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The first report of late stent thrombosis leading to acute myocardial infarction in patient receiving the new endothelial progenitor cell capture stent
International Journal of Cardiology 141 (2010) e20 – e22 www.elsevier.com/locate/ijcard
Letter to the Editor
The first report of late stent thrombosis leading to acute myocardial infarction in patient receiving the new endothelial progenitor cell capture stent Marco L. Rossi ⁎, Dennis Zavalloni, Gabriele L. Gasparini, Ruggiero Mango, Guido Belli, Patrizia Presbitero Department of Invasive Cardiology, Istituto Clinico Humanitas, Milano, Italy Received 13 June 2008; accepted 22 November 2008 Available online 9 January 2009
Abstract The endothelial progenitor cell (EPC) capture stent is a stainless steel coronary stent covered with antibodies specific to EPC's surface antigens, designed to promote the faster formation of a functional endothelial lining. This may prevent both stent thrombosis and restenosis as well as reduce the need of prolonged double antiplatelet therapy. Here we report a case of late (156 days after implantation) EPC capture stent thrombosis and re-stenosis of a second EPC capture stent occurring both in the same patient after withdrawal of clopidogrel. Intravascular ultrasound performed during his acute admission showed undersizing of the stent with thrombosis. The present case raises the question about the safety of the EPC capture stent and the need to prolong at least for 6 months double antiplatelet therapy also in patients receiving this new stent. © 2008 Elsevier Ireland Ltd. All rights reserved. Keywords: Angioplasty; Endothelial progenitor cell capture stent; Late stent thrombosis; Clopidogrel
1. Case report In December 2007 a 71-year-old man underwent coronary angiography in an Italian high volume university hospital to assess the perioperative risk from acute coronary disease with a view to a lobectomy for primary lung cancer. The patient with a history of hypertension and hyperlipidemia, had a scintigraphic presence of inducing myocardial ischemia. Coronary angiogram showed presence of two vessel coronary artery disease (CAD) with severe stenoses of the mid- and distal left anterior descending coronary artery (LAD), second diagonal (D2), and right posterior descending artery (PDA). Immediately after the ⁎ Corresponding author. Unità Operativa di Emodinamica e Cardiologia Invasiva, Istituto Clinico Humanitas, Via Manzoni 56, 20089 Rozzano, Milan, Italy. Tel.: +39 0282243601; fax: +39 0282244691. E-mail address: [email protected] (M.L. Rossi). 0167-5273/$ - see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2008.11.134
angiogram percutaneous coronary intervention (PCI) was planned. The 2 lesions in LAD were treated with the endothelial progenitor cell (EPC) capture stents on the mid-proximal (2.5 × 23 mm and 2.5× 13 mm Genous stent; OrbusNeich, Fort Lauderdale, FL) and the distal tract (2.5 × 13 mm Genous stent). Simple balloon angioplasty was performed on D2, followed by kissing balloon inflation of LAD/D2. After LAD PCI, a nonocclusive dissection of the left main coronary artery (LM) occurred. Thus a bare metal stent was used to correct the dissection (3.5 × 18 mm Driver stent; Medtronic) because a suitable EPC capture stent size was not available. The patient was discharged with the recommendation to take dual antiplatelet therapy with aspirin and clopidogrel for 2 months. In January 2008 the patient was re-admitted to the same hospital with effort angina. A coronary angiogram showed patency of the previously implanted stent and a new critical stenosis of the mid-LAD, between the stents previously implanted in the
M.L. Rossi et al. / International Journal of Cardiology 141 (2010) e20–e22
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Fig. 1. Proximal LAD EPC capture stent thrombotic occlusion.
Fig. 3. IVUS cross-section of proximal LAD after thrombectomy showing the undersizing EPC capture stent.
mid-proximal and distal LAD. A PCI was performed with an EPC capture stent on the mid-LAD (2.5 × 13 Genous stent). A PCI was also performed on the PDA using an EPC capture stent (2.5 × 18 Genous stent). Clopidogrel was given for 2 months after stent implantation. Coronary angiography performed 1 month later, in February 2008, showed no stenosis at the stent site and clopidogrel was stopped thereafter. The patient subsequently underwent pulmonary lobectomy. Aspirin was discontinued a few days before and re-started 3 days after the operation. In May 2008 the patient was admitted to our emergency room with chest pain and dyspnea. ECG showed ST segment elevation in the antero-lateral leads. The patient was immediately transferred to the cardiac catheterization laboratory and the angiogram documented a proximal LAD EPC capture stent thrombotic occlusion (156 days after stenting). The stents on the LM and PDA were patent (Fig. 1).
After thrombectomy the re-opening of the LAD was obtained. Angiography showed lumen filling defect at the stent site, a severe restenosis of the EPC capture stent previously placed in the distal LAD tract and a restenosis of D2 previously treated with balloon angioplasty (Fig. 2). Intravascular ultrasound (IVUS) showed undersizing of the previously-deployed stent in the proximal LAD tract (in which we found the in-stent thrombosis), without in-stentneo-intimal hyperplasia (Fig. 3). IVUS showed complete apposition of the distal LAD stent with re-stenosis. The undersized stent was successfully postdilated using a 3.0 × 15 mm balloon. Subsequent IVUS showed complete apposition of the deployed stent. Adjunctive balloon dilatation of distal LAD in-stent restenosis as well as on D2 was performed. Due to dissection of D2 after balloon inflation, a paclitaxel eluting stent (2.25 × 20 mm Taxus stent; Boston
Fig. 2. Restenosis of the EPC capture stent in the distal LAD tract.
Fig. 4. Final results after PCI of the proximal and distal LAD and D2.
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Scientific) was placed. Optimal result with restoration of normal (TIMI 3) flow on LCA was obtained (Fig. 4). A periprocedural intravenous bolus of abciximab followed by 12 h infusion was given. 2. Discussion Percutaneous coronary intervention (PCI) with drug eluting stent (DES) is now becoming the predominant revascularization strategy for coronary artery disease because of their favorable effects on clinical and angiographic outcomes. Although late stent thrombosis (LST) is present in both bare metal stent (BMS) and DES [1], there is a concern that DES might lead to higher rates of LST [2]. Delayed endothelialization of DES seems to be implicated in the pathophysiology of LST and it is seen as one of the most important limitations of these devices also because of the need of prolonged double antiplatelet therapy. Such therapy creates a problem for the clinician when a patient with DES implantation needs noncardiac surgery that cannot be delayed several months as recommended [3]: in these cases the withdrawal of antiplatelet agents may be followed by stent thrombosis. On the other hand, when the antiplatelet therapy is continued it may be associated with perioperative bleeding complications. The endothelial progenitor cell (EPC) capture stent is a new stainless steel coronary stent coated with murine monoclonal antihuman CD34 antibodies. It is designed to attract circulating EPCs by the antibodies immobilized on the stent surface rapidly promoting healing. It has been demonstrated that after implantation of this device a functional endothelial layer is established in 24–48 h [4]. Early surface endothelialization should reduce the processes leading to thrombosis and restenosis. For these reasons the double antiplatelet therapy is rapidly discontinued by stopping the clopidogrel 1 or 2 months after EPC capture stent implantation. This is the first report of LST of endothelial progenitor cell (EPC) capture stent. A failure to form a complete neointimal layer over the stent seems not to be the cause of LST in this case. However, as previously demonstrated, the return of endothelial function after the endothelial surface disruption due to stent deployment may take up to 6 months [5].
The physiologic alterations underlying the endothelial dysfunction associated with clopidogrel withdrawal might be at the base of LST. Notwithstanding, we cannot exclude that the reduction in flow through the undersized stent, together with a distal critical in-stent re-stenosis and the discontinuation of clopidogrel acted as primum movens for the LST. In this setting, the use of IVUS in evaluating the vessel size prior and after stent implantation appears pivotal also using this new device as every kind of DES. The present case report raises the question about the need to prolong (at least 6 month) double antiplatelet therapy also in patient receiving the EPC capture stent. Larger randomized studies will assess the safety of this new device and the opportunity to discontinue double antiplatelet therapy prematurely. Acknowledgement The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [6]. References [1] Park DW, Park SW, Lee SW, et al. Frequency of coronary arterial Late Angiographic Stent Thrombosis (LAST) in the first six months: outcomes with drug-eluting stents versus bare metal stents. Am J Cardiol 2007;99:774–8. [2] Stettler C, Wandel S, Allemann S, et al. Outcomes associated with drugeluting and bare-metal stents: a collaborative network meta-analysis. Lancet 2007;370:937–48. [3] Fleisher LA, Beckman JA, Brown KA, et al. ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2007;116: e418–99. [4] Kutryk MJ, Kuliszewski MA. In vivo endothelial progenitor cell seeding for the accelerated endothelialization of endovascular devices. Am J Cardiol 2003;92:94 L. [5] Caramori PR, Lima VC, Seidelin PH, et al. Long-term endothelial dysfunction after coronary artery stenting. J Am Coll Cardiol 1999 Nov 15;34(6):1675–9. [6] Coats AS. Ethical authorship and publishing. Int J Cardiol 2009;131: 149–50.
Letter to the Editor
The first report of late stent thrombosis leading to acute myocardial infarction in patient receiving the new endothelial progenitor cell capture stent Marco L. Rossi ⁎, Dennis Zavalloni, Gabriele L. Gasparini, Ruggiero Mango, Guido Belli, Patrizia Presbitero Department of Invasive Cardiology, Istituto Clinico Humanitas, Milano, Italy Received 13 June 2008; accepted 22 November 2008 Available online 9 January 2009
Abstract The endothelial progenitor cell (EPC) capture stent is a stainless steel coronary stent covered with antibodies specific to EPC's surface antigens, designed to promote the faster formation of a functional endothelial lining. This may prevent both stent thrombosis and restenosis as well as reduce the need of prolonged double antiplatelet therapy. Here we report a case of late (156 days after implantation) EPC capture stent thrombosis and re-stenosis of a second EPC capture stent occurring both in the same patient after withdrawal of clopidogrel. Intravascular ultrasound performed during his acute admission showed undersizing of the stent with thrombosis. The present case raises the question about the safety of the EPC capture stent and the need to prolong at least for 6 months double antiplatelet therapy also in patients receiving this new stent. © 2008 Elsevier Ireland Ltd. All rights reserved. Keywords: Angioplasty; Endothelial progenitor cell capture stent; Late stent thrombosis; Clopidogrel
1. Case report In December 2007 a 71-year-old man underwent coronary angiography in an Italian high volume university hospital to assess the perioperative risk from acute coronary disease with a view to a lobectomy for primary lung cancer. The patient with a history of hypertension and hyperlipidemia, had a scintigraphic presence of inducing myocardial ischemia. Coronary angiogram showed presence of two vessel coronary artery disease (CAD) with severe stenoses of the mid- and distal left anterior descending coronary artery (LAD), second diagonal (D2), and right posterior descending artery (PDA). Immediately after the ⁎ Corresponding author. Unità Operativa di Emodinamica e Cardiologia Invasiva, Istituto Clinico Humanitas, Via Manzoni 56, 20089 Rozzano, Milan, Italy. Tel.: +39 0282243601; fax: +39 0282244691. E-mail address: [email protected] (M.L. Rossi). 0167-5273/$ - see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2008.11.134
angiogram percutaneous coronary intervention (PCI) was planned. The 2 lesions in LAD were treated with the endothelial progenitor cell (EPC) capture stents on the mid-proximal (2.5 × 23 mm and 2.5× 13 mm Genous stent; OrbusNeich, Fort Lauderdale, FL) and the distal tract (2.5 × 13 mm Genous stent). Simple balloon angioplasty was performed on D2, followed by kissing balloon inflation of LAD/D2. After LAD PCI, a nonocclusive dissection of the left main coronary artery (LM) occurred. Thus a bare metal stent was used to correct the dissection (3.5 × 18 mm Driver stent; Medtronic) because a suitable EPC capture stent size was not available. The patient was discharged with the recommendation to take dual antiplatelet therapy with aspirin and clopidogrel for 2 months. In January 2008 the patient was re-admitted to the same hospital with effort angina. A coronary angiogram showed patency of the previously implanted stent and a new critical stenosis of the mid-LAD, between the stents previously implanted in the
M.L. Rossi et al. / International Journal of Cardiology 141 (2010) e20–e22
e21
Fig. 1. Proximal LAD EPC capture stent thrombotic occlusion.
Fig. 3. IVUS cross-section of proximal LAD after thrombectomy showing the undersizing EPC capture stent.
mid-proximal and distal LAD. A PCI was performed with an EPC capture stent on the mid-LAD (2.5 × 13 Genous stent). A PCI was also performed on the PDA using an EPC capture stent (2.5 × 18 Genous stent). Clopidogrel was given for 2 months after stent implantation. Coronary angiography performed 1 month later, in February 2008, showed no stenosis at the stent site and clopidogrel was stopped thereafter. The patient subsequently underwent pulmonary lobectomy. Aspirin was discontinued a few days before and re-started 3 days after the operation. In May 2008 the patient was admitted to our emergency room with chest pain and dyspnea. ECG showed ST segment elevation in the antero-lateral leads. The patient was immediately transferred to the cardiac catheterization laboratory and the angiogram documented a proximal LAD EPC capture stent thrombotic occlusion (156 days after stenting). The stents on the LM and PDA were patent (Fig. 1).
After thrombectomy the re-opening of the LAD was obtained. Angiography showed lumen filling defect at the stent site, a severe restenosis of the EPC capture stent previously placed in the distal LAD tract and a restenosis of D2 previously treated with balloon angioplasty (Fig. 2). Intravascular ultrasound (IVUS) showed undersizing of the previously-deployed stent in the proximal LAD tract (in which we found the in-stent thrombosis), without in-stentneo-intimal hyperplasia (Fig. 3). IVUS showed complete apposition of the distal LAD stent with re-stenosis. The undersized stent was successfully postdilated using a 3.0 × 15 mm balloon. Subsequent IVUS showed complete apposition of the deployed stent. Adjunctive balloon dilatation of distal LAD in-stent restenosis as well as on D2 was performed. Due to dissection of D2 after balloon inflation, a paclitaxel eluting stent (2.25 × 20 mm Taxus stent; Boston
Fig. 2. Restenosis of the EPC capture stent in the distal LAD tract.
Fig. 4. Final results after PCI of the proximal and distal LAD and D2.
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M.L. Rossi et al. / International Journal of Cardiology 141 (2010) e20–e22
Scientific) was placed. Optimal result with restoration of normal (TIMI 3) flow on LCA was obtained (Fig. 4). A periprocedural intravenous bolus of abciximab followed by 12 h infusion was given. 2. Discussion Percutaneous coronary intervention (PCI) with drug eluting stent (DES) is now becoming the predominant revascularization strategy for coronary artery disease because of their favorable effects on clinical and angiographic outcomes. Although late stent thrombosis (LST) is present in both bare metal stent (BMS) and DES [1], there is a concern that DES might lead to higher rates of LST [2]. Delayed endothelialization of DES seems to be implicated in the pathophysiology of LST and it is seen as one of the most important limitations of these devices also because of the need of prolonged double antiplatelet therapy. Such therapy creates a problem for the clinician when a patient with DES implantation needs noncardiac surgery that cannot be delayed several months as recommended [3]: in these cases the withdrawal of antiplatelet agents may be followed by stent thrombosis. On the other hand, when the antiplatelet therapy is continued it may be associated with perioperative bleeding complications. The endothelial progenitor cell (EPC) capture stent is a new stainless steel coronary stent coated with murine monoclonal antihuman CD34 antibodies. It is designed to attract circulating EPCs by the antibodies immobilized on the stent surface rapidly promoting healing. It has been demonstrated that after implantation of this device a functional endothelial layer is established in 24–48 h [4]. Early surface endothelialization should reduce the processes leading to thrombosis and restenosis. For these reasons the double antiplatelet therapy is rapidly discontinued by stopping the clopidogrel 1 or 2 months after EPC capture stent implantation. This is the first report of LST of endothelial progenitor cell (EPC) capture stent. A failure to form a complete neointimal layer over the stent seems not to be the cause of LST in this case. However, as previously demonstrated, the return of endothelial function after the endothelial surface disruption due to stent deployment may take up to 6 months [5].
The physiologic alterations underlying the endothelial dysfunction associated with clopidogrel withdrawal might be at the base of LST. Notwithstanding, we cannot exclude that the reduction in flow through the undersized stent, together with a distal critical in-stent re-stenosis and the discontinuation of clopidogrel acted as primum movens for the LST. In this setting, the use of IVUS in evaluating the vessel size prior and after stent implantation appears pivotal also using this new device as every kind of DES. The present case report raises the question about the need to prolong (at least 6 month) double antiplatelet therapy also in patient receiving the EPC capture stent. Larger randomized studies will assess the safety of this new device and the opportunity to discontinue double antiplatelet therapy prematurely. Acknowledgement The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [6]. References [1] Park DW, Park SW, Lee SW, et al. Frequency of coronary arterial Late Angiographic Stent Thrombosis (LAST) in the first six months: outcomes with drug-eluting stents versus bare metal stents. Am J Cardiol 2007;99:774–8. [2] Stettler C, Wandel S, Allemann S, et al. Outcomes associated with drugeluting and bare-metal stents: a collaborative network meta-analysis. Lancet 2007;370:937–48. [3] Fleisher LA, Beckman JA, Brown KA, et al. ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2007;116: e418–99. [4] Kutryk MJ, Kuliszewski MA. In vivo endothelial progenitor cell seeding for the accelerated endothelialization of endovascular devices. Am J Cardiol 2003;92:94 L. [5] Caramori PR, Lima VC, Seidelin PH, et al. Long-term endothelial dysfunction after coronary artery stenting. J Am Coll Cardiol 1999 Nov 15;34(6):1675–9. [6] Coats AS. Ethical authorship and publishing. Int J Cardiol 2009;131: 149–50.