Late Stent Thrombosis Mimicking Focal Restenosis after Sirolimus Stent Implantation: Angiographic and Intravascular Ultrasound A

Since the introduction of drug-eluting stents (DES) during interventional procedures, several randomized studies have demonstrated a significant reduction in coronary restenosis and target vessel revascularizations.^1–4 However, despite the availability of long-term data, the safety of these devices remains an open question. Coronary stent thrombosis, not detected in the first series, has been recently reported in patients treated with DES.⁵ Furthermore, two controlled studies reported a higher incidence of subacute and late stent thrombosis with DES compared to bare-metal stents (BMS).^6,7 Clopidogrel cessation was strongly associated with this event at late follow up.^6–8 Focal restenosis was the most frequent angiographic finding of in-stent restenosis reported with sirolimus-eluting stents (SES). Nevertheless, histopathological confirmation of this finding was not well reported.⁹ We present here a patient with focal restenosis after SES implantation who underwent an intravascular ultrasound study that suggested the presence of stent thrombosis. Case Report. In April 2004, a 70-year-old male with risk factors of hyperlipidemia and smoking underwent primary percutaneous coronary intervention (PCI) for an acute inferior myocardial infarction with implantation of a 4.0 mm x 18 mm Eucatech BMS to the right coronary artery (RCA) (Eucatech AG, Herten, Germany). Three days later, an additional Eucatech 2.5 mm x 13 mm BMS was deployed in a severe LAD stenosis (Figures 1 and 2). One year later, due to unstable angina and a severe distal edge restenosis in the BMS to the LAD plus significant progression of the disease in the distal portion of the LAD, a 2.5 mm x 23 mm SES was deployed (Cypher™, Cordis Corp., Miami, Florida) and was overlapped to the distal end of the BMS (Figure 3). The patient was discharged under dual antiplatelet therapy (clopidogrel plus aspirin) for 1 year after deployment of the SES. Six months after the last PCI procedure, a neoplasia of the esophagus was discovered. The patient received antineoplasic treatment with compulsory cessation of the daily doses of clopidogrel. The antineoplasic treatment achieved a significant reduction of the tumor and oncological surgery was recommended. Two weeks prior to general surgery and 3 months after clopidogrel was stopped, the patient developed unstable angina with an anterior perfusion defect detected by nuclear test. A new coronary angiogram was performed showing no changes in the previous stents to the RCA and LAD, and focal restenosis in the mid portion of the SES to the LAD (Figure 4). Intravascular ultrasound (IVUS) imaging was performed using a commercially available mechanical sector scanner (Atlantis™ 40 MHz, Boston Scientific Corp., Natick, Massachusetts), and showed absence of neointimal hyperplasia along the eluted stent in both the proximal (overlapped with the BMS) and the distal segments of the SES (Figure 5). IVUS cross-sectional area imaging strongly suggested the presence of stent thrombosis corresponding with the area of the severe focal restenosis by angiography (Figure 6). It is noteworthy that there was no intimal hyperplasia detected by IVUS throughout the entire length of the SES (Figure 5). Balloon angioplasty at 4 atmospheres was performed with successful resolution of the stenosis followed by the deployment of a heparin-coated stent (Camouflage 2.5–18 mm, Eucatech AG). Discussion. Stent thrombosis after DES implantation has been increasingly recognized and has become the most serious complication following DES therapy.^6–9 Several independent factors have been associated with an increased risk of stent thrombosis. In particular, clopidogrel discontinuation, either early or late, was identified as the most powerful predictor of this event after hospital discharge.^8,9 However, we still do not know how long clopidogrel should be taken after DES deployment: 6 months, 1 year or indefinitely. Sudden cardiac death and acute myocardial infarction have been frequently associated with stent thrombosis, regardless of the chronology of the event (subacute, late or very late). However, to our knowledge, angiographic restenosis has not been correlated with late stent thrombosis after DES implantation.¹⁰ The present case features an angiographically focal ISR with IVUS imaging suggestive of thrombotic material without evidence of neointimal hyperplasia or stent fracture. Unfortunately, IVUS was not performed after the initial DES implantation which would have allowed comparison of stent positioning at baseline and follow up. Nevertheless, no evidence of late incomplete stent apposition (ISA) was detected in the current case. ISA is an IVUS finding that can be assessed without serial evaluations and can also be accurately evaluated without baseline IVUS. Moreover, no evidence of positive remodeling was found throughout the stents with respect to the reference (nontreated) vessel.¹¹ Our observation reinforces the contemporary concern of the cardiovascular community regarding the high incidence of stent thrombosis after DES implantation. In addition, this case underlines the crucial importance of clopidogrel to maintain the long-term patency of DES. We recently reported the ERACI III results and those of the patients with late stent thrombosis who had multistent placement and concomitant DES and BMS in different vessels. All of the stent thromboses occurred at the DES sites, strongly implicating stent-inherent specific etiologies in late stent thrombosis.⁶ The case presented here is in agreement with the aforementioned data, as both BMS in the RCA and in the LAD were not associated with stent thrombosis. Since focal restenosis is the most frequent angiographic finding of in-stent restenosis after SES implantation,¹⁰ we cannot discount the possibility that late stent thrombosis could be under-reported with DES therapy, and that numerous cases of focal ISR might be similar to the one reported here. In order to determine whether this finding is sporadic or a common, but under-reported event, we advocate that all focal ISR of DES should be routinely explored using more detailed diagnostic tools such as IVUS and/or angioscopy.

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