Heart Vessels DOI 10.1007/s00380-013-0464-5
CASE REPORT
Bioresorbable scaffolds for the treatment of in-stent restenosis Oliver Do¨rr • Christoph Liebetrau • Jens Wiebe • Franziska Hecker Johannes Rixe • Helge Mo¨llmann • Christian Hamm • Holger Nef
•
Received: 19 June 2013 / Accepted: 27 December 2013 Ó Springer Japan 2014
Abstract Percutaneous coronary intervention with baremetal stents or drug-eluting stents can decrease clinical event rates compared with simple balloon angioplasty. However, stent implantation is often associated with subsequent restenosis. Bioresorbable coronary scaffolds provide short-term vessel scaffolding with drug delivery capability and are designed to avoid the long-term limitations of metallic stents such as late stent thrombosis and instent restenosis. To the best of our knowledge, we report the first case series of successful treatment of in-stent restenosis using bioresorbable scaffolds.
target vascular revascularization are still very high, especially in saphenous vein grafts [5]. Bioresorbable coronary scaffolds provide short-term vessel scaffolding with drug delivery capability and are designed to avoid the long-term limitations of metallic stents such as late stent thrombosis and in-stent restenosis (ISR) [6, 7]. We report a case series of three successful bioresorbable scaffold implantations for the treatment of ISR.
Case 1 Keywords restenosis
Bioresorbable coronary scaffolds In-stent
Background Percutaneous coronary intervention (PCI) with bare-metal stents (BMS) or drug-eluting stents (DES) can decrease clinical event rates compared with simple balloon angioplasty [1, 2]. However, stent implantation is often associated with subsequent restenosis, which is also attributed to neointimal proliferation [3, 4]. Currently, PCI using drugeluting balloons or DES is the most accepted approach for treating in-stent restenosis. However, the rates of repeated O. Do¨rr (&) J. Wiebe F. Hecker J. Rixe C. Hamm H. Nef Department of Cardiology, University of Giessen, Klinikstr. 33, 35392 Giessen, Germany e-mail: [email protected] C. Liebetrau H. Mo¨llmann C. Hamm Department of Cardiology, Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany
A 71-year-old man with known coronary artery disease (CAD) and chronic heart failure [left ventricular ejection fraction (LVEF): 25 %] presented to the Chest Pain Unit (CPU) because of worsening angina pectoris (CCS III). Electrocardiography showed ST-segment depressions in the V3-6 precordial leads, and cardiac troponin I was elevated (cTnI: 2.14 lg/l). Therefore, coronary angiography was performed immediately. Coronary angiography revealed significant ISR within a BMS (CoroFlex Blue 3.0/16 mm) of the left coronary artery (LAD) that had been implanted 2 years earlier (Fig. 1a). The ISR was visualized with optical coherence tomography (OCT: mean lumen area: 2.7 mm [2]; minimal lumen area: 1.5 mm [2]). PCI was performed via the right femoral artery using a six French-guiding catheter. First, pre-dilatation of the ISR was performed (Apex 3.0/20 mm, Boston Scientific, USA) and the lesion was visualized with OCT (Fig. 1b). A polylactate bioabsorbable coronary scaffold of 3.0/28 mm with 12 atm (ABSORB, Abbott Vascular, CA, USA) was then implanted within the BMS (Fig. 2a–b). Finally, an OCT was conducted, confirming an excellent apposition of the scaffold struts inside of the
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Heart Vessels Fig. 1 a Coronary angiography of the left coronary artery showing the in-stent restenosis (ISR) of a bare-metal stent (BMS) in the LAD. b OCT imaging of the ISR
Fig. 2 a Implantation of a bioresorbable coronary scaffold (3.0/28 mm) within the BMS. b Angiographic result after scaffold in-stent implantation. c, d OCT showing the scaffold strut apposition
BMS (mean lumen area: 6.8 mm [2], minimal lumen area: 6.4 mm [2]; mean scaffold area: 5.2 mm [2], minimal scaffold area: 4.6 mm [2]) (Fig. 2c–d). Dual antiplatelet therapy with acetylsalicylic acid and ticagrelor was recommended for 12 months after PCI. The patient was discharged from the hospital 5 days after the procedure in a good general condition.
Case 2 A 73-year-old man with a known two-vessel CAD, acute myocardial infarction 4 months previously, and arterial
123
hypertension presented to the CPU because of worsening angina pectoris (CCS III) and dyspnea. Nothing abnormal was detected by electrocardiography and echocardiography on admission. Laboratory measurements showed normal values for cardiac troponin I. The exercise stress test displayed no pathological changes. Based on his remaining clinical symptoms and medical history, coronary angiography was performed. Invasive coronary angiography showed a significant ISR within a DES (3.0/24 mm, Resolute Integrity, Medtronic, USA) at the mid-part of the circumflex coronary artery (Cx) that had been implanted 4 months earlier (Fig. 3a). OCT visualized the significance of the ISR (OCT: mean
Heart Vessels Fig. 3 a Coronary angiography of an ISR in a DES of the circumflex coronary artery. b The ISR visualized by OCT
Fig. 4 a Angiographic result after scaffold in-stent implantation. b In-stent scaffold strut apposition visualized by OCT
lumen area: 2.2 mm [2]; minimal lumen area: 1.7 mm [2]) (Fig. 3b). PCI was conducted via the right femoral artery using a six French-guiding catheter. First, pre-dilatation of the ISR was performed (Apex Monorail 2.5/15 mm, Boston Scientific; USA). Thereafter, a polylactate bioresorbable coronary scaffold (3.0/28 mm ABSORB, Abbott Vascular, CA, USA) was implanted within the metallic stent with 14 atm (Fig. 3c). The OCT performed postimplantation showed good apposition of the scaffold struts within the metallic stent (mean lumen area: 6.9 mm [2], minimal lumen area: 6.2 mm [2]; mean scaffold area: 4.9 mm [2], minimal scaffold area: 4.4 mm [2]) (Fig. 4a– b). Dual antiplatelet therapy with acetylsalicylic acid, and prasugrel was recommended for 12 months after PCI. The echocardiographic follow-up showed good regional left ventricular function without any regional wall motion
abnormalities. The patient was discharged from hospital 7 days after the procedure and was free of any symptoms.
Case 3 A 57-year-old man with a known three-vessel CAD presented to the CPU with unstable angina pectoris (CCS IV). The patient had undergone coronary artery bypass surgery 5 years previously and a PCI with DES implantation in a saphenous vein graft to the right coronary artery (RCA) 10 months previously. Echocardiography showed a moderately reduced LVEF (40 %). Invasive coronary angiography showed a significant ISR in the DES (3.0/26 mm. Resolute Integrity, Medtronic, USA) of the saphenous vein graft to the distal
123
Heart Vessels Fig. 5 a Angiography of ISR in a DES of the saphenous vein graft to the distal RCA. b Angiographic result after scaffold in-stent implantation
RCA (Fig. 5a). PCI was performed via the left femoral artery using a six French-guiding catheter. Pre-dilatation of the ISR was performed (2.0/30 mm Quantum Maveric Balloon Catheter, Boston Scientific, USA). After visual estimation, a polylactate bioresorbable coronary scaffold (3.0/28 mm ABSORB, Abbott Vascular, CA, USA) was implanted within the metallic DES. A final angiography confirmed good apposition of the scaffold struts to the vessel wall (Fig. 5b). Dual antiplatelet therapy with acetylsalicylic acid and ticagrelor was recommended for 12 months after PCI. The rest of the patient’s clinical stay was without any clinical events, and he was discharged from the hospital 5 days post-procedure.
Discussion To the best of our knowledge, we report here the first case series of successful treatment of ISR using bioresorbable scaffolds. The use of DES significantly reduced the rates of major acute coronary events and target vascular revascularization (TVR) as well as the rate of ISR compared with BMS [1, 2]. However, ISR in particular is a major challenge for interventional cardiologists. After treatment of ISR by balloon angioplasty using conventional and drugeluting balloons (DEB), BMS, or DES implantation, a high rate of subsequent restenosis has been reported [7]. However, the reduced neointimal proliferation after DES implantation is associated with an increased incidence of uncovered struts. Consequently, the lack of tissue coverage was shown to trigger platelet activation around the uncovered struts, and has been reported to be a risk factor for late stent thrombosis [7]. In this case series, we decided to perform a ‘‘first-inman’’ treatment for ISR with bioresorbable scaffolds. From
123
a theoretical standpoint, this might be of potential advantage for two reasons: Firstly, when compared with a DEB, a bioresorbable coronary scaffold provides prolonged drug delivery capability. In detail, the average drug delivery time of DEBs is \60 s compared with a release rate of 80 % over 30 days (Everolimus-Eluting Scaffold: Abbott Vascular, Santa Clara, USA). Most DEBs are coated with paclitaxel; however, the superiority of sirolimus and everolimus was reported in several clinical trials, which might be an additional advantage of everolimus-eluting bioresorbable scaffolds for this specific indication. In addition, the scaffold struts provide vessel scaffolding at the edge of the former stent, which is also not provided by DEBs. Finally, the excellent scaffold apposition was confirmed by OCT in this case series. Secondly, 2 years after bioresorbable scaffold implantation the device is expected to be completely resorbed [1, 2]. Overall, the use of fully resorbable scaffolds is feasible in this specific indication for treatment of ISR. However, randomized trials are needed to evaluate the specific advantages of ISR treatment with bioresorbable coronary scaffolds, and follow-up data must be obtained to confirm the advantages of these devices. Acknowledgments
All authors have nothing to disclose.
References 1. Stone G, Moses J, Ellis S, Schofer J, Dawkins K, Morice M, Colombo A, Schampert E, Grube E, Kirtane A, Cutlip D, Fahy M, Pocock S, Mehran R, Leon M (2007) Safety and efficacy of sirolimus and paclitaxel eluting coronary stents. N Engl J Med 356:998–1008 2. Morice M, Serruys P, Sousa J, Fajadet J, Hayashi E, Perin M, Colombo A, Schuler G, Barragan P, Guagliumi G, Molnar F, Falotico R (2002) A randomised comparison of a sirolimus-eluting
Heart Vessels
3.
4.
5.
6.
stent with a standard stent for coronary revascularization. N Engl J Med 346:1773–1780 Otsuka Y, Nakamura M, Kokubu N, Tonooka A, Inoue K, Higami T (2012) Diffuse in-stent restenosis of CYPHERÒ stent due to hypersensitivity reaction confirmed by pathohistological findings. Heart Vessels 27(1):110–113 Ikuta S, Kobuke K, Iwanaga Y, Nakauchi Y, Yamaji K, Miyazaki S (2013) Difference in neointimal coverage at chronic stage between bare metal stent and sirolimus-eluting stent evaluated at stent-strut level by optical coherence tomography. Heart Vessels. doi:10.1007/s00380-013-0376-4 Barbash IM, Waksman R (2011) Current status, challenges and future directions of drug-eluting balloons. Future Cardiol 7:765–774 Diletti R, Farooq V, Girasis C, Bourantas C, Onuma Y, Heo JH, Gogas BD, van Geuns RJ, Regar E, de Bruyne B, Dudek D,
Thuesen L, Chevalier B, McClean D, Windecker S, Whitbourn RJ, Smits P, Koolen J, Meredith I, Li X, Miquel-Hebert K, Veldhof S, Garcia-Garcia HM, Ormiston JA, Serruys PW (2013) Clinical and intravascular imaging outcomes at 1 and 2 years after implantation of absorb everolimus eluting bioresorbable vascular scaffolds in small vessels. Late lumen enlargement: does bioresorption matter with small vessel size? Insight from the ABSORB cohort B trial. Heart 99(2):98–105 7. Serruys PW, Ormiston JA, Onuma Y, Regar E, Gonzalo N, GarciaGarcia HM, Nieman K, Bruining N, Dorange C, Miquel-He´bert K, Veldhof S, Webster M, Thuesen L, Dudek D (2009) A bioabsorbable everolimus-eluting coronary stentsystem (ABSORB): 2-year outcomes and results from multiple imaging methods. Lancet 373:897–910
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CASE REPORT
Bioresorbable scaffolds for the treatment of in-stent restenosis Oliver Do¨rr • Christoph Liebetrau • Jens Wiebe • Franziska Hecker Johannes Rixe • Helge Mo¨llmann • Christian Hamm • Holger Nef
•
Received: 19 June 2013 / Accepted: 27 December 2013 Ó Springer Japan 2014
Abstract Percutaneous coronary intervention with baremetal stents or drug-eluting stents can decrease clinical event rates compared with simple balloon angioplasty. However, stent implantation is often associated with subsequent restenosis. Bioresorbable coronary scaffolds provide short-term vessel scaffolding with drug delivery capability and are designed to avoid the long-term limitations of metallic stents such as late stent thrombosis and instent restenosis. To the best of our knowledge, we report the first case series of successful treatment of in-stent restenosis using bioresorbable scaffolds.
target vascular revascularization are still very high, especially in saphenous vein grafts [5]. Bioresorbable coronary scaffolds provide short-term vessel scaffolding with drug delivery capability and are designed to avoid the long-term limitations of metallic stents such as late stent thrombosis and in-stent restenosis (ISR) [6, 7]. We report a case series of three successful bioresorbable scaffold implantations for the treatment of ISR.
Case 1 Keywords restenosis
Bioresorbable coronary scaffolds In-stent
Background Percutaneous coronary intervention (PCI) with bare-metal stents (BMS) or drug-eluting stents (DES) can decrease clinical event rates compared with simple balloon angioplasty [1, 2]. However, stent implantation is often associated with subsequent restenosis, which is also attributed to neointimal proliferation [3, 4]. Currently, PCI using drugeluting balloons or DES is the most accepted approach for treating in-stent restenosis. However, the rates of repeated O. Do¨rr (&) J. Wiebe F. Hecker J. Rixe C. Hamm H. Nef Department of Cardiology, University of Giessen, Klinikstr. 33, 35392 Giessen, Germany e-mail: [email protected] C. Liebetrau H. Mo¨llmann C. Hamm Department of Cardiology, Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany
A 71-year-old man with known coronary artery disease (CAD) and chronic heart failure [left ventricular ejection fraction (LVEF): 25 %] presented to the Chest Pain Unit (CPU) because of worsening angina pectoris (CCS III). Electrocardiography showed ST-segment depressions in the V3-6 precordial leads, and cardiac troponin I was elevated (cTnI: 2.14 lg/l). Therefore, coronary angiography was performed immediately. Coronary angiography revealed significant ISR within a BMS (CoroFlex Blue 3.0/16 mm) of the left coronary artery (LAD) that had been implanted 2 years earlier (Fig. 1a). The ISR was visualized with optical coherence tomography (OCT: mean lumen area: 2.7 mm [2]; minimal lumen area: 1.5 mm [2]). PCI was performed via the right femoral artery using a six French-guiding catheter. First, pre-dilatation of the ISR was performed (Apex 3.0/20 mm, Boston Scientific, USA) and the lesion was visualized with OCT (Fig. 1b). A polylactate bioabsorbable coronary scaffold of 3.0/28 mm with 12 atm (ABSORB, Abbott Vascular, CA, USA) was then implanted within the BMS (Fig. 2a–b). Finally, an OCT was conducted, confirming an excellent apposition of the scaffold struts inside of the
123
Heart Vessels Fig. 1 a Coronary angiography of the left coronary artery showing the in-stent restenosis (ISR) of a bare-metal stent (BMS) in the LAD. b OCT imaging of the ISR
Fig. 2 a Implantation of a bioresorbable coronary scaffold (3.0/28 mm) within the BMS. b Angiographic result after scaffold in-stent implantation. c, d OCT showing the scaffold strut apposition
BMS (mean lumen area: 6.8 mm [2], minimal lumen area: 6.4 mm [2]; mean scaffold area: 5.2 mm [2], minimal scaffold area: 4.6 mm [2]) (Fig. 2c–d). Dual antiplatelet therapy with acetylsalicylic acid and ticagrelor was recommended for 12 months after PCI. The patient was discharged from the hospital 5 days after the procedure in a good general condition.
Case 2 A 73-year-old man with a known two-vessel CAD, acute myocardial infarction 4 months previously, and arterial
123
hypertension presented to the CPU because of worsening angina pectoris (CCS III) and dyspnea. Nothing abnormal was detected by electrocardiography and echocardiography on admission. Laboratory measurements showed normal values for cardiac troponin I. The exercise stress test displayed no pathological changes. Based on his remaining clinical symptoms and medical history, coronary angiography was performed. Invasive coronary angiography showed a significant ISR within a DES (3.0/24 mm, Resolute Integrity, Medtronic, USA) at the mid-part of the circumflex coronary artery (Cx) that had been implanted 4 months earlier (Fig. 3a). OCT visualized the significance of the ISR (OCT: mean
Heart Vessels Fig. 3 a Coronary angiography of an ISR in a DES of the circumflex coronary artery. b The ISR visualized by OCT
Fig. 4 a Angiographic result after scaffold in-stent implantation. b In-stent scaffold strut apposition visualized by OCT
lumen area: 2.2 mm [2]; minimal lumen area: 1.7 mm [2]) (Fig. 3b). PCI was conducted via the right femoral artery using a six French-guiding catheter. First, pre-dilatation of the ISR was performed (Apex Monorail 2.5/15 mm, Boston Scientific; USA). Thereafter, a polylactate bioresorbable coronary scaffold (3.0/28 mm ABSORB, Abbott Vascular, CA, USA) was implanted within the metallic stent with 14 atm (Fig. 3c). The OCT performed postimplantation showed good apposition of the scaffold struts within the metallic stent (mean lumen area: 6.9 mm [2], minimal lumen area: 6.2 mm [2]; mean scaffold area: 4.9 mm [2], minimal scaffold area: 4.4 mm [2]) (Fig. 4a– b). Dual antiplatelet therapy with acetylsalicylic acid, and prasugrel was recommended for 12 months after PCI. The echocardiographic follow-up showed good regional left ventricular function without any regional wall motion
abnormalities. The patient was discharged from hospital 7 days after the procedure and was free of any symptoms.
Case 3 A 57-year-old man with a known three-vessel CAD presented to the CPU with unstable angina pectoris (CCS IV). The patient had undergone coronary artery bypass surgery 5 years previously and a PCI with DES implantation in a saphenous vein graft to the right coronary artery (RCA) 10 months previously. Echocardiography showed a moderately reduced LVEF (40 %). Invasive coronary angiography showed a significant ISR in the DES (3.0/26 mm. Resolute Integrity, Medtronic, USA) of the saphenous vein graft to the distal
123
Heart Vessels Fig. 5 a Angiography of ISR in a DES of the saphenous vein graft to the distal RCA. b Angiographic result after scaffold in-stent implantation
RCA (Fig. 5a). PCI was performed via the left femoral artery using a six French-guiding catheter. Pre-dilatation of the ISR was performed (2.0/30 mm Quantum Maveric Balloon Catheter, Boston Scientific, USA). After visual estimation, a polylactate bioresorbable coronary scaffold (3.0/28 mm ABSORB, Abbott Vascular, CA, USA) was implanted within the metallic DES. A final angiography confirmed good apposition of the scaffold struts to the vessel wall (Fig. 5b). Dual antiplatelet therapy with acetylsalicylic acid and ticagrelor was recommended for 12 months after PCI. The rest of the patient’s clinical stay was without any clinical events, and he was discharged from the hospital 5 days post-procedure.
Discussion To the best of our knowledge, we report here the first case series of successful treatment of ISR using bioresorbable scaffolds. The use of DES significantly reduced the rates of major acute coronary events and target vascular revascularization (TVR) as well as the rate of ISR compared with BMS [1, 2]. However, ISR in particular is a major challenge for interventional cardiologists. After treatment of ISR by balloon angioplasty using conventional and drugeluting balloons (DEB), BMS, or DES implantation, a high rate of subsequent restenosis has been reported [7]. However, the reduced neointimal proliferation after DES implantation is associated with an increased incidence of uncovered struts. Consequently, the lack of tissue coverage was shown to trigger platelet activation around the uncovered struts, and has been reported to be a risk factor for late stent thrombosis [7]. In this case series, we decided to perform a ‘‘first-inman’’ treatment for ISR with bioresorbable scaffolds. From
123
a theoretical standpoint, this might be of potential advantage for two reasons: Firstly, when compared with a DEB, a bioresorbable coronary scaffold provides prolonged drug delivery capability. In detail, the average drug delivery time of DEBs is \60 s compared with a release rate of 80 % over 30 days (Everolimus-Eluting Scaffold: Abbott Vascular, Santa Clara, USA). Most DEBs are coated with paclitaxel; however, the superiority of sirolimus and everolimus was reported in several clinical trials, which might be an additional advantage of everolimus-eluting bioresorbable scaffolds for this specific indication. In addition, the scaffold struts provide vessel scaffolding at the edge of the former stent, which is also not provided by DEBs. Finally, the excellent scaffold apposition was confirmed by OCT in this case series. Secondly, 2 years after bioresorbable scaffold implantation the device is expected to be completely resorbed [1, 2]. Overall, the use of fully resorbable scaffolds is feasible in this specific indication for treatment of ISR. However, randomized trials are needed to evaluate the specific advantages of ISR treatment with bioresorbable coronary scaffolds, and follow-up data must be obtained to confirm the advantages of these devices. Acknowledgments
All authors have nothing to disclose.
References 1. Stone G, Moses J, Ellis S, Schofer J, Dawkins K, Morice M, Colombo A, Schampert E, Grube E, Kirtane A, Cutlip D, Fahy M, Pocock S, Mehran R, Leon M (2007) Safety and efficacy of sirolimus and paclitaxel eluting coronary stents. N Engl J Med 356:998–1008 2. Morice M, Serruys P, Sousa J, Fajadet J, Hayashi E, Perin M, Colombo A, Schuler G, Barragan P, Guagliumi G, Molnar F, Falotico R (2002) A randomised comparison of a sirolimus-eluting
Heart Vessels
3.
4.
5.
6.
stent with a standard stent for coronary revascularization. N Engl J Med 346:1773–1780 Otsuka Y, Nakamura M, Kokubu N, Tonooka A, Inoue K, Higami T (2012) Diffuse in-stent restenosis of CYPHERÒ stent due to hypersensitivity reaction confirmed by pathohistological findings. Heart Vessels 27(1):110–113 Ikuta S, Kobuke K, Iwanaga Y, Nakauchi Y, Yamaji K, Miyazaki S (2013) Difference in neointimal coverage at chronic stage between bare metal stent and sirolimus-eluting stent evaluated at stent-strut level by optical coherence tomography. Heart Vessels. doi:10.1007/s00380-013-0376-4 Barbash IM, Waksman R (2011) Current status, challenges and future directions of drug-eluting balloons. Future Cardiol 7:765–774 Diletti R, Farooq V, Girasis C, Bourantas C, Onuma Y, Heo JH, Gogas BD, van Geuns RJ, Regar E, de Bruyne B, Dudek D,
Thuesen L, Chevalier B, McClean D, Windecker S, Whitbourn RJ, Smits P, Koolen J, Meredith I, Li X, Miquel-Hebert K, Veldhof S, Garcia-Garcia HM, Ormiston JA, Serruys PW (2013) Clinical and intravascular imaging outcomes at 1 and 2 years after implantation of absorb everolimus eluting bioresorbable vascular scaffolds in small vessels. Late lumen enlargement: does bioresorption matter with small vessel size? Insight from the ABSORB cohort B trial. Heart 99(2):98–105 7. Serruys PW, Ormiston JA, Onuma Y, Regar E, Gonzalo N, GarciaGarcia HM, Nieman K, Bruining N, Dorange C, Miquel-He´bert K, Veldhof S, Webster M, Thuesen L, Dudek D (2009) A bioabsorbable everolimus-eluting coronary stentsystem (ABSORB): 2-year outcomes and results from multiple imaging methods. Lancet 373:897–910
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