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Evaluation of coronary artery stent patency by using 64-slice multi-detector computed tomography and conventional coronary angiography: A comparison with intravascular ultrasonography
International Journal of Cardiology 166 (2013) 90–95
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Evaluation of coronary artery stent patency by using 64-slice multi-detector computed tomography and conventional coronary angiography: A comparison with intravascular ultrasonography Chi-Ling Hang a, b,⁎, Yi-Wei Lee b, c, Gary Bih-Fang Guo a, b, Ali Ahmed Youssef a, d, Hon-Kan Yip a, b, Chu-Feng Liu e, Sarah Chua a, b, Hseuh-Wen Chang f, Yu-Fan Cheng b, c, Shyh-Ming Chen a, b,⁎, 1 a
Section of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China Chang Gung University College of Medicine, Kaohsiung, Taiwan, Republic of China c Department of Radiology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China d Cardiology Department, Suez Canal University, Ismailia, Egypt e Emergency Department, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China f Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan, Republic of China b
a r t i c l e
i n f o
Article history: Received 21 May 2011 Received in revised form 19 September 2011 Accepted 9 October 2011 Available online 5 November 2011 Keywords: Multi-slice computed tomography In-stent restenosis Intravascular ultrasonography Coronary angiography
a b s t r a c t Background: Most studies have investigated the diagnostic accuracy of 64-slice multi-detector computed tomography (MDCT) to detect coronary artery stent patency by using conventional coronary angiography (CCA) as the reference standard. In this study, we compared the diagnostic accuracy of MDCT and CCA by using intravascular ultrasonography (IVUS) as the reference standard. Methods: Forty-six patients with previously implanted coronary artery stents (n = 87) underwent MDCT followed by CCA and IVUS within 24 h. Sensitivities, specificities, positive predictive values (PPV) and negative predictive values (NPV) of MDCT and CCA for detecting or excluding in-stent diameter restenosis (ISDR) by using in-stent area restenosis (ISAR) and minimal luminal area (MLA) ≤ 4.0 mm 2 of IVUS as the reference standard were determined. Results: Eight stents (9%) were judged non-evaluable using MDCT for the detection of ISDR. ISDR was detected in 28% (22/79) of the evaluable stents using CCA. When ISAR was detected using IVUS, the sensitivity, specificity, PPV, and NPV for ISDR detection by using MDCT were 71%, 96%, 91% and 86%, and the corresponding values for CCA were 64%, 96%, 90% and 83%. When MLA ≤ 4.0 mm 2 was detected using IVUS, the sensitivity, specificity, PPV, and NPV for ISDR detection by using MDCT were 87%, 96%, 91% and 95%, and for CCA were 78%, 96%, 90% and 92%. Conclusions: When ISAR with MLA ≤ 4.0 mm2was detected on IVUS, CCA and MDCT had similar diagnostic accuracies for ISDR detection. High specificity and NPV make 64-slice MDCT a reliable non-invasive method for excluding ISDR. © 2011 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Multi-detector computed tomography (MDCT) is a potential noninvasive diagnostic tool for evaluating coronary artery stent patency. However, despite the introduction of 64-slice MDCT with improved spatial and temporal resolution, the technique has not been proved reliable for assessing coronary artery stent patency probably because ⁎ Corresponding authors at: Kaohsiung Chang Gung Memorial Hospital, 123 Tai Pei Road, Niao Sung District, Kaohsiung City 83305, Taiwan, Republic of China. Tel.: +886 73702028; fax: +886 77322402. E-mail addresses: [email protected] (C.-L. Hang), [email protected] (S.-M. Chen). 1 Dr. Shyh-Ming Chen contributed significantly in the initial planning, case collection, coronary angiogram reading, and manuscript writing, and thus deserves to be a co-correspondent of this manuscript. 0167-5273/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2011.10.003
of beam-hardening artifacts and partial volume effects [1–9]. Studies have shown that 64-slice MDCT can provide as much information on coronary artery plaque morphology as do intravascular ultrasonography (IVUS) can [10–12]. Unlike MDCT or conventional coronary angiography (CCA), IVUS helps determine in-stent luminal obstruction clearly. Therefore, we investigated the feasibility of assessing coronary artery stent patency and restenosis with 64-slice MDCT and CCA, and compared the results to those obtained using IVUS as the reference standard. 2. Methods Fifty patients with previously implanted coronary artery stents were included in this study. The patients who were either scheduled for coronary angiography because of angina pectoris or had undergone stenting 6 months ago were examined with 64slice MDCT (Aquilion 64; Toshiba, Medical Systems Corporation, Tochigi-ken, Tokyo,
C.-L. Hang et al. / International Journal of Cardiology 166 (2013) 90–95 Japan). Retrospectively electrocardiography (ECG)-gated contrast-enhanced 64-slice MDCT was performed ≤ 24 h prior to CCA. We only included patients who received IVUS (2.9F; 40 MHz; Atlantis SR Pro coronary imaging catheter; Boston Scientific, Fremont, CA, USA) as a part of the catheterization procedure and who had sinus rhythm and a stable clinical condition. Patients with implanted pacemakers or automatic implantable cardioverter defibrillators, or contraindication to administration of iodinated contrast agent were not included. Four patients were excluded from the study because of IVUS machine malfunction. Thus, the final study cohort consisted of 46 patients. Each patient was instructed to lie down in the supine position in the gantry of the 64-slice MDCT scanner. Leads were attached to perform ECG and image recording simultaneously, which was necessary for interrelated image reconstruction. The study protocol included oral administration of 10 mg of propanolol before the scheduled CT scan in patients with heart rate >80 bpm. In patients with an unsatisfactory lowering of the heart rate, a higher dose of propanolol was given until the target heart rate was reached. All patients received a single dose of 0.6 mg sublingual nitroglycerin 2 min prior to the scan. This study was approved by the Ethics Committee of Chang Gung Memorial hospital and all patients had written informed consent obtained from all the patients. The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the institution's human research committee. The imaging protocol consisted of the following steps. First, a non-contrast-enhanced coronal view of the chest was obtained to determine the position of the heart, define the scan volume for further imaging, and recognize eventual coronary calcification. Then, a bolus of 70–80 mL of non-ionic contrast agent (Omnipaque 350, 350 mg I/mL; GE Healthcare, Ireland Cork, Ireland) was injected into an antecubital vein at a flow rate of 4.5–5 mL/s. Further, approximately 30–40 mL of saline solution was injected via an 18-gauge catheter. As soon as the signal in the region of interest in the ascending aorta reached a predefined threshold of 150 Hounsfield units (HU), scanning was performed automatically, and the entire volume of the heart was acquired in 8–9 s during 1 breathhold, with simultaneous recording of the electrocardiographic tracing. The MDCT scanning parameters determined according to the patient's size, were as follows: collimation, 64 × 0.5 mm; gantry rotation time, 0.4 s; pitch, 0.2–0.225; standard and stent reconstruction kernel, FC43 and FC05; tube voltage, 120 kV; and current, 400–500 mA. To determine the optimal phase and for comprehensive functional evaluation, the data sets were reconstructed with retrospective ECG gating at every 10% (between 0 and 90%) of the R–R interval with the standard kernel, adequate field of view (FOV), 512 × 512 matrix size, and 1 mm thickness with a 0.8 mm interval. The axial images obtained in the optimal phase were reconstructed with the same parameters but with a slice thickness of 0.5 mm and interval of 0.3 mm. All the data were transmitted to a workstation (Vitrea 2, Vital Images Inc, MN, USA) for post-processing. The estimated effective radiation dose was approximately 15–17.5 mSv. The MDCT images were evaluated by a radiologist with 3 years of experience in reading 64-slice MDCT data and who was blinded to the findings obtained using CCA. The radiologist subjectively rated the overall image quality for in-stent diameter restenosis (ISDR) on a 3-point scale. Images with distinct anatomic details and no noise or artifacts were rated as 3 (excellent), while those with clear anatomic details and mild or moderate increase in noise and/or artifacts not affecting the diagnostic value were rated as 2 (good). Furthermore, images with a distinct increase in noise and/or artifacts affecting diagnostic value were rated as 1 (poor). Only patients for whom high- or moderate-quality images of the stented segments had been obtained were considered for further analysis. Qualitative evaluation of ISDR of stented segments were visually classified into 3 grades using the following criteria: grade 1, none or slight neointimal proliferation; grade 2, mild neointimal proliferation but no significant restenosis (b50% narrowing); grade 3, moderate neointimal proliferation with significant restenosis or total occlusion (≥50% narrowing or occlusion). In addition, a quantitative evaluation of ISDR by MDCT was performed on those stents without ISDR by either CCA or MDCT yielding positive for ISAR or minimal luminal area ≤4.0 mm2 by IVUS (false negative). Diameters of the proximal and distal reference segments and narrower stent lumen were measured in short axis views. Degree of luminal narrowing was quantified as percent diameter stenosis by calculating the ratio between the reference segment and stent diameters. IVUS images were obtained empirically in all the patients. The image obtained for each site was manipulated such that the size and pattern were similar to that of the MDCT image, and helped clearly distinguish the vessel form the surrounding tissue, plaque, and lumen. These measurements were performed by an experienced interventional cardiologist who was not blinded to the procedures. IVUS was performed as a part of the catheterization procedure in all 46 patients. IVUS images were recorded after initiating an automated pullback of the catheter at 0.5 mm/s. IVUS images of the entire pullback were recorded on S-VHS videotape. Area measurements were performed at sites with minimal lumen and stent areas, and at proximal and distal reference sites. ISAR was defined as percent area stenosis ≥ 50% anywhere within the stent or within 5-mm segments proximal or distal to the stent margins. A significant lesion was defined as a MLA ≤6.0 mm2 for the left main coronary arteries and a MLA ≤4.0 mm2 for other epicardial coronary arteries. CCA was performed by using the standard procedure after intracoronary injection of 200 μg of nitroglycerin. Multiple views of the coronary arteries were obtained and stored on a CD-ROM. Coronary angiograms were evaluated by QCA (Quantor QCA; Siemens Medical System, Forchheim, Germany) by an independent experienced cardiologist blinded to the image source. ISDR was defined as percent diameter stenosis ≥50% anywhere within the stent or within 5-mm segments proximal or distal to the stent margins.
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3. Statistics The evaluability (the ratio of the number of evaluable segments: total number of segments) of the MDCT scan in identifying ISDR was calculated. The diagnostic accuracy of 64-slice MDCT in detecting ISDR with various degrees of luminal obstruction was evaluated using CCA as the reference standard. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for stenosis ≥50% and for lesions with diameter reduction of b50%. The capability of 64-slice MDCT and CCA to detect and quantify ISDR was compared to that of IVUS, the reference standard, to detect and quantify in-stent area restenosis (ISAR) and MLA ≤4.0 mm 2. Sensitivity, specificity, PPV, and NPV were calculated for stenosis ≥50% and for lesions with for diameter and area reduction of b50% and MLA ≤4.0 mm 2. The differences in the accuracy and evaluability of MDCT, and the standards were calculated using the chi-square test or Fisher's exact test. A 95% confidence interval was calculated from the binominal expression. A p value b0.05 was considered statistically significant. 4. Results The baseline clinical and angiographic characteristics of the patients are summarized in Tables 1 and 2. MDCT was performed ≤24 h prior to CCA and IVUS in the 46 patients with 87 stents (Table 2). Sixteen (35%) patients presented with unstable angina, and 30 (65%) patients had either stable angina or were asymptomatic. The median interval between stent implantation and MDCT was 43± 39 months. The sites of stent implantation were the left anterior descending artery (33 patients, 38%), the left circumflex artery (23 patients, 26%), and the right coronary artery (31 patients, 36%). The characteristics of the 15 types of implanted stents are summarized in Table 3. According to the qualitative analysis of the reader, 8 stents (total, 87; 9%) were judged non-evaluable using MDCT for the detection of diameter stenosis. The remaining 79 stents were depicted with good image quality in 60 stents (total, 87; 69%) and excellent image quality in 19 stents (total, 87; 22%). The evaluability of MDCT with regard to stent characteristics and index vessel is shown in Tables 4–6. Neither the stent characteristics nor the index vessels were significantly associated with the evaluability of the stented segments. ISDR was detected using CCA in 28% (22/79) of the evaluable stents and ISAR was detected using IVUS in 35% (28/79) of the evaluable stents. The diagnostic accuracy of MDCT and CCA in relation to stent characteristics and index vessel is shown in Tables 4–6. No differences were seen in the diagnostic accuracy of MDCT and CCA for ISDR identification with regard to stent characteristics or index vessels (Table 4). Furthermore, when ISAR was detected on IVUS, no significant differences were found in ISDR identification by MDCT or CCA (Tables 5 and 6). When ISDR was identified on CCA, MDCT had sensitivity, specificity, PPV, and NPV of 95%, 95%, 86%, and 98%, respectively (Table 4). When the analysis was performed with inclusion of non-evaluable Table 1 Baseline clinical characteristics of the patients⁎. Number (n) of patients Male, n (%) Age in years Diabetes mellitus, n (%) Hypertension, n (%) Smoking, n (%) Hypercholesterolemia, n (%) Previous myocardial infarction, n (%) Unstable angina, n (%) Stable angina or asymptomatic, n (%) Time lapse after last PCI (months) PCI = percutaneous coronary intervention. ⁎p was not significant for any other factor.
46 40 (87) 60.5 ± 9.7 11 (24) 24 (52) 19 (41) 28 (61) 27 (59) 16 (35) 30 (65) 43 ± 39
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C.-L. Hang et al. / International Journal of Cardiology 166 (2013) 90–95 Table 2 Baseline angiographic characteristics. Number of patients Multivessel disease stenting, n (%) 3-vessel stenting, n (%) 2-vessel stenting, n (%) Number of stents Size and site of stent implantation Left anterior descending artery, n (%) 2.5 mm 2.75 mm 3.0 mm 3.5 mm Left circumflex artery, n (%) 2.5 mm 2.75 mm 3.0 mm 3.5 mm 4.5 mm Right coronary artery, n (%) 2.75 mm 3.0 mm 3.5 mm 4.0 mm
46 16 (35) 4 (9) 12 (26) 87 33 (38) 5 4 19 5 23 (26) 5 1 11 5 1 31 (36) 2 12 15 2
segments, specificity and PPV decreased to 86% and 70%, respectively, with a sensitivity of 95% and a NPV of 98% (Table 7). When ISAR was detected on IVUS, the sensitivity, specificity, PPV, and NPV for ISDR identification by using MDCT were 71%, 96%, 91% and 86%, respectively (Table 5) and the corresponding values for CCA were 64%, 96%, 90% and 83% (Table 6). When non-evaluable segments were included, the specificity and PPV, and NPV for ISDR identification by using MDCT decreased to 86% and 73%, respectively, with a sensitivity of 73% and a NPV of 86%, and the sensitivity, specificity, PPV, and NPV for CCA were 67%, 96%, 91% and 85%, respectively (Table 7). When MLA ≤4.0 mm 2 was detected on IVUS, the sensitivity, specificity, PPV, and NPV for ISDR identification by using MDCT were 87%, 96%, 91% and 95%, respectively and the corresponding values for CCA were 78%, 96%, 90% and 92% (Table 8). When non-evaluable segments were included, the specificity and PPV for ISDR identification by using MDCT decreased to 87% and 73%, respectively with a sensitivity of 88% and a NPV of 95% and the sensitivity, specificity, PPV, and NPV for CCA were 80%, 97%, 91% and 92% (Table 8). An incorrect diagnosis of absence of ISDR (false negative) was made using both MDCT and
Table 3 Stent characteristics. Number of stents Stents/patient Stent types Drug-coated stents with strut thickness ≥ 100 μm Cypher (Johnson and Johnson) Taxus (Boston Scientific) Bare-metal stents with strut thickness b 100 μm Multilink Vision (Guidant) Multilink Pixel (Guidant) Multilink Zeta (Guidant) Palmaz–Schatz (Johnson & Johnson) Crown (Cordis) Driver (Medtronic) Baremetal stents with strut thickness ≥ 100 μm BX Velocity (Guidant) Multilink Penta (Guidant) S7 (Medtronic) AVE GFX (Medtronic) Wall (Boston Scientific) Nir (Boston Scientific) Express (Boston Scientific) Cobalt alloy stents Driver (Medtronic) Vision (Guidant) Wall (Boston Scientific)
87 1.89 15 24 14 10 34 3 2 3 3 2 21 29 6 1 5 3 1 8 5 25 21 3 1
CCA in 8 of the 28 stents deemed to have significant ISAR by using IVUS (Table 9). Five of these 8 stents with ISAR had a minimal luminal area (MLA) >4.0 mm 2, and the remaining 3 stents had an MLA ≤4.0 mm 2. Two stents showing ISAR with MLA ≤4.0 mm 2 were correctly identified using MDCT but wrongly classified using CCA (Table 9). 5. Discussion In this study, MDCT was performed ≤24 h prior to CCA, and IVUS was a part of the catheterization procedure in all study patients. Among the 87 stented segments, 79 were evaluable for ISDR by using MDCT with an overall evaluability of 91%; these findings were similar to those of recently published studies [2–5,8]. In contrast to other studies, our study revealed that factors such as stent diameter, strut thickness, stent material, stent type, and index vessel did not affect stent evaluation [4–6]. However, similar to our findings, the findings of the study conducted by Cademartiri et al. revealed no significant differences in the evaluability of stents with diameters greater than, equal to, and lesser than 3.0 mm 3. Similar to our study, the studies conducted by Schuijf et al. and Nakamura et al. revealed no association between strut thickness and stent evaluability [9,13]. Wykrzykowska et al. and Schuijf et al. reported no statistically significant variations in-stent evaluability assessed on the basis of stent placement in different locations in the index vessels [7,9]. Therefore, further larger trials are necessary to evaluate the various factors that influence ISDR evaluability. Although the role of 64-slice MDCT has been expanded to include the evaluation of coronary artery wall thickness and plaque texture, IVUS is recognized as the standard reference method [10–12,14–18]. Compared to other current techniques, IVUS is superior in identifying in-stent luminal obstruction. To our knowledge, this is the only study in English literature to evaluate coronary artery stent patency by using 64-slice MDCT and to use IVUS as a part of the catheterization procedure in all the study patients. In the study conducted by Andreini et al., IVUS was performed in patients in whom CCA revealed moderate ISDR [5]. They observed a significant variation in area measurements between MDCT and IVUS, but suggested that this variation does not affect MDCT assessment of percent in-stent restenosis [5]. In our study, the total number of stents evaluable for ISAR by using MDCT was less (40%) mostly due to motion artifacts. Thus, 64-slice MDCT is not appropriate for in-stent area assessment. Therefore, we evaluated the diagnostic accuracies of MDCT and CCA for detecting ISDR by using ISAR and MLA ≤4.0 mm 2 detection on IVUS as the reference. When ISAR was detected on IVUS, MDCT showed decreased sensitivity from high to low, decreased NPV from high to moderate, constant high specificity, and constant moderate PPV. On the other hand, when ISAR was detected on IVUS, CCA showed decreased sensitivity, moderate PPV and NPV, and high specificity. Sensitivity and NPV were lower because of a relatively high false-negative rate (an incorrect diagnosis of absence of ISDR was used using MDCT in 8 (29%) of the 28 deemed to have ISAR by IVUS and in 10 (36%) of the 28 stents using CCA). Eight of the 28 ISAR were misdiagnosed by both MDCT and CCA. Among the 8 stents showing ISAR, 3 had a MLA ≤4.0 mm 2, and repeat percutaneous coronary intervention (PCI) was performed in these 3 cases. Two of these 3 stents were incorrectly classified by CCA but correctly identified by MDCT. When ISAR in stents with MLA ≤4.0 mm 2 was detected on IVUS, which was used as the gold standard, the sensitivity and NPV of MDCT were 87% and 95%, respectively. The sensitivity and NPV of MDCT were actually higher than the corresponding values for CCA (78% and 92%). In the study by Joshi et al., in patients with intermediategrade lesions identified on CCA, absolute measurements of stenosis severity determined on MDCT correlated with those determined on IVUS but not with those determined on CCA [19]. They found that, when IVUS is used was used as the gold standard rather than CCA,
C.-L. Hang et al. / International Journal of Cardiology 166 (2013) 90–95
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Table 4 Accuracy and evaluability of 64-slice MDCT to detect in-stent diameter restenosis in comparison to CCA and in relation to stent characteristics and index vessel⁎.
Stented segments Stented artery LAD LCX RCA Stent material Stainless steel Cobalt chromium Stent type DES BMS Strut thickness (μm) b100 ≥100 Stent diameter (mm) b3.0 ≥3.0
No. of stents
Evaluability
TP
TN
FP
FN
Sensitivity
Specificity
PPV
NPV
87
91%
19
56
3
1
95% (85–100)
95% (89–100)
86% (72–100)
98% (95–100)
33 23 31
88% 96% 90%
6 4 9
21 17 18
2 0 1
0 1 0
100% 80% (45–100) 100%
91% (80–100) 100% 95% (85–100)
75% (45–100) 100% 90% (71–100)
100% 94% (84–100) 100%
61 26
92% 92%
14 5
40 16
0 3
1 0
93% (81–100) 100%
100% 84% (68–100)
100% 63% (29–96)
98% (93–100) 100%
25 62
92% 89%
5 14
18 38
0 3
0 1
100% 93% (81–100)
100% 93% (85–100)
100% 82% (64–100)
100% 97% (92–100)
34 53
88% 91%
8 11
21 35
2 1
0 1
100% 92% (76–100)
91% (80–100) 97% (92–100)
80% (55–100) 92% (76–100)
100% 97% (92–100)
17 70
100% 87%
6 13
11 45
0 3
0 1
100% 93% (79–100)
100% 94% (87–100)
100% 81% (62–100)
100% 98% (94–100)
TP = true positive; TN = true negative; FP = false positive; FN = false negative; PPV = positive predictive value; NPV = negative predictive value; LAD = left anterior descending artery; LCX = left circumflex artery; RCA = right coronary artery; BMS = bare-metal stent; DES = drug-eluting stent. ⁎ p was not significant for any other factor.
Table 5 Accuracy of 64-slice MDCT to detect in-stent diameter restenosis in comparison to in-stent area restenosis of IVUS and in relation to stent characteristics and index vessel⁎.
Stented segments Stented artery LAD LCX RCA Stent material Stainless steel Cobalt chromium Stent type DES BMS Strut thickness (μm) b100 ≥100 Stent diameter (mm) b3.0 ≥3.0
No. of stents
Evaluability
TP
TN
FP
FN
Sensitivity
Specificity
PPV
NPV
87
91%
20
49
2
8
71% (55–88)
96% (91–100)
91% (79–100)
86% (77–95)
33 23 31
88% 96% 90%
8 3 9
17 17 15
0 1 1
4 1 3
67% (40–93) 75% (33–100) 75% (51–100)
100% 94% (84–100) 94% (82–100)
100% 75% (33–100) 90% (71–100)
81% (64–98) 94% (84–100) 83% (66–100)
61 26
92% 92%
13 7
35 14
1 1
6 2
68% (48–89) 78% (51–100)
97% (92–100) 93% (81–100)
93% (79–100) 88% (65–100)
85% (75–96) 88% (71–100)
25 62
92% 89%
5 15
18 31
0 2
0 8
100% 65% (46–85)
100% () 94% (86–100)
100% 88% (73–100)
100% 79% (67–92)
34 53
88% 91%
10 10
16 33
0 2
5 3
67% (43–90) 77% (54–100)
100% 94% (87–100)
100% 83% (62–100)
76% (58–94) 92% (83–100)
17 70
100% 87%
6 14
10 39
0 2
1 7
86% (60–100) 67% (47–87)
100% 95% (89–100)
100% 88% (71–100)
91% (74–100) 85% (74–95)
⁎ p was not significant for any other factor. Abbreviations as in Table 4.
Table 6 Accuracy of CCA to detect in-stent diameter restenosis in comparison to in-stent area restenosis of IVUS and in relation to stent characteristics and index vessel for those segments assessable by 64-slice MDCT⁎.
Stented segments Stented artery LAD LCX RCA Stent material Stainless steel Cobalt chromium Stent type DES BMS Strut thickness (μm) b100 ≥100 Stent diameter (mm) b3.0 ≥3.0
No. of stents
Evaluability
TP
TN
FP
FN
Sensitivity
Specificity
PPV
NPV
87
91%
18
49
2
10
64% (47–82)
96% (91–100)
90% (77–100)
83% (73–93)
33 23 31
88% 96% 90%
6 3 9
17 16 16
0 2 0
6 1 3
50% (22–78) 75% (33–100) 75% (51–100)
100% 89% (74–100) 100%
100% 60% (17–100) 100%
74% (56–92) 94% (83–100) 84% (68–100)
61 26
92% 92%
13 5
34 15
2 0
6 4
68% (48–89) 56% (23–88)
94% (87–100) 100%
87% (69–100) 100%
85% (74–96) 79% (61–97)
25 62
92% 89%
5 13
18 31
0 2
0 10
100% 57% (36–77)
100% 94% (86–100)
100% 87% (69–100)
100% 76% (63–89)
34 53
88% 91%
8 10
16 33
0 2
7 3
53% (28–79) 77% (54–100)
100% 94% (87–100)
100% 83% (62–100)
70% (51–88) 92% (83–100)
17 70
100% 87%
6 12
10 39
0 2
1 9
86% (60–100) 57% (36–78)
100% 95% (89–100)
100% 86% (67–100)
91% (74–100) 81% (70–92)
⁎ p was not significant for any other factor. Abbreviations as in Table 4.
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C.-L. Hang et al. / International Journal of Cardiology 166 (2013) 90–95
Table 7 Accuracy of 64-slice MDCT to detect in-stent diameter restenosis in comparison to CCA and accuracy of CCA and MDCT to detect in-stent diameter restenosis in comparison to in-stent area restenosis of IVUS with inclusion of non-evaluable segments.
MDCT vs CCA CCA vs IVUS MDCT vs IVUS
No. of stents
TP
TN
FP
FN
Sensitivity
Specificity
PPV
NPV
87 87 87
21 20 22
56 55 49
9 2 8
1 10 8
95% 67% 73%
86% 96%⁎ 86%⁎
70% 91% 73%
98% 85% 86%
⁎ p = 0.048; specificity of CCA is significantly higher than MDCT. Abbreviations as in Table 4.
MDCT appeared to be more accurate, and they suggested that the limitations of CCA as a reference standard need to be considered in studies evaluating the accuracy of MDCT [19]. When non-evaluable segments were excluded, there were no differences in the diagnostic accuracy of stent characteristics or index vessels between MDCT and CCA, MDCT and IVUS or CCA and IVUS in ISDR identifications. When MLA ≤4.0 mm 2 was used as reference and non-evaluable segments were excluded, MDCT had higher specificity and NPV for excluding ISDR rather than CCA. Furthermore, when the above analysis was performed with inclusion of non-evaluable segments, MDCT and CCA had similar high NPV (95% and 92%, respectively) for excluding ISDR. Therefore, 64-slice MDCT is a reliable non-invasive tool for excluding ISDR.
Table 9 Stents without in-stent diameter restenosis by either CCA or MDCT yielding positive for in-stent area restenosis or minimal luminal area ≤4.0 mm2 by IVUS (false negative). Stents
% In-stent diameter % In-stent diameter % In-stent area Minimal luminal stenosis by MDCT stenosis by CCA stenosis by IVUS area by IVUS
No. 1 ⁎ No. 2 No. 3 No. 4 No. 5 ⁎ No. 6 ⁎ No. 7 No. 8 ⁎⁎ No. 9 ⁎⁎ No. 10
30% 45% 20% 25% 25% 25% 40% 30% ⁎⁎50% ⁎⁎52%
28% 37% 38% 38% 33% 35% 45% 41% 36% 35%
53% ⁎51% 50% 56% 57% ⁎60% ⁎56% 50% ⁎⁎53% ⁎⁎55%
>4.0 mm2 ⁎≤4.0 mm2 >4.0 mm2 >4.0 mm2 >4.0 mm2 ⁎≤4.0 mm2 ⁎≤4.0 mm2 >4.0 mm2 ⁎⁎≤4.0 mm2 ⁎⁎≤4.0 mm2
⁎ An incorrect diagnosis of absence of ISDR was made using both MDCT and CCA in stents deemed to have significant ISAR by using IVUS had an MLA ≤ 4.0 mm2. ⁎⁎ Stents showing ISAR with MLA ≤ 4.0 mm2 were correctly identified using MDCT but wrongly classified using CCA.
Finally, the estimated mean effective radiation dose (approximately, 15–17.5 mSv) in our study is higher than the radiation dose used in stress perfusion imaging (8–20 mSv) and similar to other 64-slice MDCT studies (8.2–21.4 mSv) [8]. The potential harmful effects of radiation can be reduced by modulating the electrocardiogram-controlled tube current or decreasing the tube voltage or current.
6. Limitations
7. Conclusions
The target heart rate in our study was b80 bpm, which was higher than that in other studies. In the study by Rist et al., image quality and stent assessments were not significantly affected by the elevated heart rate. The study conducted by Andreini et al. revealed that the motion artifacts caused by slice misalignment can be avoided in patients with heart rate of b60 bpm because of the limited temporal resolution [4,5]. The effects of the heart rate on the evaluability and diagnostic accuracy of MDCT for ISDR identification were not investigated. Most (70/87; 80%) stents evaluated in our study had sizes of ≥3.0 mm, so the number of stents b3.0 mm (17/87; 20%) was small. For this reason, the results concerning the stent size b3.0 mm should be interpreted carefully. The median interval of 43 months between PCI and the study is longer than the usual 12 month riskier period for in-stent restenosis. Accordingly, the results obtained in the present study may not apply to the routine follow-up of coronary stenting. In this study, the measurements were performed by only 1 MDCT reader and 1 CCA reader, both of whom were blinded to the procedures, and by an experienced interventional cardiologist, who was not blinded to the procedures. Thus, no data were available on inter-observer variability.
When ISAR with MLA ≤4.0 mm 2 was detected on IVUS, CCA and MDCT had similar diagnostic accuracies for ISDR detection. High specificity and NPV make 64-slice MDCT a reliable non-invasive method for excluding ISDR.
Table 8 Accuracy of CCA and MDCT to detect in-stent diameter restenosis in comparison to minimal luminal area ≤ 4.0 mm2 by IVUS⁎.
CCA Evaluable by MDCT Non-evaluable included MDCT Evaluable by MDCT Non-evaluable included
No. of stents
TP
TN
FP
FN
Sensitivity
Specificity
PPV
NPV
79
18
54
2
5
78%
96%
90%
92%
87
20
60
2
5
80%
97%
91%
92%
79
20
54
2
3
87%
96%
91%
95%
87
22
54
8
3
88%
87%
73%
95%
⁎ p was not significant for any other factor. Abbreviations as in Table 4.
Acknowledgments This study was supported by a grant (CMRPG860151) from the Chang Gung Memorial Hospital, Taiwan, Republic of China. The authors of this manuscript certify that they have complied with the Principles of Ethical Publishing in the International Journal of Cardiology. References [1] Rixe J, Achenbach S, Ropers D, et al. Assessment of coronary artery stent restenosis by 64-slice multi-detector computed tomography. Eur Heart J 2006;27:2567–72. [2] Ehara M, Kawai M, Surmely JF, et al. Diagnostic accuracy of coronary in-stent restenosis using 64-slice computed tomography: comparison with invasive coronary angiography. J Am Coll Cardiol 2007;49:951–9. [3] Cademartiri F, Schuijf JD, Pugliese F, et al. Usefulness of 64-slice multislice computed tomography coronary angiography to assess in-stent restenosis. J Am Coll Cardiol 2007;49:2204–10. [4] Rist C, von Ziegler F, Nikolaou K, et al. Assessment of coronary artery stent patency and restenosis using 64-slice computed tomography. Acad Radiol 2006;13: 1465–73. [5] Andreini D, Pontone G, Bartorelli AL, et al. Comparison of feasibility and diagnostic accuracy of 64-slice multidetector computed tomographic coronary angiography versus invasive coronary angiography versus intravascular ultrasound for evaluation of in-stent restenosis. Am J Cardiol 2009;103:1349–58. [6] Chung SH, Kim YJ, Hur J, et al. Evaluation of coronary artery in-stent restenosis by 64-section computed tomography. Factors affecting assessment and accurate diagnosis. J Thorac Imaging 2010;25:57–63. [7] Wykrzkowska JJ, Arbab-Zadeh A, Godoy G, et al. Assessment of in-stent restenosis using 64-MDCT: analysis of the CORE-64 multicenter international trial. AJR 2010;194:85–92. [8] Carrabba N, Bamoshmoosh M, Carusi LM, et al. Usefulness of 64-slice multidetector computed tomography for drug eluting in-stent reteosis. Am J Cardiol 2007;100:1754–8. [9] Schuijf JD, Pundziute G, Jukema JW, et al. Evaluation of patients with previous coronary stent implantation with 64-section CT. Radiology 2007;245:416–23. [10] Leber AW, Knez A, Becker A, et al. Accuracy of multidetector spiral computed tomography in identifying and differentiating the composition of coronary atherosclerotic plaques: a comparative study with intracoronary ultrasound. J Am Coll Cardiol 2004;43:1241–7.
C.-L. Hang et al. / International Journal of Cardiology 166 (2013) 90–95 [11] Tanaka A, Shimada K, Yoshida K, et al. Non-invasive assessment of plaque rupture by 64-slice multidetector computed tomography — comparison with intravascular ultrasound. Circ J 2008;72:1276–81. [12] Takaoka H, Ishibashi I, Uehara M, et al. Comparison of image characteristics of plaques in culprit coronary arteries by 64 slice CT and intravascular ultrasound in acute coronary syndromes. Int J Cardiol 2012 Oct 4;160(2):119–26. [13] Nakamura K, Funabashi N, Uehara M, et al. Impairment factors for evaluating the patency of drug-eluting stents and bare metal stents in coronary arteries by 64-slice computed tomography versus invasive coronary angiography. Int J Cardiol 2008;130:349–56. [14] Matsunaga E, Takaya N, Yokoyama T, et al. Relationship between coronary artery wall thickness measured by 64-slice multidetector computed tomography and cardiovascular risk factors. Circ J 2009;73:681–5. [15] Motoyama S, Kondo T, Anno H, et al. Atherosclerotic plaque characterisation by 0.5-mm-slice multislice computed tomographic imaging: comparison with intravascular ultrasound. Circ J 2007;71:363–6.
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[16] Hur J, Kim YJ, Lee HJ, et al. Quantification and characterization of obstructive coronary plaques using 64-slice computed tomography: a comparison with intravascular ultrasound. J Comput Assist Tomogr 2009;33:186–92. [17] Kunita E, Fujii T, Urabe Y, et al. Coronary plaque stabilization followed by color code plaqueTM analysis with 64-slice multidetector row computed tomography. Circ J 2009;73:772–5. [18] Harada K, Amano T, Uetani T, et al. Accuracy of 64-slice multidetector computed tomography for classification and quantitation of coronary plaque: comparison with integrated backscatter intravascular ultrasound. Int J Cardiol 2011;149: 95–101. [19] Joshi SB, Okabe T, Rosewell RO, et al. Accuracy of computed tomographic angiography for stenosis quantification using quantitative coronary angiography or intravascular ultrasound as the gold standard. Am J Cardiol 2009;104:1047–51.
Contents lists available at SciVerse ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Evaluation of coronary artery stent patency by using 64-slice multi-detector computed tomography and conventional coronary angiography: A comparison with intravascular ultrasonography Chi-Ling Hang a, b,⁎, Yi-Wei Lee b, c, Gary Bih-Fang Guo a, b, Ali Ahmed Youssef a, d, Hon-Kan Yip a, b, Chu-Feng Liu e, Sarah Chua a, b, Hseuh-Wen Chang f, Yu-Fan Cheng b, c, Shyh-Ming Chen a, b,⁎, 1 a
Section of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China Chang Gung University College of Medicine, Kaohsiung, Taiwan, Republic of China c Department of Radiology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China d Cardiology Department, Suez Canal University, Ismailia, Egypt e Emergency Department, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China f Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan, Republic of China b
a r t i c l e
i n f o
Article history: Received 21 May 2011 Received in revised form 19 September 2011 Accepted 9 October 2011 Available online 5 November 2011 Keywords: Multi-slice computed tomography In-stent restenosis Intravascular ultrasonography Coronary angiography
a b s t r a c t Background: Most studies have investigated the diagnostic accuracy of 64-slice multi-detector computed tomography (MDCT) to detect coronary artery stent patency by using conventional coronary angiography (CCA) as the reference standard. In this study, we compared the diagnostic accuracy of MDCT and CCA by using intravascular ultrasonography (IVUS) as the reference standard. Methods: Forty-six patients with previously implanted coronary artery stents (n = 87) underwent MDCT followed by CCA and IVUS within 24 h. Sensitivities, specificities, positive predictive values (PPV) and negative predictive values (NPV) of MDCT and CCA for detecting or excluding in-stent diameter restenosis (ISDR) by using in-stent area restenosis (ISAR) and minimal luminal area (MLA) ≤ 4.0 mm 2 of IVUS as the reference standard were determined. Results: Eight stents (9%) were judged non-evaluable using MDCT for the detection of ISDR. ISDR was detected in 28% (22/79) of the evaluable stents using CCA. When ISAR was detected using IVUS, the sensitivity, specificity, PPV, and NPV for ISDR detection by using MDCT were 71%, 96%, 91% and 86%, and the corresponding values for CCA were 64%, 96%, 90% and 83%. When MLA ≤ 4.0 mm 2 was detected using IVUS, the sensitivity, specificity, PPV, and NPV for ISDR detection by using MDCT were 87%, 96%, 91% and 95%, and for CCA were 78%, 96%, 90% and 92%. Conclusions: When ISAR with MLA ≤ 4.0 mm2was detected on IVUS, CCA and MDCT had similar diagnostic accuracies for ISDR detection. High specificity and NPV make 64-slice MDCT a reliable non-invasive method for excluding ISDR. © 2011 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Multi-detector computed tomography (MDCT) is a potential noninvasive diagnostic tool for evaluating coronary artery stent patency. However, despite the introduction of 64-slice MDCT with improved spatial and temporal resolution, the technique has not been proved reliable for assessing coronary artery stent patency probably because ⁎ Corresponding authors at: Kaohsiung Chang Gung Memorial Hospital, 123 Tai Pei Road, Niao Sung District, Kaohsiung City 83305, Taiwan, Republic of China. Tel.: +886 73702028; fax: +886 77322402. E-mail addresses: [email protected] (C.-L. Hang), [email protected] (S.-M. Chen). 1 Dr. Shyh-Ming Chen contributed significantly in the initial planning, case collection, coronary angiogram reading, and manuscript writing, and thus deserves to be a co-correspondent of this manuscript. 0167-5273/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2011.10.003
of beam-hardening artifacts and partial volume effects [1–9]. Studies have shown that 64-slice MDCT can provide as much information on coronary artery plaque morphology as do intravascular ultrasonography (IVUS) can [10–12]. Unlike MDCT or conventional coronary angiography (CCA), IVUS helps determine in-stent luminal obstruction clearly. Therefore, we investigated the feasibility of assessing coronary artery stent patency and restenosis with 64-slice MDCT and CCA, and compared the results to those obtained using IVUS as the reference standard. 2. Methods Fifty patients with previously implanted coronary artery stents were included in this study. The patients who were either scheduled for coronary angiography because of angina pectoris or had undergone stenting 6 months ago were examined with 64slice MDCT (Aquilion 64; Toshiba, Medical Systems Corporation, Tochigi-ken, Tokyo,
C.-L. Hang et al. / International Journal of Cardiology 166 (2013) 90–95 Japan). Retrospectively electrocardiography (ECG)-gated contrast-enhanced 64-slice MDCT was performed ≤ 24 h prior to CCA. We only included patients who received IVUS (2.9F; 40 MHz; Atlantis SR Pro coronary imaging catheter; Boston Scientific, Fremont, CA, USA) as a part of the catheterization procedure and who had sinus rhythm and a stable clinical condition. Patients with implanted pacemakers or automatic implantable cardioverter defibrillators, or contraindication to administration of iodinated contrast agent were not included. Four patients were excluded from the study because of IVUS machine malfunction. Thus, the final study cohort consisted of 46 patients. Each patient was instructed to lie down in the supine position in the gantry of the 64-slice MDCT scanner. Leads were attached to perform ECG and image recording simultaneously, which was necessary for interrelated image reconstruction. The study protocol included oral administration of 10 mg of propanolol before the scheduled CT scan in patients with heart rate >80 bpm. In patients with an unsatisfactory lowering of the heart rate, a higher dose of propanolol was given until the target heart rate was reached. All patients received a single dose of 0.6 mg sublingual nitroglycerin 2 min prior to the scan. This study was approved by the Ethics Committee of Chang Gung Memorial hospital and all patients had written informed consent obtained from all the patients. The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the institution's human research committee. The imaging protocol consisted of the following steps. First, a non-contrast-enhanced coronal view of the chest was obtained to determine the position of the heart, define the scan volume for further imaging, and recognize eventual coronary calcification. Then, a bolus of 70–80 mL of non-ionic contrast agent (Omnipaque 350, 350 mg I/mL; GE Healthcare, Ireland Cork, Ireland) was injected into an antecubital vein at a flow rate of 4.5–5 mL/s. Further, approximately 30–40 mL of saline solution was injected via an 18-gauge catheter. As soon as the signal in the region of interest in the ascending aorta reached a predefined threshold of 150 Hounsfield units (HU), scanning was performed automatically, and the entire volume of the heart was acquired in 8–9 s during 1 breathhold, with simultaneous recording of the electrocardiographic tracing. The MDCT scanning parameters determined according to the patient's size, were as follows: collimation, 64 × 0.5 mm; gantry rotation time, 0.4 s; pitch, 0.2–0.225; standard and stent reconstruction kernel, FC43 and FC05; tube voltage, 120 kV; and current, 400–500 mA. To determine the optimal phase and for comprehensive functional evaluation, the data sets were reconstructed with retrospective ECG gating at every 10% (between 0 and 90%) of the R–R interval with the standard kernel, adequate field of view (FOV), 512 × 512 matrix size, and 1 mm thickness with a 0.8 mm interval. The axial images obtained in the optimal phase were reconstructed with the same parameters but with a slice thickness of 0.5 mm and interval of 0.3 mm. All the data were transmitted to a workstation (Vitrea 2, Vital Images Inc, MN, USA) for post-processing. The estimated effective radiation dose was approximately 15–17.5 mSv. The MDCT images were evaluated by a radiologist with 3 years of experience in reading 64-slice MDCT data and who was blinded to the findings obtained using CCA. The radiologist subjectively rated the overall image quality for in-stent diameter restenosis (ISDR) on a 3-point scale. Images with distinct anatomic details and no noise or artifacts were rated as 3 (excellent), while those with clear anatomic details and mild or moderate increase in noise and/or artifacts not affecting the diagnostic value were rated as 2 (good). Furthermore, images with a distinct increase in noise and/or artifacts affecting diagnostic value were rated as 1 (poor). Only patients for whom high- or moderate-quality images of the stented segments had been obtained were considered for further analysis. Qualitative evaluation of ISDR of stented segments were visually classified into 3 grades using the following criteria: grade 1, none or slight neointimal proliferation; grade 2, mild neointimal proliferation but no significant restenosis (b50% narrowing); grade 3, moderate neointimal proliferation with significant restenosis or total occlusion (≥50% narrowing or occlusion). In addition, a quantitative evaluation of ISDR by MDCT was performed on those stents without ISDR by either CCA or MDCT yielding positive for ISAR or minimal luminal area ≤4.0 mm2 by IVUS (false negative). Diameters of the proximal and distal reference segments and narrower stent lumen were measured in short axis views. Degree of luminal narrowing was quantified as percent diameter stenosis by calculating the ratio between the reference segment and stent diameters. IVUS images were obtained empirically in all the patients. The image obtained for each site was manipulated such that the size and pattern were similar to that of the MDCT image, and helped clearly distinguish the vessel form the surrounding tissue, plaque, and lumen. These measurements were performed by an experienced interventional cardiologist who was not blinded to the procedures. IVUS was performed as a part of the catheterization procedure in all 46 patients. IVUS images were recorded after initiating an automated pullback of the catheter at 0.5 mm/s. IVUS images of the entire pullback were recorded on S-VHS videotape. Area measurements were performed at sites with minimal lumen and stent areas, and at proximal and distal reference sites. ISAR was defined as percent area stenosis ≥ 50% anywhere within the stent or within 5-mm segments proximal or distal to the stent margins. A significant lesion was defined as a MLA ≤6.0 mm2 for the left main coronary arteries and a MLA ≤4.0 mm2 for other epicardial coronary arteries. CCA was performed by using the standard procedure after intracoronary injection of 200 μg of nitroglycerin. Multiple views of the coronary arteries were obtained and stored on a CD-ROM. Coronary angiograms were evaluated by QCA (Quantor QCA; Siemens Medical System, Forchheim, Germany) by an independent experienced cardiologist blinded to the image source. ISDR was defined as percent diameter stenosis ≥50% anywhere within the stent or within 5-mm segments proximal or distal to the stent margins.
91
3. Statistics The evaluability (the ratio of the number of evaluable segments: total number of segments) of the MDCT scan in identifying ISDR was calculated. The diagnostic accuracy of 64-slice MDCT in detecting ISDR with various degrees of luminal obstruction was evaluated using CCA as the reference standard. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for stenosis ≥50% and for lesions with diameter reduction of b50%. The capability of 64-slice MDCT and CCA to detect and quantify ISDR was compared to that of IVUS, the reference standard, to detect and quantify in-stent area restenosis (ISAR) and MLA ≤4.0 mm 2. Sensitivity, specificity, PPV, and NPV were calculated for stenosis ≥50% and for lesions with for diameter and area reduction of b50% and MLA ≤4.0 mm 2. The differences in the accuracy and evaluability of MDCT, and the standards were calculated using the chi-square test or Fisher's exact test. A 95% confidence interval was calculated from the binominal expression. A p value b0.05 was considered statistically significant. 4. Results The baseline clinical and angiographic characteristics of the patients are summarized in Tables 1 and 2. MDCT was performed ≤24 h prior to CCA and IVUS in the 46 patients with 87 stents (Table 2). Sixteen (35%) patients presented with unstable angina, and 30 (65%) patients had either stable angina or were asymptomatic. The median interval between stent implantation and MDCT was 43± 39 months. The sites of stent implantation were the left anterior descending artery (33 patients, 38%), the left circumflex artery (23 patients, 26%), and the right coronary artery (31 patients, 36%). The characteristics of the 15 types of implanted stents are summarized in Table 3. According to the qualitative analysis of the reader, 8 stents (total, 87; 9%) were judged non-evaluable using MDCT for the detection of diameter stenosis. The remaining 79 stents were depicted with good image quality in 60 stents (total, 87; 69%) and excellent image quality in 19 stents (total, 87; 22%). The evaluability of MDCT with regard to stent characteristics and index vessel is shown in Tables 4–6. Neither the stent characteristics nor the index vessels were significantly associated with the evaluability of the stented segments. ISDR was detected using CCA in 28% (22/79) of the evaluable stents and ISAR was detected using IVUS in 35% (28/79) of the evaluable stents. The diagnostic accuracy of MDCT and CCA in relation to stent characteristics and index vessel is shown in Tables 4–6. No differences were seen in the diagnostic accuracy of MDCT and CCA for ISDR identification with regard to stent characteristics or index vessels (Table 4). Furthermore, when ISAR was detected on IVUS, no significant differences were found in ISDR identification by MDCT or CCA (Tables 5 and 6). When ISDR was identified on CCA, MDCT had sensitivity, specificity, PPV, and NPV of 95%, 95%, 86%, and 98%, respectively (Table 4). When the analysis was performed with inclusion of non-evaluable Table 1 Baseline clinical characteristics of the patients⁎. Number (n) of patients Male, n (%) Age in years Diabetes mellitus, n (%) Hypertension, n (%) Smoking, n (%) Hypercholesterolemia, n (%) Previous myocardial infarction, n (%) Unstable angina, n (%) Stable angina or asymptomatic, n (%) Time lapse after last PCI (months) PCI = percutaneous coronary intervention. ⁎p was not significant for any other factor.
46 40 (87) 60.5 ± 9.7 11 (24) 24 (52) 19 (41) 28 (61) 27 (59) 16 (35) 30 (65) 43 ± 39
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C.-L. Hang et al. / International Journal of Cardiology 166 (2013) 90–95 Table 2 Baseline angiographic characteristics. Number of patients Multivessel disease stenting, n (%) 3-vessel stenting, n (%) 2-vessel stenting, n (%) Number of stents Size and site of stent implantation Left anterior descending artery, n (%) 2.5 mm 2.75 mm 3.0 mm 3.5 mm Left circumflex artery, n (%) 2.5 mm 2.75 mm 3.0 mm 3.5 mm 4.5 mm Right coronary artery, n (%) 2.75 mm 3.0 mm 3.5 mm 4.0 mm
46 16 (35) 4 (9) 12 (26) 87 33 (38) 5 4 19 5 23 (26) 5 1 11 5 1 31 (36) 2 12 15 2
segments, specificity and PPV decreased to 86% and 70%, respectively, with a sensitivity of 95% and a NPV of 98% (Table 7). When ISAR was detected on IVUS, the sensitivity, specificity, PPV, and NPV for ISDR identification by using MDCT were 71%, 96%, 91% and 86%, respectively (Table 5) and the corresponding values for CCA were 64%, 96%, 90% and 83% (Table 6). When non-evaluable segments were included, the specificity and PPV, and NPV for ISDR identification by using MDCT decreased to 86% and 73%, respectively, with a sensitivity of 73% and a NPV of 86%, and the sensitivity, specificity, PPV, and NPV for CCA were 67%, 96%, 91% and 85%, respectively (Table 7). When MLA ≤4.0 mm 2 was detected on IVUS, the sensitivity, specificity, PPV, and NPV for ISDR identification by using MDCT were 87%, 96%, 91% and 95%, respectively and the corresponding values for CCA were 78%, 96%, 90% and 92% (Table 8). When non-evaluable segments were included, the specificity and PPV for ISDR identification by using MDCT decreased to 87% and 73%, respectively with a sensitivity of 88% and a NPV of 95% and the sensitivity, specificity, PPV, and NPV for CCA were 80%, 97%, 91% and 92% (Table 8). An incorrect diagnosis of absence of ISDR (false negative) was made using both MDCT and
Table 3 Stent characteristics. Number of stents Stents/patient Stent types Drug-coated stents with strut thickness ≥ 100 μm Cypher (Johnson and Johnson) Taxus (Boston Scientific) Bare-metal stents with strut thickness b 100 μm Multilink Vision (Guidant) Multilink Pixel (Guidant) Multilink Zeta (Guidant) Palmaz–Schatz (Johnson & Johnson) Crown (Cordis) Driver (Medtronic) Baremetal stents with strut thickness ≥ 100 μm BX Velocity (Guidant) Multilink Penta (Guidant) S7 (Medtronic) AVE GFX (Medtronic) Wall (Boston Scientific) Nir (Boston Scientific) Express (Boston Scientific) Cobalt alloy stents Driver (Medtronic) Vision (Guidant) Wall (Boston Scientific)
87 1.89 15 24 14 10 34 3 2 3 3 2 21 29 6 1 5 3 1 8 5 25 21 3 1
CCA in 8 of the 28 stents deemed to have significant ISAR by using IVUS (Table 9). Five of these 8 stents with ISAR had a minimal luminal area (MLA) >4.0 mm 2, and the remaining 3 stents had an MLA ≤4.0 mm 2. Two stents showing ISAR with MLA ≤4.0 mm 2 were correctly identified using MDCT but wrongly classified using CCA (Table 9). 5. Discussion In this study, MDCT was performed ≤24 h prior to CCA, and IVUS was a part of the catheterization procedure in all study patients. Among the 87 stented segments, 79 were evaluable for ISDR by using MDCT with an overall evaluability of 91%; these findings were similar to those of recently published studies [2–5,8]. In contrast to other studies, our study revealed that factors such as stent diameter, strut thickness, stent material, stent type, and index vessel did not affect stent evaluation [4–6]. However, similar to our findings, the findings of the study conducted by Cademartiri et al. revealed no significant differences in the evaluability of stents with diameters greater than, equal to, and lesser than 3.0 mm 3. Similar to our study, the studies conducted by Schuijf et al. and Nakamura et al. revealed no association between strut thickness and stent evaluability [9,13]. Wykrzykowska et al. and Schuijf et al. reported no statistically significant variations in-stent evaluability assessed on the basis of stent placement in different locations in the index vessels [7,9]. Therefore, further larger trials are necessary to evaluate the various factors that influence ISDR evaluability. Although the role of 64-slice MDCT has been expanded to include the evaluation of coronary artery wall thickness and plaque texture, IVUS is recognized as the standard reference method [10–12,14–18]. Compared to other current techniques, IVUS is superior in identifying in-stent luminal obstruction. To our knowledge, this is the only study in English literature to evaluate coronary artery stent patency by using 64-slice MDCT and to use IVUS as a part of the catheterization procedure in all the study patients. In the study conducted by Andreini et al., IVUS was performed in patients in whom CCA revealed moderate ISDR [5]. They observed a significant variation in area measurements between MDCT and IVUS, but suggested that this variation does not affect MDCT assessment of percent in-stent restenosis [5]. In our study, the total number of stents evaluable for ISAR by using MDCT was less (40%) mostly due to motion artifacts. Thus, 64-slice MDCT is not appropriate for in-stent area assessment. Therefore, we evaluated the diagnostic accuracies of MDCT and CCA for detecting ISDR by using ISAR and MLA ≤4.0 mm 2 detection on IVUS as the reference. When ISAR was detected on IVUS, MDCT showed decreased sensitivity from high to low, decreased NPV from high to moderate, constant high specificity, and constant moderate PPV. On the other hand, when ISAR was detected on IVUS, CCA showed decreased sensitivity, moderate PPV and NPV, and high specificity. Sensitivity and NPV were lower because of a relatively high false-negative rate (an incorrect diagnosis of absence of ISDR was used using MDCT in 8 (29%) of the 28 deemed to have ISAR by IVUS and in 10 (36%) of the 28 stents using CCA). Eight of the 28 ISAR were misdiagnosed by both MDCT and CCA. Among the 8 stents showing ISAR, 3 had a MLA ≤4.0 mm 2, and repeat percutaneous coronary intervention (PCI) was performed in these 3 cases. Two of these 3 stents were incorrectly classified by CCA but correctly identified by MDCT. When ISAR in stents with MLA ≤4.0 mm 2 was detected on IVUS, which was used as the gold standard, the sensitivity and NPV of MDCT were 87% and 95%, respectively. The sensitivity and NPV of MDCT were actually higher than the corresponding values for CCA (78% and 92%). In the study by Joshi et al., in patients with intermediategrade lesions identified on CCA, absolute measurements of stenosis severity determined on MDCT correlated with those determined on IVUS but not with those determined on CCA [19]. They found that, when IVUS is used was used as the gold standard rather than CCA,
C.-L. Hang et al. / International Journal of Cardiology 166 (2013) 90–95
93
Table 4 Accuracy and evaluability of 64-slice MDCT to detect in-stent diameter restenosis in comparison to CCA and in relation to stent characteristics and index vessel⁎.
Stented segments Stented artery LAD LCX RCA Stent material Stainless steel Cobalt chromium Stent type DES BMS Strut thickness (μm) b100 ≥100 Stent diameter (mm) b3.0 ≥3.0
No. of stents
Evaluability
TP
TN
FP
FN
Sensitivity
Specificity
PPV
NPV
87
91%
19
56
3
1
95% (85–100)
95% (89–100)
86% (72–100)
98% (95–100)
33 23 31
88% 96% 90%
6 4 9
21 17 18
2 0 1
0 1 0
100% 80% (45–100) 100%
91% (80–100) 100% 95% (85–100)
75% (45–100) 100% 90% (71–100)
100% 94% (84–100) 100%
61 26
92% 92%
14 5
40 16
0 3
1 0
93% (81–100) 100%
100% 84% (68–100)
100% 63% (29–96)
98% (93–100) 100%
25 62
92% 89%
5 14
18 38
0 3
0 1
100% 93% (81–100)
100% 93% (85–100)
100% 82% (64–100)
100% 97% (92–100)
34 53
88% 91%
8 11
21 35
2 1
0 1
100% 92% (76–100)
91% (80–100) 97% (92–100)
80% (55–100) 92% (76–100)
100% 97% (92–100)
17 70
100% 87%
6 13
11 45
0 3
0 1
100% 93% (79–100)
100% 94% (87–100)
100% 81% (62–100)
100% 98% (94–100)
TP = true positive; TN = true negative; FP = false positive; FN = false negative; PPV = positive predictive value; NPV = negative predictive value; LAD = left anterior descending artery; LCX = left circumflex artery; RCA = right coronary artery; BMS = bare-metal stent; DES = drug-eluting stent. ⁎ p was not significant for any other factor.
Table 5 Accuracy of 64-slice MDCT to detect in-stent diameter restenosis in comparison to in-stent area restenosis of IVUS and in relation to stent characteristics and index vessel⁎.
Stented segments Stented artery LAD LCX RCA Stent material Stainless steel Cobalt chromium Stent type DES BMS Strut thickness (μm) b100 ≥100 Stent diameter (mm) b3.0 ≥3.0
No. of stents
Evaluability
TP
TN
FP
FN
Sensitivity
Specificity
PPV
NPV
87
91%
20
49
2
8
71% (55–88)
96% (91–100)
91% (79–100)
86% (77–95)
33 23 31
88% 96% 90%
8 3 9
17 17 15
0 1 1
4 1 3
67% (40–93) 75% (33–100) 75% (51–100)
100% 94% (84–100) 94% (82–100)
100% 75% (33–100) 90% (71–100)
81% (64–98) 94% (84–100) 83% (66–100)
61 26
92% 92%
13 7
35 14
1 1
6 2
68% (48–89) 78% (51–100)
97% (92–100) 93% (81–100)
93% (79–100) 88% (65–100)
85% (75–96) 88% (71–100)
25 62
92% 89%
5 15
18 31
0 2
0 8
100% 65% (46–85)
100% () 94% (86–100)
100% 88% (73–100)
100% 79% (67–92)
34 53
88% 91%
10 10
16 33
0 2
5 3
67% (43–90) 77% (54–100)
100% 94% (87–100)
100% 83% (62–100)
76% (58–94) 92% (83–100)
17 70
100% 87%
6 14
10 39
0 2
1 7
86% (60–100) 67% (47–87)
100% 95% (89–100)
100% 88% (71–100)
91% (74–100) 85% (74–95)
⁎ p was not significant for any other factor. Abbreviations as in Table 4.
Table 6 Accuracy of CCA to detect in-stent diameter restenosis in comparison to in-stent area restenosis of IVUS and in relation to stent characteristics and index vessel for those segments assessable by 64-slice MDCT⁎.
Stented segments Stented artery LAD LCX RCA Stent material Stainless steel Cobalt chromium Stent type DES BMS Strut thickness (μm) b100 ≥100 Stent diameter (mm) b3.0 ≥3.0
No. of stents
Evaluability
TP
TN
FP
FN
Sensitivity
Specificity
PPV
NPV
87
91%
18
49
2
10
64% (47–82)
96% (91–100)
90% (77–100)
83% (73–93)
33 23 31
88% 96% 90%
6 3 9
17 16 16
0 2 0
6 1 3
50% (22–78) 75% (33–100) 75% (51–100)
100% 89% (74–100) 100%
100% 60% (17–100) 100%
74% (56–92) 94% (83–100) 84% (68–100)
61 26
92% 92%
13 5
34 15
2 0
6 4
68% (48–89) 56% (23–88)
94% (87–100) 100%
87% (69–100) 100%
85% (74–96) 79% (61–97)
25 62
92% 89%
5 13
18 31
0 2
0 10
100% 57% (36–77)
100% 94% (86–100)
100% 87% (69–100)
100% 76% (63–89)
34 53
88% 91%
8 10
16 33
0 2
7 3
53% (28–79) 77% (54–100)
100% 94% (87–100)
100% 83% (62–100)
70% (51–88) 92% (83–100)
17 70
100% 87%
6 12
10 39
0 2
1 9
86% (60–100) 57% (36–78)
100% 95% (89–100)
100% 86% (67–100)
91% (74–100) 81% (70–92)
⁎ p was not significant for any other factor. Abbreviations as in Table 4.
94
C.-L. Hang et al. / International Journal of Cardiology 166 (2013) 90–95
Table 7 Accuracy of 64-slice MDCT to detect in-stent diameter restenosis in comparison to CCA and accuracy of CCA and MDCT to detect in-stent diameter restenosis in comparison to in-stent area restenosis of IVUS with inclusion of non-evaluable segments.
MDCT vs CCA CCA vs IVUS MDCT vs IVUS
No. of stents
TP
TN
FP
FN
Sensitivity
Specificity
PPV
NPV
87 87 87
21 20 22
56 55 49
9 2 8
1 10 8
95% 67% 73%
86% 96%⁎ 86%⁎
70% 91% 73%
98% 85% 86%
⁎ p = 0.048; specificity of CCA is significantly higher than MDCT. Abbreviations as in Table 4.
MDCT appeared to be more accurate, and they suggested that the limitations of CCA as a reference standard need to be considered in studies evaluating the accuracy of MDCT [19]. When non-evaluable segments were excluded, there were no differences in the diagnostic accuracy of stent characteristics or index vessels between MDCT and CCA, MDCT and IVUS or CCA and IVUS in ISDR identifications. When MLA ≤4.0 mm 2 was used as reference and non-evaluable segments were excluded, MDCT had higher specificity and NPV for excluding ISDR rather than CCA. Furthermore, when the above analysis was performed with inclusion of non-evaluable segments, MDCT and CCA had similar high NPV (95% and 92%, respectively) for excluding ISDR. Therefore, 64-slice MDCT is a reliable non-invasive tool for excluding ISDR.
Table 9 Stents without in-stent diameter restenosis by either CCA or MDCT yielding positive for in-stent area restenosis or minimal luminal area ≤4.0 mm2 by IVUS (false negative). Stents
% In-stent diameter % In-stent diameter % In-stent area Minimal luminal stenosis by MDCT stenosis by CCA stenosis by IVUS area by IVUS
No. 1 ⁎ No. 2 No. 3 No. 4 No. 5 ⁎ No. 6 ⁎ No. 7 No. 8 ⁎⁎ No. 9 ⁎⁎ No. 10
30% 45% 20% 25% 25% 25% 40% 30% ⁎⁎50% ⁎⁎52%
28% 37% 38% 38% 33% 35% 45% 41% 36% 35%
53% ⁎51% 50% 56% 57% ⁎60% ⁎56% 50% ⁎⁎53% ⁎⁎55%
>4.0 mm2 ⁎≤4.0 mm2 >4.0 mm2 >4.0 mm2 >4.0 mm2 ⁎≤4.0 mm2 ⁎≤4.0 mm2 >4.0 mm2 ⁎⁎≤4.0 mm2 ⁎⁎≤4.0 mm2
⁎ An incorrect diagnosis of absence of ISDR was made using both MDCT and CCA in stents deemed to have significant ISAR by using IVUS had an MLA ≤ 4.0 mm2. ⁎⁎ Stents showing ISAR with MLA ≤ 4.0 mm2 were correctly identified using MDCT but wrongly classified using CCA.
Finally, the estimated mean effective radiation dose (approximately, 15–17.5 mSv) in our study is higher than the radiation dose used in stress perfusion imaging (8–20 mSv) and similar to other 64-slice MDCT studies (8.2–21.4 mSv) [8]. The potential harmful effects of radiation can be reduced by modulating the electrocardiogram-controlled tube current or decreasing the tube voltage or current.
6. Limitations
7. Conclusions
The target heart rate in our study was b80 bpm, which was higher than that in other studies. In the study by Rist et al., image quality and stent assessments were not significantly affected by the elevated heart rate. The study conducted by Andreini et al. revealed that the motion artifacts caused by slice misalignment can be avoided in patients with heart rate of b60 bpm because of the limited temporal resolution [4,5]. The effects of the heart rate on the evaluability and diagnostic accuracy of MDCT for ISDR identification were not investigated. Most (70/87; 80%) stents evaluated in our study had sizes of ≥3.0 mm, so the number of stents b3.0 mm (17/87; 20%) was small. For this reason, the results concerning the stent size b3.0 mm should be interpreted carefully. The median interval of 43 months between PCI and the study is longer than the usual 12 month riskier period for in-stent restenosis. Accordingly, the results obtained in the present study may not apply to the routine follow-up of coronary stenting. In this study, the measurements were performed by only 1 MDCT reader and 1 CCA reader, both of whom were blinded to the procedures, and by an experienced interventional cardiologist, who was not blinded to the procedures. Thus, no data were available on inter-observer variability.
When ISAR with MLA ≤4.0 mm 2 was detected on IVUS, CCA and MDCT had similar diagnostic accuracies for ISDR detection. High specificity and NPV make 64-slice MDCT a reliable non-invasive method for excluding ISDR.
Table 8 Accuracy of CCA and MDCT to detect in-stent diameter restenosis in comparison to minimal luminal area ≤ 4.0 mm2 by IVUS⁎.
CCA Evaluable by MDCT Non-evaluable included MDCT Evaluable by MDCT Non-evaluable included
No. of stents
TP
TN
FP
FN
Sensitivity
Specificity
PPV
NPV
79
18
54
2
5
78%
96%
90%
92%
87
20
60
2
5
80%
97%
91%
92%
79
20
54
2
3
87%
96%
91%
95%
87
22
54
8
3
88%
87%
73%
95%
⁎ p was not significant for any other factor. Abbreviations as in Table 4.
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