Stent thrombosis is rare, but very serious, with potentially fatal consequences following percutaneous coronary intervention (PCI). Traditionally, it has been classified as acute, within 48 hours, subacute up to 30 days, and late, corresponding to all cases after day 30. Acute or subacute stent thrombosis is often thought to be procedure- or lesion-related, as suggested by data from randomized studies and large registries having fairly similar rates (1–2%) between both bare-metal stents (BMS) and drug-eluting stents (DES).1–3 Late stent thrombosis (LST) with DES remains controversial, with suggestive mechanisms related to delayed stent endothelialization,4 possibly polymer-based local hypersensitivity reactions,5 discontinuation of antiplatelet therapy6 and late-acquired stent malapposition due to excessive positive remodeling.7 This report demonstrates that in a complex case, optimal stent sizing at the index procedure should not be underestimated, as flowrelated dynamics due to abnormal shear stress superimposed on a prothrombotic condition could result in LST.
Case Report. A 67-year-old male smoker with arterial hypertension and insulin-dependent diabetes was referred for coronary intervention after an acute anterolateral infarction. Angiography revealed a severe lesion in the left anterior descending artery (LAD), with a moderate lesion in the left circumflex artery (LCx) (Figure 1A). Baseline quantitative coronary angiography (QCA) showed a proximal 3.0 mm vessel with a calculated reference diameter of 2.49 mm at the culprit lesion (Figure 1B). The right coronary artery was dominant, with no significant disease, and the left ventricular function was mildly impaired. Percutaneous intervention to the LAD involved predilatation with a 2.5 x 15 mm balloon. A Taxus 2.5 x 20 mm stent (Boston Scientific Corp., Natick, Massachusetts) was deployed at 14 atm with good results (Figure 1C). Dual antiplatelet therapy with clopidogrel for 12 months and aspirin indefinitely were recommended. Six months following this acute event, the LCx was electively treated with a 2.25 x 12 mm Taxus stent. Of note, the LAD stent was fully patent with no visible instent restenosis, and clopidogrel therapy was recommended for an additional 12 months. Two weeks following the discontinuation of clopidogrel and while on aspirin, the patient presented with an acute ST-elevation anterolateral infarction. Primary coronary intervention revealed LST in the LAD (Figure 1D). Following thrombectomy (Figure 1E), a distal stenosis was observed which was subsequently treated with a 2.75 x 20 mm Taxus stent (Figure 1F). Intravascular ultrasound (IVUS) showed gross undersizing of the previously-deployed stent, with a maximal diameter of 2.8 mm in a 3.9 mm vessel (Figure 1G). There was no positive remodeling suggestive of late-acquired stent thrombosis, but visible thrombus was observed between the stent and the vessel wall (Figure 1H). The undersized stent was postdilated using a 3.5 x 20 mm balloon, which was followed by “kissing balloon” dilatation with the first diagonal. Subsequent IVUS showed complete apposition of the deployed stents, and clopidogrel was prescribed for 12 months.
Discussion. As a potential solution to in-stent restenosis observed with BMS, the widespread enthusiasm for DES is now marred by the unexpected safety concern related to the potentially catastrophic occurrence of stent thrombosis. The Bern-Rotterdam study has reported an incidence of LST in DES of 0.6% annually.8 However, this might well be an underestimation, as it was limited to angiographic criteria and not broadened to include myocardial infarction (MI) or unexplained sudden cardiac death. Approximately 70% of patients with DES thrombosis experience MI, with a high reported mortality.3,9 The incidence also increases in high-risk patients10 and in complex lesions.11 In general, a survey of the literature classifies the overall predictors of LST associated with DES into four broad groups: (1) those related to antiplatelet therapy (premature discontinuation, possible clopidogrel resistance); (2) those related to the stent platform itself (hypersensitivity to the polymer or drug, incomplete endothelialization); (3) procedural factors (lesion complexity, stent length, incomplete stent apposition); and (4) patient characteristics (diabetes and renal failure).
Our case report highlights the importance of proceduralfactors in a high-risk patient. In particular, the overreliance on a single quantitative technique (QCA) led to significant undersizing of the chosen stent. The reduction in flow through the undersized stent, together with a de novo distal lesion and the recent termination of clopidogrel therapy, acted as a nidus for the observed late thrombotic event. It is therefore paramount that proper and careful evaluation of vessel size and lesion characteristics should be undertaken prior to stenting for an unbiased assessment of the safety and predictability of DES use. The use of IVUS was crucial in the evaluation and treatment of this patient. It demonstrated that postprocedural incomplete stent apposition (ISA) was involved and effectively excluded an unhealed stent edge dissection, or late-acquired ISA (positive remodeling), as the likely cause. However, ISA does merit further investigation. Although some studies have implicated incomplete neointimal coverage of the stent12–14 in stent thrombosis, others have failed to demonstrate any correlation between postprocedure- and late-acquired ISA and this adverse effect15,16 at 12 months. In contrast, stent underexpansion and residual reference segment stenosis are emerging as predictors of DES thrombosis,17 presumably due to abnormal shear stress on the vascular wall. Our case may further exemplify this mechanism which was previously described using hemodynamic measurements in in vitro models.18 It thus emphasizes the importance of appropriate stent sizing/underexpansion and the pitfalls of QCA. Conclusion. Procedure-related causes of LST of DES should not be underestimated. Our case shows that gross undersizing of a stent based solely on QCA in a diabetic patient can lead to LST following termination of dual antiplatelet therapy, presumably because of abnormally-induced shear stresses on the vascular wall.
1. Moses JW, Leon MB, Popma JJ, et al. Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N Engl J Med 2003; 349:1315–1323.
2. Schampaert E, Moses JW, Schofer J, et al. Sirolimus-eluting stents at two years: A pooled analysis of SIRIUS, E-SIRIUS, and C-SIRIUS with emphasis on late revascularizations and stent thromboses. Am J Cardiol 2006;98:36–41.
3. Moreno R, Fernandez C, Hernandez R, et al. Drug-eluting stent thrombosis: Results from a pooled analysis including 10 randomized studies. J Am Coll Cardiol 2005;45:954–959.
4. Degertekin M, Serruys PW, Foley DP, et al. Persistent inhibition of neointimal hyperplasia after sirolimus-eluting stent implantation: Long-term (up to 2 years) clinical, angiographic, and intravascular ultrasound follow-up. Circulation 2002;106:1610–1613.
5. Virmani R, Guagliumi G, Farb A, et al. Localized hypersensitivity and late coronary thrombosis secondary to a sirolimus-eluting stent: Should we be cautious? Circulation 2004;109:701–705.
6. McFadden EP, Stabile E, Regar E, et al. Late thrombosis in drug-eluting coronary stents after discontinuation of antiplatelet therapy. Lancet 2004;364:1519–1521.
7. Feres F, Costa JR Jr, Abizaid A. Very late thrombosis after drug-eluting stents. Catheter Cardiovasc Interv 2006;68:83–88.
8. Daemen J, Wenaweser P, Tsuchida K, et al. Early and late coronary stent thrombosis of sirolimus-eluting and paclitaxel-eluting stents in routine clinical practice: Data from a large two-institutional cohort study. Lancet 2007;369:667–678.
9. Ong AT, Hoye A, Aoki J, et al. Thirty-day incidence and six-month clinical outcome of thrombotic stent occlusion after bare-metal, sirolimus, or paclitaxel stent implantation. J Am Coll Cardiol 2005;45:947–953.
10. Iakovou I, Schmidt T, Bonizzoni E, et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA 2005;293:2126–2130.
11. Kuchulakanti PK, Chu WW, Torguson R, et al. Correlates and long-term outcomes of angiographically proven stent thrombosis with sirolimus- and paclitaxel-eluting stents. Circulation 2006;113:1108–1113.
12 . Takano M, Mizuno K. Late coronary thrombosis in a sirolimus-eluting stent due to the lack of neointimal coverage. Eur Heart J 2006;27:1133.
13 . Uren NG, Schwarzacher SP, Metz JA, et al. Predictors and outcomes of stent thrombosis: An intravascular ultrasound registry. Eur Heart J 2002;23:124–132.
14 . Joner M, Finn AV, Farb A, et al. Pathology of drug-eluting stents in humans: Delayed healing and late thrombotic risk. J Am Coll Cardiol 2006;48:193–202.
15. Degertekin M, Serruys PW, Tanabe K, et al. Long-term follow-up of incomplete stent apposition in patients who received sirolimus-eluting stent for de novo coronary lesions: An intravascular ultrasound analysis. Circulation 2003;108:2747–2750.
16. Tanabe K, Serruys PW, Degertekin M, et al. Incomplete stent apposition after implantation of paclitaxel-eluting stents or bare metal stents: Insights from the randomized TAXUS II trial. Circulation 2005;111:900–905.
17 . Fujii K, Carlier SG, Mintz GS, et al. Stent underexpansion and residual reference segment stenosis are related to stent thrombosis after sirolimus-eluting stent implantation: An intravascular ultrasound study. J Am Coll Cardiol 2005;45:995–998.
18 . Sukavaneshvar S, Rosa GM, Solen KA. Enhancement of stent-induced thromboembolism by residual stenoses: Contribution of hemodynamics. Ann Biomed Eng 2000;28:182–193.