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Very late scaffold thrombosis after everolimus-eluting bioresorbable scaffold implantation in patients with unremarkable interim surveillance angiography
CARREV-01607; No of Pages 6 Cardiovascular Revascularization Medicine xxx (xxxx) xxx
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Cardiovascular Revascularization Medicine
Very late scaffold thrombosis after everolimus-eluting bioresorbable scaffold implantation in patients with unremarkable interim surveillance angiography Petra Hoppmann a, Himanshu Rai b, Roisin Colleran b, Sebastian Kufner b, Jens Wiebe b, Salvatore Cassese b, Michael Joner b,c, Karl-Ludwig Laugwitz a,c, Adnan Kastrati b,c, Robert A. Byrne b,c,⁎ a b c
Klinik und Poliklinik für Innere Medizin I, Klinikum rechts der Isar, Technische Universität München, Germany Deutsches Herzzentrum München, Technische Universität München, Germany DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Germany
a r t i c l e
i n f o
Article history: Received 7 May 2019 Accepted 24 May 2019 Available online xxxx Keywords: Bioresorbable scaffolds Very late scaffold thrombosis Optical coherence tomography Quantitative coronary angiography
a b s t r a c t Purpose: Everolimus-eluting bioresorbable scaffolds (BRS) demonstrated an increased risk of very late scaffold thrombosis (VLScT) in comparison with conventional drug-eluting stents. However, characterization of VLScT cases remains scant and the role of interim angiographic surveillance in identifying patients at risk of VLScT is unclear. We therefore set out to identify angiographic predictors of VLScT in our present case series. Methods: We analyzed a series of consecutive patients with VLScT presenting to two centers in Munich, Germany. Of interest, all patients had undergone interim planned surveillance angiography. Angiographic films were collected and reviewed and quantitative coronary angiography analysis was done at a core laboratory. Optical coherence tomography (OCT) images at presentation with VLScT were analyzed in patients with available data. Results: Nine patients presented with 10 VLScT events. Mean age was 62.6 years. Surveillance angiography (between 159 and 476 days) were unremarkable in all cases. Time from index intervention to VLScT ranged from 393 to 1494 days. Nine of 10 events occurred after discontinuation of dual antiplatelet therapy. Four patients underwent OCT. The dominant finding at the time of VLScT was scaffold discontinuity. Conclusions: In a series of patients with VLScT after treatment with BRS, routine interim surveillance angiography was available in all patients and failed to identify features predictive of subsequent adverse events. © 2019 Elsevier Inc. All rights reserved.
1. Introduction Everolimus-eluting bioresorbable scaffolds (BRS) were approved for use in Europe in 2011 and in the United States in 2016 [1]. However, manufacturing has recently been halted, due in part to concerns about risks of scaffold thrombosis. Within the first year, an approximately two-fold increase in risk of stent thrombosis was observed with BRS, mostly in the initial 30 days after implantation [2,3]. This finding suggests that technical factors such as inadequate lesion preparation, scaffold underexpansion and scaffold malapposition may play an important role [4]. Indeed, preliminary evidence suggests that adoption of specific implantation protocols may considerably ameliorate this risk [5].
Abbreviations: BRS, bioresorbable scaffolds; VLScT, very late scaffold thrombosis; OCT, optical coherence tomography; STEMI, ST-elevation myocardial infarction; NSTEMI, non ST-elevation myocardial infarction; DES, drug eluting stents. ⁎ Corresponding author at: Deutsches Herzzentrum München, Lazarettstraße, 36, Munich, Germany. E-mail address: [email protected] (R.A. Byrne).
More recently, however, concerns have emerged regarding an unanticipated increased risk of very late scaffold thrombosis (VLScT) occurring N12 months after the index procedure [6–11]. Currently, the reasons for such an increased risk are unclear and detailed analysis of incident cases may provide important insight into mechanisms and risk factors. In the present report, we describe the clinical and angiographic characteristics of ten consecutive cases of VLScT. 2. Methods We analyzed all consecutive cases of VLScT in patients presenting to two centres in Munich, Germany, who had been treated with everolimus-eluting BRS (ABSORB bioresorbable vascular scaffold, Abbott Vascular, Santa Clara, Ca., USA). Scaffold thrombosis was adjudicated according to the Academic Research Consortium criteria and VLScT was defined as the occurrence of scaffold thrombosis later than 12 months after the index intervention [12]. All had undergone interim surveillance angiography as part of clinical follow-up. Clinical data at baseline, interim surveillance and at presentation with VLScT were collected and entered into a computer database.
https://doi.org/10.1016/j.carrev.2019.05.023 1553-8389/© 2019 Elsevier Inc. All rights reserved.
Please cite this article as: P. Hoppmann, H. Rai, R. Colleran, et al., Very late scaffold thrombosis after everolimus-eluting bioresorbable scaffold implantation in patien..., Cardiovascular Revascularization Medicine, https://doi.org/10.1016/j.carrev.2019.05.023
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Adenosine diphosphate (ADP)-induced platelet aggregation (PA, in AU × min) was assessed using the Multiplate analyzer (Roche Diagnostics, Switzerland). High platelet reactivity was defined as aggregation units per minute (AU × min) ≥468 [13]. Baseline, post-procedural and surveillance coronary angiograms, as well as coronary angiograms at time of presentation with VLScT were digitally recorded and assessed off-line in the quantitative coronary angiographic (QCA) core laboratory at Intracoronary Stenting and Antithrombotic (ISA) Research Centre, Munich, Germany, using an automated edge-detection system (QAngio XA 7.3, Medis Medical Imaging Systems, Leiden, NL). Measurements were performed on cineangiograms using the same single worst-view projection at all times. QCA was performed on both the “in-stent” and “in-segment” segments including the 5-mm margins proximal and distal to the stent. Qualitative morphological lesion characteristics were characterized by standard criteria and classified according to ACC/AHA criteria. Optical coherence tomography (OCT) was performed at the discretion of the operator using a commercially available OCT imaging systems. Pullbacks were analyzed according to standardized protocol at the OCT core laboratory at ISAResearch Centre, Munich, Germany using a dedicated software (QIvus Research Edition 3.0, Medis Medical Imaging Systems, Leiden, NL). 3. Results Nine patients presented with ten VLScT events. Mean age was 62.6 years. 4 patients underwent OCT and had analyzable quality image acquisition. Patient and lesion characteristics at the time of implantation are summarized in Tables 1 and 2. A summary of timing, presentation and dual antiplatelet therapy at time of VLScT are shown in Table 3. 3.1. Patient 1 A 53-year-old man had intervention of a right coronary artery (RCA) lesion with implantation of a 3.0/18 mm BRS (Fig. 1A). Follow-up
angiography 6 months later showed a good result (Fig. 1A). 393 days after the index procedure, the patient presented with ST-elevation myocardial infarction (STEMI) and VLScT (Fig. 1A). Intraprocedural OCT examination showed scaffold discontinuity with malapposed struts in the vessel lumen and overlying thrombus (Fig. 1B). Flow was restored with thrombus aspiration and balloon dilatation with good acute angiographic result. 46 days later the patient suffered recurrent VLScT, this time under ongoing dual antiplatelet therapy with prasugrel. OCT examination of the culprit lesion was repeated and showed more marked scaffold discontinuity with overlying thrombus (Fig. 1C). The patient was treated with a metallic drug-eluting stent (DES) with good result (Fig. 1D).
3.2. Patient 2 A 66-year-old male patient underwent implantation of a 3.0/28 mm BRS in the left circumflex artery (LCX) in the setting of non-ST-elevation myocardial infarction (NSTEMI)(Fig. 2A). A stenosis of the medial left anterior descending (LAD) coronary artery was also treated with a 3.0/28 mm BRS. Six-month angiographic follow-up documented a favorable result in both lesions (Fig. 2A). 514 days after the index procedure, the patient presented with STEMI and thrombotic occlusion of the BRS in the LCX (Fig. 2A). Flow was restored after balloon dilatation and implantation of a DES. In addition, there was diffuse in stent restenosis in the mid LAD BRS, which was also treated with a DES.
3.3. Patient 3 A 68-year-old patient underwent BRS implantation in the RCA. Two 2.5 mm BRS and a total length of 36 mm were implanted (Fig. 2B). Angiographic follow-up confirmed favorable results (Fig. 2B). 702 days after the index procedure, the patient presented with VLScT and thrombotic occlusion of the distal scaffold (Fig. 2B), which was treated with balloon dilatation and DES implantation.
Table 1 Baseline clinical, lesion and procedural characteristics.
Clinical characteristics Age, (years) Male sex Diabetes Hypertension Hypercholesterolemia Current smoker Ex-smoker Family history of coronary disease Previous myocardial infarction History of coronary bypass surgery Multivessel disease Clinical presentation at index PCI Lesion and procedural characteristics Target vessel Lesion type (AHA/ACC classification) Predilatation Postdilatation Nominal balloon size (mm) Maximal balloon pressure (atm) Scaffold diameter (mm) Scaffold length (mm) Number of implanted scaffolds TIMI flow pre-PCI TIMI flow post-PCI
Patient 1
Patient 2
Patient 3
Patient 4
Patient 5
Patient 6
Patient 7
Patient 8
Patient 9
53 Yes No Yes Yes No Yes Yes No No Yes stable AP
66 Yes NIDDM Yes Yes No No No No No Yes NSTEMI
68 Yes No Yes Yes No No No No No Yes stable AP
71 Yes No Yes Yes No No No Yes No Yes stable AP
74 Yes IDDM Yes Yes No No No No No Yes STEMI
55 Yes NIDDM Yes Yes Yes No No No No Yes NSTEMI
73 Yes IDDM Yes Yes No No No No No Yes NSTEMI
48 Yes No Yes No Yes No No Yes No Yes stable AP
55 Yes No No Yes Yes No Yes No No No STEMI
RCA B1 Yes No 3.0 15 3.0 18 1 3 3
LCX B1 Yes No 3.0 10 3.0 28 1 3 3
RCA B1 Yes Yes 3.0 14 2.5 36 2 3 3
RCA B2 Yes No 3.5 14 3.5 12 1 3 3
RCA B2 Yes Yes 3.0 14 3.5 74 3 3 3
RCA B2 Yes No 3.0 15 3.5 56 2 2 3
LAD B2 Yes No 3.5 16 3.5 18 1 3 3
LCX B2 Yes No 3.5 16 3.5 30 2 3 3
LAD B2 Yes Yes 3.5 18 3.5 28 1 2 3
Abbreviations: AP, angina pectoris; IDDM, insulin-dependent diabetes mellitus; LAD, left anterior descending coronary artery; LCX, left circumflex coronary artery; RCA, right coronary artery; NIDDM, non-insulin-dependent diabetes mellitus; NSTEMI, non ST-elevation myocardial infarction; STEMI, ST-elevation myocardial infarction; TIMI, thrombolysis in myocardial infarction.
Please cite this article as: P. Hoppmann, H. Rai, R. Colleran, et al., Very late scaffold thrombosis after everolimus-eluting bioresorbable scaffold implantation in patien..., Cardiovascular Revascularization Medicine, https://doi.org/10.1016/j.carrev.2019.05.023
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Table 2 Quantitative coronary angiography findings at index procedure and follow-up.
QCA measures before index PCI Reference vessel diameter (mm) Minimal lumen diameter (mm) Diameter stenosis (%) Lesion length (mm) QCA measures after index PCI Minimal lumen diameter, in-scaffold (mm) Diameter stenosis, in-scaffold (%) Acute lumen gain, in-scaffold (mm) QCA measures at 6-month follow-up Minimal lumen diameter, in-scaffold (mm) Diameter stenosis, in-scaffold (%) Late lumen loss, in-scaffold (mm) QCA measures at very late scaffold thrombosis Minimal lumen diameter, in-scaffold (mm) Diameter stenosis, in-scaffold (%) Late lumen loss, in-scaffold (mm)
Patient 1
Patient 2
Patient 3
Patient 4
Patient 5
Patient 6
Patient 7
Patient 8
Patient 9
3.00 1.33 55.7 17.1
2.97 0.66 77.8 14.9
2.93 1.36 53.6 13.6
3.62 1.65 54.4 6.4
3.11 0.88 71.7 3.4
3.30 0.20 93.9 33.2
3.30 0.35 89.4 12.2
3.24 0.66 79.6 6.43
3.22 0.79 75.5 17.76
2.94 6.4 1.61
2.48 12.1 1.82
2.72 9.0 1.36
3.35 7.2 1.70
2.94 13.0 2.06
2.89 15.7 2.69
2.71 17.8 2.36
2.80 16.9 2.14
3.20 8.8 2.41
2.90 7.6 0.04
2.33 15.0 0.15
2.32 22.4 0.40
2.70 20.8 0.65
2.53 21.9 0.41
1.76 45.0 1.13
2.85 16.2 −0.14
3.00 12.3 −0.20
2.93 10.4 0.27
0.00a and 0.00b 100a and 100b 2.94a and 2.94b
0.00 100 2.48
0.56 80.17 2.16
0.00 100 3.35
0.56 80.04 2.38
0.59 82.75 2.3
1.06 68.19 1.65
0.00 100 2.80
1.60 52.68 1.60
Abbreviations: PCI, percutaneous coronary intervention; QCA, quantitative coronary angiography. a At first very late scaffold thrombosis. b At second very late scaffold thrombosis.
3.4. Patient 4
3.6. Patient 6
A 71-year-old patient underwent RCA intervention with implantation of a 3.5/12 mm BRS (Fig. 2C). Follow-up angiography showed good results without significant restenosis (Fig. 2C). 478 days after the index procedure, the patient presented with STEMI. Coronary angiography showed VLScT with thrombotic occlusion of the BRS in the proximal RCA (Fig. 2C). After thrombus aspiration and balloon dilatation, a DES was implanted.
A 55-year-old patient was treated with two 3.5/28 mm BRS for presentation with NSTEMI (Fig. 2E). Follow-up angiography at 15 months after the index PCI showed a satisfactory result (Fig. 2E). 866 days after the index PCI, the patient presented with STEMI caused by VLScT. ST-segment elevation resolved after administration of heparin in the emergency department. There was TIMI 3 flow by coronary angiography (Fig. 2E). OCT showed thrombotic material surrounding malapposed struts in the lumen of the distal RCA at the site of a focal scaffold discontinuity (Fig. 3A). A DES was implanted with a good procedural result.
3.5. Patient 5 A 74-year-old patient with STEMI and subtotal occlusion of the proximal and mid RCA was treated with three BRS (two 3.5/28 mm and a 3.5/18 mm devices) (Fig. 2D). Because of dissection at the distal edge of the distal BRS, a 3.0/9 mm DES was implanted. Surveillance angiography showed mild restenosis in the mid RCA (Fig. 2D), with no indication for treatment. 532 days after index PCI, the patient suffered recurrent myocardial infarction with VLScT and subtotal thrombotic occlusion within the scaffolded segment of the mid RCA (Fig. 2D). OCT showed focal scaffold discontinuity in the distal BRS with overlying thrombus and an otherwise acceptable result in the stented segment (Fig. 3A). In addition, there was restenosis with an OCT-derived percent lumen area stenosis of 54%. The lesion was treated with balloon dilation followed by implantation of DES.
3.7. Patient 7 A 73-year-old patient presented with NSTEMI and subtotal occlusion of the proximal LAD (Fig. 2F). A 3.5/18 mm BRS was implanted. Sixmonth follow-up angiography showed an excellent result in the proximal LAD (Fig. 2F). 890 days after BRS implantation, the patient was admitted to hospital with STEMI. Coronary angiography showed VLScT with subtotal thrombotic occlusion of the scaffold in the proximal LAD (Fig. 2F). OCT showed a focal area of mild to moderate restenosis, a tissue bridge possibly consequent on chronic malapposition and focal scaffold discontinuity with thrombosis overlying malapposed struts in the
Table 3 Timing, presentation and details of dual antiplatelet therapy at time of very late scaffold thrombosis.
Time between index PCI and very late scaffold thrombosis (days) Clinical presentation at very late scaffold thrombosis On dual antiplatelet therapy at very late scaffold thrombosis P2Y12 Inhibitor after Index PCI Response to antiplatelet therapy at time of index PCI (AU × min) Response to antiplatelet therapy at 6-month follow-up (AU × min)
Patient 1
Patient 2
Patient 3
Patient 4
Patient 5
Patient 6
Patient 7
Patient 8
Patient 9
393a/439b
514
702
478
532
866
890
1494
1440
STEMI no
STEMI no
STEMI no
STEMI no
STEMI no
STEMI no
NSTEMI no
STEMIa/STEMIb STEMI Noa/yesb no Clopidogrel 368
Clopidogrel Clopidogrel Clopidogrel Ticagrelor Ticagrelor Ticagrelor Clopidogrel Prasugrel 392 127 160 147 253 233 93 138
214
155
609
562
122
134
192
490
124
Abbreviations: PCI, percutaneous coronary intervention; STEMI, ST elevation myocardial infarction; NSTEMI non ST-elevation myocardial infarction. Response to antiplatelet therapy was assessed measuring ADP induced platelet aggregation using the multi-plate analyzer; measurements were performed 2 h after administration of the loading-dose of P2Y12 inhibitor at the time of index PCI and under chronic therapy with P2Y12 inhibitor at 6-month follow-up angiography. Cut-off for high platelet reactivity ≥468 AU × min. a At first very late scaffold thrombosis. b At second very late scaffold thrombosis.
Please cite this article as: P. Hoppmann, H. Rai, R. Colleran, et al., Very late scaffold thrombosis after everolimus-eluting bioresorbable scaffold implantation in patien..., Cardiovascular Revascularization Medicine, https://doi.org/10.1016/j.carrev.2019.05.023
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Fig. 1. Serial assessment of a patient with multiple VLScTs. (A) Coronary angiography at baseline (pre), after scaffold implantation (post), interval follow-up angiography (FU) and at time of presentation with VLScT for patient 1; (B) OCT imaging at the site of VLScT in the same patient showing focal scaffold discontinuity with malapposed struts in the vessel lumen and overlying thrombus (sections I–IV) with good result in the rest of the scaffold (section V); (C) OCT imaging following presentation with recurrent VLScT in the same patient showing more marked scaffold discontinuity with overlying thrombus (sections I–IV); (D): OCT appearance after stenting with conventional drug-eluting stent (sections I–III). * indicates artefact due to guide-wire; arrow indicates site of VLScT.
vessel lumen (Fig. 3B). Flow was restored after balloon dilation and DES implantation. 3.8. Patient 8 A 48-year-old male patient underwent implantation of two BRS (3.0/18 mm and 3.5/12 mm) in a lesion in the LCX artery (Fig. 2G). Six-month angiographic follow-up documented a favorable result (Fig. 2G). 1494 days after the index procedure, the patient presented with STEMI. Coronary angiography showed VLScT with thrombotic occlusion of the BRS (Fig. 2G). Flow was restored after balloon dilatation and implantation of a DES. 3.9. Patient 9 A 55-year-old male patient underwent implantation of a 3.5/28 mm BRS in a lesion in the proximal LAD in the setting of STEMI (Fig. 2H). Sixmonth angiographic follow-up documented a favorable result in this lesion (Fig. 2H). 1440 days after the index procedure, the patient presented with NSTEMI and recurrent non-sustained ventricular tachycardia. Coronary angiography with OCT imaging showed VLScT with thrombotic material and formation of a large aneurysm in the region of the implanted BRS (Fig. 2H) (Fig. 3C). The lesion was treated with DES implantation.
4. Discussion The present case series describes nine consecutive patients suffering 10 VLScT events. The series is unique since all patients had undergone planned surveillance angiography with satisfactory results in each case. Although the BRS is no longer widely available, analysis of incident cases of VLScT is important to provide insight into mechanisms and risk factors, and could have implications for the development of future devices, as well as for the management of patients already treated with BRS. Concerns with regard to VLScT were largely unexpected. It was hoped that BRS would address the small but defined risk of very late stent thrombosis observed with conventional DES. By completely resorbing after a period of temporary scaffolding of the vessel, no nidus for very late thrombosis would remain. However, studies have shown that resorption of lactic acid-based BRS in human arteries is slower than initially believed, taking anywhere between 2 and 4 years [14]. In addition, although preclinical studies with long term follow-up seemed generally favorable, occasional cases of late loss of scaffold discontinuity were observed in pig models, without evidence of a clear mechanistic etiology and without consequences for vessel patency [15]. The main findings of our case series should be discussed. First, all patients presenting with VLScT had been recommended to and did undergo routine surveillance angiography after BRS implantation. The surveillance films were reviewed and showed largely unremarkable findings. Although, some studies have shown that routine surveillance
Please cite this article as: P. Hoppmann, H. Rai, R. Colleran, et al., Very late scaffold thrombosis after everolimus-eluting bioresorbable scaffold implantation in patien..., Cardiovascular Revascularization Medicine, https://doi.org/10.1016/j.carrev.2019.05.023
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Fig. 2. Angiography at different time points. (A)–(H) Coronary angiography at baseline (pre), after scaffold implantation (post), interval follow-up angiography (FU) and at time of presentation with VLScT for patients 2 to 9 respectively. The angiographic results at time of surveillance angiography were satisfactory in all cases. Arrow indicates site of VLScT in each case; in each case, the same, best representative projection is displayed at all time points where available.
angiography does not reduce the subsequent risk of cardiac death or myocardial infarction [16], its role in identifying unexpected findings in patients treated with novel intracoronary devices is of potential value. However, our experience suggests that routine angiographic surveillance of patients following BRS implantation may not identify patients at risk of subsequent VLScT and that alternative approaches for risk stratification would be required. Second, all patients reported compliance with antiplatelet therapy, as directed by their cardiologist at the time of VLScT. Each had been recommended to receive 12 months of DAPT. At the time of VLScT, all patients were taking aspirin monotherapy. In one patient with a recurrent VLScT, this second event occurred while on treatment with aspirin and prasugrel. These findings are in agreement with observations from the ABSORB-II trial [6]. In that trial 6 patients suffered VLScT and all of them had discontinued DAPT and remained on aspirin monotherapy. This suggests that prolongation of DAPT beyond 12 months and until the BRS is likely fully resorbed should be considered in patients already treated with BRS [1]. Third, patients in our series were relatively young with intermediate lesion complexity and more than half had BRS implantation in the setting of acute coronary syndrome. Moreover, vessel size was quite large, ranging from 2.93 mm to 3.30 mm. In terms of implantation technique, postdilation with a non-compliant balloon was performed in only 3 of the 9 cases described and interventions were not OCTguided. However, although observational data have shown that implementation of a modified implantation technique is associated with reduced incidence of scaffold thrombosis at one year [5], it is unclear as to whether such an approach might reduce rates of VLScT [17]. Fourth, intracoronary imaging studies at the time of VLScT were available in 4 patients with 5 events. Of these, 3 had evidence of loss of integrity of the scaffold backbone manifesting as scaffold discontinuity and prolapse of struts into the vessel lumen. In addition, one patient exhibited marked vessel enlargement with aneurysm formation due to presumed
aggressive remodeling. These findings are concordant with observations of others. In the ABSORB Japan trial, for example, OCT imaging at the time of VLScT in 3 of the 4 patients who suffered VLScT showed strut discontinuities, malapposition and/or uncovered struts in each case [7]. A review by Sotomi et al. of the mechanisms of cases of scaffold thrombosis reported in the literature showed that in patients with VLScT attributed to scaffold recoil, positive vessel remodeling, evagination and scaffold discontinuity were frequently observed [18]. In the INVEST registry of patients with VLScT, scaffold discontinuity was the most frequent observation at VLScT with malapposition, neoatherosclerosis and underexpansion or scaffold recoil less frequently observed [19]. The extent to which the risk of VLScT events in our study could have been ameliorated by implantation technique is not known, though it seems less likely that discontinuity or remodeling years after implantation can be easily modified by procedural characteristics. 4.1. Limitations As a case series, our report is descriptive and cannot ascribe causality to the findings observed in association with VLScT. Intravascular imaging was not done at the time of angiographic surveillance and insights into risk factors for subsequent VLScT based on such imaging are not available. 5. Conclusions In this case series, routine surveillance angiography failed to identify features predictive of subsequent VLScT. Since all patients had stopped DAPT before VLScT and considering the OCT findings, prolongation of DAPT after BRS implantation may be considered. Funding NA.
Please cite this article as: P. Hoppmann, H. Rai, R. Colleran, et al., Very late scaffold thrombosis after everolimus-eluting bioresorbable scaffold implantation in patien..., Cardiovascular Revascularization Medicine, https://doi.org/10.1016/j.carrev.2019.05.023
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Declaration of Competing Interest MJ reports being a consultant for and receiving speaker fees from Biotronik and OrbusNeich. RAB reports lectures fees from B. Braun Melsungen, Biotronik, Boston Scientific and Micell Technologies and research funding to the institution from Boston Scientific and Celonova Biosciences. The other authors have no conflicts of interest to declare. References
Fig. 3. OCT correlates of VLScT. (A) OCT imaging at the site of VLScT for (patient 5) showed focal scaffold discontinuity in the distal scaffold (section I) with overlying thrombus and an otherwise acceptable result in the stented segment; (B) OCT imaging at the site of during VLScT for (patient 6) showed focal loss of scaffold integrity in the distal segment with prolapse of struts into the lumen interior (section I–II), thrombotic material surrounding the malapposed struts (panel I and II), possible neointimal bridge (section III) and moderate restenosis (panel IV–V); (C) OCT imaging in (patient 9) showed advanced scaffold degradation with positive remodeling, thrombotic material and formation of a large aneurysm in the region of the implanted BRS. * indicates artefact due to guide-wire.
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Cardiovascular Revascularization Medicine
Very late scaffold thrombosis after everolimus-eluting bioresorbable scaffold implantation in patients with unremarkable interim surveillance angiography Petra Hoppmann a, Himanshu Rai b, Roisin Colleran b, Sebastian Kufner b, Jens Wiebe b, Salvatore Cassese b, Michael Joner b,c, Karl-Ludwig Laugwitz a,c, Adnan Kastrati b,c, Robert A. Byrne b,c,⁎ a b c
Klinik und Poliklinik für Innere Medizin I, Klinikum rechts der Isar, Technische Universität München, Germany Deutsches Herzzentrum München, Technische Universität München, Germany DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Germany
a r t i c l e
i n f o
Article history: Received 7 May 2019 Accepted 24 May 2019 Available online xxxx Keywords: Bioresorbable scaffolds Very late scaffold thrombosis Optical coherence tomography Quantitative coronary angiography
a b s t r a c t Purpose: Everolimus-eluting bioresorbable scaffolds (BRS) demonstrated an increased risk of very late scaffold thrombosis (VLScT) in comparison with conventional drug-eluting stents. However, characterization of VLScT cases remains scant and the role of interim angiographic surveillance in identifying patients at risk of VLScT is unclear. We therefore set out to identify angiographic predictors of VLScT in our present case series. Methods: We analyzed a series of consecutive patients with VLScT presenting to two centers in Munich, Germany. Of interest, all patients had undergone interim planned surveillance angiography. Angiographic films were collected and reviewed and quantitative coronary angiography analysis was done at a core laboratory. Optical coherence tomography (OCT) images at presentation with VLScT were analyzed in patients with available data. Results: Nine patients presented with 10 VLScT events. Mean age was 62.6 years. Surveillance angiography (between 159 and 476 days) were unremarkable in all cases. Time from index intervention to VLScT ranged from 393 to 1494 days. Nine of 10 events occurred after discontinuation of dual antiplatelet therapy. Four patients underwent OCT. The dominant finding at the time of VLScT was scaffold discontinuity. Conclusions: In a series of patients with VLScT after treatment with BRS, routine interim surveillance angiography was available in all patients and failed to identify features predictive of subsequent adverse events. © 2019 Elsevier Inc. All rights reserved.
1. Introduction Everolimus-eluting bioresorbable scaffolds (BRS) were approved for use in Europe in 2011 and in the United States in 2016 [1]. However, manufacturing has recently been halted, due in part to concerns about risks of scaffold thrombosis. Within the first year, an approximately two-fold increase in risk of stent thrombosis was observed with BRS, mostly in the initial 30 days after implantation [2,3]. This finding suggests that technical factors such as inadequate lesion preparation, scaffold underexpansion and scaffold malapposition may play an important role [4]. Indeed, preliminary evidence suggests that adoption of specific implantation protocols may considerably ameliorate this risk [5].
Abbreviations: BRS, bioresorbable scaffolds; VLScT, very late scaffold thrombosis; OCT, optical coherence tomography; STEMI, ST-elevation myocardial infarction; NSTEMI, non ST-elevation myocardial infarction; DES, drug eluting stents. ⁎ Corresponding author at: Deutsches Herzzentrum München, Lazarettstraße, 36, Munich, Germany. E-mail address: [email protected] (R.A. Byrne).
More recently, however, concerns have emerged regarding an unanticipated increased risk of very late scaffold thrombosis (VLScT) occurring N12 months after the index procedure [6–11]. Currently, the reasons for such an increased risk are unclear and detailed analysis of incident cases may provide important insight into mechanisms and risk factors. In the present report, we describe the clinical and angiographic characteristics of ten consecutive cases of VLScT. 2. Methods We analyzed all consecutive cases of VLScT in patients presenting to two centres in Munich, Germany, who had been treated with everolimus-eluting BRS (ABSORB bioresorbable vascular scaffold, Abbott Vascular, Santa Clara, Ca., USA). Scaffold thrombosis was adjudicated according to the Academic Research Consortium criteria and VLScT was defined as the occurrence of scaffold thrombosis later than 12 months after the index intervention [12]. All had undergone interim surveillance angiography as part of clinical follow-up. Clinical data at baseline, interim surveillance and at presentation with VLScT were collected and entered into a computer database.
https://doi.org/10.1016/j.carrev.2019.05.023 1553-8389/© 2019 Elsevier Inc. All rights reserved.
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Adenosine diphosphate (ADP)-induced platelet aggregation (PA, in AU × min) was assessed using the Multiplate analyzer (Roche Diagnostics, Switzerland). High platelet reactivity was defined as aggregation units per minute (AU × min) ≥468 [13]. Baseline, post-procedural and surveillance coronary angiograms, as well as coronary angiograms at time of presentation with VLScT were digitally recorded and assessed off-line in the quantitative coronary angiographic (QCA) core laboratory at Intracoronary Stenting and Antithrombotic (ISA) Research Centre, Munich, Germany, using an automated edge-detection system (QAngio XA 7.3, Medis Medical Imaging Systems, Leiden, NL). Measurements were performed on cineangiograms using the same single worst-view projection at all times. QCA was performed on both the “in-stent” and “in-segment” segments including the 5-mm margins proximal and distal to the stent. Qualitative morphological lesion characteristics were characterized by standard criteria and classified according to ACC/AHA criteria. Optical coherence tomography (OCT) was performed at the discretion of the operator using a commercially available OCT imaging systems. Pullbacks were analyzed according to standardized protocol at the OCT core laboratory at ISAResearch Centre, Munich, Germany using a dedicated software (QIvus Research Edition 3.0, Medis Medical Imaging Systems, Leiden, NL). 3. Results Nine patients presented with ten VLScT events. Mean age was 62.6 years. 4 patients underwent OCT and had analyzable quality image acquisition. Patient and lesion characteristics at the time of implantation are summarized in Tables 1 and 2. A summary of timing, presentation and dual antiplatelet therapy at time of VLScT are shown in Table 3. 3.1. Patient 1 A 53-year-old man had intervention of a right coronary artery (RCA) lesion with implantation of a 3.0/18 mm BRS (Fig. 1A). Follow-up
angiography 6 months later showed a good result (Fig. 1A). 393 days after the index procedure, the patient presented with ST-elevation myocardial infarction (STEMI) and VLScT (Fig. 1A). Intraprocedural OCT examination showed scaffold discontinuity with malapposed struts in the vessel lumen and overlying thrombus (Fig. 1B). Flow was restored with thrombus aspiration and balloon dilatation with good acute angiographic result. 46 days later the patient suffered recurrent VLScT, this time under ongoing dual antiplatelet therapy with prasugrel. OCT examination of the culprit lesion was repeated and showed more marked scaffold discontinuity with overlying thrombus (Fig. 1C). The patient was treated with a metallic drug-eluting stent (DES) with good result (Fig. 1D).
3.2. Patient 2 A 66-year-old male patient underwent implantation of a 3.0/28 mm BRS in the left circumflex artery (LCX) in the setting of non-ST-elevation myocardial infarction (NSTEMI)(Fig. 2A). A stenosis of the medial left anterior descending (LAD) coronary artery was also treated with a 3.0/28 mm BRS. Six-month angiographic follow-up documented a favorable result in both lesions (Fig. 2A). 514 days after the index procedure, the patient presented with STEMI and thrombotic occlusion of the BRS in the LCX (Fig. 2A). Flow was restored after balloon dilatation and implantation of a DES. In addition, there was diffuse in stent restenosis in the mid LAD BRS, which was also treated with a DES.
3.3. Patient 3 A 68-year-old patient underwent BRS implantation in the RCA. Two 2.5 mm BRS and a total length of 36 mm were implanted (Fig. 2B). Angiographic follow-up confirmed favorable results (Fig. 2B). 702 days after the index procedure, the patient presented with VLScT and thrombotic occlusion of the distal scaffold (Fig. 2B), which was treated with balloon dilatation and DES implantation.
Table 1 Baseline clinical, lesion and procedural characteristics.
Clinical characteristics Age, (years) Male sex Diabetes Hypertension Hypercholesterolemia Current smoker Ex-smoker Family history of coronary disease Previous myocardial infarction History of coronary bypass surgery Multivessel disease Clinical presentation at index PCI Lesion and procedural characteristics Target vessel Lesion type (AHA/ACC classification) Predilatation Postdilatation Nominal balloon size (mm) Maximal balloon pressure (atm) Scaffold diameter (mm) Scaffold length (mm) Number of implanted scaffolds TIMI flow pre-PCI TIMI flow post-PCI
Patient 1
Patient 2
Patient 3
Patient 4
Patient 5
Patient 6
Patient 7
Patient 8
Patient 9
53 Yes No Yes Yes No Yes Yes No No Yes stable AP
66 Yes NIDDM Yes Yes No No No No No Yes NSTEMI
68 Yes No Yes Yes No No No No No Yes stable AP
71 Yes No Yes Yes No No No Yes No Yes stable AP
74 Yes IDDM Yes Yes No No No No No Yes STEMI
55 Yes NIDDM Yes Yes Yes No No No No Yes NSTEMI
73 Yes IDDM Yes Yes No No No No No Yes NSTEMI
48 Yes No Yes No Yes No No Yes No Yes stable AP
55 Yes No No Yes Yes No Yes No No No STEMI
RCA B1 Yes No 3.0 15 3.0 18 1 3 3
LCX B1 Yes No 3.0 10 3.0 28 1 3 3
RCA B1 Yes Yes 3.0 14 2.5 36 2 3 3
RCA B2 Yes No 3.5 14 3.5 12 1 3 3
RCA B2 Yes Yes 3.0 14 3.5 74 3 3 3
RCA B2 Yes No 3.0 15 3.5 56 2 2 3
LAD B2 Yes No 3.5 16 3.5 18 1 3 3
LCX B2 Yes No 3.5 16 3.5 30 2 3 3
LAD B2 Yes Yes 3.5 18 3.5 28 1 2 3
Abbreviations: AP, angina pectoris; IDDM, insulin-dependent diabetes mellitus; LAD, left anterior descending coronary artery; LCX, left circumflex coronary artery; RCA, right coronary artery; NIDDM, non-insulin-dependent diabetes mellitus; NSTEMI, non ST-elevation myocardial infarction; STEMI, ST-elevation myocardial infarction; TIMI, thrombolysis in myocardial infarction.
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Table 2 Quantitative coronary angiography findings at index procedure and follow-up.
QCA measures before index PCI Reference vessel diameter (mm) Minimal lumen diameter (mm) Diameter stenosis (%) Lesion length (mm) QCA measures after index PCI Minimal lumen diameter, in-scaffold (mm) Diameter stenosis, in-scaffold (%) Acute lumen gain, in-scaffold (mm) QCA measures at 6-month follow-up Minimal lumen diameter, in-scaffold (mm) Diameter stenosis, in-scaffold (%) Late lumen loss, in-scaffold (mm) QCA measures at very late scaffold thrombosis Minimal lumen diameter, in-scaffold (mm) Diameter stenosis, in-scaffold (%) Late lumen loss, in-scaffold (mm)
Patient 1
Patient 2
Patient 3
Patient 4
Patient 5
Patient 6
Patient 7
Patient 8
Patient 9
3.00 1.33 55.7 17.1
2.97 0.66 77.8 14.9
2.93 1.36 53.6 13.6
3.62 1.65 54.4 6.4
3.11 0.88 71.7 3.4
3.30 0.20 93.9 33.2
3.30 0.35 89.4 12.2
3.24 0.66 79.6 6.43
3.22 0.79 75.5 17.76
2.94 6.4 1.61
2.48 12.1 1.82
2.72 9.0 1.36
3.35 7.2 1.70
2.94 13.0 2.06
2.89 15.7 2.69
2.71 17.8 2.36
2.80 16.9 2.14
3.20 8.8 2.41
2.90 7.6 0.04
2.33 15.0 0.15
2.32 22.4 0.40
2.70 20.8 0.65
2.53 21.9 0.41
1.76 45.0 1.13
2.85 16.2 −0.14
3.00 12.3 −0.20
2.93 10.4 0.27
0.00a and 0.00b 100a and 100b 2.94a and 2.94b
0.00 100 2.48
0.56 80.17 2.16
0.00 100 3.35
0.56 80.04 2.38
0.59 82.75 2.3
1.06 68.19 1.65
0.00 100 2.80
1.60 52.68 1.60
Abbreviations: PCI, percutaneous coronary intervention; QCA, quantitative coronary angiography. a At first very late scaffold thrombosis. b At second very late scaffold thrombosis.
3.4. Patient 4
3.6. Patient 6
A 71-year-old patient underwent RCA intervention with implantation of a 3.5/12 mm BRS (Fig. 2C). Follow-up angiography showed good results without significant restenosis (Fig. 2C). 478 days after the index procedure, the patient presented with STEMI. Coronary angiography showed VLScT with thrombotic occlusion of the BRS in the proximal RCA (Fig. 2C). After thrombus aspiration and balloon dilatation, a DES was implanted.
A 55-year-old patient was treated with two 3.5/28 mm BRS for presentation with NSTEMI (Fig. 2E). Follow-up angiography at 15 months after the index PCI showed a satisfactory result (Fig. 2E). 866 days after the index PCI, the patient presented with STEMI caused by VLScT. ST-segment elevation resolved after administration of heparin in the emergency department. There was TIMI 3 flow by coronary angiography (Fig. 2E). OCT showed thrombotic material surrounding malapposed struts in the lumen of the distal RCA at the site of a focal scaffold discontinuity (Fig. 3A). A DES was implanted with a good procedural result.
3.5. Patient 5 A 74-year-old patient with STEMI and subtotal occlusion of the proximal and mid RCA was treated with three BRS (two 3.5/28 mm and a 3.5/18 mm devices) (Fig. 2D). Because of dissection at the distal edge of the distal BRS, a 3.0/9 mm DES was implanted. Surveillance angiography showed mild restenosis in the mid RCA (Fig. 2D), with no indication for treatment. 532 days after index PCI, the patient suffered recurrent myocardial infarction with VLScT and subtotal thrombotic occlusion within the scaffolded segment of the mid RCA (Fig. 2D). OCT showed focal scaffold discontinuity in the distal BRS with overlying thrombus and an otherwise acceptable result in the stented segment (Fig. 3A). In addition, there was restenosis with an OCT-derived percent lumen area stenosis of 54%. The lesion was treated with balloon dilation followed by implantation of DES.
3.7. Patient 7 A 73-year-old patient presented with NSTEMI and subtotal occlusion of the proximal LAD (Fig. 2F). A 3.5/18 mm BRS was implanted. Sixmonth follow-up angiography showed an excellent result in the proximal LAD (Fig. 2F). 890 days after BRS implantation, the patient was admitted to hospital with STEMI. Coronary angiography showed VLScT with subtotal thrombotic occlusion of the scaffold in the proximal LAD (Fig. 2F). OCT showed a focal area of mild to moderate restenosis, a tissue bridge possibly consequent on chronic malapposition and focal scaffold discontinuity with thrombosis overlying malapposed struts in the
Table 3 Timing, presentation and details of dual antiplatelet therapy at time of very late scaffold thrombosis.
Time between index PCI and very late scaffold thrombosis (days) Clinical presentation at very late scaffold thrombosis On dual antiplatelet therapy at very late scaffold thrombosis P2Y12 Inhibitor after Index PCI Response to antiplatelet therapy at time of index PCI (AU × min) Response to antiplatelet therapy at 6-month follow-up (AU × min)
Patient 1
Patient 2
Patient 3
Patient 4
Patient 5
Patient 6
Patient 7
Patient 8
Patient 9
393a/439b
514
702
478
532
866
890
1494
1440
STEMI no
STEMI no
STEMI no
STEMI no
STEMI no
STEMI no
NSTEMI no
STEMIa/STEMIb STEMI Noa/yesb no Clopidogrel 368
Clopidogrel Clopidogrel Clopidogrel Ticagrelor Ticagrelor Ticagrelor Clopidogrel Prasugrel 392 127 160 147 253 233 93 138
214
155
609
562
122
134
192
490
124
Abbreviations: PCI, percutaneous coronary intervention; STEMI, ST elevation myocardial infarction; NSTEMI non ST-elevation myocardial infarction. Response to antiplatelet therapy was assessed measuring ADP induced platelet aggregation using the multi-plate analyzer; measurements were performed 2 h after administration of the loading-dose of P2Y12 inhibitor at the time of index PCI and under chronic therapy with P2Y12 inhibitor at 6-month follow-up angiography. Cut-off for high platelet reactivity ≥468 AU × min. a At first very late scaffold thrombosis. b At second very late scaffold thrombosis.
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Fig. 1. Serial assessment of a patient with multiple VLScTs. (A) Coronary angiography at baseline (pre), after scaffold implantation (post), interval follow-up angiography (FU) and at time of presentation with VLScT for patient 1; (B) OCT imaging at the site of VLScT in the same patient showing focal scaffold discontinuity with malapposed struts in the vessel lumen and overlying thrombus (sections I–IV) with good result in the rest of the scaffold (section V); (C) OCT imaging following presentation with recurrent VLScT in the same patient showing more marked scaffold discontinuity with overlying thrombus (sections I–IV); (D): OCT appearance after stenting with conventional drug-eluting stent (sections I–III). * indicates artefact due to guide-wire; arrow indicates site of VLScT.
vessel lumen (Fig. 3B). Flow was restored after balloon dilation and DES implantation. 3.8. Patient 8 A 48-year-old male patient underwent implantation of two BRS (3.0/18 mm and 3.5/12 mm) in a lesion in the LCX artery (Fig. 2G). Six-month angiographic follow-up documented a favorable result (Fig. 2G). 1494 days after the index procedure, the patient presented with STEMI. Coronary angiography showed VLScT with thrombotic occlusion of the BRS (Fig. 2G). Flow was restored after balloon dilatation and implantation of a DES. 3.9. Patient 9 A 55-year-old male patient underwent implantation of a 3.5/28 mm BRS in a lesion in the proximal LAD in the setting of STEMI (Fig. 2H). Sixmonth angiographic follow-up documented a favorable result in this lesion (Fig. 2H). 1440 days after the index procedure, the patient presented with NSTEMI and recurrent non-sustained ventricular tachycardia. Coronary angiography with OCT imaging showed VLScT with thrombotic material and formation of a large aneurysm in the region of the implanted BRS (Fig. 2H) (Fig. 3C). The lesion was treated with DES implantation.
4. Discussion The present case series describes nine consecutive patients suffering 10 VLScT events. The series is unique since all patients had undergone planned surveillance angiography with satisfactory results in each case. Although the BRS is no longer widely available, analysis of incident cases of VLScT is important to provide insight into mechanisms and risk factors, and could have implications for the development of future devices, as well as for the management of patients already treated with BRS. Concerns with regard to VLScT were largely unexpected. It was hoped that BRS would address the small but defined risk of very late stent thrombosis observed with conventional DES. By completely resorbing after a period of temporary scaffolding of the vessel, no nidus for very late thrombosis would remain. However, studies have shown that resorption of lactic acid-based BRS in human arteries is slower than initially believed, taking anywhere between 2 and 4 years [14]. In addition, although preclinical studies with long term follow-up seemed generally favorable, occasional cases of late loss of scaffold discontinuity were observed in pig models, without evidence of a clear mechanistic etiology and without consequences for vessel patency [15]. The main findings of our case series should be discussed. First, all patients presenting with VLScT had been recommended to and did undergo routine surveillance angiography after BRS implantation. The surveillance films were reviewed and showed largely unremarkable findings. Although, some studies have shown that routine surveillance
Please cite this article as: P. Hoppmann, H. Rai, R. Colleran, et al., Very late scaffold thrombosis after everolimus-eluting bioresorbable scaffold implantation in patien..., Cardiovascular Revascularization Medicine, https://doi.org/10.1016/j.carrev.2019.05.023
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Fig. 2. Angiography at different time points. (A)–(H) Coronary angiography at baseline (pre), after scaffold implantation (post), interval follow-up angiography (FU) and at time of presentation with VLScT for patients 2 to 9 respectively. The angiographic results at time of surveillance angiography were satisfactory in all cases. Arrow indicates site of VLScT in each case; in each case, the same, best representative projection is displayed at all time points where available.
angiography does not reduce the subsequent risk of cardiac death or myocardial infarction [16], its role in identifying unexpected findings in patients treated with novel intracoronary devices is of potential value. However, our experience suggests that routine angiographic surveillance of patients following BRS implantation may not identify patients at risk of subsequent VLScT and that alternative approaches for risk stratification would be required. Second, all patients reported compliance with antiplatelet therapy, as directed by their cardiologist at the time of VLScT. Each had been recommended to receive 12 months of DAPT. At the time of VLScT, all patients were taking aspirin monotherapy. In one patient with a recurrent VLScT, this second event occurred while on treatment with aspirin and prasugrel. These findings are in agreement with observations from the ABSORB-II trial [6]. In that trial 6 patients suffered VLScT and all of them had discontinued DAPT and remained on aspirin monotherapy. This suggests that prolongation of DAPT beyond 12 months and until the BRS is likely fully resorbed should be considered in patients already treated with BRS [1]. Third, patients in our series were relatively young with intermediate lesion complexity and more than half had BRS implantation in the setting of acute coronary syndrome. Moreover, vessel size was quite large, ranging from 2.93 mm to 3.30 mm. In terms of implantation technique, postdilation with a non-compliant balloon was performed in only 3 of the 9 cases described and interventions were not OCTguided. However, although observational data have shown that implementation of a modified implantation technique is associated with reduced incidence of scaffold thrombosis at one year [5], it is unclear as to whether such an approach might reduce rates of VLScT [17]. Fourth, intracoronary imaging studies at the time of VLScT were available in 4 patients with 5 events. Of these, 3 had evidence of loss of integrity of the scaffold backbone manifesting as scaffold discontinuity and prolapse of struts into the vessel lumen. In addition, one patient exhibited marked vessel enlargement with aneurysm formation due to presumed
aggressive remodeling. These findings are concordant with observations of others. In the ABSORB Japan trial, for example, OCT imaging at the time of VLScT in 3 of the 4 patients who suffered VLScT showed strut discontinuities, malapposition and/or uncovered struts in each case [7]. A review by Sotomi et al. of the mechanisms of cases of scaffold thrombosis reported in the literature showed that in patients with VLScT attributed to scaffold recoil, positive vessel remodeling, evagination and scaffold discontinuity were frequently observed [18]. In the INVEST registry of patients with VLScT, scaffold discontinuity was the most frequent observation at VLScT with malapposition, neoatherosclerosis and underexpansion or scaffold recoil less frequently observed [19]. The extent to which the risk of VLScT events in our study could have been ameliorated by implantation technique is not known, though it seems less likely that discontinuity or remodeling years after implantation can be easily modified by procedural characteristics. 4.1. Limitations As a case series, our report is descriptive and cannot ascribe causality to the findings observed in association with VLScT. Intravascular imaging was not done at the time of angiographic surveillance and insights into risk factors for subsequent VLScT based on such imaging are not available. 5. Conclusions In this case series, routine surveillance angiography failed to identify features predictive of subsequent VLScT. Since all patients had stopped DAPT before VLScT and considering the OCT findings, prolongation of DAPT after BRS implantation may be considered. Funding NA.
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Declaration of Competing Interest MJ reports being a consultant for and receiving speaker fees from Biotronik and OrbusNeich. RAB reports lectures fees from B. Braun Melsungen, Biotronik, Boston Scientific and Micell Technologies and research funding to the institution from Boston Scientific and Celonova Biosciences. The other authors have no conflicts of interest to declare. References
Fig. 3. OCT correlates of VLScT. (A) OCT imaging at the site of VLScT for (patient 5) showed focal scaffold discontinuity in the distal scaffold (section I) with overlying thrombus and an otherwise acceptable result in the stented segment; (B) OCT imaging at the site of during VLScT for (patient 6) showed focal loss of scaffold integrity in the distal segment with prolapse of struts into the lumen interior (section I–II), thrombotic material surrounding the malapposed struts (panel I and II), possible neointimal bridge (section III) and moderate restenosis (panel IV–V); (C) OCT imaging in (patient 9) showed advanced scaffold degradation with positive remodeling, thrombotic material and formation of a large aneurysm in the region of the implanted BRS. * indicates artefact due to guide-wire.
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Please cite this article as: P. Hoppmann, H. Rai, R. Colleran, et al., Very late scaffold thrombosis after everolimus-eluting bioresorbable scaffold implantation in patien..., Cardiovascular Revascularization Medicine, https://doi.org/10.1016/j.carrev.2019.05.023