JACC: CARDIOVASCULAR INTERVENTIONS

VOL. 7, NO. 4, 2014

ª 2014 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION PUBLISHED BY ELSEVIER INC.

ISSN 1936-8798/$36.00 http://dx.doi.org/10.1016/j.jcin.2013.07.018

In-Stent Thin-Cap Fibroatheroma After Drug-Eluting Stent Implantation Ex-Vivo Evaluation of Optical Coherence Tomography and Intracoronary Angioscopy Kenichi Fujii, MD,* Hiroyuki Hao, MD,y Takahiro Imanaka, MD,* Taro Kawano, MD,z Tadateru Takayama, MD,z Atsushi Hirayama, MD,z Tsutomu Yamada, PHD,x Hatsue Ishibashi-Ueda, MD,k Seiichi Hirota, MD,y Tohru Masuyama, MD* Nishinomiya, Tokyo, and Suita, Japan

A 57-year-old man died of sepsis, and an autopsy was performed. Previously, he had undergone percutaneous coronary intervention of the middle left anterior descending coronary artery, with 2 sirolimuseluting stents implanted 61 months before death.

Post-mortem ex-vivo optical coherence tomography (OCT) (LightLab imaging, Westford, Massachusetts), coronary angioscopy (CAS) (FiberTech, Tokyo, Japan) imaging, and pathological examination were performed in the stented segments. OCT

Figure 1. Histopathology and Intravascular Images of In-Stent TCFA (A) A cross-sectional image of optical coherence tomography clearly showed an eccentric intimal growth with the appearance of rapid attenuation of the signals (asterisks) with a diffuse border. The signal-poor area was located inside the stent struts (arrows). In this cross section, the stent struts behind the signal-poor mass (6 to 9 o’clock) were completely invisible because of attenuation of the signal, and the thickness of the fibrous cap overlying the signal-poor area was 60 mm by optical coherence tomography image. (B) Coronary angioscopy revealed intensive yellow plaque, and there were no visible stent struts. (C) Corresponding histology from the same section of the lesion in A showed a thin fibrous cap overlying a large, lipid-rich, eccentric necrotic core, indicating a TCFA-like appearance within the stent. (Hematoxylin and eosin stain, scale bar ¼ 1 mm, allows the identification of stent struts.) Minimal thickness of the fibrous cap by histology was 52 mm. (D) Higher magnification of the neointima within the stent struts demonstrated necrotic debris with cholesterol clefts. The thin fibrous cap was infiltrated by lipid-laden macrophages. (Hematoxylin and eosin stain, scale bar ¼ 500 mm, allows the identification of the stent struts.) TCFA ¼ thin-cap fibroatheroma.

From the *Cardiovascular Division, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan; yDepartment of Surgical Pathology, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan; zDivision of Cardiology, Department of Medicine, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan; xDepartment of Pathology, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan;

and the kDepartment of Pathology, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan. The authors have reported that they have no relationships relevant to the contents of this paper to disclose. Manuscript received June 29, 2013; accepted July 3, 2013.

Fujii et al. Ex Vivo Evaluation of In-Stent Fibroatheroma

JACC: CARDIOVASCULAR INTERVENTIONS, VOL. 7, NO. 4, 2014 APRIL 2014:446–7

images showed in-stent eccentric intimal growth of moderate intimal hyperplasia with rapid attenuation of the signals with diffuse border, such as a thin-cap fibroatheroma (TCFA) in native coronary arteries (Fig. 1A). Corresponding CAS images revealed that stent struts were covered by intensive yellow neointima (Fig. 1B). Corresponding histopathologic images demonstrated a large, lipid-rich necrotic core covered with a thin fibrous cap infiltrated by lipid-laden macrophages with few smooth muscle cells (Figs. 1C and 1D). Discussion Based on recent pathological study, rupture of a TCFA-like lesion within the neointima has been reported in the long term after stent implantation and has been proposed to be responsible for very late stent thrombosis (1). To the best of our knowledge, this is the first case of ex-vivo interrogation of in-stent TCFA containing neointima after drug-eluting stent implantation with OCT and CAS by autopsy specimen. On OCT images, the lipid-rich necrotic core appears as a low-signal-intensity mass because of the strong optical absorption and scattering of lipids at light wavelengths around 1,000 nm (2). Therefore, stent struts cannot be visualized by OCT if there is a lipid-rich necrotic core within the neointima. On the other hand, stent struts behind organized fibrin thrombus can be visualized because OCT signals are not attenuated by this material (3).

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Therefore, it is important to identify the in-stent TCFAlike neointima whether stent struts behind a low-signal-intensity area are “visible” or “invisible.” Acknowledgments

The authors thank Mrs. Mayumi Oka and Mr. Gen Satoh for their technical assistance. Reprint requests and correspondence: Dr. Hiroyuki Hao, Department of Surgical Pathology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan. E-mail: [email protected]

REFERENCES

1. Nakazawa G, Otsuka F, Nakano M, et al. The pathology of neoatherosclerosis in human coronary implants: bare-metal and drug-eluting stents. J Am Coll Cardiol 2011;57:1314–22. 2. Allen TJ, Hall A, Dhillon AP, Owen JS, Beard PC. Spectroscopic photoacoustic imaging of lipid-rich plaques in the human aorta in the 740 to 1400 nm wavelength range. J Biomed Opt 2012;17: 061209. 3. Nakano M, Vorpahl M, Otsuka F, et al. Ex vivo assessment of vascular response to coronary stents by optical frequency domain imaging. J Am Coll Cardiol Img 2012;5:71–82.

Key Words: coronary angioscopy - drug-eluting stent optical coherence tomography - pathology - restenosis.

In-stent thin-cap fibroatheroma after drug-eluting stent implantation: ex-vivo evaluation of optical coherence tomography and intracoronary angioscopy.

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