel C). The decision to perform laser angioplasty was made, and an additional bolus of 4,000 IU of intravenous heparin were administered. After excimer laser ablation with a 1.7 mm catheter (Vitesse 1.7, Spectranetics, Colorado Springs, Colorado), the heterogeneous restenotic tissue fragmented into irregular masses protruding into the lumen, highly suggestive of thrombotic material (Panels IIA and IIB). After laser ablation with a 2.0 mm catheter, the thrombotic masses detached from the vessel wall, causing further lumen narrowing (Figure 1, Panels IIIA and IIIB). Post-dilatation of the stent with a 2.5 x 10 mm Maverick balloon (Boston Scientific, Natick, Massachusetts) and implantation of a sirolimus-eluting Cypher stent (Cordis Corporation, Miami, Florida) 3.5 x 23 mm were performed, with optimal angiographic result (Figure 1, Panel B). The patient was discharged home with the indication to continue life-long aspirin at a dosage of 100 mg daily and clopidogrel for 12 months at a dosage of 75 mg daily.

In-stent restenosis (ISR) represents the Achilles’ tendon of bare-metal stents as it is associated with repeat target lesion revascularization, often requiring implantation of a drug-eluting stent. Neointimal hyperplasia is the main determinant of ISR.¹ However, previous histological studies have reported the presence of new atheromatous progression with even thrombus formation inside the restenotic tissue, examined years after bare-metal stent implantation.^2,3 OCT is a novel imaging technique that, due to its high spatial resolution (10–20 µm), allows fine characterization of stent strut apposition and stent geometry, the detection of strut coverage and neointimal hyperplasia,⁴ and the identification of thrombus and coronary plaque composition.^5,6

Previous OCT studies⁷ have reported the presence of several materials with different optical properties inside the restenotic tissue after stent implantation, suggesting that different tissue constituents may contribute to ISR. Takano et al.⁸ reported the presence of various OCT signal patterns of restenotic tissue at a follow-up > 5 years after bare-metal stent implantation, consistent with several tissue types, with 67% of patients presenting lipid-laden tissue and 29% thin-cap fibroatheroma-like appearance. These authors showed the dynamic change of the restenotic tissue from neointima to atherosclerotic-like appearance in the same patients, over a late-phase period of observation, and reported the occurrence of intimal disruption and thrombus formation in restenotic tissues with lipid-laden appearance. In the present case of very late ISR, OCT documented an asymmetric restenotic tissue with heterogenous signal appearance, similar to that reported in previous studies.^7,8 We acknowledge that the lack of histopathological analysis does not allow confirmation of the thrombotic composition of the restenotic tissue and that an artifactual change in OCT signal intensity, due to a higher distance between the image wire and the part of restenotic tissue close to the stent struts, could contribute to the heterogeneous appearance itself of the restenotic tissue. However, the fragmentation of this tissue into irregular intraluminal masses with OCT features of thrombus gives support to the notion that a heterogenous OCT pattern of restenosis may contain thrombotic material and shows that restenosis may not be a benign entity.

References

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From the ¹Department of Interventional Cardiology, Istituto Clinico Humanitas IRCCS, ²Department of Cardiology, the Northern Hospital, University of Melbourne, Victoria, Australia, and ³the Institute of Cardiology, Catholic University of the Sacred Heart, Rome, Italy.
Manuscript submitted January 3, 2011, provisional acceptance given January 12, 2011, final version accepted January 17, 2011.
Address for correspondence: Dr Giuseppe Ferrante, MD, PhD, Istituto Clinico Humanitas IRCCS, Interventional Cardiology, Via Alessandro Manzoni 56, Rozzano (Milan), Italy. Email: giu.ferrante@hotmail.it