Late Stent Thrombosis Associated with Coronary Aneurysm Formation after Sirolimus-Eluting Stent Implantation

J INVASIVE CARDIOL 2007;19:E96-E98

Drug-eluting stents (DES) have been shown to be superior to bare-metal stents (BMS) in reducing the need for repeat revascularization.¹ Their use has increased rapidly with DES accounting for up to 80% of all coronary stents used in the United States.² The delayed vascular healing after DES implantation has led to concerns regarding the potential for late stent thrombosis (LST).^3,4 We report a rare cause of LST after sirolimus-eluting stent (SES) implantation associated with abnormal vessel remodeling.

Case Report. A 70-year-old female patient underwent percutaneous coronary intervention (PCI) to the left anterior descending artery (LAD) and obtuse marginal (OM) in December 2003 after an admission with non-ST-segment elevation myocardial infarction (MI). Two adjacent SES were deployed in the proximal and mid LAD (Figures 1A and B). A Driver stent (Medtronic, Inc., Minneapolis, Minnesota) was also deployed in the first OM. The patient continued aspirin indefinitely and clopidogrel for 12 months post-PCI. Twenty-one months after the index PCI she presented with an anterior ST-segment elevation MI. She was treated at a local hospital with thrombolysis and recommencement of clopidogrel. Echocardiography showed poor left ventricular systolic function. Five months later, she developed recurrent anterior ST-segment elevation MI and she was transferred to the regional cardiac center for urgent coronary angiography. This showed severe ectasia of the proximal and mid LAD with peri-stent coronary aneurysm formation and severe distal in-stent restenosis (Figure 2). The maximal lumen diameter by quantitative coronary angiography at the aneurysmal point was 4.77 mm, representing a 56% increase compared to the immediate post-stent deployment image. Although intravascular ultrasound was not performed, the guidewire was able to be passed between the SES struts and the vessel wall, suggesting that sections of the coronary vessel wall were not in contact with the stent. A filling defect in the LAD due to thrombus formation was also noted. The bare-metal stent (BMS) in the OM appeared normal. The patient was treated with heparin and abciximab. She underwent repeat PCI with deployment of a BMS to the mid-LAD. Balloon dilatation was performed in the proximal LAD to expand the SES against the arterial wall. The final angiographic result is shown in Figure 3. The patient had no further chest pain and was discharged home 5 days later. At 6-month clinical follow up the patient was doing well.

Discussion. The present case demonstrates LST (26 months post-PCI) in a patient who developed coronary aneurysm formation and stent malapposition following SES implantation. Stent thrombosis occurred despite being on aspirin and clopidogrel therapy. LST (defined as stent thrombosis >30 days post-PCI) has been reported to occur in 0.35% of patients following DES implantation.⁵ In this study by Ong et al all patients with LST presented with acute ST-segment elevation MI. The in-hospital mortality was 28.6%. In the 2 patients who died, angiographic appearances suggested the presence of coronary aneurysm formation with the guidewire passing between the outside of the stent and the vessel wall. These events occurred 25 and 26 months after paclitaxel-eluting stent (PES) implantation when the patients were stable on aspirin monotherapy. No LST events occurred in patients on dual antiplatelet therapy, which was continued for 3–6 months post-PCI.
Feres et al published two cases of LST occurring 40 months after SES and 12 months after PES implantation. In both cases there was late acquired incomplete stent apposition due to positive vessel remodeling behind the stent struts with an increase in vessel volume of >35%.⁶
Iakovou et al reported LST in 0.7% of patients at 9 months post-DES implantation.⁷ Premature discontinuation of antiplatelet therapy was the most important predictor of LST. Other independent predictors of LST were bifurcation lesions and impaired left ventricular systolic function. LST was associated with an in-hospital mortality rate of 45%.
An increased frequency of late-acquired stent malapposition has been noted with DES compared with BMS. In a subgroup analysis of SES in de novo coronary lesions (SIRIUS) trial, late-acquired stent malapposition was reported in 8.7% of SES cases and in none of the BMS cases.⁸ Late-acquired stent malapposition was associated with positive vessel remodeling and an increase in the external elastic membrane area. There were no cases of stent thrombosis after 8 months of follow up in the SES group. In this study, late-acquired stent malapposition involved the central portion of the stent. This is in contrast to cases of late-acquired stent malapposition after BMS implantation that involves the stent edges.⁹ There is concern that incomplete stent apposition in the middle of the stent can result in areas of “cul-de-sac” formation with blood-flow stagnation that can predispose the patient to stent thrombosis.
In the diabetes and sirolimus-eluting stent (DIABETES) trial, late-acquired stent malapposition was reported in 14.7% of patients after SES implantation and in none of the BMS patients.¹⁰ At 1-year follow up, there was no stent thrombosis in the patients with stent malapposition.
In our patient, we observed extensive positive vessel remodeling affecting the stented region of the coronary artery. Severe in-stent restenosis affecting the stent outflow was also observed. This would have resulted in regions of abnormal blood flow predisposing the patient to stent thrombosis. Flow was improved by relieving obstruction with BMS deployment and balloon angioplasty of the SES to restore stent apposition. We avoided further DES deployment. The patient had received a previous BMS that were not associated with significant in-stent restenosis or vascular remodeling. Coronary artery bypass grafting was considered to be high risk due to the patient’s acute presentation with ST-segment elevation MI, administration of potent antiplatelet therapy, and poor left ventricular systolic function.
Potential mechanisms of positive vascular remodeling after DES deployment include hypersensitivity reaction to the stent polymer coatings and toxic effects of antiproliferative drugs on the vessel wall. Virmani et al reported a fatal case of LST 18 months after SES implantation associated with a localized hypersensitivity reaction and coronary aneurysm formation.¹¹ An allergic response to the stent polymer coating was thought to have been the underlying cause. Animal studies have shown that stent polymer coating can cause localized inflammatory reactions in porcine coronary arteries.¹²
Although positive vessel remodeling has been noted in a significant number of cases post-DES implantation, it has not been associated with an increased risk of LST. Clinical follow up in these cases is limited to 1 year. The reported cases of LST due to positive vessel remodeling occurred >12 months post-DES deployment when clopidogrel had been discontinued. These cases may be missed if the patient dies suddenly or is not referred back to the interventional center. The risk of LST may be related to the magnitude of coronary vessel remodeling after DES deployment. In complex lesions such as very long lesions, chronic total occlusions, and bifurcation lesions, the risk of abnormal vessel remodeling is not known, as these patients have been excluded from the randomized trials. Total stent length and chronic total occlusions have been shown to be independent predictors of incomplete stent apposition after DES implantation.¹³ Continued surveillance after DES implantation is required to determine the long-term safety. Improvement in DES design with absorbable polymer coating may prevent this complication from occurring.

References

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. Isenbarger DW, Resar JR. Drug-eluting versus third-generation bare metal stents: The U.S. strategy. Int J Cardiovasc Intervent 2005;7:171–175.
3. McFadden EP, Stabile E, Regar E, et al. Late thrombosis in drug-eluting coronary stents after discontinuation of antiplatelet therapy. Lancet 2004;364:159–1521.
4. 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.
5. Ong AT, McFadden EP, Regar E, et al. Late angiographic stent thrombosis (LAST) events with drug-eluting stents. J Am Coll Cardiol 2005;45:2088–2092.
6. Feres F, Costa JR Jr, Abizaid A. Very late thrombosis after drug-eluting stents. Catheter Cardiovasc Interv 68:83–88.
7. 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.
8. Ako J, Morino Y, Honda Y, et al. Late incomplete stent apposition after sirolimus-eluting stent implantation: A serial intravascular ultrasound analysis. J Am Coll Cardiol 2005;46:1002–1005.
9. Shah VM, Mintz GS, Apple S, Weissman NJ. Background incidence of late malapposition after bare-metal stent implantation. Circulation 2002;106:1753–1755.
10. Jimenez-Quevedo P, Sabate M, Angiolillo DJ, et al. Vascular effects of sirolimus-eluting versus bare-metal stents in diabetic patients: Three-dimensional ultrasound results of the Diabetes and Sirolimus-Eluting Stent (DIABETES) trial. J Am Coll Cardiol 2006;47:2172–2179.
11. 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.
12. van der Giessen WJ, Lincoff AM, Schwartz RS, et al. Marked inflammatory sequelae to implantation of biodegradable and nonbiodegradable polymers in porcine coronary arteries. Circulation 1996;94:1690–1697.
13. Hong MK, Mintz GS, Lee CW, et al. Late stent malapposition after drug-eluting stent implantation: An intravascular ultrasound analysis with long-term follow-up. Circulation 2006;113:414–419.