A 68-year-old female underwent bare-metal stent (BMS) implantation in the right coronary artery (RCA) for ST-segment elevation myocardial infarction. Recurrent refractory restenosis with peri-stent contrast staining (PSS) formation was observed in the stented lesion at follow-up angiography at 7, 11, and 14 months after the index stent implantation. After 2 repeated interventions, this patient was referred to coronary artery bypass grafting due to occlusion of RCA and progression of proximal left anterior descending coronary artery lesion at 15 months after stent implantation. Pathologic examination of the surgically resected specimen of stented RCA segment revealed total occlusion with dense fibrous collagenous tissue and significant inflammatory cell infiltration including scattered eosinophils. Extensive loss of medial smooth muscle layer was observed in the vessel wall, which was likely to be the cause of PSS. In the course of treatment, this patient was found to have chromium allergy with positive patch test. Allergic reactions to chromium released from the stent might be one of the triggering mechanisms for in-stent restenosis and PSS after BMS implantation.
<Learning objective: Peri-stent contrast staining (PSS) was an abnormal angiographic finding suggesting presence of contrast material outside the stent border after sirolimus-eluting stent implantation. However, PSS is rarely seen with bare-metal stents (BMSs), and PSS and refractory restenosis after BMS implantation suggests the relation with metal allergy. We must think of metal allergy after the development of refractory restenosis and PSS with BMS implantation.>
Peri-stent contrast staining (PSS) was an abnormal angiographic finding suggesting presence of contrast material outside the stent border, which was found in 1.9% of the lesions or 2.5% of the patients within 12 months after sirolimus-eluting stent (SES) implantation [
]. PSS is rarely seen with bare-metal stents (BMSs). This case was found to have metal allergy and underwent a patch test in order to evaluate the relation between metal allergy and the refractory restenosis after BMS stent placement.
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Incidence, risk factors, and clinical sequelae of angiographic peri-stent contrast staining after sirolimus-eluting stent implantation.
Circulation. 2011; 123: 2382-2391
A 68-year-old female underwent bare-metal stent (BMS) implantation 3.0 mm in diameter and 30 mm in length (Driver™ stent, Medtronic, Minneapolis, MN, USA) in the right coronary artery (RCA) for ST-segment elevation myocardial infarction (Fig. 1A ). The patient had hypertension, dyslipidemia, and smoking habit, but did not have a history of autoimmune disease or vasculitis.
Follow-up angiography at 7 months after initial BMS implantation demonstrated severe stenosis at the proximal and distal parts of the stent with PSS (Fig. 1B). After the initial procedure, the patient was proved to have a history of metal allergy and subsequent patch test revealed positive responses for chromium, iridium, and palladium. Metal constituents of the implanted stent are cobalt, nickel, and chromium. Since the reason for restenosis was strongly suspected to be metal allergy, we avoided using a metal stent to treat the restenosis lesion. Coronary intervention for the in-stent restenosis lesion was performed by plain old balloon angioplasty (POBA) with a 3.0-mm diameter balloon dilatation catheter at 8 months and 11 months after the initial procedure (Fig. 1C and D).
Three months after the last intervention, coronary angiogram revealed total occlusion of the RCA and severe de novo stenosis in the left anterior descending coronary artery (LAD) (Fig. 1E). Treatment of the LAD lesion appeared to be mandatory, and use of metallic stent was considered to be prohibitive for this patient. Therefore, we decided to treat this patient with coronary artery bypass grafting (CABG) at 1 month after the coronary angiography.
During CABG surgery, stented segment of proximal RCA was harvested and pathological analysis was performed (Fig. 1F). Stented arteries were submitted for plastic embedding in methyl methacrylate.
Histological sections were stained with hematoxylin and eosin. Stented segments were totally occluded by proliferation of dense collagenous fibers (Fig. 2A ). Mild to moderate inflammatory cell infiltration was observed, which was mainly composed of lymphocytes together with small amount of scattering eosinophils, and the appearance of multinucleated foreign body giant cells was also evident in contact with the strut (Fig. 2B–D).
To our knowledge, this is the first pathologic report of refractory restenosis with PSS after BMS implantation. Pathological findings showed extensive medial destruction with inflammatory neointimal proliferation and fibrosis by dense abundant collagen fiber. Generally, restenotic lesions show the hyperplasia of smooth muscle cell and accumulation of proteoglycan. However, pathological images of this patient showed that total occlusion was constituted of a lot of collagen fiber. Previously, we reported a case of PSS after SES with extensive loss of intimal tissue and infiltration of inflammatory cells [
]. Furthermore, destructive and proliferative reaction against chromium, which is one of the constituents of the stent, was reported to provoke such refractory restenosis and PSS after SES implantation [
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- Okamoto K.
- Sato T.
- Kimura T.
- Inoue K.
Contrast staining outside the sirolimus-eluting stent leading to coronary aneurysm formation: a case of very late stent thrombosis associated with hypersensitivity reaction.
Circ Cardiovasc Interv. 2011; 4: e1-e3
]. Previous studies suggested that allergic reactions to chromium released from the stents might be one of the triggering mechanisms for in-stent restenosis [
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Diffuse in-stent restenosis of CYPHER® stent due to hypersensitivity reaction confirmed by pathohistological findings.
Heart Vessels. 2012; 27: 110-113
]. Implants can cause inflammatory hypersensitivity reactions including allergic reactions to chromium, which lead to a fibroproliferative response around the stent. A fibroproliferative and inflammatory response is also characteristically seen in restenotic tissue within coronary stents. Hypersensitivity reaction to durable polymer is generally recognized as the most dominant cause of PSS. It could be possible that remaining inflammatory reactions to the metal of the stent caused the development of refractory restenosis and PSS.
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Nickel and molybdenum contact allergies in patients with coronary in-stent restenosis.
Lancet. 2000; 356: 1895-1897
Furthermore, even after bioresorbable scaffolds implantation, severe development of PSS was reported to be associated with evidence of immature neointima and strut fractures [
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Coronary evaginations and peri-scaffold aneurysms following implantation of bioresorbable scaffolds: incidence, outcome, and optical coherence tomography analysis of possible mechanisms.
Eur Heart J. 2016; 37: 2040-2049
Minimizing the inflammatory reactions to either metal or polymer might be key for the future development of improved coronary stents.
Conflict of interest
Dr Kimura served as an advisory board member for Cordis Cardiology, Abbott Vascular, and Terumo. The remaining authors report no conflicts of interest.
- Incidence, risk factors, and clinical sequelae of angiographic peri-stent contrast staining after sirolimus-eluting stent implantation.Circulation. 2011; 123: 2382-2391
- Contrast staining outside the sirolimus-eluting stent leading to coronary aneurysm formation: a case of very late stent thrombosis associated with hypersensitivity reaction.Circ Cardiovasc Interv. 2011; 4: e1-e3
- Diffuse in-stent restenosis of CYPHER® stent due to hypersensitivity reaction confirmed by pathohistological findings.Heart Vessels. 2012; 27: 110-113
- Nickel and molybdenum contact allergies in patients with coronary in-stent restenosis.Lancet. 2000; 356: 1895-1897
- Coronary evaginations and peri-scaffold aneurysms following implantation of bioresorbable scaffolds: incidence, outcome, and optical coherence tomography analysis of possible mechanisms.Eur Heart J. 2016; 37: 2040-2049
Published online: September 09, 2016
Accepted: July 29, 2016
Received in revised form: July 28, 2016
Received: May 16, 2016
© 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
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