Cardiopulmonar y Imaging • Original Research Nagao et al. MDCT of Myocardial Ischemia in ACS Cardiopulmonary Imaging Original Research

Myocardial Ischemia in Acute Coronary Syndrome: Assessment Using 64-MDCT Michinobu Nagao1 Hiroshi Matsuoka2 Hideo Kawakami2 Hiroshi Higashino1 Teruhito Mochizuki1 Masahiko Uemura3 Susumu Shigemi2 Nagao M, Matsuoka H, Kawakami H, et al.

OBJECTIVE. We investigated the performance of 64-MDCT myocardial imaging in assessing myocardial ischemia in acute coronary syndrome (ACS). MATERIALS AND METHODS. Cardiac CT was performed in 35 patients with ACS: 24 patients with acute myocardial infarction (AMI) and 11 patients with unstable angina pectoris (UAP). We reconstructed 2D myocardial images at diastolic and systolic phases using the same raw data as those used for coronary CT angiography. The CT number in the myocardium was used as an estimate of ischemia. The myocardium was shown using a color scale that depicts faint low-density areas more clearly than gray scale. We evaluated the variations in myocardial enhancement during the cardiac cycle in the territory of the culprit lesion. In addition, we classified patients on the basis of the transmurality of myocardial enhancement and examined whether this feature correlates with myocardial damage. RESULTS. Myocardial imaging at systole showed myocardial hypoenhancement in territories of the culprit lesion in 91% of patients with ACS, 96% of patients with AMI, and 75% of patients with UAP. The hypoenhancement areas at systole tended to be more extensive than those at diastole. The transmural extent of hypoenhancement at systole correlated with myocardial damage, which was shown by myocardial biomarkers. CONCLUSION. CT myocardial imaging can be used to assess myocardial ischemia in the appropriate region of ACS with high sensitivity.

M

Keywords: acute coronary syndrome, MDCT, myocardial ischemia DOI:10.2214/AJR.08.1965 Received October 16, 2008; accepted after revision March 24, 2009. 1 Department of Radiology, Ehime University Graduate School of Medicine, Shitsukawa, Toon-city, Ehime 791-0295, Japan. Address correspondence to M. Nagao ([email protected]). 2 Department of Cardiology, Prefectural Ehime Imabari Hospital, Ehime, Japan. 3 Department of Radiology, Prefectural Ehime Imabari Hospital, Ehime, Japan.

AJR 2009; 193:1097–1106 0361–803X/09/1934–1097 © American Roentgen Ray Society

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DCT provides high-quality noninvasive images of the heart and coronary vasculature. The current-generation 64-MDCT scanners allow rapid scanning of the cardiac anatomy, require minimal patient cooperation, and have improved image quality and high diagnostic accuracy for the detection of coronary artery stenosis [1–3]. In recent studies, investigators have reported that the assessment of coronary plaque and significant stenosis using coronary 64-MDCT had a high accuracy for ruling out acute coronary syndrome (ACS) in patients with acute chest pain and may be useful for improving early triage [4, 5]. However, we acknowledge that the inability to assess coronary artery stenosis in the presence of severe calcification is a limitation of coronary CT angiography even when 64MDCT is used [1–3]; therefore, coronary CT angiography cannot detect a culprit coronary lesion in a few cases of ACS [6, 7]. Early assessment of myocardial ischemia is necessary to formulate the effective thera-

peutic treatments for ACS. In particular, if it is unclear whether a culprit lesion is present, we verify myocardial perfusion status or myocardial viability using myocardial perfusion scintigraphy and contrast-enhanced MRI [8, 9]. In recent studies, researchers have reported that late myocardial enhancement on 64-MDCT enables the noninvasive assessment of myocardial viability in re­ perfused acute myocardial infarction (AMI) [10–13]. However, late CT requires added radiation and the injection of additional contrast medium. In one of our previous studies, we found that 64-MDCT myocardial imaging enabled the assessment of myocardial enhancement during the cardiac cycle and showed a characteristic enhancement pattern for ischemia. Myocardial imaging during the first pass of contrast medium has potential as a noninvasive method for detecting myocardial ischemia at rest [14]. Accordingly, for the current study, we investigated the performance of 64-MDCT in assessing myocardial ischemia in ACS.

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Nagao et al. Materials and Methods Our study sample was composed of 35 patients with ACS (24 men and 11 women; age range, 33– 90 years; mean age, 67 years) who underwent imaging during the period from March 2006 to June 2008. The study was approved by the institutional review board and the ethics committee, and all patients consented to participate voluntarily in the study protocol.

Patients Preinterventional cardiac CT was performed in all 35 patients with ACS (ST-segment elevation myocardial infarction [STEMI], n = 21; non-STsegment elevation myocardial infarction [NSTEMI], n = 3; and unstable angina pectoris [UAP], n = 11) within 48 hours of the onset of chest pain (within 24 hours of onset in 24 patients) to identify and examine the responsible coronary lesion. Table 1 lists the patients’ characteristics. The patients diagnosed with STEMI, NSTEMI, and UAP were included. A 12-lead ECG examination was performed, and the cardiac-specific troponin level was tested in all patients admitted to the emergency department with chest discomfort. Patients with ischemic discomfort, ST-segment elevation on ECG, and elevated troponin level were defined as STEMI. In symptomatic patients with ST-segment elevation detected on 12-lead ECG, a reperfusion intervention was initiated as soon as possible and was not contingent on a biomarker assay result [15]; such patients were excluded from the current study. On the other hand, STEMI patients brought to the hospital more than 24 hours after the onset of chest pain who were free of symptoms were enrolled in the study. A total of 87 patients with ACS were admitted to our hospital during the study period. In 50 of the 87 patients, an emergent percutaneous coronary intervention was performed; they were excluded from the study. Patients with ischemic discomfort without STsegment elevation on ECG but with an elevated troponin level were defined as having NSTEMI. Class 3 or 4 patients, as classified by the Canadian Cardiovascular Society, without ST-segment elevation on ECG and without an elevated troponin level who presented with ischemic discomfort were defined as having UAP. Patients with NSTEMI and UAP were classified into high-, intermediate-, and low-risk groups using the 2002 guidelines for UAP and NSTEMI established by the American College Cardiology and American Heart Association (AHA) [16]. High-risk patients admitted within 24 hours after the onset of chest discomfort were excluded because these patients needed to undergo early coronary angiography and percutaneous coronary intervention. Highrisk patients admitted 24 hours after the onset of

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chest pain and intermediate- and low-risk patients were included in the current study. All enrolled ACS patients underwent coronary angiography within 7 days from the onset of chest discomfort (mean, 4.1 days). Coronary angiography images were obtained using 5-French catheters on an angiography system (Allura Xper FD10/10, Philips Healthcare). The acquisition parameters were as follows: 15 frames per second and manual injection of contrast medium (2.5 mL/s). The angiograms were saved to CD-ROM and were interpreted by two cardiologists with 25 and 16 years of clinical practice, respectively, who were unaware of the cardiac CT results. Identification of the coronary tree was based on the 15-segment AHA model [17]. Quantitative angiographic analysis was performed on the most severe, well-defined lesion in each segment using a previously described digital caliper method [18]. In the case of multiple lesions in a given segment, the segment was classified by the worst lesion. In the case of multiple abnormal segments per artery, the vessel was classified by the worst segment. Significant stenosis was defined as a reduction in diameter of more than 75%. The culprit lesion was identified on coronary angiography, its location of asynergy by ECG, and the location of ST-segment elevation in STEMI by the two experienced cardiologists. Patients with single-vessel disease and those with multivessel disease were enrolled in this study and underwent CT examination before percutaneous coronary intervention. In addition, we excluded patients with evidence of hemodynamic or clinical instability (i.e., systolic blood pressure < 80 mm Hg, atrial or ventricular arrhythmia), patients with a known allergy to iodinated contrast agents, and patients with a serum creatinine level of more than 1.3 mg/dL.

Biomarker Analysis Levels of creatine kinase (CK) and CK–myocardial bound (CK-MB) isoenzyme were determined on admission, at 3-hour intervals during the first 24 hours of admission, and if reinfarction was suspected. In addition, a qualitative assay for cardiac-specific troponin T (detection limit = 0.1 ng/ mL) was simultaneously performed. A troponin T level of more than 0.1 ng/mL was defined as positive. In patients who had a negative troponin T result within 6 hours of symptom onset, the test was repeated 8–12 hours after the first test.

Cardiac CT Protocol A 64-MDCT scanner (LightSpeed VCT 64, GE Healthcare) was used with the following scanning parameters: retrospective ECG gating; 912 channel detectors along the gantry and 64 channel detectors along the z-axis; tube voltage, 120 kV; tube

TABLE 1:  Demographic and Clinical Characteristics of the 35 Patients Characteristic

Value

Age, y Mean ± SD

67 ± 14

Sex, no. of patients M

24

F

11

Diagnosis, no. of patients ST-segment elevation MI

21

Non-ST-segment elevation myocardial infarction UAP

3 11

Diabetes, no. (%) of patients

17 (49)

Hypertension , no. (%) of patients

19 (54)

Hyperlipidemia, no. (%) of patients

18 (51)

Smoking, no. (%) of patients

21 (60)

Obesity, no. (%) of patients

10 (29)

Location of culprit lesion, no. of patients Left anterior descending artery

19

Left circumflex artery

5

Right coronary artery

8

Unclear (UAP patients)

3

Note— MI = myocardial ischemia, UAP = unstable angina pectoris.

current, 550–750 mA depending on patient size; scanning field of view, 50 cm; gantry rotation, 0.35 second per rotation; matrix, 512 × 512; and slice width, 0.625 mm. The helical pitch was based on the patient’s heart rate and ranged from 0.18 to 0.24. ECG-triggered dose modulation was used. A single oral dose of 25–50 mg of atenolol was administered 4 hours before MDCT if the patient’s heart rate was > 65 beats per minute (bpm). In all patients, a heart rate of less than 75 bpm was controlled by atenolol. We did not additionally medicate if the heart rate did not decrease sufficiently. Patients were scanned in the supine position; in preparation for scanning, patients received 3 L/ min of O2 inhaled through a mask and were given sublingual nitroglycerin (0.6 mg [Nitropen tablet, Nihon Kayaku]). The scanning delay was calculated using a bolus injection of nonionic contrast medium (320 mg I/mL, 4 mL/s × 10 mL of ioversol 320 [Optiray, Mallinckrodt Imaging]) to monitor the proximal part of the ascending aorta, which was defined as the region of interest. The true scan was obtained with an IV injection of 40– 60 mL, depending on the patient’s body weight, of contrast medium at a rate of 4 mL/s.

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MDCT of Myocardial Ischemia in ACS CT Myocardial Imaging Transaxial images were reconstructed using a slice thickness of 0.625 mm and 0.4-mm increments to optimize the position of the reconstruction window by increments of 5% of the cardiac cycle. The volume data were transferred to a dedicated workstation (Advantage Workstation 4.2, GE Healthcare) for postprocessing. A commercially available program (Cardiac IQ in Advantage Windows 4.2, GE Healthcare) was used to create long-axis and short-axis images through reconstruction with R-R intervals of 40–55% and using 70–85% of the cardiac cycle to minimize motion artifacts. Most cardiac images were selected with R-R intervals of 40% and 75% corresponding to end-systole and mid to late diastole, respectively. Assignment of the left ventricular segments was based on the American Society of Nuclear Cardiology and AHA statement [19]. We reconstructed horizontal long-axis, vertical long-axis, and short-axis myocardial images in end-diastolic and end-systolic phases using the same raw data as those used for coronary CT angiography. In a previous study [14], CT myocardial imaging that used a color scale at rest showed a characteristic enhancement pattern for ischemia when the CT number (in Hounsfield units [HU]) in the myocardium was used as an estimate of myocardial ischemia. Accordingly, the color scales were classified into five steps using the CT number: 20–40 HU, blue; 40–60 HU, light green; 60–80 HU, yellow; 80–100 HU, orange; and 100–140 HU, red. The warm colors (yellow, orange, and red) represent normal enhancement areas with high CT numbers, whereas the cold colors (blue and light green) represent hypoenhancement areas with low CT numbers. We identified blue areas as definite hypoenhancement areas and yellow, orange, and red areas as normal enhancement. The light green areas adjacent to blue areas were considered as border zones between normal and hypoenhancement. We evaluated variations in myocardial enhancement at systole and diastole for territories depicted as a culprit lesion by coronary angiography. In addition, on the basis of the transmurality of the hypoenhancement area at systole, patients were classified into one of three groups: Group 1 consisted of patients with an area of transmural hypoenhancement, group 2 consisted of patients with an area of localized subendocardial hypoenhancement, and group 3 consisted of patients with normal enhancement. We identified the transmural hypoenhancement as cold-colored areas diffusely distributed throughout the endocardium and epicardium, and the subendocardial hypoenhancement as cold-colored areas localized in the endocardium of less than half of myocardial

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thickness. Also, we identified a gradient of hyperenhancement in the endocardial zone and hypoenhancement in the epicardial zone as normal transmural enhancement patterns. One slice of CT myocardial imaging offers a view of systolic and diastolic phases in the same myocardial section. We evaluated myocardial enhancement of the entire short-axis, ventricle long-axis, and horizontal long-axis slices at intervals of 0.6 mm throughout the whole left ventricle. All patient-identifying information on the CT myocardial images was obscured, and the images were then randomized. Together, two cardiologists with 25 and 16 years of clinical practice and two radiologists with 18 and 13 years of clinical practice visually judged the myocardial enhancement. No information was revealed regarding patient treatment, and disagreements were solved by consensus.

Analysis of Coronary CT Angiography Coronary CT angiograms were analyzed on a workstation (Advantage Workstation 4.2) using the same data as CT myocardial imaging. Scans were analyzed by consensus of two observers unaware of the clinical data and blinded to the results of coronary angiography. A previously described 15-segment AHA model of the coronary tree was used [17]. Each identified lesion was examined using maximum-intensity-projection and multiplanar reconstruction techniques along multiple longitudinal and transverse axes. Lesions were classified by the maximal luminal diameter stenosis seen in any plane. Quantitative CT angiographic analysis was performed on the most severe well-defined lesion in each segment using a previously described digital caliper method [18]. In the case of multiple lesions in a given segment, the segment was classified by the worst lesion. In the case of multiple abnormal segments per artery, the vessel was classified by the worst segment. Significant stenosis was defined as a reduction in diameter of more than 75%.

Statistical Analysis We compared differences in the peak CK and CK-MB values and the number of stenosed coronary arteries, the value being classified, between groups on the basis of the transmurality of hypoenhancement using the Mann-Whitney U test. A probability value of less than 0.05 was considered statistically significant. We compared differences in the incidence of positive troponin results and ST elevation between groups; the results were classified on the basis of the transmurality of hypoenhancement using a chi-square test. A probability value of less than 0.05 was considered statistically significant.

Results Coronary Angiography The culprit lesion of coronary arteries was identified by coronary angiography in 32 of 35 patients with ACS (AMI, 24 patients; UAP, eight patients). The culprit lesions were located in the left anterior descending (LAD) coronary artery (n = 19), left circumflex (LCX) coronary artery (n = 5), and right coronary artery (RCA, n = 8; Table 1). Coronary angiography detected 60 significant stenoses (RCA, n = 21; LAD, n = 26; LCX, n = 13) including the culprit lesions in two vessels of 13 patients and three vessels of six patients. In three UAP patients, the culprit lesion was unclear on coronary angiography because of multiple stenosed coronary arteries. Coronary CT Angiography Coronary CT angiography detected significant coronary stenoses in all patients. The significant coronary stenosis depicted by CT angiography matched the culprit lesions depicted by coronary angiography in 29 of 32 patients with ACS (91%), 21 of 24 patients with AMI (88%), and eight of eight patients with UAP (100%). Coronary CT angiography could not detect a significant stenosis at the culprit lesion of three patients with AMI. In those three patients, coronary CT angiography pointed out significant stenoses in coronary arteries different from those with culprit lesions. Detectability of Myocardial Damage by CT Myocardial Images CT myocardial imaging showed myocardial hypoenhancement at systole in 31 of 35 patients (89%) and at diastole in 28 of 35 patients (80%) with ACS. CT myocardial imaging at systole showed hypoenhancement areas in the territory of the culprit lesion identified by coronary angiography in 29 of 32 patients with ACS (91%), 23 of 24 patients with AMI (96%), and six of eight patients with UAP (75%). In most cases of AMI, the hypoenhancement areas were distributed throughout the subendocardium and transmural myocardium. The hypoenhancement areas at systole tended to be more extensive than those at diastole (Fig. 1). In most cases of UAP, the hypoenhancement areas were localized in the subendocardium in systole and had disappeared in diastole (Fig. 2). Myocardial imaging could not detect a hypoenhancement area in two patients with UAP. The culprit lesions for those

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Fig. 1—59-year-old man with acute myocardial infarction and culprit lesion of left anterior descending (LAD) coronary artery, segment 7. A, Coronary angiography image shows significant stenosis at midportion of LAD branch (arrowhead). B, Curved multiplanar reformatted image of left anterior descending branch from coronary CT angiography shows significant stenosis (arrowhead) and area of plaque ulceration at same site as A. C and D, Vertical long-axis slices of CT myocardial images in systole show hypoenhancement areas (arrowheads, C) throughout subendocardium and epicardium in anterior wall. E and F, CT myocardial images at same slice positions as C and D in diastole show significantly reduced hypoenhancement areas at same site as C and D. G and H, Short-axis slices of CT myocardial images in systole show transmural hypoenhancement areas (arrowheads, G) in anteroseptal wall. (Fig. 1 continues on next page)

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MDCT of Myocardial Ischemia in ACS Fig. 1 (continued)—59-year-old man with acute myocardial infarction and culprit lesion of left anterior descending (LAD) coronary artery, segment 7. I and J, CT myocardial images at same slice positions as G and H in diastole show hypoenhancement areas are not visible at same site. K, Three-dimensional fused image of coronary CT angiography and myocardium with volume rendering shows broad hypoenhancement areas in anteroseptal wall (arrowheads). L, Three-dimensional fused image of coronary CT angiography and myocardium with volume rendering in diastole shows significant stenosis at midportion of LAD branch (arrowhead) and reduced hypoenhancement area at anteroseptal wall.

two patients were in the RCA in one patient and the LAD in the other. Coronary angiography detected a total of 60 significant stenosed coronary arteries; the total includes the culprit lesion. The use of an area of hypoenhancement on CT myocardial imaging to distinguish territories with and without stenosed coronary arteries yielded a sensitivity of 70% (42/60), specificity of 96% (43/45), positive predictive value of 95% (42/44), and negative predictive value of 70% (43/61). A hypoenhancement area was seen in 24 of 26 segments in stenosed LAD territories (92%), in nine of 13 segments in stenosed LCX territories (69%), and in nine of 21 segments in stenosed RCA territories (43%). The RCA territory had more false-negative segments than did the LAD and LCX territories. Two false-positive segments were in RCA territories.

I

J

K

L

group 1. The diastolic image in all patients of group 3 showed normal enhancement. Troponin results were positive in 14 of the 16 patients in group 1 (88%), 10 of 15 in group 2 (67%), and 0 of four in group 3 (0%) (Table 2). The incidence of a positive troponin level was significantly greater for group 1 than group 3 (p < 0.05). There was no significant difference between groups 1 and 2 or between groups 2 and 3. The aver-

age peak CK value for group 1 was significantly greater than those for groups 2 (p = 0.002) and 3 (p = 0.005). The average peak CK-MB value for group 1 was significantly greater than those for groups 2 (p = 0.004) and 3 (p = 0.037) (Table 2). There was no significant difference in the average peak CK and CK-MB values between groups 2 and 3. There was no significant difference in the number of coronary arteries with a significant

TABLE 2:  Myocardial Enhancement Pattern and Characteristics of Myocardial Damage Characteristic

Group 1

Group 2

Group 3

Hypoenhancement at systole, no. of patients Transmural

16

Subendocardial

15

Normal

4

Hypoenhancement at diastole, no. of patients

Relationship Between Myocardial Enhancement Pattern and Myocardial Damage On the basis of the transmurality of the hypoenhancement area at systole, patients were classified into one of three groups. There were 16 patients in group 1, 15 patients in group 2, and four patients in group 3 (Table 2). The diastolic image showed a localized subendocardial hypoenhancement or normal enhancement in 27 of 31 patients (87%) in groups 1 and 2. There were four patients with transmural hypoenhancement areas at diastole in

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Transmural

4

Subendocardial or normal

12

15

1.7

1.9

1.8

Normal Mean no. of disease vessels

4

ST elevation of ECG, no. (%) of patients

14 (88)

11 (73)

2 (50)

Positive troponin T result, no. (%) of patients

14 (88)a

10 (67)

0 (0)

Peak creatine kinase (IU/L)

2,256b

621

259

154b

36

18

Peak creatine kinase, myocardial bound (IU/L)

aThe value for group 1 is significantly greater than that for group 3.

bThe value for group 1 is significantly greater than those for groups 2 and 3.

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A

B

D

E

F

G

H

I

stenosis between any two of the three groups. There also was no significant difference in the incidence of ST elevation on ECG between any two of the three groups. On the basis of the transmurality of the hypoenhancement area at diastole, patients

were divided into one of three groups using the same classification as used in systole. There were four patients in group 1′, 22 patients in group 2′, and nine patients in group 3′. Troponin-positive patients comprised four of the four patients in group 1′ (100%), 17 of

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C Fig. 2—60-year-old man with unstable angina pectoris and culprit lesion of left anterior descending (LAD) coronary artery, segment 7. A–C, Coronary angiography images show significant stenoses at midportion of LAD branch (arrowhead, A), proximal portion of right coronary artery (arrowhead, B), and proximal portion of left circumflex branch (arrowhead, C). D and E, Vertical long-axis slices of CT myocardial images in systole show localized hypoenhancement area in subendocardium of anterior wall (arrowhead, D). F and G, CT myocardial images at same slice positions in diastole show hypoenhancement areas at same site as D and E are not visible. H and I, Short-axis slices of CT myocardial images in systole show localized subendocardial hypoenhancement areas in anteroseptal (arrow, H), lateral, and inferior (arrowheads) wall. (Fig. 2 continues on next page)

22 in group 2′ (77%), and two of nine in group 3′ (22%). There was no significant difference in the incidence of troponin-positive results between any two of the three groups. The average peak CK values were 1,682, 1,153, and 1,531 IU/L for groups 1′, 2′, and 3′,

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MDCT of Myocardial Ischemia in ACS Fig. 2 (continued)—60-year-old man with unstable angina pectoris and culprit lesion of left anterior descending (LAD) coronary artery, segment 7. J and K, CT myocardial images at same slice positions in diastole show normal enhancement areas at same sites as H and I.

respectively. The average peak CK-MB values were 129, 72, and 101 IU/L for groups 1′, 2′, and 3′, respectively. There was no significant difference in the average peak CK and CK-MB values between any two of the three groups. CT Myocardial Images in Patients With an Unclear Culprit Lesion Coronary angiography could detect the culprit lesion in the three patients with UAP. Of those three patients, CT myocardial images showed subendocardial hypoenhancement areas in the RCA and LCX territories of one patient (Fig. 3) and subendocardial hypoenhancement in the LAD territory of another patient. In the third patient, CT myocardial images showed normal enhancement in the territories of stenosed coronary arteries. Discussion We introduced a method that uses highspatial-resolution myocardial images with contrast-enhanced 64-MDCT, which enables visualization of the transmural myocardial enhancement. CT myocardial imaging can detect myocardial ischemia in ACS with high accuracy and can show the characteristic myocardial enhancement pattern for AMI and UAP during the resting cardiac cycle. The CT images of ischemic myocardium characterized the hypoenhancement area throughout the subendocardium and transmural myocardium in AMI and the localized hypoenhancement area in the subendocardium in UAP. The hypoenhancement area in systole tended to be more extensive than that in diastole in both AMI and UAP. This characteristic CT feature was more visible in the systolic image than in the diastolic image. The detectability of myocardial hypoenhancement in AMI was higher than that in UAP. In previous studies, investigators have reported that the transmural enhancement patterns on contrast-enhanced MRI provide re-

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J

K

liable information about myocardial viability in AMI [8, 9]. Our study results indicate that the transmural hypoenhancement caused by reduced myocardial perfusion correlated with myocardial damage in ACS. In particular, transmural hypoenhancement on systolic images correlated with the severity of myocardial damage expressed by troponin-positive results and CK and CK-MB values. Also, all the patients with normal enhancement at systole were troponin-negative and did not progress to myocardial infarction. On the other hand, the transmurality on diastolic images may be related to the incidence of positive troponin results, but transmurality was not correlated with CK and CK-MB values. We always used the diastolic data to reconstruct coronary CT angiography because of fewer motion artifacts in diastole [1–3]. However, the results of this study suggest that systolic imaging is more useful for assessing myocardial ischemia in ACS than is diastolic imaging. Epicardial coronary flow dominates during diastole. Cardiac contraction predominantly affects subendocardial vessels and impedes subendocardial flow more than subepicardial flow regardless of left ventricular pressure [20]. The decrease in pressure caused by a coronary stenosis results in a greater decrease in the subendocardial arteriole diameter than that of the subepicardial arterioles [21]. Consequently, systolic subendocardial flow in stenosed coronary territories shows a greater decrease than diastolic subendocardial flow. Furthermore, the subendocardium is the area of the left ventricle that is most vulnerable to the effects of hypoperfusion and ischemia [20, 22]. Microvascular resistance is affected by ischemia, with the effects most prominent in the subendocardium during systole and in the subepicardium during diastole [22, 23]. The capillary micro­ vessels showed a larger phasic change in microvascular resistance, which may function to maintain the capillary patency during sys-

tole [24]. Consequently, the increase in subendocardial resistance induced by ischemia causes a decrease in the capacitance of microvessels during systole. Systolic-dominant hypoenhancement in most territories of culprit lesions in ACS may be caused by this physiologic phenomenon. Coronary angiography could detect the culprit lesion in three patients with UAP because of the multiple stenosed lesions of their coronary arteries. In two of the three patients, CT myocardial images showed hypoenhancement areas in the territory of the specific coronary artery, thereby allowing us to identify the culprit coronary lesions in those two patients. Thus, we detected the culprit lesion in eight of 11 patients with UAP (73%) using CT myocardial imaging. CT myocardial imaging data are obtained from the same raw data as ordinary coronary CT angiography, and use of these data avoids the additional radiation exposure or pharmacologic stress associated with additional scanning. In clinical workflow, CT myocardial imaging is useful for formulating effective treatment options for UAP with an unclear culprit lesion and multiple coronary stenoses. Furthermore, CT myocardial imaging aids in the diagnosis of ischemia in atypical ACS patients who show ST depression on ECG, have a negative troponin result, and show atypical symptoms. Coronary CT angiography could not detect significant stenoses at the culprit lesion in the three patients with AMI. In those three patients, CT myocardial imaging showed hypoenhancement areas in the territories of the culprit lesions depicted by coronary angiography. In 24 patients with AMI, matching the culprit lesion detected by CT myocardial imaging with coronary angiography (96%) was superior to that of coronary CT angiography and coronary angiography (88%). Myocardial imaging has the potential to address the limitation of coronary CT angiography and to elevate the diagnostic accuracy for identifying the responsible coronary le-

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sion in AMI. Furthermore, as indicated in Figures 1D and 3C, a new concept of image fusion of both the coronary tree and the myocardium allows improved orientation ability for views of myocardial ischemia and the responsible coronary region in AMI and UAP. Three-dimensional fused imaging is better able to show the extent of hypoenhancement areas related to the culprit coronary lesion than can 2D myocardial imaging; this capability is particularly pronounced in patients with multivessel disease.

We acknowledge the following limitations of our methods. First, our sample size is relatively small. Second, motion artifacts caused by myocardial wall movement occasionally occurred, especially in systole. Horizontal bands caused by motion artifacts were sometimes seen on cardiac CT and decreased the intensity in the myocardium, especially in the inferior walls of the short-axis cardiac images. Third, the myocardial intensity in the cranial portions of the left ventricle tended to be high-

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Fig. 3—79-year-old woman with unstable angina pectoris and three-vessel disease. A, Coronary angiography image shows total occlusion at proximal left anterior descending (LAD) branch (arrowhead) and severe stenosis at proximal left circumflex branch. B, Coronary angiography image shows severe stenosis at proximal portion (arrowhead) and total occlusion of distal portion and collateral vessels to distal LAD branch. Coronary angiography could not clear culprit lesion because there were critical stenoses in three vessels. C and D, Short-axis slices of CT myocardial images in systole show subendocardial hypoenhancement areas in basal anterolateral (arrows) and inferolateral (arrowheads) wall. E and F, CT myocardial images at same slice positions in diastole show normal enhancement in anterolateral and residual hypoenhancement areas in inferolateral wall (arrowhead, E). Fixed hypoenhancement area in inferolateral wall suggests subendocardial infarction. (Fig. 3 continues on next page)

er than those in the caudal portions. Depending on the temporal resolution of the scanner, there was usually a contrast enhance delay when imaging the more caudal portion of the heart. This delay could account for the numerous false-negative and false-positive segments in the RCA territories. We often used long-axis myocardial images for assessing hypoenhancement in the inferior wall because the long-axis myocardial images were rarely affected by the banding artifact. Furthermore,

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MDCT of Myocardial Ischemia in ACS Fig. 3 (continued)—79-year-old woman with unstable angina pectoris and three-vessel disease. G and H, Three-dimensional fused images of coronary arteries and myocardium with volume rendering at systole (G) and diastole (H) show systolic hypoenhancement and diastolic normal enhancement in territory of left circumflex branch (arrowheads, G). This appearance suggests myocardial ischemia related to left circumflex branch.

we used specific cardiac filters to reduce the banding artifact and noise in the myocardium when reconstructing myocardial imaging from the raw data. Consequently, we could perform myocardial imaging with a high signal-to-noise ratio even if we used a lower radiation dose. Attempting to lower radiation exposure during CT is of major importance because of radiation exposure hazards and concerns. We used an ECG dose modulation protocol to minimize radiation exposure during cardiac CT in the current study. CT images were reconstructed at 40%, 45%, 50%, 70%, 75%, and 80% of the R-R interval of the cardiac cycle using retrospective ECG gating. ECG dose modulation changed the radiation dose to the maximum only at 75% of the R-R interval and reduced by half the dose at other phases when the patient’s body weight was less than 70 kg. ECG modulation changed the radiation dose to the maximum at 70% to 40% of the R-R interval and reduced by half the dose at 45% and 50% when the patient’s body weight was more than 70 kg. Decreasing the signal-to-noise ratio by reducing the radiation dose did not interfere with the assessment of systolic perfusion. Moreover, we used a small field of view for cardiac scanning to obtain high spatial resolution even when using a lower radiation dose. In conclusion, 64-MDCT myocardial imaging can detect myocardial ischemia in ACS with high sensitivity and can show the characteristic myocardial enhancement patterns for AMI and UAP. The transmural extent of hypoenhancement on systolic myocardial imaging correlated with the degree of myocardial damage in ACS.

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