TY - JOUR
AU - Albertucci,, Mario
AB - Abstract Intravascular imaging modalities are currently adopted to circumvent angiographic limitations. The present overview is aimed at describing the principal techniques used by an interventional cardiologist to assess both coronary atherosclerotic plaques and stent deployment results. Optical coherence tomography (OCT), intravascular ultrasound (IVUS), and near-infrared spectroscopy are currently available to address these issues. These techniques are characterized by specific advantages and limitations, making each of those applicable for specific purposes. Offline software programmes have been developed to further characterize plaque tissue, highlighting the macrophage presence or unfold coronary stent in a three-dimensional view by a carpet view. Although IVUS and OCT have been largely used for research purposes, growing evidence is supporting a clinical impact of percutaneous coronary interventions guided by those intravascular techniques, especially in the setting of complex procedures. We will provide data supporting a favourable outcome in particular describing the results of the ADAPT-DES study and CLI-OPCI registry. Optical coherence tomography, Near-infrared spectroscopy, Intravascular ultrasound, Coronary plaque, Stent, Stent thrombosis Introduction Imaging modalities Angiography is still the gold standard for assessment of atherosclerotic impairment of coronary arteries and for guidance of coronary intervention. Its main limitation is that it depicts only the luminal narrowing caused by coronary plaques, and does not show the structures located beneath, such as atherosclerotic lesions or vessel wall. For this reason, angiography may miss culprit ruptured lesions and is unable to address plaque vulnerability. Furthermore, the assessment of lesion severity at angiography can be hampered by anatomical factors. Reference vessel disease, lesion foreshortening, angulations, calcifications, and vessel overlap can complicate angiographic assessment of lesion severity. Intravascular imaging modalities are currently adopted to circumvent these angiographic limitations. In the last three decades, many intravascular imaging modalities have entered the clinical arena. Angioscopy was the first, and provided key information about the composition of the plaques and the presence of thrombus in the setting of non-ST-segment elevation myocardial infarction. Moreover, the technical complexity of angioscopy confined this technique to Japan. Intravascular ultrasound (IVUS) has been used for over 20 years and is currently the most used and well-known imaging modality. Although IVUS's ability to characterize the plaque components is limited in comparison with optical coherence tomography (OCT), the high penetration of ultrasound enables a full-depth study of the plaque and as a consequence identifies vessel remodelling, a feature of plaque vulnerability. Furthermore, IVUS easily depicts calcified plaques, providing the interventional cardiologist with key information. Optical coherence tomography is a novel imaging technique that uses infrared light and can study atherosclerotic plaques and stented segments with extreme accuracy.1,2 Compared with IVUS, which employs wave sounds, OCT has a much higher resolution.3 In fact, OCT resolution is ∼20 µm (compared with 100–150 µm with a 20 MHz IVUS transducer). This happens at the expense of the penetration depth that is dependent on plaque composition and in general <1 mm. Accordingly, OCT allows a better identification of coronary features located superficially in the plaques. Optical coherence tomography identifies plaque components differentiating calcium (Figure 1A), lipid, and fibrous tissues, and can identify vulnerable plaques (VPs) having a large lipid pool with thin-cap fibroatheroma (TCFA) or calcified nodules. Optical coherence tomography is also capable of identifying the mechanism of local coronary thrombosis, distinguishing between plaque with ulcerated (Figure 1B) vs. intact fibrous cap (IFC)3,4 and differentiating red thrombi from white ones. Figure 1 Open in new tabDownload slide Optical coherence tomography and intravascular ultrasound-near-infrared spectroscopy images of coronary atheroscleorotic plaques. (A) A calcified plaque is imaged by optical coherence tomography from 6 to 9 o'clock, as well-delineated, signal-poor regions. (B) A ruptured plaque is imaged by optical coherence tomography as fibrous cap disruption associated with intraluminal thrombus. A clear cavity formation is shown. (C) An intravascular ultrasound-near-infrared spectroscopy co-registration image showing an attenuated plaque on intravascular ultrasound cross-sectional image with a large lipid pool as detected by the near-infrared spectroscopy (depicted as yellow colour over the 360° circle). (D) A near-infrared spectroscopy chemogram showing probabilities of lipid core derived from the raw near-infrared spectroscopy spectral data, which ranges from 0 (red) to 1.00 (yellow). Figure 1 Open in new tabDownload slide Optical coherence tomography and intravascular ultrasound-near-infrared spectroscopy images of coronary atheroscleorotic plaques. (A) A calcified plaque is imaged by optical coherence tomography from 6 to 9 o'clock, as well-delineated, signal-poor regions. (B) A ruptured plaque is imaged by optical coherence tomography as fibrous cap disruption associated with intraluminal thrombus. A clear cavity formation is shown. (C) An intravascular ultrasound-near-infrared spectroscopy co-registration image showing an attenuated plaque on intravascular ultrasound cross-sectional image with a large lipid pool as detected by the near-infrared spectroscopy (depicted as yellow colour over the 360° circle). (D) A near-infrared spectroscopy chemogram showing probabilities of lipid core derived from the raw near-infrared spectroscopy spectral data, which ranges from 0 (red) to 1.00 (yellow). Near-infrared spectroscopy (NIRS) is a novel catheter-based technique that allows determination of the chemical composition of the coronary artery wall5 (Figure 1C). This is accomplished by measuring the proportion of near-infrared light diffusely reflected by the arterial wall after scattering and absorption. Near-infrared spectroscopy is nowadays the most accurate imaging technique for identifying lipid core plaques (LCPs) at risk of rupture. The near-infrared laser beam scans across multiple wavelengths generating a longitudinal image (chemogram) of the scanned artery segment (Figure 1D). Each spectral measurement is assigned a probability of LCP by the detection algorithm and displayed in a false colour map known as a chemogram, with colours ranging from red (a low probability of LCP) to yellow (a high probability of LCP). From the chemogram, a summary metric of the probability that an LCP is present in a 2 mm interval of the pullback is computed and displayed in a supplementary false colour map called a block chemogram. An additional metric is the lipid core burden index, which is computed as the fraction of valid pixels in the chemogram that exceed an LCP probability of 0.6, multiplied by 1000.5 Post-processing of optical coherence tomography and intravascular ultrasound images A post-processing analysis of both OCT and IVUS images can be carried out using the dedicated software. In particular, OCT images can be analysed using a new software programme called ‘Carpet View’, which unfolds the vessel, reconstructing it as an open structure and displaying it in a two-dimensional format.6 The software can improve the off-line serial comparisons of both coronary plaques and stented segments, enabling the matching of the imaged cross-section at different time points. Dedicated software programmes have been developed to identify and quantify macrophages using OCT images. Macrophages are inflammatory cells that play a central role in plaque instability by releasing proteolytic enzymes and other pro-inflammatory mediators, which, in turn, can lead to fibrous cap rupture and subsequent plaque thrombosis. The software is able to measure the OCT signal variance, termed normalized standard deviation (NSD), that tends to increase in the presence of a significant macrophage content.7 However, NSD may overestimate the presence of macrophage due to artefacts. Thus, other tissue property indexes have been proposed to further characterize the presence of macrophage. Granulometry applies a sieving process to the OCT pixels identifying a specific range of structures comprised between 30 and 150 µm. Macrophages are between 20 and 50 µm in size; however, they may eventually turn into larger cells called foam cells. The latter, due to their larger size, can be identified using granulometry. A two-step algorithm has been developed to identify inflammatory cells with higher accuracy. It first requires NSD measurements followed by granulometry assessment. Greyscale IVUS provides only a gross definition of plaque types. Both virtual histology (VH) IVUS and integrated backscatter (IB) IVUS have been developed to further elaborate the backscattered IVUS signal, to enhance differentiation of the major plaque components. Virtual histology-intravascular ultrasound uses an auto-regression model to generate multiple spectral parameters of the backscattered ultrasound signal to generate a tissue map of the plaque components: fibrous (dark green), fibro-fatty (yellow-green), necrotic core (red), and dense calcium (white). The PROSPECT study was the first prospective trial capable of relating plaque composition to clinical events during follow-up. Three features conveyed a worsened outcome: (i) VH-IVUS-derived TCFA, defined as a necrotic core-rich (>10%) plaque without evident overlying fibrous tissue, (ii) a per cent plaque burden of >40%, and (iii) a minimal lumen area of <4 mm.2,8 The IB-IVUS technique, which employs mathematical manipulation of the ultrasound backscatter signal, has also been developed to improve the ability of IVUS to detect VP. Integrated backscatter values for the various plaque components can then be calculated to construct colour-coded IB-IVUS maps leading to five categories: thrombus, intimal hyperplasia/lipid core, fibrous, mixed, and calcified tissues. Future directions Optical coherence tomography technologies are still evolving. Micro-OCT has a resolution of <10 μm and is currently in the development stage. It promises to identify single cells such as endothelial cells, lymphocytes, or monocytes. Future directions also include functional assessment of plaque pathobiology and inflammation through the use of OCT probes combined with novel optically active molecular imaging agents. Clinical relevance of imaging findings Coronary thrombus Optical coherence tomography can reveal fresh coronary thrombi that can be missed by angiography or IVUS and identify culprit lesions guiding their treatment. Coronary thrombus is the ultimate event leading to acute coronary syndrome (ACS) and is often associated with plaque rupture. Plaque erosion is another mechanism of coronary thrombosis, being responsible for 30% of acute coronary events.2 Our group recently studied the healing process of 10 thrombotic culprit plaques in patients with ST-segment elevation myocardial infarction, which were not treated with percutaneous coronary intervention (PCI). Optical coherence tomography was used to distinguish between ruptured fibrous cap and IFC and to follow the lesions for up to 7 months. The morphology of the ruptured plaque remained almost unchanged over time, while the margins of the evacuated rupture showed a smooth surface and fibrosis. On the other hand, IFC revealed smoothened plaque surface. Thrombus morphology at OCT changed over time. The irregular inner contour of the thrombus in the acute phase evolved into a homogeneous and smooth contour in the subacute phase. In the late follow-up period, the thrombus became organized showing a typical low backscatter rim indicating new tissue appositions. Ambiguous lesions Conventional angiography has as its main limitation the incapacity to visualize structures (e.g. plaque and vessel) located outside the lumen. Optical coherence tomography, on the other hand, can study at high-resolution superficial plaque components such as calcium, lipid pool, thrombus, and stent elements, distinguishing struts apposition from malapposition, and coverage vs. uncoverage. Comparison of optical coherence tomography and near-infrared spectroscopy-intravascular ultrasound for lipid pool assessment The identification of a lipid pool may not be easy in the presence of superficial macrophage clusters; these cells can scatter the OCT signal in the same manner as lipid pools leading to an overestimation of the lipid pool. The recent combination of NIRS with greyscale IVUS in a single imaging catheter allows simultaneous assessment of both the chemical (by NIRS) and morphological (by IVUS) characteristics of plaque composition. Specifically, NIRS can quantify plaque lipid content. Yonetsu et al.9 compared NIRS-IVUS and OCT for the detection of lipid in non-target lesions of a cohort of ACS and stable angina patients. They showed poor overall agreement between NIRS and OCT regarding detection of lipid. In particular, in the presence of superficial calcification, OCT analysis of non-target lesions led to misinterpretation of lipid content.9 In addition, histopathology studies have shown that foamy macrophages accumulating on the luminal surface of the vessel wall, which are identified in OCT by the typical appearance of a thin bright line with trailing shadows, may mimic lipid materials impeding an accurate tissue analysis of deeper structures. Previous studies carried out with OCT and NIRS showed that the presence of lipid necrotic pool is related to periprocedural myocardial infarction. In fact, a non-reflow phenomenon may occur in the presence of thrombus or large lipid pools after stent deployment, due to the embolization of thrombus or lipid components. Ongoing studies will reveal whether the use of NIRS pre-intervention can guide interventional procedures with the specific goal to avoid the non-reflow phenomenon and improve the clinical outcome. Optical coherence tomography-guided percutaneous coronary intervention Our group has recently published the CLIO-PCI study showing the clinical impact of OCT findings in improving the clinical outcome of patients undergoing PCI. The multicentre CLI-OPCI study10 investigated the role of OCT guidance. The registry compared the clinical outcome of 335 patients with OCT-guided intervention to that of a control group by means of propensity score adjustment. Optical coherence tomography guidance was found to improve the 1-year composite event rate of cardiac death or non-fatal myocardial infarction after PCI in a real-world population. The study also addressed the issue of how to treat OCT findings, indicative of suboptimal stent deployment. Based on the OCT results, 34.7% of the stented segments required further intervention with either balloon dilation (22.3%) or additional stenting (12.4%). The study showed that quantitative OCT thresholds are required in order to improve the clinical outcome of patients undergoing PCI. Some interventional cardiologists suggest the use of pre-intervention OCT guidance, with the specific goal to select the diameter and length of stents, after having achieved precious information on vessel anatomy. The CLI-POOL study brings strength to this concept by showing that incomplete stent coverage of coronary lipid pools imaged by OCT at the stent edges is associated with an increased risk of post-procedural myocardial infarction. Optical coherence tomographic studies, in patients with acute coronary syndrome, have shown that in-stent tissue protrusion due to the presence of residual thrombus is a common finding. Recent data revealed that residual intrastent thrombus is related to periprocedural myocardial infarction if left untreated.11 Preliminary data showed that additional OCT-driven in-stent balloon dilatation can significantly reduce the percentage of in-stent thrombus area without worsening the microcirculatory indexes. As another crucial application, OCT can clarify mechanisms of restenosis (Figure 2A) and thrombosis (Figure 2B) early or late after the index procedure, guiding repeat revascularization and thus minimizing the risk of additional adverse events. Assessment of stent under-expansion by OCT can be obtained by comparing the minimal stent area with the reference lumen area. In addition, a threshold of absolute minimum lumen cross-sectional area within the stent could be applied, with an area of at least 5.0–5.5 mm2 previously advocated as the target minimum stent area to prevent failure.12 A recent study from our group, the CLI-THRO study, evaluated the incidence of suboptimal OCT results in 21 consecutive patients exhibiting subacute thrombosis. The patients were matched 1 : 2 with a control group of 42 patients from the Rome Heart Research core laboratory database. Optical coherence tomography showed that minimum lumen area and minimum stent area measurements were significantly smaller in the stent thrombosis group together with a higher frequency of stent under-expansion, edge dissection, and reference lumen narrowing.11 Figure 2 Open in new tabDownload slide Representative optical coherence tomography images for restenosis and stent thrombosis. (A) Restenotic tissue with aspects compatible with neoatherosclerosis. Neointimal tissue shows a high attenuation from 5 to 9 o'clock, indicating a lipid-rich plaque. (B) Intraluminal thrombus associated with significant neointimal proliferation inside a stent. The patient had an acute myocardial infarction due to late stent thrombosis. Figure 2 Open in new tabDownload slide Representative optical coherence tomography images for restenosis and stent thrombosis. (A) Restenotic tissue with aspects compatible with neoatherosclerosis. Neointimal tissue shows a high attenuation from 5 to 9 o'clock, indicating a lipid-rich plaque. (B) Intraluminal thrombus associated with significant neointimal proliferation inside a stent. The patient had an acute myocardial infarction due to late stent thrombosis. Intravascular ultrasound-guided percutaneous coronary intervention Randomized studies conducted in the 1990s evaluated the usefulness of an IVUS-guided bare-metal stent expansion to reduce restenosis. Most of these studies were underpowered and restricted to non-complex lesions. After the introduction of drug-eluting stents (DESs), the benefits of IVUS were questioned given the improved outcomes with DESs compared with bare-metal stents. A recent sub-study of the ADPAT-DES trial compared IVUS and angiography-guided PCIs in terms of 1-year outcomes.13 The study enrolled 8583 consecutive patients, with IVUS being utilized in 39% of patients. Interestingly, in the IVUS-guided arm, the interventional cardiologist changed the PCI strategy in 74% of patients, mainly employing larger stents or balloons. The overall 1-year rate of adjudicated major adverse cardiac events (MACEs), defined as cardiac death, definite/probable stent thrombosis, or myocardial infarction, was significantly less in the IVUS-guided group compared with the angiography-guided group (3.1 vs. 4.7%; hazard ratio 0.67; 95% confidence interval 0.53–0.84; P = 0.0006).13 However, the difference was mainly due to a reduced incidence of definite/probable stent thrombosis together with a less frequent rate of spontaneous and target vessel-related myocardial infarction. The benefits of IVUS were especially evident in patients with ACS and complex lesions, although significant reductions in MACEs were present in all patient subgroups including those with stable angina and single-vessel disease.13 Recent meta-analyses combining randomized studies and registries relative to the DES era confirmed the conclusions reached by the ADAPT-DES trial, further highlighting the clinical benefits to be gained from an IVUS-guided approach.12 In contrast with these data, a large registry conducted in London from 2004 to 2011 on 41 688 stable and unstable patients revealed no significant difference in patients treated with an IVUS-guided PCI when compared with an angiographic procedure in terms of all-cause mortality at a median follow-up period of 3.3 years.14 Such a study questions the role of an IVUS-guided strategy in the presence of new-generation DES, having an improved delivery and safety. The AVIO trial15 addressed a different approach to optimize stenting that is based on the IVUS assessment of media-to-media diameter. The study had a randomized design, comparing IVUS optimized DES implantation with angiographic guidance, and included only complex lesions such as bifurcations, long lesions, chronic total occlusions, or small vessels. The goal was to obtain in the IVUS arm an optimal stent expansion, by choosing an optimal non-compliant balloon size (OBS) for post-dilatation. The OBS was determined by averaging the media-to-media diameters of the distal and proximal stent segments and the site of maximal narrowing within the stent. The AVIO criteria were safely applied and led to larger final stent lumen areas. Conclusions Intravascular imaging techniques have been extensively used for research purposes. They have allowed a better understanding of both coronary atherosclerosis and stent complications. Recent evidence is supporting a possible clinical use of IC imaging techniques in guiding PCI. Complex anatomy like ambiguous or complex lesions, or acute coronary syndromes, are fields of potential application for intravascular techniques with the aim of improving clinical outcomes. Funding The present EHJ Suppl. issue has been funded by E.S. Health Science Foundation. Conflict of interest: none declared. References 1 Prati F , Regar E , Mintz GS , Arbustini E , Di Mario C , Jang IK , Akasaka T , Costa M , Guagliumi G , Grube E , Ozaki Y , Pinto F , Serruys PW . 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TI - New techniques of intravessel imaging in coronary atherosclerosis
JF - European Heart Journal Supplements
DO - 10.1093/eurheartj/suv014
DA - 2015-03-01
UR - https://www.deepdyve.com/lp/oxford-university-press/new-techniques-of-intravessel-imaging-in-coronary-atherosclerosis-gSwfmFd6bL
SP - A58
VL - 17
IS - suppl_A
DP - DeepDyve
ER -