From the Peter Munk Cardiac Centre, Toronto General Hospital, University Health Network, Toronto, Canada. The authors report no conflicts of interest regarding the content herein. Dr. Džavík was supported in part by the Brompton Funds Professorship in Interventional Cardiology. Manuscript submitted September 12, 2008 and accepted December 2, 2008. Address for correspondence: Vladimír Džavík, MD, FRCPC, FAHA, FSCAI, Interventional Cardiology Program, 6 Eaton North, Room 246, 200 Elizabeth Street, Toronto General Hospital, Toronto, Ontario, Canada M5G 2C4. E-mail: firstname.lastname@example.org
ABSTRACT: De novo atherosclerosis arising within a coronary stent is rare and generally occurs many years after stent deployment. We describe a case of restenosis in a patient presenting with angina 8 years after original stent deployment. Intravascular ultrasound greyscale imaging and virtual histology demonstrated that this “neointima” was calcified.
J INVASIVE CARDIOL 2009;21:141–143
It is generally understood that following deployment of a coronary stent, reendothelialization occurs with variable deposition of a hypocellular fibrous tissue, the neointima, within the lumen. This can result in an early restenosis phase after which the vessel stabilizes and no recurrent stenosis then arises. We describe the case of a de novo calcified atherosclerotic lesion developing some years after deployment of a bare-metal stent (BMS). The nature of this “in-stent restenosis” (ISR) was further elucidated using intravascular ultrasound (IVUS) virtual histology (VH). Case Presentation. A 71-year-old male ex-smoker with a history of hyperlipidemia and coronary artery disease was referred to our center for intervention. He had first presented to a cardiologist in March 2000 with stable anginal symptoms and went on to undergo percutaneous coronary intervention (PCI) of his mid-left anterior descending artery (LAD) with a single BMS. Subsequent angiography prompted by a return of his angina in October 2000 revealed ISR, which was treated by balloon angioplasty only, and de novo disease in a large marginal branch, which was treated by deployment of another single BMS. One year later, he returned with progressive anginal symptoms, and diffuse ISR of the marginal-branch BMS was demonstrated. He underwent vascular brachytherapy to this lesion and the original LAD stent remained patent at this time. A repeat angiogram in 2002 failed to demonstrate any significant disease progression and he remained well. The patient re-presented in 2005 with stable symptoms and was medically managed until January 2008, when an increase in his symptoms prompted referral for further investigation. Angiography revealed what appeared to be focal ISR, approximately 50% in severity, within the LAD stent and a patent obtuse marginal stent (Figure 1). Focal calcification of the LAD was noted. A decision was made to further define the apparently moderate ISR lesion with IVUS. The procedure was undertaken via a 6 Fr right radial sheath. IVUS imaging using an Eagle Eye® Gold catheter (Volcano Therapeutics Inc., San Diego, California) of the LAD was performed and demonstrated significant diffuse disease occurring throughout the stent length with both proximal and distal edge stenoses (Figure 2). The minimal lumen diameter was 2.0 mm (reference vessel diameter, or original stent lumen diameter, 4.0 mm) with a minimal lumen area of 3.1 mm2 (reference vessel area, stent area 11.6 mm2, 73% stenosis). Of most interest was the appearance of significant calcification within the stent lumen, that is, a calcified neointima. This impression was confirmed by IVUS-VH imaging (Figure 2), which demonstrated a fibrous plaque with diffuse white specks of calcification and areas of more dense calcium deposits, typical of de novo atherosclerosis. Discussion. This case raises several interesting issues. The obtuse marginal stent, previously treated with vascular brachytherapy, remained widely patent. The (untreated) BMS in the LAD had the angiographic appearance of focal restenosis, a pattern more commonly associated with drug-eluting stents1 and, as is frequently the case, IVUS greyscale imaging emphasized the discrepancy between angiographic estimation of disease and true plaque burden.2 Most interestingly, however, the restenotic plaque was found to be composed of a diffusely calcified tissue, with obvious echo-dense fibrous plaque, rather than the homogenous echogenic tissue typical of neointima. De novo atherosclerosis within a stent is rare, but has been reported previously, and in those cases described, it occurs many years after stent deployment, as was found in this patient.3 The new atherosclerotic lesion occurs within a previously “healed” lumen, making foreign body reaction to the stent struts less likely, although a chronic inflammatory reaction cannot be excluded without histological examination. IVUS-VH offers an in vivo opportunity to assess plaque morphology. While in vitro, this technology has been shown to have 93–99% accuracy when used to identify the four different types of atherosclerotic plaques (e.g., fibrous, fibro-fatty, dense calcium and necrotic core), the in vivo correlation of IVUS-VH data analysis with histopathology also shows a high accuracy (predictive accuracy 92.9% for fibrous, 93.4% for fibro-fatty, 94.4% for necrotic core and 99.3% for dense calcium regions, respectively).4 It has not, however, been validated for use with in-stent tissue. Contrast angiography is a relatively insensitive tool for the detection of calcification, whereas IVUS imaging has greater sensitivity, and calcified plaques can be characterized as superficial or deep.5 In this instance, the within-lumen calcification was superficial. Calcification of the neointima which composes a restenotic lesion — the stent-within-a-stent — has not, to our knowledge, been reported before. Its treatment in this case remained the same. We proceeded to PCI, which involved balloon predilatation with deployment of a single Taxus® 2.75 x 32 mm stent (Boston Scientific Corp., Natick, Massachusetts) at 20 atm. Multiple balloon inflations with Quantum™ 3.25 x 8 mm and 3.5 x 8 mm balloons (Boston Scientific) at high pressures post stent deployment were required in order to optimally deploy the stent (Figure 1c). Post-procedure IVUS revealed a well-apposed stent.
1. Colombo A, Orlic D, Stankovic G, et al. Preliminary observations regarding angiographic pattern of restenosis after rapamycin-eluting stent implantation. Circulation 2003;107:2178–2180. 2. Nicholls SJ, Andrews J, Moon K-W. Exploring the natural history of atherosclerosis with intravascular ultrasound. Expert Rev Cardiovasc Ther 2007;5:295–306. 3. Hasegawa K, Tamai H, Kyo E, et al. Histopathological findings of new in-stent lesions developed beyond five years. Catheter Cardiovasc Interv 2006;68:554–558. 4. Sangiorgi G, Clementi F, Cola C, Biondi-Zoccai G. Plaque vulnerability and related coronary event prediction by intravascular ultrasound with virtual histology: It’s a long way to tipperary? Catheter Cardiovasc Interv 2007;70:203–210. 5. Uren N, Yock P, Fitzgerald P. Intravascular ultrasound image interpretation: Normal arteries, abnormal vessels, and atheroma types pre- and post-intervention. In: Siegel R (ed.). Intravascular Ultrasound Imaging in Coronary Artery Disease. New York: Marcel Dekker. 1998, pp. 19–37.