Cardiovascular Revascularization Medicine 11 (2010) 52–56

Case Reports

Late drug-eluting stent thrombosis: importance of intravascular ultrasound

Andrew McCann⁎, Andrew MacIsaac, Robert J. WhitbournReceived 18 August 2008; received in revised form 21 December 2008; accepted 22 December 2008

Abstract We report two cases of late occurring drug-eluting stent thrombosis (ST) where coronary

⁎ Corresponding aE-mail address: ab

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angiography failed to identify the cause but intravascular ultrasound (IVUS) revealed underlyingmechanical problems with the initial stent deployment. Mechanical factors such as stentunderexpansion and residual edge stenoses may be more important in the pathogenesis of latedrug-eluting ST than previously recognized. Intravascular ultrasound is required to reliably detectthese problems and optimize subsequent reintervention.Crown Copyright © 2010 Published by Elsevier Inc. All rights reserved.

Keywords: Coronary artery disease; Imaging; Stent underexpansion

1. Introduction

Recent data suggest patients suffering late stent throm-bosis (LST) of drug-eluting stents (DES) are at high risk ofrecurrent ST, with an incidence of almost 20% at 3-yearfollow-up [1]. As the etiological factors responsible for LSTare not completely understood, the optimal treatment of thesepatients remains unclear. Delayed endothelialization,adverse vessel remodeling, and premature withdrawal ofantiplatelet therapy are important, but technical issues relatedto suboptimal stent deployment may be more common thanpreviously recognized [2–5].

We report a case of late and very late stent thrombosis(VLST), 4 and 30 months after successful DES implantation.In both instances, coronary angiography failed to identify themechanism of ST, but intravascular ultrasound (IVUS)revealed significant residual stenoses.

1.1. Case 1

A 41-year-old male presented with unstable angina. Riskfactors included hypercholesterolemia and smoking. Cor-onary angiography revealed a subtotal occlusion of the first

uthor.mccann74@hotmail.com (A. McCann).

front matter. Crown Copyright © 2010 Published by Elsev008.12.006

marginal branch (OM1) of a dominant left circumflexartery (Fig. 1A). There was minor coronary disease of theleft anterior descending (LAD) artery and the rightcoronary (RCA) artery. Left ventricular systolic functionwas normal. Prior to intervention, he was preloaded with300 mg of aspirin, 600 mg of clopidogrel, and 5000 U ofheparin. The OM1 was predilated with a 2.0×8-mmballoon, and a 2.25×8-mm Taxus DES (Boston Scientific,Natick, MA, USA) was deployed at 12 atm. Finalangiography revealed a well-deployed stent, no evidenceof edge dissection but a moderate stenosis of thesidebranch. This required no intervention on the basis ofpreserved flow and no signs of ischemia (Fig. 1B).Medications at discharge included aspirin, clopidogrel,atenolol, and atorvastatin.

At routine 12-month review the patient was asympto-matic. Clopidogrel was ceased with the advice to continueaspirin and other medications indefinitely. Ten days later, hepresented to a regional hospital with an inferolateral ST-elevation myocardial infarction complicated by in-hospitalventricular fibrillation. Thrombolysis (reteplase) was givenwith resolution of chest pain and electrocardiographicabnormalities. He was transferred to our institution forfurther management. Coronary angiography the followingday showed the previously stented OM1 to be widely patentwith minor progression of atheroma distal to the stent(Fig. 1C). The LAD and RCA were unchanged. He was

ier Inc. All rights reserved.

Fig. 1. A 42-year-old male underwent Taxus stent implantation (2.25×8 mm) into the circumflex marginal artery. a) Prior to stenting there is a subtotalocclusion of the first obtuse marginal; b) Final angiogram after stent implantation; c) 12 months later following thrombolysis for an inferolateralmyocardial infarct.

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discharged on indefinite dual antiplatelet therapy withaspirin and clopidogrel.

Eighteen months later, while continuing to take aspirinand clopidogrel he suffered an episode of chest painaccompanied by a minor elevation of cardiac enzymes.The patient was commenced on therapeutic intravenousunfractionated heparin. Repeat coronary angiography 24 h

Fig. 2. a) Coronary angiogram 28 months after stent implantation following anclopidogrel. There is visible thrombus in mid stent; b) Angiography following IVUSstent; C) distal reference; D) distal lesion; E) mid-stent following repeat stenting. Twhich was under-appreciated at angiography (D).

after presentation showed a hazy filling defect in the mid-OM1 stent suggestive of thrombus and an ostial stenosis inthe sidebranch of OM1 (Fig. 2A). Intravenous abciximab andlow-pressure balloon angioplasty to 8 atm with a 2.0×8-mmballoon resulted in angiographic improvement. Visualassessment and subsequent quantitative coronary angiogra-phy (QCA) demonstrated minimal residual stenosis (Fig. 2,

episode of recurrent stent thrombosis despite compliance with aspirin andguided stenting. Lower panels: IVUS images: A) proximal reference; B) midhere is focal underexpansion at the mid-stent (B) and a severe distal stenosis,

Table 1

A B C D E

QCAMLD (mm) – 2.25 – 1.74 2.7RVD (mm) 2.5 2.38 2.8Stenosis (%) 10 27% 4%EEM Area (mm2) 11.69 11.83 8.81 5.6 11.4Vessel diameter (mm) 3.6×4.1 3.7×4.0 3.1×3.5 2.4×3.0 3.8×3.9Lumen area (mm2) 5.15 2.54 6.25 2.3 7.0Lumen diameter (mm) – 1.6×1.9 2.62×2.97 1.5×1.9 2.8×3.0

QCA=Quantitative coronary angiography; MLD=minimum lumen dia-meter; RVD=reference vessel diameter; EEM=cross-sectional area ofexternal elastic membrane.

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Table 1). IVUS was performed to define the mechanism ofrecurrent ST. There was significant focal underexpansion ofthe mid-stent (B) and a severe stenosis distal to the stent notreadily apparent angiographically (D).

Repeat percutaneous intervention was undertaken.Sequential predilatation to the sidebranch ostium(2.5×12-mm Voyager balloon, Abbott Vascular, SantaClara, CA, USA) and the main branch stent (3.0×12-mmVoyager balloon) were performed at 12 atm, followed by

Fig. 3. A 55-year-old female with previous Taxus stenting to the LAD. Four monanterior STEMI. Upper panels: Coronary angiography following thrombolysis. Lowstent there is a severe outflow stenosis (MLA 2.69mm2). Abbreviations as in Figu

kissing balloon inflation to 8 atm. Next, the more distal lesionwas stented at nominal pressure using a 3.0×20-mm Libertebare-metal stent overlapping the more proximal stent. High-pressure postdilatation was performed to 22 atm using a3.0×10-mm NC Mercury balloon (Abbott Vascular). Finalangiographic result was excellent (Fig. 2B). Repeat IVUSconfirmed complete expansion of the stents. The patient wasadvised to continue lifelong aspirin and clopidogrel for afurther 6 months. He remains well at 10 months' follow-up.

1.2. Case 2

A 55-year-old woman underwent stenting to the mid-LAD for diffuse in-stent restenosis of a bare-metal stent. A2.75×32-mm Taxus stent and a 2.75×12-mm Taxus stentwere deployed at nominal pressure from distal to proximalLAD in an overlapping fashion. Postdilatation was per-formed at high pressure (3.0×12-mm Quantum balloon to20 atm). She had a history of chronic renal impairment,hypertension, and hypercholesterolemia. Medications atdischarge included aspirin, clopidogrel, simvastatin, rami-pril, and atenolol.

ths after stenting the ostium LAD, when aspirin was ceased she suffered aner panels: IVUS images: A) proximal reference; B) mid stent; C) Distal to there 2.

55A. McCann et al. / Cardiovascular Revascularization Medicine 11 (2010) 52–56

Nineteen months later she developed recurrent angina.Angiography revealed an ostial LAD stenosis proximal tothe stented segment. A 2.75×32-mm Taxus Liberte DESwas deployed to 14 atm, overlapping the previouslystented mid-LAD. High-pressure postdilatation was per-formed (3.0×8-mm Quantum Maverick to 22 atm). Shewas continued on long-term dual antiplatelet therapy withaspirin and clopidogrel.

Four months later, the patient developed persistenthematuria necessitating semi-urgent cystoscopy. Aspirinwas ceased 3 days prior to the procedure but she wascontinued on clopidogrel peri-procedurally. The day after thecystoscopy, she presented to a regional hospital with chestpain accompanied by ST-segment elevation in the anteriorchest leads. Thrombolysis was given with resolution of painand electrocardiographic abnormalities. CK peaked at2500 IU/l. She was transferred to our institution for furthermanagement. Subsequent angiography the following dayshowed a widely patent stented segment of the proximal andmid LAD. There was a step-down in size at the distal stentedge (Fig. 3B, arrow C) and an apparently normal distalvessel. By QCA this was determined to be a mild stenosisonly (minimum lumen diameter 1.8 mm, reference vesseldiameter 2.4 mm corresponding to a 25% stenosis). IVUSrevealed well-apposed stents with no visible neointimalproliferation. Immediately distal to the stent, there was asevere stenosis corresponding to the step-down in vessel size(Fig. 3, arrow C; lumen diameter 1.6×2.1 mm, vesseldiameter 2.9×3.5 mm, lumen area 2.7 mm2). This wasstented with a 2.25×12-mm Taxus stent at 12 atm andpostdilated with a 2.5×8-mm noncompliant balloon to16 atm. Repeat IVUS was performed and showed a well-expanded and apposed stent.

2. Discussion

We describe two cases of late occurring ST (30 and4 months) after successful deployment of paclitaxel-elutingstents. In the first case, recurrent LST occurred despite dualtherapy with aspirin and clopidogrel due to the combinationof severe stent underexpansion, progressive outflow disease,and a significant sidebranch stenosis. The true severity ofthese abnormalities could only be determined by IVUSwhich guided and optimized subsequent intervention.

In the second case, peri-operative LST occurred onclopidogrel monotherapy 4 months following long-segmentLAD stenting. In this setting, one might attribute ST solely todelayed stent endothelialization given only minor angio-graphic abnormalities and recent aspirin discontinuation.However, in addition to delayed endothelialization, IVUSshowed a significant outflow stenosis which required stenting.

The etiology and optimal treatment for LST remainunclear. Most cases of early and subacute ST relate totechnical problems at the time of stent deployment such asstent underexpansion, unstented residual disease, or unrec-

ognized edge dissections. However, these factors areconsidered less important in the pathogenesis of LSTwhere premature antiplatelet therapy cessation and drug- orpolymer-induced arterial changes (such as delayed endothe-lialization, adverse vessel remodeling, endothelial dysfunc-tion, inflammation) have received the greatest emphasis inthe literature [6]. However, IVUS is far more sensitive thanangiography at detecting features such as stent under-expansion and stent malapposition [7]. As IVUS is notroutinely performed in all cases of LST the true incidence ofmechanical contributors to LST may be underestimated.Several reports utilizing routine IVUS after late DESthrombosis have identified a high incidence of suboptimalstent deployment and other technical problems. The mostcommon findings included stent underexpansion, unstentedresidual inflow/outflow lesions, and jailing of significantsidebranches [3–5]. Stent malapposition has also beenvariably associated with LST and may be particularlyimportant in cases of VLST [5]. The value of routineIVUS during initial DES implantation has not been evaluatedin a randomized control trial, but recent propensity-matcheddata suggest IVUS has the potential to influence treatmentstrategy and reduce rates of DES thrombosis [8].

Most cases of LST occur after withdrawal of dualantiplatelet therapy (50–75% of cases in two large registries)[9,10]. However, those patients who do suffer ST on dualantiplatelet therapy tend to have smaller minimum luminalareas (4.24±0.96 mm2) compared with patients who developSTon aspirin alone (5.30±1.15 mm2) [2]. These observationssuggest combination antiplatelet therapy is masking anunderlying predisposition to ST in many instances andsupport the notion that mechanical problems underlie manycases of LST. As our cases highlight, failure to recognizetechnical problems with the initial stent deployment andattributing ST solely to discontinuation of antiplatelettherapy place the patient at risk of recurrent ST.

3. Conclusions

Technical issues of suboptimal stent deployment mayexplain many cases of LST and VLST. Recognition of thesemechanical problems is important to prevent episodes ofrecurrent stent thrombosis. Intravascular ultrasound isrequired to reliably detect these problems and optimizesubsequent reintervention.

References

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[2] Okabe T, Mintz GS, Buch AN, Roy P, Hong YJ, Smith KA, TorgusonR, Gevorkian N, Xue Z, Satler LF, et al. Intravascular ultrasoundparameters associated with stent thrombosis after drug-eluting stentdeployment. Am J Cardiol 2007;100(4):615–20.

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[3] Fujii K, Carlier SG, Mintz GS, Yang YM, Moussa I, Weisz G, DangasG, Mehran R, Lansky AJ, Kreps EM, et al. Stent underexpansion andresidual reference segment stenosis are related to stent thrombosis aftersirolimus-eluting stent implantation: an intravascular ultrasound study.J Am Coll Cardiol 2005;45(7):995–8.

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[8] Roy P, Steinberg DH, Sushinsky SJ, Okabe T, Pinto Slottow TL,Kaneshige K, Xue Z, Satler LF, Kent KM, Suddath WO, et al. Thepotential clinical utility of intravascular ultrasound guidance in patientsundergoing percutaneous coronary intervention with drug-elutingstents. Eur Heart J 2008;29(15):1851–7.

[9] Daemen J, Wenaweser P, Tsuchida K, Abrecht L, Vaina S, Morger C,Kukreja N, Juni P, Sianos G, Hellige G, et al. Early and late coronarystent thrombosis of sirolimus-eluting and paclitaxel-eluting stents inroutine clinical practice: data from a large two-institutional cohortstudy. Lancet 2007;369(9562):667–78.

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