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Frequency domain optical coherence tomography for guidance of coronary stenting
International Journal of Cardiology 166 (2013) 722–728
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Frequency domain optical coherence tomography for guidance of coronary stenting Nicola Viceconte a, Pak Hei Chan a, Eduardo Alegria Barrero a, Liviu Ghilencea a, Alistair Lindsay a, Nicolas Foin b, Carlo Di Mario a,⁎ a b
Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, UK Biomedical Engineering Department, Imperial College, London, UK
a r t i c l e
i n f o
Article history: Received 8 July 2011 Received in revised form 1 October 2011 Accepted 27 November 2011 Available online 30 December 2011 Keywords: Frequency domain optical coherence tomography Percutaneous coronary intervention Coronary lesion assessment Stent optimization
a b s t r a c t Objective: To evaluate the role of Frequency domain optical coherence tomography (FD-OCT) in guiding stent implantation procedures. Methods: Dragonfly™-imaging catheter was used pre-intervention, after pre-dilatation or at various stages of stent deployment/post-dilatation to assess lesion severity, characteristics and guide stent expansion/apposition. Results: We performed 398 OCT pull-backs in 108 consecutive patients. The 371 pull-backs analysable, had an average length of 35 mm and encompassed 193 lesions (1.8 lesions per patient). Seventy-six percent of patient had AHA-ACC-class B–C lesions. In the pre-intervention group deferral of treatment was decided for 13/68 pullbacks (19.1%), whereas strategies different from conventional predilatation (e.g. thrombectomy, rotablator, cuttingballoon) were decided in 23 cases (33.8%). After full lesion dilatation 96 pullbacks (25.9%, pre-stenting group) were performed, 46 (47.9%) of which suggested proceeding directly with stenting while 50 (52.1%) suggesting further treatment. Out of the 207 pullbacks in post-stenting group, 29 (14%) suggested new stent implantation because of dissection or residual stenosis; 64 (30.9%) suggested further optimization with high pressure/larger-sized balloon. Average number of pull-backs per patient was 3.4 requiring 75.8± 19.3 ml of iopamidol. No major complications were observed. Five cases (4.6%) of contrast-induced nephropathy were reported. Conclusions: Repeated examinations with FD-OCT can be safely used to guide stent selection and improve stent expansion and apposition. © 2011 Elsevier Ireland Ltd. All rights reserved.
1. Introduction 1.1. Background and objective Optical coherence tomography (OCT) has greater resolution and better definition of luminal contours and strut position than intravascular ultrasound, the established standard for guidance of coronary stenting. OCT, however, requires clearance of blood during acquisition. When OCT acquisition was performed using a slow pull-back speed (3 mm/s), as required by time domain analysis, the use of OCT for procedural guidance when repeated examinations over long segments are required, was impractical. Frequency domain (FD) analysis allows an increase of the OCT acquisition rate to the point that the pull-back speed can be 6–7 times faster (20 mm/s) and still have better transversal and
Abbreviations: FD-OCT, Frequency domain optical coherence tomography; AHA-ACC, American Heart Association-American College of Cardiology; IVUS, Intravascular Ultrasound; MLCSA, Minimal Luminal Cross Sectional Area; FFR, Fractional flow Reserve; TD, Time Domain; ISA, Incomplete Stent Apposition; L/VLST, late/very late stent thrombosis; BMS, Bare Metal Stent; DES, Drug Eluting stent; LM, Left Main; SVG, Safenous Vein Graft. ⁎ Corresponding author at: Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, Sydney Street, SW3 6NP, London, UK. Tel./fax: +44 20 7352 8121, +44 7799067639 (Mobile). E-mail address: [email protected] (C. Di Mario). 0167-5273/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2011.11.090
longitudinal resolution than with time domain analysis [1,2]. This study reports a singe centre experience of the use of FD-OCT in consecutive patients studied with multiple pull-backs to guide lesion treatment and stent implantation at the Royal Brompton hospital since its introduction in 2009. 2. Methods 2.1. Patient selection Between September 2009 and December 2010, 134 consecutive patients were studied with FD-OCT at the Royal Brompton Hospital. We identified three different indications for OCT: 1) Pre-intervention: in patients with a sufficient minimal diameter to allow contrast penetration distal to the stenosis with the catheter across the lesion or after predilatation with 1.5 or 2.0 mm balloons, FD-OCT was used to determine whether a lesion of intermediate severity deserved treatment and/or to provide information on plaque characteristics (e.g. calcification, lesion length, relationship with branches) important to facilitate procedural planning. 2) Pre-stenting: when the operator felt that the lesion was sufficiently expanded to deploy a stent, FD-OCT was used to confirm that lesion preparation was optimal and select the most appropriate stent length and diameter. 3) Post-stenting: FD-OCT was used after angiographic guided optimisation with highpressure stent deployment and post-dilatation with non compliant balloons to confirm optimal stent expansion and lesion coverage or guide further post-dilatation with larger balloons/higher pressure or the implantation of additional stents proximal and/or distal due to residual uncovered stenoses or dissections.
N. Viceconte et al. / International Journal of Cardiology 166 (2013) 722–728 2.2. OCT acquisition
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3. Results
A non-occlusive technique was used in all cases. A 2.7 Fr C7 Dragonfly™ Imaging Catheter (St Jude Medical LightLab, St. Paul, MN, USA), flushed with undiluted contrast and calibrated before the acquisition, was inserted over the guidewire distal to the lesion of interest. Acquisition was performed during continuous flushing of 2–5 mL/s of iodixanol (Visipaque™ 320 mg I/ml GE Healthcare, Amersham, UK) using a Medrad power injector. Pullback speed was set at 20 mm/s, with a length of vessel segment analysed between 30 and 54 mm (maximal pull-back length allowed by the system). Pull-back was manually started when sufficient blood clearance was obtained, allowing readjustment of the speed of contrast injection if blood was still partially obscuring the image. OCT analysis was performed on-line using the C7 system and off-line using a dedicated OCT Review Workstation (St Jude Medical LightLab, St. Paul, MN, USA). Proprietary patented software, loaded in a beta release version also on the C7 system for on-line use since February 2010, generates a mask of the OCT lumen image defining a plurality of scan lines and identifying the lumen/tissue interface along each scan line. After identification of valid neighbouring contour segments, interpolation was used to fill the missing contour data. If extensive interpolation was required jeopardising the likely correctness of the computed contour the system indicated to the user the image frames possibly in need of manual adjustment. Together with contour detection the system displays automatically all the measurements during pull-back and allows identification of the minimal luminal cross sectional area (MLCSA) and comparison of this measurement with the measurements of used defined proximal and distal reference cross-sections [3] (Fig. 1). Creatinine values were measured in all patients before and after procedure, contrast induced nephropathy was defined as increasing in creatinine level more than 25% of the baseline value [4]. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology.
Out of the134 consecutive patients assessed with FD-OCT between September 2009 and December 2010, 26 patients (110 pull backs, 21.6%) were excluded as they were studied only as a planned follow up for the evaluation of late strut apposition and coverage within predefined research protocols (LEADERS, RESOLUTE, etc.) [5,6]. We allocated the remaining 398 pull-backs obtained in 108 patients according to the three predefined indications above. The average pullback length was 35.1 ± 15.4 mm (range 9.6 to 54.0 mm) with wide variation caused by the premature interruption of the pullback because blood artefacts developed or because the OCT reached the guiding catheter in short proximal lesions or in long lesions requiring 2 sequential pull-backs. Among these 108 patients, 85 were men (75%) with a mean age of 53.0±9.6 years, 11 (10.2%) presented with an acute coronary syndrome. A total of 193 lesions were studied (1.8 lesions/patient), most of them complex. (Table 1) Most of the patients (89, 82.4%) had only one vessel studied, 16 (14.8%) had two vessels analysed and only in three patients (2.8%), OCT was performed in more than two vessels. The average number of pull-backs per patient was 3.4 (range 1–13), Fig. 2.
2.3. Statistical analysis
3.2. Changes in strategy due to OCT analysis
Categorical variables were expressed as percentage. Continuous variables were expressed as mean ± standard deviation (SD), and compared using paired T-test. A p value of b 0.05 was considered to be statistically significant, and all reported p-values are 2-sided. All analysis were performed using STATA 10.1 statistical software (Statacorp, Texas, USA).
Out of 398 pull-backs, we excluded 27 pullbacks (6.8%) due to poor quality (insufficient blood clearance, catheter damage, lesion incompletely assessed). Among the remaining 371 pullbacks in 108 patients, 68 (18.3%, pre-intervention group) were performed before a balloon was
3.1. Patient characteristics
Fig. 1. a: OCT long view reconstruction; multiple segments are encoded in red (red flagging) to identify the inability of the system to recognise the lumen area. b: poor saline flush; c: vessel irregularity after cutting balloon; d: bifurcation lesion after stenting.
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Table 1 Patient Characteristics. Number
%
Male Age (mean; SD⁎) Smoker Hypertension Hypercholesterolemia Family history of CAD† Diabetes Mellitus Previous PCI‡ Previous CABG§ Acute coronary syndromes Stable angina or silent ischemia
85 53 ± 9.6 45 75 91 56 34 71 28 11 97
75.0 – 41.7 69.4 84.3 51.9 23.2 65.8 25.9 10.2 89.8
ACC/AHA lesion classification Type A B C Non significant lesions
n (193) 37 57 90 9
% 19.2 29.5 46.6 4.7
n 9 33 34 5
% 8.3 30.1 31.5 4.6
Out of the 207 pullbacks performed in the post-stenting group, 29 (7.8%) suggested the need of a new stent implantation because of dissection or severe residual stenosis proximal/distal and 64 (30.9%) suggested further optimization with high pressure or larger size balloon. (Fig. 5) The remaining 114 pullbacks (55.1%) showed no need of additional steps to optimise results. The change in patient treatment strategy due to the FD-OCT evaluation is illustrated in Table 2. In order to minimise contrast load, once the largest balloon and highest pressure felt feasible and safe was used, a very final pull-back was performed only in a minority of the lesions requiring sequential steps for optimisation. Eight patients received complete serial evaluation, including final assessment after the largest balloon/highest pressure/last stent. MLCSA within the stent after optimization increased from 4.97 ± 1.68 mm2 to 5.42 ± 1.68 mm2, (pb 0.0001). The average luminal area gain was 0.45 mm2 (9.56 ± 3.14% increase compared with the preOCT optimised lumen area). The mean increase in balloon diameter was 0.31 ± 0.22 mm (8.61± 5.68%). Two patients were treated using a non compliant balloon of the same diameter but at a greater pressure (from 14.5 ± 7.8 Atm to 22.9 ± 5.2 Atm).
Special lesion subset CTO|| Bifurcations In-stent-restenosis Left main lesion ⁎ Standard Deviation. † Coronary Artery Disease. ‡ Percutaneous Coronary interventions. § Coronary Artery Bypass Grafting. || Chronic Total Occlusion.
inserted, mainly to decide whether an intervention was needed in the presence of stenoses of intermediate or ambiguous severity, or after a 1.5–2.0 mm balloon was specifically used to allow lesion visualisation with FD-OCT. After 13 pullbacks (19.1%) deferral of treatment was decided because the lesion did not match the expected criteria for severity. The need for specific lesion preparation (Rotablation, Cutting Balloon or thrombectomy) was defined in 23 pullbacks (33.8%) and a strategy on the length of lesion to cover and its relationship with bifurcations was established (Figs. 3–4). Following information from 32 OCT pullbacks (47.1%) conventional pre-dilatation was performed, but the information still helped the identification of optimal balloon length, type (compliant or not compliant) and diameter. After full lesion dilatation 96 pullbacks (25.9%, pre-stenting group) were performed, 46 (47.9%) of which suggested to proceed directly with stenting and clarified the optimal stent length and diameter, 50 (52.1%) suggesting the use of further preliminary treatment (additional high pressure dilatation or larger cutting/high pressure balloon). In the “pre-intervention” and “after post-dilatation” groups, plaque components were evaluated (total of 164 pullbacks). The extension of calcifications was classified into: mild (b90° of the vessel circumference), moderate (90°–180°), and severe (>180°) [7]. Moderate calcification was found in 27 pullbacks (16.5%), severe calcification was observed in 11 pullbacks (6.7%).
3.3. Safety and feasibility Thanks to its small calibre (diameter 2.7 Fr, 0.89 mm), the OCT catheter could easily cross the lesion/stent in the majority of cases, including some highly calcific lesions before pre-dilatation. We noticed, however, a reduced pushability of the catheter after prolonged use and in four cases the DragonFly catheter stopped at the proximal stent edge or at the ostium of a side-branch covered by a stent despite successful kissing balloon dilatation. Due to the high pullback speed, the average amount of contrast required during OCT pullback was 22.1 ± 4.7 ml. No major complications such as ventricular tachyarrhythmia, heart block, profound bradycardia (b40 beats per minute), coronary dissection or air embolism were observed. The mean time added to the procedure by the serial OCT examinations was 15.4 ± 8.2 min, including OCT catheter preparation, connection to the power injector, initialization of OCT system and insertion/withdrawal of the OCT catheter. The average total amount of additional contrast per patient required for the serial OCT examinations was 75.8± 19.3 ml. The mean creatinins value before and after the procedure was 89.3 ± 24.4 and 90.9 ± 23.0 mmol/l respectively. Five cases (4.6%) of contrast-induced nephropathy were observed but creatinine rapidly returned to the preintervention level within 48–72 hours with no need for haemofiltration or dialysis. 3.4. Efficacy of the automatic analysis system Red flagging, indicating possible inaccuracies in the detection of the vessel contour, covered 15.1% of the total pull-back length. Inaccuracies corresponded to segments with incomplete blood clearance, bifurcations, dissections or highly irregular lumen contours, proximal segments with the lumen boundaries outside the 4 mm of maximal depth. (Fig. 1) In 306 pull-backs (60.2%), the system was able to identify
Fig. 2. Number of pull-backs per patients. Note that 3 or more pull-backs were used in 61% of cases, suggesting that a stepwise approach was allowed by repeated pull-backs.
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Fig. 3. NSTEMI with stent thrombosis 4 yrs after paclitaxel eluting stent. (a–a1) filling defect of the proximal segment of LAD; OCT shows protruding thrombus (asterisk) (b); thrombus extracted with Hunter Catheter (c–d); angiographic finding after thrombus aspiration (d); OCT show residual luminal Thrombus (e) leading to a further successful aspiration with a different extraction catheter (Pronto) (f).
Fig. 4. Angiographic and OCT images: In stent Restenosis of proximal LAD, close to the first septal takeoff, MLA 2.53 mm2 (a–b); d: OCT show intimal dissection after 3.0 mm cutting balloon inflation (asterisk), not visible in the angiographic control; area has increased to 7.18 mm2 (c); final angiographic result (e), OCT control demonstrates a luminal area of 8.89 mm2, with good apposition of the stent struts (f).
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Fig. 5. 76 year old lay presented with stable effort angina. A) Angiogram showing proximal-mid LAD lesion of intermediate severity. A1) OCT image showing proximal reference of 10.23 mm2 with thin-capped soft lipid plaque (asterisk). A2) OCT demonstrating MLA of 3.37 mm2. A3) OCT showing distal reference of 6.66 mm2 with calcific plaque (white arrow). We decided to stent the lesion as MLA is b 4 mm2. B) Angiogram showing post-stenting result. B1) showing proximal stent strut malapposition; B2) showing segment with MLA of 8.78 mm2 with good strut apposition; B3) OCT demonstrating floating stent struts towards diagonal bifurcation (yellow arrows) C) Angiogram showing postdilatation for stent optimization, angiographically exactly the same but OCT could demonstrate an improvement in several aspects: C1) Good strut apposition after postdilatation with 4.0 mm non-compliant balloon, resulting in MLA of 13.18 mm2; C2) MLA increase from 8.78 mm2 to 9.91 mm2 after post-dilatation 3.5 mm high pressure balloon at 40 atm resulting in vessel more circular in shape compared with B2; C3) Better strut apposition was achieved towards the SB after kissing balloon inflation.
the MLCSA correctly and in 217 pull-backs (42.7%) also provided an immediate accurate measurement of this key quantitative parameter required for procedural guidance. Manual readjustments of the position of the MLCSA or contour corrections were greatly facilitated by the availability of a longitudinal view with superimposed measurements. 4. Discussion 4.1. OCT: from research to clinical applications Previous studies had demonstrated the unique features offered by OCT as a research tool, mainly to assess thrombus, intimal rupture, Table 2 Interventional stage when OCT was performed and changes in strategy prompted by the examination. Indications of OCT pull-back in the target vessel Pre-intervention - Deferral of planned PCIa - Identification of optimal balloon size, length, type - Suggestion of specific lesion preparation Thrombectomy Rotablator Cutting Balloon After pre-dilatation of lesion - Identification of optimal stent diameter and length - Further pre-treatment before stenting After stenting - Additional stent implantation - Expansion with higher pressure/larger balloon - No further changes from planned strategy a
Percutaneous coronary intervention.
Total number of pull-backs
% of total pullbacks (371)
68 13 32
18.3 19.1 47.1
23 3 6 14 96 46
33.8 4.4 8.8 20.6 25.9 47.9
50 207 29 64
52.1 55.8 14 30.9
114
55.1
lipid laden plaques and the thickness of their fibrous cap, strut apposition and late coverage [5,6,8–17]. The short length of the segments assessable with time-domain OCT (most often using a proximal occlusion balloon but also with a non-occlusive technique), dissuaded operators to move to clinical applications such as guidance of percutaneous coronary interventions [18]. The widespread application of a non-occlusive technique using Monorail OCT catheters and the rapid pull-back speed (≥20 mm/s) allowed by newer generation FD-OCT systems revived the interest in OCT for procedural guidance. Imola et al. in a recent study used FDOCT in 91 patients (33 of which were ACS) to assess lesion severity and result after stent implantation [19]. The preparation of the DragonFly catheter is simple, with an automatic calibration and purge of air with undiluted contrast using a high pressure syringe, and can be performed while the case is started. The pull-back duration is negligible and the review process is simpler than with ultrasound because all the lumen contours and measurements are already automatically displayed so that an expert operator can rapidly extract the relevant clinical information and decide the consequent procedural steps. It is not surprising that the time required for OCT was very short in spite of many pull-backs performed. The additional requirement of contrast remained disappointingly high. We included the contrast for the OCT catheter preparation and the contrast lost during the connection with the pressure injector. We also preferred to use the “manual” mode to start pull-back, waiting for the operator to give the command when there was perfect blood clearance. This method allowed us to abort the pull-back when clearance was suboptimal; sparing a full injection to acquire low quality images but possibly resulting in an overall greater contrast consumption. We often inserted the OCT catheter before repeating the planned angiographic control so that the same contrast was used for angiographic lesion assessment and to clear the blood during pull-back. Therefore, the “additional” contrast used for OCT was possibly overestimated because it was not entirely injected in the patient and replaced contrast required anyway for angiographic controls.
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None of the patients had severe renal failure consequent to contrast overload but we performed OCT only when we completed angiographic optimisation of results before and after stenting and often avoided the final OCT control when we felt no further interventions were likely to be triggered by a new study. On a positive side, the arrhythmias and chest discomfort caused in the past by the need of transient proximal balloon occlusion and of a prolonged selective contrast injection are not a concern using the new non-occlusive technique and rapid pullback speed of FD-OCT. 4.2. OCT use in different phases of PCI OCT can be used to assess the severity of the stenosis pre intervention but, in the absence of specific longitudinal trials or large comparison with FFR, criteria originally developed for ultrasound were applied [20–23]. Recent studies have challenged these parameters suggesting that the absolute measurement of MLCSA proposed as the threshold to trigger interventions (b4.0 mm2), are only applicable in large proximal epicardial vessels and are grossly overestimated in distal vessels or diffusely diseased arteries. Using OCT instead of IVUS does not correct these fundamental pitfalls which justify the superiority of Fractional Flow Reserve (FFR) myo for this particular application. Still in many intermediate or ambiguous lesions the distinction between severe and moderate stenoses is very obvious and a technique of intravascular imaging avoiding the ring down artefacts and showing more clearly the lumen/wall interface can only increase reliability [24]. Unlike FFR, OCT provides a wealth of information on lesion characteristics such as presence and type of thrombus, thin-cap fibro-atheroma, plaque ulceration, and superficial calcification which can help guide the procedure, often making it worthwhile to initially dilate with a small balloon to allow preliminary OCT examination of the lesion. The lower rate of calcification compared to previous IVUS studies [7] is probably related to the inability of the OCT to detect deep calcified lesions. [5] For in-stent restenosis, OCT provides information on the degree and localization of neo-intimal hyperplasia and can easily measure the stent area as stent struts remain clearly visualised. In a recent study, it was shown to be more efficacious than IVUS for the assessment of the severity of neo-intimal hyperplasia [25]. OCT pull-backs provide different but potentially equally useful information when used after the lesion has been prepared, before proceeding with stent implantation. Identification of an inadequate vessel response to balloon inflation may lead to the use of bigger/ higher pressure balloon(s) or other devices but also invariably helps to fine tune stent selection, both in terms of length and diameter of the delivery balloon. OCT images and measurements pre-stenting can also help the post-dilatation strategy, when it is clear that proximal stent optimisation with a larger balloon or postdilatation at higher pressures of a more resistant segment are required. The general principle, is to proceed with optimisation based on angiography and the information collected during the initial pre-stent examination and use OCT only when the angiographic appearance looks adequate to confirm optimal stent expansion and lesion coverage. This approach is already standard among experienced IVUS operators, but OCT requires more attention than IVUS to avoid a large number of repeated pull-backs in order to avoid an excessive contrast load. 4.3. OCT v IVUS criteria to guide stent expansion and strut apposition The sharp contrast wall/lumen with very small artefacts around stent struts allows immediate automatic measurements of high accuracy in the majority of pull-backs. This represents a clear advantage over IVUS but comes at a price: the low penetration of OCT, not substantially improved moving from Time Domain (TD)- to FD-OCT, makes the assessment of the total vessel diameter (media-to-media) unpractical and limited to a minority of distal reference segments with small amount of fibrotic or fibro-calcified plaque. When the vessel area
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cannot be identified in the reference segment, almost the norm in the proximal segment, the identification of the proximal and distal points where to implant a stent requires a synergistic combination of angiographic and OCT assessment. A large proximal lumen area, irrespective of the presence and extent of plaque encroachment, offers a valid target to anchor the proximal end of the stent and select the optimal balloon diameter for proximal stent expansion. In principle, with OCT the selection of balloon diameter is most often based on the lumen and not on the vessel area/diameter. The initial criteria proposed by Colombo et al. were based on a combination of vessel and lumen area/diameter and the Milan group has recently proposed simplified criteria (AVIO) to select optimal balloon size based on vessel area measurements [20]. The poor compliance of the investigators in reaching these targets (46% in an initial pilot study, unable to demonstrate significant differences in final MLCSA, let alone clinical advantages) suggests that vessel based criteria are too cumbersome for practical use. For this reason criteria for IVUS optimization used in different large multicentre studies have relied on a comparison of the MLCSA of the stented segment with the distal reference area or with the mean reference vessel area [22,26,27]. OCT has clear advantages compared with IVUS for the assessment of lumen area. OCT measurements obtained directly from automatic contour detection or after minor manual adjustment of the detected contours are much more appealing than cumbersome manual tracing of multiple cross-section of the IVUS examination. Expert IVUS “operators” or interpreters quickly analysing the IVUS pull-back after acquisition are a luxury that, besides live courses, is only available in few leading interventional centres outside Japan and this is one of the main reasons, probably above catheter cost, of the limited penetration of IVUS in the USA and Europe. Strut apposition has always been part of the criteria of optimal stent deployment and can be exquisitely assessed by OCT and imaging. Pathological studies have shown that incomplete stent apposition (ISA) is correlated with thrombus detection and late/very late stent thrombosis (L/VLST). ISA might delay neointimal healing of the stent and incomplete endothelialization of the struts is a common morphologic finding in fatal cases of L-VLST [28–32]. No correlation between ISA and adverse events such as stent thrombosis was assessed in IVUS sub-studies of BMS v DES studies but these studies dealt with very simple lesions and used a technique such a s IVUS which is not ideal to assess but the most extremes instances of ISA [33,34]. 4.3.1. Limitations of OCT for procedural guidance This is a retrospective review of a consecutive series of interventions in complex lesions. At this early stage of application of OCT, we did not try to systematically predefine the strategy, including balloon length and diameter, we were going to adopt if no imaging guidance was available. The identification of cases for whom OCT led to a change in strategy is then somewhat arbitrary because the strategical decisions respond to the general practice of centres with a high volume of intravascular imaging to base their decisions on an integrated analysis of angiography and IVUS or, in this study, OCT. Showing that OCT safely leads to strategy changes increasing lumen area and optimising lesion coverage and strut apposition does not mean that the changes obtained are clinically helpful. The disappointing results of some IVUS studies in the past for guidance of stent implantation should be carefully considered when claims are made that OCT can improve restenosis and reduce late thrombosis. In this study we did not perform any comparison of IVUS and FD OCT for measurement of MLCSA post-stenting, an important necessary step to understand the relative merits of IVUS and OCT. OCT is often unable to delineate the lumen contours in large vessels such as the LM or SVGs, especially when the OCT catheter lies eccentric in the vessel [35]. IVUS also has a clear advantage in ostial lesions because the guiding catheter can be easily disengaged during the IVUS examination while it must remain engaged to clear the blood during OCT pullback. This is a retrospective
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analysis of a single centre, which has started working with OCT in 2003. Newcomers in the field will need to go through a learning curve but the clarity of the OCT images and the availability of automated measurements suggest that this can be much steeper than the IVUS learning curve. Also, the patient spectrum would vary among different centres. In very simple lesions it is unlikely major gains can be achieved with any imaging strategy. Conceptually, lumen based criteria of expansion, the only possible with OCT, have limited ability to optimally increase the lumen size in long lesions, overlapping stents and in vessels with distal tapering because the distal reference lumen used to guide expansion does not reflect the true size of the optimal lumen several cm more proximal. Alternatives can be offered by algorithms to detect abrupt changes in stent area compared with neighbouring segments and creative criteria to guide the safe use of balloons with a diameter based on an average of proximal and distal reference weighted according to the relative distance of the segment of interest from the two reference segments. The automated area–length OCT measurements lend themselves to an easy implementation of such algorithms, guiding the application of focal high pressure balloons. (Fig. 5) The need of contrast injection during acquisition precludes the use of OCT in patients with presence or high risk of renal failure. Different types of contrast have been proposed but this resulted in a suboptimal image quality or introduced unbearable regulatory hurdles for approval. 5. Conclusions Frequency domain optical coherence tomography can be safely used to meet clinical applications of procedural guidance traditionally reserved for IVUS. Acknowledgement The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology. References [1] Takarada S, Imanishi T, Liu Y, et al. Advantage of next-generation frequency-domain optical coherence tomography compared with conventional time-domain system in the assessment of coronary lesion. Catheter Cardiovasc Interv 2010;75:202–6. [2] Kataiwa H, Tanaka A, Kitabata H, et al. Head to head comparison between the conventional balloon occlusion method and the non-occlusion method for optical coherence tomography. Int J Cardiol 2011;146:186–90. [3] Schmitt JM, Friedman JM, Petroff C, Elbasiony A. United States Patent Application 20110071404 Kind Code A1. March 24, 2011. [4] Harjai KJ, Raizada A, Shenoy C, et al. A comparison of contemporary definitions of contrast nephropathy in patients undergoing percutaneous coronary intervention and a proposal for a novel nephropathy grading system. Am J Cardiol Mar. 2008;101:812–9. [5] Barlis P, Regar E, Serruys PW, et al. An optical coherence tomography study of a biodegradable vs. durable polymer-coated limus-eluting stent: a LEADERS trial sub-study. Eur Heart J 2010;31:165–76. [6] Serruys PW, Silber S, Garg S, et al. Comparison of zotarolimus-eluting and everolimus-eluting coronary stents. N Engl J Med 2010;363:136–46. [7] Mintz GS, Popma JJ, Pichard AD, et al. Patterns of calcification in coronary artery disease. A statistical analysis of intravascular ultrasound and coronary angiography in 1155 lesions. Circulation 1995;91:1959–65. [8] Yonetsu T, Kakuta T, Lee T, et al. In vivo critical fibrous cap thickness for rupture-prone coronary plaques assessed by optical coherence tomography. Eur Heart J 2011;32:1251–9. [9] Kume T, Okura H, Kawamoto T, et al. Assessment of the coronary calcification by optical coherence tomography. EuroIntervention 2011;6:768–72. [10] Guagliumi G, Costa MA, Sirbu V, et al. Strut coverage and late malapposition with paclitaxel-eluting stents compared with bare metal stents in acute myocardial infarction: optical coherence tomography substudy of the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONSAMI) Trial. Circulation 2011;123:274–81.
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Randomized comparison of coronary stent implantation under ultrasound or angiographic guidance to reduce stent restenosis (OPTICUS Study). Circulation 2001;104:1343–9. [24] Kang SJ, Lee JY, Ahn JM, et al. Validation of intravascular ultrasound-derived parameters with fractional flow reserve for assessment of coronary stenosis severity. Circ Cardiovasc Interv 2011;4:65–71. [25] Kwon SW, Kim BK, Kim TH, et al. Qualitative assessment of neointimal tissue after drug-eluting stent implantation: Comparison between follow-up optical coherence tomography and intravascular ultrasound. Am Heart J 2011;161:367–72. [26] Albiero R, Rau T, Schluter M, et al. Comparison of immediate and intermediate-term results of intravascular ultrasound versus angiography-guided Palmaz-Schatz stent implantation in matched lesions. Circulation 1997;96:2997–3005. [27] Fitzgerald PJ, Oshima A, Hayase M, et al. Final results of the Can Routine Ultrasound Influence Stent Expansion (CRUISE) study. Circulation 2000;102:523–30. [28] Ozaki Y, Okumura M, Ismail TF, et al. Local determinants of thrombus formation following sirolimus-eluting stent implantation assessed by optical coherence tomography K. JACC Cardiovasc Interv 2009;2:459–66. [29] Cook S, Wenaweser P, Togni M, et al. Incomplete stent apposition and very late stent thrombosis after drug-eluting stent implantation. Circulation 2007;115: 2426–34. [30] Farb A, Burke AP, Kolodgie FD, Virmani R. Pathological mechanisms of fatal late coronary stent thrombosis in humans. Circulation 2003;108:1701–6. [31] Joner M, Finn AV, Farb A, et al. Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk. J Am Coll Cardiol 2006;48:193–202. [32] Finn AV, Joner M, Nakazawa G, et al. Pathological correlates of late drug-eluting stent thrombosis: strut coverage as a marker of endothelialization. Circulation 2007;115:2435–41. [33] Hoffmann R, Morice MC, Moses JW, et al. 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International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Frequency domain optical coherence tomography for guidance of coronary stenting Nicola Viceconte a, Pak Hei Chan a, Eduardo Alegria Barrero a, Liviu Ghilencea a, Alistair Lindsay a, Nicolas Foin b, Carlo Di Mario a,⁎ a b
Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, UK Biomedical Engineering Department, Imperial College, London, UK
a r t i c l e
i n f o
Article history: Received 8 July 2011 Received in revised form 1 October 2011 Accepted 27 November 2011 Available online 30 December 2011 Keywords: Frequency domain optical coherence tomography Percutaneous coronary intervention Coronary lesion assessment Stent optimization
a b s t r a c t Objective: To evaluate the role of Frequency domain optical coherence tomography (FD-OCT) in guiding stent implantation procedures. Methods: Dragonfly™-imaging catheter was used pre-intervention, after pre-dilatation or at various stages of stent deployment/post-dilatation to assess lesion severity, characteristics and guide stent expansion/apposition. Results: We performed 398 OCT pull-backs in 108 consecutive patients. The 371 pull-backs analysable, had an average length of 35 mm and encompassed 193 lesions (1.8 lesions per patient). Seventy-six percent of patient had AHA-ACC-class B–C lesions. In the pre-intervention group deferral of treatment was decided for 13/68 pullbacks (19.1%), whereas strategies different from conventional predilatation (e.g. thrombectomy, rotablator, cuttingballoon) were decided in 23 cases (33.8%). After full lesion dilatation 96 pullbacks (25.9%, pre-stenting group) were performed, 46 (47.9%) of which suggested proceeding directly with stenting while 50 (52.1%) suggesting further treatment. Out of the 207 pullbacks in post-stenting group, 29 (14%) suggested new stent implantation because of dissection or residual stenosis; 64 (30.9%) suggested further optimization with high pressure/larger-sized balloon. Average number of pull-backs per patient was 3.4 requiring 75.8± 19.3 ml of iopamidol. No major complications were observed. Five cases (4.6%) of contrast-induced nephropathy were reported. Conclusions: Repeated examinations with FD-OCT can be safely used to guide stent selection and improve stent expansion and apposition. © 2011 Elsevier Ireland Ltd. All rights reserved.
1. Introduction 1.1. Background and objective Optical coherence tomography (OCT) has greater resolution and better definition of luminal contours and strut position than intravascular ultrasound, the established standard for guidance of coronary stenting. OCT, however, requires clearance of blood during acquisition. When OCT acquisition was performed using a slow pull-back speed (3 mm/s), as required by time domain analysis, the use of OCT for procedural guidance when repeated examinations over long segments are required, was impractical. Frequency domain (FD) analysis allows an increase of the OCT acquisition rate to the point that the pull-back speed can be 6–7 times faster (20 mm/s) and still have better transversal and
Abbreviations: FD-OCT, Frequency domain optical coherence tomography; AHA-ACC, American Heart Association-American College of Cardiology; IVUS, Intravascular Ultrasound; MLCSA, Minimal Luminal Cross Sectional Area; FFR, Fractional flow Reserve; TD, Time Domain; ISA, Incomplete Stent Apposition; L/VLST, late/very late stent thrombosis; BMS, Bare Metal Stent; DES, Drug Eluting stent; LM, Left Main; SVG, Safenous Vein Graft. ⁎ Corresponding author at: Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, Sydney Street, SW3 6NP, London, UK. Tel./fax: +44 20 7352 8121, +44 7799067639 (Mobile). E-mail address: [email protected] (C. Di Mario). 0167-5273/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2011.11.090
longitudinal resolution than with time domain analysis [1,2]. This study reports a singe centre experience of the use of FD-OCT in consecutive patients studied with multiple pull-backs to guide lesion treatment and stent implantation at the Royal Brompton hospital since its introduction in 2009. 2. Methods 2.1. Patient selection Between September 2009 and December 2010, 134 consecutive patients were studied with FD-OCT at the Royal Brompton Hospital. We identified three different indications for OCT: 1) Pre-intervention: in patients with a sufficient minimal diameter to allow contrast penetration distal to the stenosis with the catheter across the lesion or after predilatation with 1.5 or 2.0 mm balloons, FD-OCT was used to determine whether a lesion of intermediate severity deserved treatment and/or to provide information on plaque characteristics (e.g. calcification, lesion length, relationship with branches) important to facilitate procedural planning. 2) Pre-stenting: when the operator felt that the lesion was sufficiently expanded to deploy a stent, FD-OCT was used to confirm that lesion preparation was optimal and select the most appropriate stent length and diameter. 3) Post-stenting: FD-OCT was used after angiographic guided optimisation with highpressure stent deployment and post-dilatation with non compliant balloons to confirm optimal stent expansion and lesion coverage or guide further post-dilatation with larger balloons/higher pressure or the implantation of additional stents proximal and/or distal due to residual uncovered stenoses or dissections.
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3. Results
A non-occlusive technique was used in all cases. A 2.7 Fr C7 Dragonfly™ Imaging Catheter (St Jude Medical LightLab, St. Paul, MN, USA), flushed with undiluted contrast and calibrated before the acquisition, was inserted over the guidewire distal to the lesion of interest. Acquisition was performed during continuous flushing of 2–5 mL/s of iodixanol (Visipaque™ 320 mg I/ml GE Healthcare, Amersham, UK) using a Medrad power injector. Pullback speed was set at 20 mm/s, with a length of vessel segment analysed between 30 and 54 mm (maximal pull-back length allowed by the system). Pull-back was manually started when sufficient blood clearance was obtained, allowing readjustment of the speed of contrast injection if blood was still partially obscuring the image. OCT analysis was performed on-line using the C7 system and off-line using a dedicated OCT Review Workstation (St Jude Medical LightLab, St. Paul, MN, USA). Proprietary patented software, loaded in a beta release version also on the C7 system for on-line use since February 2010, generates a mask of the OCT lumen image defining a plurality of scan lines and identifying the lumen/tissue interface along each scan line. After identification of valid neighbouring contour segments, interpolation was used to fill the missing contour data. If extensive interpolation was required jeopardising the likely correctness of the computed contour the system indicated to the user the image frames possibly in need of manual adjustment. Together with contour detection the system displays automatically all the measurements during pull-back and allows identification of the minimal luminal cross sectional area (MLCSA) and comparison of this measurement with the measurements of used defined proximal and distal reference cross-sections [3] (Fig. 1). Creatinine values were measured in all patients before and after procedure, contrast induced nephropathy was defined as increasing in creatinine level more than 25% of the baseline value [4]. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology.
Out of the134 consecutive patients assessed with FD-OCT between September 2009 and December 2010, 26 patients (110 pull backs, 21.6%) were excluded as they were studied only as a planned follow up for the evaluation of late strut apposition and coverage within predefined research protocols (LEADERS, RESOLUTE, etc.) [5,6]. We allocated the remaining 398 pull-backs obtained in 108 patients according to the three predefined indications above. The average pullback length was 35.1 ± 15.4 mm (range 9.6 to 54.0 mm) with wide variation caused by the premature interruption of the pullback because blood artefacts developed or because the OCT reached the guiding catheter in short proximal lesions or in long lesions requiring 2 sequential pull-backs. Among these 108 patients, 85 were men (75%) with a mean age of 53.0±9.6 years, 11 (10.2%) presented with an acute coronary syndrome. A total of 193 lesions were studied (1.8 lesions/patient), most of them complex. (Table 1) Most of the patients (89, 82.4%) had only one vessel studied, 16 (14.8%) had two vessels analysed and only in three patients (2.8%), OCT was performed in more than two vessels. The average number of pull-backs per patient was 3.4 (range 1–13), Fig. 2.
2.3. Statistical analysis
3.2. Changes in strategy due to OCT analysis
Categorical variables were expressed as percentage. Continuous variables were expressed as mean ± standard deviation (SD), and compared using paired T-test. A p value of b 0.05 was considered to be statistically significant, and all reported p-values are 2-sided. All analysis were performed using STATA 10.1 statistical software (Statacorp, Texas, USA).
Out of 398 pull-backs, we excluded 27 pullbacks (6.8%) due to poor quality (insufficient blood clearance, catheter damage, lesion incompletely assessed). Among the remaining 371 pullbacks in 108 patients, 68 (18.3%, pre-intervention group) were performed before a balloon was
3.1. Patient characteristics
Fig. 1. a: OCT long view reconstruction; multiple segments are encoded in red (red flagging) to identify the inability of the system to recognise the lumen area. b: poor saline flush; c: vessel irregularity after cutting balloon; d: bifurcation lesion after stenting.
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Table 1 Patient Characteristics. Number
%
Male Age (mean; SD⁎) Smoker Hypertension Hypercholesterolemia Family history of CAD† Diabetes Mellitus Previous PCI‡ Previous CABG§ Acute coronary syndromes Stable angina or silent ischemia
85 53 ± 9.6 45 75 91 56 34 71 28 11 97
75.0 – 41.7 69.4 84.3 51.9 23.2 65.8 25.9 10.2 89.8
ACC/AHA lesion classification Type A B C Non significant lesions
n (193) 37 57 90 9
% 19.2 29.5 46.6 4.7
n 9 33 34 5
% 8.3 30.1 31.5 4.6
Out of the 207 pullbacks performed in the post-stenting group, 29 (7.8%) suggested the need of a new stent implantation because of dissection or severe residual stenosis proximal/distal and 64 (30.9%) suggested further optimization with high pressure or larger size balloon. (Fig. 5) The remaining 114 pullbacks (55.1%) showed no need of additional steps to optimise results. The change in patient treatment strategy due to the FD-OCT evaluation is illustrated in Table 2. In order to minimise contrast load, once the largest balloon and highest pressure felt feasible and safe was used, a very final pull-back was performed only in a minority of the lesions requiring sequential steps for optimisation. Eight patients received complete serial evaluation, including final assessment after the largest balloon/highest pressure/last stent. MLCSA within the stent after optimization increased from 4.97 ± 1.68 mm2 to 5.42 ± 1.68 mm2, (pb 0.0001). The average luminal area gain was 0.45 mm2 (9.56 ± 3.14% increase compared with the preOCT optimised lumen area). The mean increase in balloon diameter was 0.31 ± 0.22 mm (8.61± 5.68%). Two patients were treated using a non compliant balloon of the same diameter but at a greater pressure (from 14.5 ± 7.8 Atm to 22.9 ± 5.2 Atm).
Special lesion subset CTO|| Bifurcations In-stent-restenosis Left main lesion ⁎ Standard Deviation. † Coronary Artery Disease. ‡ Percutaneous Coronary interventions. § Coronary Artery Bypass Grafting. || Chronic Total Occlusion.
inserted, mainly to decide whether an intervention was needed in the presence of stenoses of intermediate or ambiguous severity, or after a 1.5–2.0 mm balloon was specifically used to allow lesion visualisation with FD-OCT. After 13 pullbacks (19.1%) deferral of treatment was decided because the lesion did not match the expected criteria for severity. The need for specific lesion preparation (Rotablation, Cutting Balloon or thrombectomy) was defined in 23 pullbacks (33.8%) and a strategy on the length of lesion to cover and its relationship with bifurcations was established (Figs. 3–4). Following information from 32 OCT pullbacks (47.1%) conventional pre-dilatation was performed, but the information still helped the identification of optimal balloon length, type (compliant or not compliant) and diameter. After full lesion dilatation 96 pullbacks (25.9%, pre-stenting group) were performed, 46 (47.9%) of which suggested to proceed directly with stenting and clarified the optimal stent length and diameter, 50 (52.1%) suggesting the use of further preliminary treatment (additional high pressure dilatation or larger cutting/high pressure balloon). In the “pre-intervention” and “after post-dilatation” groups, plaque components were evaluated (total of 164 pullbacks). The extension of calcifications was classified into: mild (b90° of the vessel circumference), moderate (90°–180°), and severe (>180°) [7]. Moderate calcification was found in 27 pullbacks (16.5%), severe calcification was observed in 11 pullbacks (6.7%).
3.3. Safety and feasibility Thanks to its small calibre (diameter 2.7 Fr, 0.89 mm), the OCT catheter could easily cross the lesion/stent in the majority of cases, including some highly calcific lesions before pre-dilatation. We noticed, however, a reduced pushability of the catheter after prolonged use and in four cases the DragonFly catheter stopped at the proximal stent edge or at the ostium of a side-branch covered by a stent despite successful kissing balloon dilatation. Due to the high pullback speed, the average amount of contrast required during OCT pullback was 22.1 ± 4.7 ml. No major complications such as ventricular tachyarrhythmia, heart block, profound bradycardia (b40 beats per minute), coronary dissection or air embolism were observed. The mean time added to the procedure by the serial OCT examinations was 15.4 ± 8.2 min, including OCT catheter preparation, connection to the power injector, initialization of OCT system and insertion/withdrawal of the OCT catheter. The average total amount of additional contrast per patient required for the serial OCT examinations was 75.8± 19.3 ml. The mean creatinins value before and after the procedure was 89.3 ± 24.4 and 90.9 ± 23.0 mmol/l respectively. Five cases (4.6%) of contrast-induced nephropathy were observed but creatinine rapidly returned to the preintervention level within 48–72 hours with no need for haemofiltration or dialysis. 3.4. Efficacy of the automatic analysis system Red flagging, indicating possible inaccuracies in the detection of the vessel contour, covered 15.1% of the total pull-back length. Inaccuracies corresponded to segments with incomplete blood clearance, bifurcations, dissections or highly irregular lumen contours, proximal segments with the lumen boundaries outside the 4 mm of maximal depth. (Fig. 1) In 306 pull-backs (60.2%), the system was able to identify
Fig. 2. Number of pull-backs per patients. Note that 3 or more pull-backs were used in 61% of cases, suggesting that a stepwise approach was allowed by repeated pull-backs.
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Fig. 3. NSTEMI with stent thrombosis 4 yrs after paclitaxel eluting stent. (a–a1) filling defect of the proximal segment of LAD; OCT shows protruding thrombus (asterisk) (b); thrombus extracted with Hunter Catheter (c–d); angiographic finding after thrombus aspiration (d); OCT show residual luminal Thrombus (e) leading to a further successful aspiration with a different extraction catheter (Pronto) (f).
Fig. 4. Angiographic and OCT images: In stent Restenosis of proximal LAD, close to the first septal takeoff, MLA 2.53 mm2 (a–b); d: OCT show intimal dissection after 3.0 mm cutting balloon inflation (asterisk), not visible in the angiographic control; area has increased to 7.18 mm2 (c); final angiographic result (e), OCT control demonstrates a luminal area of 8.89 mm2, with good apposition of the stent struts (f).
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Fig. 5. 76 year old lay presented with stable effort angina. A) Angiogram showing proximal-mid LAD lesion of intermediate severity. A1) OCT image showing proximal reference of 10.23 mm2 with thin-capped soft lipid plaque (asterisk). A2) OCT demonstrating MLA of 3.37 mm2. A3) OCT showing distal reference of 6.66 mm2 with calcific plaque (white arrow). We decided to stent the lesion as MLA is b 4 mm2. B) Angiogram showing post-stenting result. B1) showing proximal stent strut malapposition; B2) showing segment with MLA of 8.78 mm2 with good strut apposition; B3) OCT demonstrating floating stent struts towards diagonal bifurcation (yellow arrows) C) Angiogram showing postdilatation for stent optimization, angiographically exactly the same but OCT could demonstrate an improvement in several aspects: C1) Good strut apposition after postdilatation with 4.0 mm non-compliant balloon, resulting in MLA of 13.18 mm2; C2) MLA increase from 8.78 mm2 to 9.91 mm2 after post-dilatation 3.5 mm high pressure balloon at 40 atm resulting in vessel more circular in shape compared with B2; C3) Better strut apposition was achieved towards the SB after kissing balloon inflation.
the MLCSA correctly and in 217 pull-backs (42.7%) also provided an immediate accurate measurement of this key quantitative parameter required for procedural guidance. Manual readjustments of the position of the MLCSA or contour corrections were greatly facilitated by the availability of a longitudinal view with superimposed measurements. 4. Discussion 4.1. OCT: from research to clinical applications Previous studies had demonstrated the unique features offered by OCT as a research tool, mainly to assess thrombus, intimal rupture, Table 2 Interventional stage when OCT was performed and changes in strategy prompted by the examination. Indications of OCT pull-back in the target vessel Pre-intervention - Deferral of planned PCIa - Identification of optimal balloon size, length, type - Suggestion of specific lesion preparation Thrombectomy Rotablator Cutting Balloon After pre-dilatation of lesion - Identification of optimal stent diameter and length - Further pre-treatment before stenting After stenting - Additional stent implantation - Expansion with higher pressure/larger balloon - No further changes from planned strategy a
Percutaneous coronary intervention.
Total number of pull-backs
% of total pullbacks (371)
68 13 32
18.3 19.1 47.1
23 3 6 14 96 46
33.8 4.4 8.8 20.6 25.9 47.9
50 207 29 64
52.1 55.8 14 30.9
114
55.1
lipid laden plaques and the thickness of their fibrous cap, strut apposition and late coverage [5,6,8–17]. The short length of the segments assessable with time-domain OCT (most often using a proximal occlusion balloon but also with a non-occlusive technique), dissuaded operators to move to clinical applications such as guidance of percutaneous coronary interventions [18]. The widespread application of a non-occlusive technique using Monorail OCT catheters and the rapid pull-back speed (≥20 mm/s) allowed by newer generation FD-OCT systems revived the interest in OCT for procedural guidance. Imola et al. in a recent study used FDOCT in 91 patients (33 of which were ACS) to assess lesion severity and result after stent implantation [19]. The preparation of the DragonFly catheter is simple, with an automatic calibration and purge of air with undiluted contrast using a high pressure syringe, and can be performed while the case is started. The pull-back duration is negligible and the review process is simpler than with ultrasound because all the lumen contours and measurements are already automatically displayed so that an expert operator can rapidly extract the relevant clinical information and decide the consequent procedural steps. It is not surprising that the time required for OCT was very short in spite of many pull-backs performed. The additional requirement of contrast remained disappointingly high. We included the contrast for the OCT catheter preparation and the contrast lost during the connection with the pressure injector. We also preferred to use the “manual” mode to start pull-back, waiting for the operator to give the command when there was perfect blood clearance. This method allowed us to abort the pull-back when clearance was suboptimal; sparing a full injection to acquire low quality images but possibly resulting in an overall greater contrast consumption. We often inserted the OCT catheter before repeating the planned angiographic control so that the same contrast was used for angiographic lesion assessment and to clear the blood during pull-back. Therefore, the “additional” contrast used for OCT was possibly overestimated because it was not entirely injected in the patient and replaced contrast required anyway for angiographic controls.
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None of the patients had severe renal failure consequent to contrast overload but we performed OCT only when we completed angiographic optimisation of results before and after stenting and often avoided the final OCT control when we felt no further interventions were likely to be triggered by a new study. On a positive side, the arrhythmias and chest discomfort caused in the past by the need of transient proximal balloon occlusion and of a prolonged selective contrast injection are not a concern using the new non-occlusive technique and rapid pullback speed of FD-OCT. 4.2. OCT use in different phases of PCI OCT can be used to assess the severity of the stenosis pre intervention but, in the absence of specific longitudinal trials or large comparison with FFR, criteria originally developed for ultrasound were applied [20–23]. Recent studies have challenged these parameters suggesting that the absolute measurement of MLCSA proposed as the threshold to trigger interventions (b4.0 mm2), are only applicable in large proximal epicardial vessels and are grossly overestimated in distal vessels or diffusely diseased arteries. Using OCT instead of IVUS does not correct these fundamental pitfalls which justify the superiority of Fractional Flow Reserve (FFR) myo for this particular application. Still in many intermediate or ambiguous lesions the distinction between severe and moderate stenoses is very obvious and a technique of intravascular imaging avoiding the ring down artefacts and showing more clearly the lumen/wall interface can only increase reliability [24]. Unlike FFR, OCT provides a wealth of information on lesion characteristics such as presence and type of thrombus, thin-cap fibro-atheroma, plaque ulceration, and superficial calcification which can help guide the procedure, often making it worthwhile to initially dilate with a small balloon to allow preliminary OCT examination of the lesion. The lower rate of calcification compared to previous IVUS studies [7] is probably related to the inability of the OCT to detect deep calcified lesions. [5] For in-stent restenosis, OCT provides information on the degree and localization of neo-intimal hyperplasia and can easily measure the stent area as stent struts remain clearly visualised. In a recent study, it was shown to be more efficacious than IVUS for the assessment of the severity of neo-intimal hyperplasia [25]. OCT pull-backs provide different but potentially equally useful information when used after the lesion has been prepared, before proceeding with stent implantation. Identification of an inadequate vessel response to balloon inflation may lead to the use of bigger/ higher pressure balloon(s) or other devices but also invariably helps to fine tune stent selection, both in terms of length and diameter of the delivery balloon. OCT images and measurements pre-stenting can also help the post-dilatation strategy, when it is clear that proximal stent optimisation with a larger balloon or postdilatation at higher pressures of a more resistant segment are required. The general principle, is to proceed with optimisation based on angiography and the information collected during the initial pre-stent examination and use OCT only when the angiographic appearance looks adequate to confirm optimal stent expansion and lesion coverage. This approach is already standard among experienced IVUS operators, but OCT requires more attention than IVUS to avoid a large number of repeated pull-backs in order to avoid an excessive contrast load. 4.3. OCT v IVUS criteria to guide stent expansion and strut apposition The sharp contrast wall/lumen with very small artefacts around stent struts allows immediate automatic measurements of high accuracy in the majority of pull-backs. This represents a clear advantage over IVUS but comes at a price: the low penetration of OCT, not substantially improved moving from Time Domain (TD)- to FD-OCT, makes the assessment of the total vessel diameter (media-to-media) unpractical and limited to a minority of distal reference segments with small amount of fibrotic or fibro-calcified plaque. When the vessel area
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cannot be identified in the reference segment, almost the norm in the proximal segment, the identification of the proximal and distal points where to implant a stent requires a synergistic combination of angiographic and OCT assessment. A large proximal lumen area, irrespective of the presence and extent of plaque encroachment, offers a valid target to anchor the proximal end of the stent and select the optimal balloon diameter for proximal stent expansion. In principle, with OCT the selection of balloon diameter is most often based on the lumen and not on the vessel area/diameter. The initial criteria proposed by Colombo et al. were based on a combination of vessel and lumen area/diameter and the Milan group has recently proposed simplified criteria (AVIO) to select optimal balloon size based on vessel area measurements [20]. The poor compliance of the investigators in reaching these targets (46% in an initial pilot study, unable to demonstrate significant differences in final MLCSA, let alone clinical advantages) suggests that vessel based criteria are too cumbersome for practical use. For this reason criteria for IVUS optimization used in different large multicentre studies have relied on a comparison of the MLCSA of the stented segment with the distal reference area or with the mean reference vessel area [22,26,27]. OCT has clear advantages compared with IVUS for the assessment of lumen area. OCT measurements obtained directly from automatic contour detection or after minor manual adjustment of the detected contours are much more appealing than cumbersome manual tracing of multiple cross-section of the IVUS examination. Expert IVUS “operators” or interpreters quickly analysing the IVUS pull-back after acquisition are a luxury that, besides live courses, is only available in few leading interventional centres outside Japan and this is one of the main reasons, probably above catheter cost, of the limited penetration of IVUS in the USA and Europe. Strut apposition has always been part of the criteria of optimal stent deployment and can be exquisitely assessed by OCT and imaging. Pathological studies have shown that incomplete stent apposition (ISA) is correlated with thrombus detection and late/very late stent thrombosis (L/VLST). ISA might delay neointimal healing of the stent and incomplete endothelialization of the struts is a common morphologic finding in fatal cases of L-VLST [28–32]. No correlation between ISA and adverse events such as stent thrombosis was assessed in IVUS sub-studies of BMS v DES studies but these studies dealt with very simple lesions and used a technique such a s IVUS which is not ideal to assess but the most extremes instances of ISA [33,34]. 4.3.1. Limitations of OCT for procedural guidance This is a retrospective review of a consecutive series of interventions in complex lesions. At this early stage of application of OCT, we did not try to systematically predefine the strategy, including balloon length and diameter, we were going to adopt if no imaging guidance was available. The identification of cases for whom OCT led to a change in strategy is then somewhat arbitrary because the strategical decisions respond to the general practice of centres with a high volume of intravascular imaging to base their decisions on an integrated analysis of angiography and IVUS or, in this study, OCT. Showing that OCT safely leads to strategy changes increasing lumen area and optimising lesion coverage and strut apposition does not mean that the changes obtained are clinically helpful. The disappointing results of some IVUS studies in the past for guidance of stent implantation should be carefully considered when claims are made that OCT can improve restenosis and reduce late thrombosis. In this study we did not perform any comparison of IVUS and FD OCT for measurement of MLCSA post-stenting, an important necessary step to understand the relative merits of IVUS and OCT. OCT is often unable to delineate the lumen contours in large vessels such as the LM or SVGs, especially when the OCT catheter lies eccentric in the vessel [35]. IVUS also has a clear advantage in ostial lesions because the guiding catheter can be easily disengaged during the IVUS examination while it must remain engaged to clear the blood during OCT pullback. This is a retrospective
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analysis of a single centre, which has started working with OCT in 2003. Newcomers in the field will need to go through a learning curve but the clarity of the OCT images and the availability of automated measurements suggest that this can be much steeper than the IVUS learning curve. Also, the patient spectrum would vary among different centres. In very simple lesions it is unlikely major gains can be achieved with any imaging strategy. Conceptually, lumen based criteria of expansion, the only possible with OCT, have limited ability to optimally increase the lumen size in long lesions, overlapping stents and in vessels with distal tapering because the distal reference lumen used to guide expansion does not reflect the true size of the optimal lumen several cm more proximal. Alternatives can be offered by algorithms to detect abrupt changes in stent area compared with neighbouring segments and creative criteria to guide the safe use of balloons with a diameter based on an average of proximal and distal reference weighted according to the relative distance of the segment of interest from the two reference segments. The automated area–length OCT measurements lend themselves to an easy implementation of such algorithms, guiding the application of focal high pressure balloons. (Fig. 5) The need of contrast injection during acquisition precludes the use of OCT in patients with presence or high risk of renal failure. Different types of contrast have been proposed but this resulted in a suboptimal image quality or introduced unbearable regulatory hurdles for approval. 5. Conclusions Frequency domain optical coherence tomography can be safely used to meet clinical applications of procedural guidance traditionally reserved for IVUS. Acknowledgement The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology. References [1] Takarada S, Imanishi T, Liu Y, et al. Advantage of next-generation frequency-domain optical coherence tomography compared with conventional time-domain system in the assessment of coronary lesion. Catheter Cardiovasc Interv 2010;75:202–6. [2] Kataiwa H, Tanaka A, Kitabata H, et al. Head to head comparison between the conventional balloon occlusion method and the non-occlusion method for optical coherence tomography. Int J Cardiol 2011;146:186–90. [3] Schmitt JM, Friedman JM, Petroff C, Elbasiony A. United States Patent Application 20110071404 Kind Code A1. March 24, 2011. [4] Harjai KJ, Raizada A, Shenoy C, et al. A comparison of contemporary definitions of contrast nephropathy in patients undergoing percutaneous coronary intervention and a proposal for a novel nephropathy grading system. Am J Cardiol Mar. 2008;101:812–9. [5] Barlis P, Regar E, Serruys PW, et al. An optical coherence tomography study of a biodegradable vs. durable polymer-coated limus-eluting stent: a LEADERS trial sub-study. Eur Heart J 2010;31:165–76. [6] Serruys PW, Silber S, Garg S, et al. Comparison of zotarolimus-eluting and everolimus-eluting coronary stents. N Engl J Med 2010;363:136–46. [7] Mintz GS, Popma JJ, Pichard AD, et al. Patterns of calcification in coronary artery disease. A statistical analysis of intravascular ultrasound and coronary angiography in 1155 lesions. Circulation 1995;91:1959–65. [8] Yonetsu T, Kakuta T, Lee T, et al. In vivo critical fibrous cap thickness for rupture-prone coronary plaques assessed by optical coherence tomography. Eur Heart J 2011;32:1251–9. [9] Kume T, Okura H, Kawamoto T, et al. Assessment of the coronary calcification by optical coherence tomography. EuroIntervention 2011;6:768–72. [10] Guagliumi G, Costa MA, Sirbu V, et al. Strut coverage and late malapposition with paclitaxel-eluting stents compared with bare metal stents in acute myocardial infarction: optical coherence tomography substudy of the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONSAMI) Trial. Circulation 2011;123:274–81.
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