Case Report and Brief Review

Focal In-Stent Restenosis and In-Stent Thrombosis within the Same Bare-Metal Stent 5 Years after Deployment (Full Title Below)

Focal In-Stent Restenosis and In-Stent Thrombosis within the Same Bare-Metal Stent 5 Years after Deployment in a Saphenous Vein Graft Francis A. Ponnuthurai, MBBCh, FRACP, DDU, William J. van Gaal, MBBS, FRACP, Keith M. Channon, MD, FRCP From John Radcliffe Hospital, Oxfordshire, United Kingdom. The authors report no conflicts of interest regarding the content herein. Manuscript submitted June 4, 2007, provisional acceptance given July 23, 2007, manuscript accepted August 15, 2007. Address for correspondence: Francis Ponnuthurai, MBBCh, FRACP, Department of Cardiology, Level 2, John Radcliffe Hospital, Headley Way, Headington, Oxford, Oxfordshire OX3 9DU, United Kingdom. E-mail: larryponnuthurai@googlemail.com.
Focal In-Stent Restenosis and In-Stent Thrombosis within the Same Bare-Metal Stent 5 Years after Deployment in a Saphenous Vein Graft Francis A. Ponnuthurai, MBBCh, FRACP, DDU, William J. van Gaal, MBBS, FRACP, Keith M. Channon, MD, FRCP From John Radcliffe Hospital, Oxfordshire, United Kingdom. The authors report no conflicts of interest regarding the content herein. Manuscript submitted June 4, 2007, provisional acceptance given July 23, 2007, manuscript accepted August 15, 2007. Address for correspondence: Francis Ponnuthurai, MBBCh, FRACP, Department of Cardiology, Level 2, John Radcliffe Hospital, Headley Way, Headington, Oxford, Oxfordshire OX3 9DU, United Kingdom. E-mail: larryponnuthurai@googlemail.com.
ABSTRACT: Complications of percutaneous coronary intervention include in-stent restenosis (ISR) and in-stent thrombosis (IST) which have different underlying pathophysiological processes and different treatment strategies. ISR is primarily due to excessive neointimal growth and occurs in 20–30% of bare-metal stents (BMS).1,2 Drug-eluting stents (DES) have decreased the rates of ISR (3–5 but are potentially associated with increased IST related to delayed arterial healing and stent strut exposure.6 ISR of BMS typically occurs within 6 months of stent deployment. IST usually occurs within 12 months of DES deployment. We present a case of focal ISR and IST within the same BMS, confirmed with intravascular ultrasound, 5 years after deployment in a saphenous vein graft. J INVASIVE CARDIOL 2007;19:E369–E371 Case Report. A 55-year-old male with a past history of coronary artery bypass graft (CABG) surgery, underwent coronary angiography for post-infarct angina following an acute inferior ST-elevation myocardial infarction (STEMI) treated with thrombolysis. Five years earlier, the proximal vein graft to his left circumflex marginal vessel (SVG-LCxOM) was directly stented with a 3.5 x 9 mm bare-metal stent (BMS) (Medtronic Inc., Minneapolis, Minnesota). Coronary angiography revealed a patent LIMA-LAD and a patent SVG-LCx. The SVG-LCxOM was thought to be the culprit vessel and demonstrated 2 severe focal lesions in the proximal and distal segments of the BMS (Figures 1A and B). The initial management strategy was to perform intravascular ultrasound (IVUS) to further delineate the in-stent pathology prior to percutaneous coronary intervention (PCI). A 6 Fr left coronary bypass guide catheter (Medtronic) engaged the SVG-LCxOM after 90 u/kg of unfractionated heparin were administered intravenously, a clopidogrel loading dose (300 mg) 24 hours previously and chronic aspirin. The lesions were crossed with a BMW wire (Guidant Corp., Indianapolis, Indiana). IVUS analysis using the Atlantis Pro i-lab system (Boston Scientific Corp., Natick, Massachusetts) showed a well-expanded 3.5 x 9 mm BMS, and the pathology of the proximal in-stent lesion to be in-stent restenosis (ISR) (Figure 2B). The distal in-stent lesion on angiography prior to wiring matched a lucency on IVUS consistent with in-stent thrombosis (IST) (Figure 2A). The treatment strategy was to use balloon angioplasty initially and then repeat IVUS analysis. A FilterWire EZ embolic protection system (Boston Scientific) was inserted into the distal SVG-LCxOM. A contrast bolus during IVUS interrogation of the distal stent lucency suggested IST. The thrombus was removed by the mechanical force of the bolus injection during IVUS visualization. The FilterWire system was removed and the basket material sent for photographic analysis (Figure 3). The focal ISR was initially predilated to 8 atm with a 3.0 x 10 mm Cutting Balloon (Boston Scientific) before a 4.0 x 20 mm Taxus® drug-eluting stent (DES) (Boston Scientific) was deployed at 14 atm. The stented segment was postdilated with a 4.0 x 9 mm noncompliant Monorail balloon (Boston Scientific) to 22 atm. Post-procedure IVUS showed satisfactory stent strut expansion. The patient was discharged the next day on long-term dual antiplatelet therapy with clopidogrel and aspirin. Discussion. The presentation, timeframe and treatment of ISR and IST may differ because of differences in underlying pathophysiology. To our knowledge, the combination ISR and IST as separate entities within the same stent has not been widely reported, and this is the latest case (5 years after deployment) of BMS thrombosis described in the literature. Symptomatic ISR usually manifests as recurrent angina rather than acute myocardial infarction (MI) or sudden death because these lesions consist of intimal hyperplasia and fibrous tissue and are less prone to rupture and acute thrombosis than de novo lesions.7 IST may manifest as an abrupt vessel occlusion with a high incidence of MI, emergency CABG or death (45%).8 ISR is more frequent in BMS, related primarily to excessive neointimal endothelialization as a result of smooth muscle cell proliferation and excessive extracellular matrix production.9,10 ISR rates are increased with greater stent length, number of stents used, small vessel lesions, occluded vessels, ostial or bifurcation lesions and vein grafts.11–16 ISR treatment includes high-pressure balloon/cutting balloon angioplasty, usually in conjunction with DES insertion, to inhibit excessive endothelialization. IST has a multifactorial pathology including chronic inflammation (increased lymphocytes and macrophages), hypersensitivity (eosinophilic infiltration), malapposition (positive remodeling — arterial wall expansion), incomplete apposition (suboptimal deployment) and ISR with superimposed thrombosis, but is primarily related to delayed arterial healing (poor endothelialization and peristrut fibrin deposition).17 Although the comparison of IST incidence between BMS and DES is complicated by restenosis with superimposed thrombosis, prior brachytherapy and alternate antiplatelet regimens, IST is generally thought to occur more frequently and later with DES. IST management aims at dissolving and mechanically dispersing the thrombus. This treatment strategy may include the use of multiple balloon angioplasty inflations in conjunction with glycoprotein IIb/IIIa inhibition, thrombectomy devices and/or distal protection devices. Our case has several interesting features including the appearance of both restenosis and thrombosis within the same stent. Given that the management of ISR and IST differ, we recommend the use of IVUS for all cases of in-stent PCI. Secondly, the long delay in presentation of stent complications is unusual and of concern in the current environment of increasing evidence of very late IST, primarily in DES. The very late thrombus formation in our patient occurred within a BMS, which, to our knowledge, has not been described beyond 2 years.18 Finally, this case highlights the potential problem with two pathologies within the same stent. That is, by deploying a DES for ISR in the presence of IST, the presence of thrombus and the inflammatory milieu may act as a substrate for further in situ thrombus formation.19,20 We have, thus, recommended long-term dual antiplatelet therapy with aspirin and clopidogrel for this patient. Conclusion. 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