Very Late Drug-Eluting Stent Thrombosis Related to Incomplete Stent Endothelialization: (Full title below)

Very Late Drug-Eluting Stent Thrombosis Related to Incomplete Stent Endothelialization: In-Vivo Demonstration by Optical Coherence Tomography

________________________ ABSTRACT: Very late drug-eluting stent (DES) thrombosis is a rare but potentially life-threatening event that has become a major cause of concern. Delayed arterial healing with incomplete endothelialization is probably a pivotal factor related with DES thrombosis. Optical coherence tomography (OCT) is a new high-resolution intracoronary imaging technique that allows detailed evaluation of stent neointimal coverage. We present a case of very late DES thrombosis that was evaluated with OCT, demonstrating incomplete endothelialization as the probable main mechanism of stent thrombosis. This case illustrates the ability of OCT for in-vivo identification of stent coverage and its potential role in the evaluation of stent thrombosis mechanisms. J INVASIVE CARDIOL 2009;21:488–490 Key words: stent; thrombosis; optical coherence tomography Case Description A 75-year-old male with a history of arterial hypertension, dyslipidemia and Type II diabetes mellitus suffered a non-Q-wave inferior acute myocardial infarction (AMI). The right coronary artery (RCA) showed multi-segment disease with a long lesion at the proximal-mid segment (Figure 1A) and severe stenosis at the posterior descending artery (PDAA) and posterolateral branch (Figure 1B). His left ventricular ejection fraction was 55%. Percutaneous coronary intervention (PCI) of the RCA was performed. The lesion at the proximal-mid segment was predilated with a 2.5 x 20 mm balloon and a 3 x 28 mm Taxus Liberté stent (Boston Scientific Corp., Natick, Massachusetts) was implanted with a good angiographic result. Additionally, 2 other Taxus stents were implanted at the PDA (2.5 x 16 mm) and posterolateral branch (2.75 x 20 mm) also with a good angiographic result (Figure 1C). The patient was discharged without in-hospital events and remained asymptomatic on atenolol, enalapril, atorvastatin and dual antiplatelet therapy. One year later, clopidogrel was withdrawn, maintaining aspirin treatment. Thirty-five months after the first AMI he complained of sudden acute chest pain, and an inferoposterior AMI with right ventricle involvement was diagnosed. Urgent coronary angiography revealed complete thrombotic in-stent occlusion of the proximal RCA (Figure 2A). An intravenous (IV) bolus of abciximab was administered and primary PCI was performed using aspiration thrombectomy with a 6 Fr Export XT catheter (Medtronic, Inc., Minneapolis, Minnesota), recovering thrombolysis in myocardial infarction (TIMI)-3 distal flow. Then, a severe narrowing with intraluminal appearance of thrombus was identified at the distal border of the stent (Figure 2B). Both stents in the distal branches were patent. In order to ascertain the mechanism of stent thrombosis, an optical coherence tomographic (OCT) probe (Imagewire, Lightlab Imaging, Westford, Massachusetts) was advanced to the distal RCA and images were obtained using a non-occlusive technique, with 2 mm/sec of motorized pullback during automated injection of dye (iodixanol) through the guiding catheter. OCT revealed abundant in-stent remnant thrombus (Figure 3C) and adequate stent expansion and apposition, without strut fracture. Just distally to the stent border, a lipid-rich plaque without signs of rupture was evident (Figure 3A). Interestingly, some stent struts in the 12 mm segment near the distal border of the stent were uncovered by neointimal tissue (maximum 6 uncovered struts per section with a ratio of uncovered-to-total struts per section of 55%) (Figures 3B–4A). Of note, in the distal segment of the stent, small fragments of thrombus were clearly attached to the uncovered struts (Figure 4B). Of contrast, struts at the proximal part of the stent were covered by a thin, homogeneous and signal-rich layer, likely corresponding with neointimal coverage (Figure 3D). Finally, a 3 x 15 mm bare-metal stent (Driver, Medtronic, Inc.) was directly implanted at the mid-RCA, overlapped with the previous stent, with a good angiographic result (Figure 2C) confirmed by OCT examination. Discussion Late stent thrombosis after drug-eluting stent (DES) implantation is a rare but often dire event that has become a major cause of concern.1 Although the cause of late DES thrombosis is likely multifactorial,2 delayed arterial healing has been described as a pivotal related factor. Autopsy studies have shown incomplete endothelialization and persistent fibrin deposition in DES compared with bare-metal stents (BMS).3 OCT is a new intravascular imaging technique based on the analysis of backscattered near-infrared light that provides ultra-high image resolution (10–20 microns).4 This technique has demonstrated its ability for the evaluation of coronary vulnerable plaques, guidance during percutaneous coronary intervention procedures and evaluation of neointimal stent coverage.5 OCT has demonstrated impaired coverage of DES compared with BMS.6 DES coverage is often constituted by a thin layer of neointimal tissue,7 which is frequently under the resolution range of intravascular ultrasound (IVUS). IVUS is very useful to investigate potential causes of stent thrombosis, like stent underexpansion, malapposition or strut fracture. However, the image resolution capacity of IVUS (approximately 120 microns) is not enough to allow the accurate evaluation of stent neointimal coverage. Our findings suggest that OCT may be useful for accurate identification the mechanisms of late DES thrombosis. This case illustrates the ability of OCT for in-vivo detection of impaired endothelialization of DES and its potential role in the evaluation of very late stent thrombosis mechanisms. We think that OCT can identify underexpansion and strut fracture and, given its high resolution, may be better than IVUS to identify minor grades of stent malapposition and the thin neointimal coverage of DES. In our case, the finding of thrombus surrounding the uncovered struts after thrombectomy suggests that incomplete endothelialization, with exposure of the thrombogenic stent surface, may be related to the development of thrombosis and supports the hypothesis of a link between delayed arterial healing and late stent thrombosis. ______________________ From the Interventional Cardiology Unit, Cardiology Department. La Paz University Hospital, Madrid, Spain. The authors report no financial relationships or conflicts of interest regarding the content therein. Manuscript submitted April 15, 2009, provisional acceptance given May 4, 2009, final version accepted May 18, 2009. Address for correspondence: Santiago Jiménez-Valero, MD, Departamento de Hemodinámica y Cardiología Intervencionista, Hospital Universitario La Paz, Avda. Castellana 261, 28046, Madrid, Spain. E-mail: sjvcardio@yahoo.es

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