doi: 10.1161/CIRCIMAGING.108.786962
Original Articles |
Evaluation of Coronary Atherosclerosis by Multislice Computed Tomography in Patients With Acute Myocardial Infarction and Without Significant Coronary Artery Stenosis
A Comparative Study With Quantitative Coronary Angiography
From the Division of Cardiology (A.A., A.M., F.U., D.L., D.A.), Department of Heart and Lung, and Department of Radiology (F.C., E.M., A.P., M.F., G.C.), Azienda Ospedaliero-Universitaria di Parma, Italy.
Correspondence to Annachiara Aldrovandi, MD, Division of Cardiology, Department of Heart and Lung, Azienda Ospedaliero-Universitaria di Parma, 43100 Parma, Italy. E-mail aldrovandiac{at}yahoo.it
Received April 22, 2008; accepted September 24, 2008.
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Abstract |
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Background— It is known that 9% to 31% of women and 4% to 14% of men with acute myocardial infarction have normal coronary arteries or nonsignificant coronary disease at angiography. These patients represent a diagnostic and therapeutic challenge. Multislice computed tomography (CT) can noninvasively identify the presence of coronary plaques even in the absence of significant coronary artery stenosis. This study evaluated the role of 64-slice CT, in comparison with coronary angiography, in detecting and characterizing coronary atherosclerosis in patients with acute myocardial infarction without significant coronary artery stenosis.
Methods and Results— Thirty consecutive patients with acute myocardial infarction but without significant coronary stenosis at coronary angiography underwent 64-slice CT. All coronary segments were quantitatively analyzed by means of coronary angiography (CA-QCA) and 64-slice CT (CT-QCA). Forty-seven (10.4%) of the 450 coronary segments were not evaluable by CT. The mean proximal reference diameters at CT-QCA and CA-QCA were, respectively, 2.88±0.75 mm and 2.65±0.9 mm; the overall correlation between CT-QCA and CA-QCA for quantification of reference diameter was rs=0.77; P<0.001. The mean percent stenosis was 14.4±8.0% at CT-QCA and 4.0±11.0% at CA-QCA and the correlation was rs=0.11; P=0.03. Overall CT-QCA showed the presence of 50 plaques, of which only 11 were detected by CA-QCA. CT-QCA identified 25 plaques in infarct-related coronary arteries. Positive remodeling was present in 38 of the 50 plaques (76%), with a higher prevalence in the coronary plaques not visualized by CA-QCA (82.1% versus 54.5%).
Conclusions— CT-QCA correlates well with CA-QCA in terms of coronary reference diameter analysis, but not stenosis quantification. Multislice CT can detect coronary atherosclerotic plaques in segments of nonstenotic coronary arteries that are underestimated by CA and may have an incremental diagnostic value for the diagnosis of acute myocardial infarction in patients without significant coronary stenosis at CA.
Key Words: angiography • coronary disease • imaging • myocardial infarction
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Introduction |
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Acute myocardial infarction (AMI) is attributable to coronary artery thrombosis, complicating an atherosclerotic coronary plaque usually in the presence of obstructive coronary artery disease. However, it is known that an AMI may occur even in patients without significant coronary artery stenosis at coronary angiography, because it may be due to the disruption of mildly stenotic "vulnerable" plaques, which are undetectable by conventional coronary angiography and may lead to thrombotic complications.1,2 It has been reported that 9% to 31% of women and 4% to 14% of men with AMI have a normal coronary angiogram.3–6 Coronary angiography is the reference method for assessing coronary artery disease, but, intravascular ultrasound and pathological studies indicate that it underestimates the extent of coronary atherosclerosis, especially in case of mild disease.7,8 Moreover, it is known that coronary angiography may not detect early stage atherosclerosis, because of the outward remodeling of atherosclerotic plaques.9 Intravascular ultrasound, which is the current standard of reference for the assessment of coronary plaque volume and morphology, can only be used to study coronary lesions in the proximal segments of major vessels.10
Clinical Perspective see p 205
Multislice computed tomography (MSCT) is an emerging technique that allows the noninvasive detection of coronary artery stenosis and atherosclerotic plaques. A number of studies have shown that MSCT can reliably quantify plaque volumes in vivo and identify the major morphological features of atherosclerotic lesions.11–13
The aim of this study was to evaluate the accuracy of quantitative 64-slice CT (CT-QCA) in identifying and quantifying atherosclerotic coronary lesions in comparison with quantitative coronary angiography (CA-QCA) in a population of patients with AMI without significant coronary artery stenosis.
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Methods |
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Patient Selection
We evaluated 30 consecutive AMI patients with normal coronary arteries or nonsignificant coronary stenosis at coronary angiography. Myocardial infarction was defined as (1) typical chest pain lasting >20 minutes; (2) persistent electrocardiographic changes; and (3) increased cardiac enzymes (Troponin I >99 percentile and creatine kinase MB (CK MB) levels to more than twice the upper normal limit).
The study exclusion criteria were (1) the presence of any coronary stenosis causing a 
50% reduction in lumen diameter, as evaluated by QCA; (2) a history of previous myocardial infarction or cardiomyopathy; (3) creatinine clearance <30 mL/min; and (4) an allergic reaction after contrast administration during coronary angiography. The localization of myocardial infarction was based on wall motion abnormalities detected by means of left ventriculography and transthoracic echocardiography. All of the patients gave their written informed consent to the study protocol, which was approved by the Institutional Review Board. The authors had full access to and take full responsibility for the integrity of the data. All authors have read and agree to the manuscript as written.
Study Protocol
Patients with AMI without significant coronary artery stenosis at coronary angiography were asked to undergo 64-slice CT within 3 days of coronary angiography.
Coronary Angiography and CA-QCA
Selective conventional coronary angiography was performed using standard techniques (Innova 2000 GE, General Electric). Standard multiple projections were recorded for left and right coronary arteries, and 0.2 mg intracoronary nitrates were administered before contrast injection for the projections used for QCA analysis. Left ventriculography was performed in the right oblique projection. The coronary angiograms were analyzed using an off-line computer-based software (MEDIS CMS version 6.0; MEDIS Imaging Systems) with an automatic edge-contour detection algorithm after standard and previously validated qualitative and quantitative parameters and definitions.14–16 The angiograms were analyzed by an independent and experienced operator unaware of the results of MSCT. The automatic edge detection program determines the vessel contours by assessing brightness along scan lines perpendicular to the vessel center. To achieve the best filling with contrast medium of the arterial segment, an image was selected from the second or third cardiac cycle after contrast administration. The software was calibrated using the outer diameter of the contrast-filled catheter. CT-QCA measurements were performed in all coronary segments, according to the 15-segment American Heart Association classification.17 For each coronary segment, an end-diastolic frame was selected in a perpendicular projection with minimal foreshortening and branch overlap. In the presence of a coronary lesion, the frame that best showed the stenosis at its most severe degree was selected for analysis. The following parameters were calculated: (1) proximal and distal reference vessel diameter; (2) minimal lumen diameter; and (3) percent diameter stenosis, calculated as 100 (1–minimal lumen diameter/reference vessel diameter).
MSCT Data Acquisition
All of the MSCT examinations were performed using a 64-slice CT scanner (Sensation 64 Cardiac, Siemens). First, an unenhanced scan was made using standardized parameters: 64 (32x2) slices per rotation, 0.6-mm detector collimation, gantry rotation time 330 ms, table feed 3.84 mm/rotation, tube voltage 120 kV, tube current 150 mAs, and prospective X-ray tube modulation. This was followed by the CT angiographic acquisition using the following parameters: 64 (32x2) number of slices per rotation, 0.6-mm detector collimation, gantry rotation time 330 ms, effective temporal resolution 165 ms, spatial resolution 0.4 mm3, tube voltage 120 kV, tube current 900 mAs. Sublingual nitroglycerin 0.3 mg were administered to all patients before the examination. When heart rate was >65 bpm, intravenous β-blocker (atenolol 5 to 10 mg) was administered. Between 80 and 100 mL of nonionic contrast material (Iomeron 400, Bracco, Milan, Italy) were administered in the antecubital vein at a flow rate of 4 to 6 mL/s followed by a 50-mL saline chaser. A bolus tracking technique was used to synchronize the arrival of the contrast in the coronary arteries, and the scan was started once contrast attenuation in a preselected region of interest in the ascending aorta reached a predefined threshold of +100 Hounsfield Units (HU). All of the images were acquired during an inspiratory breath hold of approximately 10 to 12 seconds, with the simultaneous recording of the patient’s ECG.
MSCT Data Analysis
The CT data set were analyzed by 2 independent and experienced readers unaware of the CA-QCA using an off-line workstation software package (Leonardo, Siemens Medical Solutions). To obtain optimal image quality, data sets of the reconstructed coronary vessels were created at least at 2 points of the cardiac cycle using a retrospective ECG gating algorithm (1 diastolic cardiac phase usually at –350 ms from the R waves and 1 end-systolic phase at +300 ms). In the presence of motion artifacts, additional reconstructions were made at different time points of the R–R interval.
The analysis was performed using multiplanar reconstruction of the original axial images of the coronary arteries. As for in the case of QCA, all coronary segments were analyzed according to the American Heart Association classification. Each coronary segment was delimited by identifiable side-branches in both image modalities.
Any discernible structure that could be assigned to the coronary artery wall, which had a CT density less than the contrast-enhanced coronary lumen and greater than the surrounding epicardial fat tissue and could be identified in at least 2 independent planes, was considered as a noncalcified coronary atherosclerotic plaque. Any structure with a density of 130 HU that could be visualized separately from the contrast-enhanced coronary lumen (because it was "embedded" within a noncalcified plaque or because its density was above the contrast-enhanced lumen), which could be assigned to the coronary artery wall and identified in at least 2 independent planes, was considered a calcified atherosclerotic plaque.12
The display settings used for the lumen and plaque analysis were manipulated to achieve optimal separation between the vessel lumen, wall, and surrounding tissue.
For each coronary segment, a cross-sectional image was created perpendicular to the centerline of the vessel, and the vessel area at the proximal tract and 5 mm from the proximal point of measurement was calculated, with the corresponding diameters. The mean of the diameters was used as the reference vessel diameter for comparison with QCA. In the presence of coronary plaque, the vessel area at the plaque site, the plaque area, the minimum lumen diameter, and the percent stenosis were determined as was the remodeling index. Positive vessel remodeling was defined as a vessel area at plaque site/reference vessel area ratio of >1.05. Plaque attenuation was measured and plaques were classified as calcified if HU >130, noncalcified if <130 HU, or mixed in the presence of areas with densities both >130 HU and <130 HU.
Statistical Analysis
The quantitative data are presented as mean values±SD. Spearman correlation coefficient and Bland–Altman analysis were used to compare the vessel diameter measurements and the CT and CA quantifications of lesion severity and a probability value <0.01 was considered significant. The continuous variables were compared by means of the t test, and the categorical variables were compared by means of the 
2 test. Statistical analysis was performed with SPSS version 12.0 (SPSS Inc).
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Results |
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Thirty patients were enrolled in the study and underwent MSCT after coronary angiography. Their clinical characteristics are shown in Table 1. MSCT was obtained 6.5±4.1 day after AMI and 4.6±3.8 days after coronary angiography. Forty-seven (10.4%) of the 450 coronary segments were not assessable by MSCT because of motion artifacts or small size (mean diameter, 1.25±0.50 mm); all of the nonassessable segments were distal coronary tracts or side branches (Table 2).
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Coronary Diameter Analysis
The mean proximal reference diameter was 2.65±0.90 mm at CA-QCA and 2.88±0.75 mm at CT-QCA. The overall correlation between the CT-QCA and CA-QCA for quantification of coronary diameters was rs=0.77; P<0.001 (Figure 1). CT-QCA tended to overestimate coronary size, with a systematic error of +8.6% (Figure 2). The mean minimal lumen diameter was 2.24±0.87 mm at CA-QCA and 2.69±0.87 mm at CT-QCA (rs=0.72; P<0.001).
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Coronary Stenosis Analysis
The mean percent stenosis was 14.4±8.0% at CA-QCA and 4.0±11.0% at CT-QCA (rs=0.11; P=0.03). In the coronary segments with atherosclerotic plaques, the mean percent stenosis was 34.0±11% at CT-QCA and 16.8±9% at CA-QCA (rs=0.11; P=0.37) (Figure 3). The mean plaque area at CT-QCA was 4.7±2.1 mm2. Mean Agatston coronary calcium score was 106.6±258.5 (range, 0 to 1325; median, 13.4). CT-QCA revealed the presence of 50 plaques (19 noncalcified, 12 mixed, and 19 calcified), of which only 11 were also detected by CA-QCA. In 4 patients, CT-QCA showed the complete absence of coronary plaques. The coronary plaque distribution is shown in Table 2. Positive remodeling was present in 38 lesions (76%; mean remodeling index, 1.2±0.3). In particular, positive remodeling was present in as many as 32 of the 39 plaques (82.1%) identified by CT but not visualized by CA-QCA, and in only 6 of the 11 plaques identified also by CA-QCA (54.5%).
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Infarct-Related Artery Analysis
CT-QCA identified 25 plaques in infarct-related arteries in 19 patients, of which 17 were located in proximal segments and 8 in midsegments, whereas CA-QCA identified 8 plaques in infarct-related arteries, with 6 plaques in proximal segments and 2 in midsegments. Fourteen plaques in infarct-related arteries were noncalcified, 5 were mixed, and 6 were calcified; in noninfarct-related arteries, 14 plaques were calcified, 5 were noncalcified, and 6 were mixed. The mean percent stenosis and remodeling index were not significantly different between infarct-related and noninfarct-related arteries plaques (1.20±0.20 versus 1.21±0.19; P=0.92; Table 3).
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Discussion |
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Our findings highlight the differences in evaluating coronary atherosclerosis between conventional coronary angiography and 64-slice CT. Although the 2 methods correlate well in terms of coronary diameter analysis, the correlation in detecting nonsignificant coronary artery stenosis is limited.
We found that 64-slice CT, given its almost isotropic voxel resolution, can accurately measure and quantitatively analyze coronary arteries, showing a good correlation with CA-QCA (rs=0.77). Only a few studies have systematically compared the accuracy of measuring coronary artery lumen diameters by means of CT and CA.18,19 A previous study by Cury et al19 showed only a moderate correlation (r=0.48) between 16-slice CT and QCA. The tendency of CT to overestimate coronary artery size is probably because of its more limited spatial resolution in comparison with CA, which does not allow an exact definition of outer vessel boundaries, and the use of image display settings focused on plaque detection.
In the case of nonsignificant coronary artery disease, there are substantial differences in coronary stenosis quantification between CT-QCA and CA-QCA. In our study, CT-QCA detected a significant number of coronary plaques that were not seen by CA-QCA and was capable of characterizing the composition of coronary plaques on the basis of their density, distinguishing between calcified and noncalcified plaques. Moreover, in segments with coronary plaques, mean percent stenosis calculated by CT-QCA was significantly higher in comparison to CA-QCA (34.0±11.0% versus 16.8±9.0%).
MSCT directly identifies coronary plaques, whereas conventional coronary angiography images the lumen contour of coronary vessels but does not provide any information concerning the vessel wall and plaque volume and may, therefore, underestimate the atherosclerotic burden and possible vulnerable plaques leading to AMI (Figures 4 and 5
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Intracoronary ultrasound is the "gold standard" for plaque detection and quantification of noncritically stenotic lesions, but it is invasive and time consuming and cannot be used extensively in all coronary arteries, but only in selected proximal coronary segments. Its clinical applicability is therefore usually limited to assessing a few coronary segments, whereas in the clinical setting of angiographically normal coronary arteries, an extensive analysis is needed. MSCT has the advantage of allowing a noninvasive evaluation of the complete coronary artery tree.
Preliminary studies have also shown that CT can assess the morphology and composition of culprit lesions in patients with acute coronary syndrome,20,21 which show a higher prevalence of noncalcified plaque and positive remodeling index.22,23
In our population of patients with AMI, CT-QCA revealed the presence of 25 plaques in infarct-related artery compared with only 8 plaques detected by CA-QCA; most of the coronary plaques in infarct-related arteries were noncalcified.
Moreover in our study, CT identified positive remodeling in a large number of plaques (76%), with a much higher prevalence in the group of plaques detected only by CT-QCA (82.1% versus 54.5%). This finding confirms that coronary angiography identifies mainly negatively remodeled plaques, and it has limitations in the evaluation of positive remodeled coronary plaques.
In 4 patients, CT-QCA showed the complete absence of any coronary plaque; a different diagnosis may therefore be hypothesized in this subgroup, such as possible myocarditis or embolic myocardial infarction.
In patients with AMI, demonstrating the absence of significant coronary stenosis at coronary angiography may challenge the diagnosis. However, it is known that the prognosis of these patients is similar to that of patients with AMI and significant coronary disease. The use of CT-CA may confirm the diagnosis of myocardial infarction on an atherosclerotic basis and therefore may support the use of optimal antithrombotic therapy and secondary prevention therapy.
In 7 patients, it was not possible to define the infarct-related artery clearly, because of the absence of wall motion abnormalities. Left ventriculography and transthoracic echocardiogram are the most widely used techniques to evaluate the localization and extent of myocardial infarction, but they have a limited sensitivity in identifying small areas of necrosis. Cardiac magnetic resonance with gadolinium enhancement can detect areas of myocardial fibrosis and differentiate in vivo myocardial scarring because of ischemic etiology or myocarditis, and it may have an incremental role over standard imaging techniques in this setting. MSCT is an attractive noninvasive method for the analysis of coronary plaques, but it is limited by radiation exposure, which vary from 15 to 21 mSV24 per examination, although the introduction of the prospective gating technique has the potential to reduce radiation exposure to 1.1 to 3.0 mSV.25
In conclusion, CT-CA may be a valuable noninvasive imaging method of assessing overall plaque burden and may complement coronary angiography in patients with AMI without significant coronary stenosis, although it is still limited in identifying culprit lesions in this population.
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Acknowledgments |
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Disclosures
None.
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Related Article
CLINICAL PERSPECTIVE
Almost 15% of patients with acute myocardial infarction have normal or near normal coronary arteries at coronary angiography. The absence of significant coronary stenosis may challenge the diagnosis; however, coronary atherosclerosis may be present even in angiographically normal coronary arteries, because of outward remodeling of coronary arteries in the presence of mild atherosclerotic plaques not affecting the coronary lumen, and myocardial infarction may occur because of disruption of only mildly stenotic plaque. Multislice computed tomography is a new noninvasive imaging technique that allows detection of atherosclerotic coronary plaques. In our study, we demonstrate that in patients with myocardial infarction without significant coronary stenosis, multislice computed tomography may evaluate atherosclerotic burden and detect a significant number of coronary plaques not seen by coronary angiography. These findings may support the use of optimal antithrombotic and secondary prevention therapy to reduce the risk of future events.
Circ Cardiovasc Imaging 2008 1: 205-211.
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