Very Late Thrombosis After Subintimal Sirolimus-Eluting Stent Implantation During Percutaneous Coronary (FULL TITLE BELOW)
FULL TITLE: Very Late Thrombosis After Subintimal Sirolimus-Eluting Stent Implantation During Percutaneous Coronary Intervention for Chronic Total Occlusion
ABSTRACT: The clinical significance of late-acquired incomplete stent apposition (ISA) after drug-eluting stent (DES) implantation remains controversial. In a case report, late-acquired ISA occurred after a DES was implanted into the subintimal space during percutaneous coronary intervention (PCI) for chronic total occlusion (CTO). However, to our knowledge, there is no report of very late thrombosis of such a case. The present case report describes a late-acquired ISA occurring in the true lumen side external to the subintimally located sirolimus-eluting stent implanted during PCI for a CTO, resulting in very late stent thrombosis (VLST). The late-acquired ISA was observed by intravascular ultrasound and optical coherence tomography at the time of follow-up angiography after VLST.
J INVASIVE CARDIOL 2010;22:E162–E165
Very late thrombosis after drug-eluting stent (DES) implantation has emerged as an important late complication of percutaneous coronary intervention (PCI). Late stent thrombosis beyond 12 months occurs more frequently with DES than with bare-metal stents.1 Although the clinical significance of late-acquired incomplete stent apposition (ISA) after DES implantation remains controversial, intravascular ultrasound (IVUS) examination of late DES thrombosis often shows ISA at the time of the event. A significant gap between struts and vessel wall or aneurysm formation might reduce local blood flow that promotes platelet adhesion and the coagulation cascade.2 We present a case in which late-acquired ISA occurred in the true lumen side external to a subintimally located sirolimus-eluting stent (SES) implanted during PCI for chronic total occlusion (CTO), resulting in very late stent thrombosis (VLST).
Case Report. A 48-year-old male with chest pain on physical exertion was admitted to the hospital in September 2006. Coronary angiography revealed a CTO of the mid left anterior descending artery (LAD) with collateral flow from the left circumflex artery (Figure 1A). Although it was difficult to pass the lesion with a stiff guidewires due to calcification, a Conquest 12g wire (Asahi Intech, Nagoya, Japan) was advanced into the distal LAD true lumen. Coronary angiography showed a double-barrel phenomenon that consisted of the lumen with a guidewire and a lumen with a septal and a small diagonal branch in the CTO site. The angiogram seemed to show a small dissection at the CTO site (Figure 1B). An Eagle Eye Gold™ IVUS catheter (Volcano Therapeutics, Rancho Cordova, California) was located in a false lumen that was separated from the true lumen with a small diagonal branch (Figure 1C). This probably occurred because the guidewire entered the false lumen and advanced into the subintima because of calcification, then crossing into the distal true lumen. A 2.5 x 28 mm Cypher™ SES (Cordis Corp., Miami Lakes, Florida) was implanted from the proximal true lumen passing to the distal true lumen via the mid false lumen (Figure 1D). Then, a final kissing-balloon dilatation of the LAD and the diagonal branch was performed. Final angiography showed that there was no residual stenosis in the SES, but a small diagonal branch was occluded by the SES (Figure 1E). Post-procedural IVUS showed complete stent-vessel wall apposition. However, a small diagonal branch was occluded by the SES (Figure 1F). Dual antiplatelet therapy with aspirin (200 mg/day) and ticlopidine (200 mg/day) was continued for 3 months.
Angiography at two subsequent follow up examinations was performed. In July 2007, repeat follow-up coronary angiography showed pools of contrast medium external to the stented site and a small diagonal branch that was occluded by implanted SES appeared (Figure 2A). In May 2008, repeat coronary angiography also showed no in-stent restenosis. However, pools of contrast medium appeared more clearly and looked like multiple aneurysms (Figure 2B).
In September 2008, the patient presented again with chest pain at rest and was immediately taken by an ambulance. The electrocardiogram showed ST-segment elevation in leads V 3–6. Echocardiography showed regional motion abnormality in the anteroseptal wall. Emergency coronary angiography revealed total occlusion of the stented site due to thrombosis (Figure 2C). After a guidewire was passed through the lesion, we performed a thrombectomy and balloon angioplasty using a 3.0 mm balloon catheter. Final angiography showed good stent dilatation and the reoccluded diagonal branch (Figure 3). Dual antiplatelet therapy with aspirin (200 mg/day) and clopidogrel (75 mg/day) was resumed. In March 2009, 6-month follow-up coronary angiography showed pools of contrast medium and a small diagonal branch reappearing. Subsequently, we performed IVUS (Atlantis SR Pro2™, Boston Scientific Corp., Natick, Massachusetts) and optical coherence tomography (OCT) (ImageWire™, LightLab Imaging, Westford, Massachusetts). Serial IVUS quantitative analysis showed late-acquired ISA due to positive arterial remodeling (increase in mean vessel area 13.6 to 21.0 mm2) (Figures 1F and 3). These areas were observed at the sites of the pooling of contrast medium observed angiographically. The angiographic findings were similar to the phenomenon of pooling of contrast medium that was seen before VLST. At the site of late-acquired ISA on the IVUS image, there is a normal structure composed of three layers that indicates true lumen external to the stent strut on OCT images (Figure 3). Therefore, IVUS and OCT demonstrated stent malapposition in the true lumen side.
Discussion. There has been a case report that late-acquired ISA occurred after DES was implanted into the subintimal space during PCI for CTO.3 However, to our knowledge, there is no report of very late thrombosis in such a case. Although it is generally accepted that most cases of late-acquired ISA are not associated with clinical adverse cardiovascular events,4,5 Cook et al reported that some cases of very late thrombosis after DES implantation showed evidence of positive remodeling with a high incidence of ISA.6 The mechanism of late-acquired ISA due to positive remodeling is thought to be related to cytostatic effects of sirolimus on neointimal formation,4,5 and localized hypersensitivity to the polymer coating.7
In this case, IVUS and OCT showed late-acquired ISA due to positive remodeling external to the SES implanted in the false lumen. These areas of remodeling were observed at the sites of the contrast medium pooling. Although the cause of late-acquired ISA in this case is unclear, Hong et al have suggested that subintimal passage of the guidewire and stenting of the false lumen might cause injury to the adventitial layer, contributing to late stent malapposition.4 Moreover, stenting of a CTO lesion was one of the independent predictors of late stent malapposition.4 Ako et al suggested that late-acquired ISA in SES occurs due to delayed neointimal formation in disease-free segments of the vessel.5 SES implanted into the false lumen exists in the space free of atherosclerotic plaques, between the medial layer and the adventitial layer, because the boundary between a true lumen and a false lumen is an external elastic membrane. Therefore, in this case, there is a possibility that injury to the adventitial layer and delayed neointimal formation in the plaque-free segments of the false lumen resulted in late-acquired ISA.
It is still controversial how long dual antiplatelet therapy should be continued in patients with late-acquired ISA, particularly after SES thrombosis. Luscher et al suggested that prolonged dual-platelet inhibition must be considered in high-risk patients, balanced against the risk of bleeding.8 At present, therefore, dual antiplatelet therapy with aspirin and clopidogrel should be continued.
CTO recanalization sometimes is associated with stent deployment in the false lumen and may predispose to (very) late stent thrombosis (VLST). Use of parallel wire technique may decrease the chances of long segments of false lumen recanalization. This case highlights the careful vigilant follow-up of such cases. Dual antiplatelet therapy indefinitely should be continued in these patients to avoid the chances of VLST.
— Samin K. Sharma, MD
Mount Sinai Medical Center, New York, New York
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From the Department of Cardiology, Tokushima Red Cross Hospital, Komatsushima, Japan.
The authors report no conflicts of interest regarding the content herein.
Manuscript submitted January 4, 2010 and accepted February 1, 2010.
Address for correspondence: Shinichiro Miyazaki, MD, Department of Cardiology, Tokushima Red Cross Hospital, 103 Irinokuchi, Komatsushima-cho, Komatsushima 773-8502, Japan. E-mail address: firstname.lastname@example.org