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Pre-Emptive OCT-Guided Angioplasty of Vulnerable Intermediate Coronary Lesions: Results from the Prematurely Halted PECTUS-Trial

Pre-Emptive OCT-Guided Angioplasty of Vulnerable Intermediate Coronary Lesions: Results from the... Hindawi Journal of Interventional Cardiology Volume 2020, Article ID 8821525, 8 pages https://doi.org/10.1155/2020/8821525 Research Article Pre-Emptive OCT-Guided Angioplasty of Vulnerable Intermediate Coronary Lesions: Results from the Prematurely Halted PECTUS-Trial 1 2 1 2 Jan-Quinten Mol , Michiel J. Bom, Peter Damman, Paul Knaapen, and Niels van Royen Department of Cardiology, Radboud University Medical Center, Nijmegen, Netherlands Department of Cardiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands Correspondence should be addressed to Niels van Royen; niels.vanroyen@radboudumc.nl Received 1 September 2020; Accepted 24 October 2020; Published 7 December 2020 Academic Editor: "ach N. Nguyen Copyright © 2020 Jan-Quinten Mol et al. "is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Objectives. To assess the safety and efficacy of pre-emptive treatment of optical coherence tomography- (OCT-) derived vul- nerable, non-flow-limiting, non-culprit lesions in patients with myocardial infarction (MI). Background. Intracoronary imaging with OCT can aid in the decision to treat non-flow-limiting lesions by identifying vulnerable plaques. Pre-emptive treatment of these lesions might improve patient outcome by “sealing” these plaques. Bioresorbable vascular scaffolds (BVS) have theoretical benefit for this treatment because they dissolve completely over time. Methods. In patients presenting with MI, non-culprit lesions with a fractional flow reserve≥0.8 were imaged with OCT. Vulnerable plaques were randomised to either percutaneous coronary intervention (PCI) with bioresorbable vascular scaffold (BVS) placement or optimal medicinal therapy (OMT). "e primary outcome was a composite of all-cause mortality, non-fatal MI, and unplanned revascularisation at 1-year follow-up. Results. "e trial was stopped prematurely after retraction from the market of the Absorb BVS. At that time, a total of 34 patients were randomised. At two years, the composite endpoint occurred 3 times (18.8%) in the BVS group and 1 time (6.3%) in the OMT group. Apart from one elective PCI for stable angina in the OMT group, no target lesions in any group were revascularised. Conclusions. Pre-emptive stenting of vulnerable plaques had no evident benefit compared to conservative treatment. However, due to the low number of included patients, no definite conclusions could be drawn. Identifying and potentially treating vulnerable plaques remains an important target for future research. "is trial is registered under https://www.trialregister.nl/trial/ NL4177 on 08-12-2015. It has been advocated that anatomic plaque character- 1. Introduction ization using intracoronary imaging could further aid the Although percutaneous coronary intervention and phar- treatment decision for non-culprit lesions in ACS. Several macologic therapies have improved the prognosis for pa- pathology studies have shown that there are certain mor- tients with acute coronary syndrome (ACS), recurrent major phological plaque characteristics that make an atheroscle- adverse cardiac events (MACE) are still common. Such rotic plaque vulnerable to rupture and subsequent events may occur at the original culprit lesion site, at pre- myocardial infarction (MI). "ese lesions generally have a existing non-culprit lesions or at newly developed lesions. large necrotic core and a thin overlying fibrous cap and are For non-culprit lesions, intracoronary physiology can guide frequently referred to as thin-cap fibroatheromas (TCFA) in the decision to perform stent placement. However, the [2]. "ese features have also been prospectively identified in MACE rate in ACS patients after FFR-guided deferral of vivo. In the PROSPECT study, a cohort of ACS patients stent placement in these non-culprit lesions is high as underwent three-vessel intravascular ultrasound (IVUS) for compared to stable coronary artery disease (CAD) [1]. the assessment of plaque morphology during the index 2 Journal of Interventional Cardiology invasive coronary angiography [3]. After a median follow-up randomised to either PCI and subsequent stenting with a of 3.4 years, it was shown that non-culprit lesions identified BVS (Figure 2) or optimal medical therapy in a 1 :1 fashion. No more than one lesion per patient was randomised, even if as TCFA had a hazard ratio of 3.35 for causing future MACE. Nevertheless, the use of IVUS for assessing plaque com- multiple vulnerable plaques were identified. "e choice ponents is hampered by its relatively limited spatial reso- which lesion to target was left at the discretion of the op- lution. In pathology studies, the average fibrous cap erator, but preferably, the most proximal lesion was selected thickness of ruptured plaques at autopsy was 23μm, and and with consideration of the following hierarchy: first, the 95% of all ruptured caps measured less than 65μm [4], left anterior descending artery and, second, the right cor- whereas IVUS only has a spatial resolution of 100μm. Since onary artery in patients with a right dominant coronary PROSPECT, Optical Coherence Tomography (OCT) circulation or the left circumflex artery in patients with a left intracoronary imaging has become available. OCT has a dominant circulation. Patients with only FFR-positive or much higher spatial resolution of approximately 10μm, only non-vulnerable lesions were excluded from the study which truly allows for measurement of fibrous cap thickness. protocol and subjected to clinical follow-up in a registry. Additionally, OCT is able to identify infiltrating macro- phages, which is another hallmark of unstable lesions [5]. 2.2. OCT Analysis. OCT analysis of target lesions was per- "is intravascular imaging technique, therefore, seems to be formed in real time during the ICA. Analysis of any addi- more suitable for the evaluation of plaque morphology [6]. tional “non-target” lesions that were captured on the OCT Identifying vulnerable plaques in vivo has led to the pullback was performed offline using an offline review hypothesis of preventive intervention of these lesions. A workstation (Abbott, formerly St Jude Medical, USA). small study has shown that stenting TCFA resulted in the Evaluation of the images was based on tissue characteristics development of neointima, thereby “sealing” the vulnerable as previously described in OCT expert consensus papers plaque [7]. A bioresorbable vascular scaffold (BVS) might [10]. A plaque was deemed “vulnerable” if it contained two have a theoretical benefit for this treatment because it of the following characteristics: a lipid arc (defined as a dissolves completely over time. "erefore, we initiated the diffusely bordered signal-poor region) of more than 90 PECTUS trial, a multicenter randomised controlled trial degrees, a cap thickness (defined as a signal-rich band comparing PCI with BVS (Absorb) placement versus Op- overlying a lipid core) of <65μm, and either cap rupture or timal Medicinal "erapy (OMT) of OCT-determined vul- thrombus formation. nerable, FFR-negative, non-culprit lesions in patients with myocardial infarction (NL4177). "e trial was stopped prematurely after the reporting of 2.3. Medicinal +erapy. Patients in both groups received increased stent-thrombosis and the subsequent retraction pharmacologic treatment according to current guidelines. from the market of the Absorb stent [8, 9]. At that time, a Due to the reporting of increased stent-thrombosis of BVS total of 34 out of the 500 planned patients were enrolled in compared to metallic stents during the trial, all randomised the trial. Here, we report the OCT characteristics and the patients were recommended to continue dual antiplatelet clinical outcomes of these 34 patients. therapy (DAPT) for at least 3 years if they tolerated DAPT without bleeding complications and were not at high 2. Materials and Methods bleeding risk (e.g., prior bleeding on DAPT, coagulopathy, or oral anticoagulant use). 2.1. Study Flow. A flowchart of the study design is shown in Figure 1. Patients presenting to the hospital with a myo- cardial infarction (ST-elevation or a non-ST-elevation) were 2.4. Outcome Measure and Power Analysis. "e primary screened for potential inclusion in the study. Patients were outcome of this trial was a composite of all-cause mortality, treated according to the current guidelines for the man- non-fatal MI, and unplanned revascularisation at 1-year agement of ACS, including referral for invasive coronary Secondary outcomes included the composite outcome at 2 angiography (ICA) and (potential) PCI of the culprit artery. and 5 years and the individual components at 1, 2, and 5 Patients were subsequently approached for participation in years. Based on an expected event rate of 5% in the inter- the study if any intermediate non-culprit stenoses were vention group versus 13% in the OMT group, with a two- identified during ICA and if they were eligible for inclusion sided alpha of 5% and a drop-out rate of 10%, 500 patients based on the criteria listed in Table 1. were needed to demonstrate superiority of BVS stenting of After obtaining informed consent, patients underwent a vulnerable plaques. re-ICA during which the non-culprit lesions were evaluated for physiological significance by fractional flow reserve 3. Results (FFR). FFR-positive (<0.80) lesions were treated with PCI according to current guidelines. All non-flow-limiting Inclusion in the study started in March of 2016 and was (FFR≥ 0.80) lesions were imaged with OCT. OCT Images subsequently halted in March of 2017. A total of 63 patients were acquired using a commercially available frequency- underwent re-ICA with FFR-measurements of non-culprit domain OCT system (Abbott, formerly St Jude Medical, lesions (Figure 1). In nine patients, the non-culprit lesions USA). Trained personnel evaluated the OCTimages of target were FFR-positive, and hence, subsequent revascularisation lesions for plaque vulnerability. Vulnerable plaques were was performed. Of the remaining 54 patients, 52 underwent Journal of Interventional Cardiology 3 STEMI/NSTEMI with treatment of culprit lesion Presence of intermediate non-culprit lesion FFR < 0.8 Exclusion aer FFR FFR-measurement (9) No lesions with FFR ≥ non-culprit stenosis Exclusion + PCI 0.8. (9) (63) Patients refused OCT. FFR ≥ 0.8 (2) (54) Not vulnerable Exclusion aer OCT OCT assessment of (11) Lesion not vulnerable. vulnerability Exclusion (11) (52) Vessel diameter to large for BVS implant. Vulnerable (41) (7) Randomisation (34) Lost to follow-up Withdrawal of consent. PCI with BVS OMT (1) (17) (17) Migrated to another country. Not traceable. (1) 2-year follow-up 2-year follow-up (16) (16) Figure 1: Study Flowchart. BVS, bioresorbable vascular scaffold, FFR, fractional flow reserve, NSTEMI, non-ST-elevation myocardial infarction, OCT, optical coherence tomography, OMT, optimal medicinal therapy, PCI, percutaneous coronary intervention, STEMI, ST- elevation myocardial infarction. OCT imaging of a total of 59 FFR-negative lesions, whereas 2 (Table 3) were as follows: the average fibrous cap thickness patients refused OCT imaging. Among the 52 that underwent was 50.0μm± 10.3 in the BVS group vs. 50.6μm± 10.0 in the OMTgroup. A plaque rupture or thrombus was identified in OCT imaging, a vulnerable target lesion could be identified in 41 (79%) patients. Of all 59 OCT pullbacks of FFR-negative 1 (6.25%) of the target lesions in the BVS group vs. 2 (12.5%) lesions, 44 (75%) showed a vulnerable lesion. Seven patients in the OMT group. 100% of target lesions in both groups were excluded due to a vessel diameter too large for BVS contained a lipid arc of >90 degrees. "e average minimal implantation, resulting in a total of 34 patients who were lumen area was 2.69± 0.99 mm in the BVS group and eventually randomised (17 BVS vs. 17 OMT). Apart from one 2.57± 1.07 mm in the OMT group. In the BVS group, the withdrawal of consent in the BVS group and one lost to average minimal lumen area changed from 2.69± 0.99 mm follow-up in the OMT group, two-year follow-up was ob- to 6.55± 1.81 mm after stent placement. Analysis of the tained of all participants that were included up to that point. OCT images beyond the angiographically targeted lesions Table 2 shows patient baseline characteristics. "e mean revealed the average presence of 0.2± 0.4 additional vul- age of participants was 62.1± 10.4 years in BVS vs. 70.3± 5.9 nerable non-target lesions and 0.7± 1.1 additional non- years in the OMTgroup. "e percentage of male participants vulnerable non-target lesions per OCT-pullback in the BVS was 75.0% in BVS vs. 75.0% in OMT. STEMI was the initial group. In the OMT group, an additional 0.5± 0.8 vulnerable presentation in 43% in BVS vs. 50% in OMT. OCT char- non-target lesions and 0.9± 0.7 non-vulnerable non-target acteristics of the target lesions in the randomised groups lesions were identified. 4 Journal of Interventional Cardiology Table 1: Inclusion and exclusion criteria. Inclusion criteria Exclusion criteria Clinical Clinical (i) Age ≥18 years (i) Pregnancy (ii) Clinical presentation of STEMI or NSTEMI (ii) Severe kidney disease defined as an eGFR <30 ml/min (iii) Previous CABG (iv) Indication for revascularization by CABG (v) Estimated life expectancy <1 year Angiographical Angiographical (i) Presence of residual, intermediate CAD (diameter stenosis (i) Target vessel diameter <2.5 mm or >4.0 mm of 30–90%), with the possibility of plaque vulnerability (ii) Anatomy of lesion unsuitable for OCT catheter crossing or imaging (aorta-ostial lesions, small diameter segment, and severe calcifications) (iii) Anatomy unsuitable for BVS placement (left main, bifurcation, and side branch (>2 mm) involvement) (iv) Target lesion is (a) In-stent restenosis (b) Chronic total occlusion (c) In the same vessel as treated culprit lesion (d) In the same segment as a previously implanted stent/scaffold BVS, bioresorbable vascular scaffold, CABG, coronary artery bypass grafting, CAD, coronary artery disease, NSTEMI, Non-ST-elevation myocardial in- farction, OCT, optical coherence tomography, STEMI, ST-elevation myocardial infarction. During two-year follow-up, a total of 12 clinical events non-complex lesions. "is is also in line with the midterm were recorded, of which 4 were adjudicated as MACE results of BVS in STEMI-patients [11]. (Table 4). "e number of MACE was 3 in the BVS group and We observed a lower-than-expected rate of MACE 1 in the OMT group. "e events in the BVS group were a (6.3%) in the OMTgroup. In comparison, the 2-year follow- up results of the FAME trial showed a MACE rate of 17.9% non-cardiac death and two non-study vessel-related MIs. "e sole MACE in the OMTgroup was a non-cardiac death. in patients who had undergone complete FFR-guided Apart from one elective PCI for stable angina in the OMT revascularisation [12]. A possible explanation for these group, no target lesions in any group were revascularised discrepancies, in addition to the limited patient population, during the two-year follow-up. could be that patients in this trial were advised to continue DAPT for up to 3 years after the index event. Current guidelines recommend physiological measure- ments to determine the hemodynamic significance of an- 4. Discussion giographic intermediate lesions, based on several large trials In the PECTUS trial, patients with myocardial infarction and [13, 14]. Despite the obvious benefit of FFR-measurements an FFR-negative OCT-based vulnerable non-culprit lesion in guiding revascularisation, long-term follow-up patients were randomised between an intervention with a BVS and with deferred lesions still show significant event rates. "e 5- optimal medical therapy. Due to the low number of included year follow-up of the FAME trial demonstrated a 28% event patients, no robust conclusions can be drawn with respect to rate in patients who had been treated with FFR-guided the safety or efficacy of preventive stenting of these plaques complete revascularisation [15]. Additionally, some studies based on this study. Nevertheless, there were some notable have suggested that FFR-guided treatment decision based on results. In the 34 patients that were randomised, MACE studies in patients with stable CAD cannot simply be occurred 3 times (18.8%) in the BVS group and once (6.3%) adopted in ACS patients [1, 16]. "erefore, besides treatment in the OMT group. "is would indicate that stenting of or referral based on physiological significance, anatomical vulnerable lesions with BVS has no evident benefit com- characteristics might further improve treatment decision. In pared to medical treatment or might even result in worse support of this, recent multicentre non-invasive imaging outcomes. However, no case of MACE was related to a target studies have clearly shown that the use of anatomical im- lesion. "e only target lesion-related event was an elective aging with coronary computed tomography angiography PCI due to stable angina in the OMT group. "is is in (CCTA) leads to a more favourable prognosis as compared contrast with the AIDA trial [8], in which patients under- to standard of care using functional testing [17]. Addi- going PCI were randomised between BVS and metallic tionally, a recent small single-center trial demonstrated stents. In this trial, target vessel failure at 2-year follow-up superiority of image-guided intervention compared with had occurred in 11.7% of patients with BVS. Additionally, no physiology-guided intervention [18]. Although these results device thrombosis was seen in the current study. "is could have to be confirmed in larger trials, they hint at the ad- suggest that BVS implantation is related to relatively low ditional value of anatomical information in guiding coro- device-related complications in these non-flow-limiting nary intervention. Journal of Interventional Cardiology 5 B length: 0.06 mm C angle: 134.9° 1mm (a) (b) 1mm (c) (d) Figure 2: OCT with angiography coregistration of a patient randomised to BVS placement. (a) Angiogram shows an intermediate stenosis in the proximal circumflex coronary artery (white marker). (b) OCTof the stenosis reveals a vulnerable plaque (lipid arc>90 with a cap of 60μm). (c) Angiogram shows the same lesions as in A (white marker) after BVS placement. (d). OCTshows BVS placement over vulnerable plaque with good stent apposition. In PECTUS, a plaque was considered eligible for ran- Table 2: Baseline characteristics. domisation if it showed two characteristics of vulnerability. Whilst all randomised target lesions contained a lipid arc of BVS (n � 16) OMT (n � 16) >90 degrees, only 9% of these lesions showed a plaque rupture Age—years 62.1± 10.4 70.3± 5.9 or thrombus. Even though these, and other characteristics such Sex—n (%) as neointimal vascularisation and fibrous cap inflammation, Male 12 (75) 12 (75) have all been associated with plaque rupture, there is no clear Female 4 (25) 4 (25) answer as to what (combination of) feature(s) is the most Clinical presentation—n (%) hazardous. Nonetheless, the body of evidence linking plaque STEMI 7 (43) 8 (50) morphology to MACE is growing. Following PROSPECT, the NSTEMI 9 (57) 8 (50) VIVA and ATHEROREMO-IVUS studies also showed an Target vessel—n (%) association between IVUS-derived characteristics of vulnera- LAD 6 (37.5) 7 (43.75) bility and MACE [3, 19, 20]. Moreover, this association is also Cx 6 (37.5) 6 (37.5) found in other imaging modalities such as near infrared RCA 4 (25) 3 (18.75) spectroscopy (NIRS) and CCTA [21, 22]. Because of the Average FFR 0.90± 0.07 0.90± 0.06 novelty of the technique, validation studies for the ability of BVS, bioresorbable vascular scaffold, Cx, circumflex artery, LAD, left an- OCT to detect vulnerable plaques are scarce. In the recent terior descending artery, FFR, fractional flow reserve, NSTEMI, Non-ST- CLIMA study, investigators analysed images of 1003 patients elevation myocardial infarction, OMT, optimal medicinal therapy, RCA, right coronary artery, STEMI, ST-elevation myocardial infarction, who had undergone OCT-imaging of the proximal LAD in the 6 Journal of Interventional Cardiology Table 3: Target lesion OCT characteristics. BVS (n � 16) OMT (n � 16) Average cap thickness—μm 50.0± 10.3 50.6± 10.0 Plaque rupture or thrombus—n (%) 1 (6.25%) 2 (12.5%) Lesions with >1 lipid quadrant—n (%) 16 (100%) 16 (100%) Average MLA—mm 2.69± 0.99 2.57± 1.07 Average MLA after PCI—mm 6.55± 1.81 — Average number of additional non-target lesions per pullback 0.9± 1.3 1.4± 0.8 (i) Vulnerable 0.2± 0.4 0.5± 0.8 (ii) Non-vulnerable 0.7± 1.1 0.9± 0.7 BVS, bioresorbable vascular scaffold, OCT, optical coherence tomography, OMT, optimal medicinal therapy, MLA, minimal lumen area, PCI, percutaneous coronary intervention. Table 4: Clinical events. FFR of Target Target Time after No. Group target Event MACE lesion segment randomisation lesion related Cardiac arrest due to pulseless electrical activity during BVS implantation, for which chest compressions were performed for 1 minute and During BVS atropine was given, after which return of 1 (1) BVS LAD-mid (7) 0.82 No Yes implant spontaneous circulation occurred. No mechanical complication was seen. Postprocedural troponin values were not elevated. Episode was attributed to a vagal reaction. Elective PCI of proximal and distal RCA (in-stent restenosis distal RCA) because of progressive angina. 1 (2) BVS LAD-mid (7) 0.82 6 months No No No pre-intervention FFR was performed because stenosis in distal RCA was 90%. Cardiac arrest due to ventricular fibrillation. ICA shows left main coronary artery occlusion, for which 2 BVS LAD-mid (7) 0.81 4 months Yes No PCI was performed. OCT shows good patency of BVS in the mid LAD. Non-cardiac death due to obstruction hydrocephalus 3 BVS LAD-mid (7) 0.84 24 months Yes No caused by metastasized lung carcinoma. 4 BVS RCA-prox (1) 0.93 23 months Elective PCI of LAD-mid because of stable angina. No No Infected hematoma of the femoral puncture site/ 5 BVS LAD-mid (7) 0.86 8 days No No closure device. STEMI with PCI of distal RCA (culprit). Additional occlusion of a small MO2 branch. "is occlusion was 6 BVS Cx-mid (13) 0.95 15 months not intervened upon as patient was free of Yes No complaints after PCI of the RCA. BVS in the mid-Cx was patent. Non-cardiac death due to aspiration pneumonia in 7 OMT LAD-mid (7) 0.87 12 months patient with lymphoma and metastasized squamous Yes No cell carcinoma. Hospital admission with chest pain and slightly elevated cardiac troponin levels without rise/fall. 8 OMT Cx-mid (13) 1.00 24 months No No ICA showed no obstructive coronary artery disease. Complaints were attributed to hypertension. 9 OMT Cx-prox (1) 0.83 22 months Lobectomy for newly diagnosed lung carcinoma. No No Same day as 10 OMT MO1 (12) 0.97 Transient binocular diplopia after ICA. No No randomisation Elective PCI of the mid LAD (target segment) and proximal RCA due to stable angina and optimisation 11 OMT LAD-mid (7) 0.89 24 months for esophageal cancer-related chemotherapy. No No Yes pre-intervention FFR was performed because the wire could not pass the mid-LAD. BVS, bioresorbable vascular scaffold, Cx, circumflex artery, FFR, fractional flow reserve, ICA, invasive coronary angiography, LAD, left anterior descending artery, MACE, major adverse cardiac event, MLA, minimal lumen area, MO, obtuse marginal artery, OCT, optical coherence tomography, OMT, optimal medicinal therapy, PCI, percutaneous coronary intervention, RCA, right coronary artery, STEMI, ST-elevation myocardial infarction. Journal of Interventional Cardiology 7 context of a clinically indicated ICA. "is study showed that the CAD: Coronary artery disease combination of four morphological plaque features was an TCFA: "in-cap fibroatheroma independent predictor of MACE with a hazard ratio of 7.54 at 1 IVUS: Intravascular ultrasound year [23]. In CLIMA, however, the OCT imaging was per- STEMI: ST-elevation myocardial infarction formed on a fixed segment of the coronary artery tree as NSTEMI: Non-ST-elevation myocardial infarction opposed to a segment based on angiographic stenosis. ICA: Invasive coronary angiography "erefore, the technique was evaluated more as a tool for DAPT: Dual antiplatelet therapy prognostic risk stratification instead of imaging based lesion CCTA: Coronary computed tomography angiography treatment. "e same holds true for the other intravascular NIRS: Near-infrared spectroscopy imaging studies. Data on “targeted” intravascular imaging of CABG: Coronary artery bypass grafting angiographically defined stenoses is still lacking. Several studies MLA: Minimal lumen area. are currently trying to address this gap in knowledge. Among them are the COMBINE study (NCT02989740) and PECTUS- Data Availability obs study (NCT03857971). In line with the current PECTUS trial, the above- "e data used to support the findings of this study are mentioned FORZA trial also assessed OCT-guided PCI [18]. available from the corresponding author upon request. In this study, 350 patients were randomised between FFR- guided or OCT-guided PCI of angiographically intermediate Ethical Approval coronary lesions. At 13-month follow-up, patients in the OCT-guided group had significantly less MACE or signif- "is trial was approved by the Medical Ethics Committee of icant angina compared to patients in the FFR-guided group. the Vrije Universiteit Medical Center and has, therefore, However, the decision whether or not to stent a lesion in the been performed in accordance with the ethical standards laid OCT group was based on a combination of OCT-derived down in the 1964 Declaration of Helsinki and its later area stenosis, minimal lumen area, and the presence of amendments. plaque rupture. "erefore, apart from plaque rupture, this study did not take characteristics of vulnerability into ac- Consent count. In contrast, two other randomised studies that are currently being conducted have a similar design to PECTUS. Informed consent was given by all participants. "e PROSPECT-ABSORB (NCT02171065) and PREVENT (NCT02316886) both randomise patients with residual non- Conflicts of Interest obstructive vulnerable plaques to either BVS placement or optimal medicinal therapy although they differ in the in- Dr. Van Royen reports grants from Philips, grants from travascular imaging modality used. Abbott, grants from Biotronik, and personal fees from Medtronic, outside the submitted work. Dr. Damman re- 5. Limitations ports personal fees from Philips, outside the submitted work. "e other authors have no conflicts of interest to declare. "e main limitation of the PECTUS trial is the low number of included patients due to the early termination of the trial. Acknowledgments 6. Conclusions "is trial was financially supported by Abbott Vascular and Health Holland. In conclusion, the PECTUS trial could not shed light on the theoretical benefit of preventive stenting of non-flow-lim- References iting vulnerable lesions due to early termination of the trial. Nonetheless, the concept of identifying and potentially [1] A. Hakeem, M. M. Edupuganti, A. Almomani et al., “Long- treating vulnerable plaques remains an important field for term prognosis of deferred acute coronary syndrome lesions future research given the relatively large MACE rates as based on nonischemic fractional flow reserve,” Journal of the reported for this specific cohort of patients. American College of Cardiology, vol. 68, no. 11, pp. 1181–1191, [2] M. J. Bom, D. J. V. D. Heijden, E. Kedhi et al., “Early detection Abbreviations and treatment of the vulnerable coronary plaque,” Circula- tion: Cardiovascular Imaging, vol. 10, no. 5, 2017. OCT: Optical coherence tomography [3] G. W. Stone, A. Maehara, A. J. Lansky et al., “A prospective MI: Myocardial infarction natural-history study of coronary atherosclerosis,” New En- PCI: Percutaneous coronary intervention gland Journal of Medicine, vol. 364, no. 3, pp. 226–235, 2011. FFR: Fractional flow reserve [4] A. P. Burke, A. Farb, G. T. Malcom, Y.-H. Liang, J. Smialek, BVS: Bioresorbable vascular scaffold and R. Virmani, “Coronary risk factors and plaque mor- OMT: Optimal medicinal therapy phology in men with coronary disease who died suddenly,” ACS: Acute coronary syndrome New England Journal of Medicine, vol. 336, no. 18, MACE: Major adverse cardiac events pp. 1276–1282, 1997. 8 Journal of Interventional Cardiology [5] G. J. Tearney, H. Yabushita, S. L. Houser et al., “Quantification stenosis: a single-center trial,” JACC: Cardiovascular Inter- ventions, vol. 13, no. 1, pp. 49–58, 2000. of macrophage content in atherosclerotic plaques by optical coherence tomography,” Circulation, vol. 107, no. 1, [19] P. A. Calvert, D. R. Obaid, M. O’Sullivan et al., “Association between IVUS findings and adverse outcomes in patients with pp. 113–119, 2003. [6] T. Kubo, T. Imanishi, S. Takarada et al., “Assessment of culprit coronary artery disease,” JACC: Cardiovascular Imaging, vol. 4, no. 8, pp. 894–901, 2011. lesion morphology in acute myocardial infarction,” Journal of [20] J. M. Cheng, H. M. Garcia-Garcia, S. P. M. D. Boer et al., “In the American College of Cardiology, vol. 50, no. 10, pp. 933– vivo detection of high-risk coronary plaques by radio- 939, 2007. frequency intravascular ultrasound and cardiovascular out- [7] C. V. Bourantas, P. W. Serruys, S. Nakatani et al., “Bio- come: results of the ATHEROREMO-IVUS study,” European resorbable vascular scaffold treatment induces the formation Heart Journal, vol. 35, no. 10, pp. 639–647, 2014. of neointimal cap that seals the underlying plaque without [21] R. Waksman, C. D. Di Mario, R. Torguson et al., “Identifi- compromising the luminal dimensions: a concept based on cation of patients and plaques vulnerable to future coronary serial optical coherence tomography data,” EuroIntervention, events with near-infrared spectroscopy intravascular ultra- vol. 11, no. 8, pp. 746–756, 2015. sound imaging: a prospective, cohort study,” +e Lancet, [8] J. J. Wykrzykowska, R. P. Kraak, S. H. Hofma et al., “Bio- vol. 394, no. 10209, pp. 1629–1637, 2019. resorbable scaffolds versus metallic stents in routine PCI,” [22] M. Ferencik, T. Mayrhofer, D. O. Bittner et al., “Use of New England Journal of Medicine, vol. 376, no. 24, high-risk coronary atherosclerotic plaque detection for risk pp. 2319–2328, 2017. stratification of patients with stable chest pain: a secondary [9] D. J. Kereiakes, S. G. Ellis, C. Metzger et al., “3-Year clinical analysis of the PROMISE randomized clinical trial,” JAMA outcomes with everolimus-eluting bioresorbable coronary Cardiology, vol. 3, no. 2, p. 144, 2018. scaffolds,” Journal of the American College of Cardiology, [23] F. Prati, E. Romagnoli, L. Gatto et al., “Relationship between vol. 70, no. 23, pp. 2852–2862, 2017. coronary plaque morphology of the left anterior descending [10] F. Prati, E. Regar, G. S. Mintz et al., “Expert review document artery and 12 months clinical outcome: the CLIMA study,” on methodology, terminology, and clinical applications of European Heart Journal, vol. 41, no. 3, pp. 383–391, 2020. optical coherence tomography: physical principles, method- ology of image acquisition, and clinical application for as- sessment of coronary arteries and atherosclerosis,” European Heart Journal, vol. 31, no. 4, pp. 401–415, 2010. [11] S. Cassese, Y. Katagiri, R. A. Byrne et al., “Angiographic and clinical outcomes of STEMI patients treated with bio- resorbable or metallic everolimus-eluting stents: a pooled analysis of individual patient data,” EuroIntervention, vol. 15, no. 16, pp. 1451–1457, 2020. [12] N. H. J. Pijls, W. F. Fearon, P. A. L. Tonino et al., “Fractional flow reserve versus angiography for guiding percutaneous coronary intervention in patients with multivessel coronary artery disease,” Journal of the American College of Cardiology, vol. 56, no. 3, pp. 177–184, 2010. [13] P. A. L. Tonino, B. D. Bruyne, N. H. J. Pijls et al., “Fractional flow reserve versus angiography for guiding percutaneous coronary intervention,” New England Journal of Medicine, vol. 360, no. 3, pp. 213–224, 2009. [14] P. C. Smits, M. Abdel-Wahab, F.-J. Neumann et al., “Frac- tional flow reserve-guided multivessel angioplasty in myo- cardial infarction,” New England Journal of Medicine, vol. 376, no. 13, pp. 1234–1244, 2017. [15] L. X. V. Nunen, F. M. Zimmermann, P. A. L. Tonino et al., “Fractional flow reserve versus angiography for guidance of PCI in patients with multivessel coronary artery disease (FAME): 5-year follow-up of a randomised controlled trial,” +e Lancet, vol. 386, no. 10006, pp. 1853–1860, 2015. [16] S. M. Mehta, J. P. Depta, E. Novak et al., “Association of lower fractional flow reserve values with higher risk of adverse cardiac events for lesions deferred revascularization among patients with acute coronary syndrome,” Journal of the American Heart Association, vol. 4, no. 8, Article ID e002172, [17] D. E. Newby, P. D. Adamson, C. Berry et al., “Coronary CT angiography and 5-year risk of myocardial infarction,” +e New England Journal of Medicine, vol. 379, no. 10, pp. 924– 933, 2018. [18] F. Burzotta, A. M. Leone, C. Aurigemma et al., “Fractional flow reserve or optical coherence tomography to guide management of angiographically intermediate coronary http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Interventional Cardiology Hindawi Publishing Corporation

Pre-Emptive OCT-Guided Angioplasty of Vulnerable Intermediate Coronary Lesions: Results from the Prematurely Halted PECTUS-Trial

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Copyright © 2020 Jan-Quinten Mol et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Hindawi Journal of Interventional Cardiology Volume 2020, Article ID 8821525, 8 pages https://doi.org/10.1155/2020/8821525 Research Article Pre-Emptive OCT-Guided Angioplasty of Vulnerable Intermediate Coronary Lesions: Results from the Prematurely Halted PECTUS-Trial 1 2 1 2 Jan-Quinten Mol , Michiel J. Bom, Peter Damman, Paul Knaapen, and Niels van Royen Department of Cardiology, Radboud University Medical Center, Nijmegen, Netherlands Department of Cardiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands Correspondence should be addressed to Niels van Royen; niels.vanroyen@radboudumc.nl Received 1 September 2020; Accepted 24 October 2020; Published 7 December 2020 Academic Editor: "ach N. Nguyen Copyright © 2020 Jan-Quinten Mol et al. "is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Objectives. To assess the safety and efficacy of pre-emptive treatment of optical coherence tomography- (OCT-) derived vul- nerable, non-flow-limiting, non-culprit lesions in patients with myocardial infarction (MI). Background. Intracoronary imaging with OCT can aid in the decision to treat non-flow-limiting lesions by identifying vulnerable plaques. Pre-emptive treatment of these lesions might improve patient outcome by “sealing” these plaques. Bioresorbable vascular scaffolds (BVS) have theoretical benefit for this treatment because they dissolve completely over time. Methods. In patients presenting with MI, non-culprit lesions with a fractional flow reserve≥0.8 were imaged with OCT. Vulnerable plaques were randomised to either percutaneous coronary intervention (PCI) with bioresorbable vascular scaffold (BVS) placement or optimal medicinal therapy (OMT). "e primary outcome was a composite of all-cause mortality, non-fatal MI, and unplanned revascularisation at 1-year follow-up. Results. "e trial was stopped prematurely after retraction from the market of the Absorb BVS. At that time, a total of 34 patients were randomised. At two years, the composite endpoint occurred 3 times (18.8%) in the BVS group and 1 time (6.3%) in the OMT group. Apart from one elective PCI for stable angina in the OMT group, no target lesions in any group were revascularised. Conclusions. Pre-emptive stenting of vulnerable plaques had no evident benefit compared to conservative treatment. However, due to the low number of included patients, no definite conclusions could be drawn. Identifying and potentially treating vulnerable plaques remains an important target for future research. "is trial is registered under https://www.trialregister.nl/trial/ NL4177 on 08-12-2015. It has been advocated that anatomic plaque character- 1. Introduction ization using intracoronary imaging could further aid the Although percutaneous coronary intervention and phar- treatment decision for non-culprit lesions in ACS. Several macologic therapies have improved the prognosis for pa- pathology studies have shown that there are certain mor- tients with acute coronary syndrome (ACS), recurrent major phological plaque characteristics that make an atheroscle- adverse cardiac events (MACE) are still common. Such rotic plaque vulnerable to rupture and subsequent events may occur at the original culprit lesion site, at pre- myocardial infarction (MI). "ese lesions generally have a existing non-culprit lesions or at newly developed lesions. large necrotic core and a thin overlying fibrous cap and are For non-culprit lesions, intracoronary physiology can guide frequently referred to as thin-cap fibroatheromas (TCFA) in the decision to perform stent placement. However, the [2]. "ese features have also been prospectively identified in MACE rate in ACS patients after FFR-guided deferral of vivo. In the PROSPECT study, a cohort of ACS patients stent placement in these non-culprit lesions is high as underwent three-vessel intravascular ultrasound (IVUS) for compared to stable coronary artery disease (CAD) [1]. the assessment of plaque morphology during the index 2 Journal of Interventional Cardiology invasive coronary angiography [3]. After a median follow-up randomised to either PCI and subsequent stenting with a of 3.4 years, it was shown that non-culprit lesions identified BVS (Figure 2) or optimal medical therapy in a 1 :1 fashion. No more than one lesion per patient was randomised, even if as TCFA had a hazard ratio of 3.35 for causing future MACE. Nevertheless, the use of IVUS for assessing plaque com- multiple vulnerable plaques were identified. "e choice ponents is hampered by its relatively limited spatial reso- which lesion to target was left at the discretion of the op- lution. In pathology studies, the average fibrous cap erator, but preferably, the most proximal lesion was selected thickness of ruptured plaques at autopsy was 23μm, and and with consideration of the following hierarchy: first, the 95% of all ruptured caps measured less than 65μm [4], left anterior descending artery and, second, the right cor- whereas IVUS only has a spatial resolution of 100μm. Since onary artery in patients with a right dominant coronary PROSPECT, Optical Coherence Tomography (OCT) circulation or the left circumflex artery in patients with a left intracoronary imaging has become available. OCT has a dominant circulation. Patients with only FFR-positive or much higher spatial resolution of approximately 10μm, only non-vulnerable lesions were excluded from the study which truly allows for measurement of fibrous cap thickness. protocol and subjected to clinical follow-up in a registry. Additionally, OCT is able to identify infiltrating macro- phages, which is another hallmark of unstable lesions [5]. 2.2. OCT Analysis. OCT analysis of target lesions was per- "is intravascular imaging technique, therefore, seems to be formed in real time during the ICA. Analysis of any addi- more suitable for the evaluation of plaque morphology [6]. tional “non-target” lesions that were captured on the OCT Identifying vulnerable plaques in vivo has led to the pullback was performed offline using an offline review hypothesis of preventive intervention of these lesions. A workstation (Abbott, formerly St Jude Medical, USA). small study has shown that stenting TCFA resulted in the Evaluation of the images was based on tissue characteristics development of neointima, thereby “sealing” the vulnerable as previously described in OCT expert consensus papers plaque [7]. A bioresorbable vascular scaffold (BVS) might [10]. A plaque was deemed “vulnerable” if it contained two have a theoretical benefit for this treatment because it of the following characteristics: a lipid arc (defined as a dissolves completely over time. "erefore, we initiated the diffusely bordered signal-poor region) of more than 90 PECTUS trial, a multicenter randomised controlled trial degrees, a cap thickness (defined as a signal-rich band comparing PCI with BVS (Absorb) placement versus Op- overlying a lipid core) of <65μm, and either cap rupture or timal Medicinal "erapy (OMT) of OCT-determined vul- thrombus formation. nerable, FFR-negative, non-culprit lesions in patients with myocardial infarction (NL4177). "e trial was stopped prematurely after the reporting of 2.3. Medicinal +erapy. Patients in both groups received increased stent-thrombosis and the subsequent retraction pharmacologic treatment according to current guidelines. from the market of the Absorb stent [8, 9]. At that time, a Due to the reporting of increased stent-thrombosis of BVS total of 34 out of the 500 planned patients were enrolled in compared to metallic stents during the trial, all randomised the trial. Here, we report the OCT characteristics and the patients were recommended to continue dual antiplatelet clinical outcomes of these 34 patients. therapy (DAPT) for at least 3 years if they tolerated DAPT without bleeding complications and were not at high 2. Materials and Methods bleeding risk (e.g., prior bleeding on DAPT, coagulopathy, or oral anticoagulant use). 2.1. Study Flow. A flowchart of the study design is shown in Figure 1. Patients presenting to the hospital with a myo- cardial infarction (ST-elevation or a non-ST-elevation) were 2.4. Outcome Measure and Power Analysis. "e primary screened for potential inclusion in the study. Patients were outcome of this trial was a composite of all-cause mortality, treated according to the current guidelines for the man- non-fatal MI, and unplanned revascularisation at 1-year agement of ACS, including referral for invasive coronary Secondary outcomes included the composite outcome at 2 angiography (ICA) and (potential) PCI of the culprit artery. and 5 years and the individual components at 1, 2, and 5 Patients were subsequently approached for participation in years. Based on an expected event rate of 5% in the inter- the study if any intermediate non-culprit stenoses were vention group versus 13% in the OMT group, with a two- identified during ICA and if they were eligible for inclusion sided alpha of 5% and a drop-out rate of 10%, 500 patients based on the criteria listed in Table 1. were needed to demonstrate superiority of BVS stenting of After obtaining informed consent, patients underwent a vulnerable plaques. re-ICA during which the non-culprit lesions were evaluated for physiological significance by fractional flow reserve 3. Results (FFR). FFR-positive (<0.80) lesions were treated with PCI according to current guidelines. All non-flow-limiting Inclusion in the study started in March of 2016 and was (FFR≥ 0.80) lesions were imaged with OCT. OCT Images subsequently halted in March of 2017. A total of 63 patients were acquired using a commercially available frequency- underwent re-ICA with FFR-measurements of non-culprit domain OCT system (Abbott, formerly St Jude Medical, lesions (Figure 1). In nine patients, the non-culprit lesions USA). Trained personnel evaluated the OCTimages of target were FFR-positive, and hence, subsequent revascularisation lesions for plaque vulnerability. Vulnerable plaques were was performed. Of the remaining 54 patients, 52 underwent Journal of Interventional Cardiology 3 STEMI/NSTEMI with treatment of culprit lesion Presence of intermediate non-culprit lesion FFR < 0.8 Exclusion aer FFR FFR-measurement (9) No lesions with FFR ≥ non-culprit stenosis Exclusion + PCI 0.8. (9) (63) Patients refused OCT. FFR ≥ 0.8 (2) (54) Not vulnerable Exclusion aer OCT OCT assessment of (11) Lesion not vulnerable. vulnerability Exclusion (11) (52) Vessel diameter to large for BVS implant. Vulnerable (41) (7) Randomisation (34) Lost to follow-up Withdrawal of consent. PCI with BVS OMT (1) (17) (17) Migrated to another country. Not traceable. (1) 2-year follow-up 2-year follow-up (16) (16) Figure 1: Study Flowchart. BVS, bioresorbable vascular scaffold, FFR, fractional flow reserve, NSTEMI, non-ST-elevation myocardial infarction, OCT, optical coherence tomography, OMT, optimal medicinal therapy, PCI, percutaneous coronary intervention, STEMI, ST- elevation myocardial infarction. OCT imaging of a total of 59 FFR-negative lesions, whereas 2 (Table 3) were as follows: the average fibrous cap thickness patients refused OCT imaging. Among the 52 that underwent was 50.0μm± 10.3 in the BVS group vs. 50.6μm± 10.0 in the OMTgroup. A plaque rupture or thrombus was identified in OCT imaging, a vulnerable target lesion could be identified in 41 (79%) patients. Of all 59 OCT pullbacks of FFR-negative 1 (6.25%) of the target lesions in the BVS group vs. 2 (12.5%) lesions, 44 (75%) showed a vulnerable lesion. Seven patients in the OMT group. 100% of target lesions in both groups were excluded due to a vessel diameter too large for BVS contained a lipid arc of >90 degrees. "e average minimal implantation, resulting in a total of 34 patients who were lumen area was 2.69± 0.99 mm in the BVS group and eventually randomised (17 BVS vs. 17 OMT). Apart from one 2.57± 1.07 mm in the OMT group. In the BVS group, the withdrawal of consent in the BVS group and one lost to average minimal lumen area changed from 2.69± 0.99 mm follow-up in the OMT group, two-year follow-up was ob- to 6.55± 1.81 mm after stent placement. Analysis of the tained of all participants that were included up to that point. OCT images beyond the angiographically targeted lesions Table 2 shows patient baseline characteristics. "e mean revealed the average presence of 0.2± 0.4 additional vul- age of participants was 62.1± 10.4 years in BVS vs. 70.3± 5.9 nerable non-target lesions and 0.7± 1.1 additional non- years in the OMTgroup. "e percentage of male participants vulnerable non-target lesions per OCT-pullback in the BVS was 75.0% in BVS vs. 75.0% in OMT. STEMI was the initial group. In the OMT group, an additional 0.5± 0.8 vulnerable presentation in 43% in BVS vs. 50% in OMT. OCT char- non-target lesions and 0.9± 0.7 non-vulnerable non-target acteristics of the target lesions in the randomised groups lesions were identified. 4 Journal of Interventional Cardiology Table 1: Inclusion and exclusion criteria. Inclusion criteria Exclusion criteria Clinical Clinical (i) Age ≥18 years (i) Pregnancy (ii) Clinical presentation of STEMI or NSTEMI (ii) Severe kidney disease defined as an eGFR <30 ml/min (iii) Previous CABG (iv) Indication for revascularization by CABG (v) Estimated life expectancy <1 year Angiographical Angiographical (i) Presence of residual, intermediate CAD (diameter stenosis (i) Target vessel diameter <2.5 mm or >4.0 mm of 30–90%), with the possibility of plaque vulnerability (ii) Anatomy of lesion unsuitable for OCT catheter crossing or imaging (aorta-ostial lesions, small diameter segment, and severe calcifications) (iii) Anatomy unsuitable for BVS placement (left main, bifurcation, and side branch (>2 mm) involvement) (iv) Target lesion is (a) In-stent restenosis (b) Chronic total occlusion (c) In the same vessel as treated culprit lesion (d) In the same segment as a previously implanted stent/scaffold BVS, bioresorbable vascular scaffold, CABG, coronary artery bypass grafting, CAD, coronary artery disease, NSTEMI, Non-ST-elevation myocardial in- farction, OCT, optical coherence tomography, STEMI, ST-elevation myocardial infarction. During two-year follow-up, a total of 12 clinical events non-complex lesions. "is is also in line with the midterm were recorded, of which 4 were adjudicated as MACE results of BVS in STEMI-patients [11]. (Table 4). "e number of MACE was 3 in the BVS group and We observed a lower-than-expected rate of MACE 1 in the OMT group. "e events in the BVS group were a (6.3%) in the OMTgroup. In comparison, the 2-year follow- up results of the FAME trial showed a MACE rate of 17.9% non-cardiac death and two non-study vessel-related MIs. "e sole MACE in the OMTgroup was a non-cardiac death. in patients who had undergone complete FFR-guided Apart from one elective PCI for stable angina in the OMT revascularisation [12]. A possible explanation for these group, no target lesions in any group were revascularised discrepancies, in addition to the limited patient population, during the two-year follow-up. could be that patients in this trial were advised to continue DAPT for up to 3 years after the index event. Current guidelines recommend physiological measure- ments to determine the hemodynamic significance of an- 4. Discussion giographic intermediate lesions, based on several large trials In the PECTUS trial, patients with myocardial infarction and [13, 14]. Despite the obvious benefit of FFR-measurements an FFR-negative OCT-based vulnerable non-culprit lesion in guiding revascularisation, long-term follow-up patients were randomised between an intervention with a BVS and with deferred lesions still show significant event rates. "e 5- optimal medical therapy. Due to the low number of included year follow-up of the FAME trial demonstrated a 28% event patients, no robust conclusions can be drawn with respect to rate in patients who had been treated with FFR-guided the safety or efficacy of preventive stenting of these plaques complete revascularisation [15]. Additionally, some studies based on this study. Nevertheless, there were some notable have suggested that FFR-guided treatment decision based on results. In the 34 patients that were randomised, MACE studies in patients with stable CAD cannot simply be occurred 3 times (18.8%) in the BVS group and once (6.3%) adopted in ACS patients [1, 16]. "erefore, besides treatment in the OMT group. "is would indicate that stenting of or referral based on physiological significance, anatomical vulnerable lesions with BVS has no evident benefit com- characteristics might further improve treatment decision. In pared to medical treatment or might even result in worse support of this, recent multicentre non-invasive imaging outcomes. However, no case of MACE was related to a target studies have clearly shown that the use of anatomical im- lesion. "e only target lesion-related event was an elective aging with coronary computed tomography angiography PCI due to stable angina in the OMT group. "is is in (CCTA) leads to a more favourable prognosis as compared contrast with the AIDA trial [8], in which patients under- to standard of care using functional testing [17]. Addi- going PCI were randomised between BVS and metallic tionally, a recent small single-center trial demonstrated stents. In this trial, target vessel failure at 2-year follow-up superiority of image-guided intervention compared with had occurred in 11.7% of patients with BVS. Additionally, no physiology-guided intervention [18]. Although these results device thrombosis was seen in the current study. "is could have to be confirmed in larger trials, they hint at the ad- suggest that BVS implantation is related to relatively low ditional value of anatomical information in guiding coro- device-related complications in these non-flow-limiting nary intervention. Journal of Interventional Cardiology 5 B length: 0.06 mm C angle: 134.9° 1mm (a) (b) 1mm (c) (d) Figure 2: OCT with angiography coregistration of a patient randomised to BVS placement. (a) Angiogram shows an intermediate stenosis in the proximal circumflex coronary artery (white marker). (b) OCTof the stenosis reveals a vulnerable plaque (lipid arc>90 with a cap of 60μm). (c) Angiogram shows the same lesions as in A (white marker) after BVS placement. (d). OCTshows BVS placement over vulnerable plaque with good stent apposition. In PECTUS, a plaque was considered eligible for ran- Table 2: Baseline characteristics. domisation if it showed two characteristics of vulnerability. Whilst all randomised target lesions contained a lipid arc of BVS (n � 16) OMT (n � 16) >90 degrees, only 9% of these lesions showed a plaque rupture Age—years 62.1± 10.4 70.3± 5.9 or thrombus. Even though these, and other characteristics such Sex—n (%) as neointimal vascularisation and fibrous cap inflammation, Male 12 (75) 12 (75) have all been associated with plaque rupture, there is no clear Female 4 (25) 4 (25) answer as to what (combination of) feature(s) is the most Clinical presentation—n (%) hazardous. Nonetheless, the body of evidence linking plaque STEMI 7 (43) 8 (50) morphology to MACE is growing. Following PROSPECT, the NSTEMI 9 (57) 8 (50) VIVA and ATHEROREMO-IVUS studies also showed an Target vessel—n (%) association between IVUS-derived characteristics of vulnera- LAD 6 (37.5) 7 (43.75) bility and MACE [3, 19, 20]. Moreover, this association is also Cx 6 (37.5) 6 (37.5) found in other imaging modalities such as near infrared RCA 4 (25) 3 (18.75) spectroscopy (NIRS) and CCTA [21, 22]. Because of the Average FFR 0.90± 0.07 0.90± 0.06 novelty of the technique, validation studies for the ability of BVS, bioresorbable vascular scaffold, Cx, circumflex artery, LAD, left an- OCT to detect vulnerable plaques are scarce. In the recent terior descending artery, FFR, fractional flow reserve, NSTEMI, Non-ST- CLIMA study, investigators analysed images of 1003 patients elevation myocardial infarction, OMT, optimal medicinal therapy, RCA, right coronary artery, STEMI, ST-elevation myocardial infarction, who had undergone OCT-imaging of the proximal LAD in the 6 Journal of Interventional Cardiology Table 3: Target lesion OCT characteristics. BVS (n � 16) OMT (n � 16) Average cap thickness—μm 50.0± 10.3 50.6± 10.0 Plaque rupture or thrombus—n (%) 1 (6.25%) 2 (12.5%) Lesions with >1 lipid quadrant—n (%) 16 (100%) 16 (100%) Average MLA—mm 2.69± 0.99 2.57± 1.07 Average MLA after PCI—mm 6.55± 1.81 — Average number of additional non-target lesions per pullback 0.9± 1.3 1.4± 0.8 (i) Vulnerable 0.2± 0.4 0.5± 0.8 (ii) Non-vulnerable 0.7± 1.1 0.9± 0.7 BVS, bioresorbable vascular scaffold, OCT, optical coherence tomography, OMT, optimal medicinal therapy, MLA, minimal lumen area, PCI, percutaneous coronary intervention. Table 4: Clinical events. FFR of Target Target Time after No. Group target Event MACE lesion segment randomisation lesion related Cardiac arrest due to pulseless electrical activity during BVS implantation, for which chest compressions were performed for 1 minute and During BVS atropine was given, after which return of 1 (1) BVS LAD-mid (7) 0.82 No Yes implant spontaneous circulation occurred. No mechanical complication was seen. Postprocedural troponin values were not elevated. Episode was attributed to a vagal reaction. Elective PCI of proximal and distal RCA (in-stent restenosis distal RCA) because of progressive angina. 1 (2) BVS LAD-mid (7) 0.82 6 months No No No pre-intervention FFR was performed because stenosis in distal RCA was 90%. Cardiac arrest due to ventricular fibrillation. ICA shows left main coronary artery occlusion, for which 2 BVS LAD-mid (7) 0.81 4 months Yes No PCI was performed. OCT shows good patency of BVS in the mid LAD. Non-cardiac death due to obstruction hydrocephalus 3 BVS LAD-mid (7) 0.84 24 months Yes No caused by metastasized lung carcinoma. 4 BVS RCA-prox (1) 0.93 23 months Elective PCI of LAD-mid because of stable angina. No No Infected hematoma of the femoral puncture site/ 5 BVS LAD-mid (7) 0.86 8 days No No closure device. STEMI with PCI of distal RCA (culprit). Additional occlusion of a small MO2 branch. "is occlusion was 6 BVS Cx-mid (13) 0.95 15 months not intervened upon as patient was free of Yes No complaints after PCI of the RCA. BVS in the mid-Cx was patent. Non-cardiac death due to aspiration pneumonia in 7 OMT LAD-mid (7) 0.87 12 months patient with lymphoma and metastasized squamous Yes No cell carcinoma. Hospital admission with chest pain and slightly elevated cardiac troponin levels without rise/fall. 8 OMT Cx-mid (13) 1.00 24 months No No ICA showed no obstructive coronary artery disease. Complaints were attributed to hypertension. 9 OMT Cx-prox (1) 0.83 22 months Lobectomy for newly diagnosed lung carcinoma. No No Same day as 10 OMT MO1 (12) 0.97 Transient binocular diplopia after ICA. No No randomisation Elective PCI of the mid LAD (target segment) and proximal RCA due to stable angina and optimisation 11 OMT LAD-mid (7) 0.89 24 months for esophageal cancer-related chemotherapy. No No Yes pre-intervention FFR was performed because the wire could not pass the mid-LAD. BVS, bioresorbable vascular scaffold, Cx, circumflex artery, FFR, fractional flow reserve, ICA, invasive coronary angiography, LAD, left anterior descending artery, MACE, major adverse cardiac event, MLA, minimal lumen area, MO, obtuse marginal artery, OCT, optical coherence tomography, OMT, optimal medicinal therapy, PCI, percutaneous coronary intervention, RCA, right coronary artery, STEMI, ST-elevation myocardial infarction. Journal of Interventional Cardiology 7 context of a clinically indicated ICA. "is study showed that the CAD: Coronary artery disease combination of four morphological plaque features was an TCFA: "in-cap fibroatheroma independent predictor of MACE with a hazard ratio of 7.54 at 1 IVUS: Intravascular ultrasound year [23]. In CLIMA, however, the OCT imaging was per- STEMI: ST-elevation myocardial infarction formed on a fixed segment of the coronary artery tree as NSTEMI: Non-ST-elevation myocardial infarction opposed to a segment based on angiographic stenosis. ICA: Invasive coronary angiography "erefore, the technique was evaluated more as a tool for DAPT: Dual antiplatelet therapy prognostic risk stratification instead of imaging based lesion CCTA: Coronary computed tomography angiography treatment. "e same holds true for the other intravascular NIRS: Near-infrared spectroscopy imaging studies. Data on “targeted” intravascular imaging of CABG: Coronary artery bypass grafting angiographically defined stenoses is still lacking. Several studies MLA: Minimal lumen area. are currently trying to address this gap in knowledge. Among them are the COMBINE study (NCT02989740) and PECTUS- Data Availability obs study (NCT03857971). In line with the current PECTUS trial, the above- "e data used to support the findings of this study are mentioned FORZA trial also assessed OCT-guided PCI [18]. available from the corresponding author upon request. In this study, 350 patients were randomised between FFR- guided or OCT-guided PCI of angiographically intermediate Ethical Approval coronary lesions. At 13-month follow-up, patients in the OCT-guided group had significantly less MACE or signif- "is trial was approved by the Medical Ethics Committee of icant angina compared to patients in the FFR-guided group. the Vrije Universiteit Medical Center and has, therefore, However, the decision whether or not to stent a lesion in the been performed in accordance with the ethical standards laid OCT group was based on a combination of OCT-derived down in the 1964 Declaration of Helsinki and its later area stenosis, minimal lumen area, and the presence of amendments. plaque rupture. "erefore, apart from plaque rupture, this study did not take characteristics of vulnerability into ac- Consent count. In contrast, two other randomised studies that are currently being conducted have a similar design to PECTUS. Informed consent was given by all participants. "e PROSPECT-ABSORB (NCT02171065) and PREVENT (NCT02316886) both randomise patients with residual non- Conflicts of Interest obstructive vulnerable plaques to either BVS placement or optimal medicinal therapy although they differ in the in- Dr. Van Royen reports grants from Philips, grants from travascular imaging modality used. Abbott, grants from Biotronik, and personal fees from Medtronic, outside the submitted work. Dr. Damman re- 5. Limitations ports personal fees from Philips, outside the submitted work. "e other authors have no conflicts of interest to declare. "e main limitation of the PECTUS trial is the low number of included patients due to the early termination of the trial. Acknowledgments 6. Conclusions "is trial was financially supported by Abbott Vascular and Health Holland. In conclusion, the PECTUS trial could not shed light on the theoretical benefit of preventive stenting of non-flow-lim- References iting vulnerable lesions due to early termination of the trial. Nonetheless, the concept of identifying and potentially [1] A. Hakeem, M. M. Edupuganti, A. Almomani et al., “Long- treating vulnerable plaques remains an important field for term prognosis of deferred acute coronary syndrome lesions future research given the relatively large MACE rates as based on nonischemic fractional flow reserve,” Journal of the reported for this specific cohort of patients. American College of Cardiology, vol. 68, no. 11, pp. 1181–1191, [2] M. J. Bom, D. J. V. D. Heijden, E. Kedhi et al., “Early detection Abbreviations and treatment of the vulnerable coronary plaque,” Circula- tion: Cardiovascular Imaging, vol. 10, no. 5, 2017. OCT: Optical coherence tomography [3] G. W. Stone, A. Maehara, A. J. Lansky et al., “A prospective MI: Myocardial infarction natural-history study of coronary atherosclerosis,” New En- PCI: Percutaneous coronary intervention gland Journal of Medicine, vol. 364, no. 3, pp. 226–235, 2011. FFR: Fractional flow reserve [4] A. P. Burke, A. Farb, G. T. Malcom, Y.-H. Liang, J. Smialek, BVS: Bioresorbable vascular scaffold and R. Virmani, “Coronary risk factors and plaque mor- OMT: Optimal medicinal therapy phology in men with coronary disease who died suddenly,” ACS: Acute coronary syndrome New England Journal of Medicine, vol. 336, no. 18, MACE: Major adverse cardiac events pp. 1276–1282, 1997. 8 Journal of Interventional Cardiology [5] G. J. Tearney, H. Yabushita, S. L. Houser et al., “Quantification stenosis: a single-center trial,” JACC: Cardiovascular Inter- ventions, vol. 13, no. 1, pp. 49–58, 2000. of macrophage content in atherosclerotic plaques by optical coherence tomography,” Circulation, vol. 107, no. 1, [19] P. A. Calvert, D. R. Obaid, M. O’Sullivan et al., “Association between IVUS findings and adverse outcomes in patients with pp. 113–119, 2003. [6] T. Kubo, T. Imanishi, S. Takarada et al., “Assessment of culprit coronary artery disease,” JACC: Cardiovascular Imaging, vol. 4, no. 8, pp. 894–901, 2011. lesion morphology in acute myocardial infarction,” Journal of [20] J. M. Cheng, H. M. Garcia-Garcia, S. P. M. D. Boer et al., “In the American College of Cardiology, vol. 50, no. 10, pp. 933– vivo detection of high-risk coronary plaques by radio- 939, 2007. frequency intravascular ultrasound and cardiovascular out- [7] C. V. Bourantas, P. W. Serruys, S. Nakatani et al., “Bio- come: results of the ATHEROREMO-IVUS study,” European resorbable vascular scaffold treatment induces the formation Heart Journal, vol. 35, no. 10, pp. 639–647, 2014. of neointimal cap that seals the underlying plaque without [21] R. Waksman, C. D. Di Mario, R. Torguson et al., “Identifi- compromising the luminal dimensions: a concept based on cation of patients and plaques vulnerable to future coronary serial optical coherence tomography data,” EuroIntervention, events with near-infrared spectroscopy intravascular ultra- vol. 11, no. 8, pp. 746–756, 2015. sound imaging: a prospective, cohort study,” +e Lancet, [8] J. J. Wykrzykowska, R. P. Kraak, S. H. Hofma et al., “Bio- vol. 394, no. 10209, pp. 1629–1637, 2019. resorbable scaffolds versus metallic stents in routine PCI,” [22] M. Ferencik, T. Mayrhofer, D. O. Bittner et al., “Use of New England Journal of Medicine, vol. 376, no. 24, high-risk coronary atherosclerotic plaque detection for risk pp. 2319–2328, 2017. stratification of patients with stable chest pain: a secondary [9] D. J. Kereiakes, S. G. Ellis, C. Metzger et al., “3-Year clinical analysis of the PROMISE randomized clinical trial,” JAMA outcomes with everolimus-eluting bioresorbable coronary Cardiology, vol. 3, no. 2, p. 144, 2018. scaffolds,” Journal of the American College of Cardiology, [23] F. Prati, E. Romagnoli, L. Gatto et al., “Relationship between vol. 70, no. 23, pp. 2852–2862, 2017. coronary plaque morphology of the left anterior descending [10] F. Prati, E. Regar, G. S. Mintz et al., “Expert review document artery and 12 months clinical outcome: the CLIMA study,” on methodology, terminology, and clinical applications of European Heart Journal, vol. 41, no. 3, pp. 383–391, 2020. optical coherence tomography: physical principles, method- ology of image acquisition, and clinical application for as- sessment of coronary arteries and atherosclerosis,” European Heart Journal, vol. 31, no. 4, pp. 401–415, 2010. [11] S. Cassese, Y. Katagiri, R. A. Byrne et al., “Angiographic and clinical outcomes of STEMI patients treated with bio- resorbable or metallic everolimus-eluting stents: a pooled analysis of individual patient data,” EuroIntervention, vol. 15, no. 16, pp. 1451–1457, 2020. [12] N. H. J. Pijls, W. F. Fearon, P. A. L. Tonino et al., “Fractional flow reserve versus angiography for guiding percutaneous coronary intervention in patients with multivessel coronary artery disease,” Journal of the American College of Cardiology, vol. 56, no. 3, pp. 177–184, 2010. [13] P. A. L. Tonino, B. D. Bruyne, N. H. J. Pijls et al., “Fractional flow reserve versus angiography for guiding percutaneous coronary intervention,” New England Journal of Medicine, vol. 360, no. 3, pp. 213–224, 2009. [14] P. C. Smits, M. Abdel-Wahab, F.-J. Neumann et al., “Frac- tional flow reserve-guided multivessel angioplasty in myo- cardial infarction,” New England Journal of Medicine, vol. 376, no. 13, pp. 1234–1244, 2017. [15] L. X. V. Nunen, F. M. Zimmermann, P. A. L. Tonino et al., “Fractional flow reserve versus angiography for guidance of PCI in patients with multivessel coronary artery disease (FAME): 5-year follow-up of a randomised controlled trial,” +e Lancet, vol. 386, no. 10006, pp. 1853–1860, 2015. [16] S. M. Mehta, J. P. Depta, E. Novak et al., “Association of lower fractional flow reserve values with higher risk of adverse cardiac events for lesions deferred revascularization among patients with acute coronary syndrome,” Journal of the American Heart Association, vol. 4, no. 8, Article ID e002172, [17] D. E. Newby, P. D. Adamson, C. Berry et al., “Coronary CT angiography and 5-year risk of myocardial infarction,” +e New England Journal of Medicine, vol. 379, no. 10, pp. 924– 933, 2018. [18] F. Burzotta, A. M. Leone, C. Aurigemma et al., “Fractional flow reserve or optical coherence tomography to guide management of angiographically intermediate coronary

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