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An unusual case of acute coronary syndrome late after stent implantation
Journal of Cardiology Cases (2012) 5, e143—e146
Available online at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/jccase
Case Report
An unusual case of acute coronary syndrome late after stent implantation Riccardo Gorla (MD) ∗, Andrea Macchi (MD), Irene Franzoni (MD), Isabella Rosa (MD), Fabio Buzzetti (MD), Maria Cristina Pedrigi (MD), Alberto Margonato (MD) Cardiology and Coronary Intensive Care Unit, San Raffaele Hospital, Milan, Italy Received 5 September 2011; received in revised form 13 February 2012; accepted 9 March 2012
KEYWORDS Acute coronary syndrome; Very late stent thrombosis; Neoatherosclerosis
Summary We report a case of a 66-year-old Caucasian male who presented to our department with unstable angina in July 2011. He had a medical history of trivessel coronary artery disease and underwent several percutaneous coronary interventions (2003, 2004, and 2006). The latest coronary angiography, performed in January 2011, showed mild intimal hyperplasia within the proximal left anterior descending segment, treated with a sirolimus-eluting stent in 2003. On admission, electrocardiogram was positive for a recent acute coronary syndrome, so the patient underwent coronary angiography, which showed proximal left anterior descending stent thrombosis, occurred eight years after drug-eluting stent implantation. Intravascular ultrasound revealed a soft plaque rupture within the stented segment, which was the cause of stent thrombosis. So the lack of endothelialization over stent struts is not the only mechanism determining acute coronary syndromes late after stent implantation. In-stent neoatherosclerosis, frequently disregarded, is another possible actor especially of very late thrombotic events. However, the pathogenesis of this phenomenon has not been clearly established. © 2012 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
Introduction Drug-eluting stents (DES) are thought to be superior to baremetal stents (BMS) in reducing restenosis rates. However, due to the use of this technology, stent thrombosis, the most
∗ Corresponding author at: Cardiology and Coronary Intensive Care Unit, San Raffaele Hospital, via Olgettina 60, 20132 Milan, Italy. Tel.: +39 02 26437752; fax: +39 02 93291315. E-mail address: [email protected] (R. Gorla).
dangerous complication of DES, has been reported more frequently in recent times [1,2]. The main mechanism is known to be the lack of complete endothelialization over stent struts and is considered to be responsible for most acute coronary syndromes late after percutaneous coronary intervention (PCI). However, in-stent neoatherosclerosis, frequently disregarded, could be another possible actor of some late and very late thrombotic events. The present case report describes a very late stent thrombosis caused by a soft plaque rupture within the stented segment eight years after DES implantation.
1878-5409/$ — see front matter © 2012 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jccase.2012.03.005
e144
Figure 1 Coronary angiography showing mild intimal hyperplasia (arrow) within the proximal left anterior descending stented segment.
Case report A 66-year-old Caucasian male with hypertension, a family history of coronary artery disease, and former smoker was referred to our department for a clinical evaluation for unstable angina in July 2011. He had a medical history of trivessel coronary artery disease and underwent several PCIs with DES implantation of proximal left anterior descending artery (2003), proximal circumflex artery (2004), and medium-distal right coronary artery (2006). The latest coronary angiography was performed in January 2011 and showed mild intimal hyperplasia within the proximal left anterior descending stented segment (Fig. 1), which had been treated with a sirolimus-eluting stent in 2003.
R. Gorla et al.
Figure 2 Coronary angiography showing an intrastent proximal left anterior descending subocclusion (arrow).
On admission to our department, the patient related that he had been suffering from unstable angina for two weeks, with an episode at rest. The electrocardiogram was positive for a recent acute coronary syndrome. The following day, the patient underwent coronary angiography which showed an intrastent proximal left anterior descending subocclusion (Fig. 2); intravascular ultrasound showed a soft plaque rupture with a thrombus localized only at the rupture site; the previous implanted stent did not appear to be not well expanded (Fig. 3A and B). We preferred to treat the patient with two everolimus-eluting stents (Promus Element 3.5 mm × 20 mm and 3 mm × 20 mm; Boston Scientific, Natick, MA, USA) because of the high prognostic value of the left anterior descending proximal tract, in order to reduce the risk of restenosis as much as possible. After 3 months, the patient was asymptomatic and underwent an exercise
Figure 3 (A and B) Intravascular ultrasound revealing a soft plaque rupture (arrows) within the stented segment, which determined stent thrombosis.
An unusual case of acute coronary syndrome late after stent implantation stress echocardiogram that resulted negative for inducible ischemia.
Discussion Late and very late stent thrombosis are important but rare complications of DES, occurring up to eight years after stent implantation. In fact, while these stents have reduced rates of restenosis and late lumen loss compared to BMS, late and very late stent thrombosis, a life-threatening complication of this technology, has emerged as a major concern [1,2]. The etiology is likely to be multifactorial and it is still not completely understood. However several risk factors have been investigated. Some of them are procedure-related factors such as stent under expansion, late malapposition, incomplete apposition, strut penetration into a necrotic core lesion, and arterial dissection. On the other hand, patient-related factors include diabetes, chronic renal failure, low left ventricular ejection fraction, and in-stent restenosis [3]. Moreover aspirin and clopidogrel resistance are emerging as major risk factors, which could be responsible for some thrombotic events. Bouman et al. have observed that early stent thrombosis was frequently associated with clopidogrel resistance while, especially in some cases of late stent thrombosis, aspirin or dual antiplatelet therapy resistance were more prevalent [4]. The pathophysiology of late and very late stent thrombosis is unclear, as well. The most recognized mechanism, as clinical imaging and autopsy studies confirmed, is the lack of complete endothelialization over stent struts, which in patients receiving DES is approximately 20% at 2 years [5]. Other well known mechanisms include local hypersensitivity reactions due to the polymers used in the manufacture of earlier generations of DES and extensive fibrin deposition, especially for first-generation DES [6]. However, in some cases, the real mechanism underlying late and very late stent thrombosis could be plaque rupture, determined by in-stent neoatherosclerosis. The incidence and type of this phenomenon have been only recently investigated with histologic studies by Nakazawa et al. [7]. These authors found a different underlying plaque morphology after implantation of DES and BMS: unstable lesions, such as thin-cap fibroatheromas and ruptured plaques were more frequent in DES, whereas fibrocalcific and pathological intimal thickening were more common in BMS. Moreover, the incidence of this phenomenon was different between DES and BMS, according to time after implantation. In fact, in less than 2 years span, DES had a greater incidence of any neoatherosclerosis (peri-strut foamy macrophage clusters and fibroatheromas) than BMS; between 2 and 6 years, DES still had a higher incidence of neoatherosclerosis, while after 6 years no significant differences were observed between the two devices. Unstable neoatherosclerotic lesions were identified in BMS > 5 years and in DES < 2 years and this could possibly explain some cases of late stent thrombotic events [5,7,8]. However, the underlying process responsible for the development of neoatherosclerosis after stent implantation is still unknown.
e145
Joner et al. hypothesized that it may involve the inability to maintain a fully functional endothelialized luminal surface within the stented segment. A possible reason of why neoatherosclerosis develops faster in DES than BMS could be related to drug effects, which damage the endothelial stem cells and create a proinflammatory environment, leading to monocyte adherence, subendothelial migration, and plaque formation [9]. Farb et al. suggest that neoatherosclerosis within stented segment is associated either with delayed arterial healing and lethal injury to smooth muscle cells and endothelial cells [10].
Conclusions The lack of endothelialization over stent struts is not the only mechanism determining acute coronary syndromes late after stent implantation. In-stent neoatherosclerosis is thought to be responsible especially for very late thrombotic events and its role has been demonstrated by histologic studies. Unfortunately, there is not a specific therapy for very late stent thrombosis prevention except for antiplatelet therapy continuation, which could be one of the leading causes of very late stent thrombosis [11]. This reminds us once again the importance of lifestyle changes and optimal medical therapy for the treatment of our patients and prevention of atherothrombotic disease progression.
References [1] Morice MC, Serruys PW, Sousa JE, Fajadet J, Ban Hayashi E, Perin M, Colombo A, Schuler G, Barragan P, Guagliumi G, Molnàr F, Falotico R. A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization. RAVEL Study Group. N Engl J Med 2002;346:1773—80. [2] Moses JW, Leon MB, Popma JJ, Fitzgerald PJ, Holmes DR, O’Shaughnessy C, Caputo RP, Kereiakes DJ, Williams DO, Teirstein PS, Jaeger JL, Kuntz RE, SIRIUS Investigators. Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N Engl J Med 2003;349:1315—23. [3] Panduranga P, Al-Mukhaini M. Very late stent thrombosis of sirolimus-eluting stent 59 months after implantation: a first report from the Middle-East and review of literature. Heart Views 2011;12:22—5. [4] Bouman HJ, van Werkum JW, Breet NJ, ten Cate H, Hackeng CM, ten Berg JM. A case—control study on platelet reactivity in patients with coronary stent thrombosis. J Thromb Haemost 2011;9:909—16. [5] Takano M, Yamamoto M, Xie Y, Murakami D, Inami S, Okamatsu K, Seimiya K, Ohba T, Seino Y, Mizuno K. Serial longterm evaluation of neointimal stent coverage and thrombus after sirolimus-eluting stent implantation by use of coronary angioscopy. Heart 2007;93:1353—6. [6] Nakazawa G. Stent thrombosis of drug eluting stent: pathological perspective. JACC 2011;58:84—91. [7] Nakazawa G, Otsuka F, Nakano M, Vorpahl M, Yazdani SK, Ladich E, Kolodgie FD, Finn AV, Virmani R. The pathology of neoatherosclerosis in human coronary implants: bare-metal and drug-eluting stents. JACC 2011;57:1314—22. [8] Virmani R, Kolodgie FD, Burke AP, Farb A, Schwartz SM. Lessons from sudden coronary death: a comprehensive morphological
e146 classification scheme for atherosclerotic lesions. Arterioscler Thromb Vasc Biol 2000;20:1262—75. [9] Joner M, Nakazawa G, Finn AV, Quee SC, Coleman L, Acampado E, Wilson PS, Skorija K, Cheng Q, Xu X, Gold HK, Kolodgie FD, Virmani R. Endothelial cell recovery between comparator polymer-based drug-eluting stents. JACC 2008;52: 333—42.
R. Gorla et al. [10] Farb A, Shroff S, John M, Sweet W, Virmani R. Late arterial responses (6 and 12 months) after (32)P beta-emitting stent placement: sustained intimal suppression with incomplete healing. Circulation 2001;103:1912—9. [11] Al-Dehneh A, Virk H, Alkhouri Y, Hamdan A, Bikkina M. Drugeluting stent thrombosis 1,659 days after stent deployment. Tex Heart Inst J 2010;37:343—6.
Available online at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/jccase
Case Report
An unusual case of acute coronary syndrome late after stent implantation Riccardo Gorla (MD) ∗, Andrea Macchi (MD), Irene Franzoni (MD), Isabella Rosa (MD), Fabio Buzzetti (MD), Maria Cristina Pedrigi (MD), Alberto Margonato (MD) Cardiology and Coronary Intensive Care Unit, San Raffaele Hospital, Milan, Italy Received 5 September 2011; received in revised form 13 February 2012; accepted 9 March 2012
KEYWORDS Acute coronary syndrome; Very late stent thrombosis; Neoatherosclerosis
Summary We report a case of a 66-year-old Caucasian male who presented to our department with unstable angina in July 2011. He had a medical history of trivessel coronary artery disease and underwent several percutaneous coronary interventions (2003, 2004, and 2006). The latest coronary angiography, performed in January 2011, showed mild intimal hyperplasia within the proximal left anterior descending segment, treated with a sirolimus-eluting stent in 2003. On admission, electrocardiogram was positive for a recent acute coronary syndrome, so the patient underwent coronary angiography, which showed proximal left anterior descending stent thrombosis, occurred eight years after drug-eluting stent implantation. Intravascular ultrasound revealed a soft plaque rupture within the stented segment, which was the cause of stent thrombosis. So the lack of endothelialization over stent struts is not the only mechanism determining acute coronary syndromes late after stent implantation. In-stent neoatherosclerosis, frequently disregarded, is another possible actor especially of very late thrombotic events. However, the pathogenesis of this phenomenon has not been clearly established. © 2012 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
Introduction Drug-eluting stents (DES) are thought to be superior to baremetal stents (BMS) in reducing restenosis rates. However, due to the use of this technology, stent thrombosis, the most
∗ Corresponding author at: Cardiology and Coronary Intensive Care Unit, San Raffaele Hospital, via Olgettina 60, 20132 Milan, Italy. Tel.: +39 02 26437752; fax: +39 02 93291315. E-mail address: [email protected] (R. Gorla).
dangerous complication of DES, has been reported more frequently in recent times [1,2]. The main mechanism is known to be the lack of complete endothelialization over stent struts and is considered to be responsible for most acute coronary syndromes late after percutaneous coronary intervention (PCI). However, in-stent neoatherosclerosis, frequently disregarded, could be another possible actor of some late and very late thrombotic events. The present case report describes a very late stent thrombosis caused by a soft plaque rupture within the stented segment eight years after DES implantation.
1878-5409/$ — see front matter © 2012 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jccase.2012.03.005
e144
Figure 1 Coronary angiography showing mild intimal hyperplasia (arrow) within the proximal left anterior descending stented segment.
Case report A 66-year-old Caucasian male with hypertension, a family history of coronary artery disease, and former smoker was referred to our department for a clinical evaluation for unstable angina in July 2011. He had a medical history of trivessel coronary artery disease and underwent several PCIs with DES implantation of proximal left anterior descending artery (2003), proximal circumflex artery (2004), and medium-distal right coronary artery (2006). The latest coronary angiography was performed in January 2011 and showed mild intimal hyperplasia within the proximal left anterior descending stented segment (Fig. 1), which had been treated with a sirolimus-eluting stent in 2003.
R. Gorla et al.
Figure 2 Coronary angiography showing an intrastent proximal left anterior descending subocclusion (arrow).
On admission to our department, the patient related that he had been suffering from unstable angina for two weeks, with an episode at rest. The electrocardiogram was positive for a recent acute coronary syndrome. The following day, the patient underwent coronary angiography which showed an intrastent proximal left anterior descending subocclusion (Fig. 2); intravascular ultrasound showed a soft plaque rupture with a thrombus localized only at the rupture site; the previous implanted stent did not appear to be not well expanded (Fig. 3A and B). We preferred to treat the patient with two everolimus-eluting stents (Promus Element 3.5 mm × 20 mm and 3 mm × 20 mm; Boston Scientific, Natick, MA, USA) because of the high prognostic value of the left anterior descending proximal tract, in order to reduce the risk of restenosis as much as possible. After 3 months, the patient was asymptomatic and underwent an exercise
Figure 3 (A and B) Intravascular ultrasound revealing a soft plaque rupture (arrows) within the stented segment, which determined stent thrombosis.
An unusual case of acute coronary syndrome late after stent implantation stress echocardiogram that resulted negative for inducible ischemia.
Discussion Late and very late stent thrombosis are important but rare complications of DES, occurring up to eight years after stent implantation. In fact, while these stents have reduced rates of restenosis and late lumen loss compared to BMS, late and very late stent thrombosis, a life-threatening complication of this technology, has emerged as a major concern [1,2]. The etiology is likely to be multifactorial and it is still not completely understood. However several risk factors have been investigated. Some of them are procedure-related factors such as stent under expansion, late malapposition, incomplete apposition, strut penetration into a necrotic core lesion, and arterial dissection. On the other hand, patient-related factors include diabetes, chronic renal failure, low left ventricular ejection fraction, and in-stent restenosis [3]. Moreover aspirin and clopidogrel resistance are emerging as major risk factors, which could be responsible for some thrombotic events. Bouman et al. have observed that early stent thrombosis was frequently associated with clopidogrel resistance while, especially in some cases of late stent thrombosis, aspirin or dual antiplatelet therapy resistance were more prevalent [4]. The pathophysiology of late and very late stent thrombosis is unclear, as well. The most recognized mechanism, as clinical imaging and autopsy studies confirmed, is the lack of complete endothelialization over stent struts, which in patients receiving DES is approximately 20% at 2 years [5]. Other well known mechanisms include local hypersensitivity reactions due to the polymers used in the manufacture of earlier generations of DES and extensive fibrin deposition, especially for first-generation DES [6]. However, in some cases, the real mechanism underlying late and very late stent thrombosis could be plaque rupture, determined by in-stent neoatherosclerosis. The incidence and type of this phenomenon have been only recently investigated with histologic studies by Nakazawa et al. [7]. These authors found a different underlying plaque morphology after implantation of DES and BMS: unstable lesions, such as thin-cap fibroatheromas and ruptured plaques were more frequent in DES, whereas fibrocalcific and pathological intimal thickening were more common in BMS. Moreover, the incidence of this phenomenon was different between DES and BMS, according to time after implantation. In fact, in less than 2 years span, DES had a greater incidence of any neoatherosclerosis (peri-strut foamy macrophage clusters and fibroatheromas) than BMS; between 2 and 6 years, DES still had a higher incidence of neoatherosclerosis, while after 6 years no significant differences were observed between the two devices. Unstable neoatherosclerotic lesions were identified in BMS > 5 years and in DES < 2 years and this could possibly explain some cases of late stent thrombotic events [5,7,8]. However, the underlying process responsible for the development of neoatherosclerosis after stent implantation is still unknown.
e145
Joner et al. hypothesized that it may involve the inability to maintain a fully functional endothelialized luminal surface within the stented segment. A possible reason of why neoatherosclerosis develops faster in DES than BMS could be related to drug effects, which damage the endothelial stem cells and create a proinflammatory environment, leading to monocyte adherence, subendothelial migration, and plaque formation [9]. Farb et al. suggest that neoatherosclerosis within stented segment is associated either with delayed arterial healing and lethal injury to smooth muscle cells and endothelial cells [10].
Conclusions The lack of endothelialization over stent struts is not the only mechanism determining acute coronary syndromes late after stent implantation. In-stent neoatherosclerosis is thought to be responsible especially for very late thrombotic events and its role has been demonstrated by histologic studies. Unfortunately, there is not a specific therapy for very late stent thrombosis prevention except for antiplatelet therapy continuation, which could be one of the leading causes of very late stent thrombosis [11]. This reminds us once again the importance of lifestyle changes and optimal medical therapy for the treatment of our patients and prevention of atherothrombotic disease progression.
References [1] Morice MC, Serruys PW, Sousa JE, Fajadet J, Ban Hayashi E, Perin M, Colombo A, Schuler G, Barragan P, Guagliumi G, Molnàr F, Falotico R. A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization. RAVEL Study Group. N Engl J Med 2002;346:1773—80. [2] Moses JW, Leon MB, Popma JJ, Fitzgerald PJ, Holmes DR, O’Shaughnessy C, Caputo RP, Kereiakes DJ, Williams DO, Teirstein PS, Jaeger JL, Kuntz RE, SIRIUS Investigators. Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N Engl J Med 2003;349:1315—23. [3] Panduranga P, Al-Mukhaini M. Very late stent thrombosis of sirolimus-eluting stent 59 months after implantation: a first report from the Middle-East and review of literature. Heart Views 2011;12:22—5. [4] Bouman HJ, van Werkum JW, Breet NJ, ten Cate H, Hackeng CM, ten Berg JM. A case—control study on platelet reactivity in patients with coronary stent thrombosis. J Thromb Haemost 2011;9:909—16. [5] Takano M, Yamamoto M, Xie Y, Murakami D, Inami S, Okamatsu K, Seimiya K, Ohba T, Seino Y, Mizuno K. Serial longterm evaluation of neointimal stent coverage and thrombus after sirolimus-eluting stent implantation by use of coronary angioscopy. Heart 2007;93:1353—6. [6] Nakazawa G. Stent thrombosis of drug eluting stent: pathological perspective. JACC 2011;58:84—91. [7] Nakazawa G, Otsuka F, Nakano M, Vorpahl M, Yazdani SK, Ladich E, Kolodgie FD, Finn AV, Virmani R. The pathology of neoatherosclerosis in human coronary implants: bare-metal and drug-eluting stents. JACC 2011;57:1314—22. [8] Virmani R, Kolodgie FD, Burke AP, Farb A, Schwartz SM. Lessons from sudden coronary death: a comprehensive morphological
e146 classification scheme for atherosclerotic lesions. Arterioscler Thromb Vasc Biol 2000;20:1262—75. [9] Joner M, Nakazawa G, Finn AV, Quee SC, Coleman L, Acampado E, Wilson PS, Skorija K, Cheng Q, Xu X, Gold HK, Kolodgie FD, Virmani R. Endothelial cell recovery between comparator polymer-based drug-eluting stents. JACC 2008;52: 333—42.
R. Gorla et al. [10] Farb A, Shroff S, John M, Sweet W, Virmani R. Late arterial responses (6 and 12 months) after (32)P beta-emitting stent placement: sustained intimal suppression with incomplete healing. Circulation 2001;103:1912—9. [11] Al-Dehneh A, Virk H, Alkhouri Y, Hamdan A, Bikkina M. Drugeluting stent thrombosis 1,659 days after stent deployment. Tex Heart Inst J 2010;37:343—6.