From the Department of Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea. The authors report no financial relationships or conflicts of interest regarding the content herein. Manuscript submitted March 6, 2009, provisional acceptance given April 23, 2009, and final version accepted April 27, 2009. *Address for correspondence: Seung-Jung Park, MD, Department of Cardiology, University of Ulsan College of Medicine, Cardiac Center, Asan Medical Center, 388-1 Poongnap-dong, Songpa-gu, Seoul, 138-736, Korea. E-mail: email@example.com
_______________________________________________ ABSTRACT:Late complications of drug-eluting stent, such as stent malapposition or aneurysm formation have emerged major concern. However, there is no available standard therapeutic guideline about them because the clinical course of those is variable and long-term follow-up data is not sufficient. A case presented here is acute ST-elevation myocardial infarction as a result of very late stent thrombosis developed in a patient with stent malapposition and peri-stent aneurysm formation 52 months after sirolimus-eluting stent implantation. In conclusion, more careful long-term follow-up studies are required to access the significance of these late vascular pathologic changes.
J INVASIVE CARDIOL 2009;21:E175–E177 Key words: stent thrombus, myocardial infarction, aneurysm In the drug-eluting stent (DES) era, millions of patients with coronary artery disease have received coronary artery stents. As compared with bare-metal stent, DES dramatically reduce neointimal proliferation and restenosis rates, leading to a significant reduction of repeat revascularizations.1 However, stent thrombosis occurring in the late or very late phase is a major concern to DES safety.2,3 We present the case of a patient who suffered acute ST-elevation myocardial infarction (STEMI) complicated by very late stent thrombosis, late malapposition and aneurysm formation 52 months after Cypher™ sirolimus-eluting stent (SES) implantation (Cordis Corp., Miami Lakes, Florida). Case Description. A 49-year-old male, status 52 months post-implantation of 3 SESs in the left anterior descending artery (LAD), presented with acute anterior STEMI. The patient was a 30-pack-per-year smoker and had hyperlipidemia without a history of diabetes mellitus or hypertension. At the index procedure 52 months prior, the LAD lesion was totally occluded, with excellent collateralization from the right coronary artery (RCA). The lesions at the circumflex artery and right coronary artery were not significant. The ejection fraction was 69% without wall-motion abnormality. He thus underwent successful recanalization and received multiple stents with overlapping of 3.0 × 13 mm, 3.5 × 33 mm and 2.5 x 13 mm SES in the LAD (Figures 1A and 1B). After discharge, he continued on atenolol, simvastatin and triple antiplatelet therapy with aspirin, clopidogrel and cilostazole for 6 months. Thereafter, he terminated clopidogrel and cilostazol and continued aspirin monotherapy. Six months after stenting, the patient underwent angiographic surveillance as shown in Figures 1C and 1D. Angiography and intravascular ultrasound (IVUS) showed an absence of in-stent restenosis or aneurysm formation. There was only insignificant intimal plaque and mild stent malapposition in the stented segment (Figure 1D). During the following 52 months, the patients remained asymptomatic with a negative stress test. On the day of admission, the patient developed a severe anterior chest pain during bicycle exercise. His resting ECG showed prominent new ST-segment elevations > 1 mm in leads V1–V4. The patient’s left ventricular ejection fraction (LVEF) was reduced to 45%, with akinesia at the anterior and apical walls. Emergent coronary angiography revealed total occlusion of the entire segment of the LAD stents (Figure 2A). After crossing the lesion with a 0.014 inch BMW guidewire (Guidant Corp., Santa Clara, California), IVUS examination was attempted using the 40 MHz IVUS catheter (Boston Scientific Corp., Natick, Massachusetts), but difficulties were encountered in the advancement of IVUS catheter into the diseased vessel. Therefore, the lesion was dilated with a 2.5 x 20 mm balloon (Pleon, Biotronik, Inc., Berlin, Germany), with significant residual narrowing (Figure 2B). In order to assess the luminal pathology, IVUS examination was tried again and showed aneurysmal dilatation and significant plaque inside and behind the entire SES (Figure 2D). Because of significant plaque and dissection in the entire segment of SES, the lesion was implanted with 3.5 x 28 mm, 3.5 x 28 mm and 2.75 x 28 mm everolimus-eluting stents (Xience-V™, Abbott Vascular, Abbott Park, Illinois) with a successful angiographic result (Figure 2C). The patient recovered uneventfully and was discharged with the antiplatelet medications aspirin, clopidogrel and cilostazole. Discussion. This case report features acute STEMI as a result of very late stent thrombosis that developed in a patient with stent malapposition and persistent aneurysm formation after SES implantation. The pathologic mechanism of late DES thrombosis is likely multifactorial.4 Virmani et al previously demonstrated pathological specimens from patients who died of late DES thrombosis due to delayed arterial healing characterized by incomplete reendothelialization as the cardinal risk factor, and other factors such as coronary artery aneurysm due to hypersensitivity reaction and late stent malapposition.4–6 Also, premature discontinuation of antiplatelet medication, renal failure, diabetes and low ejection fraction have been identified as predisposing factors in several studies.7,8 According to the ACC/AHA/ SCAI 2007 guideline, all patients who have received DES should be given clopidogrel 75 mg/day for at least 12 months.9 However, at the time of initial coronary stenting 4 years prior, the duration of dual antiplatelet therapy was recommended for at least 3 months after Cypher stent implantation.9 But in our case, even though the patient received aspirin and clopidogrel for 6 months as recommended, thrombosis occurred 45 months after clopidogrel discontinuation despite aspirin continuation. In the majority of cases, late stent thrombosis occurred just after discontinuation of antiplatelet therapy.10 This indicates that another mechanism other than discontinuation of antiplatelet medication might be involved in the occurrence of very late stent thrombosis. In our patient’s case, it was unlikely that the vascular pathology had significantly progressed to aneurysm formation combined with stent malapposition 4 years after stenting, as 6-month angiography and IVUS showed only a mild degree of stent malapposition. Previous studies showed that late stent malapposition after DES implantation was not associated with adverse events.11,12 In contrast, from a registry of 40 autopsies of patients treated with DES (68 stents), malapposition was observed in 2 of 14 cases.4 This was consistent with the IVUS study demonstrating that stent malapposition and underexpansion are significantly associated with stent thrombosis.13 In addition, a previous autopsy case showed a fatal result of late stent thrombosis at 18 months after SES implantation associated with a localized hypersensitivity reaction and coronary artery aneurysm formation.5 Moreover, there are two other reports about coronary aneurysm formation occurring within 2 weeks of the procedure that required surgical intervention.14 The surgical findings showed inflammation at the site of aneurysm formation, which suggested a hypersensitivity reaction to the metal, the polymer or the drug.14 In the present case, extensive, persistent aneurysm formation of the stented region, malapposition with positive remodeling and placement of multiple stents would have resulted in abnormal blood flow in the patient with a predisposition to stent thrombosis. Conclusion. We report a case of very late stent thrombosis 52 months after SES implantation and 45 months after clopidogrel discontinuation in the presence of late stent malapposition and coronary artery aneurysm. Careful long-term follow-up studies are required to establish a reasonable therapeutic guideline to treat DES-related late vascular changes such as malapposition or aneurysm formation.
2. Lagerqvist B, James SK, Stenestrand U, et al. Long-term outcomes with durg-eluting stents versus bare-metal stents in Sweden. N Engl J Med 2007;356:1009‚Äì1019.
3. 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‚Äì998.
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‚Äì202.
5. Virmani R, Guagliumi G, Farb A, Musumeci G, et al. Localized hypersensitivity and late coronary thrombosis secondary to a sirolimus-eluting stent: Should we be cautious? Circulation 2004:109:701‚Äì705.
6. Luscher TF, Steffel J, Eberli FR, et al. Drug-eluting stent and coronary thrombosis: Biological mechanisms and clinical implications. Circulation 2007;115:1051‚Äì1058.
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‚Äì2130.
8. 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.
9. King SB III, Smith SC Jr, Hirshfeld JW Jr,et al. ACC/AHA/SCAI. 2007 Focused update of the ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention: A report of the American College of Cardiology/American Heart Association Task Force on Practice guidelines. J Am Coll Cardiol 2008;51:172‚Äì209.
10. Park DW, Park SW, Park KH, et al. Frequency of and risk factors for stent thrombosis after drug-eluting stent implantation during long-term follow-up. Am J Cardiol 2006;98:352‚Äì356.
11. 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‚Äì419.
12. Ako J, Morino Y, Honda Y, Hassan A, et al. Late incomplete stent apposition after sirolimus- eluting stent implantation: A serial intravascular ultrasound analysis. J Am Coll Cardiol 2005;46:1002‚Äì1005.
13. Alfonso F, Suarez A, Angiolillo DJ, et al. Findings of intravascular ultrasound during acute stent thrombosis. Heart 2004;90:1455‚Äì1459.
14. Gupta RK, Sapra R, Kaul U. Early aneurysm formation after drug-eluting stent implantation: An unusual life-threatening complication. J Invasive Cardiol 2006;18:E140‚ÄìE142.