Article

Combined NIRS and IVUS imaging detects vulnerable plaque using a single catheter system: A head-to-head comparison with OCT

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

Aims: The presence of thin-cap fibroatheromas (TCFA) is associated with high risk of acute coronary syndrome, hence their early detection may identify high-risk patients. In the present study we investigated the ability of a combined imaging catheter with near-infrared spectroscopy (NIRS) plus intravascular ultrasound (IVUS) to detect TCFA in patients with stable coronary artery disease. Methods and results: Optical coherence tomography (OCT) and combined NIRS-IVUS assessment were performed on identical coronary segments. IVUS analysis provided per-segment minimal cross-sectional area (CSA), plaque length (PL), plaque burden (PB), plaque volume (PV), and remodelling index (RI). OCT was used as the gold-standard reference to define TCFA (fibrous cap thickness <65 μm). Plaque lipid content was estimated by NIRS (lipid core burden index [LCBI]). OCT-defined TCFA was present in 18 of 76 segments. IVUS revealed that OCT-defined TCFA were positively remodelled lesions with greater PB and PV, smaller CSA, and longer PL, while NIRS revealed greater LCBI per 2 mm segment (LCBI2mm) (all p<0.001). Greatest accuracy for OCT-defined TCFA detection was achieved using LCBI2mm >315 with RI >1.046 as a combined criterion value. Conclusions: OCT-defined TCFA are characterised by positive vessel remodelling, high plaque burden and greater lipid core burden as assessed by dual NIRS-IVUS imaging.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... The prospect study presented that lesions with plaque burden (PB) ≥ 70% and minimal lumen area (MLA) ≤ 4 mm 2 on intravascular ultrasound (IVUS) imaging increased the risk of MACE [4]. A high lipid burden assessed by intravascular near-infrared spectroscopy (NIRS) suggested increased the risk of future MACE [5], and combined NIRS-IVUS imaging study presented its potential to detect TCFA [6]. ...
... The raw spectra of NIRS estimate the probability of the presence of an atherosclerotic lipid core and measurements are displayed as a chemogram -a digit code NIRS map [6]. The NIRS map analysis allows calculation of lipid core burden index (LCBI) in 4 mm pullback compartments. ...
... According to the previously published studies, the following vulnerable lesions were identified by OCT and NIRS-IVUS imaging. OCT-defined TCFA as described above, IVUS vulnerable plaque defined as lesion with PB > 70% and MLA < 4 mm 2 (PROSPECT study) [4], and NIRS-IVUS TCFA described previously as LCBI 4 mm > 265 with simultaneous positive RI of the vessel [6] and lesions with LCBI 4 mm > 400, which was the threshold of lipid burden for observed culprit STEMI lesions [8]. ...
Article
Full-text available
Background: Fractional flow reserve (FFR) assesses a functional impact of the atheroma on the myocardial ischemia, but it does not take into account the morphology of the lesion. Previous optical coherence tomography (OCT), intravascular ultrasound (IVUS) and near infrared spectroscopy (NIRS) studies presented their potential to detect vulnerable plaque, which is not possible by FFR assessment. With the following study, the intermediate lesions were assessed by FFR, OCT and combined NIRS-IVUS imaging to identify plaque vulnerability. Methods: 13 intermediate lesions were analyzed simultaneously by FFR, OCT and combined NIRS-IVUS imaging. Results: Two lesions were found to have FFR ≤ 0.80 (0.65 and 0.76). The other 11 lesions had FFR > 0.80 with a mean FFR 0.88 ± 0.049. Two lesions with FFR ≤ 0.80 had plaque burden (PB) > 70% and minimal lumen area (MLA) < 4 mm², but neither of these 2 lesions were identified as OCT defined thin fibrous cap atheroma (TCFA), or NIRS-IVUS possible TCFA. Among the other 11 lesions with FFR > 0.80, 8 were identified as OCT-defined TCFA, 4 had PB > 70%, 6 had MLA < 4 mm², 2 had both plaque burden > 70% and MLA < 4 mm², 3 lesions were identified as NIRS-IVUS possible TCFA, and 4 lesions had LCBI > 400. Conclusions: The FFR-negative lesions pose traits of vulnerability as assessed simultaneously by IVUS, OCT and NIRS imaging.
... However, it has not been implemented on a large scale in clinical practice. 21,22 The aim of this systematic review was to perform a systematic analysis of the studies characterizing vulnerable plaque features visualized using invasive imaging methods such as optical coherence tomography and intravascular ultrasound, in order to identify the most efficient invasive technique that can be used for plaque characterization in patients with acute myocardial infarction. ...
... The present study was performed using the methodology Furthermore, studies analyzing less than thirty coronary plaques, those not providing relevant data, those related to non-coronary vulnerable plaques such as carotid plaques, or only ex-vivo studies were excluded. 15,19,20,22,25 Part 2 compared the IVUS-and OCT-derived plaque characteristics in 587 ruptured versus non-ruptured cor- 15 Tian et al. 20 Takahashi et al. 19 Kume et al. 25 Roleder et al. 22 28 Kato et al. 27 Yonetsu et al. 26 Tian et al. 20 20,26,27,28 Part 3 consisted of the analysis of two studies reporting on OCT-and IVUS-derived plaque characteristics of 173 culprit and non-culprit coronary plaques from 232 patients with acute coronary syndromes. 20,29 Part 4 consisted of the analysis of data on the lipid content of 302 plaques from 302 patients. ...
... The present study was performed using the methodology Furthermore, studies analyzing less than thirty coronary plaques, those not providing relevant data, those related to non-coronary vulnerable plaques such as carotid plaques, or only ex-vivo studies were excluded. 15,19,20,22,25 Part 2 compared the IVUS-and OCT-derived plaque characteristics in 587 ruptured versus non-ruptured cor- 15 Tian et al. 20 Takahashi et al. 19 Kume et al. 25 Roleder et al. 22 28 Kato et al. 27 Yonetsu et al. 26 Tian et al. 20 20,26,27,28 Part 3 consisted of the analysis of two studies reporting on OCT-and IVUS-derived plaque characteristics of 173 culprit and non-culprit coronary plaques from 232 patients with acute coronary syndromes. 20,29 Part 4 consisted of the analysis of data on the lipid content of 302 plaques from 302 patients. ...
Article
Full-text available
The A total number of 432 studies were identified, 420 through database searching and 12 through manual searching. Eight duplicate studies were removed, leaving a total number of 424 studies to be screened. Twenty-six studies only available in Abstract-only form were excluded, resulting in 398 studies checked for eligibility. Eleven studies fulfilled the eligibility criteria and were included in this systematic analysis. Plaque vulnerability was investigated in plaques with thin cap fibroatheroma (TCFA) versus those with thick cap fibroatheroma, in ruptured coronary plaques versus non-ruptured coronary plaques, in culprit versus non-culprit lesions and in lipid-rich versus non-lipid-rich plaques. A total of 1,568 coronary plaques in 1,225 patients with acute coronary syndromes (ACS) who underwent both IVUS and OCT for analysis of plaque features were included in the final analysis. The review identified the following IVUS-derived features as significantly correlated with plaque vulnerability: plaque burden (p <0.001), remodeling index (p <0.001), external elastic membrane cross-sectional area (p <0.001), and the amount of necrotic core (p <0.001), while OCT-derived features characterizing unstable plaque were TCFA (p <0.001), lipid arch (p <0.001), accumulation of macrophages (p = 0.03), and presence of intracoronary thrombus (p <0.001). Both IVUS and OCT are invasive imaging techniques able to provide relevant information on the vulnerability of coronary atheromatous plaques, identifying, as they do, various plaque features significantly associated with unstable plaques. Information provided by the two techniques is complementary, and both methods can serve as a useful clinical diagnostic tool, especially in cases of ACS patients undergoing a revascularization procedure.
... Vulnerable plaques characterized as "positive vessel remodeling" have a lipid core and a fibrous cap less than 65 m thick. These features define them as a thin-cap fibroatheroma (TCFA) [2][3][4][5]. If a TCFA ruptures, it exposes the plaque's core to platelets, and the thrombosis of coronary arteries occurs [6]. ...
... NIRS alone is oriented to the detection of lipids within the vessel wall but coregistered with IVUS images provides information about the plaque composition and its burden simultaneously. As it was previously presented, NIRS-IVUS poses the ability to detect vulnerable plaques [1,2,[13][14][15][16]. ...
... LCBI is helpful in assessing the risk of plaque rupture and the use of preventative strategies during PCI. Plaque with large LCP and identified by NIRS maxLCBI 4 mm of ≥500 suggested high risk plaque [2,15,21]. ...
Article
Full-text available
Background . Detecting and identifying vulnerable plaque, which is prone to rupture, is still a challenge for cardiologist. Such lipid core-containing plaque is still not identifiable by everyday angiography, thus triggering the need to develop a new tool where NIRS-IVUS can visualize plaque characterization in terms of its chemical and morphologic characteristic. The new tool can lead to the development of new methods of interpreting the newly obtained data. In this study, the algorithm to fully automated lipid pool detection on NIRS images is proposed. Method . Designed algorithm is divided into four stages: preprocessing (image enhancement), segmentation of artifacts, detection of lipid areas, and calculation of Lipid Core Burden Index. Results . A total of 31 NIRS chemograms were analyzed by two methods. The metrics, total LCBI, maximal LCBI in 4 mm blocks, and maximal LCBI in 2 mm blocks, were calculated to compare presented algorithm with commercial available system. Both intraclass correlation (ICC) and Bland-Altman plots showed good agreement and correlation between used methods. Conclusions . Proposed algorithm is fully automated lipid pool detection on near infrared spectroscopy images. It is a tool developed for offline data analysis, which could be easily augmented for newer functions and projects.
... NIRS detects lipids within plaques, and the amount of lipids is measured as a lipid core burden index (maxLCBI4mm). Lesions with maxLCBI4mm ≥ 265 are identified as thin cap fibrous atheroma (TCFA) [14] and are associated with an increased risk of post-PCI myocardial infarction (MI) [15,16]. ...
... NIRS simultaneously distinguishes lipid-core plaques (LCP), which are associated with increased risk of periprocedural MI and restenosis rates following stent implantation [38][39][40]. The specific lipid-rich lesions with maxLCBI4mm ≥265 were defined as TCFA [14]. In our study, QFR-positive lesions were characterized by greater maxLCBI4mm. ...
Article
Full-text available
Quantitative flow ratio (QFR) is a new opportunity to analyze functional stenosis during invasive coronary angiography. Together with a well-known intravascular ultrasound (IVUS) and a new player in the field, near-infrared spectroscopy (NIRS), it is gaining a lot of interest. The aim of the study was to compare QFR results with integrated IVUS-NIRS results acquired simultaneously in the same coronary lesion. We retrospectively enrolled 66 patients in whom 66 coronary lesions were assessed by NIRS-IVUS and QFR. Lesions were divided into two groups based on QFR results as QFR-positive group (QFR ≤ 0.8) or QFR-negative group (QFR > 0.8). Based on ROC curve analysis, the best cut-off values of minimal lumen area (MLA), minimal lumen diameter (MLD) and percent diameter stenosis for predicting QFR ≤ 80 were 2.4 (AUC 0.733, 95%CI 0.61, 0.834), 1.6 (AUC 0.768, 95%CI 0.634, 0.872) and 59.5 (AUC 0.918, 95%CI 0.824, 0.971), respectively. In QFR-positive lesions, the maxLCBI4mm was significantly higher than in QFR-negative lesions (450.12 ± 251.0 vs. 329.47 ± 191.14, p = 0.046). The major finding of the present study is that values of IVUS-MLA, IVUS-MLD and percent diameter stenosis show a good efficiency in predicting QFR ≤ 0.80. Moreover, QFR-positive lesions are characterized by higher maxLCBI4mm as compared to the QFR-negative group.
... 27 Ota et al. 28 showed that positive remodelling positively correlates with the NIRS-defined maxLCBI 4mm value in 100 lesions of 67 patients with stable CAD and NSTE-ACS. Our data are in line with Roleder et al. 29 who investigated the ability of IVUS/NIRS to detect OCT-defined TCFA in patients with stable coronary disease. They found that OCT-defined TCFA is characterized by positive vessel remodelling, high plaque burden, and higher maxLCBI 4mm value. ...
... They found that OCT-defined TCFA is characterized by positive vessel remodelling, high plaque burden, and higher maxLCBI 4mm value. However, while the study of Roleder et al. 29 focused on segments with OCT-defined TCFA in a single vessel in 60 patients with stable CAD, we specifically focused on the maxLCBI 4mm segment in line with the recently published Lipid-Rich Plaque Study, 14 which showed that the maxLCBI 4mm segment is an independent predictor of future events on a patient-and lesion-level. Moreover, the current study is the largest with >100 patients and the only one applying all clinically available intracoronary imaging methods simultaneously in two non-IRAs in acute myocardial infarction patients, i.e. those at the highest risk for recurrent events. ...
Article
Aims: We assessed morphological features of near-infrared spectroscopy (NIRS)-detected lipid-rich plaques (LRPs) by using optical coherence tomography (OCT) and intravascular ultrasound (IVUS). Methods and results: IVUS-NIRS and OCT were performed in the two non-infarct-related arteries (non-IRAs) in patients undergoing percutaneous coronary intervention for treatment of an acute coronary syndrome. A lesion was defined as the 4 mm segment with the maximum amount of lipid core burden index (maxLCBI4mm) of each LRP detected by NIRS. We divided the lesions into three groups based on the maxLCBI4mm value: <250, 250-399, and ≥400. OCT analysis and IVUS analysis were performed blinded for NIRS. We measured fibrous cap thickness (FCT) by using a semi-automated method. A total of 104 patients underwent multimodality imaging of 209 non-IRAs. NIRS detected 299 LRPs. Of those, 41% showed a maxLCBI4mm <250, 39% a maxLCBI4mm 251-399, and 19% a maxLCBI4mm ≥400. LRPs with a maxLCBI4mm ≥400, as compared with LRPs with a maxLCBI4mm 250-399 and <250, were more frequently thin-cap fibroatheroma (TCFA) (42.1% vs. 5.1% and 0.8%; P < 0.001) with a smaller minimum FCT (80 μm vs. 110 μm and 120 μm; P < 0.001); a higher IVUS-derived percent atheroma volume (53% vs. 53% and 44%; P < 0.001) and a higher remodelling index (1.08 vs. 1.02 and 1.01; P < 0.001). MaxLCBI4mm correlated with OCT-derived FCT (r = 0.404; P < 0.001) and was the best predictor for TCFA with an optimal cut-off value of 401 (area under the curve = 0.882; P < 0.001). Conclusion: LRPs with increasing maxLCBI4mm exhibit OCT and IVUS features of presumed plaque vulnerability including TCFA morphology, increased plaque burden, and positive remodelling.
... 86 Studies using NIRS have shown that large lipid content, rather than plaque burden, is associated with thin cap fibroatheroma features. 25,87 Larger lipid core burden has been shown to accurately differentiate between culprit and nonculprit lesion in ST-elevation MI patients 88 and has been associated with higher risk for periprocedural myocardial infarction. 89 Interestingly, combination with IVUS may allow for concomitant appreciation of both plaque structure and composition, 90 comparing favorably with OCT. ...
... 89 Interestingly, combination with IVUS may allow for concomitant appreciation of both plaque structure and composition, 90 comparing favorably with OCT. 87 Despite recent studies linking lipid-rich, NIRS-defined nonculprit plaque presence with a 4-fold risk for adverse events (all-cause mortality, nonfatal ACS, stroke, and unplanned revascularizationexcluding those definitely related to the initial culprit lesion) 91 within the first year of follow-up, it cannot be inferred whether these were actually triggered by the detected vulnerable plaque (thus being amenable to preventive stenting) or by other, not assessed lesions (NIRS was only performed over a vessel segment). The latter could have very well been nonvulnerable lesions at the examination time, and their progression would reflect the need to reduce the atherosclerotic burden as a whole, rather than perform localized treatment. ...
Article
Full-text available
Atherosclerosis is the most common form of vascular disease and constitutes the major cause of death, with 17.5 million related deaths annually (31% of global mortality).[1][1] Atherosclerotic plaque represents the hallmark lesion of atherosclerosis. Most, but not all,[2][2], [3][3] acute cardiac
... In this latest study, as compared to OCT, the NIRS-IVUS system demonstrated a sensitivity and specificity of 97% and 96% for identifying OCT-PR, 93% and 99% for OCT-PE and 100% and 99% for OCT-CN, respectively [83]. Furthermore, several comparative studies investigated the diagnostic performance of NIRS in comparison to VH-IVUS and OCT in identifying TCFAs: NIRS-derived maxLCBI4mm was found to correlate with IVUS-derived positive remodeling in a study by Ota et al. [84] and with OCT-derived thin FC and the prevalence of TCFA in a population of CCS patients [85] (Figure 7). Furthermore, Zanchin et al. investigated the morphological features of NCL in a population of 104 ACS patients through multimodal intracoronary imaging: they found that NIRS-derived LRPs exhibited a high rate of IVUS-derived and OCT-derived signs of vulnerability [86]. ...
Article
Full-text available
Atherosclerotic cardiovascular disease is the leading cause of morbidity and mortality worldwide. Several cardiovascular risk factors are implicated in atherosclerotic plaque promotion and progression and are responsible for the clinical manifestations of coronary artery disease (CAD), ranging from chronic to acute coronary syndromes and sudden coronary death. The advent of intravascular imaging (IVI), including intravascular ultrasound, optical coherence tomography and near-infrared diffuse reflectance spectroscopy has significantly improved the comprehension of CAD pathophysiology and has strengthened the prognostic relevance of coronary plaque morphology assessment. Indeed, several atherosclerotic plaque phenotype and mechanisms of plaque destabilization have been recognized with different natural history and prognosis. Finally, IVI demonstrated benefits of secondary prevention therapies, such as lipid-lowering and anti-inflammatory agents. The purpose of this review is to shed light on the principles and properties of available IVI modalities along with their prognostic significance.
... 11 The introduction of dual-sensor NIRS intravascular ultrasound (NIRS-IVUS) allowed simultaneous assessment and thus a co-localization of lipids and plaque volume. 12 By combining these intravascular imaging techniques with computational fluid dynamics (CFD) to compute WSS, the interplay between WSS and LRP can be investigated. ...
Article
Full-text available
Aims: Low wall shear stress (WSS) is acknowledged to play a role in plaque development through its influence on local endothelial function. Also, lipid-rich plaques (LRPs) are associated with endothelial dysfunction. However, little is known about the interplay between WSS and the presence of lipids with respect to plaque progression. Therefore, we aimed to study the differences in WSS-related plaque progression between LRPs, non-LRPs, or plaque-free regions in human coronary arteries. Methods and results: In the present single-centre, prospective study, 40 patients who presented with an acute coronary syndrome successfully underwent near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) and optical coherence tomography (OCT) of at least one non-culprit vessel at baseline and completed a 1-year follow-up. WSS was computed applying computational fluid dynamics to a three-dimensional reconstruction of the coronary artery based on the fusion of the IVUS-segmented lumen with a CT-derived centreline, using invasive flow measurements as boundary conditions. For data analysis, each artery was divided into 1.5 mm/45° sectors. Plaque growth based on IVUS-derived percentage atheroma volume change was compared between LRPs, non-LRPs, and plaque-free wall segments, as assessed by both OCT and NIRS. Both NIRS- and OCT-detected lipid-rich sectors showed a significantly higher plaque progression than non-LRPs or plaque-free regions. Exposure to low WSS was associated with a higher plaque progression than exposure to mid or high WSS, even in the regions classified as a plaque-free wall. Furthermore, low WSS and the presence of lipids had a synergistic effect on plaque growth, resulting in the highest plaque progression in lipid-rich regions exposed to low shear stress. Conclusion: This study demonstrates that NIRS- and OCT-detected lipid-rich regions exposed to low WSS are subject to enhanced plaque growth over a 1-year follow-up. The presence of lipids and low WSS proves to have a synergistic effect on plaque growth.
... 18 The NIRS analysis generates a total LCBI measurement based on the amount of lipid in the investigated artery and detects the 4-mm segment with maximum LCBI (maxL-CBI4mm). 19 All NIRS parameter measurements are fully automated, quantitative, and generated in real-time during catheter pull-back, enabling immediate integration into the catheterization laboratory workflow and clinical decision-making. ...
Article
Full-text available
Intravascular imaging techniques such as intravascular ultrasound (IVUS) and optical coherence tomography (OCT) are able to provide valuable insights on vessel size and structure, including plaque composition. Unfortunately, both techniques miss the possibility of quantifying the amount of cholesterol content in the vessel wall, an essential piece of information to assess plaque vulnerability. The presence of a large lipid core covered by a thin fibrous cap with prominent inflammation within the shoulder region of the cap identifies plaques most likely to rupture. Retrospective analysis of serial angiographies has suggested that in nearly two-thirds of patients presenting with acute coronary syndrome (ACS), a coronary angiogram obtained weeks or months before the acute episode revealed that the culprit lesion site had a noncritical (< 70%, mostly < 50%) diameter narrowing, highlighting the importance of the different plaque features. A consequence of the excellent performance of second-generation drug-eluting stents is the prevalence of adverse events after ACS caused by lesions different from the stented culprit lesion. Techniques that empower clinicians to identify suspected vulnerable plaques offer clinically relevant information that can be used to escalate the aggressiveness of the new costly therapeutic agents targeted at reducing plaque vulnerability (PCSK9 inhibitors, SGLT2 inhibitors, etc.).
... Optical coherence tomography is an imaging modality that enables us to identify coronary plaque features with high-resolution imaging quality (3,4). Several previous studies compared NIRS-IVUS and optical coherence tomography (OCT) findings and showed associations between NIRS-detected great lipid core burden index (LCBI) and OCT-detected plaque vulnerability in stable patients (5) and non-infarct-related arteries (6). Recently, a NIRS-IVUS and OCT study (7) has proposed NIRS-IVUS-derived criteria to predict the OCTderived plaque morphologies of the culprit lesions of acute myocardial infarction. ...
Article
Full-text available
Background Near-infrared spectroscopy (NIRS) provides the localization of lipid-rich components in coronary plaques. However, morphological features in NIRS-detected lipid-rich plaques (LRP) are unclear. Methods A total of 140 de novo culprit lesions in 140 patients with the acute coronary syndrome (ACS) who underwent NIRS and optical coherence tomography (OCT) examinations for the culprit lesions at the time of percutaneous coronary interventions were investigated. We defined a NIRS-LRP as a lesion with a maximum lipid core burden index of 4 mm [LCBI 4mm ] > 500 in the culprit plaque. Clinical demographics, angiographic, and OCT findings were compared between the patients with NIRS-LRP ( n = 54) vs. those without NIRS-LRP ( n = 86). Uni- and multivariable logistic regression analyses were performed to examine the independent OCT morphological predictors for NIRS-LRP. Results Clinical demographics showed no significant differences between the two groups. The angiographic minimum lumen diameter was smaller in the NIRS-LRP group than in the non- NIRS-LRP group. In OCT analysis, the minimum flow area was smaller; lipid angle, lipid length, the prevalence of thin-cap fibroatheroma, and cholesterol crystals were greater in the NIRS-LRP group than in the non-NIRS-LRP group. Plaque rupture and thrombi were more frequent in the NIRS-LRP group, albeit not significant. In a multivariable logistic regression analysis, presence of thin-cap fibroatheroma [odds ratio (OR): 2.56; 95% CI: 1.12 to 5.84; p = 0.03] and cholesterol crystals (OR: 2.90; 95% CI: 1.20 to 6.99; p = 0.02) were independently predictive of NIRS-LRP. Conclusions In ACS culprit lesions, OCT-detected thin-cap fibroatheroma and cholesterol crystals rather than plaque rupture and thrombi were closely associated with a great lipid-core burden.
... Nonetheless, it has been repeatedly demonstrated that high LCBI (i.e., lipid rich plaque) represents a vulnerable plaque and low LCBI a stable lesion (7)(8)(9)(10)(20)(21)(22)(23). High LCBI also correlates with thin cap fibroatheroma detected on optical coherence tomography imaging (24). Nakagawa et al. demonstrated that high LCBI represents a vulnerable lesion for CAS (14). ...
Article
Full-text available
Background: Long-term effect of carotid stenting (CAS) on the stabilization of the plaque is almost unrecognized. Vascular healing and remodeling might seal the atherosclerotic plaque with neointimal hyperplasia decreasing the vulnerability. We aimed to assess long-term change in the lipid signal, stent and luminal dimensions and restenosis after CAS with the intravascular ultrasound (IVUS) and near-infrared spectroscopy (NIRS) imaging. Methods: We performed follow-up angiography and NIRS-IVUS imaging of 58 carotid stents in 52 patients. Median time from CAS to the follow-up examination was 31 months (range, 5-56). The lipid signal of the stented segment was calculated from a NIRS-derived chemogram (a spectroscopic map) as the lipid core burden index (LCBI, a dimensionless number from 0 to 1,000). Planimetric and volumetric measurements from IVUS were performed to assess change in minimal stent area (MSA), minimal luminal area (MLA), stent and luminal volume, late stent expansion and percentage in-stent restenosis (ISR) volume. Results: During the follow-up period, the mean (±SD) LCBI significantly decreased from 32±56 to 17±27 (P=0.002). The mean stent volume significantly increased from 717±302 to 1,019±429 mm3 (P<0.001) with mean stent expansion 43%±24%. The mean luminal volume increased from 717±302 to 760±359 mm3 (P=0.025) due to ISR encroaching 26%±15% of the stent volume. Conclusions: Lipid signal decreased during the follow-up period suggesting stabilization of the plaque. Late stent expansion was balanced with neointimal hyperplasia. Trial registration: The trial is registered under clinicaltrials.gov NCT03141580.
... Interobserver agreement on maximal lipid arc was similarly good (intraclass correlation coefficient [ICC] 0.82-0.90). 14,16, 19 OCT detection of ...
Article
Full-text available
Background:Optical coherence tomographic (OCT) imaging has enabled identification of lipid, with increasing interest in how it may affect coronary interventions and clinical outcomes. This review summarizes the available evidence around OCT identification of lipid and its effect on interventions, clinical events, and the natural history of coronary disease. Methods and Results:We conducted a scoping review using the Medline, HealthStar, and Embase databases for articles published between 1996 and 2021. We screened 1,194 articles and identified 51 for inclusion in this study, summarizing the key findings. The literature supports a common OCT definition of lipid as low-signal regions with diffuse borders, validated against histology and other imaging modalities with acceptable intra- and inter-rater reliability. There is evidence that OCT-identified lipid at the site of stent implantation increases the risk of edge dissection, incomplete stent apposition, in-stent tissue protrusion, decreased coronary flow after stenting, side branch occlusion, and post-procedural cardiac biomarker increases. In mostly retrospective studies, lipid indices measured at non-stented sites are associated with plaque progression and the development of recurrent ischemic events. Conclusions:There is extensive literature supporting the ability of OCT to identify lipid and demonstrating a substantial impact of lipid on percutaneous coronary intervention outcomes. Future work to prospectively evaluate the effect of the characteristics of lipid-rich plaques on long-term clinical outcomes is needed.
... Recently there has been intense interest in multi-modality intravascular imaging probes that provide complementary structural and molecular information. These probes include combinations such as US with photoacoustic (PA) imaging (6,28) or with near-infrared spectroscopy (NIRS) (5,29). A potential strong advantage of OpUS probes, as compared to their electronic counterparts, is that the optical fibers used to generate and receive ultrasound can also be used to transmit light for PA and NIRS. ...
Article
Full-text available
Conventional intravascular ultrasound (IVUS) devices use piezoelectric transducers to electrically generate and receive US. With this paradigm, there are numerous challenges that restrict improvements in image quality. First, with miniaturization of the transducers to reduce device size, it can be challenging to achieve the sensitivities and bandwidths required for large tissue penetration depths and high spatial resolution. Second, complexities associated with manufacturing miniaturized electronic transducers can have significant cost implications. Third, with increasing interest in molecular characterization of tissue in-vivo, it has been challenging to incorporate optical elements for multimodality imaging with photoacoustics (PA) or near-infrared spectroscopy (NIRS) whilst maintaining the lateral dimensions suitable for intracoronary imaging. Optical Ultrasound (OpUS) is a new paradigm for intracoronary imaging. US is generated at the surface of a fiber optic transducer via the photoacoustic effect. Pulsed or modulated light is absorbed in an engineered coating on the fiber surface and converted to thermal energy. The subsequent temperature rise leads to a pressure rise within the coating, which results in a propagating ultrasound wave. US reflections from imaged structures are received with optical interferometry. With OpUS, high bandwidths (31.5 MHz) and pressures (21.5 MPa) have enabled imaging with axial resolutions better than 50 μm and at depths >20 mm. These values challenge those of conventional 40 MHz IVUS technology and show great potential for future clinical application. Recently developed nanocomposite coating materials, that are highly transmissive at light wavelengths used for PA and NIRS light, can facilitate multimodality imaging, thereby enabling molecular characterization.
... Indeed, in the present study, the NC content was significantly larger in positively remodeled vessels than their un-remodeled counterparts. This finding was consistent with a report by Roleder et al. [35]. This may lead to local inability of the stenotic vascular segment to dilate to the same extent as the rest of the vessel, the result of which would be a larger translesional pressure drop and lower FFR value [19]. ...
Article
Full-text available
Fractional flow reserve (FFR) may not be immune from hemodynamic perturbations caused by both vessel and lesion related factors. The aim of this study was to investigate the impact of plaque- and vessel wall-related features of vulnerability on the hemodynamic effect of intermediate coronary stenoses. Methods and Results: In this cross-sectional study, patients referred to catheterization laboratory for clinically indicated coronary angiography were prospectively screened for angiographically intermediate stenosis (50-80%). Seventy lesions from 60 patients were evaluated. Mean angiographic stenosis was 62.1 ± 16.3%. After having performed FFR assessment, intravascular ultrasound (IVUS) was performed over the FFR wire. Virtual histology IVUS was used to identify the plaque components and thin cap fibroatheroma (TCFA). TCFA was significantly more frequent (65 vs. 38%, p = 0.026), and necrotic core volume (26.15 ± 14.22 vs. 16.21 ± 8.93 mm3, p = 0.04) was significantly larger in the positively remodeled than non-remodeled vessels. Remodeling index correlated with necrotic core volume (r = 0.396, p = 0.001) and with FFR (r = -0. 419, p = 0.001). With respect to plaque components, only necrotic core area (r = -0.262, p = 0.038) and necrotic core volume (r = -0.272, p = 0.024) were independently associated with FFR. In the multivariable model, presence of TCFA was independently associated with significantly lower mean FFR value as compared to absence of TCFA (adjusted, 0.71 vs. 0.78, p = 0.034). Conclusion: The current study demonstrated that for a given stenosis geometry, features of plaque vulnerability such as necrotic core volume, TCFA, and positive remodeling may influence the hemodynamic relevance of intermediate coronary stenoses.
... On the other hand, OCT has the highest spatial resolution (axial resolution 15-20 µm) among intracoronary imaging devices, which enables the precise measurement of the cap thickness (104)(105)(106). OCT has been well-validated, and its estimations correlated well with the corresponding pathophysiological findings (107,108). ...
Article
Full-text available
Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) have been developed and improved as both diagnostic and guidance tools for interventional procedures over the past three decades. IVUS has a resolution of 100 μm with a high tissue penetration and capability of assessing the entire structure of a coronary artery including the external elastic membrane, whereas OCT has a higher resolution of 10–20 μm to assess endoluminal structures with a limited tissue penetration compared to IVUS. Recently, two companies, CONAVI and TERUMO, integrated IVUS and OCT into a single catheter system. With their inherent strength and limitations, the combined IVUS and OCT probes are complementary and work synergistically to enable a comprehensive depiction of coronary artery. In this review, we summarize the performance of the two intracoronary imaging modalities—IVUS and OCT—and discuss the expected potential of the novel hybrid IVUS–OCT catheter system in the clinical field.
... The amount of lipids is measured as a lipid core burden index ( max LCBI 4mm ). Roleder et al. [10] and Inaba et al. [11] identified TCFA as lesions with max LCBI 4mm ≥ 323. ...
Article
Full-text available
Background: Previous studies suggest that higher plasma concentrations of several lipid molecules are associated with higher lipid core burden index (LCBI) NIRS imaging. The aim of this study was to investigate whether an association between plasma lipids depends on plaque morphology (thin cap fibrous atheroma [TCFA] vs. non-TFCA) as measured by near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS). Methods: 64 patients retrospectively enrolled were diagnosed with stable coronary artery disease or acute coronary syndrome who underwent NIRS-IVUS imaging. Before percutaneous coronary intervention, blood samples were collected for measurement of serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (HDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides. Patients were divided into two groups based on maxLCBI4mm and IVUS imaging. Those with maxLCBI4mm ≥ 323 were included into TCFA group (n = 35) while others were assigned to the non-TCFA group (n = 29). Results: Thin cap fibrous atheroma (TCFA) lesions were significantly longer than the non-TCFA lesions (25.66 ± 9.56 vs. 17.03 ± 9.22, p = 0.001). TCFA characterizes greater plaque burden (78.4 [70.9, 82.2] vs. 72.70 [64.77, 76,05]; p = 0.021) and plaque volume (176.1 [110.75, 247.5] vs. 68.1 [55.58, 143.35]; p = 0.000) as compared to non-TCFA. In TCFA suspected lesions, there was no correlation between maxLCBI4mm and LDL levels (r = 0.105, p = 0.549) nor TC levels (r = -0.035, p = 0.844) but a negative correlation was found between HDL-C and maxLCBI4mm (r = -0.453, p = 0.007). Conclusions: The present study showed that there was no correlation between plasma LDL-C, TCH and TG level and the amount of lipids in coronary plaque assessed by NIRS in both TCFA and non-TCFA groups. Only HDL-C correlated with maxLCBI4mm in TCFA lesions.
... NIRS has been used to assess the lipid content of plaques by identifying the presence of cholesterol monohydrate and cholesterol ester. This has been validated in histopathological studies [4] and in comparison to OCT [17]. There are several characteristics of NIRS that make it an attractive intracoronary imaging tool. ...
Article
Full-text available
Purpose of Review The purpose of this article is to review the basic principles of near-infrared spectroscopy (NIRS) and its contemporary role in intracoronary imaging. Recent Findings NIRS has been demonstrated to effectively detect culprit lesions in acute coronary syndromes (ACS) and to potentially identify vulnerable plaque. Lipid-rich plaques detected by NIRS are also associated with higher incidence of future adverse cardiac events. Plaques with high lipid content detected by NIRS have been shown to predict periprocedural myocardial infarction during percutaneous coronary intervention (PCI). The beneficial effects of high-intensity statin therapy in terms of plaque regression and plaque stabilization have also been demonstrated using NIRS. Summary NIRS is a valuable intracoronary imaging tool to assess lipid burden in atherosclerotic plaques and has been validated against histopathologic data. The commercially available dual-modality NIRS-intravascular ultrasound (IVUS) catheter further provides complementary data regarding lesion and vessel characteristics, thereby facilitating planning and optimization of PCI. Finally, the ability of NIRS to detect vulnerable plaque opens up potential new opportunities for risk stratification and intensification of secondary preventive measures.
... The combination of IVUS and NIRS in a single catheter provides an IVUS image within a lipid-rich area. This unique image includes information about a potentially-vulnerable plaque in patients with stable coronary artery disease [21] and is used to associate plaque characteristics with future clinical events [9]. Limitations attributed to low resolution remainimaging high risk plaque characteristics as thin fibrous cap atheroma and estimating the neo-intimal stent strut coverage is still not feasible using NIRS-IVUS. ...
Article
Computational cardiology is the scientific field devoted to the development of methodologies that enhance our mechanistic understanding, diagnosis and treatment of cardiovascular disease. In this regard, the field embraces the extraordinary pace of discovery in imaging, computational modeling and cardiovascular informatics at the intersection of atherogenesis and vascular biology. This article highlights existing methods, practices, and computational models and proposes new strategies to support a multidisciplinary effort in this space. We focus on the means by which to leverage and coalesce these multiple disciplines to advance translational science and computational cardiology. Analyzing the scientific trends and understanding the current needs we present our perspective for the future of cardiovascular treatment.
... The accuracy of NIRS to detect lipid core-containing atherosclerotic plaques has been validated in coronary autopsy specimens 1 and in vivo 2 . NIRS has been utilised to assess coronary atherosclerosis and the effect of various interventions on the lipid signal in coronary plaques [3][4][5] . Studies with NIRS have demonstrated that the presence of lipid-rich coronary plaques in patients undergoing percutaneous coronary intervention (PCI) is related to the incidence of cardiovascular events during long-term follow-up 6,7 , the risk of periprocedural myocardial infarction during PCI [8][9][10] , and presentation with stable angina versus acute coronary syndrome 11,12 . ...
Article
Full-text available
Aims: Catheter-based intravascular near-infrared spectroscopy (NIRS) detects a lipid signal from atherosclerotic plaque. The aim of this study was to describe the effect of carotid artery stenting (CAS) on the lipid signal in a carotid stenosis. Methods and results: We performed NIRS combined with intravascular ultrasound (IVUS) during 120 CAS procedures. Minimal luminal area (MLA) and plaque burden (PB) at the site of MLA were measured with IVUS and lipid core burden index (LCBI), maximal LCBI in a 4-mm segment of the artery (LCBImax) and LCBI in a 4-mm segment at the site of MLA (LCBImla) with NIRS-derived chemograms. NIRS-IVUS imaging was performed at baseline, after stent implantation and after balloon postdilatation. The most common lesion type was the fibrocalcific plaque (76%). Lipid-rich plaque (LCBImax ≥400) was present in 33% of carotid stenoses and in 20% at the site of MLA. Median MLA increased significantly from baseline to stent implantation (3.63 mm2 to 5.56 mm2, P<0.001) and to postdilatation (5.56 mm2 to 12.03 mm2, P<0.001). Median LCBI, LCBImax and LCBImla significantly decreased from baseline to stent implantation: LCBI (60 to 8, P<0.001), LCBImax (294 to 60, P<0.001) and LCBImla (124 to 0, P<0.001). Postdilatation of the stent had no further significant effect on median LCBI (8 to 5, P=0.890), LCBImax (60 to 50, P=0.690) and LCBImla (0 to 0, P=0.438). Conclusions: Carotid artery stenting significantly reduced the NIRS-derived lipid core burden index at the stented segment.
... It seems that even OCT based TCFA definition is not ideal for discrimination of risk plaque phenotype in DM patients. The best approach may be a dual source of information composed of IVUS-VH for necrotic core detection and OCT for fibrous cap measurement [50] or even better near-infrared spectroscopy IVUS (for highly sensitive lipid pool detection) and OCT [51]. The behavior of TCFA over the period of 1 year has been studied by IVUS-VH in patients with stable coronary artery disease [52], and using non-culprit plaques in patients with acute myocardial infarction [53]. ...
Article
Full-text available
Background Coronary atherosclerosis progresses faster in patients with diabetes mellitus (DM) and causes higher morbidity and mortality in such patients compared to non-diabetics ones (non-DM). We quantify changes in plaque volume and plaque phenotype during lipid-lowering therapy in DM versus non-DM patients using advanced intracoronary imaging. Methods We analyzed data from 61 patients with stable angina pectoris included to the PREDICT trial searching for prediction of plaque changes during intensive lipid-lowering therapy (40 mg rosuvastatin daily). Geometrically correct, fully 3-D representation of the vascular wall surfaces and intravascular ultrasound virtual histology (IVUS-VH) defined tissue characterization was obtained via fusion of two-plane angiography and IVUS-VH. Frame-based indices of plaque morphology and virtual histology analyses were computed and averaged in 5 mm long baseline/follow-up registered vessel segments covering the entire length of the two sequential pullbacks (baseline, 1-year). We analyzed 698 5-mm-long segments and calculated the Liverpool active plaque score (LAPS). Results Despite reaching similar levels of LDL cholesterol (DM 2.12 ± 0.91 mmol/l, non-DM 1.8 ± 0.66 mmol/l, p = 0.21), DM patients experienced, compared to non-DM ones, higher progression of mean plaque area (0.47 ± 1.15 mm² vs. 0.21 ± 0.97, p = 0.001), percent atheroma volume (0.7 ± 2.8% vs. − 1.4 ± 2.5%, p = 0.007), increase of LAPS (0.23 ± 1.66 vs. 0.13 ± 1.79, p = 0.018), and exhibited more locations with TCFA (Thin-Cap Fibro-Atheroma) plaque phenotype in 5 mm vessel segments (20.3% vs. 12.5%, p = 0.01). However, only non-DM patients reached significant decrease of LDL cholesterol. Plaque changes were more pronounced in PIT (pathologic intimal thickening) compared to TCFA with increased plaque area in both phenotypes in DM patients. Conclusion Based on detailed 3D analysis, we found advanced plaque phenotype and further atherosclerosis progression in DM patients despite the same reached levels of LDLc as in non-DM patients. Trial registration ClinicalTrials.gov identifier: NCT01773512
... In a recent report, Wang et al. showed that necrotic-rich plaques have the ability to fluoresce (near infrared autofluoresnce imaging-NIRAF) when they are excited with NIRF light at 633 nm. 30 The safety and the efficacy of OCT-NIRAF in the characterization of atherosclerosis was been tested in a small study involving 12 patients undergoing PCI. 31 The acquired NIRAF emission intensities were co-registered offline with the OCT imaging data. A strong NIRAF signal was seen in regions of plaque with high-risk features such as lipid containing plaques, thin-fibrous caps, macrophages and ruptured plaques with overlaying thrombus. ...
Article
Full-text available
Coronary artery disease remains the leading cause of death in the developed world. Over recent years, research has been focused on the development of diagnostic intravascular imaging techniques that enable assessment of plaque composition and morphology, and allow identification of vulnerable, high-risk lesions. Nevertheless recent studies of coronary atherosclerosis have shown that invasive modalities have a limited accuracy in detecting lesions that will progress and cause events, whilst histology-based studies also highlighted the limitations of invasive imaging in assessing plaque characteristics. To overcome these drawbacks, multimodality imaging has been proposed. Although it is apparent that coronary imaging with two or three imaging modalities is time consuming and is associated with a risk of complications, evidence from small clinical studies demonstrated that it provides incremental information about plaque pathology and biology and underscored the need to develop dual-probe hybrid imaging catheters that would enable complete and comprehensive assessment of plaque morphology. This paper reviews the current clinical evidence that supports the use of multimodality intravascular imaging in the study of atherosclerosis, summarizes the key findings of the first invasive imaging studies that utilize hybrid dual-probe catheters, and discusses the limitations of combined intravascular imaging that restrict its broad application in both the clinical and research arena.
... A study conducted in 17 patients who underwent NIRS and OCT imaging showed modest linear correlation between LCBI and maximum lipid arc and lipid index measured by OCT (r 2 = 0.319, P = 0.003, and r 2 = 0.404, P = 0.001, respectively) [82]. Furthermore, Roleder et al. [83] conducted a study which aimed to evaluate the accuracy of NIRS-IVUS-imaging modality to detect TCFA in 60 patients with stable CAD, by comparison to OCT used as the gold-standard reference to define TCFA (cap thickness of <65 μm). They showed that OCT-defined TCFA was characterized by positive vessel remodeling with higher lipid-core burden, while NIRS revealed greater LCBI per 2-mm segment (LCBI 2mm ) >315 with a remodeling index >1.046 ...
... Despite its inability to measure the depth of lipids in the vessel wall or the fibrous cap thickness, Saybolt et al. showed that early and persistent accumulation of total arterial lipid detected by NIRS was associated with the future development of TCFAs in serial imaging of 37 arteries in a diseased pig model [41]. Efforts to combine NIRS with other imaging modalities, notably IVUS, have resulted in better correlation between imaging and histology [42,43], proving that while NIRS remains a useful tool in the catheterization laboratory, it lacks the potential to replace other imaging modalities and remains mostly a research commodity. ...
Article
Full-text available
Purpose of Review Atherosclerotic plaque rupture remains the primary mechanism resulting in myocardial infarction and death. Better detection of the vulnerable atherosclerotic plaque, one which is at “high risk” of rupturing, will allow earlier and more effective intervention to preventing myocardial infarction in susceptible patients. In the following manuscript, we review recent developments in the assessment of vulnerable plaque via invasive imaging. The evidence, limitations, and future prospects of various intravascular imaging modalities (optical coherence tomography (OCT), intravascular ultrasound (IVUS), angioscopy, and near-infrared spectroscopy (NIRS)) are summarized. Recent Findings The vulnerable plaque has unique signature depending on the imaging modality used in the diagnostic process. We show illustrative examples from every modality and we shed light on emergent technologies, aiming at providing the reader with an understanding of the interaction between modalities. We also present the concept of three-dimensional plaque assessment and explore the role of invasive imaging in helping to understand the most recently identified mechanism of stent failure: neoatherosclerosis. Summary As all these invasive imaging modalities have proven to be safe and feasible, recent efforts have focused on software development aiming at increasing the ease of use of these technologies, allowing faster and more accurate online display of images, and one can forecast a future in which one catheter can be used to give state of the art imaging, which will be combined with computational algorithms, allowing image-derived physiological assessment of CAD lesions, as well as virtual projections of the effects (physiological, mortality, morbidity) of a planned intervention on target vessel.
... OCT-derived TCFA compared to non-TCFA has been described as lesions containing greater plaque burden and positive remodeling with a predominance of lipid component and less fibrous plaque [18]. Some authors have tried to combine two or even three intravascular imaging modalities in order to increase the accuracy in identifying TCFA [19][20][21]. As described by Fujii et al. in an ex vivo validation study [20], the combined use of OCT and IVUS might improve the accuracy compared to either OCT or IVUS alone. ...
Article
Full-text available
Objectives: We sought to assess a new modality of radiofrequency intravascular ultrasound (IVUS) called iMAP-IVUS (Boston Scientific, Santa Clara, California) during the evaluation of patients presenting with high-risk acute coronary syndromes. Background: There are limited data on plaque tissue characterization and phenotype classification using iMAP-IVUS. Methods: In the iWonder study patients presenting with ST-elevation myocardial infarction (STEMI) or non-STEMI underwent three-vessel grayscale IVUS and iMAP-IVUS tissue characterization prior to percutaneous intervention. In total 385 lesions from 100 patients were divided into culprit (n = 100) and nonculprit (n = 285) lesions. Lesion phenotype was classified as (i) thin-cap fibroatheroma (iMAP-derived TCFA); (ii) thick-cap fibroatheroma; (iii) pathological intimal thickening; (iv) fibrotic plaque; and (v) fibrocalcific plaque. Results: Culprit lesions had smaller minimum lumen cross-sectional area (MLA) with greater plaque burden compared to non-culprit lesions. Volumetric analysis showed that culprit lesions had longer length and larger vessel and plaque volumes compared to non-culprit lesions. iMAP-IVUS revealed that culprit lesions presented more NC and fibrofatty volume, both at lesion level and at the MLA site (all P < 0.001). Any fibroatheroma was more frequently identified in culprit lesions compared with non-culprit lesions (93% vs. 78.9%, P = 0.001), anywhere within the lesion 19.0%, P < 0.001) as well as at the MLA site (18.0% vs. 9.5%, P = 0.07). Conclusions: Three-vessel radiofrequency iMAP-IVUS demonstrated a greater plaque burden and higher prevalence of any fibroatheroma as well as iMAP-derived TCFAs in culprit versus non-culprit lesions in patients presenting with STEMI or non-STEMI undergoing percutaneous coronary intervention. © 2017 Wiley Periodicals, Inc.
... LCBI 4mm .144) to detect TCNA are lower than the threshold that predicts peri-procedural MI in native coronary arteries (as reported in the Color Registry and Canary trial). 19,20 However, these values are in agreement with our previous report and validate our classification of neoatherosclerosis on OCT. 7 The lower LCBI values are consistent with the concept that neointimal growth in ISR is spatially limited in comparison with positive remodelling in native coronary arteries where plaque burden can grow to a considerable size. Furthermore, delayed re-endothelialization in DES acts as a nidus for lipid deposition and as such the pathophysiological mechanisms for the development of TCNA may be less related to overall plaque burden as it is in native coronary arteries 21 and is likely related to spatial localization of lumen-centric lipid deposition as we have described. ...
Article
Aims Near-infrared spectroscopy (NIRS) has been employed to assess the composition of the atherosclerotic plaques in native coronary arteries. However, little is known about the detection of neoatherosclerosis by NIRS in in-stent restenosis (ISR). The aim of the study was to assess the relationship between the distribution of lipid determined by NIRS and morphology of ISR on optical coherence tomography (OCT). Methods and results We performed both NIRS and OCT in 39 drug-eluting stents with ISR. Values of lipid-core burden index (LCBI) derived by NIRS were compared with the OCT-derived thickness of the fibrous cap covering neoatherosclerotic lesions. A total of 22 (49%) in-stent neointimas were identified as lipid rich by both NIRS and OCT. There was good agreement between OCT and NIRS in identifying lipid within in-stent neointima (kappa = 0.60, 95% CI: 0.34–0.86). OCT identified thin-cap neoatheromas (TCNA) (<65 µm) in 12 stents (23%). The minimal cap thickness of in-stent neoatherosclerotic plaque measured by OCT correlated with the maxLCBI4mm (maximal LCBI per 4 mm) within the stent (r = −0.77, P< 0.01). Moreover, maxLCBI4mm was able to accurately predict TCNA with a cut-off value of >144. Conclusion NIRS correlates with OCT identification of lipids in stented vessels and is able to predict the presence of thin fibrous cap neoatheroma.
... Dixon et al. showed that lipid core plaque extending into and beyond the intended stent margine has implications for stent length selection and optimal lesion coverage [34] . Lipid core burden index calculated by software for 4 mm length of coronary artery (maxLCBI4mm) higher or equal 500 has a direct relation to the risk of periprocedural myocardial infarction during stenting353637. Several important prognostic trials like Prospect and Lipid-rich plaque (LRP) study using detection of lipid core plaque as a marker for subsequent clinical event are ongoing [31,38]. ...
Article
Full-text available
Coronary angiography is still the most widely used method for the assessment of lumen of coronary arteries and for diagnosis and treatment of coronary artery disease. New imaging modalities of coronary arteries play an increasing role in interventional cardiology. Intravascular ultrasound (IVUS) is the oldest technology, however due to its high tissue penetration remains very important for imaging of left main coronary artery and saphenous vein grafts. IVUS was used in many clinical trials and clinical experience with it is huge. Optical coherence tomography (OCT) is a new, very fast developing method. It has ten times higher axial resolution than IVUS. It gives us the opportunity to assess the inner structures of coronary artery wall, to evaluate the characteristics of atherosclerotic plaques, quality of stent implantation and its healing. It helps us to find the culprit lesion of acute coronary syndrome in some cases, to diagnose the cause of stent thrombosis, and to evaluate stent apposition which has a direct relation to prognosis. We use it to perform complex percutaneous coronary interventions and after heart transplantation to diagnose the vascular graft disease. We strongly believe that OCT is important for the assessment of plaque instability and patient´s prognosis. Near infrared spectroscopy combined with IVUS can distinguish fibrous from lipid core plaques. Lipid core burden index is in relation to a risk of periprocedural myocardial infarction and to prognosis. It is the only method which can sufficiently detect the amount of lipids in coronary wall.
... Results from the histology showed that combined IVUS-NIRS analysis poses a high accuracy in detection of fibroatheromas [4]. On the other hand clinical observation suggested that NIRS-IVUS made possible detection of OCT defined TCFA as positively remodeled vessel with LCBI 2mm > 315 [37]. ...
Article
Intravascular ultrasound (IVUS), optical coherence tomography (OCT) and near infrared spectroscopy (NIRS) allows for a thorough analysis of the atheroma's morphology in vivo. Moreover, it helps to guide coronary intervention and assess the results of stenting. IVUS, OCT and NIRS provide unique data about the analyzed tissue and thus all of them complement each other. Their application in daily clinical practice helps to understand the underlying pathology of disease and may contribute to the improvement of outcomes in coronary interventions.
... Most recently, Komukai et al. reported the benefits of atorvastatin on plaque characteristics using OCT [44]. Other studies have indeed demonstrated the power of multimodality imaging in various settings [45][46][47]. YELLOW II is a prospective study ( Figure 2) designed to extend our understanding by assessing whether high dose statin therapy (rosuvastatin 40 mg daily) favourably alters plaque characteristics as well as linking these changes to increased HDL function and alterations in macrophage gene expression and behaviour. The HDL hypothesis essentially states that a reduction of plasma HDL concentration may accelerate the development of atherosclerosis by impairing the clearance of cholesterol from the arterial wall. ...
... This finding is of clinical relevance because the combination of high lipid lesion content and RI is an important predictor of thin-cap fibroatheroma occurrence, 17 which has been suggested to be a vulnerable plaque phenotype. Although the intended role of VH-IVUS was to describe in vivo, vulnerable plaque morphologies, such as necrotic core, concerns have been raised about the accuracy of this method. ...
Article
Full-text available
Aims: Vessel remodelling is commonly observed in coronary atherosclerosis, but factors influencing remodelling, such as plaque lipid content, remain poorly described. Methods and results: Remodelling index (RI) was calculated as the ratio of lesion to proximal and distal references external membrane area and was categorized as follows: positive (PR; RI > 1.05), intermediate (IR; RI 0.95-1.05), and negative remodelling (NR; RI < 0.95). RI was studied by near-infrared spectroscopy (NIRS) as a function of lipid content metrics, including the maximal 4 mm lipid core burden index of the segment (maxLCBI4 mm) and intravascular ultrasound (IVUS) lesion plaque burden (PB). The authors further stratified the analysis according to obstructive (≥50%) and non-obstructive (<50%) lesions using quantitative coronary angiography. Receiver-operating characteristic curves were performed to describe the maxLCBI4 mm level associated with PR. From May 2012 to November 2014, 100 de novo lesions from 67 patients underwent simultaneous NIRS-IVUS. PR was found in 28% of the lesions. There was a positive linear correlation between RI and maxLCBI4 mm (ρ = 0.58; P < 0.001). Although PR lesions had a larger PB than NR or IR (P < 0.001), the correlation of RI with maxLCBI4 mm was stronger compared with plaque volume (ρ = 0.18; P = 0.07) and with per cent PB (ρ = 0.41; P < 0.001). This relationship remained significant for obstructive (ρ = 0.72; P < 0.001) and non-obstructive lesions (ρ = 0.48; P < 0.001). By receiver-operating characteristic curve analysis, values of maxLCBI4 mm ≥ 439 were predictive for PR (area under the curve = 0.79, 95% confidence interval: 0.69-0.89). Conclusion: In vivo coronary lesion remodelling is positively correlated with lipid plaque content assessed by NIRS rather than simply PB. Thus, the use of NIRS can potentially aid in further stratifying vulnerable lesions.
... NIRS provides only compositional information regarding the plaque, but does not require a bloodless field(51) and can help discriminate between calcium and necrotic core, which can often be misinterpreted on OCT(52). A comparison using a hybrid NIRS-IVUS catheter with OCT showed that plaque burden, positive remodeling, and lipid index measured by the hybrid catheter were associated with OCT-TCFA(53).A hybrid NIRS-OCT catheter is in development, and a proof-of-concept demonstration has been published, DIMENSIONAL RECONSTRUCTION. As the technology of OCT becomes more refined and image acquisition faster, it has become possible to perform 3-dimensional reconstructions of the coronary anatomy by fusing x-ray and OCT data (55,56). ...
Article
After 2 decades of development and use in interventional cardiology research, optical coherence tomography (OCT) has now become a core intravascular imaging modality in clinical practice. Its unprecedented spatial resolution allows visualization of the key components of the atherosclerotic plaque that appear to confer "vulnerability" to rupture-namely the thickness of the fibrous cap, size of the necrotic core, and the presence of macrophages. The utility of OCT in the evaluation of plaque composition can provide insights into the pathophysiology of acute coronary syndrome and the healing that occurs thereafter. A brief summary of the principles of OCT technology and a comparison with other intravascular imaging modalities is presented. The review focuses on the current evidence for the use of OCT in identifying vulnerable plaques in acute coronary syndrome and its limitations. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Chapter
Atherosclerosis is a progressive disease that is characterized by the accumulation of lipids, cholesterol, fibrous constituents, monocytes, and various other inflammatory cells in the arterial wall. Atherosclerosis is one of the major causes of morbidity and mortality in developed countries. An integrated intravascular imaging modality that can detect and characterize vulnerable plaques will provide a critically important tool for monitoring the progression of disease and evaluating the efficacy of intervention.
Chapter
Coronary artery disease (CAD) is the leading cause of global mortality. Vulnerable atherosclerotic plaque, which is composed of a large lipid-rich necrotic core (NC) infiltrated with abundant macrophages and a thin fibrous cap, is widely recognized to be the main cause of underlying acute coronary artery disease. Dual-modality imaging technologies are valuable tools that are able to provide both structure and molecular contrast for characterization and quantification of cardiovascular tissue and have shown the improved capability of diagnosis of cardiovascular disease. This chapter outlines several representative dual-modality intravascular imaging systems which combine IVOCT or IVUS with NIRS or NIRF imaging technologies. In addition, the in vivo and ex vivo experimental results obtained by these dual modality imaging systems are presented and discussed.
Article
Advances in our understanding of the natural history and biology of atherosclerotic vascular disease led to the concept of a vulnerable plaque (VP), which is predisposed towards more rapid progression and acute coronary events. With newer technologies, we now have at our disposal high quality imaging studies, both invasive and noninvasive, which show promise in identifying plaque characteristics that make it more vulnerable. Upcoming trials aim to evaluate the utility of imaging VP in predicting clinical events. We discuss the role of VP imaging in managing atherosclerotic vascular disease.
Article
Full-text available
Filter-no reflow (FNR) is a phenomenon wherein flow improves after the retrieve of distal protection. Near-infrared spectroscopy with intravascular ultrasound (NIRS–IVUS) enables lipid detection. We evaluated the predictors of FNR during PCI using NIRS–IVUS. Thirty-two patients who underwent PCI using the Filtrap® for acute coronary syndrome (ACS) were enrolled. The culprit plaque (CP) was observed using NIRS–IVUS. Total lipid-core burden index (T-LCBI) and maximal LCBI over any 4-mm segment (max-LCBI4mm) within CP were evaluated. T-LCBI/max–LCBI4mm ratio within CP was calculated as an index of the extent of longitudinal lipid expansion. The attenuation grade (AG) and remodeling index (RI) in CP were analyzed. AG was scored based on the extent of attenuation occupying the number of quadrants. The patients were divided into FNR group (N = 8) and no-FNR group (N = 24). AG was significantly higher in FNR group than in no-FNR group (1.6 ± 0.6 vs. 0.9 ± 0.42, p = 0.01). RI in FNR group tended to be greater than in no-FNR group. T-LCBI/max–LCBI4mm ratio within the culprit plaque was significantly higher in FNR group than in no-FNR group (0.50 ± 0.10 vs. 0.33 ± 0.13, p < 0.01). In multivariate logistic regression analysis, AG > 1.04 (odds ratio [OR] 18.4, 95% confidence interval [CI] 1.5–215.7, p = 0.02) and T-LCBI/max–LCBI4mm ratio > 0.42 (OR 14.4, 95% CI 1.2–176.8, p = 0.03) were independent predictors for the occurrence of FNR. The use of T-LCBI/max–LCBI4mm ratio within CP might be an effective marker to predict FNR during PCI in patients with ACS.
Chapter
Intravascular ultrasound (IVUS) has evolved as the first clinical imaging modality to directly visualize vessel wall pathology. Because the ultrasound signal is able to penetrate the vessel wall, the entire cross-section can be interrogated in real time; biological processes such as plaque burden, plaque composition, vessel remodeling, and restenosis can be assessed. In addition, IVUS provides optimal guidance for interventional procedures. Along with the progress in interventional technology and increasing complexity of interventional sites in aging populations, IVUS continues to play a vital role in improving outcomes. Current technology in invasive imaging has two main aims: further improvement of spatial and tissue resolution, and physiologic assessment of the target sites. Achievement of these aims helps to optimize the quality and outcomes of catheter-based cardiovascular interventions.
Article
Aims: We aimed to compare intravascular ultrasound with virtual histology (VH-IVUS), optical coherence tomography (OCT) and near-infrared spectroscopy (NIRS) for their ability to quantify the true amount and characterise the nature of released plaque material during bioresorbable vascular scaffold (BVS) implantation into right coronary artery (RCA) lesions using a distal occlusion and aspiration device. Methods and results: Seventeen patients underwent BVS implantation into the right coronary artery under distal protection with intracoronary imaging using VH-IVUS, OCT and NIRS. The amount of released plaque material and its lipid content (LC) were determined. Necrotic core volume and minimal fibrous cap thickness correlated with the amount of released plaque material (r=0.80 and r=-0.65, respectively) and its LC (r=0.75 and r=-0.78, respectively), but not maximal lipid core burden index (LCBI). OCT-identified thin-cap fibroatheromata (TCFA) were associated with the greatest amount of released plaque material compared to non-TCFA (46.8 [29.0;49.2] mg vs. 14.2 [11.3;19.4] mg; p=0.003) and LC (4.4 [4.0;4.8] mg vs. 2.0 [1.8;2.5] mg; p=0.000). Conclusions: VH-IVUS and OCT but not NIRS parameters quantify and characterise the amount of released plaque material. TCFA is associated with the highest amount of released plaque material and may therefore benefit from the use of protection devices.
Article
Full-text available
Understanding of the pathophysiological mechanisms is the cornerstone of preventive and treatment strategies in the battle against coronary artery disease. Hyperlipidemia, arterial hypertension, smoking and diabetes, are established risk factors affecting coronary vasculature. However, the focal formation of atherosclerotic lesions in certain arterial regions underscores that local factors are implicated in the initiation and progression of atherosclerosis. Introduction of novel imaging modalities and technological advances offered new insights and acknowledged intravascular hemodynamics, and particularly flow-derived endothelial shear stress as a critical factor in the natural history of coronary artery disease. In this review we aim to present current evidence on the role of pro-inflammatory endothelial shear stress in all key steps of the atherosclerotic process and its complications, describe the available imaging techniques assessing shear stress values and discuss current limitations as well as future perspectives of implementing intracoronary hemodynamics into clinical practice.
Article
Objectives: The aim of this study was to evaluate sex differences in plaque morphology in stable coronary artery disease (CAD) patients using a multimodality intravascular imaging approach. Background: Differences in atherosclerotic burden and plaque morphology between men and women is a focus of treatment and preventative measures. Methods: We retrospectively analyzed data from 383 patients with stable CAD who were referred for angiography and underwent optical coherence tomography. Among them, 128 also underwent intravascular ultrasound (IVUS)/near infrared spectroscopy. Results: Of the 383 patients included in the study, 268 were men and 115 were women. Women tended to be older (66 ± 10 years of age vs. 62 ± 11 years of age; p = 0.002) and have more comorbidities including hypertension (97% vs. 90%; p = 0.031), diabetes with insulin use (18% vs. 10%; p = 0.043), obesity (body mass index 30 kg/m(2) vs. 28 kg/m(2); p = 0.022), and lower estimated glomerular filtration rate (88 ml/min/1.73m(2) vs. 98 ml/min/1.73m(2); p = 0.001). Optical coherence tomography data demonstrated that there was no sex difference in plaque morphology as characterized by maximum lipid arc, lipid length, lipid volume index, minimum cap thickness, incidence of thin cap fibroatheroma, microvessels, macrophages, and calcification. There was also no difference in maximal lipid core burden index at the 4-mm maximal segment as seen on near infrared spectroscopy. Plaque characteristics by IVUS were similar between men and women except for an increase in plaque burden in men compared to women in the reference segment (44.4 vs. 39.3; p = 0.031). After adjusting for age, body mass index, percutaneous coronary intervention history, and clinical risk factors, sex was not found to be an independent predictor of severe plaque burden by IVUS. Conclusion: Among men and women with stable CAD referred for coronary angiography, there was no difference in plaque characteristics as assessed by multimodality imaging. These findings, which are hypothesis generating, suggest that equally aggressive primary and secondary preventive efforts irrespective of sex must be undertaken.
Article
Objectives: The aim of this study was to identify the predictors of side branch (SB) ostial stenosis developed after provisional stenting of the main vessel (MV) using optical coherence tomography (OCT). Background: Provisional stenting remains the main approach to treatment of bifurcation lesions; however, it may result in the narrowing of SB ostium. There is little information about underlying plaque morphology of the MV lesion and its potential impact on the SB after provisional stenting. Methods: Patients with stable coronary disease with angiographic MV lesion not involving SB were included in a prospective single center study. The primary outcome was significant SB ostium stenosis (SBOS), defined as residual stenosis of >50% after MV stenting. Results: Thirty bifurcation lesions in 30 patients were analyzed in the study. Poststenting significant SBOS was observed in 30% of patients. The MV lesions with SBOS > 50% were characterized by a higher prevalence of lipid rich plaques (100 vs. 64%, p = 0.040) and spotty calcifications (60 vs. 0%, p = 0.005). Maximal lipid arcs were greater (257° vs. 132°, p = 0.001) and lipid volume index was higher (1380 vs. 574, p = 0.012) in the SBOS >50% group. Multivariate logistic regression analysis identified maximal lipid arc (odds ratio (OR): 1.014, p = 0.038) and the presence of lipid plaque contralateral to SB ostium (OR: 8.14, p = 0.046) before stenting as independent predictors of significant SBOS after PCI. Conclusions: High lipid content of the MV lesion and a contralateral location of lipid in the bifurcation area may contribute to SBOS after provisional stenting. © 2016 Wiley Periodicals, Inc.
Article
Advances in atherosclerosis imaging technology and research have provided a range of diagnostic tools to characterize high-risk plaque in vivo; however, these important vascular imaging methods additionally promise great scientific and translational applications beyond this quest. When combined with conventional anatomic-and hemodynamic-based assessments of disease severity, cross-sectional multimodal imaging incorporating molecular probes and other novel noninvasive techniques can add detailed interrogation of plaque composition, activity, and overall disease burden. In the catheterization laboratory, intravascular imaging provides unparalleled access to the world beneath the plaque surface, allowing tissue characterization and measurement of cap thickness with micrometer spatial resolution. Atherosclerosis imaging captures key data that reveal snapshots into underlying biology, which can test our understanding of fundamental research questions and shape our approach toward patient management. Imaging can also be used to quantify response to therapeutic interventions and ultimately help predict cardiovascular risk. Although there are undeniable barriers to clinical translation, many of these hold-ups might soon be surpassed by rapidly evolving innovations to improve image acquisition, coregistration, motion correction, and reduce radiation exposure. This article provides a comprehensive review of current and experimental atherosclerosis imaging methods and their uses in research and potential for translation to the clinic.
Article
Objectives: This study sought to evaluate the diagnostic performance of optical frequency domain imaging (OFDI) for recognition of coronary plaque morphologies and to assess additive values of integrated backscatter intravascular ultrasound (IB-IVUS) in detection of vulnerable plaque. Background: Precise diagnosis of coronary lesions susceptible to plaque rupture and thrombosis may serve to stratify the risk of future coronary events and to make decisions for appropriate treatment of choice. Methods: Twenty-seven coronary arteries from 14 human autopsy hearts were interrogated ex vivo by OFDI and IB-IVUS. Imaged segments were sectioned at 3 mm intervals where a total of 360 pairs of cross-sectional images coregistered to histology were investigated. Results: Overall, OFDI could depict various plaque components and structures such as fibrous tissue, sheet and nodular calcification, lipid, cholesterol crystals, and healed plaque rupture. OFDI could detect 14 of 18 thin-cap fibroatheroma (TCFA), however, the diagnostic accuracy was not high (positive predictive value [PPV] = 60.9%, κ = 0.664; area under the curve [AUC]: 0.88) mainly because of signal interference from macrophages. Further, we defined IB-IVUS-derived TCFA by recursive partitioning analysis as: 1) cross-sectional % lipid area >65.1%; 2) % lipid area >32.3 but <65.1% with plaque area >10.5 mm(2), where TCFA detection by IB-IVUS alone was marginal (PPV = 50.0%, κ = 0.545; AUC: 0.82). However, when IB-IVUS was combined with OFDI, all pseudo OFDI-derived TCFA (non-TCFA on histology) were excluded. Accordingly, PPV of TCFAs diagnosed by both OFDI and IB-IVUS was improved to 100.0% (κ = 0.704; AUC: 0.93). Conclusions: OFDI could recognize detailed morphologies of human coronary plaque. However, diagnostic accuracy of both OFDI alone and IB-IVUS alone to identify TCFA is limited. Combination of IB-IVUS with OFDI improved the accuracy for TCFA detection, suggesting hybrid imaging or further development of novel devices will be required to identify coronary lesions responsible for future events.
Article
The aim of this study is to compare the relative merits of optical coherence tomography (OCT), intravascular ultrasound (IVUS), and near infrared spectroscopy (NIRS) in patients with coronary artery disease for the prediction of periprocedural myocardial infarction (MI). Although several individual intravascular imaging modalities have been employed to predict periprocedural MI, it is unclear which of the imaging tools would best allow prediction of this complication. We retrospectively analyzed 110 patients who underwent OCT, IVUS, and NIRS. Periprocedural MI was defined as a post-procedural cardiac troponin I (cTnI) elevation above 3× the upper limit of normal; analysis was also performed for cTnI ≥5× the upper limit of normal. cTnI ≥3× was observed in 10 patients (9%) and 8 patients had cTnI ≥5×. By OCT, minimum cap thickness was significantly lower (55 vs. 90 μm, p < 0.01), and the plaque burden by IVUS (84 ± 9% vs. 77 ± 8%, p < 0.01) and maximum 4-mm lipid core burden index by NIRS (556 vs. 339, p < 0.01) were greater in the cTnI ≥3× group. Multivariate logistic regression analysis identified cap thickness as the only independent predictor for cTnI ≥3× the upper limit of normal (odds ratio [OR]: 0.90, p = 0.02) or cTnI ≥5× (OR: 0.91, p = 0.04). If OCT findings were excluded from the analysis, plaque burden (OR: 1.13, p = 0.045) and maximum 4-mm lipid core burden index (OR: 1.003, p = 0.037) emerged to be the independent predictors. OCT-based fibrous cap thickness is the most important predictor of periprocedural MI. In the absence of information about cap thickness, NIRS lipid core or IVUS plaque burden best determined the likelihood of the periprocedural event. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Article
Full-text available
To test the hypothesis that near-infrared spectroscopy (NIRS) combined with intravascular ultrasound (IVUS) would provide novel information of human coronary plaque characterization. Greyscale-IVUS, virtual histology (VH)-IVUS, and NIRS were compared in 131 native lesions (66 vessels) that were interrogated during catheterization by all three modalities. Greyscale-IVUS detected attenuated and echolucent plaques correlated with NIRS-detected lipid-rich areas. Attenuated plaques contained the highest NIRS probability of lipid core, followed by echolucent plaques. By VH-IVUS, 93.5% of attenuated plaques contained confluent necrotic core (NC) and were classified as VH-derived fibroatheromas (FAs). Although 75.0% of echolucent plaques were classified as VH-FAs, VH-NC was seen surrounding an echolucent zone, but not within any echolucent zone; and echolucent zones themselves contained fibrofatty and/or fibrous tissue. All calcified plaques with arc >90° contained >10% VH-NC (range 16.0-41.2%) and were classified as calcified VH-FAs, but only 58.5% contained NIRS-detected lipid core. A positive relationship between VH-derived %NC and NIRS-derived lipid core burden index was found in non-calcified plaques, but not in calcified plaques. Combining NIRS with IVUS contributes to the understanding of plaque characterization in vivo. Further studies are warranted to determine whether combining NIRS and IVUS will contribute to the assessment of high-risk plaques to predict outcomes in patients with coronary artery disease.
Article
Full-text available
Atherosclerotic plaques that lead to acute coronary syndromes often occur at sites of angiographically mild coronary-artery stenosis. Lesion-related risk factors for such events are poorly understood. In a prospective study, 697 patients with acute coronary syndromes underwent three-vessel coronary angiography and gray-scale and radiofrequency intravascular ultrasonographic imaging after percutaneous coronary intervention. Subsequent major adverse cardiovascular events (death from cardiac causes, cardiac arrest, myocardial infarction, or rehospitalization due to unstable or progressive angina) were adjudicated to be related to either originally treated (culprit) lesions or untreated (nonculprit) lesions. The median follow-up period was 3.4 years. The 3-year cumulative rate of major adverse cardiovascular events was 20.4%. Events were adjudicated to be related to culprit lesions in 12.9% of patients and to nonculprit lesions in 11.6%. Most nonculprit lesions responsible for follow-up events were angiographically mild at baseline (mean [±SD] diameter stenosis, 32.3±20.6%). However, on multivariate analysis, nonculprit lesions associated with recurrent events were more likely than those not associated with recurrent events to be characterized by a plaque burden of 70% or greater (hazard ratio, 5.03; 95% confidence interval [CI], 2.51 to 10.11; P<0.001) or a minimal luminal area of 4.0 mm(2) or less (hazard ratio, 3.21; 95% CI, 1.61 to 6.42; P=0.001) or to be classified on the basis of radiofrequency intravascular ultrasonography as thin-cap fibroatheromas (hazard ratio, 3.35; 95% CI, 1.77 to 6.36; P<0.001). In patients who presented with an acute coronary syndrome and underwent percutaneous coronary intervention, major adverse cardiovascular events occurring during follow-up were equally attributable to recurrence at the site of culprit lesions and to nonculprit lesions. Although nonculprit lesions that were responsible for unanticipated events were frequently angiographically mild, most were thin-cap fibroatheromas or were characterized by a large plaque burden, a small luminal area, or some combination of these characteristics, as determined by gray-scale and radiofrequency intravascular ultrasonography. (Funded by Abbott Vascular and Volcano; ClinicalTrials.gov number, NCT00180466.).
Article
Full-text available
Aims: To evaluate the feasibility of the combined use of virtual histology (VH)-intravascular ultrasound (IVUS) and optical coherence tomography (OCT) for detecting in vivo thin-cap fibroatheroma (TCFA). Methods and results: In 56 patients with angina, 126 plaques identified by IVUS findings were analysed using both VH-IVUS and OCT. IVUS-derived TCFA was defined as an abundant necrotic core (>10% of the cross-sectional area) in contact with the lumen (NCCL) and %plaque-volume >40%. OCT-derived TCFA was defined as a fibrous cap thickness of <65 microm overlying a low-intensity area with an unclear border. Plaque meeting both TCFA criteria was defined as definite-TCFA. Sixty-one plaques were diagnosed as IVUS-derived TCFA and 36 plaques as OCT-derived TCFA. Twenty-eight plaques were diagnosed as definite-TCFA; the remaining 33 IVUS-derived TCFA had a non-thin-cap and eight OCT-derived TCFA had a non-NCCL (in discord with NCCL visualized by VH-IVUS, mainly due to misreading caused by dense calcium). Based on IVUS findings, definite-TCFA showed a larger plaque and vessel volume, %plaque-volume, higher vessel remodelling index, and greater angle occupied by the NCCL in the lumen circumference than non-thin-cap IVUS-derived TCFA. Conclusion Neither modality alone is sufficient for detecting TCFA. The combined use of OCT and VH-IVUS might be a feasible approach for evaluating TCFA.
Article
Background— A method is needed to identify nonstenotic, lipid-rich coronary plaques that are likely to cause acute coronary events. Near-infrared (NIR) spectroscopy can provide information on the chemical composition of tissue. We tested the hypothesis that NIR spectroscopy can identify plaque composition and features associated with plaque vulnerability in human aortic atherosclerotic plaques obtained at the time of autopsy. Methods and Results— A total of 199 samples from 5 human aortic specimens were analyzed by NIR spectroscopy. Features of plaque vulnerability were defined by histology as presence of lipid pool, thin fibrous cap (<65 μm by ocular micrometry), and inflammatory cell infiltration. An InfraAlyzer 500 spectrophotometer was used. Spectral absorbance values were obtained as log (1/R) data from 1100 to 2200 nm at 10-nm intervals. Principal component regression was used for analysis. An algorithm was constructed with 50% of the samples used as a reference set; blinded predictions of plaque composition were then performed on the remaining samples. NIR spectroscopy sensitivity and specificity for histological features of plaque vulnerability were 90% and 93% for lipid pool, 77% and 93% for thin cap, and 84% and 89% for inflammatory cells, respectively. Conclusions— NIR spectroscopy can identify plaque composition and features associated with plaque vulnerability in postmortem human aortic specimens. These results support efforts to develop an NIR spectroscopy catheter system to detect vulnerable coronary plaques in living patients.
Article
Background — In vivo studies with intravascular ultrasound have shown that complex plaque anatomy and plaque rupture are more frequent in the presence of marked outward remodeling. A large lipid core and a high macrophage count are recognized histological markers for plaque vulnerability. The link between plaque vulnerability in terms of these markers and remodeling in coronary arteries has not been explored. Methods and Results — In 88 male subjects who died suddenly with coronary artery disease, 108 plaques were studied. The percent remodeling was calculated. Lesions with remodeling ≥0% were considered to have positive remodeling, and those in which remodeling was <0% were considered to have negative remodeling. Percent lipid core and macrophage count at the plaque were assessed. Of 108 plaque sites, 64 (59.2%) had undergone no remodeling or positive remodeling, and 44 (40.7%) had negative remodeling (vessel shrinkage). Lesions with positive remodeling, compared with lesions with vessel shrinkage, had a larger lipid core (percent mean lipid core was 39.0±21.0% versus 22.3±23.1%, respectively; P <0.0001) and a higher macrophage count (mean macrophage count was 15.6±12.3 versus 8.9±11.6, respectively; P =0.005). Conclusions — We have shown that coronary artery plaques with positive remodeling have a higher lipid content and macrophage count, both markers of plaque vulnerability. These results may explain why plaque rupture is often apparent at sites with only modest luminal stenoses (but marked positive remodeling).
Article
Objectives: To define the incidence of stent thrombosis (ST) and/or AMI (ST/AMI) associated with temporary or permanent suspension of dual antiplatelet therapy (DAPT) after coronary drug-eluting stent (DES) implantation in “real-world” patients, and additional factors influencing these events. Background: Adherence to DAPT is critical for avoiding ST following DES implantation. However, the outcomes of patients undergoing antiplatelet therapy withdrawal following DES implantation remain to be clearly described. Methods: Patients receiving DES from 05/01/2003 to 05/01/2008 were identified from a single-center registry. Complete follow-up data were available for 5,681 patients (67% male, age 66 ± 11 years, duration 1,108 ±446 days) who were included in this analysis. Results: Uninterrupted DAPT was maintained in 4,070/5,681 (71.6%) patients, with an annual ST/AMI rate of 0.43%. Antiplatelet therapy was commonly ceased for gastrointestinal-related issues, dental procedures or noncardiac/nongastrointestinal surgery. Temporary DAPT suspension occurred in 593/5,681 (10.4%) patients for 17.6 ± 74.1 days, with 6/593 (1.0%) experiencing ST/AMI during this period. Of patients permanently ceasing aspirin (n = 187, mean 338 ± 411 days poststenting), clopidogrel (n = 713, mean 614 ± 375 days) or both agents (n = 118, mean 459 ± 408 days), ST/AMI was uncommon with an annual rate of 0.1–0.2%. Overall, independent predictors of ST/AMI were unstable initial presentation, uninterrupted DAPT and lower left ventricular ejection fraction. Factors predicting uninterrupted DAPT included diabetes, unstable presentation, prior MI, left main coronary PCI, and multivessel coronary disease. Conclusions: In real-world practice, rates of ST/AMI following DES implantation are low, but not insignificant, following aspirin and/or clopidogrel cessation. Use of uninterrupted DAPT appears more common in high-risk patients. (J Interven Cardiol 2012;25:482–492)
Article
Previous angiographic studies have suggested that the future risk for major adverse cardiovascular events (MACEs) is related to coronary stenosis severity. The aim of this study was to use the grayscale and virtual histology (VH)-intravascular ultrasound (IVUS) data from the Providing Regional Observations to Study Predictors of Events in the Coronary Tree (PROSPECT) study to identify underlying lesion morphologic characteristics that might explain these findings. In PROSPECT, patients presenting with acute coronary syndromes in whom percutaneous coronary intervention was successful underwent 3-vessel grayscale and VH-IVUS and were followed for a median of 3.4 years for the incidence of MACEs. Overall, 3,115 nonculprit lesions detected by IVUS were divided into quartiles according to baseline angiographic diameter stenosis. From the first to fourth quartiles, there were increases in the prevalence of lesions with IVUS minimum luminal areas ≤ 4 mm(2), IVUS plaque burden ≥ 70%, and VH-IVUS thin-cap fibroatheroma (13.4%, 22.0%, 24.2%, and 30.3%, respectively, p <0.001), along with an increased frequency of plaque ruptures and greater necrotic core volumes. The incidence of lesions with plaque burden ≥ 70%, minimum luminal area ≤ 4 mm(2), and VH thin-cap fibroatheroma was highest in the fourth quartile (0%, 0.4%, 0.4%, and 2.8% in the first through fourth quartiles, respectively, p <0.001). Three-year MACE rates were also highest in the fourth quartile (0.3%, 0.7%, 1.3%, and 5.1%, respectively, p <0.001). In conclusion, increasing angiographic diameter stenosis was associated with an increased frequency of grayscale and VH-IVUS lesion morphologic features that have been associated with adverse events and that may, in part, explain why future MACEs were related to baseline lesion severity.
Article
Conflicting data have been reported about the association between plaque composition and remodelling index (RI). The aim of this study is to evaluate the relationship between plaque morphology obtained by optical coherence tomography (OCT) and arterial remodelling. OCT and intravascular ultrasound imaging pull back was performed at corresponding sites on 94 lesions in 47 patients. OCT plaque characteristics for lipid content, fibrous cap thickness, thin-cap fibroatheroma (TCFA), plaque rupture, thrombus, calcification and erosion were derived using validated criteria. Compared with intermediate/negative remodelling (RI<1.0), positive remodelling (RI>1.0) was associated with presence of higher lipid pool (2.86 ± 0.42 vs. 2.20 ± 0.78; p<0.001), thin fibrous cap (47.86 ± 25.43 μm vs. 74.41 ± 32.41 μm; p<0.001), TCFA>3mm (82.1% vs. 22.7%; p<0.0001), plaque rupture and thrombus (42.8% vs. 19.7%; p = 0.024), and higher plaque burden (73.70 vs. 70.70; p = 0.048). No difference was observed in the presence of calcification and plaque erosions. Coronary lesions with positive remodelling show higher incidences of vulnerable plaque and plaque rupture across the lesion length. This potentially explains the correlation between unstable coronary syndromes and positive remodelling.
Article
The purpose of this study was to evaluate the effect of statin treatment on coronary plaque composition and morphology by optical coherence tomography (OCT), grayscale and integrated backscatter (IB) intravascular ultrasound (IVUS) imaging. Although previous studies have demonstrated that statins substantially improve cardiac mortality, their precise effect on the lipid content and fibrous cap thickness of atherosclerotic coronary lesions is less clear. While IVUS lacks the spatial resolution to accurately assess fibrous cap thickness, OCT lacks the penetration of IVUS. We used a combination of OCT, grayscale and IB-IVUS to comprehensively assess the impact of pitavastatin on plaque characteristics. Prospective serial OCT, grayscale and IB-IVUS of nontarget lesions was performed in 42 stable angina patients undergoing elective coronary intervention. Of these, 26 received 4 mg pitavastatin after the baseline study; 16 subjects who refused statin treatment were followed with dietary modification alone. Follow-up imaging was performed after a median interval of 9 months. Grayscale IVUS revealed that in the statin-treated patients, percent plaque volume index was significantly reduced over time (48.5 ± 10.4%, 42.0 ± 11.1%; p = 0.033), whereas no change was observed in the diet-only patients (48.7 ± 10.4%, 50.4 ± 11.8%; p = NS). IB-IVUS identified significant reductions in the percentage lipid volume index over time (34.9 ± 12.2%, 28.2 ± 7.5%; p = 0.020); no change was observed in the diet-treated group (31.0 ± 10.7%, 33.8 ± 12.4%; p = NS). While OCT demonstrated a significant increase in fibrous cap thickness (140 ± 42 μm, 189 ± 46 μm; p = 0.001), such changes were not observed in the diet-only group (140 ± 35 μm, 142 ± 36 μm; p = NS). Differences in the changes in the percentage lipid volume index (-6.8 ± 8.0% vs. 2.8 ± 9.9%, p = 0.031) and fibrous cap thickness (52 ± 32 μm vs. 2 ± 22 μm, p < 0.001) over time between the pitavastatin and diet groups were highly significant. Statin treatment induces favorable plaque morphologic changes with an increase in fibrous cap thickness, and decreases in both percentage plaque and lipid volume indexes.
Article
The goal of this study was to evaluate the feasibility of imaging the aorta of apolipoprotein E-deficient (ApoE(-/-)) mice for the detection of atherosclerosis and macrophages using optical coherence tomography (OCT) compared with histology. Atherosclerosis was induced by high-fat diet in 7-week-old ApoE(-/-) mice for 10 (n=7) and 22 (n=7) weeks. Nine-week-old ApoE(-/-) mice (n=7) fed a standard chow diet were used as controls. OCT images of a 10-mm descending aorta in situ were performed in 4 mice for each, and plaque and macrophages were determined at 0.5-mm intervals. Automated detection and quantification of macrophages were performed independently using a customized algorithm. Coregistered histological cross-sections were stained with hematoxylin-eosin, Mac-3, and von Kossa. Three mice in each group had en face OCT imaging to detect macrophages, which were compared with lipid-positive area with Sudan IV. OCT images were successfully acquired in all mice. OCT and histology were able to discriminate macrophages and plaque among the 3 groups and showed excellent correlation for (1) visual detection of plaque (r=0.98) and macrophages (r=0.93), (2) automated detection and quantification of macrophages by OCT versus Mac-3-positive area (r=0.92), and (3) en face OCT detection of macrophages versus Sudan IV-positive area (r=0.92). Murine intra-aortic OCT is feasible and shows excellent correlation with histology for detection of atherosclerotic plaque and macrophages.
Article
Whereas acute coronary syndromes (ACS) typically develop from the rupture of lipid core plaque (LCP), lesions causing stable angina are believed to be composed of fibrocalcific plaque. In this study, intracoronary near-infrared spectroscopy (NIRS) was used to determine the frequency of LCP at target and remote sites in patients with ACS versus those with stable angina. The study was performed in patients having ≥1 target lesion identified by invasive angiography who also underwent NIRS before intervention. LCP was defined as a 2-mm segment on the NIRS block chemogram having a strong positive reading indicated by a bright-yellow color. Patients with ACS and those with stable angina were compared for the frequency of LCP at target and remote sites. Among 60 patients (46.7% with ACS) undergoing invasive angiography and NIRS, 68 target lesions were identified. Although target lesions in patients with ACS were more frequently composed of LCP than targets in patients with stable angina (84.4% versus 52.8%, P=0.004), approximately one half of target lesions in patients with stable angina contained LCP. LCPs anatomically remote from the target lesion were frequent in patients with ACS and less common in patients with stable angina (73.3% versus 17.6%, P=0.002). Target lesions responsible for ACS were frequently composed of LCP; in addition, LCPs often were found in remote, nontarget areas. Both target and remote LCPs were more common in patients with ACS than in those with stable angina. Approximately one half of target lesions in stable patients were also composed of LCP.
Article
Objectives: To investigate if previously reported gender-based outcome disparities following percutaneous coronary intervention (PCI) are applicable in a large and racially-diverse cohort in the drug eluting stent (DES) era. Background: It is generally believed that women suffer inferior outcomes compared to men after PCI. However, various strategies have evolved that may have mitigated this imbalance, including improved medical therapy, attention to risk-factors, and procedural advances of PCI including DES. Methods: We identified 13,752 patients (4,761 female, 34.6%) with complete follow-up data who underwent de novo lesion PCI from 04/2003 to 04/2009. Relevant data were extracted from an IRB-approved registry. Results: Compared to males, females were significantly older (69.0 vs. 64.8 years) and more frequently from a minority or non-Caucasian background. Females smoked less, but more were hypertensive and/or diabetic. Women had higher HDL, but also higher LDL cholesterol levels. More women presented with an unstable coronary syndrome and required left anterior descending artery PCI. While unadjusted post-PCI mortality rates were higher in females versus males (30 days, 1.3 vs. 0.8%, P = 0.009; 1 year, 6.1 vs. 4.8%, P = 0.001; 3 year, 10.4 vs. 8.4%, P < 0.0001), multivariable regression analyses failed to identify female gender as an independent predictor of mortality. Propensity-adjusted modeling confirmed that females were not at intrinsically higher risk for mortality after PCI. Conclusions: Females undergoing PCI exhibit more comorbidities and adverse prognostic factors than males. However, risk-adjusted analyses identified that gender is not an independent predictor of mortality after PCI in the DES era. © 2011 Wiley Periodicals, Inc.
Article
ONE OF THE GOALS OF INTRAVASCULAR IMAGING IS SPECIFIC IN VIVO IDENTIFICATION OF VULNERABLE PLAQUES, which are likely to cause acute coronary syndrome. Intravascular optical coherence tomography (OCT) is a recent technique that is used for coronary plaque characterization, and is rapidly gaining
Article
The purpose of this study was to assess plaque characteristics of optical coherence tomography (OCT)-derived thin-cap fibroatheroma (TCFA) by integrated backscatter intravascular ultrasound (IB-IVUS). Radiofrequency signal-derived IVUS tissue characterization technology has become clinically available and provided objective and quantitative plaque characteristics of the coronary vessel wall. Integrated backscatter IVUS is one of the tissue characterization methods that can possibly provide quantitative plaque characteristics of the OCT-derived TCFA. Eighty-one coronary lesions with plaque burden >40% were selected and analyzed with both IB-IVUS and OCT. The OCT-derived TCFA was defined as a presence of thin fibrous cap (<65 μm) overlying a signal-poor lesion with diffuse border representing a lipid-rich plaque. By conventional gray-scale IVUS, external elastic membrane (EEM) cross-sectional area (CSA), lumen CSA, plaque plus media (P+M) CSA, plaque burden and remodeling index were measured. By IB-IVUS, plaque characteristics were further classified as fibrosis, dense fibrosis, calcification, or lipid pool. Optical coherence tomography identified 40 TCFAs (49%) and 41 non-TCFAs. The EEM CSA, P+M CSA, plaque burden, and remodeling index were significantly larger in OCT-derived TCFA than non-TCFA. By IB-IVUS, percentage lipid pool area (= lipid pool area/P+M CSA × 100) was significantly higher (62.4 ± 12.8% vs. 38.4 ± 13.1%, p<0.0001) and percentage fibrosis area (= fibrosis area/P+M CSA × 100) was significantly lower (34.6 ± 11.4% vs. 50.5 ± 8.7%, p<0.0001) in OCT-derived TCFA than non-TCFA. By receiver-operator characteristic curve analysis, percentage lipid pool area ≥55%, percentage fibrosis area ≤41%, and remodeling index ≥1.0 were predictors of OCT-derived TCFA. The OCT-derived TCFA had larger plaque burden and positive remodeling with predominant lipid component and less fibrous plaque assessed by IB-IVUS.
Article
The aim of this study was to investigate the possibility of 64-slice multislice computed tomography (MSCT) to detect vulnerable plaque derived by optical coherence tomography. From September 2007 through December 2009, 122 lesions in 81 patients were evaluated by 64-slice MSCT and optical coherence tomography. Based on optical coherence tomographic findings, lesions were classified as thin-capped fibroatheroma (TCFA; n=37) and non-TCFA (n=85). Mean computed tomographic density value of the lesion was lower and remodeling index was larger in the TCFA group (44.9 ± 19.2 vs 78.7 ± 25.0 HU, p <0.0001; 1.14 ± 0.20 vs 0.95 ± 0.16, p<0.0001, respectively). Mean computed tomographic density value was correlated and remodeling index was inversely correlated with fibrous cap thickness (r=0.605, p<0.0001; r=-0.591, p<0.0001, respectively). Optimal threshold of mean computed tomographic value and remodeling index identified by receiver operating characteristic curve were 62.4 HU and 1.08 (area under the curve 0.859 and 0.781). Signet ringlike appearance was observed more frequently in the TCFA group (65% vs 16%, p<0.0001). In multivariate analysis, independent predictors of TCFA were mean computed tomographic density value ≤62.4 HU (odds ratio 8.20, 95% confidential interval 2.49 to 27.0, p=0.0005), remodeling index ≥1.08 (odds ratio 6.10, 95% confidential interval 2.04 to 18.2, p=0.0012), and signet ringlike appearance (odds ratio 6.33, 95% confidential interval 2.03 to 19.7, p=0.0014). In conclusion, based on comparisons with optical coherence tomographic findings, 64-slice MSCT may have the potential to detect vulnerable plaque.
Article
To determine whether catheter-based near-infrared spectroscopy (NIRS) signals obtained with a novel catheter-based system from coronaries of patients are similar to those from autopsy specimens and to assess initial safety of NIRS device. An intravascular NIRS system for detection of lipid core-containing plaques (LCP) has been validated in human coronary autopsy specimens. The SPECTACL (SPECTroscopic Assessment of Coronary Lipid) trial was a parallel first-in-human multicenter study designed to demonstrate the applicability of the LCP detection algorithm in living patients. Intracoronary NIRS was performed in patients undergoing percutaneous coronary intervention. Acquired spectra were blindly compared with autopsy NIRS signals with multivariate statistics. To meet the end point of spectral similarity, at least two-thirds of the scans were required to have >80% of spectra similar to the autopsy spectra. A total of 106 patients were enrolled; there were no serious adverse events attributed to NIRS. Spectroscopic data could not be obtained in 17 (16%) patients due to technical limitations, leaving 89 patients for analysis. Spectra from 30 patients were unblinded to test the calibration of the LCP detection algorithm. Of the remaining 59 blinded cases, after excluding 11 due to inadequate data, spectral similarity was demonstrated in 40 of 48 spectrally adequate scans (83% success rate, 95% confidence interval: 70% to 93%, median spectral similarity/pullback: 96%, interquartile range 10%). The LCP was detected in 58% of 60 spectrally similar scans from both cohorts. This intravascular NIRS system safely obtained spectral data in patients that were similar to those from autopsy specimens. These results demonstrate the feasibility of invasive detection of coronary LCP with this novel system. (SPECTACL: SPECTroscopic Assessment of Coronary Lipid; NCT00330928).
Article
In a computed tomographic (CT) angiography study, we identified the characteristics of atherosclerotic lesions that were associated with subsequent development of acute coronary syndrome (ACS). The CT characteristics of culprit lesions in ACS include positive vessel remodeling (PR) and low-attenuation plaques (LAP). These 2 features have been observed in the lesions that have already resulted in ACS, but their prospective relation to ACS has not been previously described. In 1,059 patients who underwent CT angiography, atherosclerotic lesions were analyzed for the presence of 2 features: PR and LAP. The remodeling index, and plaque and LAP areas and volumes were calculated. The plaque characteristics of lesions resulting in ACS during the follow-up of 27 +/- 10 months were evaluated. Of the 45 patients showing plaques with both PR and LAP (2-feature positive plaques), ACS developed in 10 (22.2%), compared with 1 (3.7%) of the 27 patients with plaques displaying either feature (1-feature positive plaques). In only 4 (0.5%) of the 820 patients with neither PR nor LAP (2-feature negative plaques) did ACS develop. None of the 167 patients with normal angiograms had acute coronary events (p < 0.001). ACS was independently predicted by PR and/or LAP (hazard ratio: 22.8, 95% confidence interval: 6.9 to 75.2, p < 0.001). Among 2- or 1-feature positive segments, those resulting in ACS demonstrated significantly larger remodeling index (126.7 +/- 3.9% vs. 113.4 +/- 1.6%, p = 0.003), plaque volume (134.9 +/- 14.1 mm(3) vs. 57.8 +/- 5.7 mm(3), p < 0.001), LAP volume (20.4 +/- 3.4 mm(3) vs. 1.1 +/- 1.4 mm(3), p < 0.001), and percent LAP/total plaque area (21.4 +/- 3.7 mm(2) vs. 7.7 +/- 1.5 mm(2), p = 0.001) compared with segments not resulting in ACS. The patients demonstrating positively remodeled coronary segments with low-attenuation plaques on CT angiography were at a higher risk of ACS developing over time when compared with patients having lesions without these characteristics.
Article
The purpose of this study was to assess the relationship between plaque color evaluated by coronary angioscopy and fibrous cap thickness estimated by optical coherence tomography (OCT) in vivo. Yellow color intensity of coronary plaque evaluated by coronary angioscopy might be associated with plaque vulnerability. Seventy-seven coronary artery plaques in patients with acute coronary syndrome were observed by angioscopy and OCT. Plaque color was graded as white, light yellow, yellow, or intensive yellow. There were significant differences among the groups classified by plaque color with respect to the fibrous cap thickness estimated by OCT: 389 +/- 74 mum in white plaques, 228 +/- 51 microm in light yellow plaques, 115 +/- 28 microm in yellow plaques, and 59 +/- 14 microm in intensive yellow plaques (p < 0.0001). In Spearman rank-order correlation analysis, there was a significant negative correlation between yellow color intensity and fibrous cap thickness (p < 0.0001). Furthermore, 80% of intensive yellow plaques were thin cap fibroatheroma with a cap thickness of < or =65 microm. The plaque color in coronary angioscopy was determined by the fibrous cap thickness, which was assessed by OCT. Although coronary angioscopy remains a specialized research tool, it might allow us to evaluate plaque vulnerability.
Article
Objectives: This study sought to assess agreement between an intravascular near-infrared spectroscopy (NIRS) system and histology in coronary autopsy specimens. Background: Lipid core plaques cannot be detected by conventional tests, yet are suspected to be the cause of most acute coronary syndromes. Near-infrared spectroscopy is widely used to determine the chemical content of substances. A NIRS system has been developed and used successfully in 99 patients. Methods: Scanning NIRS was performed through blood in 212 coronary segments from 84 autopsy hearts. One histologic section was analyzed for every 2 mm of artery. Lipid core plaque of interest (LCP) was defined as a lipid core >60 degrees in circumferential extent, >200-microm thick, with a mean fibrous cap thickness <450 microm. The first 33 hearts were used to develop the algorithm; the subsequent 51 validation hearts were used in a prospective, double-blind manner to evaluate the accuracy of NIRS in detecting LCP. A NIRS-derived lipid core burden index for an entire artery was also validated by comparison to histologic findings. Results: The LCPs were present in 115 of 2,649 (4.3%) sections from the 51 validation hearts. The algorithm prospectively identified LCP with a receiver-operator characteristic area of 0.80 (95% confidence interval [CI]: 0.76 to 0.85). The lipid core burden index detected the presence or absence of any fibroatheroma with an area under the curve of 0.86 (95% CI: 0.81 to 0.91). A retrospective analysis of lipid core burden index conducted in extreme artery segments with either no or extensive fibroatheroma yielded an area under the curve of 0.96 (95% CI: 0.92 to 1.00), confirming the accuracy of spectroscopy in identifying plaques with markedly different lipid content under ideal circumstances. Conclusions: This novel catheter-based NIRS system accurately identified lipid core plaques through blood in a prospective study in coronary autopsy specimens. It is expected that this novel capability will be of assistance in the management of patients with coronary artery disease.
Article
OCT achieves high-resolution and image differentiation of vascular tissues to a degree that has not been previously possible with any method except excisional biopsy. Thus, OCT represents a promising new diagnostic technology for intracoronary imaging, which could permit the in vivo evaluation of critical vascular pathology.
Article
Cigarette smoking and abnormal serum cholesterol concentrations are risk factors for acute coronary syndromes, but the underlying mechanisms are poorly understood. We studied whether cigarette smoking and abnormal cholesterol values may precipitate acute coronary thrombosis and sudden death resulting from either rupture of vulnerable coronary plaques or erosion of plaques. We examined the hearts of 113 men with coronary disease who had died suddenly and also analyzed their coronary risk factors. We found an acute coronary thrombus in each of 59 men, and severe narrowing of the coronary artery by an atherosclerotic plaque without acute thrombosis (stable plaque) in 54. Cases of acute thrombosis were divided into two groups: 41 resulting from rupture of a vulnerable plaque (a thin fibrous cap overlying a lipid-rich core), and 18 resulting from the erosion of a fibrous plaque rich in smooth-muscle cells and proteoglycans. Vulnerable plaques that had not ruptured were counted in each heart. Cigarette smoking was a risk factor in 44 (75 percent) of the men with acute thrombosis, as compared with 22 (41 percent) of the men with stable plaques (P<0.001). The mean (+/-SD) ratio of serum total cholesterol to high-density lipoprotein (HDL) cholesterol was markedly elevated in the men who died of acute thrombosis with plaque rupture (mean, 8.5+/-4.0) but only mildly elevated in the men without acute thrombosis (5.5+/-2.4; P<0.001) and in the men with thrombi overlying eroded plaques (5.0+/-1.8; P<0.001). Multivariate analysis showed an association between an elevated ratio of serum total cholesterol to HDL cholesterol and the presence of vulnerable plaques (P<0.001). Among men with coronary disease who die suddenly, abnormal serum cholesterol concentrations - particularly elevated ratios of total cholesterol to HDL cholesterol - predispose patients to rupture of vulnerable plaques, whereas cigarette smoking predisposes patients to acute thrombosis.
Article
To relate local arterial geometry with markers that are thought to be related to plaque rupture. Plaque rupture often occurs at sites with minor luminal stenosis and has retrospectively been characterized by colocalization of inflammatory cells. Recent studies have demonstrated that luminal narrowing is related with the mode of atherosclerotic arterial remodeling. We obtained 1,521 cross section slices at regular intervals from 50 atherosclerotic femoral arteries. Per artery, the slices with the largest and smallest lumen area, vessel area and plaque area were selected for staining on the presence of macrophages (CD68), T-lymphocytes (CD45RO), smooth muscle cells (alpha-actin) and collagen. Inflammation of the cap or shoulder of the plaque was observed in 33% of all cross sections. Significantly more CD68 and CD45RO positive cells, more atheroma, less collagen and less alpha-actin positive staining was observed in cross sections with the largest plaque area and largest vessel area vs. cross sections with the smallest plaque area and smallest vessel area, respectively. No difference in the number of inflammatory cells was observed between cross sections with the largest and smallest lumen area. Intraindividually, pathohistologic markers previously reported to be related to plaque vulnerability were associated with a larger plaque area and vessel area. In addition, inflammation of the cap and shoulder of the plaque was a common finding in the atherosclerotic femoral artery.
Article
To determine the morphologic features of coronary plaques associated with acute coronary syndrome, we prospectively followed patients with atherosclerotic disease identified by intravascular ultrasound (IVUS). Although clinical evaluation of the vulnerable atherosclerotic plaque is important, few data exist regarding the morphology of the vulnerable plaque in clinical settings. We examined 114 coronary sites without significant stenosis by angiography (<50% diameter stenosis) in 106 patients. All the sites exhibited atherosclerotic lesions by IVUS. These lesions consisted of 22 concentric and 92 eccentric plaques with a percent plaque area averaging 59 +/- 12%. During the follow-up period of 21.8 +/- 6.4 months (range 1 to 24), 12 patients had an acute coronary event at a previously examined coronary site at an average of 4.0 +/- 3.4 months after the initial IVUS study. All the preexisting plaques related to the acute events exhibited an eccentric pattern and the mean percent plaque area was 67 +/- 9%, which was greater than plaque area in the other 90 patients without acute events (57 +/- 12%, p < 0.05). There was no statistically significant difference in lumen area between two patient groups (6.7 +/- 3.0 vs. 7.5 +/- 3.7 mm2). Among 12 coronary sites with an acute occlusion, 10 sites contained the echolucent zones, eight of these shallow and two deep, likely representing a lipid-rich core. In 90 sites without acute events, an echolucent zone in the shallow portion was seen at only four sites (p < 0.05). Large eccentric plaque containing an echolucent zone by IVUS can be at increased risk for instability even though the lumen area is preserved at the time of initial study. Compensatory enlargement of vessel wall due to remodeling may contribute to the relatively small degree of stenosis by angiography.
Article
We studied 108 cases of sudden coronary death at autopsy. Any calcification was present in 55% of men and women under 40 years; all hearts showed some calcification by age 50 in men, and by age 60 in women. The only risk factor independently associated with increased calcification was diabetes mellitus, in women only. The degree of calcification was greatest for acute and healed plaque ruptures, and the least for plaque erosion. Calcification in coronary atherosclerosis appears to be delayed in women, is greatest in women diabetics, and is associated with one type of plaque instability, namely plaque rupture.
Article
We examined the association between the features of the culprit lesion in coronary artery disease (CAD) and clinical presentation as shown by intravascular ultrasound (IVUS). The association between coronary remodeling pattern and clinical presentation of CAD is unclear. We analyzed 125 selected patients who underwent preintervention IVUS. Acute myocardial infarction (AMI) and unstable angina pectoris (UAP) were categorized as an acute coronary syndrome (ACS), and stable angina pectoris (SAP) and old myocardial infarction (OMI) as stable CAD. Coronary remodeling patterns and plaque morphology of the culprit lesion obtained by IVUS were analyzed in terms of their association with clinical presentation or angiographic morphology. Angiographically complex lesions were associated with ACS and OMI. In patients with a complex lesion, positive remodeling was observed more frequently than in those with a simple lesion. In AMI and UAP, positive remodeling was observed more frequently than in SAP and OMI (82% vs. 78% vs. 33% vs. 40%, respectively, p < 0.0001). The remodeling ratio was greater in AMI and UAP than in SAP and OMI (1.26 +/- 0.15 vs. 1.11 +/- 0.10 vs. 0.94 +/- 0.11 vs. 0.96 +/- 0.13, respectively, p < 0.0001). Furthermore, within ACS, the remodeling ratio was greater in AMI than in UAP (1.26 +/- 0.15 vs. 1.11 +/- 0.10, respectively, p < 0.05), whereas the frequency of positive remodeling was not different. Positive remodeling was more frequently observed in ACS than in stable CAD. Moreover, the degree of positive remodeling was greater in AMI than in UAP. These results may reflect the impact of remodeling types and its degree in the culprit lesion of CAD on clinical presentation.
Article
The aim of this study was to evaluate the feasibility and the ability of intravascular optical coherence tomography (OCT) to visualize the components of coronary plaques in living patients. Disruption of a vulnerable coronary plaque with subsequent thrombosis is currently recognized as the primary mechanism for acute myocardial infarction. Although such plaques are considered to have a thin fibrous cap overlying a lipid pool, imaging modalities in current clinical practice do not have sufficient resolution to identify thin (< 65 microm) fibrous caps. Optical coherence tomography is a new imaging modality capable of obtaining cross-sectional images of coronary vessels at a resolution of approximately 10 microm. The OCT images and corresponding histology of 42 coronary plaques were compared to establish OCT criteria for different types of plaques. Atherosclerotic lesions with mild to moderate stenosis were identified on angiograms in 10 patients undergoing cardiac catheterization. Optical coherence tomography and intravascular ultrasound (IVUS) images of these sites were obtained in all patients without complication. Comparison between OCT and histology demonstrated that lipid-rich plaques and fibrous plaques have distinct OCT characteristics. A total of 17 IVUS and OCT image pairs obtained from patients were compared. Axial resolution measured 13 +/- 3 microm with OCT and 98 +/- 19 microm with IVUS. All fibrous plaques, macrocalcifications and echolucent regions identified by IVUS were visualized in corresponding OCT images. Intimal hyperplasia and echolucent regions, which may correspond to lipid pools, were identified more frequently by OCT than by IVUS. Intracoronary OCT appears to be feasible and safe. Optical coherence tomography identified most architectural features detected by IVUS and may provide additional detailed structural information.
Article
High-resolution visualization of atherosclerotic plaque morphology may be essential for identifying coronary plaques that cause acute coronary events. Optical coherence tomography (OCT) is an intravascular imaging modality capable of providing cross-sectional images of tissue with a resolution of 10 micro m. To date, OCT imaging has not been investigated in sufficient detail to assess its accuracy for characterizing atherosclerotic plaques. The aim of this study was to establish objective OCT image criteria for atherosclerotic plaque characterization in vitro. OCT images of 357 (diseased) atherosclerotic arterial segments obtained at autopsy were correlated with histology. OCT image criteria for 3 types of plaque were formulated by analysis of a subset (n=50) of arterial segments. OCT images of fibrous plaques were characterized by homogeneous, signal-rich regions; fibrocalcific plaques by well-delineated, signal-poor regions with sharp borders; and lipid-rich plaques by signal-poor regions with diffuse borders. Independent validation of these criteria by 2 OCT readers for the remaining segments (n=307) demonstrated a sensitivity and specificity ranging from 71% to 79% and 97% to 98% for fibrous plaques, 95% to 96% and 97% for fibrocalcific plaques, and 90% to 94% and 90% to 92% for lipid-rich plaques, respectively (overall agreement, kappa=0.83 to 0.84). The interobserver and intraobserver reliabilities of OCT assessment were high (kappa values of 0.88 and 0.91, respectively). Objective OCT criteria are highly sensitive and specific for characterizing different types of atherosclerotic plaques. These results represent an important step in validating this new intravascular imaging modality and will provide a basis for the interpretation of intracoronary OCT images obtained from patients.
Article
Atherosclerotic plaque stability is related to histological composition. However, current diagnostic tools do not allow adequate in vivo identification and characterization of plaques. Spectral analysis of backscattered intravascular ultrasound (IVUS) data has potential for real-time in vivo plaque classification. Eighty-eight plaques from 51 left anterior descending coronary arteries were imaged ex vivo at physiological pressure with the use of 30-MHz IVUS transducers. After IVUS imaging, the arteries were pressure-fixed and corresponding histology was collected in matched images. Regions of interest, selected from histology, were 101 fibrous, 56 fibrolipidic, 50 calcified, and 70 calcified-necrotic regions. Classification schemes for model building were computed for autoregressive and classic Fourier spectra by using 75% of the data. The remaining data were used for validation. Autoregressive classification schemes performed better than those from classic Fourier spectra with accuracies of 90.4% for fibrous, 92.8% for fibrolipidic, 90.9% for calcified, and 89.5% for calcified-necrotic regions in the training data set and 79.7%, 81.2%, 92.8%, and 85.5% in the test data, respectively. Tissue maps were reconstructed with the use of accurate predictions of plaque composition from the autoregressive classification scheme. Coronary plaque composition can be predicted through the use of IVUS radiofrequency data analysis. Autoregressive classification schemes performed better than classic Fourier methods. These techniques allow real-time analysis of IVUS data, enabling in vivo plaque characterization.
Article
The current understanding of the pathophysiology of coronary artery disease is based largely on postmortem studies. Optical coherence tomography (OCT) is a high-resolution ( approximately 10 microm), catheter-based imaging modality capable of investigating detailed coronary plaque morphology in vivo. Patients undergoing cardiac catheterization were enrolled and categorized according to their clinical presentation: recent acute myocardial infarction (AMI), acute coronary syndromes (ACS) constituting non-ST-segment elevation AMI and unstable angina, or stable angina pectoris (SAP). OCT imaging was performed with a 3.2F catheter. Two observers independently analyzed the images using the previously validated criteria for plaque characterization. Of 69 patients enrolled, 57 patients (20 with AMI, 20 with ACS, and 17 with SAP) had analyzable images. In the AMI, ACS, and SAP groups, lipid-rich plaque (defined by lipid occupying > or =2 quadrants of the cross-sectional area) was observed in 90%, 75%, and 59%, respectively (P=0.09). The median value of the minimum thickness of the fibrous cap was 47.0, 53.8, and 102.6 microm, respectively (P=0.034). The frequency of thin-cap fibroatheroma (defined by lipid-rich plaque with cap thickness < or =65 microm) was 72% in the AMI group, 50% in the ACS group, and 20% in the SAP group (P=0.012). No procedure-related complications occurred. OCT is a safe and effective modality for characterizing coronary atherosclerotic plaques in vivo. Thin-cap fibroatheroma was more frequently observed in patients with AMI or ACS than SAP. This is the first study to compare detailed in vivo plaque morphology in patients with different clinical presentations.
Article
Atherosclerotic yellow plaques identified by coronary angioscopy are considered as vulnerable plaques. However, characteristics of yellow plaques are not well understood. Optical coherence tomography (OCT) provides accurate tissue characterization in vivo and has the capability to measure fibrous cap thickness covering a lipid plaque. Characteristics of yellow plaques identified by angioscopy were evaluated by OCT. We examined 205 plaques of 41 coronary arteries in 26 patients. In OCT analysis, plaques were classified as fibrous or lipid. Minimal lumen area of the plaque, arch of the lipid, and fibrous cap thickness on the lipid plaque were measured. Yellow grade of the plaque was defined as 0 (white), 1 (light yellow), 2 (medium yellow), or 3 (dark yellow) based on the angioscopy. A total of 149 plaques were diagnosed as lipid plaques. Neither the minimal lumen area nor the arch of the lipid was related to the yellow grade. There was an inverse relationship between color grade and the fibrous cap thickness (grade 0 [n = 45] 218 +/- 89 microm, grade 1 [n = 40] 101 +/- 8 microm, grade 2 [n = 46] 72 +/- 10 microm, and grade 3 [n = 18] 40 +/- 14 microm; p <0.05). Sensitivity and specificity of the angioscopy-identified yellow plaque for having a thin fibrous cap (thickness <or=110 microm) were 98% and 96%, respectively. In conclusion, angioscopy-identified yellow plaques frequently were lipid tissue with an overlying thin fibrous cap. Fibrous caps of the intense yellow plaques were very thin, and these plaques might be structurally vulnerable.