- Email: [email protected]
Diagnostic performance of 320-slice computed tomography coronary angiography for symptomatic patients in clinical practice
EJINME-03358; No of Pages 6 European Journal of Internal Medicine xxx (2016) xxx–xxx
Contents lists available at ScienceDirect
European Journal of Internal Medicine journal homepage: www.elsevier.com/locate/ejim
Original Article
Diagnostic performance of 320-slice computed tomography coronary angiography for symptomatic patients in clinical practice Futoshi Yamanaka ⁎, Koki Shishido, Tomoki Ochiai, Noriaki Moriyama, Kazuki Tobita, Tomoyuki Tani, Kyosuke Furuhashi, Kazuya Sugitatsu, Daisuke Hachinohe, Tadashi Wada, Shingo Mizuno, Hidetaka Suenaga, Yutaka Tanaka, Masato Murakami, Junya Matsumi, Saeko Takahashi, Takeshi Akasaka, Shinji Tanaka, Shigeru Saito Department of Cardiology and Catheterization Laboratory, Shonankamakura General Hospital, Kamakura, Japan
a r t i c l e
i n f o
Article history: Received 21 February 2016 Received in revised form 1 August 2016 Accepted 14 September 2016 Available online xxxx Keywords: Computed tomography X-ray Angina pectoris Coronary vasospasm
a b s t r a c t Objective: Multi-slice computed tomography (MSCT) coronary angiography has been reported as an effective alternative to invasive conventional coronary angiography (CCA) for the diagnosis of coronary artery disease (CAD). However, in previous reports, the diagnostic accuracy of MSCT has not been significant enough to be of benefit in symptomatic patients. The aim of this study was to identify the usefulness of 320-slice computed tomography coronary angiography (320-CTA) for symptomatic patients in terms of the diagnostic accuracy of 320-CTA and the prevalence of vasospastic angina pectoris (VSAP) within the study cohort. Methods: We retrospectively analyzed 513 consecutive symptomatic patients with suspected CAD who had undergone 320-CTA and CCA. We determined the diagnostic accuracy of 320-CTA using CCA as the reference standard. Ergonovine provocation tests were performed on patients without significant coronary artery stenosis on CCA. Results: Of the total cohort of 513 symptomatic patients, 39% had obstructive CAD. The patient based analysis of the accuracy of 320-CTA showed a sensitivity of 91.0%, a specificity of 71.0%, a positive predictive value of 66.5%, and a negative predictive value of 92.5%. Of the 314 symptomatic patients who did not have significant coronary artery stenosis on CCA, 58 (18%) were diagnosed with VSAP using ergonovine provocation tests. Discussion: The negative and positive predictive values indicate that 320-CTA cannot replace CCA for symptomatic patients. Indeed, a combination of CCA and ergonovine provocation tests should be taken into consideration for symptomatic patients. © 2016 Published by Elsevier B.V. on behalf of European Federation of Internal Medicine.
1. Introduction Coronary artery disease (CAD) is the leading cause of death and a major cause of disability worldwide [1]. In patients with suspected CAD, an evaluation demonstrating the presence and severity of CAD is necessary to provide appropriate clinical management. Conventional coronary angiography (CCA) has been the gold standard for the clinical imaging of CAD. CCA can precisely determine the extent, location, and severity of coronary obstructive lesions, and identify patients who require revascularization. Multi-slice computed tomography (MSCT) coronary angiography has been described as an effective alternative to invasive coronary angiography [2,3]. On the other hand, previous reports have found that MSCT coronary angiography has an unacceptable negative predictive value for symptomatic patients, compared with that
⁎ Corresponding author at: Shonankamakura General Hospital, 1370-1 Okamoto, Kamakura, Kanagawa, Japan. E-mail address: [email protected] (F. Yamanaka).
of CCA [4]. However, these reports were based on the less accurate 64slice version of MSCT coronary angiography. The 320-slice version of MSCT has a wide area detector which enables a greater coverage per gantry rotation and whole heart coverage in a single heat beat. Regarding suspected stable angina pectoris, current guidelines recommend the use of MSCT coronary angiography when considering the pretest probability of disease [5,6]. The guidelines do not take into account the diagnostic accuracy of the developed MSCT coronary angiography, because the diagnostic performance of 320-MSCT coronary angiography in routine clinical practice has not been studied enough. Moreover, the guidelines do not consider the prevalence of vasospastic angina pectoris (VSAP) in symptomatic patients. VSAP is a well-known disease that can cause cardiac death if not treated appropriately [7–9]. Therefore, an accurate diagnosis of VSAP through the use of a provocation test is considerable. No previous studies have evaluated the prevalence of VSAP in patients without significant coronary artery stenosis on computed tomography coronary angiography (CTA). This study aimed to identify the usefulness of 320-slice computed tomography coronary angiography (320-CTA) for symptomatic patients
http://dx.doi.org/10.1016/j.ejim.2016.09.012 0953-6205/© 2016 Published by Elsevier B.V. on behalf of European Federation of Internal Medicine.
Please cite this article as: Yamanaka F, et al, Diagnostic performance of 320-slice computed tomography coronary angiography for symptomatic patients in clinical practice, Eur J Intern Med (2016), http://dx.doi.org/10.1016/j.ejim.2016.09.012
2
F. Yamanaka et al. / European Journal of Internal Medicine xxx (2016) xxx–xxx
in terms of determining the diagnostic accuracy of 320-CTA and to determine the prevalence of vasospastic angina pectoris (VSAP) within the study cohort. 2. Patients and methods Between October 2010 and March 2014, 4482 consecutive patients who were clinically suspected of having CAD underwent 320-CTA. CCA was performed, if 320-CTA findings suggested significant organic coronary artery stenosis, or if it did not suggest significant organic stenosis in spite of symptoms suggestive of CAD. Patients were excluded from the study if they had undergone coronary interventions or CABG surgery, were undergoing hemodialysis, had congestive heart failure classified as New York Heart Association Class III or IV, had aortic stenosis, or had an allergy to contrast media. Fig. 1 shows the patient eligibility for study participation. We enrolled 4482 patients who were suspected of having CAD in the study. Of these patients, 1558 underwent CCA within 3 months, and of these patients, 952 were symptomatic. Of the patients who were symptomatic, 236 were excluded because they had a history of percutaneous coronary intervention, 66 were excluded because they had a history of CABG surgery, 11 were excluded because of hemodialysis, and 27 were excluded because of arrhythmia (12 patients had atrial fibrillation and 25 had frequent premature atrial or ventricular contractions). Eightynine patients with circumferential deposits of calcium in their coronary vessels were excluded from the study. Therefore, a total of 513 eligible patients with suspected CAD were analyzed. 2.1. Scan protocol and image reconstruction All CT scans were performed using a 320-detector CT scanner (Aquilion ONE; Toshiba Medical Systems Corporation, Tochigi-ken, Japan) with 320 detector rows, each 0.5 mm wide, and a gantry rotation time of 350 ms. The tube voltage was 120 kV and the current was automatically adapted to the patient's body mass index and thoracic anatomy. We used a prospective electrocardiographic gating method. For prospective scanning, the phase window was set at 5–85% of the R–R interval for patients with a heart rate of b65 beats/min. Beta
blockers were administered to patients whose heart rates were ≥ 65 beats/min. The start delay was defined by bolus tracking in the ascending aorta, and the scan start was automatically initiated after reaching the threshold level of the baseline Hounsfield units plus 100 Hounsfield units. The contrast medium was injected into an antecubital vein over 10 s and the volume of the contrast medium was adapted according to the patient's body weight (22.2 mg/kg). All of the images were acquired during an inspiratory breath hold. An initial dataset was reconstructed at 75% of the R–R interval, with a slice thickness of 0.50 mm and a reconstruction interval of 0.25 mm. For each patient, the reconstruction of the data with a minimum level of artifacts was undertaken at the CT console by reconstructing the available 5% intervals. The images were then transferred to an image post-processing workstation (Ziostation, Tokyo, Japan). The image sets available on the workstation included axial reconstructed images sent from the CT unit, multi-planar and curved planar reconstructions that had been rotated through 360° along the course of each coronary artery and the major side branches, and thin-slab maximum-intensity projection images that were created at the workstation. 2.2. CT image quality analysis Two reviewers with N3 years of experience in MSCT coronary angiography reviewed all of the CT images. The first reviewer was not informed of the patient's clinical information, and the images were evaluated independently at different times. The three main coronary arteries and their major side branches down to a minimum diameter of 1.5 mm were identified. The images of the vessels were assessed and categorized into three groups: “excellent”, which included those without any artifacts and calcifications that would interfere with the evaluation of the coronary vessels; “fine”, which included those with minor artifacts and calcifications, but evaluation of the vessel lumen was possible; and “poor”, which included those with motion artifacts or circumflex calcifications that prevented evaluation of the coronary artery lumen. We excluded those images from the analysis that were categorized as “poor”. If there were any discrepancies between the reviewers with regard to the quality of the images of the vessels or the severity
Fig. 1. Patient flow chart. PCI = percutaneous coronary intervention; CABG = coronary artery bypass graft surgery; PVC = premature ventricular contraction; PAC = premature atrial contraction.
Please cite this article as: Yamanaka F, et al, Diagnostic performance of 320-slice computed tomography coronary angiography for symptomatic patients in clinical practice, Eur J Intern Med (2016), http://dx.doi.org/10.1016/j.ejim.2016.09.012
F. Yamanaka et al. / European Journal of Internal Medicine xxx (2016) xxx–xxx
3
Fig. 2. Computed tomography coronary angiography in a case with a high calcium score of 1064. A; angiographic view, B; left anterior descending curved multiplanar reformation (MPR) image, C; right coronary artery curved MPR image.
of the coronary artery stenosis, CCA and coronary spasm provocation tests were done. 2.3. CCA and coronary spasm provocation tests CCA was performed within 90 days of the 320-CTA. CCA was performed using standard techniques and at least two different views were obtained for each main vessel. Significant coronary artery stenosis was defined as luminal narrowing of N50%, which was based on visual estimations from the coronary angiographs. The stenosis was evaluated in the worst angiographic view. After CCA, the ergonovine provocation test was performed on patients who did not have significant coronary artery stenosis in a main vessel. Ergonovine was injected into the left coronary artery (20–80 μg) and the right coronary artery (20–40 μg). Coronary angiography was performed 2 min after the coronary injection of ergonovine. Positive criteria for the ergonovine provocation test were coronary occlusion or narrowing of the coronary artery (N90% stenosis) accompanied by chest pain and a change in the ECG. Ergonovine provocation tests were not performed on patients who did not consent to pharmacological provocation tests or in cases in which the diagnostic catheter was unstable. The provocation tests were performed after a N 24 h washout period for calcium channel blockers and nitrates. 2.4. Statistical analysis The categorical variables are presented as numbers and percentages. The continuous variables are expressed as the mean ± standard deviation. Descriptive statistics were used to analyze the per-patient accuracy of 320-CTA. The diagnostic performance of 320-CTA in the detection of
Table 1 Baseline characteristics of the 513 patients. Number of patients Gender (female) Age (years) Body mass index (kg/m2) Risk factors of CAD Diabetes mellitus Hypertension Dyslipidemia Family history of CAD Current smoking Chronic kidney disease (eGFR b 60) eGFR (ml/min) Angina at presentation (CCS classification) Class 1 Class 2 Class 3 Class 4
significant CAD was determined using the sensitivity, specificity, positive predictive value (PPV), and the negative predictive value (NPV) parameters and their corresponding 95% confidence intervals (CIs), and was compared with CCA as the reference standard. The statistical software package used for the analysis of the data was PASW Statistics for Windows, Version 18.0 for Windows (SPSS Inc., Chicago, IL, USA).
3. Results The patient clinical characteristics are presented in Table 1. The median age of patients was 69 years and 39.6% were female. Most patients had a history of hypertension or dyslipidemia. Table 2 shows the specifics associated with CT coronary angiography and CCA assessments undertaken in this study. Beta blockers were administered to N80% of patients before the scans. Multi-vessel disease was seen in 26% of patients. Table 3a compares the accuracy of CT coronary angiography in the present study compared with previous landmark studies. In the present study, the sensitivity, specificity, PPV, and NPV of 320-CTA for the diagnosis of patients with at least one coronary stenosis of N 50% as assessed by CCA, were 91.0% (95% CI: 0.862–0.942), 71.0% (95% CI: 0.658–0.758), 66.5% (95% CI: 0.607–0.719), and 92.5% (95% CI: 0.885–0.952), respectively. Per-vessel analysis is shown in Table 3b. Fig. 3 shows that 39% of the symptomatic patients had obstructive CAD. Of the 314 symptomatic patients who did not have significant coronary artery stenosis, 58 (18%) were diagnosed with VSAP using the ergonovine provocation test. Beta blockers were administered to over 90% of this population. There was no case that short acting beta blocker led to aggravate vasospastic angina pectoris.
Table 2 Characteristics of CT coronary angiography and conventional coronary angiography. 513 203 (39.6) 69 ± 10 23.6 ± 3.4 99 (19.3) 309 (60.2) 298 (58.1) 117 (22.8) 61 (11.9) 70 (13.6) 66.1 ± 14.0 298 (58.1) 168 (32.7) 32 (6.2) 4 (0.8)
CAD; Coronary artery disease, eGFR; estimated glomerular filtration rate, CCS classification; Canadian Cardiovascular Society classification.
Characteristics of CT coronary angiography Heart rate on CT coronary angiography (beats/min) Beta-blocker administered before scan Nitroglycerin administered One-beat reconstruction Radiation exposure (mSv) Median Mean ± SD
60 ± 11 420 (81.9) 508 (99.0) 374 (72.9) 3.45 4.69 ± 3.8
Characteristics of conventional coronary angiography Patients with obstructive CAD Multi-vessel diseases Left main trunk Left anterior descending artery Left circumflex Right coronary artery
199 26 (25) 4 (0.8) 112 (21.7) 63 (12.2) 56 (10.8)
CT; computed tomography, CAD; coronary artery disease.
Please cite this article as: Yamanaka F, et al, Diagnostic performance of 320-slice computed tomography coronary angiography for symptomatic patients in clinical practice, Eur J Intern Med (2016), http://dx.doi.org/10.1016/j.ejim.2016.09.012
4
F. Yamanaka et al. / European Journal of Internal Medicine xxx (2016) xxx–xxx
Table 3a The accuracy per-patient analysis of CT coronary angiography of the present study and the previous landmark study.
Present study CORE 64 ACCURACY
n
CAD prevalence
Sensitivity
Specificity
PPV
NPV
513 230 291
39% 25% 56%
91% 95% 85%
71% 83% 90%
67% 64% 91%
93% 99% 83%
Table 3b The accuracy per-vessel analysis of CT coronary angiography of the present study.
RCA LMT LAD LCx
Sensitivity
Specificity
PPV
NPV
90.1% 100% 94.9% 82.9%
92.3% 99.6% 80.3% 93.5%
65.3% 77.8% 63.9% 66.7%
98.3% 100% 97.7% 97.2%
CAD; coronary artery disease, PPV; positive predictive value, NPV; negative predictive value, RCA; right coronary artery, LMT; left main trunk, LAD; left anterior descending artery, LCx; left circumflex.
4. Discussion In the present study, the sensitivity, specificity, PPV, and NPV were determined to be 91.0%, 71.0%, 66.5%, and 92.5%, respectively, for the diagnostic accuracy of 320-CTA in symptomatic patients. The PPV and the NPV were lower than those previously reported [2]. In addition, 18% of the symptomatic patients who did not have a significant organic coronary artery stenosis were diagnosed with VSAP. Given the prevalence of VSAP, CCA and ergonovine provocation tests should be taken into consideration for symptomatic patients who are suspected of having CAD. Budoff et al. reported a high NPV for 64-MSCT [2]. However, multicenter prospective clinical trials do not often reflect routine clinical practice, because only patients with well-controlled heart rates and extremely low calcium scores of b600 are included in clinical trials. In routine clinical practice, however, some patients do not achieve good heart rate control. The more important clinical implication, however, is that we fail to diagnose VSAP in symptomatic patients who do not have a significant coronary artery stenosis. The precise prevalence of VSAP is unclear, but it has been reported that the presence of VSAP is associated with cardiac death, non-fatal myocardial infarctions, hospitalization caused by unstable angina pectoris, and heart failure [10,11]. The
ergonovine provocation test has an acceptable level of safety, is effective in diagnosing VSAP, and provides useful information for risk predictions in VSAP patients. However, spasm provocation is not routinely undertaken in most hospitals at present. Patients with angina and no significant coronary artery stenosis are often misdiagnosed as having noncardiac chest pain. Some cases of vasospastic angina have culminated in major clinical adverse events, including cardiac death; therefore, we consider that CCA and ergonovine provocation tests are feasible and advisable approaches for symptomatic patients. CT coronary angiography has been described as a tool that is characterized by high NPV. In the present study, the NPV was 92.5%. Previous studies that have used 64-MSCT have reported NPVs of 99% [2] and 83% [4]; hence, there is a considerable difference in the NPVs between these studies. That is a possible reason why the variability depends on the prevalence of CAD within the study populations. The NPV was 99% for a cohort with a CAD prevalence of 25% in the Coronary Artery Evaluation Using 64-Row Multi-detector Computed Tomography Angiography (CORE 64) trial, and 83% for a cohort with a CAD prevalence of 56% in the Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography trial. In this study, the NPV was 92.5% for a cohort with a CAD prevalence of 39%. High disease prevalence rates reduce the NPV. Given the prevalence of CAD among the study populations, the accuracy does not appear to differ between 64-MSCT and 320-CTA. Generally, the prevalence of CAD in symptomatic populations is higher than it is in asymptomatic populations. In a symptomatic population, 320-CTA did not generate an extremely high NPV. Given the prevalence of VSAP, the combination of CCA and the ergonovine provocation test should be taken into consideration. Several reports demonstrated feasibility and accuracy of 320-MDCT coronary angiography. However, these studies have enrolled a very limited number of patients [12,13]. We are considering that it is difficult to determine the true accuracy of MDCT coronary angiography in such a small population. Only one systematic review includes a large number as much as the present study [14]. However, in the entire population included into systematic review, mean age is 60 years old, whereas mean age in the present study is 69 years old. Population generation is different between two research studies. Furthermore, systematic review is based on selected patient's data with excellent condition from a total of 7 small studies. Previous studies have analyzed the diagnostic accuracy persegment, but we did not undertake such an analysis because our study aims were to find significant organic coronary artery stenosis and
Fig. 3. Of the symptomatic patients, 39% had obstructive coronary artery disease. Of 315 symptomatic patients without significant coronary artery stenosis, 58 patients (18%) were diagnosed with vasospastic angina pectoris using the ergonovine provocation test.
Please cite this article as: Yamanaka F, et al, Diagnostic performance of 320-slice computed tomography coronary angiography for symptomatic patients in clinical practice, Eur J Intern Med (2016), http://dx.doi.org/10.1016/j.ejim.2016.09.012
F. Yamanaka et al. / European Journal of Internal Medicine xxx (2016) xxx–xxx
determine the prevalence of VSAP, which causes chest symptoms. The diagnostic accuracy per patient is more important for guiding clinical decision making than the per-segment analysis. For the same reason, we did not compare the diagnostic accuracy in patients with low heart rates versus high heart rates in a sinus rhythm, or between patients in sinus rhythm versus non-sinus rhythms. It remains critical to reduce the heart rate to create a half-scan reconstruction algorithm using data from a single heartbeat and potentially reduce the radiation dose. In the present study we administered beta blockers to patients without contraindications. Ultimately, 92.1% of our patients received beta blockers and heart rates of b 65 beats/min were achieved in all of these patients. In the present study, the ergonovine provocation test was performed in 78% of symptomatic patients without a significant organic coronary artery stenosis. The ergonovine provocation test requires stable positioning of the catheter. We were unable to perform the ergonovine provocation test on some patients in whom it was anatomically difficult to stabilize the catheter. Furthermore, we did not perform the ergonovine provocation test in patients with extremely high blood pressure or without informed consent. Clinically, the most noteworthy implication of this study is that at least 18% of patients without a significant organic coronary artery stenosis were diagnosed with VSAP. The first major limitation of this study is that it was a retrospective analysis performed using data from a single center. Patient's selection bias can't be eliminated. Patients with congestive heart failure or suspected unstable angina pectoris and so on, did not undergo CT coronary angiography. Moreover, the analyzed population is limited in the entire population. However, these patients were selected on same basis of previous landmark study. Furthermore, this report included ergonovine provocation test results. In routine medical practice, we examine both angina pectoris patients who have an organic stenosis and VSAP patients. Therefore, we consider that our research reflects daily clinical practice. Furthermore, our research was based on a large amount of prospectively collected data collected by the staff at one large facility, which therefore reflects daily medical practice. Although multicenter clinical studies are statistically powerful, it is difficult to perform research prospectively using unique protocols in multicenter studies. For example, it would be difficult to perform ergonovine provocation tests using a prospective multicenter registry. A second limitation of this study is that we did not take into account the Agatston score, which is a measure of coronary artery calcium levels [15]. The coronary artery calcification score is reportedly related to the total amount of plaque in the coronary artery [16]. Moreover, severe vascular calcification prevents an evaluation of the degree of coronary artery stenosis because blooming artifacts associated with the calcification itself overestimate the degree of coronary stenosis. In the CORE 64 trial, patients with calcium scores of N 600 were excluded. However, the Agatston score was not a component of the inclusion criteria of the present study. That is because the Agatston score also includes calcifications that are exterior to the vessels, not just within in the vessels. Calcifications exterior to the vessels do not prevent an evaluation of the degree of coronary artery stenosis (Fig. 2). As previously described, advances in CT and image reconstruction software are ensuring that imaging scans are more accurate and use less radiation [17,18]. In this study, we qualitatively assessed patients with circumferential calcifications that involved half of the vessel's circumference, which totally disrupts imaging of the coronary artery lumen by any method. We excluded 89 patients who had circumferential calcifications that involved more than half of the vessel circumference. When the circumferential calcification involved b 50% of the vessel circumference, we were able to evaluate the coronary vessel lumen using curved multi-planar reconstruction images and axial views. The third limitation of this study is that it was limited to an Asian population, and the results did not evaluate racial differences in relation to the prevalence of VSAP. There have been some reports that the prevalence of VSAP is higher in Japanese patients. However, there are few reports regarding the
5
ergonovine provocation test in a western population. Ethnic variability may have affected the prevalence of VSAP in our study. Additional studies are needed. 5. Conclusion This study demonstrates the real-world diagnostic performance of 320-CTA in symptomatic patients who were suspected of having CAD. The NPV and PPV indicated that 320-CTA cannot replace CCA for symptomatic patients. Hence, a combination of CCA and the ergonovine provocation test should be taken into consideration for patients with symptoms of CAD. Conflict of interests The authors state that they have no conflicts of interest. Acknowledgments We thank the radiation technologists (Toshimitsu Shimizu et al.) at the Department of Radiology, Shonankamakura General Hospital, Japan for their excellent work. References [1] Tourlouki E, Matalas AL, Panagiotakos DB. Dietary habits and cardiovascular disease risk in middle-aged and elderly populations: a review of evidence. Clin Interv Aging 2009;4:319–30. [2] Budoff MJ, Dowe D, Jollis JG, Gitter M, Sutherland J, Halamert E, et al. 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;52:1724–32. [3] Moss AJ, Newby DE. CT coronary angiographic evaluation of suspected anginal chest pain. Heart, 2016;102(4):263–8. [4] Miller JM, Rochitte CE, Dewey M, Arbab-Zadeh A, Niinuma H, Gottlieb I, et al. Diagnostic performance of coronary angiography by 64-row CT. N Engl J Med 2008;359: 2324–36. [5] Taylor AJ, Cerqueira M, Hodgson JM, Mark D, Min J, O'Gara P, et al. 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. Circulation 2010;122:e525–55. [6] Yan RT, Miller JM, Rochitte CE, Dewey M, Niinuma H, Clouse ME, et al. Predictors of inaccurate coronary arterial stenosis assessment by CT angiography. JACC Cardiovasc Imaging 2013;6:963–72. [7] Matsue Y, Suzuki M, Nishizaki M, Hojo R, Hashimoto Y, Sakurada H. Clinical implications of an implantable cardioverter-defibrillator in patients with vasospastic angina and lethal ventricular arrhythmia. J Am Coll Cardiol 2012;60:908–13. [8] Jaffe AS. Vasospasm and type 2 AMI? Am J Med 2015;128:329–30. [9] Omar HR, Mangar D, Camporesi EM. A woman with recurrent chest pain and ST-segment elevation. Eur J Intern Med 2015. [10] Takagi Y, Yasuda S, Takahashi J, Tsunoda R, Ogata Y, Seki A, et al. Clinical implications of provocation tests for coronary artery spasm: safety, arrhythmic complications, and prognostic impact: multicentre registry study of the Japanese Coronary Spasm Association. Eur Heart J 2013;34:258–67. [11] Shin ES, Lee JH, Yoo SY, Park Y, Hong YJ, Kim MH, et al. A randomised, multicentre, double blind, placebo controlled trial to evaluate the efficacy and safety of cilostazol in patients with vasospastic angina. Heart 2014;100:1531–6. [12] Nasis A, Leung MC, Antonis PR, Cameron JD, Lehman SJ, Hope SA, et al. Diagnostic accuracy of noninvasive coronary angiography with 320-detector row computed tomography. Am J Cardiol Nov 15 2010;106(10):1429–35. [13] de Graaf FR, Schuijf JD, van Velzen JE, Kroft LJ, de Roos A, Reiber JH, et al. Diagnostic accuracy of 320-row multidetector computed tomography coronary angiography in the non-invasive evaluation of significant coronary artery disease. Eur Heart J Aug 2010;31(15):1908–15. [14] Gaudio C, Pelliccia F, Evangelista A, Tanzilli G, Paravati V, Pannarale G, et al. 320-Row computed tomography coronary angiography vs. conventional coronary angiography in patients with suspected coronary artery disease: a systematic review and meta-analysis. Int J Cardiol Sep 30 2013;168(2):1562–4. http://dx.doi.org/10.1016/ j.ijcard.2012.12.067 [Epub 2013 Jan 22]. [15] Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte Jr M, Detrano R. Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol 1990;15:827–32.
Please cite this article as: Yamanaka F, et al, Diagnostic performance of 320-slice computed tomography coronary angiography for symptomatic patients in clinical practice, Eur J Intern Med (2016), http://dx.doi.org/10.1016/j.ejim.2016.09.012
6
F. Yamanaka et al. / European Journal of Internal Medicine xxx (2016) xxx–xxx
[16] Simons DB, Schwartz RS, Edwards WD, Sheedy PF, Breen JF, Rumberger JA. Noninvasive definition of anatomic coronary artery disease by ultrafast computed tomographic scanning: a quantitative pathologic comparison study. J Am Coll Cardiol 1992;20:1118–26. [17] Yin WH, Lu B, Li N, Han L, Hou ZH, Wu RZ, et al. Iterative reconstruction to preserve image quality and diagnostic accuracy at reduced radiation dose in coronary CT
angiography: an intraindividual comparison. JACC Cardiovasc Imaging 2013;6: 1239–49. [18] Kruk M, Noll D, Achenbach S, Mintz GS, Pregowski J, Kaczmarska E, et al. Impact of coronary artery calcium characteristics on accuracy of CT angiography. JACC Cardiovasc Imaging 2014;7:49–58.
Please cite this article as: Yamanaka F, et al, Diagnostic performance of 320-slice computed tomography coronary angiography for symptomatic patients in clinical practice, Eur J Intern Med (2016), http://dx.doi.org/10.1016/j.ejim.2016.09.012
Contents lists available at ScienceDirect
European Journal of Internal Medicine journal homepage: www.elsevier.com/locate/ejim
Original Article
Diagnostic performance of 320-slice computed tomography coronary angiography for symptomatic patients in clinical practice Futoshi Yamanaka ⁎, Koki Shishido, Tomoki Ochiai, Noriaki Moriyama, Kazuki Tobita, Tomoyuki Tani, Kyosuke Furuhashi, Kazuya Sugitatsu, Daisuke Hachinohe, Tadashi Wada, Shingo Mizuno, Hidetaka Suenaga, Yutaka Tanaka, Masato Murakami, Junya Matsumi, Saeko Takahashi, Takeshi Akasaka, Shinji Tanaka, Shigeru Saito Department of Cardiology and Catheterization Laboratory, Shonankamakura General Hospital, Kamakura, Japan
a r t i c l e
i n f o
Article history: Received 21 February 2016 Received in revised form 1 August 2016 Accepted 14 September 2016 Available online xxxx Keywords: Computed tomography X-ray Angina pectoris Coronary vasospasm
a b s t r a c t Objective: Multi-slice computed tomography (MSCT) coronary angiography has been reported as an effective alternative to invasive conventional coronary angiography (CCA) for the diagnosis of coronary artery disease (CAD). However, in previous reports, the diagnostic accuracy of MSCT has not been significant enough to be of benefit in symptomatic patients. The aim of this study was to identify the usefulness of 320-slice computed tomography coronary angiography (320-CTA) for symptomatic patients in terms of the diagnostic accuracy of 320-CTA and the prevalence of vasospastic angina pectoris (VSAP) within the study cohort. Methods: We retrospectively analyzed 513 consecutive symptomatic patients with suspected CAD who had undergone 320-CTA and CCA. We determined the diagnostic accuracy of 320-CTA using CCA as the reference standard. Ergonovine provocation tests were performed on patients without significant coronary artery stenosis on CCA. Results: Of the total cohort of 513 symptomatic patients, 39% had obstructive CAD. The patient based analysis of the accuracy of 320-CTA showed a sensitivity of 91.0%, a specificity of 71.0%, a positive predictive value of 66.5%, and a negative predictive value of 92.5%. Of the 314 symptomatic patients who did not have significant coronary artery stenosis on CCA, 58 (18%) were diagnosed with VSAP using ergonovine provocation tests. Discussion: The negative and positive predictive values indicate that 320-CTA cannot replace CCA for symptomatic patients. Indeed, a combination of CCA and ergonovine provocation tests should be taken into consideration for symptomatic patients. © 2016 Published by Elsevier B.V. on behalf of European Federation of Internal Medicine.
1. Introduction Coronary artery disease (CAD) is the leading cause of death and a major cause of disability worldwide [1]. In patients with suspected CAD, an evaluation demonstrating the presence and severity of CAD is necessary to provide appropriate clinical management. Conventional coronary angiography (CCA) has been the gold standard for the clinical imaging of CAD. CCA can precisely determine the extent, location, and severity of coronary obstructive lesions, and identify patients who require revascularization. Multi-slice computed tomography (MSCT) coronary angiography has been described as an effective alternative to invasive coronary angiography [2,3]. On the other hand, previous reports have found that MSCT coronary angiography has an unacceptable negative predictive value for symptomatic patients, compared with that
⁎ Corresponding author at: Shonankamakura General Hospital, 1370-1 Okamoto, Kamakura, Kanagawa, Japan. E-mail address: [email protected] (F. Yamanaka).
of CCA [4]. However, these reports were based on the less accurate 64slice version of MSCT coronary angiography. The 320-slice version of MSCT has a wide area detector which enables a greater coverage per gantry rotation and whole heart coverage in a single heat beat. Regarding suspected stable angina pectoris, current guidelines recommend the use of MSCT coronary angiography when considering the pretest probability of disease [5,6]. The guidelines do not take into account the diagnostic accuracy of the developed MSCT coronary angiography, because the diagnostic performance of 320-MSCT coronary angiography in routine clinical practice has not been studied enough. Moreover, the guidelines do not consider the prevalence of vasospastic angina pectoris (VSAP) in symptomatic patients. VSAP is a well-known disease that can cause cardiac death if not treated appropriately [7–9]. Therefore, an accurate diagnosis of VSAP through the use of a provocation test is considerable. No previous studies have evaluated the prevalence of VSAP in patients without significant coronary artery stenosis on computed tomography coronary angiography (CTA). This study aimed to identify the usefulness of 320-slice computed tomography coronary angiography (320-CTA) for symptomatic patients
http://dx.doi.org/10.1016/j.ejim.2016.09.012 0953-6205/© 2016 Published by Elsevier B.V. on behalf of European Federation of Internal Medicine.
Please cite this article as: Yamanaka F, et al, Diagnostic performance of 320-slice computed tomography coronary angiography for symptomatic patients in clinical practice, Eur J Intern Med (2016), http://dx.doi.org/10.1016/j.ejim.2016.09.012
2
F. Yamanaka et al. / European Journal of Internal Medicine xxx (2016) xxx–xxx
in terms of determining the diagnostic accuracy of 320-CTA and to determine the prevalence of vasospastic angina pectoris (VSAP) within the study cohort. 2. Patients and methods Between October 2010 and March 2014, 4482 consecutive patients who were clinically suspected of having CAD underwent 320-CTA. CCA was performed, if 320-CTA findings suggested significant organic coronary artery stenosis, or if it did not suggest significant organic stenosis in spite of symptoms suggestive of CAD. Patients were excluded from the study if they had undergone coronary interventions or CABG surgery, were undergoing hemodialysis, had congestive heart failure classified as New York Heart Association Class III or IV, had aortic stenosis, or had an allergy to contrast media. Fig. 1 shows the patient eligibility for study participation. We enrolled 4482 patients who were suspected of having CAD in the study. Of these patients, 1558 underwent CCA within 3 months, and of these patients, 952 were symptomatic. Of the patients who were symptomatic, 236 were excluded because they had a history of percutaneous coronary intervention, 66 were excluded because they had a history of CABG surgery, 11 were excluded because of hemodialysis, and 27 were excluded because of arrhythmia (12 patients had atrial fibrillation and 25 had frequent premature atrial or ventricular contractions). Eightynine patients with circumferential deposits of calcium in their coronary vessels were excluded from the study. Therefore, a total of 513 eligible patients with suspected CAD were analyzed. 2.1. Scan protocol and image reconstruction All CT scans were performed using a 320-detector CT scanner (Aquilion ONE; Toshiba Medical Systems Corporation, Tochigi-ken, Japan) with 320 detector rows, each 0.5 mm wide, and a gantry rotation time of 350 ms. The tube voltage was 120 kV and the current was automatically adapted to the patient's body mass index and thoracic anatomy. We used a prospective electrocardiographic gating method. For prospective scanning, the phase window was set at 5–85% of the R–R interval for patients with a heart rate of b65 beats/min. Beta
blockers were administered to patients whose heart rates were ≥ 65 beats/min. The start delay was defined by bolus tracking in the ascending aorta, and the scan start was automatically initiated after reaching the threshold level of the baseline Hounsfield units plus 100 Hounsfield units. The contrast medium was injected into an antecubital vein over 10 s and the volume of the contrast medium was adapted according to the patient's body weight (22.2 mg/kg). All of the images were acquired during an inspiratory breath hold. An initial dataset was reconstructed at 75% of the R–R interval, with a slice thickness of 0.50 mm and a reconstruction interval of 0.25 mm. For each patient, the reconstruction of the data with a minimum level of artifacts was undertaken at the CT console by reconstructing the available 5% intervals. The images were then transferred to an image post-processing workstation (Ziostation, Tokyo, Japan). The image sets available on the workstation included axial reconstructed images sent from the CT unit, multi-planar and curved planar reconstructions that had been rotated through 360° along the course of each coronary artery and the major side branches, and thin-slab maximum-intensity projection images that were created at the workstation. 2.2. CT image quality analysis Two reviewers with N3 years of experience in MSCT coronary angiography reviewed all of the CT images. The first reviewer was not informed of the patient's clinical information, and the images were evaluated independently at different times. The three main coronary arteries and their major side branches down to a minimum diameter of 1.5 mm were identified. The images of the vessels were assessed and categorized into three groups: “excellent”, which included those without any artifacts and calcifications that would interfere with the evaluation of the coronary vessels; “fine”, which included those with minor artifacts and calcifications, but evaluation of the vessel lumen was possible; and “poor”, which included those with motion artifacts or circumflex calcifications that prevented evaluation of the coronary artery lumen. We excluded those images from the analysis that were categorized as “poor”. If there were any discrepancies between the reviewers with regard to the quality of the images of the vessels or the severity
Fig. 1. Patient flow chart. PCI = percutaneous coronary intervention; CABG = coronary artery bypass graft surgery; PVC = premature ventricular contraction; PAC = premature atrial contraction.
Please cite this article as: Yamanaka F, et al, Diagnostic performance of 320-slice computed tomography coronary angiography for symptomatic patients in clinical practice, Eur J Intern Med (2016), http://dx.doi.org/10.1016/j.ejim.2016.09.012
F. Yamanaka et al. / European Journal of Internal Medicine xxx (2016) xxx–xxx
3
Fig. 2. Computed tomography coronary angiography in a case with a high calcium score of 1064. A; angiographic view, B; left anterior descending curved multiplanar reformation (MPR) image, C; right coronary artery curved MPR image.
of the coronary artery stenosis, CCA and coronary spasm provocation tests were done. 2.3. CCA and coronary spasm provocation tests CCA was performed within 90 days of the 320-CTA. CCA was performed using standard techniques and at least two different views were obtained for each main vessel. Significant coronary artery stenosis was defined as luminal narrowing of N50%, which was based on visual estimations from the coronary angiographs. The stenosis was evaluated in the worst angiographic view. After CCA, the ergonovine provocation test was performed on patients who did not have significant coronary artery stenosis in a main vessel. Ergonovine was injected into the left coronary artery (20–80 μg) and the right coronary artery (20–40 μg). Coronary angiography was performed 2 min after the coronary injection of ergonovine. Positive criteria for the ergonovine provocation test were coronary occlusion or narrowing of the coronary artery (N90% stenosis) accompanied by chest pain and a change in the ECG. Ergonovine provocation tests were not performed on patients who did not consent to pharmacological provocation tests or in cases in which the diagnostic catheter was unstable. The provocation tests were performed after a N 24 h washout period for calcium channel blockers and nitrates. 2.4. Statistical analysis The categorical variables are presented as numbers and percentages. The continuous variables are expressed as the mean ± standard deviation. Descriptive statistics were used to analyze the per-patient accuracy of 320-CTA. The diagnostic performance of 320-CTA in the detection of
Table 1 Baseline characteristics of the 513 patients. Number of patients Gender (female) Age (years) Body mass index (kg/m2) Risk factors of CAD Diabetes mellitus Hypertension Dyslipidemia Family history of CAD Current smoking Chronic kidney disease (eGFR b 60) eGFR (ml/min) Angina at presentation (CCS classification) Class 1 Class 2 Class 3 Class 4
significant CAD was determined using the sensitivity, specificity, positive predictive value (PPV), and the negative predictive value (NPV) parameters and their corresponding 95% confidence intervals (CIs), and was compared with CCA as the reference standard. The statistical software package used for the analysis of the data was PASW Statistics for Windows, Version 18.0 for Windows (SPSS Inc., Chicago, IL, USA).
3. Results The patient clinical characteristics are presented in Table 1. The median age of patients was 69 years and 39.6% were female. Most patients had a history of hypertension or dyslipidemia. Table 2 shows the specifics associated with CT coronary angiography and CCA assessments undertaken in this study. Beta blockers were administered to N80% of patients before the scans. Multi-vessel disease was seen in 26% of patients. Table 3a compares the accuracy of CT coronary angiography in the present study compared with previous landmark studies. In the present study, the sensitivity, specificity, PPV, and NPV of 320-CTA for the diagnosis of patients with at least one coronary stenosis of N 50% as assessed by CCA, were 91.0% (95% CI: 0.862–0.942), 71.0% (95% CI: 0.658–0.758), 66.5% (95% CI: 0.607–0.719), and 92.5% (95% CI: 0.885–0.952), respectively. Per-vessel analysis is shown in Table 3b. Fig. 3 shows that 39% of the symptomatic patients had obstructive CAD. Of the 314 symptomatic patients who did not have significant coronary artery stenosis, 58 (18%) were diagnosed with VSAP using the ergonovine provocation test. Beta blockers were administered to over 90% of this population. There was no case that short acting beta blocker led to aggravate vasospastic angina pectoris.
Table 2 Characteristics of CT coronary angiography and conventional coronary angiography. 513 203 (39.6) 69 ± 10 23.6 ± 3.4 99 (19.3) 309 (60.2) 298 (58.1) 117 (22.8) 61 (11.9) 70 (13.6) 66.1 ± 14.0 298 (58.1) 168 (32.7) 32 (6.2) 4 (0.8)
CAD; Coronary artery disease, eGFR; estimated glomerular filtration rate, CCS classification; Canadian Cardiovascular Society classification.
Characteristics of CT coronary angiography Heart rate on CT coronary angiography (beats/min) Beta-blocker administered before scan Nitroglycerin administered One-beat reconstruction Radiation exposure (mSv) Median Mean ± SD
60 ± 11 420 (81.9) 508 (99.0) 374 (72.9) 3.45 4.69 ± 3.8
Characteristics of conventional coronary angiography Patients with obstructive CAD Multi-vessel diseases Left main trunk Left anterior descending artery Left circumflex Right coronary artery
199 26 (25) 4 (0.8) 112 (21.7) 63 (12.2) 56 (10.8)
CT; computed tomography, CAD; coronary artery disease.
Please cite this article as: Yamanaka F, et al, Diagnostic performance of 320-slice computed tomography coronary angiography for symptomatic patients in clinical practice, Eur J Intern Med (2016), http://dx.doi.org/10.1016/j.ejim.2016.09.012
4
F. Yamanaka et al. / European Journal of Internal Medicine xxx (2016) xxx–xxx
Table 3a The accuracy per-patient analysis of CT coronary angiography of the present study and the previous landmark study.
Present study CORE 64 ACCURACY
n
CAD prevalence
Sensitivity
Specificity
PPV
NPV
513 230 291
39% 25% 56%
91% 95% 85%
71% 83% 90%
67% 64% 91%
93% 99% 83%
Table 3b The accuracy per-vessel analysis of CT coronary angiography of the present study.
RCA LMT LAD LCx
Sensitivity
Specificity
PPV
NPV
90.1% 100% 94.9% 82.9%
92.3% 99.6% 80.3% 93.5%
65.3% 77.8% 63.9% 66.7%
98.3% 100% 97.7% 97.2%
CAD; coronary artery disease, PPV; positive predictive value, NPV; negative predictive value, RCA; right coronary artery, LMT; left main trunk, LAD; left anterior descending artery, LCx; left circumflex.
4. Discussion In the present study, the sensitivity, specificity, PPV, and NPV were determined to be 91.0%, 71.0%, 66.5%, and 92.5%, respectively, for the diagnostic accuracy of 320-CTA in symptomatic patients. The PPV and the NPV were lower than those previously reported [2]. In addition, 18% of the symptomatic patients who did not have a significant organic coronary artery stenosis were diagnosed with VSAP. Given the prevalence of VSAP, CCA and ergonovine provocation tests should be taken into consideration for symptomatic patients who are suspected of having CAD. Budoff et al. reported a high NPV for 64-MSCT [2]. However, multicenter prospective clinical trials do not often reflect routine clinical practice, because only patients with well-controlled heart rates and extremely low calcium scores of b600 are included in clinical trials. In routine clinical practice, however, some patients do not achieve good heart rate control. The more important clinical implication, however, is that we fail to diagnose VSAP in symptomatic patients who do not have a significant coronary artery stenosis. The precise prevalence of VSAP is unclear, but it has been reported that the presence of VSAP is associated with cardiac death, non-fatal myocardial infarctions, hospitalization caused by unstable angina pectoris, and heart failure [10,11]. The
ergonovine provocation test has an acceptable level of safety, is effective in diagnosing VSAP, and provides useful information for risk predictions in VSAP patients. However, spasm provocation is not routinely undertaken in most hospitals at present. Patients with angina and no significant coronary artery stenosis are often misdiagnosed as having noncardiac chest pain. Some cases of vasospastic angina have culminated in major clinical adverse events, including cardiac death; therefore, we consider that CCA and ergonovine provocation tests are feasible and advisable approaches for symptomatic patients. CT coronary angiography has been described as a tool that is characterized by high NPV. In the present study, the NPV was 92.5%. Previous studies that have used 64-MSCT have reported NPVs of 99% [2] and 83% [4]; hence, there is a considerable difference in the NPVs between these studies. That is a possible reason why the variability depends on the prevalence of CAD within the study populations. The NPV was 99% for a cohort with a CAD prevalence of 25% in the Coronary Artery Evaluation Using 64-Row Multi-detector Computed Tomography Angiography (CORE 64) trial, and 83% for a cohort with a CAD prevalence of 56% in the Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography trial. In this study, the NPV was 92.5% for a cohort with a CAD prevalence of 39%. High disease prevalence rates reduce the NPV. Given the prevalence of CAD among the study populations, the accuracy does not appear to differ between 64-MSCT and 320-CTA. Generally, the prevalence of CAD in symptomatic populations is higher than it is in asymptomatic populations. In a symptomatic population, 320-CTA did not generate an extremely high NPV. Given the prevalence of VSAP, the combination of CCA and the ergonovine provocation test should be taken into consideration. Several reports demonstrated feasibility and accuracy of 320-MDCT coronary angiography. However, these studies have enrolled a very limited number of patients [12,13]. We are considering that it is difficult to determine the true accuracy of MDCT coronary angiography in such a small population. Only one systematic review includes a large number as much as the present study [14]. However, in the entire population included into systematic review, mean age is 60 years old, whereas mean age in the present study is 69 years old. Population generation is different between two research studies. Furthermore, systematic review is based on selected patient's data with excellent condition from a total of 7 small studies. Previous studies have analyzed the diagnostic accuracy persegment, but we did not undertake such an analysis because our study aims were to find significant organic coronary artery stenosis and
Fig. 3. Of the symptomatic patients, 39% had obstructive coronary artery disease. Of 315 symptomatic patients without significant coronary artery stenosis, 58 patients (18%) were diagnosed with vasospastic angina pectoris using the ergonovine provocation test.
Please cite this article as: Yamanaka F, et al, Diagnostic performance of 320-slice computed tomography coronary angiography for symptomatic patients in clinical practice, Eur J Intern Med (2016), http://dx.doi.org/10.1016/j.ejim.2016.09.012
F. Yamanaka et al. / European Journal of Internal Medicine xxx (2016) xxx–xxx
determine the prevalence of VSAP, which causes chest symptoms. The diagnostic accuracy per patient is more important for guiding clinical decision making than the per-segment analysis. For the same reason, we did not compare the diagnostic accuracy in patients with low heart rates versus high heart rates in a sinus rhythm, or between patients in sinus rhythm versus non-sinus rhythms. It remains critical to reduce the heart rate to create a half-scan reconstruction algorithm using data from a single heartbeat and potentially reduce the radiation dose. In the present study we administered beta blockers to patients without contraindications. Ultimately, 92.1% of our patients received beta blockers and heart rates of b 65 beats/min were achieved in all of these patients. In the present study, the ergonovine provocation test was performed in 78% of symptomatic patients without a significant organic coronary artery stenosis. The ergonovine provocation test requires stable positioning of the catheter. We were unable to perform the ergonovine provocation test on some patients in whom it was anatomically difficult to stabilize the catheter. Furthermore, we did not perform the ergonovine provocation test in patients with extremely high blood pressure or without informed consent. Clinically, the most noteworthy implication of this study is that at least 18% of patients without a significant organic coronary artery stenosis were diagnosed with VSAP. The first major limitation of this study is that it was a retrospective analysis performed using data from a single center. Patient's selection bias can't be eliminated. Patients with congestive heart failure or suspected unstable angina pectoris and so on, did not undergo CT coronary angiography. Moreover, the analyzed population is limited in the entire population. However, these patients were selected on same basis of previous landmark study. Furthermore, this report included ergonovine provocation test results. In routine medical practice, we examine both angina pectoris patients who have an organic stenosis and VSAP patients. Therefore, we consider that our research reflects daily clinical practice. Furthermore, our research was based on a large amount of prospectively collected data collected by the staff at one large facility, which therefore reflects daily medical practice. Although multicenter clinical studies are statistically powerful, it is difficult to perform research prospectively using unique protocols in multicenter studies. For example, it would be difficult to perform ergonovine provocation tests using a prospective multicenter registry. A second limitation of this study is that we did not take into account the Agatston score, which is a measure of coronary artery calcium levels [15]. The coronary artery calcification score is reportedly related to the total amount of plaque in the coronary artery [16]. Moreover, severe vascular calcification prevents an evaluation of the degree of coronary artery stenosis because blooming artifacts associated with the calcification itself overestimate the degree of coronary stenosis. In the CORE 64 trial, patients with calcium scores of N 600 were excluded. However, the Agatston score was not a component of the inclusion criteria of the present study. That is because the Agatston score also includes calcifications that are exterior to the vessels, not just within in the vessels. Calcifications exterior to the vessels do not prevent an evaluation of the degree of coronary artery stenosis (Fig. 2). As previously described, advances in CT and image reconstruction software are ensuring that imaging scans are more accurate and use less radiation [17,18]. In this study, we qualitatively assessed patients with circumferential calcifications that involved half of the vessel's circumference, which totally disrupts imaging of the coronary artery lumen by any method. We excluded 89 patients who had circumferential calcifications that involved more than half of the vessel circumference. When the circumferential calcification involved b 50% of the vessel circumference, we were able to evaluate the coronary vessel lumen using curved multi-planar reconstruction images and axial views. The third limitation of this study is that it was limited to an Asian population, and the results did not evaluate racial differences in relation to the prevalence of VSAP. There have been some reports that the prevalence of VSAP is higher in Japanese patients. However, there are few reports regarding the
5
ergonovine provocation test in a western population. Ethnic variability may have affected the prevalence of VSAP in our study. Additional studies are needed. 5. Conclusion This study demonstrates the real-world diagnostic performance of 320-CTA in symptomatic patients who were suspected of having CAD. The NPV and PPV indicated that 320-CTA cannot replace CCA for symptomatic patients. Hence, a combination of CCA and the ergonovine provocation test should be taken into consideration for patients with symptoms of CAD. Conflict of interests The authors state that they have no conflicts of interest. Acknowledgments We thank the radiation technologists (Toshimitsu Shimizu et al.) at the Department of Radiology, Shonankamakura General Hospital, Japan for their excellent work. References [1] Tourlouki E, Matalas AL, Panagiotakos DB. Dietary habits and cardiovascular disease risk in middle-aged and elderly populations: a review of evidence. Clin Interv Aging 2009;4:319–30. [2] Budoff MJ, Dowe D, Jollis JG, Gitter M, Sutherland J, Halamert E, et al. 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;52:1724–32. [3] Moss AJ, Newby DE. CT coronary angiographic evaluation of suspected anginal chest pain. Heart, 2016;102(4):263–8. [4] Miller JM, Rochitte CE, Dewey M, Arbab-Zadeh A, Niinuma H, Gottlieb I, et al. Diagnostic performance of coronary angiography by 64-row CT. N Engl J Med 2008;359: 2324–36. [5] Taylor AJ, Cerqueira M, Hodgson JM, Mark D, Min J, O'Gara P, et al. 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. Circulation 2010;122:e525–55. [6] Yan RT, Miller JM, Rochitte CE, Dewey M, Niinuma H, Clouse ME, et al. Predictors of inaccurate coronary arterial stenosis assessment by CT angiography. JACC Cardiovasc Imaging 2013;6:963–72. [7] Matsue Y, Suzuki M, Nishizaki M, Hojo R, Hashimoto Y, Sakurada H. Clinical implications of an implantable cardioverter-defibrillator in patients with vasospastic angina and lethal ventricular arrhythmia. J Am Coll Cardiol 2012;60:908–13. [8] Jaffe AS. Vasospasm and type 2 AMI? Am J Med 2015;128:329–30. [9] Omar HR, Mangar D, Camporesi EM. A woman with recurrent chest pain and ST-segment elevation. Eur J Intern Med 2015. [10] Takagi Y, Yasuda S, Takahashi J, Tsunoda R, Ogata Y, Seki A, et al. Clinical implications of provocation tests for coronary artery spasm: safety, arrhythmic complications, and prognostic impact: multicentre registry study of the Japanese Coronary Spasm Association. Eur Heart J 2013;34:258–67. [11] Shin ES, Lee JH, Yoo SY, Park Y, Hong YJ, Kim MH, et al. A randomised, multicentre, double blind, placebo controlled trial to evaluate the efficacy and safety of cilostazol in patients with vasospastic angina. Heart 2014;100:1531–6. [12] Nasis A, Leung MC, Antonis PR, Cameron JD, Lehman SJ, Hope SA, et al. Diagnostic accuracy of noninvasive coronary angiography with 320-detector row computed tomography. Am J Cardiol Nov 15 2010;106(10):1429–35. [13] de Graaf FR, Schuijf JD, van Velzen JE, Kroft LJ, de Roos A, Reiber JH, et al. Diagnostic accuracy of 320-row multidetector computed tomography coronary angiography in the non-invasive evaluation of significant coronary artery disease. Eur Heart J Aug 2010;31(15):1908–15. [14] Gaudio C, Pelliccia F, Evangelista A, Tanzilli G, Paravati V, Pannarale G, et al. 320-Row computed tomography coronary angiography vs. conventional coronary angiography in patients with suspected coronary artery disease: a systematic review and meta-analysis. Int J Cardiol Sep 30 2013;168(2):1562–4. http://dx.doi.org/10.1016/ j.ijcard.2012.12.067 [Epub 2013 Jan 22]. [15] Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte Jr M, Detrano R. Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol 1990;15:827–32.
Please cite this article as: Yamanaka F, et al, Diagnostic performance of 320-slice computed tomography coronary angiography for symptomatic patients in clinical practice, Eur J Intern Med (2016), http://dx.doi.org/10.1016/j.ejim.2016.09.012
6
F. Yamanaka et al. / European Journal of Internal Medicine xxx (2016) xxx–xxx
[16] Simons DB, Schwartz RS, Edwards WD, Sheedy PF, Breen JF, Rumberger JA. Noninvasive definition of anatomic coronary artery disease by ultrafast computed tomographic scanning: a quantitative pathologic comparison study. J Am Coll Cardiol 1992;20:1118–26. [17] Yin WH, Lu B, Li N, Han L, Hou ZH, Wu RZ, et al. Iterative reconstruction to preserve image quality and diagnostic accuracy at reduced radiation dose in coronary CT
angiography: an intraindividual comparison. JACC Cardiovasc Imaging 2013;6: 1239–49. [18] Kruk M, Noll D, Achenbach S, Mintz GS, Pregowski J, Kaczmarska E, et al. Impact of coronary artery calcium characteristics on accuracy of CT angiography. JACC Cardiovasc Imaging 2014;7:49–58.
Please cite this article as: Yamanaka F, et al, Diagnostic performance of 320-slice computed tomography coronary angiography for symptomatic patients in clinical practice, Eur J Intern Med (2016), http://dx.doi.org/10.1016/j.ejim.2016.09.012