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Diagnostic Accuracy of 256-row Computed Tomographic Angiography for Detection of Obstructive Coronary Artery Disease Using Invasive Quantitative Coronary Angiography as Reference Standard
Diagnostic Accuracy of 256-row Computed Tomographic Angiography for Detection of Obstructive Coronary Artery Disease Using Invasive Quantitative Coronary Angiography as Reference Standard Oleg Petcherski, MDa, Tamar Gaspar, MDb, David A. Halon, MBChBa, Nathan Peled, MDb, Ronen Jaffe, MDa, Ron Molnar, MDb, Basil S. Lewis, MDa, and Ronen Rubinshtein, MDa,* We assessed the performance of a new-generation, 256-row computed tomography (CT) scanner for detection of obstructive coronary artery disease (CAD) compared to invasive quantitative coronary angiography. A total 121 consecutive symptomatic patients without known CAD referred for invasive coronary angiography (age 59 – 12 years, 37% women) underwent clinically driven 256-row coronary computed tomographic angiography (CCTA) before the invasive procedure. Obstructive CAD (>50% diameter stenosis) was assessed visually on CCTA by 2 independent observers using the 18-segment society of cardiovascular CT model and on invasive angiograms using quantitative coronary angiography (the reference standard). Observers were unaware of the findings from the alternate modality. Nonassessable coronary computed tomographic angiographic segments were considered obstructive for the purpose of analysis. Quantitative coronary angiography demonstrated obstructive CAD in 145 segments in 82 of 121 patients (68%). Overall, 1,677 coronary segments were available for comparative analysis, of which 39 (2.3%) were nonassessable by CCTA, mostly because of heavy calcification. Patient-based and segmentbased analysis showed a sensitivity of 100% and 97% (95% confidence interval 95% to 100%) and specificity of 69% (95% confidence interval 55% to 84%) and 97% (confidence interval 96% to 98%), respectively. Four segments with obstructive CAD in 4 patients were not detected by CCTA. All 4 patients had additional coronary obstructions identified by CCTA. The predictive accuracy was 90% (range 85% to 95%) for patient based and 97% (96% to 98%) for segment based analysis. In conclusion, 256-row CCTA showed high sensitivity and high predictive accuracy for detection of obstructive CAD in patients without previously known disease. Although coronary calcification might still interfere with analysis, the rate of nonassessable segments was low. Ó 2013 Elsevier Inc. All rights reserved. (Am J Cardiol 2013;111:510e515)
Coronary computed tomographic angiography (CCTA) allows rapid scanning of the heart and great vessels, requires minimal patient cooperation, and has high diagnostic accuracy for identifying coronary stenosis1e6 and coronary atheromatous plaques.7e11 Multicenter studies evaluating the accuracy of 64-slice computed tomography (CT)12,13 for diagnosing obstructive coronary artery disease (CAD), reported high sensitivity in relation to the commonly used reference standard for diagnosis—invasive coronary angiography (ICA). The newest generation computed tomography (CT) scanners have introduced new techniques to improve spatial and temporal resolution and therefore image quality14 and might allow improved diagnostic accuracy. However, few data are available a Department of Cardiovascular Medicine, and bDepartment of Radiology, Lady Davis Carmel Medical Center and Ruth and Bruce Rappaport School of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. Manuscript received July 15, 2012; revised manuscript received and accepted October 22, 2012. See page 514 for disclosure information. *Corresponding author: Tel: (972) 4-825-0288; fax: (972)-4-825-0972. E-mail address: [email protected] (R. Rubinshtein).
0002-9149/12/$ - see front matter Ó 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjcard.2012.10.036
assessing the performance characteristics of new-generation CT scanners in general and specifically of the new-generation 256-row CT scanners. The purpose of the present study was to evaluate the diagnostic accuracy of 256-row CCTA in the detection of obstructive CAD in symptomatic patients without previously known disease using quantitative coronary angiography (QCA) assessment of ICA as the reference standard.15,16 Methods The present retrospective, observational, single-center study was approved by the institutional review board with waiver of informed consent. The cohort included consecutive symptomatic patients without previously diagnosed CAD who underwent 256-row CCTA in our institution within a 2-year period followed by ICA within <2 months after CCTA. Patients presented either as elective outpatients or as emergency department patients with atypical chest pain and without high-risk features (i.e., without ongoing/recurrent angina, typical ST-segment deviation suggestive of ischemia, or an elevated troponin level), and were referred for CCTA to “rule out” acute coronary syndrome. www.ajconline.org
Coronary Artery Disease/Diagnostic Accuracy of 256-row Coronary CTA Table 1 Baseline characteristics of 121 patients undergoing coronary computed tomographic angiography (CCTA) and invasive coronary angiography (ICA) Variable
Value
Age (yrs) Mean SD Range Women Hypertension* Diabetes mellitus Hyperlipidemia† Smoking history Family history of CADz Peripheral vascular disease Body mass index (kg/m2) Median Interquartile range Agatston calcium score Median Interquartile range Acute presentation (emergency department)
59 12 30e86 45 (37%) 85 (70%) 32 (26%) 82 (68%) 53 (44%) 32 (26%) 6 (5%) 27 24e30 12 6e517 79 (65%)
* Blood pressure >140/90 mm Hg or treatment with antihypertensive medication. † Total serum cholesterol level 5 mmol/L or treatment with lipidlowering drugs. z CAD in first-degree relatives <55 (men) or <65 (women) years old.
Table 2 Anatomic distribution of 145 segments with obstructive coronary artery disease (CAD) by quantitative coronary angiography (QCA) of invasive coronary angiography (ICA) Coronary Artery Segment
n
Left main Left anterior descending (and branches) Left circumflex (and branches) Right (and branches)
3 56
Intermediate branch
31 53
Detailed Distribution Proximal, 18; mid, 27; distal or branches, 11 Proximal, 12; distal or branches, 19 Proximal, 12; mid, 22; distal or branches, 19
2
Patients were eligible for inclusion in the study if they were >18 years old and were in sinus rhythm. In the present retrospective study, the exclusion criteria were known CAD and/or previous revascularization. No patient was excluded because of poor-quality CCTA. Patients with iodine allergy, renal function impairment (creatinine clearance <60 ml/min), or pregnancy were not included. A routine structured interview on the day of CCTA provided information regarding the baseline data and risk factors. CCTA was performed using a 256-row scanner (Brilliance iCT, Philips Healthcare, Cleveland Ohio), which has a longitudinal coverage of 8 cm, offers options for different rotation times. which can be as fast as 0.27 second, and has a 120-kW generator. CCTA was performed either as prospectively triggered “step-and-shoot” mode or with helical retrospective electrocardiographic (ECG) gating. ECG-based tube current modulation was used when possible with retrospective gating.
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Table 3 Extent of obstructive coronary artery disease (CAD) among 121 patients undergoing invasive coronary angiography (ICA) Variable Coronary arteries involved (n) 0 1 2 3 Left main Left main or 3 vessels
n (%) 39 53 22 4 3 7
(32) (44) (18) (3) (2) (6)
Oral and/or intravenous b blockers were used to lower the heart rate when it was >70 beats/min. Sublingual nitroglycerine (0.4 mg) was given before CCTA for all patients with systolic blood pressure of 110 mm Hg and no clinical contraindications (e.g., aortic stenosis or suspected pulmonary embolism). The coronary artery calcium score (Agatston units [AU]) was measured on a nonenhanced scan (using prospective ECG triggering), and a contrast-enhanced scan was then performed using a bolus of 69 11 ml (range 50-100) Iohexol (Omnipaque 350 mg Iodine/ml, GE Healthcare, Princeton, New Jersey) injected into an antecubital vein at a flow rate of 5 to 6 ml/s, followed by a mixed 50% contrast/saline injection and then a 20- to 30-ml saline chaser bolus. The iohexol dose was calculated according to the following formula: (predicted scan time in seconds þ 5) intravenous contrast flow rate. The scans were performed at 120 kV (or 100 kV in 14 patients with a body mass index <24 kg/m2 and a heart rate at rest of <60 beats/min in last 6 months of the study) with a slice collimation of 128 0.625 mm, with dual z-focal spot positions (which leads to a double number of simultaneous imaged slices per gantry rotation; therefore 256-row acquisition), and a rotation time of 0.27 or 0.33 second. The helical scans (retrospective ECG gating) were performed with an effective tube current (rotation time product normalized by the pitch) in the range of 900 to 1,500 mA (effective), depending on the body mass index and body habitus, and a pitch of 0.14 to 0.18. The “step-and-shoot” mode scans were performed in patients with a stable heart rhythm and a heart rate <65 beats/min with a tube currentex-ray “ON” time product of 160 to 300 mAs. The scanner provided several predefined protocols that determined the pitch and rotation time for each protocol according to the scanning mode, heart rate, and whether a “bariatric mode” (high mA) was used (to allow optimal temporal resolution at all settings). Radiation exposure was assessed as dose-length-product (product of scan length and CT dose index). Reconstruction was performed using a window centered at 75% of the R-R interval as the default. For heart rates >70 beats/min, an earlier reconstruction phase (usually 45%) was frequently used with retrospective gating. The interpretation and diagnosis of CAD on CCTA scans was performed separately by 2 experienced readers (R.R., T.G.), who were unaware of the invasive angiographic results. The 2 reports included the clinical reading (before ICA) and post hoc reading by the alternate reader. The post hoc readers were also unaware of the clinical presentation. If disagreement occurred between the 2 readers, the results were adjudicated by a third reader (N.P.). Interpretation of
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Table 4 Diagnostic accuracy of 256-slice coronary computed tomographic angiography (CCTA) for detection of obstructive coronary artery disease (CAD) Parameter Sensitivity Specificity Negative predictive value Positive predictive value Predictive accuracy
Segment-based Analysis 141/145 1,486/1,532 1,486/1,490 141/187 1,627/1,677
(97%, 95e100%) (97%, 96e98%) (99.7%, 99.5e100%) (75%, 69e82%) (97%, 96e98%)
Patient-based Analysis 82/82 27/39 27/27 82/94 109/121
(100%) (69%, 55e84%) (100%) (87%, 81e94%) (90%, 85e95%)
Data are presented as absolute values used to calculate percentages; data in parentheses are percentages with 95% confidence intervals.
Figure 1. Significant stenosis (black arrows) at left anterior descending coronary artery demonstrated by 256-row CCTA (A) and invasive angiography (B) in 43-year-old man with acute chest pain but normal troponin level and normal ECG findings.
the results was performed on the scanner workstation (Extended Brilliance Workstation, Philips Healthcare) with all available techniques, including curved multiplanar reformations. Obstructive CAD was defined as >50% diameter stenosis. Recording and analysis were performed using the 18-segment Society of Cardiovascular Computed Tomography model.17 Four coronary segments were defined as “proximal”: the left main stem, proximal left anterior descending artery, proximal left circumflex artery, and proximal right coronary artery. All ICA procedures were performed using the standard technique with the Judkins femoral or radial artery approach. QCA was performed off-line using the Coronary Artery Analysis System, version 3.2 (Pie Medical Imaging, Maastricht, The Netherlands) by a different observer (O.P. or D.A.H.) who had no knowledge of the CCTA results. The proximal and distal reference vessel diameters and minimal lumen diameter of the suspected lesion were recorded using the catheter shaft diameter for calibration, and the percentage of diameter stenosis was calculated using the same 18-segment Society of Cardiovascular Computed Tomography model as for CCTA analysis. Nonassessable segments on CCTA were considered obstructive for the purposes of the primary analysis.18 The performance characteristics (patient-based, vessel-based, and segment-based) of CCTA to detect obstructive CAD were calculated using QCA as the reference standard. Differences between the false-positive rates in patients with and without an elevated calcium score were calculated using the chi-square test. p Values <0.05 were considered significant. Statistical analysis was performed using the
Statistix, version 8, software package (Analytical Software, Tallahassee, Florida). Results Among 1,477 patients undergoing CCTA during the study period, 931 had no previously known CAD (63%). Of these 931 patients, 121 (37% women, age range 30 to 86 years) met the study inclusion criteria. The patients’ baseline characteristics are presented in Table 1. No scan was excluded because of poor diagnostic quality. The mean heart rate during the scans was 61 8 beats/min (range 42e82). With the advances in scanner software during the study period, the scanning modes changed. In general, most scans during the first study year were performed with retrospective gating, and most scans performed during the second study year were performed using prospective ECG triggering (“step-and-shoot” mode). Overall, 67 patients (55%) were scanned using the “step-and-shoot” mode and 54 (45%) using retrospective ECG gating. In 14 patients (12%), a tube voltage of 100 kV was used. The median doselength-product was 438 mGy cm (range 160 to 1,392), resulting in a median effective radiation dose estimate of 6.1 mSv (range 2.2 to 19.5) using a conversion coefficient k of 0.014 for the chest. QCA demonstrated obstructive CAD (>50% diameter stenosis) in 145 segments among the 82 of 121 patients (68%). The detailed anatomic distributions of the obstructive segments and extent of CAD are presented in Tables 2 and 3. The results of the pre-CCTA, nonenhanced CT scans for calcium scoring showed a wide range of AU values, as expected (Table 1). A total of 56 patients had a low calcium
Coronary Artery Disease/Diagnostic Accuracy of 256-row Coronary CTA
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Table 5 Diagnostic accuracy of 256-slice coronary computed tomographic angiography (CCTA) for detection of obstructive coronary artery disease (CAD) in relation to vessel analyzed (segment-based analysis) Parameter Sensitivity Specificity Negative predictive value Positive predictive value Predictive accuracy
LAD (and LM) 57/59 528/546 528/530 57/75 585/605
(97%, 92e100%) (97%, 95e98%) (99.6%, 99.1e100%) (76%, 66e86%) (97%, 95e98%)
LC (and Intermediate Branch) 32/33 454/465 454/455 32/43 486/498
(97%, 91e100) (98%, 96e99) (99.8%, 99.3e100) (74%, 61e88) (98%, 96e99)
Right 52/53 504/521 504/505 52/69 556/574
(98%, 95e100) (97%, 95e98) (99.8%, 99.4e100) (75%, 65e85) (97%, 95e98)
Data are presented as absolute values used to calculate percentages; data in parentheses are percentages with 95% confidence intervals. LAD ¼ left anterior descending coronary artery; LC ¼ left circumflex coronary artery; LM ¼ left main coronary artery.
score (<100 AU), of whom 26 patients had a 0 calcium score. A total of 35 patients had a high calcium score (>400 AU). After CCTA, 1,677 coronary segments were available for comparative analysis (between CCTA and QCA of ICA), of which 39 (2.3%) in 16 patients were nonassessable by CCTA. The most frequent cause of an inability to assess a segment was heavy calcification in 26 of 39 segments. Other reasons included low intravascular contrast or excessive image noise in 7 and significant motion artifacts in 6 segments. Nonassessable segments were considered obstructive for the purpose of the present analysis. Overall, of the 145 segments with obstructive CAD on QCA, CCTA correctly identified 141 (sensitivity 97%, Table 4). An example is shown in Figure 1. Four segments with obstructive CAD in 4 different patients were not detected by CCTA. All 4 patients had additional coronary obstructions identified by CCTA (and QCA). Hence, the patient-based sensitivity was 100%. All 4 false-negative segments were mildly calcified. Two were in the proximal left anterior descending artery, one in the proximal left circumflex artery, and one at the mid-right coronary artery. There were 46 false-positive segments (2.7%) on CCTA that were mostly due to calcification obscuring the arterial lumen. Patient-based analysis showed that 12 patients had false-positive CCTA findings. leading to a positive predictive value of 87% and a suboptimal specificity of 69%. Nonetheless, the predictive accuracy (97% per segment and 90% per patient) was high (Table 4). An elevated total calcium score (>400 AU), present in 35 patients, led to a numerically greater rate of false-positive results (6 of 35, 17%; vs 6 of 86, 7%) than in those with a lower calcium score (p ¼ 0.09). However, it is noteworthy that the false-positive results were mostly related to localized, heavy calcification rather than to a greater total AU score. Regardless of the calcium score, the sensitivity (per patient) was 100% (Table 4). High predictive accuracy was recorded for all vessel territories (vessel-based analysis presented in Table 5). The sensitivity and specificity remained high for both proximal (93% and 97%, respectively) and distal (99% and 97%, respectively) coronary segments. Discussion The present study has shown that in symptomatic patients with chest pain referred for ICA, 256-row CCTA has high diagnostic accuracy compared to QCA. The sensitivity and negative predictive value from a patient-based analysis were both 100%; thus, the CCTA did not miss any patients with
obstructive CAD. Moreover, the rate of nonassessable segments was low (2.3%), allowing a meaningful evaluation of almost all available coronary segments. Few data describing the diagnostic accuracy of the newgeneration CT scanners are available. The initial experience with 256-row CCTA has shown promising results in a mixed group of patients with known or suspected CAD19 and in cohorts of smaller size.20 However, our study is the largest to date to report the performance characteristics (for the diagnosis of obstructive CAD) of this scanner in a group of real world patients without previously known CAD. The use of (off-line) QCA as an objective measure of ICA stenosis strengthens the findings of our study. The finding of a very high negative predictive value (100% per patient, 99.7% per segment) in this selected cohort with a high disease prevalence (68% of patients) is particularly encouraging. It is to be expected that the negative predictive value will remain high in other patient populations with a lower prevalence of obstructive CAD who are those likely to benefit most from CCTA according to current guidelines.21,22 The 256-row scanner used in our study has several features designed to enhance image quality. It has a fast rotation time of 0.27 second (especially advantageous with faster heart rates) and a powerful X-ray tube (allowing a tube current 1,000 mA); however, it also comes equipped with dose-saving technologies.23 The radiation exposure was 64% less in patients scanned with prospective triggering in the present study. These properties enable it to provide high instantaneous energy (1,000 mA) with only a modest increase in radiation exposure when using prospective electrocardiographic triggering.24 The 256-row scanner allows the use of 120-kV (tube voltage) with greater tube current (than that with the previous 64-slice system), which theoretically should reduce image noise and consequently improves the contrastto-noise ratio. Thus, among the theoretical advantages is the improved ability to provide sufficient image quality in the obese population.23,25 The routine use of b blockers and the improved temporal resolution contribute to the low rate of nonassessable segments demonstrated in our study, which we believe is the most significant advance of new-generation scanners compared to older systems. The initial results demonstrating high diagnostic accuracy and a low rate of nonassessable segments have also been reported with other new-generation scanners such as the GE high-definition scanner (GE Healthcare, Milwuakee, Wisconsin)26 and the 320-row scanner (Aquilion ONE, Toshiba Medical Systems, Otawara, Japan),27 which allows 16-cm coverage and the possibility to process data from
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a single heart beat. Several (mostly single-center) studies have also demonstrated the high accuracy of dual-source technology,28,29 which allows high temporal resolution and additional reduction in the radiation dose in selected patients using the high pitch mode.30 Our results have demonstrated the possibly of improved accuracy of new-generation scanners compared to the results obtained with 64-slice systems.12,13 However, even with the 256 slices, just as with the 64-slice systems, the degree of calcification can affect the image quality and therefore the diagnostic accuracy.31 In the present study, the presence of heavy calcification was the main cause of failure to assess a segment. It seems that even with the latest CT technology, calcification still poses a diagnostic challenge. Nonetheless, despite the false-positive findings, mostly related to calcification, 82 of 94 (87%) of this symptomatic patient cohort with “positive” CCTA findings had obstructive CAD on QCA. In addition, among the 4 false-negative segments, small calcifications might have also played a role. A post hoc review of these cases revealed small calcifications in relatively large vessels (>3 mm). This combination created a “patent lumen” view among CCTA readers, but the diameter stenosis was >50% using ICA QCA. Another important issue to be considered when assessing CCTA performance and clinical applicability is the radiation dose. The consistent trend toward a lower radiation dose with dedicated protocols such as prospective ECG triggering (used in 55% of our cohort) or with the use of 100-KV tube voltage (used in 12% of patients) was also apparent in our study. The median dose-length-product among our cohort was 438 mGy cm and gradually decreased during the study period with implementation of the aforementioned dose-saving technologies. It seems that if patient-related factors such as body mass index or heart rate are considered, excellent image quality can still be achieved, even with dose-saving technologies.32 If this trend will continue, it might tip the balance of the clinical risk/benefit ratio in favor of CCTA for a wider range of patient populations. The study might have “verification bias” (post-test referral bias), because the decision to perform invasive angiography (the reference standard) was influenced by the outcome of the diagnostic test (CCTA). After CCTA, more symptomatic patients with a greater prevalence of CAD would likely be referred to ICA (selection bias). However, the negative predictive value remained high, and would be expected to be at least as great in patients with a lower prevalence of obstructive CAD. Disclosures Drs. Gaspar and Peled have received research grants from Philips Healthcare (Andover, Massachusetts). 1. Nikolaou K, Flohr T, Knez A, Rist C, Wintersperger B, Johnson T, Reiser MF, Becker CR. Advances in cardiac CT imaging: 64-slice scanner. Int J Cardiovasc Imaging 2004;20:535e540. 2. Hoffmann MH, Shi H, Schmitz BL, Schmid FT, Lieberknecht M, Schulze R, Ludwig B, Kroschel U, Jahnke N, Haerer W, Brambs HJ, Aschoff AJ. Noninvasive coronary angiography with multislice computed tomography. JAMA 2005;293:2471e2478. 3. Achenbach S, Daniel WG. Computed tomography of the coronary arteries: more than meets the (angiographic) eye. J Am Coll Cardiol 2005;46: 155e157.
4. Mollet NR, Cademartiri F, van Mieghem CA, 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: 2318e2323. 5. 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;46:552e557. 6. Pugliese F, Mollet NR, Runza G, van Mieghem C, Meijboom WB, Malagutti P, Baks T, Krestin GP, deFeyter PJ, Cademartiri F. Diagnostic accuracy of non-invasive 64-slice CT coronary angiography in patients with stable angina pectoris. Eur Radiol 2006;16:575e582. 7. Schroeder S, Kopp AF, Baumbach A, Meisner C, Kuettner A, Georg C, Ohnesorge B, Herdeg C, Claussen CD, Karsch KR. Noninvasive detection and evaluation of atherosclerotic coronary plaques with multislice computed tomography. J Am Coll Cardiol 2001;37:1430e1435. 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;109:14e17. 9. Caussin C, Ohanessian A, Ghostine S, Jacq L, Lancelin B, Dambrin G, Sigal-Cinqualbre A, Angel CY, Paul JF. Characterization of vulnerable nonstenotic plaque with 16-slice computed tomography compared with intravascular ultrasound. Am J Cardiol 2004;94:99e104. 10. Leber AW, Knez A, von Ziegler F, Becker A, Nikolaou K, Paul S, Wintersperger B, Reiser M, Becker CR, Steinbeck G, Boekstegers P. Quantification of obstructive and nonobstructive coronary lesions by 64-slice computed tomography: a comparative study with quantitative coronary angiography and intravascular ultrasound. J Am Coll Cardiol 2005;46:147e154. 11. Leber AW, Becker A, Knez A, von Ziegler F, Sirol M, Nikolaou K, Ohnesorge B, Fayad ZA, Becker CR, Reiser M, Steinbeck G, Boekstegers P. Accuracy of 64-slice computed tomography to classify and quantify plaque volumes in the proximal coronary system: a comparative study using intravascular ultrasound. J Am Coll Cardiol 2006;47:672e677. 12. Miller JM, Rochitte CE, Dewey M, Arbab-Zadeh A, Niinuma H, Gottlieb I, Paul N, Clouse ME, Shapiro EP, Hoe J, Lardo AC, Bush DE, de Roos A, Cox C, Brinker J, Lima JA. Diagnostic performance of coronary angiography by 64-row CT. N Engl J Med 2008;359: 2324e2336. 13. Budoff MJ, Dowe D, Jollis JG, Gitter M, Sutherland J, Halamert E, Scherer M, Bellinger R, Martin A, Benton R, Delago A, Min JK. Diagnostic performance of 64-multidetector row coronary computed tomographic angiography for evaluation of coronary artery stenosis in individuals without known coronary artery disease: results from the prospective multicenter ACCURACY (Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography) trial. J Am Coll Cardiol 2008;52: 1724e1732. 14. Kalra MK, Brady TJ. Current status and future directions in technical developments of cardiac computed tomography. J Cardiovac Comput Tomogr 2008;2:71e80. 15. Boogers MJ, Schuijf JD, Kitslaar PH, van Werkhoven JM, de Graaf FR, Boersma E, van Velzen JE, Dijkstra J, Adame IM, Kroft LJ, de Roos A, Schreur JH, Heijenbrok MW, Jukema JW, Reiber JH, Bax JJ. Automated quantification of stenosis severity on 64-slice CT: a comparison with quantitative coronary angiography. JACC Cardiovasc Imaging 2010;3:699e709. 16. Van der Zwet PM, Reiber JH. A new approach for the quantification of complex lesion morphology: the gradient field transform; basic principles and validation results. J Am Coll Cardiol 1994;24:216e224. 17. Raff GL, Abidov A, Achenbach S, Berman DS, Boxt LM, Budoff MJ, Cheng V, DeFrance T, Hellinger JC, Karlsberg RP, Society of Cardiovascular Computed Tomography. SCCT guidelines for the interpretation and reporting of coronary computed tomographic angiography. J Cardiovasc Comput Tomogr 2009;3:122e136. 18. Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig LM, Lijmer JG, Moher D, Rennie D, de Vet HC, Standards for Reporting of Diagnostic Accuracy. Towards complete and accurate reporting of studies of diagnostic accuracy: the STARD initiative. BMJ 2003;326:41e44.
Coronary Artery Disease/Diagnostic Accuracy of 256-row Coronary CTA 19. Chao SP, Law WY, Kuo CJ, Hung HF, Cheng JJ, Lo HM, Shyu KG. The diagnostic accuracy of 256-row computed tomographic angiography compared with invasive coronary angiography in patients with suspected coronary artery disease. Eur Heart J 2010;31:1916e1923. 20. Korosoglou G, Mueller D, Lehrke S, Steen H, Hosch W, Heye T, Kauczor HU, Giannitsis E, Katus HA. Quantitative assessment of stenosis severity and atherosclerotic plaque composition using 256slice computed tomography. Eur Radiol 2010;20:1841e1850. 21. Taylor AJ, Cerqueira M, Hodgson JM, Mark D, Min J, O’Gara P, Rubin GD. ACCF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/SCMR 2010 appropriate use criteria for cardiac computed tomography: a report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, the Society of Cardiovascular Computed Tomography, the American College of Radiology, the American Heart Association, the American Society of Echocardiography, the American Society of Nuclear Cardiology, the North American Society for Cardiovascular Imaging, the Society for Cardiovascular Angiography and Interventions, and the Society for Cardiovascular Magnetic Resonance. J Am Coll Cardiol 2010;56: 1864e1894. 22. Hamm CW, Bassand JP, Agewall S, Bax J, Boersma E, Bueno H, Caso P, Dudek D, Gielen S, Huber K, Ohman M, Petrie MC, Sonntag F, Uva MS, Storey RF, Wijns W, Zahger D, ESC Committee for Practice Guidelines, Bax JJ, Auricchio A, Baumgartner H, Ceconi C, Dean V, Deaton C, Fagard R, Funck-Brentano C, Hasdai D, Hoes A, Knuuti J, Kolh P, McDonagh T, Moulin C, Poldermans D, Popescu BA, Reiner Z, Sechtem U, Sirnes PA, Torbicki A, Vahanian A, Windecker S, Document Reviewers, Windecker S, Achenbach S, Badimon L, Bertrand M, Bøtker HE, Collet JP, Crea F, Danchin N, Falk E, Goudevenos J, Gulba D, Hambrecht R, Herrmann J, Kastrati A, Kjeldsen K, Kristensen SD, Lancellotti P, Mehilli J, Merkely B, Montalescot G, Neumann FJ, Neyses L, Perk J, Roffi M, Romeo F, Ruda M, Swahn E, Valgimigli M, Vrints CJ, Widimsky P. ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: the Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 2011;32:2999e3054. 23. Walker MJ, Olszewski ME, Desai MY, Halliburton SS, Flamm SD. New radiation dose saving technologies for 256-slice cardiac computed tomography angiography. Intl J Cardiovasc Imaging 2009;25:189e199.
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24. Domachevsky L, Gaspar T, Peled N, Shnapp M, Halon DA, Lewis BS, Rubinshtein R, Hazzan D, Vembar M, Samoilov S. Non-invasive cardiac imaging of morbidly obese patients using the Brilliance iCT. Medicamundi 2010;54:29e34. 25. Segev OL, Gaspar T, Halon DA, Peled N, Domachevsky L, Lewis BS, Rubinshtein R. Image quality in obese patients undergoing 256-row computed tomography coronary angiography. Int J Cardiovasc Imaging 2012;28:633e639. 26. LaBounty TM, Earls JP, Leipsic J, Heilbron B, Mancini GB, Lin FY, Dunning AM, Min JK. Effect of a standardized quality-improvement protocol on radiation dose in coronary computed tomographic angiography. Am J Cardiol 2010;106:1663e1667. 27. de Graaf FR, Schuijf JD, van Velzen JE, Kroft LJ, de Roos A, Reiber JH, Boersma E, Schalij MJ, Spanó F, Jukema JW, van der Wall EE, Bax JJ. Diagnostic accuracy of 320-row multidetector computed tomography coronary angiography in the non-invasive evaluation of significant coronary artery disease. Eur Heart J 2010;31:1908e1915. 28. Guo SL, Guo YM, Zhai YN, Ma B, Wang P, Yang KH. Diagnostic accuracy of first generation dual-source computed tomography in the assessment of coronary artery disease: a meta-analysis from 24 studies. Int J Cardiovasc Imaging 2011;27:755e771. 29. Salavati A, Radmanesh F, Heidari K, Dwamena BA, Kelly AM, Cronin P. Dual-source computed tomography angiography for diagnosis and assessment of coronary artery disease: systematic review and meta-analysis. J Cardiovasc Comput Tomogr 2012;6:78e90. 30. Achenbach S, Goroll T, Seltmann M, Pflederer T, Anders K, Ropers D, Daniel WG, Uder M, Lell M, Marwan M. Detection of coronary artery stenoses by low-dose, prospectively ECG-triggered, high-pitch spiral coronary CT angiography. JACC Cardiovasc Imaging 2011;4:328e337. 31. Vavere AL, Arbab-Zadeh A, Rochitte CE, Dewey M, Niinuma H, Gottlieb I, Clouse ME, Bush DE, Hoe JW, de Roos A, Cox C, Lima JA, Miller JM. Coronary artery stenoses: accuracy of 64detector row CT angiography in segments with mild, moderate, or severe calcification—a subanalysis of the CORE-64 trial. Radiology 2011;261:100e108. 32. Blankstein R, Bolen MA, Pale R, Murphy MK, Shah AB, Bezerra HG, Sarwar A, Rogers IS, Hoffmann U, Abbara S, Cury RC, Brady TJ. Use of 100 kV versus 120 kV in cardiac dual source computed tomography: effect on radiation dose and image quality. Int J Cardiovasc Imaging 2011;27:579e586.
Coronary computed tomographic angiography (CCTA) allows rapid scanning of the heart and great vessels, requires minimal patient cooperation, and has high diagnostic accuracy for identifying coronary stenosis1e6 and coronary atheromatous plaques.7e11 Multicenter studies evaluating the accuracy of 64-slice computed tomography (CT)12,13 for diagnosing obstructive coronary artery disease (CAD), reported high sensitivity in relation to the commonly used reference standard for diagnosis—invasive coronary angiography (ICA). The newest generation computed tomography (CT) scanners have introduced new techniques to improve spatial and temporal resolution and therefore image quality14 and might allow improved diagnostic accuracy. However, few data are available a Department of Cardiovascular Medicine, and bDepartment of Radiology, Lady Davis Carmel Medical Center and Ruth and Bruce Rappaport School of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. Manuscript received July 15, 2012; revised manuscript received and accepted October 22, 2012. See page 514 for disclosure information. *Corresponding author: Tel: (972) 4-825-0288; fax: (972)-4-825-0972. E-mail address: [email protected] (R. Rubinshtein).
0002-9149/12/$ - see front matter Ó 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjcard.2012.10.036
assessing the performance characteristics of new-generation CT scanners in general and specifically of the new-generation 256-row CT scanners. The purpose of the present study was to evaluate the diagnostic accuracy of 256-row CCTA in the detection of obstructive CAD in symptomatic patients without previously known disease using quantitative coronary angiography (QCA) assessment of ICA as the reference standard.15,16 Methods The present retrospective, observational, single-center study was approved by the institutional review board with waiver of informed consent. The cohort included consecutive symptomatic patients without previously diagnosed CAD who underwent 256-row CCTA in our institution within a 2-year period followed by ICA within <2 months after CCTA. Patients presented either as elective outpatients or as emergency department patients with atypical chest pain and without high-risk features (i.e., without ongoing/recurrent angina, typical ST-segment deviation suggestive of ischemia, or an elevated troponin level), and were referred for CCTA to “rule out” acute coronary syndrome. www.ajconline.org
Coronary Artery Disease/Diagnostic Accuracy of 256-row Coronary CTA Table 1 Baseline characteristics of 121 patients undergoing coronary computed tomographic angiography (CCTA) and invasive coronary angiography (ICA) Variable
Value
Age (yrs) Mean SD Range Women Hypertension* Diabetes mellitus Hyperlipidemia† Smoking history Family history of CADz Peripheral vascular disease Body mass index (kg/m2) Median Interquartile range Agatston calcium score Median Interquartile range Acute presentation (emergency department)
59 12 30e86 45 (37%) 85 (70%) 32 (26%) 82 (68%) 53 (44%) 32 (26%) 6 (5%) 27 24e30 12 6e517 79 (65%)
* Blood pressure >140/90 mm Hg or treatment with antihypertensive medication. † Total serum cholesterol level 5 mmol/L or treatment with lipidlowering drugs. z CAD in first-degree relatives <55 (men) or <65 (women) years old.
Table 2 Anatomic distribution of 145 segments with obstructive coronary artery disease (CAD) by quantitative coronary angiography (QCA) of invasive coronary angiography (ICA) Coronary Artery Segment
n
Left main Left anterior descending (and branches) Left circumflex (and branches) Right (and branches)
3 56
Intermediate branch
31 53
Detailed Distribution Proximal, 18; mid, 27; distal or branches, 11 Proximal, 12; distal or branches, 19 Proximal, 12; mid, 22; distal or branches, 19
2
Patients were eligible for inclusion in the study if they were >18 years old and were in sinus rhythm. In the present retrospective study, the exclusion criteria were known CAD and/or previous revascularization. No patient was excluded because of poor-quality CCTA. Patients with iodine allergy, renal function impairment (creatinine clearance <60 ml/min), or pregnancy were not included. A routine structured interview on the day of CCTA provided information regarding the baseline data and risk factors. CCTA was performed using a 256-row scanner (Brilliance iCT, Philips Healthcare, Cleveland Ohio), which has a longitudinal coverage of 8 cm, offers options for different rotation times. which can be as fast as 0.27 second, and has a 120-kW generator. CCTA was performed either as prospectively triggered “step-and-shoot” mode or with helical retrospective electrocardiographic (ECG) gating. ECG-based tube current modulation was used when possible with retrospective gating.
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Table 3 Extent of obstructive coronary artery disease (CAD) among 121 patients undergoing invasive coronary angiography (ICA) Variable Coronary arteries involved (n) 0 1 2 3 Left main Left main or 3 vessels
n (%) 39 53 22 4 3 7
(32) (44) (18) (3) (2) (6)
Oral and/or intravenous b blockers were used to lower the heart rate when it was >70 beats/min. Sublingual nitroglycerine (0.4 mg) was given before CCTA for all patients with systolic blood pressure of 110 mm Hg and no clinical contraindications (e.g., aortic stenosis or suspected pulmonary embolism). The coronary artery calcium score (Agatston units [AU]) was measured on a nonenhanced scan (using prospective ECG triggering), and a contrast-enhanced scan was then performed using a bolus of 69 11 ml (range 50-100) Iohexol (Omnipaque 350 mg Iodine/ml, GE Healthcare, Princeton, New Jersey) injected into an antecubital vein at a flow rate of 5 to 6 ml/s, followed by a mixed 50% contrast/saline injection and then a 20- to 30-ml saline chaser bolus. The iohexol dose was calculated according to the following formula: (predicted scan time in seconds þ 5) intravenous contrast flow rate. The scans were performed at 120 kV (or 100 kV in 14 patients with a body mass index <24 kg/m2 and a heart rate at rest of <60 beats/min in last 6 months of the study) with a slice collimation of 128 0.625 mm, with dual z-focal spot positions (which leads to a double number of simultaneous imaged slices per gantry rotation; therefore 256-row acquisition), and a rotation time of 0.27 or 0.33 second. The helical scans (retrospective ECG gating) were performed with an effective tube current (rotation time product normalized by the pitch) in the range of 900 to 1,500 mA (effective), depending on the body mass index and body habitus, and a pitch of 0.14 to 0.18. The “step-and-shoot” mode scans were performed in patients with a stable heart rhythm and a heart rate <65 beats/min with a tube currentex-ray “ON” time product of 160 to 300 mAs. The scanner provided several predefined protocols that determined the pitch and rotation time for each protocol according to the scanning mode, heart rate, and whether a “bariatric mode” (high mA) was used (to allow optimal temporal resolution at all settings). Radiation exposure was assessed as dose-length-product (product of scan length and CT dose index). Reconstruction was performed using a window centered at 75% of the R-R interval as the default. For heart rates >70 beats/min, an earlier reconstruction phase (usually 45%) was frequently used with retrospective gating. The interpretation and diagnosis of CAD on CCTA scans was performed separately by 2 experienced readers (R.R., T.G.), who were unaware of the invasive angiographic results. The 2 reports included the clinical reading (before ICA) and post hoc reading by the alternate reader. The post hoc readers were also unaware of the clinical presentation. If disagreement occurred between the 2 readers, the results were adjudicated by a third reader (N.P.). Interpretation of
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Table 4 Diagnostic accuracy of 256-slice coronary computed tomographic angiography (CCTA) for detection of obstructive coronary artery disease (CAD) Parameter Sensitivity Specificity Negative predictive value Positive predictive value Predictive accuracy
Segment-based Analysis 141/145 1,486/1,532 1,486/1,490 141/187 1,627/1,677
(97%, 95e100%) (97%, 96e98%) (99.7%, 99.5e100%) (75%, 69e82%) (97%, 96e98%)
Patient-based Analysis 82/82 27/39 27/27 82/94 109/121
(100%) (69%, 55e84%) (100%) (87%, 81e94%) (90%, 85e95%)
Data are presented as absolute values used to calculate percentages; data in parentheses are percentages with 95% confidence intervals.
Figure 1. Significant stenosis (black arrows) at left anterior descending coronary artery demonstrated by 256-row CCTA (A) and invasive angiography (B) in 43-year-old man with acute chest pain but normal troponin level and normal ECG findings.
the results was performed on the scanner workstation (Extended Brilliance Workstation, Philips Healthcare) with all available techniques, including curved multiplanar reformations. Obstructive CAD was defined as >50% diameter stenosis. Recording and analysis were performed using the 18-segment Society of Cardiovascular Computed Tomography model.17 Four coronary segments were defined as “proximal”: the left main stem, proximal left anterior descending artery, proximal left circumflex artery, and proximal right coronary artery. All ICA procedures were performed using the standard technique with the Judkins femoral or radial artery approach. QCA was performed off-line using the Coronary Artery Analysis System, version 3.2 (Pie Medical Imaging, Maastricht, The Netherlands) by a different observer (O.P. or D.A.H.) who had no knowledge of the CCTA results. The proximal and distal reference vessel diameters and minimal lumen diameter of the suspected lesion were recorded using the catheter shaft diameter for calibration, and the percentage of diameter stenosis was calculated using the same 18-segment Society of Cardiovascular Computed Tomography model as for CCTA analysis. Nonassessable segments on CCTA were considered obstructive for the purposes of the primary analysis.18 The performance characteristics (patient-based, vessel-based, and segment-based) of CCTA to detect obstructive CAD were calculated using QCA as the reference standard. Differences between the false-positive rates in patients with and without an elevated calcium score were calculated using the chi-square test. p Values <0.05 were considered significant. Statistical analysis was performed using the
Statistix, version 8, software package (Analytical Software, Tallahassee, Florida). Results Among 1,477 patients undergoing CCTA during the study period, 931 had no previously known CAD (63%). Of these 931 patients, 121 (37% women, age range 30 to 86 years) met the study inclusion criteria. The patients’ baseline characteristics are presented in Table 1. No scan was excluded because of poor diagnostic quality. The mean heart rate during the scans was 61 8 beats/min (range 42e82). With the advances in scanner software during the study period, the scanning modes changed. In general, most scans during the first study year were performed with retrospective gating, and most scans performed during the second study year were performed using prospective ECG triggering (“step-and-shoot” mode). Overall, 67 patients (55%) were scanned using the “step-and-shoot” mode and 54 (45%) using retrospective ECG gating. In 14 patients (12%), a tube voltage of 100 kV was used. The median doselength-product was 438 mGy cm (range 160 to 1,392), resulting in a median effective radiation dose estimate of 6.1 mSv (range 2.2 to 19.5) using a conversion coefficient k of 0.014 for the chest. QCA demonstrated obstructive CAD (>50% diameter stenosis) in 145 segments among the 82 of 121 patients (68%). The detailed anatomic distributions of the obstructive segments and extent of CAD are presented in Tables 2 and 3. The results of the pre-CCTA, nonenhanced CT scans for calcium scoring showed a wide range of AU values, as expected (Table 1). A total of 56 patients had a low calcium
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Table 5 Diagnostic accuracy of 256-slice coronary computed tomographic angiography (CCTA) for detection of obstructive coronary artery disease (CAD) in relation to vessel analyzed (segment-based analysis) Parameter Sensitivity Specificity Negative predictive value Positive predictive value Predictive accuracy
LAD (and LM) 57/59 528/546 528/530 57/75 585/605
(97%, 92e100%) (97%, 95e98%) (99.6%, 99.1e100%) (76%, 66e86%) (97%, 95e98%)
LC (and Intermediate Branch) 32/33 454/465 454/455 32/43 486/498
(97%, 91e100) (98%, 96e99) (99.8%, 99.3e100) (74%, 61e88) (98%, 96e99)
Right 52/53 504/521 504/505 52/69 556/574
(98%, 95e100) (97%, 95e98) (99.8%, 99.4e100) (75%, 65e85) (97%, 95e98)
Data are presented as absolute values used to calculate percentages; data in parentheses are percentages with 95% confidence intervals. LAD ¼ left anterior descending coronary artery; LC ¼ left circumflex coronary artery; LM ¼ left main coronary artery.
score (<100 AU), of whom 26 patients had a 0 calcium score. A total of 35 patients had a high calcium score (>400 AU). After CCTA, 1,677 coronary segments were available for comparative analysis (between CCTA and QCA of ICA), of which 39 (2.3%) in 16 patients were nonassessable by CCTA. The most frequent cause of an inability to assess a segment was heavy calcification in 26 of 39 segments. Other reasons included low intravascular contrast or excessive image noise in 7 and significant motion artifacts in 6 segments. Nonassessable segments were considered obstructive for the purpose of the present analysis. Overall, of the 145 segments with obstructive CAD on QCA, CCTA correctly identified 141 (sensitivity 97%, Table 4). An example is shown in Figure 1. Four segments with obstructive CAD in 4 different patients were not detected by CCTA. All 4 patients had additional coronary obstructions identified by CCTA (and QCA). Hence, the patient-based sensitivity was 100%. All 4 false-negative segments were mildly calcified. Two were in the proximal left anterior descending artery, one in the proximal left circumflex artery, and one at the mid-right coronary artery. There were 46 false-positive segments (2.7%) on CCTA that were mostly due to calcification obscuring the arterial lumen. Patient-based analysis showed that 12 patients had false-positive CCTA findings. leading to a positive predictive value of 87% and a suboptimal specificity of 69%. Nonetheless, the predictive accuracy (97% per segment and 90% per patient) was high (Table 4). An elevated total calcium score (>400 AU), present in 35 patients, led to a numerically greater rate of false-positive results (6 of 35, 17%; vs 6 of 86, 7%) than in those with a lower calcium score (p ¼ 0.09). However, it is noteworthy that the false-positive results were mostly related to localized, heavy calcification rather than to a greater total AU score. Regardless of the calcium score, the sensitivity (per patient) was 100% (Table 4). High predictive accuracy was recorded for all vessel territories (vessel-based analysis presented in Table 5). The sensitivity and specificity remained high for both proximal (93% and 97%, respectively) and distal (99% and 97%, respectively) coronary segments. Discussion The present study has shown that in symptomatic patients with chest pain referred for ICA, 256-row CCTA has high diagnostic accuracy compared to QCA. The sensitivity and negative predictive value from a patient-based analysis were both 100%; thus, the CCTA did not miss any patients with
obstructive CAD. Moreover, the rate of nonassessable segments was low (2.3%), allowing a meaningful evaluation of almost all available coronary segments. Few data describing the diagnostic accuracy of the newgeneration CT scanners are available. The initial experience with 256-row CCTA has shown promising results in a mixed group of patients with known or suspected CAD19 and in cohorts of smaller size.20 However, our study is the largest to date to report the performance characteristics (for the diagnosis of obstructive CAD) of this scanner in a group of real world patients without previously known CAD. The use of (off-line) QCA as an objective measure of ICA stenosis strengthens the findings of our study. The finding of a very high negative predictive value (100% per patient, 99.7% per segment) in this selected cohort with a high disease prevalence (68% of patients) is particularly encouraging. It is to be expected that the negative predictive value will remain high in other patient populations with a lower prevalence of obstructive CAD who are those likely to benefit most from CCTA according to current guidelines.21,22 The 256-row scanner used in our study has several features designed to enhance image quality. It has a fast rotation time of 0.27 second (especially advantageous with faster heart rates) and a powerful X-ray tube (allowing a tube current 1,000 mA); however, it also comes equipped with dose-saving technologies.23 The radiation exposure was 64% less in patients scanned with prospective triggering in the present study. These properties enable it to provide high instantaneous energy (1,000 mA) with only a modest increase in radiation exposure when using prospective electrocardiographic triggering.24 The 256-row scanner allows the use of 120-kV (tube voltage) with greater tube current (than that with the previous 64-slice system), which theoretically should reduce image noise and consequently improves the contrastto-noise ratio. Thus, among the theoretical advantages is the improved ability to provide sufficient image quality in the obese population.23,25 The routine use of b blockers and the improved temporal resolution contribute to the low rate of nonassessable segments demonstrated in our study, which we believe is the most significant advance of new-generation scanners compared to older systems. The initial results demonstrating high diagnostic accuracy and a low rate of nonassessable segments have also been reported with other new-generation scanners such as the GE high-definition scanner (GE Healthcare, Milwuakee, Wisconsin)26 and the 320-row scanner (Aquilion ONE, Toshiba Medical Systems, Otawara, Japan),27 which allows 16-cm coverage and the possibility to process data from
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a single heart beat. Several (mostly single-center) studies have also demonstrated the high accuracy of dual-source technology,28,29 which allows high temporal resolution and additional reduction in the radiation dose in selected patients using the high pitch mode.30 Our results have demonstrated the possibly of improved accuracy of new-generation scanners compared to the results obtained with 64-slice systems.12,13 However, even with the 256 slices, just as with the 64-slice systems, the degree of calcification can affect the image quality and therefore the diagnostic accuracy.31 In the present study, the presence of heavy calcification was the main cause of failure to assess a segment. It seems that even with the latest CT technology, calcification still poses a diagnostic challenge. Nonetheless, despite the false-positive findings, mostly related to calcification, 82 of 94 (87%) of this symptomatic patient cohort with “positive” CCTA findings had obstructive CAD on QCA. In addition, among the 4 false-negative segments, small calcifications might have also played a role. A post hoc review of these cases revealed small calcifications in relatively large vessels (>3 mm). This combination created a “patent lumen” view among CCTA readers, but the diameter stenosis was >50% using ICA QCA. Another important issue to be considered when assessing CCTA performance and clinical applicability is the radiation dose. The consistent trend toward a lower radiation dose with dedicated protocols such as prospective ECG triggering (used in 55% of our cohort) or with the use of 100-KV tube voltage (used in 12% of patients) was also apparent in our study. The median dose-length-product among our cohort was 438 mGy cm and gradually decreased during the study period with implementation of the aforementioned dose-saving technologies. It seems that if patient-related factors such as body mass index or heart rate are considered, excellent image quality can still be achieved, even with dose-saving technologies.32 If this trend will continue, it might tip the balance of the clinical risk/benefit ratio in favor of CCTA for a wider range of patient populations. The study might have “verification bias” (post-test referral bias), because the decision to perform invasive angiography (the reference standard) was influenced by the outcome of the diagnostic test (CCTA). After CCTA, more symptomatic patients with a greater prevalence of CAD would likely be referred to ICA (selection bias). However, the negative predictive value remained high, and would be expected to be at least as great in patients with a lower prevalence of obstructive CAD. Disclosures Drs. Gaspar and Peled have received research grants from Philips Healthcare (Andover, Massachusetts). 1. Nikolaou K, Flohr T, Knez A, Rist C, Wintersperger B, Johnson T, Reiser MF, Becker CR. Advances in cardiac CT imaging: 64-slice scanner. Int J Cardiovasc Imaging 2004;20:535e540. 2. Hoffmann MH, Shi H, Schmitz BL, Schmid FT, Lieberknecht M, Schulze R, Ludwig B, Kroschel U, Jahnke N, Haerer W, Brambs HJ, Aschoff AJ. Noninvasive coronary angiography with multislice computed tomography. JAMA 2005;293:2471e2478. 3. Achenbach S, Daniel WG. Computed tomography of the coronary arteries: more than meets the (angiographic) eye. J Am Coll Cardiol 2005;46: 155e157.
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