Author + information
- Received November 15, 2013
- Revision received January 15, 2014
- Accepted February 18, 2014
- Published online May 13, 2014.
- Dennis T.L. Wong, MBBS (Hons), PhD∗,†∗ (, )
- Brian S. Ko, MBBS (Hons), PhD∗,
- James D. Cameron, MBBS, MD∗,
- Darryl P. Leong, MBBS (Hons), MPH, PhD†,
- Michael C.H. Leung, MBBS (Hons), PhD∗,
- Yuvaraj Malaiapan, MBBS∗,
- Nitesh Nerlekar, MBBS∗,
- Marcus Crossett, Ba App Sc‡,
- John Troupis, MBBS∗,‡,
- Ian T. Meredith, MBBS (Hons), PhD∗ and
- Sujith K. Seneviratne, MBBS∗
- ∗Monash Cardiovascular Research Centre, Department of Medicine, Monash Medical Centre, Monash University and MonashHeart, Monash Health, Clayton, Australia
- †Discipline of Medicine, University of Adelaide, Adelaide, Australia
- ‡Department of Diagnostic Imaging, Monash Medical Centre, Southern Health, Melbourne, Australia
- ↵∗Reprint requests and correspondence:
Dr. Dennis T. L. Wong, MonashHeart, Monash Medical Centre, 246 Clayton Road, Clayton, Victoria, Australia.
Objectives The goal of this study was to compare the diagnostic accuracy of combined computed tomography perfusion (CTP) + computed tomography angiography (CTA), transluminal attenuation gradient by 320-detector row computed tomography (TAG320) + CTA, and CTP + TAG320 + CTA (multidetector computed tomography–integrated protocol [MDCT-IP]) assessment in predicting significant fractional flow reserve (FFR).
Background CTA has limited specificity for predicting functionally significant stenoses. Novel CT techniques, including adenosine stress CTP and TAG320, may improve the diagnostic accuracy of CTA.
Methods CTA, CTP, and TAG320 were assessed using 320-detector row MDCT. Patients who underwent CTA, CTP, and FFR assessment on invasive coronary angiography were included. CTP was assessed using the visual perfusion assessment. TAG320 was defined as the linear regression coefficient between luminal attenuation and axial distance. A TAG320 cutoff value of −15.1 HU/10 mm as previously described was defined as significant. Functionally significant coronary stenosis was defined as FFR ≤0.8.
Results The cohort included 75 patients (age 64.1 ± 10.8 years, 52 men) and 44 (35%) FFR-significant vessels. In 127 vessels, CTA predicted FFR-significant stenosis with 89% sensitivity and 65% specificity compared with MDCT-IP, which showed 88% sensitivity and 83% specificity. In 97 vessels in which the results of all techniques were available, TAG320 + CTA (area under the curve [AUC] = 0.844) and CTP + CTA (AUC = 0.845) had comparable per-vessel diagnostic accuracy (p = 0.98). The diagnostic accuracy of MDCT-IP (AUC = 0.91) was superior to TAG320 + CTA or CTP + CTA (p = 0.01).
Conclusions In vessels without significant calcification or artefact, TAG320 + CTA and CTP + CTA provide comparable diagnostic accuracy for functional assessment of coronary artery stenosis. MDCT-IP may provide the best diagnostic accuracy for functional assessment of coronary artery stenosis.
Coronary computed tomography angiography (CTA) is an established noninvasive method for the assessment of the coronary artery anatomy. It is particularly useful for the exclusion of coronary artery disease because of the technique's established high sensitivity and negative predictive value (NPV) (1). However, CTA has been shown to have limited specificity and positive predictive value (PPV) for predicting functionally significant stenoses (2). Several methods, such as computed tomography (CT) stress myocardial perfusion imaging (CTP), transluminal attenuation gradient (TAG), and coronary CTA–derived computed fractional flow reserve (FFR), have been developed in an attempt to improve the diagnostic accuracy of CTA (3–5). Although CTP has been demonstrated to enhance detection for functionally significant stenoses, it requires additional iodinated contrast and radiation exposure (3,6,7). The diagnostic accuracy of TAG by 320-detector row CT (TAG320), which enables near isophasic, single-beat imaging of the entire coronary tree, has been recently demonstrated (4). However, no studies have compared the diagnostic accuracy of CTA, CTP, and TAG320. Our primary aim was to compare the diagnostic accuracy of CTA, combined CTP + CTA, and combined TAG320 + CTA assessments. Furthermore, we assessed the diagnostic accuracy of an integrated approach (MDCT-IP) that combines CTA, CTP, and TAG320 assessments. Invasive fractional flow reserve (FFR), a well-established and highly accurate invasive method to assess the functional significance of coronary stenosis, was used as the reference standard (8,9).
We examined consecutive patients who underwent CTA, CTP, and FFR assessment in our institution within a 2-month interval, between July 2009 and May 2011. This included symptomatic patients with known coronary artery disease who were considered for revascularization, and symptomatic patients with suspected coronary artery disease awaiting invasive coronary angiography. In all cases, cardiac CT was performed for the purpose of research. FFR was performed in vessels with ≥30% visual stenosis on diagnostic coronary angiography. Subtotally occluded and occluded vessels were excluded. Exclusion criteria included age younger than 40 years, atrial fibrillation, high-grade atrioventricular block, renal insufficiency (estimated glomerular filtration rate <60 ml/min/1.73 m2), bronchospastic lung disease requiring long-term steroid therapy, morbid obesity (body mass index [BMI] ≥40 kg/m2), myocardial infarction within 3 months, history of coronary artery bypass grafting or intractable heart failure, and contraindications to iodinated contrast. Patients were instructed to refrain from smoking or using tea, aminophylline, calcium antagonists, or nitrates for 24 h before the tests. For TAG320 analysis, patients with more than 50% stenosis in the left main coronary artery, branch vessel disease, distal vessel disease <2 mm in diameter, or chronic total occlusions were not included. The study was approved by our institutional human research ethics committee.
Invasive coronary angiography and FFR
Invasive coronary angiography was performed as per standard clinical practice via either a femoral or radial approach. For FFR, the pressure wire (Certus Pressure Wire, St. Jude Medical Systems, St. Paul, Minnesota) was calibrated and electronically equalized with the aortic pressure before being placed distal to the stenosis in the distal third of the coronary artery being interrogated. Intracoronary glyceryl trinitrate (100 μg) was injected to minimize vasospasm. Intravenous adenosine was administered (140 μg/kg/min) through an intravenous line in the antecubital fossa. At steady-state hyperemia, FFR was assessed using the RadiAnalyzer Xpress (Radi Medical Systems, Uppsala, Sweden), calculated by dividing the mean coronary pressure measured with the pressure sensor placed distal to the stenosis by the mean aortic pressure measured through the guide catheter. A FFR of ≤0.8 was taken to define ischemia in the interrogated artery and its supplied territory (8,10).
Quantitative coronary angiography
Quantitative coronary angiography (QCA) was undertaken on all coronary arteries ≥1.5-mm diameter, employing a 19-segment coronary model according to the SYNTAX classification (11). QCA was performed using a semiautomated edge detection system (QAngio XA 7.3, Medis, Leiden, the Netherlands) by an experienced cardiologist (B.S.K.) who was blinded to FFR and CT findings.
Cardiovascular medications were ceased 48 h before CTA, apart from beta-blockers. On arrival, an 18-gauge intravenous line was inserted in the right antecubital vein for administration of contrast. Oral and/or intravenous metoprolol was given if the resting heart rate was >65 beats/min. Patients were scanned on a 320-detector-row CT scanner (Aquilion ONE, Toshiba Medical Systems, Otawara, Japan). The scan was acquired during injection of 55 ml of 100% iohexal 56.6 g/75 ml (Omnipaque 350, GE Healthcare, Chalfont St Giles, United Kingdom) at 5 ml/s, followed by 20 ml of a 30:70 mixture of contrast and saline, followed by 30 ml of saline. Scanning was triggered in the arterial phase using automated contrast bolus tracking with the region of interest placed in the descending aorta, and automatically triggered at 300 HU.
Scan parameters for rest coronary CTA were as follows: detector collimation 320 × 0.5 mm; tube current 300 to 500 mA (depending on BMI); tube voltage 120 kV if BMI ≥25 (100 kV if BMI <25); gantry rotation time 350 ms; and temporal resolution 175 ms. Prospective electrocardiographic gating was used covering 70% to 80% of the R-R interval. For images acquired at heart rates ≤65 beats/min, scanning was completed within a single R-R interval utilizing a 180° segment. In patients with a heart rate >65 beats/min, data segments from 2 consecutive beats were used for multisegment reconstruction with improved temporal resolution of 87 ms. Images were reconstructed using the filtered back-projection technique with the FC03 algorithm.
The stress perfusion scan was performed 20 min after coronary CTA with intravenous adenosine infusion (140 μg/kg/min for 3 min), using prospective electrocardiographic gating covering phases 70% to 95% of the R-R interval, tube settings, and contrast dose as for the rest scan. The effective radiation dose was calculated by multiplying the dose–length product by a constant (k = 0.014 mSv/mGy/cm) (12).
Coronary artery analysis in coronary CTA
CTA images were analyzed on a dedicated workstation (Vitrea FX 2.0, Vital Images, Minnetonka, Minnesota) by 2 experienced CT angiographers (M.C.H.L. and S.K.S.) blinded to QCA and FFR results. The CT angiographers read independently of each other, and discrepant readings were reconciled by consensus. Image quality was determined by a 3-point scale: 1 = poor, 2 = moderate, and 3 = good. All segments ≥1.5 mm were analyzed using the same 19-segment coronary model for QCA (11). Each coronary segment was visually assessed for degree of luminal stenosis, and a vessel was considered significant if there was ≥1 segment that was nonevaluable or with ≥50% luminal stenosis.
Perfusion assessment was performed using both the stress and rest images. Datasets were reconstructed at 3% R-R intervals using a reconstruction kernel (FC03) that incorporates beam hardening correction (6,13). The phase with the least cardiac motion was selected, and images were interpreted using a narrow window width and level setting (W300/L150), and an averaged multiplanar reconstruction slice thickness of 3 to 5 mm, according to the American Heart Association 17-myocardial segment model (14) with disagreement resolved by a third reader. Segments with significant overlying artefacts were deemed uninterpretable and excluded from analysis. Each segment was scored for the presence or absence of a perfusion defect. Each myocardial segment was specifically matched to its subtending major epicardial artery, as determined by the course of the artery and its branches on coronary CTA. For the combined coronary CTA + CTP analysis, vessels were considered significant when coronary CTA demonstrated ≥50% stenosis and was associated with a reversible perfusion defect in the vessel's subtended territory.
Transluminal attenuation gradient
The centerline was determined for each major coronary artery and was manually corrected if necessary. Cross-sectional images perpendicular to the vessel centerline were then reconstructed. The region of interest contour (size = 1 mm2) was positioned in the center of the cross-sectional images. The position of the region of interest was manually adjusted. The mean luminal radiological attenuation (in Hounsfield units) was measured at 5-mm intervals, from the ostium to a distal level where the cross-sectional area fell below 2.0 mm2. TAG320 was determined from the change in Hounsfield units per 10-mm length of the coronary artery and defined as the linear regression coefficient between intraluminal radiological attenuation (in Hounsfield units) and length from the ostium (in millimeters) (4,15). A TAG320 cutoff of −15.1 HU/10 mm was defined as significant, as previously described (4). For the combined TAG320 + CTA assessment, vessels were classified as negative if CTA <50% stenosis. Vessels were classified as positive if CTA ≥50% and TAG320 was ≤−15.1 HU/10 mm.
The stenosis and plaque characteristics were classified in each lesion. Vessels were classified as noncalcified if the most stenotic segment was noncalcified. Vessels were classified as calcified if the most stenotic segment was calcified or partially calcified.
MDCT integrated TAG320 and CTP protocol (MDCT-IP)
The MDCT-IP was classified negative if stenosis <50% was detected on CTA. If the CTA showed ≥50% stenosis, the MDCT-IP was classified as positive if a perfusion defect was detected on CTP in a territory corresponding to the stenosis or if the TAG320 was ≤−15.1 HU/10 mm (Fig. 1).
Continuous variables are expressed as mean ± SD or median (quartiles) as appropriate, whereas categorical variables are expressed as percentages. Continuous and categorical variables were compared using the Student t test, Mann-Whitney test, or chi-square test as appropriate. Owing to the repeated measures nature of the study, a generalized estimating equation approach was used, assuming a binomial probability distribution.
Receiver-operating characteristic curve analysis was performed to evaluate the discriminatory ability of CTA, CTP + CTA, TAG320 + CTA, and MDCT-IP for FFR ≤0.8. The incremental value of adding TAG320 and CTP to CTA in discriminating significant FFR was assessed using the integrated discrimination improvement (IDI) index as described by Pencina et al. (16):where “new” refers to a model containing a novel diagnostic tool of interest in addition to conventional risk-predictors, and “old” pertains to the model containing only the conventional risk markers. IS and IP are the integrals of sensitivity and 1 − specificity, respectively. In addition, the category-free net reclassification index (NRI) for identification of FFR ≤0.8 using TAG320 over CTA was calculated (16).
Statistical analysis was performed with SPSS version 18.0 (SPSS, Chicago, Illinois) and STATA version 12.1 (StataCorp., College Station, Texas). A p value <0.05 was considered statistically significant.
Seventy-five consecutive patients who underwent CTA, CTP, and clinically indicated coronary angiography, as well as assessment of FFR, were studied. A total of 127 vessels were evaluated. TAG320 analysis could be performed in 64 patients (85%) and 97 vessels (76.4%). Vessels were nonevaluable because of the intramyocardial course of the left anterior descending artery (n = 3), branch or small vessel (n = 8), calcified disease (n = 15), and significant artefact (n = 4). The overall patient cohort age was 64.0 ± 10.8 years, with 52 (69%) men. Patient characteristics are summarized in Table 1. The mean estimated radiation effective dose for CTA, CTP, and CTA + CTP in our study was 4.6, 4.8, and 9.8 mSv, respectively. The CT scan parameters are summarized in Table 2.
Fractional flow reserve
FFR was measured successfully in all 75 patients, involving 127 vessels (57 left anterior descending arteries, 31 left circumflex arteries, and 39 right coronary arteries). Thirty-eight (51%) patients received FFR interrogation in the territory of 1 vessel, 22 (29%) in 2 vessels, and 15 (20%) had the territories of all 3 vessels interrogated. Overall, FFR readings ranged from 0.32 to 1.0 (mean 0.82 ± 0.15). Forty-four vessels (35%) were classified with functionally significant stenoses with FFR ≤0.8, whereas 83 vessels had FFR >0.8.
Accuracy of invasive QCA compared with FFR
On a per-vessel basis, 37 (29%) vessels had ≥50% stenosis on QCA, whereas 12 (9%) had ≥70% stenosis. The sensitivity, specificity, PPV, and NPV of QCA of ≥50% in predicting significant FFR were 61%, 88%, 73%, and 81%, respectively. Meanwhile, the sensitivity, specificity, PPV, and NPV of QCA ≥70% in predicting significant FFR were 25%, 99%, 92%, and 71%, respectively (Table 3).
Accuracy of coronary CTA compared with FFR
There were 22 (17%) vessels that had severe calcification in which significant stenosis could not be excluded. These vessels were classified as ≥50% stenosis and were included in the analysis. In the vessels interrogated with FFR, 68 (54%) vessels were identified to have ≥50% stenosis on CTA. The sensitivity, specificity, PPV, and NPV of CTA for the identification of FFR-significant stenoses were 89%, 65%, 57%, and 92%, respectively (Table 3). The c-statistic of CTA for the prediction of FFR ≤0.8 was 0.77 (0.68 to 0.85).
Accuracy of combined CTP and CTA assessment compared with FFR
The combined CTP and CTA assessment could be performed in 123 (97%) vessels. CTP assessment could not be performed in 4 vessels because of artefacts. On a per-vessel basis, 32 (25%) vessels were identified to have ≥50% stenosis on CTA with a corresponding perfusion defect identified on CTP. The sensitivity, specificity, PPV, and NPV of the combined assessment of CTP + CTA for the identification of FFR-significant stenoses were 76%, 89%, 78%, and 88%, respectively (Table 3). The c-statistic for combined assessment of CTP + CTA for the prediction of FFR ≤0.8 was 0.825 (0.74 to 0.91).
Accuracy of TAG320 and of combined TAG320 + CTA compared with FFR
The TAG320 and combined TAG320 + CTA assessments could be performed in 97 (78%) vessels. Median TAG320 in FFR-significant vessels was significantly lower when compared with nonsignificant vessels (−19 [−26 to −13] vs. −10 [−16 to −5] HU/10 mm, p < 0.001). A TAG320 cutoff of −15.1 HU/10 mm predicted FFR ≤0.8 with a sensitivity of 71%, specificity of 77%, PPV of 63%, and NPV of 83%, respectively. When CTA was combined with TAG320, this yielded a sensitivity of 73%, specificity of 97%, PPV of 92%, and NPV of 87% (Table 3). The c-statistic for the combined assessment of TAG320 + CTA for the prediction of FFR ≤0.8 was 0.848 (0.752 to 0.944).
Accuracy of MDCT-IP compared with FFR
The MDCT-IP approach could be performed in 117 vessels. On a per-vessel analysis, 35 (28%) vessels were identified to be significant. The sensitivity, specificity, PPV, and NPV of CTA for the identification of FFR significant stenoses were 88%, 83%, 74%, and 93%, respectively (Table 3). The c-statistic for combined assessment of CTP + TAG320 + CTA (MDCT-IP) for the prediction of FFR ≤0.8 was 0.854 (0.778 to 0.93).
Comparison of CTP + CTA, TAG320 + CTA, and MDCT-IP in predicting FFR
In the comparison of the diagnostic accuracy of the combined assessment of CTP + CTA, TAG320 + CTA, and MDCT-IP, 97 vessels that could be assessed by all 3 methods were included for analysis. Using the generalized estimating equation, the predictive value of CTP + CTA (p = 0.003) and TAG320 + CTA (p = 0.002) were comparable. The c-statistics for the combined assessment of CTP + CTA (0.845) and TAG320 + CTA (0.844) were also comparable (p = 0.98). The c-statistic for MDCT-IP was 0.905. On a global comparison of receiver-operating characteristic curves for all 3 methods, MDCT-IP was the best predictor of significant FFR (p = 0.01). The MDCT-IP approach resulted in a marked increase in sensitivity and a mild decrease in specificity compared with CTA + CTP and CTA + TAG320 (Table 4). The diagnostic accuracy of the 3 methods in 97 vessels is summarized in Table 4.
Accuracy of CTP + CTA, TAG320 + CTA, and MDCT-IP in predicting FFR in calcified vessels
Fifty of 127 vessels were classified as calcified based on qualitative assessment. TAG320 + CTA assessment was limited to 38 vessels, CTP + CTA and MDCT-IP could be performed in 48 and 46 vessels, respectively. The diagnostic accuracy of all 3 assessments is presented in the Online Appendix.
Incremental value of adding CTP to CTA, and TAG320 to CTA in discriminating significant FFR
There was incremental value in adding CTP to CTA assessment for detection of significant FFR by the IDI index. The IDI for the addition of CTP to CTA for detection of significant FFR was 0.18 (p < 0.0001), whereas the category-free NRI was 1.30 (p < 0.0001). There was also incremental value in adding TAG320 to CTA assessment for detection of significant FFR by NRI (1.39, p < 0.0001) and IDI (0.21, p = 0.0002).
Incremental value of adding CTP and TAG320 to CTA in discriminating significant FFR
There was also convincing evidence of the incremental value of adding CTP and TAG320 to CTA assessment (MDCT-IP) for detection of significant FFR by NRI (1.46, p < 0.0001) and IDI (0.26, p < 0.0001). In addition, MDCT-IP also had incremental value over TAG320 + CTA assessment by NRI (0.93, p < 0.0001) and IDI (0.12, p < 0.0001). MDCT-IP also had incremental value over CTP + CTA assessment by NRI (1.45, p < 0.0001) and IDI (0.10, p < 0.0001).
In this study, we have compared for the first time, to our knowledge, the diagnostic accuracy of the combined assessment of CTP + CTA and of TAG320 + CTA obtained using 320-detector row CT with invasive functional standard, FFR, as reference. We have also demonstrated for the first time the diagnostic accuracy of an integrated approach (MDCT-IP) that combines 3 modalities (CTA, CTP, and TAG320) in discriminating functionally significant coronary arterial stenoses.
TAG320, CTP, and CTA assessment on 320-detector row CT with FFR as the reference standard
On the basis of the results from the FAME (Fractional flow reserve [FFR] vs. Angiography in Multivessel Evaluation) study, it is widely accepted that revascularization based on the functional significance of coronary artery stenoses as opposed to anatomic assessment translates to lower cost and better outcome (8). Therefore, FFR, which is the gold standard of functional assessment of coronary artery stenosis, was chosen as the reference in this study. Ideally, the anatomic and functional significance of disease can be determined using a single noninvasive imaging modality in a single examination. To date, the only noninvasive method that has shown promise is MDCT, with previous studies having demonstrated the diagnostic accuracy and incremental predictive value of combined CTP and CTA assessment over CTA alone (6,17). However, this assessment requires 2 separate (stress and rest) scans that require additional radiation exposure and contrast. In our study, combined CTP and CTA assessment was associated with a mean radiation dose of 9.8 mSv compared with 4.6 mSv for CTA alone. Therefore, efforts have been made to develop MDCT techniques that can assess the functional significance of coronary artery stenoses without adenosine administration and additional contrast and radiation. TAG is a technique based on the kinetics of iodinated contrast across coronary artery stenoses that has recently shown promise for coronary artery stenosis assessment (15,18) (Fig. 2). The 320-detector row CT, by enabling near isophasic, single-beat imaging of the entire coronary tree, is ideal for TAG assessment (4,19). We have recently demonstrated the diagnostic accuracy and incremental predictive value of combined CTA and TAG320 assessment over CTA alone on a 320-detector CT (4). Nonetheless, no studies have compared the diagnostic accuracy of the combined assessment of CTP + CTA and TAG320 + CTA. In addition, the diagnostic accuracy of the combined assessment of CTP + TAG320 + CTA (MDCT-IP) has not been described.
Diagnostic accuracy of CTA, combined CTP + CTA, and TAG320 + CTA assessments
The high sensitivity (89%) and NPV (92%), but modest specificity (65%) and PPV (57%), of CTA in our study is comparable to previous studies (2,17). Meanwhile, there have only been 3 previous studies that have compared the diagnostic accuracy of combined CTP and CTA assessment with FFR as the reference standard (3,6,17). The improved specificity (89%), but reduced sensitivity (76%), with combined CTP and CTA assessment in our study is comparable to the 3 previous studies that have described specificities that ranged from 90% to 95% and sensitivities of 68% to 87%. The diagnostic accuracy of the combined TAG320 and CTA assessment has only been reported in our previous study (4). Combined TAG320 and CTA in this study showed excellent specificity (97%) with modest sensitivity (73%), whereas the c-statistic was 0.848, which is comparable to our previous study (area under the curve [AUC] = 0.89). It is, however, likely to be superior to the diagnostic accuracy (AUC = 0.63) of TAG assessment on 64-detector row MDCT (20).
Comparison of the diagnostic accuracy of combined CTP + CTA, TAG320 + CTA, and CTP + TAG320 + CTA (MDCT-IP)
Calcified disease remains an important challenge for the interpretation of CTA. Up to 33% of patients may have unevaluable coronary segments as a result of the presence of extensive calcification (17,21). Our study had a higher prevalence of calcified vessels (50 vessels, 39%) compared with some recent studies (24 vessels, 29%) (20), which may limit CTA and TAG320 assessment. As a result, 22 vessels could not be reliably assessed by CTA, whereas TAG320 assessment could not be performed in 9% of patients. Because TAG320 assessment involves measurement of mean luminal radiological attenuation (Hounsfield units) at 5-mm intervals from the ostium to a distal level, it is more susceptible to the influence of calcification and artefact in the entire epicardial coronary artery course (Fig. 3). Its diagnostic utility is also uncertain in branch vessel disease. These factors limited the number of vessels that could be assessed by TAG320 in this study.
In order to compare the diagnostic accuracy of CTP + CTA, TAG320 + CTA, and MDCT-IP, we compared 97 vessels that were successfully assessed by all 3 methods. To our knowledge, this is the first study that has compared the diagnostic accuracy of these novel assessments. We found that the diagnostic accuracy of the combined assessment of TAG320 + CTA (AUC = 0.844) and combined CTP + CTA (AUC = 0.845) was comparable. In addition, we demonstrated that the combined assessment of CTP + TAG320 + CTA (MDCT-IP) had the best diagnostic accuracy (AUC = 0.91). The MDCT-IP approach was superior to the combined assessment of TAG320 + CTA or CTP + CTA. Our study highlights a potential practical application for MDCT as a “1-stop shop” noninvasive assessment of coronary artery stenosis that might also address function. In this cohort, the addition of CTP resulted in the successful evaluation of 123 (97%) vessels. The addition of CTP to CTA and TAG320 analysis significantly increased the number of vessels that could be evaluated in this study.
Our results represent a retrospective single-center experience involving 75 patients who underwent clinically indicated FFR, and hence needs confirmation with larger prospective multicenter studies with FFR performed routinely or on a research basis. In the studied cohort, 3-vessel FFR data were not available, hence limiting the general applicability of our findings. We have accordingly presented the accuracy data on a per-vessel basis. Although there is incremental predictive value of TAG320 when added to CTA, its utility at this stage is limited to vessels without significant calcification, vessels with a cross-sectional area greater than 2.0 mm2 (or diameter greater than 1.6 mm), and vessels not affected by artefact anywhere along their entire course. Despite the well-controlled heart rate (mean of 55 beats/min) of patients in this study, which has a high prevalence of patients with known coronary artery disease, TAG320 evaluation cannot be done in all vessels because heavily calcified vessels are often not evaluable by TAG320. In this study, calcium scores were not performed. We therefore could not explore whether a certain cutoff of the calcium score would render TAG320 uninterpretable, leading to the need for CTP as an upfront ischemic assessment in certain patients. Future studies and technological advances are required to improve the utility of TAG320 in these vessels. In addition, the utility of TAG320 also needs to be validated using more current acquisition and reconstruction protocols such as the model-based iterative reconstruction algorithm (“AIDR-3D”). Lastly, the interpretation of CTP has been performed in the same setting as CTA, which may introduce bias. Combined interpretation has been chosen as recommended by guidelines, in preference to separate blinded interpretations of CTA and CTP (13).
Based on the results of the study, combined assessment of TAG320 + CTA and of CTP + CTA provides comparable diagnostic accuracy for functional assessment of coronary artery stenosis in vessels without significant calcification or artefacts. Combined assessment of TAG320 + CTP + CTA (MDCT-IP) may provide improved diagnostic accuracy for functional assessment of coronary artery stenosis. Larger studies are required to determine the diagnostic and prognostic value of these assessments.
For a supplemental table, please see the online version of this article.
Dr. Meredith has received honoraria for serving on strategic advisory boards of Boston Scientific and Medtronic. Dr. Seneviratne has been an invited speaker at a Toshiba-sponsored meeting. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Wong and Ko contributed equally to this work.
- Abbreviations and Acronyms
- area under the curve
- body mass index
- computed tomography
- coronary computed tomography angiography
- computed tomography perfusion
- fractional flow reserve
- integrated discrimination improvement
- integrated protocol
- multidetector computed tomography
- negative predictive value
- net reclassification index
- positive predictive value
- quantitative coronary angiography
- transluminal attenuation gradient by 320-detector row computed tomography
- Received November 15, 2013.
- Revision received January 15, 2014.
- Accepted February 18, 2014.
- American College of Cardiology Foundation
- Budoff M.J.,
- Dowe D.,
- Jollis J.G.,
- et al.
- Meijboom W.B.,
- Van Mieghem C.A.,
- van Pelt N.,
- et al.
- Ko B.S.,
- Cameron J.D.,
- Meredith I.T.,
- et al.
- Wong D.T.,
- Ko B.S.,
- Cameron J.D.,
- et al.
- Koo B.K.,
- Erglis A.,
- Doh J.H.,
- et al.
- Ko B.S.,
- Cameron J.D.,
- Leung M.,
- et al.
- Kern M.J.,
- Samady H.
- Cerqueira M.D.,
- Weissman N.J.,
- Dilsizian V.,
- et al.
- Bettencourt N.,
- Chiribiri A.,
- Schuster A.,
- et al.
- Chow B.J.,
- Kass M.,
- Gagne O.,
- et al.
- Steigner M.L.,
- Mitsouras D.,
- Whitmore A.G.,
- et al.
- Yoon Y.E.,
- Choi J.H.,
- Kim J.H.,
- et al.
- Blankstein R.,
- Shturman L.D.,
- Rogers I.S.,
- et al.