Yukio Ozaki, M Okumura, TF Ismail 2, S Motoyama, H. Naruse, K. Hattori, H. Kawai, M. Sarai, J. Ishii, Jagat Narula 3
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1 Culprit Lesion Characteristics in Acute Coronary Syndrome and Stable Angina Assessed by Optical Coherence Tomography (OCT), Angioscopy, IVUS and Multidetector Computed Tomography (MDCT) Yukio Ozaki, M Okumura, TF Ismail 2, S Motoyama, H. Naruse, K. Hattori, H. Kawai, M. Sarai, J. Ishii, Jagat Narula 3 Fujita Health University Hospital, Toyoake, Japan Imperial College, National Heart & Lung Institute, London, UK University of California, Irvine, USA
2 Conflict of Interest: None Declared Background Pathological studies have indicated that ACS lesions have either rupturedfibrous (RFCACS) or intact (IFCACS) fibrous caps. Whereas CTangiographic characteristics of RFCACS include lowattenuation plaques and positive plaque remodelling, features associated with IFCACS have not been previously described. The aim of this study was to assess the CT characteristics of IFCACS lesions.
3 Background Pathological and clinical optical coherence tomography (OCT) studies have indicated that ACS lesions have either rupturedfibrous (RFCACS; Plaque Rupture) or intact (IFC ACS; Plaque Erosion) fibrous caps. Whereas CTangiographic characteristics of RFCACS include lowattenuation plaques and positive plaque remodelling, features associated with IFCACS have not been previously described. The aim of this study was to assess the CT characteristics of IFCACS lesions.
4 Inclusion and Exclusion Criteria Patients with nonstsegment elevation myocardial infarction (NSTEMI), unstable angina (UA) and stable angina were studied. Patients were excluded from the study when they had contraindications to antiplatelet therapy. CTO and LMT lesions were excluded from the study. The study was approved by local ethics committees and was carried out according to the guidelines of the Declaration of Helsinki. Written informed consent was obtained from all patients. Definitions of IFCACS IFCACS was defined as the presence of an intact fibrous cap (i.e., the absence of plaque rupture) by OCT associated with the presence of thrombus by angioscopy or OCT.
5 Patients Of the 74 patients 66 patients underwent 64slice MDCT prior to multiple intracoronary imagings, while the remaining 8 patients did not have 64slice MDCT prior to intracoronary imaging before PCI. All 66 underwent 64slice MDCT, OCT, IVUS, angioscopy and QCA before PCI. Intracoronary imaging and QCA were also performed after coronary stenting. Of these 66 patients, 57 demonstrated images of sufficient quality with all five modalities; 20 had NSTEMI, 15 had unstable angina and 22 stable.
6 Ozaki Y. et al. Eur Heart J. 2010;31: Optical Coherence Tomography (OCT) A inch OCT image wire (LightLab Imaging, MA). Following the careful passage of the inch OCT image wire through the lesion, the proximal occlusion balloon catheter was inflated and lactated Ringer s solution was continuously flushed. Motorized pullback was started at a rate of 1.0 mm/s. The images were saved in the OCT image system digitally. Optical Probe High resolution (14 nm) 2D/3D images Tissue Characteristics Doppler(CFR)
7 Angioscopy and IVUS Coronary angioscopy (Vecmova, Clinical Supply, Gifu, Japan) was performed after the OCT examination during the injection of low molecular dextran with and without balloon occlusion, while blood was cleared away from the view by this injection Following OCT and coronary angioscopy, a mechanical IVUS imaging catheter (40MHz, 2.5Fr, Boston Scientific, Natick, MA) was introduced over a 0.014inch guidewire and positioned distal to the lesion. Lesion geometry was then imaged by using a motorized pullback. ACS* SAP* *de Feyter PJ, Ozaki Y. et al, Circulation 1995;92:140813
8 64slice Multidetector Computed Tomography The 64slice MDCT was performed by Aquilion 64 system (Toshiba, Tokyo) with the ECG synchronization. To avoid motion artifact a heart rate was reduced less than 70 beats/min by oral betablocker before the examination. A bolus of 80 ml contrast medium was injected intravenously. The simultaneous helical scanning was done with a slice thickness of 0.5mm, gantry speed of 0.40 to 0.45 s/rotation and tube voltage of 135 kv at the current of 110 mas. Image reconstruction frames selected for analysis were middiastolic to minimize motion artifact using retrospective ECG gating. Images were estimated by M900 QUADRA (ZIOSoft, Tokyo) and the plaque density was expressed using Hunsfield unit (HU). Motoyama S, et al. J Am Coll Cardiol 2007;50:31926.
9 Statistical Analysis All continuous values are expressed as mean+sd for normally distributed data or median+interquartile range for nonparametric data. Differences between parametric continuous variables were assessed using unpaired or paired ttests as appropriate. Differences between nonparametric continuous variables were evaluated using the Mann Whitney Utest, and for paired variables, the Wilcoxon test. Differences in categorical variables were assessed using the chisquared and Fisher s exact tests as appropriate. The ANOVA test was used to assess differences in continuous variables between the three groups. Where a significant difference was detected, multiple comparison analysis was performed. Considering intracluster correlation (ICC), we only performed statistical estimations in single lesion in one patient based analysis. Twotailed values of p<0.05 were considered significant.
10 Baseline Clinical and Angiographic Characteristics RFCACS IFCACS Stable Angina pvalue Patients (n) Age (years) Male (n, %) NSTEMI (n, %) UAP (n, %) Stable Angina (n, %) ± (100) 15 (60) 10 (40) ±8.2 8 (80) 4 (40) 6 (60) ± (100) 22 (100) Diabetes (n, %) 8 (32) 3 (30) 8 (36) Hypertension (%) 12 (48) 6 (60) 13 (59) Hypercholesterolemia(%) 12 (48) 6 (60) 10 (45) Smokers (n, %) Nonsmoker 10 (38) 1 (9) 7 (35) Exsmoker 9 (46) 2 (18) 12 (60) Current smoker 6 (17) 7 (73) 3 (5)
11 Baseline Angiographic Characteristics Culprit Lesions (n) RCA/LAD/LCX (n, %) Lesion type (A/B1/B2/C, n) QCA RD pre (mm) QCA MLD pre (mm) RFCACS IFCACS Stable Angina pvalue / 13/ 1 0/ 13/ 12/ ± ±0.20 4/ 5/ 1 1/ 4/ 5/ ± ±0.22 5/ 14/ 3 2/ 11/ 9/ ± ± Nonculprit lesions in nonculprit vessel by CTA RFCACS IFCACS Stable Angina pvalue NonCulprit Lesions (n) Average lesion severity (%) 42±19 32±12 46± NCP < 30 HU (n, %) 7 (37) 2 (25) 1 (8) Spotty calcification (n, %) 5 (26) 2 (25) 2 (16) Positive Remodeling (n, %) 10 (53) 1 (13) 2 (16) 0.044
12 Lesion (n) OCT RFCACS IFCACS Stable Angina pvalue 22 Fibrous cap thickness(μm) 45±12 * 131±57 * 321±146 * Lipid angle > 2quads (n, %) 23 (92) 4 (40) 5 (23) TCFA (n, %) 23 (92) 2 (20) 2 (9) Thrombus (n, %) 25 (100) 10 (100) 4 (18) Angioscopy RFCACS IFCACS Stable Angina pvalue Thrombus 22 (88) 10 (100) 3 (14) Mural thrombus 13 (52) 7 (70) 3 (14) Protruding thrombus 9 (36) 3 (30) 0 (0) Yellow plaque 21 (84) 7 (70) 12 (55) White plaque 4 (16) 3 (30) 10 (45) 0.088
13 Lesion (n) IVUS(mm 2 ) Vessel area pre Lumen area pre Plaque area pre Prox. ref. vessel area Distal. ref. vessel area Remodeling index IVUS RFCACS IFCACS Stable Angina ± ± ± ± ± ±0.12 * ± ± ± ± ± ±0.08 * ± ± ± ± ± ±0.11 * pvalue (ANOVA) * : p<0.05
14 64slice MDCT RFCACS IFCACS Stable Angina pvalue (ANOVA) Lesion (n) 64slice MDCT(n,%) NCP < 30 HU NCP from 30 to 150 HU Spotty calcification Large calcification Remodelling index Positive remodelling LAP & PR (88) 25 (100) 22 (80) 3 (12) 1.15±0.06 * 24 (96) 22 (88) 10 4 (40) 10 (100) 2 (20) 1 (10) 1.02±0.08 * 2 (20) 1 (10) 22 4 (18) 22 (100) 5 (23) 13 (59) 0.99±0.09 * 3 (14) 0 (0) * : p<0.05
15 Impact of IFC (Plaque Erosion) on ACS Approximately onethird of lesions responsible for major coronary thrombi on pathological analysis are secondary to plaque erosions. Shaar and colleagues reported that unlike ruptured plaques, eroded plaques showed constrictive remodelling, and did not necessarily demonstrate voluminous plaques nor necrotic cores. These lesions revealed a unique proteoglycan substrate, which facilitates endothelial sloughing and thrombogenecity. It is reasonable to presume that nondisrupted culprit lesions (IFCACS) in our study would represent plaque erosions.
16 Clinical Implications CT coronary angiography (CTA) has been employed as a useful modality to differentiate patients with or without significant coronary artery disease noninvasively and stratify the risk of subsequent events. CTA is able to successfully characterise ruptured plaques as low attenuation plaque with positive remodelling. However, this study has demonstrated that CTA fails to characterise lesions at risk of IFCACS which could be responsible for one third of ACS from common coronary atherosclerosis. Our findings suggest the need for future work to clarify the value of CTA for assessing risk in patients with IFCACS.
17 Conclusions The IFCACS lesions based on OCT and angioscopic characteristics demonstrated less low attenuation plaque and less positive remodelling than ruptured plaques by CTangiography. Since there are no unique CT features of nonruptured culprit lesions to enable their clear distinction from stable lesions, it will be difficult to develop CTbased noninvasive imaging techniques to allow the clear identification of subjects at high risk of developing ACS due to IFC.
18 Fujita Health University, Toyoake, Japan
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