Is There a Relation between Non-Calcifying Coronary

Original Research Cardiology 2008;110:241–248 DOI: 10.1159/000112407

Received: June 7, 2007 Accepted after revision: July 13, 2007 Published online: December 12, 2007

Is There a Relation between Non-Calcifying Coronary Plaques and Acute Coronary Syndromes? A Retrospective Study Using Multislice Computed Tomography Gudrun Feuchtner a Thomas Postel b Franz Weidinger b Matthias Frick b Hannes Alber b Wolfgang Dichtl b Daniel Jodocy a Ammar Mallouhi a Otmar Pachinger b Dieter zur Nedden a Guy J. Friedrich b Clinical Departments of a Radiology II and b Cardiology, Innsbruck Medical University, Innsbruck , Austria

Abstract Objectives: The purpose of this study was to assess whether different coronary plaque types as classified by multislice computed tomography (CT) are retrospectively correlated with acute coronary syndromes (ACS) in an unselected study population. Methods: Sixty-three consecutive patients were examined with 16-slice CT coronary angiography. Coronary plaque types were classified as calcifying type 1, mixed (calcifying 1 non-calcifying) type 2, mixed (non-calcifying 1 calcifying) type 3, and non-calcifying type 4. Patients who had an ACS within 17 days were included. All patients underwent invasive coronary angiography. Results: Fifty-eight patients (92%) had coronary plaques evaluated by CT: 18 type 1 (31%), 10 type 2 (17%), 16 type 3 (28%) and 14 type 4 (24%). The presence of a non-calcifying plaque component (types 2–4; 40 of 63 patients, 63%) was correlated with ACS (n = 15; 24%) (p ! 0.001). Only type 3 was significantly correlated with ACS (p = 0.01), but plaque types 2 and 4 were not. The diagnostic accuracy of CT for detection of stenosis 150% in proximal

© 2007 S. Karger AG, Basel 0008–6312/08/1104–0241$24.50/0 Fax +41 61 306 12 34 E-Mail [email protected] www.karger.com

Accessible online at: www.karger.com/crd

segments was: sensitivity 98%, specificity 90%, negative predictive value 97%, positive predictive value 97% per patient. Conclusions: Mixed calcifying/non-calcifying plaques with a predominantly non-calcifying component (type 3) as classified by multislice CT are retrospectively correlated with ACS. Copyright © 2007 S. Karger AG, Basel

Introduction

The value of multislice computed tomography (CT) coronary angiography in the clinical work-up of patients with suspected coronary artery disease is currently under investigation. Sixteen-slice CT coronary angiography has already shown promising results for the detection of coronary artery stenosis 150% in proximal coronary segments [1–4]. Recently published studies using a new 64slice CT technology have reported an improved diagnostic accuracy for the detection of coronary stenosis 150% [5, 6]. Multislice CT coronary angiography also allows an assessment of coronary plaque composition: non-calcifying plaque can be differentiated from calcifying plaque [7–10] based on CT densities.

Gudrun M. Feuchtner, MD Clinical Department of Radiology II, Innsbruck Medical University Anichstr. 35, AT–6020 Innsbruck (Austria) Tel. +43 512 504 81 898, Fax +43 512 504 24 029 E-Mail [email protected]

Downloaded by: Medical University Vienna - University Library 149.148.252.245 - 8/13/2016 9:44:02 AM

Key Words Multislice computed tomography ⴢ Coronary angiography ⴢ Coronary artery disease ⴢ Coronary plaques ⴢ Acute coronary syndrome

Methods Study Population A total of 63 patients (47 males and 16 females) with suspected coronary artery disease including different clinical presentations (asymptomatic, atypical chest pain, stable and unstable angina pectoris) and ACS – non-ST elevation myocardial infarction (NSTEMI) and ST elevation myocardial infarction (STEMI) – within less than 17 days prior to the CT examination were examined between March 2003 and July 2005 with multislice CT angiography and invasive angiography within 3 weeks. Patient exclusion criteria were renal dysfunction (creatinine 11.2 mmol/dl), iodine allergy, hyperthyroidism, pregnancy, heart failure (New York Heart Association class III–IV), plasmocytoma, multiple myeloma and absolute cardiac arrhythmia (e.g., atrial fibrillation). The Institutional Review Board approved this study. Written informed consent was obtained from all patients. CT Examination Technique All examinations were performed using a 16-row multidetector CT scanner (Sensation 16TM, Siemens Medical Systems, Forchheim, Germany). Coronary Calcium Score The following scan parameters were used: detector collimation 16 ! 1.5 mm, table feed 3.8 mm/rotation, gantry rotation 0.5 s, 130 mAs, 120 kV, increment 3, effective slice thickness 3 mm, medium convolution kernel B 35 f, and retrospective electrocardiogram (ECG) gating at 60–80% of the RR interval. The coronary calcium was quantified using dedicated coronary calcium scoring software on a computed workstation (LeonardoTM, Siemens Medical Systems), and data were expressed using Agatston units, volume and mass score. CT Coronary Angiography Detector collimation was 16 ! 0.75 mm, table translation speed 6.7 mm/s, gantry rotation time 0.42 s, tube current 400–500 mAs, tube voltage 120 kV, and the effective radiation dose ranged between 6.7 and 13 mSv [23]. A ␤-blocker was injected intrave-

242

Cardiology 2008;110:241–248

nously (5 ml metoprolol; BelocTM, Schering, Germany) before the examination if the heart rate was 180 bpm. A bolus of 80–100 ml iodine contrast agent iodixanol (Visipaque 320TM, Amersham Health) was injected intravenously into an antecubital vein at a flow rate of 3–4 ml/s using a power injector (Ulrich Medizintechnik, Germany). Scan delay was calculated by measuring CT attenuation values at the ascending aorta utilizing dedicated software (DynEvaTM, Siemens), after the injection of a 20-ml test bolus of contrast agent. The time point of the highest CT attenuation was taken as the scan delay. Scanning was performed during a single inspiratory breath hold. A data set containing axial images was reconstructed with 60% overlapping slices and 1 mm effective slice width, by applying smooth convolution kernel (B 10 f) in patients without coronary calcification or a medium smooth convolution kernel (B 30 f) in patients with calcifying plaque (image matrix 512 ! 512 and field of view 130–190 mm) and by using retrospective ECG gating during mid-to-end diastole (60–80% of RR interval) or mid-late systole (30–40% of RR interval) dependent on the heart rate. These axial images were transferred to a dedicated off-line computed workstation (Leonardo, Siemens Medical Systems). Coronary arteries were postprocessed using multiplanar reformation, maximum intensity projection and volume-rendering technique (VRT). Cross-sectional slices (1 mm) of each coronary artery were generated by applying multiplanar reformation and following a center line through the vessel. Each image was evaluated for the presence of coronary plaque. CT Image Analysis Coronary arteries were reviewed according to the American Heart Association/American College of Cardiology segmentbased classification (15 segments) [3]. Only plaques located at proximal segments were taken for the analysis (segments 1, 2, 5, 6, 7 and 11). All coronary segments were assessed, whether calcifying plaque (diagnostic criterion: positive calcium score and hyperdense lesion) or non-calcifying plaque (diagnostic criterion: a negative calcium score exactly on plaque site and hypodense lesion) was present, and which plaque component was predominant per segment. Coronary plaques were classified as follows: type 1 = calcifying; type 2 = mixed (calcifying 1 non-calcifying component); type 3 = mixed (non-calcifying 1 calcifying component), and type 4 = non-calcifying plaque. The mean CT density of noncalcifying plaques was measured within a region of interest placed in a cross-sectional image. If more than 1 cross-sectional image of a non-calcifying plaque was available, all images were measured and the mean value was calculated. Significant coronary stenosis was defined as a lumen diameter reduction of 150% by 2 experienced observers (G.F. and A.M.) in consensus reading and blinded to the invasive angiography. Only proximal coronary segments were taken for the calculation of the diagnostic accuracy (segments 1, 2, 5, 6, 7 and 11). Clinical Presentation The clinical presentation of the patients was graded on a 3point scale: 0 = no clinical symptoms; 1 = atypical angina pectoris; 2 = stable angina pectoris, and 3 = either unstable angina pectoris, ACS within 17 days prior to CT examination (NSTEMI or STEMI) or myocardial infarction within at least 7 months. NSTEMI/ ACS was defined as troponin T elevation 1 0.010 ␮g/l, ECG abnormalities (e.g., negative T wave) and acute chest pain.

Feuchtner et al.


It is well known from intracoronary ultrasonography (ICUS) investigations that vulnerable plaques are characterized by a lipid core [11, 12]. Non-calcifying coronary plaques as identified by multislice CT have low CT densities, suggesting a lipid plaque component. Therefore, they might be predictors of acute cardiac events. However, whether non-calcifying plaques represent ‘vulnerable plaques’ or not is unknown and currently controversially discussed. Therefore, the purpose of this study was to assess whether there is a retrospective correlation of different coronary plaque types (types 1–4; non-calcifying, mixed, calcifying) as classified by using multislice CT with acute coronary syndromes (ACS) in unselected patients referred to multislice CT coronary angiography.

Non-calcifying n = 14 (24%)

Calcifying n = 18 (31%)

Mixed (C > N) n = 2 (13%)

Non-calcifying n = 5 (33%)

Fig. 1. a Overall distribution of coronary

plaque types. Coronary plaques were detected in 58 of 63 patients (92%). b Coronary plaque types in patients with acute cardiac events (n = 15). Note that none of the patients with an acute cardiac event had only calcifying plaque (type 1). N = Non-calcifying plaque component; C = calcifying plaque component.

Mixed (C > N) n = 10 (17%)

Mixed (N > C) n = 16 (28%)

a

Type 1

Type 3

Type 2

Type 4

Table 1. Demographic data and coronary risk profile (63 pa-

Mixed (N > C) n = 8 (54%) Type 2

b

Type 3 Type 4

Results

tients)

61 44–77 47 16 28/63 (44.4) 22/63 (34.9) 3/63 (4.7) 39/63 (61.9)

Figures in parentheses are percentages.

Invasive Coronary Angiography Invasive coronary angiography was performed (by F.W. or G.F.) via a right femoral artery approach with Judkins technique using a 6- to 7-french catheter and a iodine contrast agent with a concentration of 320 mg/dl (Visipaque, Amersham Health). Images were made in biplanar projections (30° right anterior oblique and 60° left anterior oblique). Intracoronary Ultrasonography ICUS was performed using a 3.2-french catheter (Boston Scientific) with 30 MHz and 1 mm/s pullback. Statistical Analysis Statistical analysis was performed using SSPSTM software (version 8.0, SPSS Inc., Chicago, Ill., USA). The presence of a non-calcifying plaque component (yes/no) and the different plaque types were correlated with ACS (yes/no) with the ␹2 test and Fisher’s exact test. The severity of the clinical presentation (grades 0–3) was correlated with the coronary plaque type (0–4) using Spearman’s rank correlation. The difference in CT densities between the various plaque types was tested with an unpaired t test.

Coronary Plaque Types Classified by Multislice CT and ACS

The demographic data of patients and their coronary risk factors are listed in table 1. Coronary plaques were found in 58 of 63 patients (92%); the overall distribution of different coronary plaque types is shown in figure 1a. The remaining 5 patients did not have coronary artery disease (fig. 2). There was no discrepancy in plaque types in 50 of 58 patients (86%) among the different coronary segments. Eight patients had 2 different plaque types in whom the predominant plaque type, or the culprit lesion in the case of ACS, was taken for analysis. Coronary Plaque Types as Classified by Multislice CT versus ACS The presence of a non-calcifying plaque component (types 2–4; 40 of 63 patients, 63.5%) was correlated with ACS (15 of 63 patients, 23.8%; p ! 0.001, Fisher’s exact test; p = 0.002, ␹2 test). The mixed plaque type 3 (noncalcifying 1 calcifying component; n = 16) was significantly correlated with ACS (p = 0.01, Fisher’s exact test) (fig. 3). Mixed plaque type 2 (calcifying 1 non-calcifying, n = 10; p = 1.0) (fig. 4) and non-calcifying plaque type 4 (n = 14) (fig. 5) were not correlated with ACS (p = 0.3). Table 2 shows the characteristics of patients in whom an ACS was recorded within 17 days prior to the CT examination. The interobserver agreement for plaque type classification per patient was excellent (weighted Cohen’s ␬ value 0.9). Coronary Plaque Type as Determined by Multislice CT versus the Clinical Presentation of the Patients The severity of the patients’ clinical presentations (grades 0–3) was correlated with the coronary plaque Cardiology 2008;110:241–248

243


Age, years Mean Range Gender Male Female Coronary risk factors Hypercholesterolemia Cigarette smoking Diabetes Arterial hypertension

Fig. 4. Coronary plaque type 2 (mixed calcifying/non-calcifying;

Fig. 2. Multislice CT coronary angiography showing normal coronary arteries without plaques; 3-dimensional by applying VRT.

predominantly calcifying) (white arrows) shown with multislice CT in a 72-year-old male with stable angina. Aberrant circumflex (CX) artery arising from the right coronary artery (RCA) ostium and coursing between the ascending aorta (AA) and the left atrium. The black line (B) indicates the plane of a cross-sectional image through the proximal CX. LAD = Left anterior descending coronary artery. Inset: In between the calcifying plaque (C) component, a small hypodense non-calcifying plaque (N) was found. * = Lumen.

Table 2. Characteristics of patients with ACS (15 patients)

Mean age 8 SD, years 6389.2 ACS within 17 days to CT examination NSTEMI 4 (26.7) STEMI 11 (73.3) Coronary stenosis >50% (ICA) Yes 13 (86.7) No 2 (13.3) Figures in parentheses are percentages. ICA = Invasive coronary angiography. Fig. 3. Plaque type 3 with proximal 90% stenosis of the left ante-

type (0–4; p = 0.0001, ␹2 test). An increasing severity of the clinical presentation was associated with an increasing non-calcifying plaque component (r = 0.46, p = 0.0003, Spearman’s rank correlation) (fig. 6). Calcifying plaque (type 1) (fig. 7) had a high prevalence (12 of 18 patients, 66%) in patients with stable angina pectoris. 244

Cardiology 2008;110:241–248

CT Density Measurement of Non-Calcifying Coronary Plaques by Multislice CT versus ACS The CT density of a non-calcifying plaque component could be measured in 31 patients. In the remaining patients who had non-calcifying plaques, the non-calcifying plaque component was too small in order to place the appropriate region of interest in between calcifying plaques. The CT density of the non-calcifying plaque component of mixed plaque type 2, i.e. 94.1 8 44.1 Hounsfield units (HU; mean 8 SD) (n = 6), was slightly Feuchtner et al.


rior descending coronary artery by multislice CT. Insets are showing 90° cross-sectional images through the plaque. N = Noncalcifying plaque component; C = calcifying plaque component; L = lumen.

higher than in mixed plaque type 3 (81.6 8 57.6 HU; n = 12) and in non-calcifying plaque type 4 (60.3 8 47.7 HU; n = 13). There was no statistically significant difference in HU between the different plaque types (unpaired t test). There was also no statistical difference in HU between the patients with (n = 13) and without (n = 18) acute cardiac events (67.6 8 16.5 vs. 77.6 8 11.0 HU; p = 0.61, unpaired t test). Diagnostic Accuracy of 16-Slice CT for the Detection of Coronary Stenosis 150% per Patient versus Invasive Coronary Angiography Forty-five of the 58 patients with coronary artery disease (77.5%) had at least 1 stenosis 150%. The sensitivity of 16-slice CT for the detection of coronary stenosis 150% in proximal segments (1, 2, 5, 6, 7 and 11) was 98% (43 of 45 patients; 95% CI 88–99), the specificity 90% (95% CI 68– 98), the negative predictive value 97%, and the positive predictive value 97%. Three patients were excluded because the CT scan was regarded as ‘not assessable’ due to heavy coronary calcification which caused severe artifacts (blooming, beam hardening, partial volume) completely obscuring the coronary artery lumen. Invasive angiography revealed significant stenosis in 2 of those 3 patients, but 1 patient had nonobstructive calcifying plaque. Diagnostic Accuracy of Multislice CT for the Classification of the Coronary Plaque Type versus ICUS ICUS was performed in 17 of the 63 patients. The noncalcifying plaque component was correctly detected in 15 of the 17 patients by multislice CT. The non-calcifying component of 2 mixed plaques (type 2) as determined by ICUS was not seen by using multislice CT. One mixed plaque type 3 was falsely classified as type 2 by using multislice CT. The sensitivity of multislice CT for the correct detection of a non-calcifying plaque component (types 2–4) was 89% and the specificity 100%.

This retrospective study shows a correlation between ACS and a non-calcifying coronary plaque component as detected by multislice CT in an unselected study population. However, only mixed calcifying/non-calcifying plaques (type 3) with a predominant non-calcifying component were significantly correlated with acute cardiac syndromes. In all patients with ACS, the culprit lesion had a non-calcifying plaque component. This finding Coronary Plaque Types Classified by Multislice CT and ACS

rysm (white arrows); 3-dimensional by using multislice CT (VRT).

was also observed in a recently published study by Hoffmann et al. [13]. These data support the concept that the presence of non-calcifying plaques may be associated with plaque Cardiology 2008;110:241–248

245


Discussion

Fig. 5. a Plaque type 4 (non-calcifying) by multislice CT (white arrow). b Invasive angiography confirmed 190% stenosis (white arrow). This patient had an ACS. c A poststenotic coronary aneu-

12

n = 63 r = 0.45 p < 0.001

10

Patients (n)

8

6

CLIN 0 1 2 3

4

2

0 1

2 Plaque type

3

4

Fig. 6. Coronary plaque type versus clinical presentation (CLIN). The prevalence of the different coronary plaque types – 0 (no plaque), type 1 (calcifying), type 2 (mixed, predominantly calcifying), type 3 (mixed, predominantly non-calcifying), and type 4 (purely non-calcifying) – as classified by multislice CT related to the clinical presentation of the patients (0 = no symptoms, 1 = atypical chest pain, 2 = stable angina, 3 = unstable angina or ACS). Note that the prevalence of stable angina was highest in patients with calcifying plaque (type 2), but only 3 patients had unstable angina symptoms without signs of ACS/NSTEMI. In contrast, most of the patients with plaque type 3 had an ACS (n = 11).

vulnerability and that non-calcifying plaque may represent a potential risk factor for ACS. Intravascular ultrasonography has shown that ‘vulnerable plaques’ have an atheroma mass 1 40% and a thin cap !250 ␮m [11, 12]. Histologically, those lesions frequently have a lipid-rich, necrotic core and microcalcification [11]. The visualization of tissue on multislice CT is based on CT densities (expressed in HU). Fatty tissue has lower CT densities than fibrous tissue, and fibrous tissue has lower CT densities than calcifying structures. Several studies have already shown that non-calcifying plaque can be distinguished from calcifying plaque [7–10] based on the visibility of hyperdense (calcifying) or hypodense (non-calcifying) lesions (fig. 5) and on the quantification of CT densities, respectively. In a comparative study with intravascular ultrasound, lipid-rich plaque had a mean CT density of 49 8 22 HU, fibrotic plaque 91 8 22 HU and calcifying plaque 391 8 156 HU [7]. However, a significant overlap of CT densities between lipid-rich and fibrous plaques has been reported in 2 studies conducted 246

Cardiology 2008;110:241–248

Fig. 7. Plaque type 1 (calcifying). Asymptomatic 58-YOM with a high coronary risk profile and a high coronary calcium score (1.311 Agatston units). Inset: a transverse plane through the vessel. This lesion was graded as 40% stenosis by invasive angiography. The proximal left anterior descending coronary artery showed multiple calcifying plaques (C). L = Lumen.

by Leber et al. [7] and Pohle et al. [10] indicating that an accurate differentiation between lipid-rich and fibrous plaque based on CT densities is not possible. Moreover, the vast majority of coronary plaque is composed of mixed calcifying/non-calcifying lesions [9]. It is well known from angiographic studies that most myocardial infarctions occur at sites that previously caused only mild-to-moderate luminal stenosis. In histological studies of patients with coronary artery disease who died suddenly, the plaque at the culprit lesion site shows evidence of rupture in 70% of patients and superficial erosion in 30% of patients. Acute superimposed thrombosis leads to luminal obstruction [14]. We have also found nonobstructive coronary artery disease in 2 patients who had ACS. The majority of patients (overall 77%) had 150% stenosis at proximal coronary segments, which could be detected with a high diagnostic accuracy on a per-patient-based analysis which has also been reported by other studies [1–5]. Our data also show that an increasing non-calcifying plaque component is correlated with an increasing severity of clinical symptoms ranging from stable to unstable angina and ACS. In contrast, the highest prevalence of calcifying plaque (66%) was found in patients with stable angina. This finding is in accordance with 2 previous studies [9, 15] showing a higher prevalence of non-calciFeuchtner et al.


0

fying lesions in patients with acute myocardial infarction (n = 21) compared with patients with stable angina pectoris (n = 19) [15] and showing a high prevalence (65%) of calcifying plaque in patients with stable angina pectoris (n = 78) [9]. There was no significant difference in CT densities of the non-calcifying plaque component in patients with and without ACS which might be explained as follows: first, atherosclerotic plaque formation is a complex, biological process which develops slowly over years following different stages. Initially, there is subendothelial lipid accumulation, a stadium which is not related to plaque vulnerability, so called ‘early lesions’ which later develop to ‘intermediate’ lesions. Early plaque stadium is reversible and may be influenced, e.g., with statins. Afterwards, the transformation of early and intermediate lesions to plaques with central necrosis, signs of inflammations and microcalcification leads to plaque instability and ‘vulnerability’. Statins are currently discussed to have pleiotropic, anti-inflammatory effects on plaques and may induce plaque regression [16–21]. Therefore, intense medication (e.g., high-dose treatment with statins) could lead to a stabilization of these plaques. Second, the absolute CT density of a coronary plaque can be influenced by intrinsic factors related to the CT examination technique, e.g., the variability of the intracoronary contrast attenuation [22] or artifacts such as partial volume. Furthermore, limited spatial resolution of 16-slice CT (0.5 mm3) may be insufficient for the resolution and measurement of a very small lipid core. And last but not least, superimposed thrombosis may have similar CT densities to lipid-rich/fibrous non-calcifying plaque. In summary, our data suggest that non-calcifying plaques as detected by multislice CT may represent either ‘early/intermediate lesions’ or ‘vulnerable plaque’, and their differentiation based on the measurement of CT

densities by 16-slice CT is not possible because in both groups, in patients with and without ACS, the non-calcifying plaques had similar CT densities. However, there was a tendency towards lower CT densities if the non-calcifying plaque component increased in relation to the calcium burden. Limitation A small non-calcifying plaque component may be missed by using 16-slice CT when compared with ICUS, because adjacent calcification may cause blurring, partial volume and beam-hardening artifacts and because the spatial resolution of ICUS is superior to 16-slice CT. However, the overall sensitivity and specificity of 16-slice CT for the detection of a non-calcifying plaque component was high (89 and 100%, respectively) in our study when compared with ICUS. Radiation exposure of 16-slice CT ranges between 6.7 and 10.9 mSv for males and between 8.1 and 13 mSv for females [23], which is slightly above invasive angiography (2.7–15.3 mSv, depending on patient and procedure) [24] and significantly lower compared with a myocardial single positron emission CT (20 mSv) [25].

Conclusion

Mixed, predominant non-calcifying plaques (type 3) as identified by multislice CT coronary angiography are retrospectively correlated with ACS. Therefore, multislice CT may have the potential to identify patients who are at a higher risk of an ACS if plaque type 3 is present. However, prospective outcome studies are required in order to determine whether this hypothesis is true or not. Additionally, those patients might benefit from different therapeutic strategies (e.g., intense medication with statins).

References

Coronary Plaque Types Classified by Multislice CT and ACS

3 Kuettner A, Kopp A, Schroeder S, Rieger T, Brunn J, Meisner C, Heuschmid M, Trabold T, Burgstahler C, Martensen J, Schoebel W, Selbmann HK, Claussen CD: Diagnostic accuracy of multidetector computed angiography in patients with angiographically proven coronary artery disease. J Am Coll Cardiol 2004;43:831–839.

4 Hoffmann U, Moselewski F, Cury RC, Ferencik M, Jang IK, Diaz LJ, Abbara S, Brady TJ, Achenbach S: Predictive value of 16-slice multidetector spiral computed tomography to detect significant obstructive coronary artery disease in patients at high risk for coronary artery disease: patient- versus segment-based analysis. Circulation 2004; 110: 2638–2643.

Cardiology 2008;110:241–248

247


1 Hoffmann M, Shi H, Schmitz B, Schmid FT, Lieberknecht M, Schulze R, Ludwig B, Kroschel U, Jahnke N, Haerer W, Brambs HJ, Aschoff AJ: Non-invasive coronary angiography with multislice computed tomography. JAMA 2005;293:2471–2478. 2 Mollet NR, Cademartiri F, Krestin GP, McFadden EP, Arampatzis CA, Serruys PW, de Feyter PJ: Improved diagnostic accuracy with 16-row multi-slice computed tomography coronary angiography. J Am Coll Cardiol 2005;45:128–132.

248

11 Schaar JA, De Korte CL, Mastik F, Strijder C, Pasterkamp G, Boersma E, Serruys PW, Van Der Steen AF: Characterizing vulnerable plaque features with intravascular elastography. Circulation 2003;108:2636–2641. 12 Schaar JA, Muller JE, Falk E, Virmani R, Fuster V, Serruys PW, Colombo A, Stefanadis C, Ward Casscells S, Moreno PR, Maseri A, van der Steen AF: Terminology for highrisk and vulnerable coronary artery plaques. Report of a meeting on the vulnerable plaque, June 17 and 18, 2003, Santorini, Greece. Eur Heart J 2004;25:1077–1082. 13 Hoffmann U, Moselewski F, Nieman K, Jang IK, Ferencik M, Rahman AM, Cury RC, Abbara S, Joneidi-Jafari H, Achenbach S, Brady TJ: Noninvasive assessment of plaque morphology and composition in culprit and stable lesions in acute coronary syndrome and stable lesions in stable angina by multidetector computed tomography. J Am Coll Cardiol 2006;47:1655–1662. 14 Schoenhagen P, Tuzcu EM, Ellis SG: Plaque vulnerability, plaque rupture, and acute coronary syndromes: (multi)-focal manifestation of a systemic disease process. Circulation 2002;106:760–762. 15 Leber AW, Knez A, White CW, Becker A, von Ziegler F, Muehling O, Becker C, Reiser M, Steinbeck G, Boekstegers P: Composition of coronary atherosclerotic plaques in patients with acute myocardial infarction and stable angina pectoris determined by contrast-enhanced multislice computed tomography. Am J Cardiol 2003;91:714–718. 16 Nissen SE, Tuzcu EM, Schoenhagen P, Brown BG, Ganz P, Vogel RA, Crowe T, Howard G, Cooper CJ, Brodie B, Grines CL, DeMaria AN, REVERSAL Investigators: Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis: a randomized controlled trial. JAMA 2004;291:1071–1080. 17 Schartl M, Bocksch W, Koschyk D, Voelker W, Karsch KR, Kreuzer J, Hausmann D, Beckmann S, Gross M: Use of intravascular ultrasound to compare effects of different strategies of lipid-lowering therapy on plaque volume and composition in patients with coronary artery disease. Circulation 2001; 104:387–392.

Cardiology 2008;110:241–248

18 Corti R, Fayad Z, Worthley S, Helft G, Chesebro J, Mercuri M, Badimon JJ: Effects of lipid-lowering by simvastatin on human atherosklerotic lesions. Circulation 2001; 104: 249. 19 Corti R, Fuster V, Fayad Z, Worthley SG, Helft G, Smith D, Weinberger J, Wentzel J, Mizsei G, Mercuri M, Badimon JJ: Lipidlowering by simvastatin induces regression of human atherosclerotic lesions. Circulation 2002;106:2884–2887. 20 Jensen LO, Thayssen P, Pedersen KE, Stender S, Haghfelt T: Regression of coronary atherosclerosis by simvastatin: a serial with intravascular ultrasound study. Circulation 2004; 110:265–270. 21 Okazaki S, Yokoyama T, Miyauchi K, Shimada K, Kurata T, Sato H, Daida H: Early statin treatment in patients with acute coronary syndrome: demonstration of the beneficial effect on atherosclerotic lesions by serial volumetric intravascular ultrasound analysis during half a year after coronary event. The ESTABLISH Study. Circulation 2004; 110: 1061–1068. 22 Cademartiri F, Mollet NR, Runza G: Influence of intracoronary attenuation on coronary plaque measurements using multislice computed tomography: observations in an ex vivo model of coronary computed tomography angiography. Eur Radiol 2005; 15: 1426–1431. 23 Hunold P, Vogt FM, Schmermund A, Debatin JF, Kerkhoff G, Budde T, Erbel R, Ewen K, Barkhausen J: Radiation exposure during cardiac CT: effective doses at multi-detector row CT and electron-beam CT. Radiology 2003;226:145–152. 24 Stisova V: Effective dose to patient during cardiac interventional procedures. Radiat Prot Dosimetry 2004;111:271–274. 25 Picano E: Economic and biological costs of cardiac imaging. Cardiovasc Ultrasound 2005;25:13.

Feuchtner et al.


5 Mollet N, Cademartiri F, Mieghem C, Runza G, McFadden EP, Baks T, Serruys PW, Krestin GP, de Feyter PJ: High-resolution spiral computed tomography coronary angiography in patients referred for diagnostic conventional coronary angiography. Circulation 2005;112:2318–2323. 6 Raff GL, Gallagher MJ, O’Neill WW, Goldstein JA: Diagnostic accuracy of noninvasive coronary angiography using 64-slice spiral computed tomography. J Am Coll Cardiol 2005;46:552–557. 7 Leber AW, Knez A, Becker A, Becker C, von Ziegler F, Nikolaou K, Rist C, Reiser M, White C, Steinbeck G, Boekstegers P: Accuracy of multidetector spiral computed tomography in identifying and differentiating the composition of coronary atherosclerotic plaques: a comparative study with intracoronary ultrasound. J Am Coll Cardiol 2004;43: 1241–1247. 8 Achenbach S, Moselewski F, Ropers D, Ferencik M, Hoffmann U, MacNeill B, Pohle K, Baum U, Anders K, Jang IK, Daniel WG, Brady TJ: Detection of calcified and noncalcified coronary atherosclerotic plaque by contrast-enhanced, submillimeter multidetector spiral computed tomography: a segment-based comparison with intravascular ultrasound. Circulation 2004;109:14–17. 9 Mollet NR, Cademartiri F, Nieman K, Saia F, Lemos PA, McFadden EP, Serruys PW, Krestin GP, de Feyter PJ: Noninvasive assessment of coronary plaque burden using multislice computed tomography. Am J Cardiol 2005; 95: 1165–1169. 10 Pohle K, Achenbach S, Macneill B, Ropers D, Ferencik M, Moselewski F, Hoffmann U, Brady TJ, Jang IK, Daniel WG: Characterization of non-calcified coronary atherosclerotic plaque by multi-detector row CT: comparison to IVUS. Atherosclerosis 2007; 190: 174–180.