Intracoronary Imaging of Vulnerable Plaque—From Clinical Research to Everyday Practice
Abstract
:1. Introduction
2. Vulnerable Plaque and Its Visualization
2.1. Pathology of Vulnerable Plaque
2.2. Intravascular Ultrasound (GS-IVUS, VH-IVUS, HD-IVUS)
2.2.1. Grey Scale Intravascular Ultrasound (GS-IVUS)
2.2.2. Virtual Histology Intravascular Ultrasound (VH-IVUS)
2.3. Near-Infrared Spectroscopy (NIRS)
2.4. Optical Coherence Tomography (OCT)
The Impact of OCT Finding on Patients’ Risk
2.5. OCT vs. VH-IVUS and NIRS
2.6. Fused Imaging
2.6.1. Concept of Vulnerable Plaque in Fusion Imaging
2.6.2. NIRS-IVUS Imaging
2.6.3. IVUS-OCT Imaging
2.6.4. NIRS-OCT IMAGING/NIR(A)F-OCT Imaging
2.6.5. NIRF-OCT-IVUS Imaging
2.7. Fusion of Coronary Angiography and IVUS/OCT in 3D Reconstructions
2.8. High-Frequency and Dual-Frequency IVUS
3. Summary and Future Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Authors/Study/Publication Year | Modalities | Study Size | Study Objective | Main Results | Main Limitations |
---|---|---|---|---|---|
Rodriguez-Granillo, 2005 [36] | IVUS-VH | 55 patients | To assess the prevalence of intravascular ultrasound (IVUS)-derived thin-cap fibroatheroma (IDTCFA) and its relationship with the clinical presentation using spectral analysis of IVUS radiofrequency data. Definition of IDTCFA lesions—focal, necrotic-core-rich (≥10% of the cross-sectional area) plaques being in contact with the lumen, percent atheroma volume (PAV) ≥40%. | IVUS-VH identified IDTCFA as a more prevalent finding in ACS than in stable angina patients. ACS patients had a significantly higher incidence of IDTCFA than stable patients (0.7 (IQR 0.0 to 1.3) IDTCFA/cm vs. 0.2 (IQR 0.0 to 0.7) IDTCFA/cm, p = 0.031). | The lack of a direct comparison between IVUS-VH and histopathology |
Stone, 2011 [23] PROSPECT [NCT00180466] | IVUS-VH | 697 patients (313 had TCFA) | To confirm that ACS arise from atheromas with certain histopathological characteristics, and that these characteristics are not necessarily dependent on the degree of angiographic stenosis at that site. | In multivariate analysis, the authors found that plaque burden ≥70%, TCFA and minimal lumen area ≤4.0 mm2 were independent predictors of non-culprit lesion related major adverse cardiac events in lesion-level analysis. Importantly, the rate of MACE increased from HR 3.90 (95% CI, 2.25–6.76) with TCFA alone to HR 11.05 (95% CI, 4.39–27.82) when combining all of the described plaque futures. | Only the proximal 6 to 8 cm of the coronary tree were examined. All 106 non-culprit lesions associated with recurrent events were evaluated with the use of baseline angiography, but only 55 of these lesions were seen on gray-scale ultrasonography and only 51 were seen on radiofrequency intravascular ultrasonography. |
Calvert, 2011 [24] VIVA | IVUS-VH | 170 patients | TCFA identified by VH-IVUS are associated with major adverse cardiac events (MACE) in individual-plaque or whole-patient analysis. | The study showed that VH-IVUS TCFA was associated with MACE. The non-culprit lesion factors associated with non-restenotic MACE included VHTCFA (hazard ratio (HR): 7.53, p = 0.038) and plaque burden >70% (HR: 8.13, p = 0.011). VHTCFA (HR: 8.16, p = 0.007), plaque burden >70% (HR: 7.48, p < 0.001) and minimum luminal area <4.0 mm2 (HR: 2.91, p = 0.036) were associated with total MACE. | The definitions of TCFAs in VH-IVUS did not exactly match the histopathological definitions. VH-IVUS tended to overestimate the number of TCFAs compared to histology, and some histological ThCFAs were classified as VHTCFAs. |
Brown, 2015 [22] | IVUS-VH, OCT | 258 ROI from 14 human hearts | The combination of VH-IVUS and OCT improves the identification of TCFA. | Combined VH-IVUS/OCT imaging markedly improved TCFA identification. The sensitivity, specificity and diagnostic accuracy for TCFA identification were 63.6%, 78.1% and 76.5% for VH-IVUS and 72.7%, 79.8% and 79.0% for OCT. Combining VH-defined fibroatheroma and fibrous cap thickness ≤85 μm over three continuous frames improved TCFA identification, with a diagnostic accuracy of 89.0%. | Small study size; small longitudinal mismatches between imaging modalities |
Cheng, 2014 [25] ATHEROREMO | IVUS-GS, IVUS-VH | 581 patients | To investigate the prognostic value of the in vivo detection of high-risk coronary plaques by intravascular ultrasound (IVUS) in patients undergoing coronary angiography. | The study showed that presence of TCFA in non-culprit coronary artery is associated with greater incidence of death and ACS at 1 year follow-up. The presence of TCFA lesions was significantly associated with the composite of death or ACS only (present 7.5% vs. absent 3.0%; adjusted HR: 2.51, 95% CI: 1.15–5.49; p = 0.021). TCFA with a plaque burden of at least 70% were associated with a higher MACE rate both in the first 6 months (p = 0.011) and after 6 months (p < 0.001) of follow-up, while smaller TCFA lesions were only associated with a higher MACE rate after 6 months (p = 0.033). | The relatively small number of endpoints did not allow for the evaluation of whether adding IVUS imaging to a prognostic model with conventional risk factors would result in improved risk prediction. Missing repeat intracoronary imaging with IVUS virtual histology. |
Fuji, 2015 [17] | IVUS-GS, OCT | 165 coronary arteries from 60 autopsy hearts | To assess the accuracy of optical coherence tomography (OCT), gray-scale intravascular ultrasound (IVUS), and their combination for detecting thin-cap fibroatheromas (TCFA). A total of 685 pairs of images of OCT and IVUS were compared with histology. | PPV increased from 41% to 69% after IVUS and OCT combination. The sensitivity, specificity, PPV, NPV and DA of the combined use of OCT and IVUS for characterizing TCFA using histology as a standard were 92%, 99%, 69%, 99% and 99%, respectively. | The low prevalence of TCFA in histology (2%) may affect the statistical power to assess the diagnostic accuracy of TCFA. |
Prati, 2020 [37] CLIMA | IVOCT | 1003 | To explore the predictive value of multiple high-risk plaque features in the same coronary lesion (minimum lumen area (MLA), fibrous cap thickness (FCT), lipid arc circumferential extension and presence of optical coherence tomography (OCT)-defined macrophages). | At 1 year, the primary clinical endpoint was observed in 37 patients (3.7%). In a total of 1776 lipid plaques, presence of MLA < 3.5 mm2 (hazard ratio (HR) 2.1, 95% confidence interval (CI) 1.1–4.0), FCT < 75 µm (HR 4.7, 95% CI 2.4–9.0), lipid arc circumferential extension > 180° (HR 2.4, 95% CI 1.2–4.8) and OCT-defined macrophages (HR 2.7, 95% CI 1.2–6.1) were all associated with increased risk of the primary endpoint. The pre-specified combination of plaque features (simultaneous presence of the four OCT criteria in the same plaque) was observed in 18.9% of patients experiencing the primary endpoint and was an independent predictor of events (HR 7.54, 95% CI 3.1–18.6). OCT-based classification showed limited sensitivity (positive predictive value 19.4%), but high specificity (negative predictive value 96.9%) for the primary endpoint, and remained an independent predictor of 1 year events after correction for the other confounding variables. | The registry included patients with various clinical presentation and cardiovascular risk profiles uniquely pooled by the intraprocedural OCT assessment of proximal LAD. The combination of the four high-risk plaque features was uncommon. |
Kedhi, 2021 [38] COMBINE | IVOCT | 482 | To study the impact of optical coherence tomography (OCT)-detected thin-cap fibroatheroma (TCFA) on the clinical outcomes of diabetes mellitus (DM) patients with fractional flow reserve (FFR)-negative lesions. | Among DM patients with ≥1 FFR-negative lesions, TCFA-positive patients represented 25% of this population and were associated with a five-fold higher rate of MACE despite the absence of ischaemia. The Cox regression multivariable analysis identified TCFA as the strongest predictor of major adverse clinical events (MACE) (hazard ratio 5.12; 95% confidence interval 2.12–12.34; p < 0.001). |
IVUS vs. OCT | Comment | |
---|---|---|
Assessment of non-calcified and non-LM coronary plaques before stent implantation | Equal | OCT may provide more information regarding plaque composition (for example lipid plaque and optimal stent edge placement). |
Assessment of calcified and non-LM coronary plaques before stent implantation | OCT better | Calcification obstructs penetration of the ultrasound (casting acoustic shadow). |
Assessment of LM coronary plaques before stent implantation | IVUS better | OCT may be used in non-ostial LM lesions provided proper blood removal. |
Optimalization after stent implantation | OCT better | Images from OCT due to high resolution may be easier to interpret provided proper blood removal (not possible in LM ostial lesions). |
Spontaneous coronary dissection | IVUS better or equal | OCT may provide easier interpretation of SCAD and is used in clinical practice; however, contrast flush may propagate SCAD. |
Stent failure | OCT | Higher resolution and easier interpretation with OCT. |
Neoatherosclerosis | OCT | Higher resolution and easier interpretation with OCT. |
Imaging in setting of ACS | OCT | OCT may provide information regarding the mechanism of ACS including plaque rapture, erosion or calcified nodule. |
CTO | IVUS | OCT requires contrast flush, which is not possible in CTO. Moreover, when using OCT, it is not possible to provide continuous visualization of one chosen coronary artery. |
CKD stage 4 | IVUS | OCT requires continuous contrast flush during pullback. |
Authors/Publication Year/Study | Fused Imaging Modalities | Study Size | Objectives | Main Results | Main Limitations |
---|---|---|---|---|---|
Goldstein [75], 2011 COLOR Registry [NCT00831116] | NIRS-IVUS | 62 | Prospective identification of LCP with catheter-based near-infrared spectroscopy (NIRS) may predict an increased risk of periprocedural MI and facilitate development of preventive measures. | The primary finding of the study is that in patients with coronary artery disease, PCI of lesions with a large lipid core (maxLCBI4mm ≥ 500 by NIRS) is associated with a 50% risk of periprocedural MI (95% CI, 28–62), compared with only a 4.2% risk (95% CI, 0.8–11) for lesions without a large lipid core (maxLCBI4mm < 500 by NIRS). | The number, type, timing and frequency of biomarker determination were not standardized. A small sample size. |
Kini, 2013, [44] YELLOW [NCT01567826)] | NIRS-IVUS | 86 patients | To determine the impact of short-term intensive statin therapy on intracoronary plaque lipid content. | The median reduction (95% confidence interval) in LCBI4mm max was significantly greater in the intensive versus standard group (−149.1 [−210.9 to −42.9] vs. 2.4 [−36.1 to 44.7]; p = 0.01). Short-term intensive statin therapy may reduce lipid content in obstructive lesions. | A small sample size and short duration of follow-up. The baseline LCBI was significantly higher in patients randomly allocated to intensive versus standard therapy. |
Puri [76] 2015 | NIRS-IVUS | 116 coronary arteries of 51 autopsied hearts | To assess the relationships between intravascular ultrasound (IVUS)-derived PB and arterial remodeling with near-infrared spectroscopy (NIRS)-derived lipid content in ex vivo and in vivo human coronary arteries. | Lesion-based analyses demonstrated the highest LCBI and remodeling index within coronary fibroatheroma (P trend < 0.001 and 0.02 versus all plaque groups, respectively). Prediction models demonstrated similar abilities of PB, LCBI and the remodeling index for discriminating fibroatheroma (c indices: 0.675, 0.712, and 0.672, respectively). A combined PB + LCBI analysis significantly improved fibroatheroma detection accuracy (c index 0.77, p = 0.028 versus PB; net-reclassification index 43%, p = 0.003). | Small study size and on autopsied heart |
Waksman [43] 2019 LRP Study NCT02033694 | NIRS-IVUS | 1271 patients | To investigate the relationship between LRPs detected by NIRS-intravascular ultrasound imaging at unstented sites and subsequent coronary events from new culprit lesions. | The 2-year cumulative incidence of NC-MACE was 9% (n = 103). The unadjusted hazard ratio (HR) for NC-MACE was 1.21 (95% CI 1.09–1.35; p = 0.0004) for each 100-unit increase in maxLCBI4mm and the adjusted HR was 1.18 (1.05–1.32; p = 0.0043). In patients with a maxLCBI4mm over 400, the unadjusted HR for NC-MACE was 2.18 (1.48–3.22; p < 0.0001) and the adjusted HR was 1.89 (1.26–2.83; p = 0.0021). | |
Terada [46], 2021 PROSPECT II | NIRS-IVUS, OCT | 244 patients | To investigate the ability of combined near-infrared spectroscopy and intravascular ultrasound (NIRS-IVUS) to differentiate plaque rupture (PR), plaque erosion (PE) or calcified nodule (CN) in acute myocardial infarction (AMI). | NIRS-measured maxLCBI4mm was significantly largest in OCT-PR (705 (interquartile range (IQR): 545 to 854)), followed by OCT-CN (355 (IQR: 303 to 478)) and OCT-PE (300 (IQR: 126 to 357)) (p < 0.001). The NIRS-IVUS classification algorithm using plaque cavity, convex calcium and max LCBI4mm showed 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. | Recognition of PR, PE and CN using OCT as a reference, without considering the intrinsic and insurmountable limitations of OCT technology. Aspiration thrombectomy and balloon angioplasty prior to imaging may have induced iatrogenic rupture of the fibrous cap and reduced the lipid composition of the PR. |
Li [77] 2015 | IVUS-OCT | 50 human coronary arteries (in vitro) | To investigate the capability of recognition of vulnerable plaques using this IVUS-OCT technology. | Histology confirmed that TCFA and false TCFA can be differentiated using IVUS-OCT images. The full integration of the two complementary techniques of OCT and IVUS permits accurate evaluation of total plaque burden and plaque morphology by using an in vitro human cadaver study. | Limited study size and only on autopsied vessel |
Ughi [78], 2016 | OCT-NIRAF | 12 patients | First clinical imaging of human coronary arteries in vivo using a multimodality OCT and near-infrared autofluorescence (NIRAF) intravascular imaging system and catheter. | High-quality intracoronary OCT and NIRAF image data (>50 mm pullback length) were successfully acquired without complication in all patients. In a substudy of 4 repeated pullbacks, NIRAF reproducibility was excellent with an average Pearson’s correlation coefficient of 0.925 ± 0.015. | Small study |
Liang [79], 2014 | NIRF-OCT-IVUS | - | The study presented a trimodality imaging system and an intravascular endoscopic probe for the detection of early-stage atherosclerotic plaques. | The first ex vivo imaging of a normal New Zealand white rabbit aorta in which two model plaques had been planted inside the blood vessel wall. | Large dimension of probe Long imaging time |
GS-IVUS | VH-IVUS | NIRS | OCT | |
---|---|---|---|---|
Fibroatheroma | Can identify lipid plaque—so-called “soft” plaque—which is described as the area with low echogenicity in contrast to the reference adventitia. | VH-IVUS cannot directly identify fibroatheroma. Fibroatheroma is described as the presence of 10% confluent necrotic core with an overlying layer of fibrous tissue on three consecutive frames (2). | Shows the probability of lipid as yellow pixels on the chemogram and lipid core burden index (LCBI). | Can identify lipid plaque described as signal-poor regions with diffuse borders (lipid pool) and overlying signal-rich bands (fibrous caps), accompanied by high signal attenuation. Due to this limitation, it is frequently not possible to assess the diameter of the artery with lipid plaque. |
Calcification | Bright echo obstructing penetration of the ultrasound (casting acoustic shadow). Due to this limitation, the depth of calcification cannot be measured. | Visible as white pixels. | NA | Signal-poor regions with sharply delineated borders and limited shadowing. Due to good visualization of calcification, it is very easy to measure both the depth and angle of calcification. |
Fibrocalcific plaque | Mixed plaque containing fibrous plaque and calcifications (1). | Presence of 10% confluent dense calcium without confluent necrotic core (2). | NA | NA |
Calcific nodule | Calcification protruding to the lumen. | NA | NA | Calcification protruding to the lumen. |
TCFA | GS-IVUS does not have a resolution high enough to visualize TCFA. | VH-IVUS cannot identify TCFA directly. TCFA is described as the presence of 10% confluent necrotic core in direct contact with the lumen on three consecutive frames (2). | NA | Lipid plaque with a minimum thickness of the fibrous cap of less than 65 μm or 80 μm and with lipid occupying >90° in circumference. |
Erosion | NA | NA | NA | Presence of attached thrombus overlying an intact and visualized plaque (3). |
Rupture | Plaque ulceration with possible remnants of the fibrous cap at the edges. Usually hard to identify. | NA | NA | Disruption of fibrous cap with visible cavity. |
Thrombus | Intraluminal mass with layered or pedunculated appearance. Usually hard to distinguish from soft plaque. | Thrombus may be visible on VH-IVUS as plaque. | NA | Protruding mass either attached to the luminal surface or floating within the lumen (4). |
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Legutko, J.; Bryniarski, K.L.; Kaluza, G.L.; Roleder, T.; Pociask, E.; Kedhi, E.; Wojakowski, W.; Jang, I.-K.; Kleczynski, P. Intracoronary Imaging of Vulnerable Plaque—From Clinical Research to Everyday Practice. J. Clin. Med. 2022, 11, 6639. https://doi.org/10.3390/jcm11226639
Legutko J, Bryniarski KL, Kaluza GL, Roleder T, Pociask E, Kedhi E, Wojakowski W, Jang I-K, Kleczynski P. Intracoronary Imaging of Vulnerable Plaque—From Clinical Research to Everyday Practice. Journal of Clinical Medicine. 2022; 11(22):6639. https://doi.org/10.3390/jcm11226639
Chicago/Turabian StyleLegutko, Jacek, Krzysztof L. Bryniarski, Grzegorz L. Kaluza, Tomasz Roleder, Elzbieta Pociask, Elvin Kedhi, Wojciech Wojakowski, Ik-Kyung Jang, and Pawel Kleczynski. 2022. "Intracoronary Imaging of Vulnerable Plaque—From Clinical Research to Everyday Practice" Journal of Clinical Medicine 11, no. 22: 6639. https://doi.org/10.3390/jcm11226639
APA StyleLegutko, J., Bryniarski, K. L., Kaluza, G. L., Roleder, T., Pociask, E., Kedhi, E., Wojakowski, W., Jang, I. -K., & Kleczynski, P. (2022). Intracoronary Imaging of Vulnerable Plaque—From Clinical Research to Everyday Practice. Journal of Clinical Medicine, 11(22), 6639. https://doi.org/10.3390/jcm11226639