Features of Ruptured Plaque vs Thin-Cap Fibroatheroma in ACS
Consecutive ACS patients who underwent both OCT and IVUS examinations of all 3 coronary arteries between January 2010 and October 2012 were included in the analysis. All OCT and IVUS images were digitally stored and submitted to the Massachusetts General Hospital OCT core laboratory for analysis. Patients included ST-segment elevation myocardial infarction (STEMI), non-STEMI, and unstable angina. STEMI was defined as continuous chest pain that lasted >30 min, arrival at the hospital within 12 h from the onset of symptoms, ST-segment elevation >0.1 mV in ≥2 contiguous leads, or new left bundle branch block on the 12-lead electrocardiogram (ECG), and elevated cardiac markers (creatine kinase-myocardial band or troponin T/I). Non-STEMI was defined as ischemic symptoms in the absence of ST-segment elevation on ECG with elevated cardiac markers. Unstable angina was defined as angina at rest, accelerated angina, or new onset angina. The culprit lesion was identified by the combination of left ventricular wall motion abnormalities, ECG findings, and angiographic lesion morphology. Ninety-five ACS patients underwent both OCT and IVUS examinations of all 3 major epicardial coronary arteries during the same procedure. From these patients, 13 patients were excluded: suboptimal OCT (n = 2) or IVUS (n = 3) image quality, unsuccessful OCT or IVUS pullbacks, and no clearly identified RCP, RNCP, or TCFA. Finally, 82 patients were included in this study.
This study was performed in accordance with the Declaration of Helsinki with regard to investigation in humans and the study protocol was approved by the ethics committee of the Second Affiliated Hospital of Harbin Medical University (Harbin, China), and all patients provided written informed consent.
Aspirin (200 mg), clopidogrel (300 mg), and heparin (100 U/kg) were administered before cardiac catheterization. IVUS and OCT examinations were performed in patients with Thrombolysis in Myocardial Infarction flow grade 3. IVUS examinations were performed using the 40 MHz Atlantis Pro catheter (Boston Scientific) after intracoronary administration of 100 to 200 μg nitroglycerin. An IVUS catheter was inserted into the coronary artery through a 6- to 7-F coronary guiding catheter over a 0.014-inch guidewire. The transducer was pulled back automatically at 0.5 mm/s. After the IVUS procedure, time-domain OCT (M2/M3 Cardiology Imaging System, St. Jude Medical, Westford, Massachusetts) was performed as previously described. The IVUS and OCT imaging were performed in all 3 coronary arteries.
OCT images were analyzed using proprietary software (LightLab Imaging, Inc., Westford, Massachusetts) at the MGH OCT core laboratory by 2 experienced investigators. Plaques were classified into 2 categories: 1) fibrous plaque (homogeneous high signal region); or 2) lipid plaque (low signal region with diffuse border). Identification of 2 separate plaques in the same vessel required a ≥5 mm reference segment between them; if not, they were considered 1 long lesion. If the nonculprit lesion was lipid plaque, lipid arc was measured at every 1 mm interval throughout the entire lesion, and fibrous cap thickness (FCT) was measured at its thinnest part 3 times and the average value was calculated. A TCFA was defined as a lipid-rich plaque (maximum lipid arc >90°) with fibrous cap <65 μm (Figure 1A).
(Enlarge Image)
Figure 1.
Representative Optical Coherence Tomography Images
(A) Thin-cap fibroatheroma (yellow arrows) was defined as a plaque with fibrous cap <65 μm overlying a lipid-rich plaque (maximum lipid arc >90°). (B) Ruptured plaque was defined as a plaque with fibrous cap discontinuity (red arrows) and cavity formation (red asterisk) inside the plaque. (C) Microchannels are observed as black holes within a plaque (white arrows). (D) Macrophage accumulations are shown as bright spots with high signal variances (yellow arrowheads). (E) Cholesterol crystals were defined as thin, linear regions of high intensity within the plaque (red arrowheads). (F) Thrombus was defined as an irregular mass protruding into the lumen that had a dimension ≥250 μm (white arrowheads).
On the basis of the plaque morphology, ruptured plaque was defined as a lipid plaque with fibrous cap discontinuity and cavity formation inside the plaque (Figure 1B). Ruptured plaque was divided into RCP group and RNCP group. In ruptured plaque, FCT was measured at the thinnest part of the remnant fibrous cap. The minimum FCT values from each OCT image were used for analysis. Lipid arc was also evaluated as described previously. Lipid length was measured on the longitudinal view. A microvessel was defined as a black hole with a diameter of 50 to 300 μm within a plaque that was present on at least 3 consecutive frames (Figure 1C). Macrophage accumulation on the OCT images was defined as increased signal intensity within the plaque, accompanied by heterogeneous backward shadows (Figure 1D). Presence of cholesterol crystals was defined by the presence of linear and highly reflecting structures within the plaques (Figure 1E). Calcification was also recorded when an area with low backscatter and a sharp border was identified inside a plaque. Thrombus was defined as an irregular mass protruding into the lumen that had a measured dimension ≥250 μm (Figure 1F).
For each plaque, the corresponding IVUS images were selected using fiduciary points such as side branches, calcifications, and/or stents. IVUS image analysis was performed at an independent core laboratory at the MGH. All IVUS images were analyzed using a semiautomatic software (EchoPlaque, Indec Systems, Mountain View, California) by 2 independent reviewers. When there was discordance between the observers, a consensus reading was obtained.
Quantitative IVUS measurements included the external elastic membrane (EEM), lumen cross-sectional area (CSA), and the plaque plus media (P+M) CSA. The plaque burden was calculated as the P+M CSA divided by the lesion EEM CSA multiplied by 100. The reference was the image frame showing the largest lumen within 10 mm proximal and distal from the target lesions. The remodeling index was calculated as the EEM CSA at the minimal lumen area site divided by the average of the proximal and distal reference EEM CSA.
Coronary angiograms were analyzed using offline software (CAAS 5.10.1, Pie Medical Imaging BV, Maastricht, the Netherlands). Reference diameter, minimum lumen diameter, and diameter stenosis were determined after calibration using the tip of the catheter.
Statistical analysis was performed with SPSS version 17.0 (SPSS, Chicago, Illinois) and MedCalc version 12.7 (MedCalc Software, Mariakerke, Belgium). Categorical data were presented as counts (proportions) and were compared using either a chi-square test or Fisher exact test. Continuous variables were tested for normal distribution by the nonparametric 1-sample Kolmogorov-Smirnov test. Continuous variables were expressed as mean ± SD for normally distributed variables and as median (25, 75th percentiles) for non-normally distributed variables, and compared by use of the independent sample Student t test or Mann-Whitney U test, when appropriate. In order to take into account the within-subject correlation due to multiple lesions analyzed within the same patient, comparisons of morphological characteristics between RCP, RNCP, and TCFA were carried out by means of the Generalized Estimating Equations approach. Bonferroni's correction for the multiple comparisons among these 3 groups was applied, thus a p value <0.017 (0.05/3) was considered statistically significant. Receiver-operating characteristic curve analyses were performed to determine the best cutoff values (using Youden Index) of morphologic characteristics for discriminating RCP, RNCP, and TCFA, and the areas under the curve (AUCs) as well as the sensitivities, specificities, positive and negative predictive values of the diagnostic test. For receiver-operating characteristic analyses, a p value <0.05 was considered statistically significant.
Methods
Study Population
Consecutive ACS patients who underwent both OCT and IVUS examinations of all 3 coronary arteries between January 2010 and October 2012 were included in the analysis. All OCT and IVUS images were digitally stored and submitted to the Massachusetts General Hospital OCT core laboratory for analysis. Patients included ST-segment elevation myocardial infarction (STEMI), non-STEMI, and unstable angina. STEMI was defined as continuous chest pain that lasted >30 min, arrival at the hospital within 12 h from the onset of symptoms, ST-segment elevation >0.1 mV in ≥2 contiguous leads, or new left bundle branch block on the 12-lead electrocardiogram (ECG), and elevated cardiac markers (creatine kinase-myocardial band or troponin T/I). Non-STEMI was defined as ischemic symptoms in the absence of ST-segment elevation on ECG with elevated cardiac markers. Unstable angina was defined as angina at rest, accelerated angina, or new onset angina. The culprit lesion was identified by the combination of left ventricular wall motion abnormalities, ECG findings, and angiographic lesion morphology. Ninety-five ACS patients underwent both OCT and IVUS examinations of all 3 major epicardial coronary arteries during the same procedure. From these patients, 13 patients were excluded: suboptimal OCT (n = 2) or IVUS (n = 3) image quality, unsuccessful OCT or IVUS pullbacks, and no clearly identified RCP, RNCP, or TCFA. Finally, 82 patients were included in this study.
This study was performed in accordance with the Declaration of Helsinki with regard to investigation in humans and the study protocol was approved by the ethics committee of the Second Affiliated Hospital of Harbin Medical University (Harbin, China), and all patients provided written informed consent.
Acquisition of IVUS and OCT Images
Aspirin (200 mg), clopidogrel (300 mg), and heparin (100 U/kg) were administered before cardiac catheterization. IVUS and OCT examinations were performed in patients with Thrombolysis in Myocardial Infarction flow grade 3. IVUS examinations were performed using the 40 MHz Atlantis Pro catheter (Boston Scientific) after intracoronary administration of 100 to 200 μg nitroglycerin. An IVUS catheter was inserted into the coronary artery through a 6- to 7-F coronary guiding catheter over a 0.014-inch guidewire. The transducer was pulled back automatically at 0.5 mm/s. After the IVUS procedure, time-domain OCT (M2/M3 Cardiology Imaging System, St. Jude Medical, Westford, Massachusetts) was performed as previously described. The IVUS and OCT imaging were performed in all 3 coronary arteries.
OCT Analysis
OCT images were analyzed using proprietary software (LightLab Imaging, Inc., Westford, Massachusetts) at the MGH OCT core laboratory by 2 experienced investigators. Plaques were classified into 2 categories: 1) fibrous plaque (homogeneous high signal region); or 2) lipid plaque (low signal region with diffuse border). Identification of 2 separate plaques in the same vessel required a ≥5 mm reference segment between them; if not, they were considered 1 long lesion. If the nonculprit lesion was lipid plaque, lipid arc was measured at every 1 mm interval throughout the entire lesion, and fibrous cap thickness (FCT) was measured at its thinnest part 3 times and the average value was calculated. A TCFA was defined as a lipid-rich plaque (maximum lipid arc >90°) with fibrous cap <65 μm (Figure 1A).
(Enlarge Image)
Figure 1.
Representative Optical Coherence Tomography Images
(A) Thin-cap fibroatheroma (yellow arrows) was defined as a plaque with fibrous cap <65 μm overlying a lipid-rich plaque (maximum lipid arc >90°). (B) Ruptured plaque was defined as a plaque with fibrous cap discontinuity (red arrows) and cavity formation (red asterisk) inside the plaque. (C) Microchannels are observed as black holes within a plaque (white arrows). (D) Macrophage accumulations are shown as bright spots with high signal variances (yellow arrowheads). (E) Cholesterol crystals were defined as thin, linear regions of high intensity within the plaque (red arrowheads). (F) Thrombus was defined as an irregular mass protruding into the lumen that had a dimension ≥250 μm (white arrowheads).
On the basis of the plaque morphology, ruptured plaque was defined as a lipid plaque with fibrous cap discontinuity and cavity formation inside the plaque (Figure 1B). Ruptured plaque was divided into RCP group and RNCP group. In ruptured plaque, FCT was measured at the thinnest part of the remnant fibrous cap. The minimum FCT values from each OCT image were used for analysis. Lipid arc was also evaluated as described previously. Lipid length was measured on the longitudinal view. A microvessel was defined as a black hole with a diameter of 50 to 300 μm within a plaque that was present on at least 3 consecutive frames (Figure 1C). Macrophage accumulation on the OCT images was defined as increased signal intensity within the plaque, accompanied by heterogeneous backward shadows (Figure 1D). Presence of cholesterol crystals was defined by the presence of linear and highly reflecting structures within the plaques (Figure 1E). Calcification was also recorded when an area with low backscatter and a sharp border was identified inside a plaque. Thrombus was defined as an irregular mass protruding into the lumen that had a measured dimension ≥250 μm (Figure 1F).
IVUS Analysis
For each plaque, the corresponding IVUS images were selected using fiduciary points such as side branches, calcifications, and/or stents. IVUS image analysis was performed at an independent core laboratory at the MGH. All IVUS images were analyzed using a semiautomatic software (EchoPlaque, Indec Systems, Mountain View, California) by 2 independent reviewers. When there was discordance between the observers, a consensus reading was obtained.
Quantitative IVUS measurements included the external elastic membrane (EEM), lumen cross-sectional area (CSA), and the plaque plus media (P+M) CSA. The plaque burden was calculated as the P+M CSA divided by the lesion EEM CSA multiplied by 100. The reference was the image frame showing the largest lumen within 10 mm proximal and distal from the target lesions. The remodeling index was calculated as the EEM CSA at the minimal lumen area site divided by the average of the proximal and distal reference EEM CSA.
Quantitative Coronary Angiography
Coronary angiograms were analyzed using offline software (CAAS 5.10.1, Pie Medical Imaging BV, Maastricht, the Netherlands). Reference diameter, minimum lumen diameter, and diameter stenosis were determined after calibration using the tip of the catheter.
Statistical Analysis
Statistical analysis was performed with SPSS version 17.0 (SPSS, Chicago, Illinois) and MedCalc version 12.7 (MedCalc Software, Mariakerke, Belgium). Categorical data were presented as counts (proportions) and were compared using either a chi-square test or Fisher exact test. Continuous variables were tested for normal distribution by the nonparametric 1-sample Kolmogorov-Smirnov test. Continuous variables were expressed as mean ± SD for normally distributed variables and as median (25, 75th percentiles) for non-normally distributed variables, and compared by use of the independent sample Student t test or Mann-Whitney U test, when appropriate. In order to take into account the within-subject correlation due to multiple lesions analyzed within the same patient, comparisons of morphological characteristics between RCP, RNCP, and TCFA were carried out by means of the Generalized Estimating Equations approach. Bonferroni's correction for the multiple comparisons among these 3 groups was applied, thus a p value <0.017 (0.05/3) was considered statistically significant. Receiver-operating characteristic curve analyses were performed to determine the best cutoff values (using Youden Index) of morphologic characteristics for discriminating RCP, RNCP, and TCFA, and the areas under the curve (AUCs) as well as the sensitivities, specificities, positive and negative predictive values of the diagnostic test. For receiver-operating characteristic analyses, a p value <0.05 was considered statistically significant.
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