Implantation of 1st generation drug-eluting stents (DESs) has significantly reduced the incidence of restenosis and the need for repeat revascularization, compared to previously used bare-metal stents.1)2) However, increased use of DESs has raised safety issues regarding the occurrence of stent thrombosis.3)4) In the 1st generation DES, persistence of polymer even after complete elution of drugs may cause either hypersensitivity reaction or inflammation in the stented coronary segments, and both these conditions are associated with increased risk for stent thrombosis.5) To overcome this life-threatening complication, many newly designed DESs have been developed. Compared to previous DESs, the biolimus A9-eluting stent (BES, Nobori®, Terumo Corporation, Tokyo, Japan) has the characteristics of abluminally applied drug polymer matrix and biodegradable polymer (i.e., polymer degradation over the period of 6 to 9 months).6) We experienced a rare case of late stent thrombosis in patients who underwent implantation of a BES and follow-up optical coherence tomography (OCT) for investigation of late stent thrombosis.

An 80-year old woman suffered from sudden onset of chest pain and dyspnea, and visited the emergency room. She had a history of hypertension, hyperthyroidism and major depressive disorder. Five months prior to admission, she visited the cardiology outpatient clinic for the further evaluation of syncope. The coronary computer tomography and coronary angiography revealed significant stenosis at the mid-portion of the left anterior descending artery (mLAD; B2, 80%, III, 0) (Fig. 2A) and a BES (Nobori® 3.0×24 mm) was successfully deployed, without residual narrowing (Fig. 2B) at that time. Pulmonary congestion in both lung fields, suggestive of pulmonary edema, was noticed on the chest X-ray; newly developed Q wave was visible at leads V1-4 on the electrocardiogram (Fig. 1); recent regional wall motion abnormality (i.e., akinesia without thinning) was detected in the left anterior descending artery territory, and the left ventricular ejection fraction was reduced by 30% on the echocardiogram at this time. Cardiac enzyme was slightly elevated (Troponin-T 0.124 ng/mL). Emergency follow-up angiogram was performed under the impression of non-ST elevation myocardial infarction, caused by late stent thrombosis. The follow-up angiogram showed subtotal occlusion at the mid-portion of the left anterior descending artery, the same segment of previous stent implantation 5 months ago (B2, 99%, II, 0) (Fig. 2C). Immediately after thrombus aspiration with the thrombus aspiration catheter (Thrombuster II®, Kaneka Corp. Japan), OCT was performed for investigation of both morphologic features and underlying cause of late stent thrombosis. The OCT showed layered appearance of neointmal hyperplasia and neointimal rupture within the previously stented segment (Fig. 3A and B). Considering that the stent thrombosis was not due to delay of stent strut endothelialization, balloon angioplasty with a drug eluting balloon (SeQuent please®, B. Braun Melsungen AG, Germany) was successfully performed at the mid-portion of the left anterior descending artery with no residual stenosis, however jailed diagonal branch (Figs. 2D and 3C). After the surgical procedure, she was discharged 3 days later, without any significant complications.

Occurrence of stent thrombosis has been the major concern after implantation of 1st generation DESs. Iakovou et al.3) reported 1.3% incidence of stent thrombosis in patients who received DES implantation. In addition, 45% of the patients who experienced stent thrombosis died. Daemen et al.4) also reported that stent thrombosis occurring within 30 days after DES implantation increases 0.6% annually. While occurrence of acute or subacute stent thrombosis (i.e., onset of stent thrombosis within 30 days after stent implantation) is mainly related to procedural factors, development of late or very late stent thrombosis has different characteristics. Previous pathologic studies showed that delayed stent strut endothelialization and potential prothrombotic properties of the DES itself (i.e., persistence of polymer even after complete elution of drugs) are important factors that may lead to late stent thrombosis.7)8) A recent intravascular ultrasound study by Lee et al.9) showed that neointimal rupture within the stent area was observed in 43.5% of 23 patients with very late stent thrombosis, after 1st generation DES implantation. A pathologic study reported that DES therapy may accelerate atherosclerosis, while reducing restenosis.10) Therefore, new DESs with a biodegradable polymer have been developed to avoid complications caused by persistence of polymer. Several studies compared the outcomes (i.e., cardaic death, myocardial infarction, and stent thrombosis) of BESs with those of 1st generation DESs and concluded that BESs were not inferior to 1st generation DESs and that both suitable alternatives and long term outcomes were neeed.11)

Despite of these favorable conditions of a BESs compared to 1st generation DESs, accelerated neointimal proliferation, abnormal neointimal morphology (i.e., layered appearance of the neointima) and additional neointimal rupture were observed in this patient with late stent thrombosis within a relatively shorter period of time (i.e., about 5 months) after implantation of a BES. Due to high resolution images of the OCT, the cause of stent thrombosis was more precisely diagnosed than in previous cases using IVUS or other modalities.