“Black Hole” Restenosis after Sirolimus-Eluting Stent Implantation

Author Affiliations: From the Department of Cardiology, The Cardiovascular Institute, Tokyo, Japan. The authors report no conflicts of interest regarding the content herein. Manuscript submitted November 8, 2007, provisional acceptance given April 23, 2008, and accepted April 28, 2008. Address for correspondence: Yoshitaka Shiratori, MD, Department of Cardiology, The Cardiovascular Institute, 7-3-10 Roppongi, Minato-ku, Tokyo, Japan. E-mail: cib16710@syd.odn.ne.jp

_______________________________________________ ABSTRACT: In several reports, the “black hole” (BH) phenomenon was reported as a homogeneous echolucent appearance by intravascular ultrasound. We discuss an experience with angioscopic and pathological assessment for the BH phenomenon.

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J INVASIVE CARDIOL 2008;20:E253–E255 An echolucent tissue named “black hole” (BH) has been reported after intracoronary brachytherapy with intravascular ultrasound (IVUS). Recently, BH was reported after sirolimus-eluting stent (SES) implantation. However, the characteristics of BH have not been fully elucidated. We report a case of BH after SES implantation examined by coronary angioscopy and microscopy. Case Report. On October 29, 2004, a 69-year-old male who had a bare-metal stent (BMS) implanted in the right coronary artery (RCA) 5 years previously underwent emergent percutaneous coronary intervention (PCI) for anterior myocardial infarction (MI). On angiography, in-stent stenosis was observed?at the RCA. On December 7, 2004 (39 days after his MI), 2 Cypher™ SES (3.0 x 13 mm and 3.0 x 13 mm) were implanted sequentially into the in-stent stenotic site. Dual antiplatelet therapy (100 mg/day of aspirin and 200 mg/day of ticlopidine) was started from the day of the MI and was continued. At the beginning of August 2005, he developed shortness of breath on exertion and was admitted to the hospital for heart failure without elevation of cardiac enzymes or electrocardiographic changes. No clinical signs associated with acute coronary syndrome was observed. After improvement of his heart failure, re-angiography was performed for suspicion of silent ischemia on September 1, 2005 (9 months after SES implantation). Recurrent focal restenosis was observed at the site of overlap of the 2 stents. IVUS imaging showed an echolucent (dark) zone in the restenotic segment, which appeared to be identical to the “black hole” phenomenon (Figure 1). A thin translucent tissue was observed at the restenotic segment by coronary angioscopy (Figure 2). Directional coronary atherectomy was performed, and a tissue sample (2 mg) was obtained. Microscopic analysis revealed two layers of the tissue: one containing an abundance of fibrin, and the other only a small number of smooth muscle cells and unremarkable inflammatory cells. An immunohistochemical study showed that there was no massive deposition of proteoglycans such as versican and decorin (Figure 3). These observations suggested that the tissue containing an abundance of fibrin was a thrombus. Discussion. A group from the Netherlands first identified the BH phenomenon in 1999. Characteristically, BH had a homogeneous black appearance without attenuation and was distinguished from typical neointimal hyperplasia. Histological examination of atherectomy specimens of BH tissue after brachytherapy revealed a hypocellular matrix with proteoglycans such as biglycan.1–3 Recently, BH has also been reported in the setting of drug-eluting stents (DES). In 2006, Costa et al reported that the BH phenomenon was often observed in SES restenosis after treatment of saphenous vein graft lesions (50% versus 0%; p = 0.0017) or treatment of BMS restenosis (75% versus 32%; p = 0.035).4 Costa et al reported that BH was observed in 10 patients (19.6%) in the SECURE (Compassionate Use of Sirolimus-Eluting Stent) trial and in 2 patients (2.5%) in the DIABETES (DIABETes and sirolimus Eluting Stent) trial. In that report, the BH appearance of neointimal hyperplasia tissue was speculated to be a consequence of death and/or mutation of neointimal cells in the early stage of endothelial healing following balloon angioplasty or stent deployment.5 However, there have been no reports published about a histological analysis of echolucent tissue BH after DES implantation. We report observations on IVUS images of BH appearance with additional angioscopic and pathological observations. Angioscopic and pathological studies suggested that, in our case report, the BH appearance was characteristic of a thrombus. Previous reports have shown that BH appearance in IVUS images indicated abundant proteoglycan accumulation with smooth muscle cells.1–3 Other reports have suggested that other contents, such as thrombus or necrotic tissue, could show an echolucent appearance in IVUS images.6,7 This phenomenon may be explained by a variety of tissue contents such as proteoglycan, thrombus or necrotic core. BH containing abundant fibrin was observed at the site of overlap of 2 SES in the present case. It was reported that hemodynamic effects and areas of blood stagnation might lead to drug pooling, allowing uneven drug distribution in the arterial wall.8 Balakrishman et al reported computational models that raised awareness that elution of drug is not simply a property of drug diffusion and washout, but that flow, interstrut distance, number of struts, and overlapping struts all determine the amount of drug deposition and distribution beyond levels achieved exclusively by arterial wall contact.9 We speculate that this phenomenon at the site of overlapping stents is implicated in uneven drug deposition and distribution, and suggest that an association with delayed arterial healing manifested by persistent fibrin deposition and poor endothelialization may offer a pathophysiological explanation for the phenomenon of late thrombosis in the DES setting. Further observations, especially in pathophysiological studies, may reveal this distinctive appearance.

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