+ MODEL Hellenic Journal of Cardiology (2016) xx, 1e3 Available online at www.sciencedirect.com ScienceDirect journal homepage: http://www.journals.elsevier.com/ hellenic-journal-of-cardiology/ CASE REPORT Management of a severely calcified neoatherosclerosis plaque analyzed by intravascular ultrasound ´mez-Mariscal, MD*, Julio Garcı´a-Tejada, MD, Eloy Go ´rrez, MD Elena Puerto Garcı´a-Martı´n, MD, Ana Miguel-Gutie Cardiology Department, University Hospital Doce de Octubre, Madrid, Spain Received 15 September 2016; received in revised form October 2016; accepted 24 October 2016 KEYWORDS Neoatherosclerosis; Late stent failure; Bare metal stent; Intravascular ultrasound Introduction One of the most concerning problems of the coronary-stent era is the development of in-stent restenosis (ISR).1 ISR has been described as a three-phase process with early proliferation of intimal cells within the first to 12 months followed by a regression period from months to years.2 However, in a number of patients, long-term follow-up Abbreviations: ISR, In-stent restenosis; BMS, Bare metal stent; IVUS, Intravascular ultrasound; DES, Drug-eluted stent; OCT, Optical coherence tomography * Corresponding author Eloy Gomez Mariscal, Servicio de Cardiologı´a, Hospital Universitario Doce de Octubre, Avda de Co ´rdoba s/n, 28041, Madrid, Spain E-mail address: eloy.gomez@salud.madrid.org (E Go ´mez-Mariscal) Peer review under responsibility of Hellenic Cardiological Society has exhibited a re-narrowing and development of de novo neoatherosclerosis.3 This phenomenon is important because it is closely related to many cases of late stent failure, such as late ISR or plaque rupture and late stent thrombosis In many cases, a new percutaneous coronary intervention can successfully solve the problem, although recurrences are common.3,4 We report a case of severely calcified neoatherosclerosis in a bare metal stent implanted 10 years prior Case Report A 58-year-old male previous smoker with dyslipidemia had received a 2.75Â20 mm bare metal stent (BMS) in the proximal segment of the circumflex artery 10 years prior due to stable angor The left anterior descending and the right coronary arteries had no significant lesions The patient was being treated with acetylsalicylic acid, http://dx.doi.org/10.1016/j.hjc.2016.10.004 1109-9666/ª 2016 Hellenic Cardiological Society Publishing services by Elsevier B.V This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) Please cite this article in press as: Go ´mez-Mariscal E, et al., Management of a severely calcified neoatherosclerosis plaque analyzed by intravascular ultrasound, Hellenic Journal of Cardiology (2016), http://dx.doi.org/10.1016/j.hjc.2016.10.004 + MODEL atorvastatin and a beta blocker with a suitable control of the cardiovascular risk factors He arrived at our hospital after being asymptomatic for 10 years, after which he again developed stable angor symptoms An ergometric examination was positive for stable angor A new coronary angiography was completed and showed no changes in the left anterior descending or the right coronary arteries, but in the circumflex artery, severe diffuse in-stent restenosis was observed (Fig 1A) We evaluated the restenosis by intravascular ultrasound (IVUS), which demonstrated high neointimal proliferation with severe calcium deposition and an acoustic shadow that did not allow visualization of the stent struts (Fig 1B, C) However, we did observe adequate expansion and apposition of the struts, and the stent did not seem to be damaged or fractured Furthermore, the in-stent proliferation was greatest at the most distal portion of the stent, where it covered nearly the entire surface of the stent Due to the severe calcification, we decided to dilate the neoatherosclerotic lesion at a high pressure (26 Atm) using a 2.5 mm non-compliant balloon Once we achieved a satisfactory angiographic result, we implanted a 2.75Â28 mm drug eluted stent (DES) at 18 Atm Although the risk of neoatherosclerosis is higher with a DES, it is preferred due to the lower risk of ISR Subsequently, we confirmed the expansion of the stent by IVUS and observed good expansion despite the calcification (Fig 2) Six months later, the patient remained asymptomatic, and a new ergometric examination was negative for stable angor Discussion Understanding the mechanisms of neoatherosclerosis is important because of the association between neoatherosclerosis and some cases of late stent failure.1 Histopathological studies and intracoronary imaging techniques have shown that the neoatherosclerotic intima is heterogeneous and differs from early restenosis neointima The neoatherosclerotic intima is primarily composed of cholesterol crystals, foaming macrophages and smooth muscle cells with a thin-cap fibroatheroma.5,6 However, it is actually rare to find a severe calcification E Go ´mez-Mariscal et al as was observed in our patient, and only a few cases with this singular condition have been reported.7 Scanning electron microscopy has revealed disordered cells in the instent regions instead of the correctly positioned cells in the healthy endothelium This phenomenon and the local peristrut inflammation justify the higher permeability as well as macrophage and smooth cells infiltration, which leads to more lipid uptake and the occurrence of neoatherosclerosis plaques.8 Neoatherosclerosis also leads to greater development of intraintimal microvessels and hemorrhage compared with cases of early restenosis.5,6 Nevertheless, it is important to note that there is no relationship between the native atherosclerotic plaque treated with the stent and the lesion that develops within the stent.3 The development of intracoronary imaging techniques as IVUS or optical coherence tomography (OCT) has allowed us to learn more about ISR OCT has shown areas with an incomplete endothelial lining and neointimal hyperplasia that explains the absence of the endothelial protection.7 This suggests that ISR is a continuous spectrum, including smooth muscle cell proliferation to neoatherosclerosis.6 Furthermore, imaging techniques are important in guiding treatment during the angiography.9 In our case, due to the IVUS, we could determine the severity of the calcified restenosis and used imaging tools to guide adequate dilation of the neoatherosclerotic lesion before implanting of the stent Furthermore, we were also able to later confirm the correct apposition of the struts on this complex plaque Some studies have tried to determine differences in the neoatherosclerosis observed between DES and BMS The incidence of neoatherosclerosis is higher in lesions treated with the first generations of DES than in those treated with BMS, and this phenomenon occurs earlier in those with DES.8 In addition to the stent type and the stent age, it has also been noted that current smoking, chronic kidney disease, absence of angiotensin-converting enzyme inhibitors/ angiotensin II receptor blockade, hypertension and prestent LDL-cholesterol levels were independently associated with the development of neoatherosclerosis.10 The most important complication of the neoatherosclerosis is the late stent thrombosis The absence of endothelialization covering the struts is the primary cause of thrombosis, primarily of DES, but the rupture of Figure Coronary angiography and IVUS images (A) A severe lesion in the proximal circumphlex artery The white lines indicate the area shown by the intravascular ultrasound images (B) and (C), where we can appreciate the severely calcification of the neoatherosclerotic lesion (white arrows) Please cite this article in press as: Go ´mez-Mariscal E, et al., Management of a severely calcified neoatherosclerosis plaque analyzed by intravascular ultrasound, Hellenic Journal of Cardiology (2016), http://dx.doi.org/10.1016/j.hjc.2016.10.004 + MODEL Severely calcified neoatherosclerosis analyzed by intravascular ultrasound Figure Coronary angiography and IVUS images (A) Final circumphlex artery after the revascularization The white lines indicate the area shown by the intravascular ultrasound images (B) and (C) neoatherosclerotic lesions, although is rare, is emerging as another cause of this severe complication.8 Conclusions Neoatherosclerosis is an important cause of late stent failure, exhibiting a different histopathological presentation from early restenosis Although neoatherosclerosis has been mainly studied in BMS, it has recently been described in both BMS and DES, and its importance is growing in the latter, as it is more frequent and occurs earlier Acknowledgments The authors have no conflicts of interest References Tsigkas GG, Karantalis V, Hahalis G, Alexopoulos D Stent restenosis, pathophysiology and treatment options: a 2010 update Hellenic J Cardiol 2011 MareApr;52(2):149e157 Kozuki A, Shinke T, Otake H, et al Temporal course of vessel healing and 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Kang SJ, Virmani R, Nakano M, Ueda Y In-stent neoatherosclerosis: a final common pathway of late stent failure J Am Coll Cardiol 2012;59(23):2051e2057 Karanasos A, Muramatsu T, Diletti R, et al Early and late optical coherence tomography findings following everolimuseluting bioresorbable vascular scaffold implantation in myocardial infarction: a preliminary report Hellenic J Cardiol 2015 Mar-Apr;56(2):125e135 10 Yonetsu T, Kato K, Kim SJ, et al Predictors for neoatherosclerosis: a retrospective observational study from the optical coherence tomography registry Circ Cardiovasc Imaging 2012;5(5):660e666 Please cite this article in press as: Go ´mez-Mariscal E, et al., Management of a severely calcified neoatherosclerosis plaque analyzed by intravascular ultrasound, Hellenic Journal of Cardiology (2016), http://dx.doi.org/10.1016/j.hjc.2016.10.004 ... Please cite this article in press as: Go ´mez-Mariscal E, et al., Management of a severely calcified neoatherosclerosis plaque analyzed by intravascular ultrasound, Hellenic Journal of Cardiology (2016),... calcification of the neoatherosclerotic lesion (white arrows) Please cite this article in press as: Go ´mez-Mariscal E, et al., Management of a severely calcified neoatherosclerosis plaque analyzed by. .. Coronary angiography and IVUS images (A) Final circumphlex artery after the revascularization The white lines indicate the area shown by the intravascular ultrasound images (B) and (C) neoatherosclerotic