Author + information
- Received March 13, 2006
- Revision received May 2, 2006
- Accepted May 31, 2006
- Published online December 19, 2006.
- Joanne D. Schuijf, MSc⁎,†,‡,
- William Wijns, MD, PhD§,
- J. Wouter Jukema, MD, PhD⁎,‡,
- Douwe E. Atsma, MD, PhD⁎,
- Albert de Roos, MD, PhD†,
- Hildo J. Lamb, MD, PhD†,
- Marcel P.M. Stokkel, MD, PhD∥,
- Petra Dibbets-Schneider, MSc∥,
- Isabel Decramer, MSc§,¶,
- Pieter De Bondt, MD, PhD#,
- Ernst E. van der Wall, MD, PhD⁎,‡,
- Piet K. Vanhoenacker, MD¶ and
- Jeroen J. Bax, MD, PhD⁎,⁎ ()
- ↵⁎Reprint requests and correspondence:
Dr. Jeroen J. Bax, Department of Cardiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, the Netherlands.
Objectives The aim of this study was to perform a head-to-head comparison between multi-slice computed tomography (MSCT) and myocardial perfusion imaging (MPI) in patients with an intermediate likelihood of coronary artery disease (CAD) and to compare non-invasive findings to invasive coronary angiography.
Background Multi-slice computed tomography detects atherosclerosis, whereas MPI detects ischemia; how these 2 techniques compare in patients with an intermediate likelihood of CAD is unknown.
Methods A total of 114 patients, mainly with intermediate likelihood of CAD, underwent both MSCT and MPI. The MSCT studies were classified as having no CAD, nonobstructive (<50% luminal narrowing) CAD, or obstructive CAD. Myocardial perfusion imaging examinations were classified as showing normal or abnormal (reversible and/or fixed defects). In a subset of 58 patients, invasive coronary angiography was performed.
Results On the basis of the MSCT data, 41 patients (36%) were classified as having no CAD, of whom 90% had normal MPI. A total of 33 patients (29%) showed non-obstructive CAD, whereas at least 1 significant (≥50% luminal narrowing) lesion was observed in the remaining 40 patients (35%). Only 45% of patients with an abnormal MSCT had abnormal MPI; even in patients with obstructive CAD on MSCT, 50% still had a normal MPI. In the subset of patients undergoing invasive angiography, the agreement with MSCT was excellent (90%).
Conclusions Myocardial perfusion imaging and MSCT provide different and complementary information on CAD, namely, detection of atherosclerosis versus detection of ischemia. As compared to invasive angiography, MSCT has a high accuracy for detecting CAD in patients with an intermediate likelihood of CAD.
In the evaluation of patients with suspected coronary artery disease (CAD), the role of non-invasive imaging has increased exponentially over the past decades. Particularly in patients with an intermediate before-test likelihood of CAD, non-invasive imaging plays an important role in risk stratification and selection of further treatment strategies. Traditionally, the detection of CAD by non-invasive imaging was based on assessment of the hemodynamic significance of the stenoses through visualization of inducible ischemia. For this purpose, myocardial perfusion imaging (MPI) with gated single-photon emission computed tomography (SPECT) has been used extensively (1).
More recently, multi-slice computed tomography (MSCT) has been proposed as an alternative imaging modality for evaluation of patients with suspected CAD. With the recently introduced 64-slice MSCT, high sensitivity and specificity for the detection of significant (≥50% luminal narrowing) stenoses have been reported (2–7). However, because MSCT visualizes coronary artery stenoses directly, rather than the hemodynamic significance of the lesions, it is important to recognize that, unlike MPI, the technique identifies atherosclerosis rather than ischemia.
Thus far, data regarding the diagnostic accuracy of MSCT have been obtained in populations undergoing invasive coronary angiography because of a high likelihood of CAD. In contrast, the value of MSCT in patients with a lower likelihood of CAD remains to be established, despite the fact that this population represents the target population for noninvasive diagnostic imaging. Moreover, the relative merits of MPI and MSCT in patients with an intermediate likelihood of CAD remain to be established. Accordingly, the aim of the present study was to perform a head-to-head comparison between MSCT and MPI in patients with mainly an intermediate likelihood of CAD, including women. In addition, the noninvasive findings were compared to invasive coronary angiography in a subset of patients.
Patients and study protocol
The study group consisted of 114 consecutive patients who presented to the outpatient clinic (Leiden, the Netherlands, and Aalst, Belgium) for the evaluation of chest pain without history of CAD in whom non-invasive imaging with gated SPECT was clinically indicated. In addition to MPI, patients underwent non-invasive coronary angiography with MSCT within 1 month. Exclusion criteria were: 1) known allergy to iodinated contrast agent; 2) renal insufficiency (serum creatinine >120 mmol/l); 3) atrial fibrillation; 4) pregnancy; and 5) known CAD, defined as history of myocardial infarction or coronary revascularization and/or presence of 1 or more angiographically documented coronary stenoses with ≥50% luminal diameter (8,9). For each patient, the baseline clinical characteristics (type of symptoms and risk factors) were recorded (10). Before-test likelihood of CAD was determined according to the Diamond and Forrester method using percent cutoffs of <13.4%, >87.2%, and in between for low, high, and intermediate before-test likelihood, respectively (11). The study protocol was approved by the ethics committee and informed consent was obtained.
MSCT coronary angiography
In the first 28 patients, data acquisition was performed using a 16-slice MSCT scanner (Aquilion 16, Toshiba Medical Systems, Otawara, Japan) with a collimation of 16 × 0.5 as previously described (9). In the remaining 86 patients, imaging was performed using a 64-slice MSCT scanner (Aquilion 64, Toshiba Medical Systems, Japan, or Sensation 64, Siemens, Forchheim, Germany). Accordingly, data were acquired with a collimation of either 64 × 0.5 mm or 32 × 2 × 0.6 mm and a tube rotation time of 400 or 330 ms, respectively. For the Aquilion 64, the tube current was 300 mA at 120 kV for patients with normal posture. In patients with higher body mass indexes, tube current was increased to 350 or 400 mA at 135 kV. For the Siemens 64, tube currents up to 550 ms at 120 kV were available. During 16-slice MSCT, non-ionic contrast material was administered in the antecubital vein with an amount of 130 to 140 ml, depending on the total scan time, and a flow rate of 4 ml/s (Xenetix 300) followed by a saline flush. Similarly, for 64-slice MSCT, 80 to 110 ml, again depending on the total scan time, was administered with a flow rate of 5 ml/s (Iomeron 400), resulting in comparable contrast doses for 16- and 64-slice MSCT. Subsequently, data sets were reconstructed and transferred to a remote workstation as previously described (9). Briefly, images were initially reconstructed at 75% of the cardiac cycle. In case of motion artifacts, a representative single slice was reconstructed throughout the cardiac cycle in steps of 20 ms to determine the most optimal additional reconstruction phases.
Multi-slice computed tomography examinations were evaluated on a patient level and vessel level by an experienced operator blinded to the gated MPI data for the presence of significant (≥50% luminal narrowing) stenoses. For this purpose, both the original axial dataset as well as curved multiplanar reconstructions were used. The MSCT studies, or coronary arteries, without significant or obstructive stenoses were further classified as completely normal or as having non-obstructive CAD when atherosclerotic lesions <50% of luminal diameter were present.
Stress-rest gated myocardial perfusion imaging
In all patients, stress-rest MPI (using either technetium-99m tetrofosmin or technetium-99m sestamibi) was performed with symptom-limited bicycle exercise or pharmacologic (dipyridamole, adenosine, or dobutamine) stress (12). Data were acquired with either a dual-head SPECT camera (Vertex Epic ADAC Pegasus, Philips Medical Systems, Eindhoven, the Netherlands; n = 27) or a triple-head SPECT camera (GCA 9300/HG, Toshiba Corp., Tokyo, Japan; n = 87) followed by reconstruction into long- and short-axis projections perpendicular to the heart axis; data were presented in polar map format (normalized to 100%), and a 17-segment model was used in which myocardial segments were allocated to the territories of the different coronary arteries as previously described (13,14). Perfusion defects were identified on the stress images (segmental tracer activity <75% of maximum) and divided into ischemia (reversible defects, with ≥10% increase in tracer uptake on the resting images) or scar tissue (irreversible defects). Accordingly, examinations were classified as being either normal or abnormal, the latter being further divided into those demonstrating reversible defects and those demonstrating irreversible defects. The gated images were used to assess regional wall motion to improve differentiation between perfusion abnormalities and attenuation artifacts (15).
Conventional coronary angiography
A total of 58 patients were referred for conventional coronary angiography on the basis of clinical presentation and/or imaging findings at the discretion of the referring cardiologist. Conventional coronary angiography was performed according to standard clinical protocols. Coronary angiograms were evaluated by 2 experienced observers blinded to the MSCT data using the same classification as used for the MSCT studies (normal; significant stenoses, defined as ≥50% luminal narrowing; or non-obstructive atherosclerosis).
Continuous variables were described as mean values ± SD. Comparisons between patient groups were performed using 1-way ANOVA for continuous variables and the chi-square test with Yates’ correction for categorical variables. A p value <0.05 was considered statistically significant.
In total, 114 patients (64 men, 50 women, average age 60 ± 11 years) were enrolled and underwent both MSCT and stress-rest gated SPECT within 1 month of each other (mean 16 ± 10 days). Patient characteristics are described in detail in Table 1.Before-test likelihood of CAD according to Diamond and Forrester was low, intermediate, and high, respectively, in 7 (6%), 97 (85%), and 10 (9%) patients. For men, these percentages were, respectively, 3%, 84%, and 13%. In women, before-test likelihood was low in 10%, intermediate in 86%, and high in 4%. On the basis of clinical presentation and/or imaging results, 58 patients (38 men, 20 women, average age 63 ± 10 years) were referred for invasive coronary angiography. Clinical parameters of these patients are provided in Table 2.In this subset, before-test likelihood of CAD was low, intermediate, or high in 1 (2%), 48 (83%), and 9 patients (15%), respectively.
MSCT coronary angiography
Average heart rate during MSCT data acquisition was 66 ± 15 beats/min. On the basis of the MSCT images, 41 patients (36%) were classified as having no CAD. A total of 33 patients (29%) showed non-obstructive CAD, whereas at least 1 significant ≥50% luminal narrowing was observed in the remaining 40 patients (35%). Analysis on a vessel basis resulted in 342 coronary arteries, of which 157 (46%) were normal. Coronary artery disease was identified in the remaining 185 coronary arteries, with at least 1 significant lesion in 62 (18%) coronary arteries.
Stress-rest gated myocardial perfusion imaging
In the majority of patients, stress testing was performed with symptom-limited bicycle exercise (n = 72; 63%). In those patients, at least 85% of maximum age-predicted heart rate was achieved if no stress-induced symptoms or changes in electrocardiogram or blood pressure occurred. In the remaining patients, pharmacologic stress was applied using adenosine (n = 30; 26%), dobutamine (n = 7; 7%), or dipyridamole (n = 5; 3%). Normal myocardial perfusion in both stress and rest images was observed in 77 patients (68%). In the remaining 37 patients, reversible and fixed defects were observed in 28 and 12 patients, respectively; 3 patients showed both fixed and reversible defects. On a vascular territory basis, 284 territories (83%) showed normal myocardial perfusion, whereas reversible and fixed defects were observed in 38 (11%) and 20 (6%) vascular territories, respectively.
Conventional coronary angiography
Of 58 patients undergoing invasive coronary angiography, no abnormalities were seen in 9 patients (16%), whereas 22 patients (38%) showed nonobstructive CAD. In the remaining 27 patients (47%), at least 1 significant narrowing was detected.
Relation between findings on MSCT angiography and MPI
As demonstrated in Figure 1,the majority of patients with a normal MSCT study showed normal perfusion on MPI (n = 37, 90%). In patients with an abnormal MSCT study (with either obstructive or nonobstructive CAD), 40 patients (55%) had a normal MPI, whereas 33 (45%) had an abnormal MPI.
In Figure 2,the distribution of MPI results among patients with either obstructive or nonobstructive CAD on MSCT is depicted. In patients with obstructive CAD on MSCT, abnormal perfusion was observed in 20 patients (50%). Of these patients, 7 and 15 patients showed fixed or reversible defects, respectively. Of note, in all patients with stress-testing by means of exercise and a normal MPI despite an abnormal MSCT, adequate heart rate (>85% of predicted maximum heart rate) was achieved. The majority of patients (n = 20, 61%) with nonobstructive CAD on MSCT had normal perfusion on MPI. In the remaining 13 patients (39%), reversible defects were observed in 11, with only 2 patients showing fixed defects. An example of a patient with abnormal MSCT but normal MPI is provided in Figure 3.
In a separate analysis depicted in Table 3,results were compared between data obtained with 16- and 64-slice MSCT, indicating no significant differences in distribution of normal and abnormal MPI examinations for the different MSCT categories.
In total, 342 coronary arteries and related perfusion territories were evaluated. The majority of the 157 normal coronary arteries on MSCT showed normal MPI as well (n = 142, 90%). Also, in 143 of 185 vascular territories corresponding to coronary arteries with abnormal MSCT (77%), normal perfusion was demonstrated. In coronary arteries showing nonobstructive CAD on MSCT, normal MPI was obtained in 104 of 123 corresponding vascular territories (85%). Finally, 24 of 62 coronary arteries (39%) with obstructive CAD on MSCT showed abnormal myocardial perfusion.
Comparison of MSCT and MPI to conventional coronary angiography in 58 patients
The relation of findings on MSCT, MPI, and conventional coronary angiography is illustrated in the flowcharts in Figure 4.All patients with normal MSCT (n = 9) had normal coronary arteries on conventional coronary angiography; the majority of these patients (n = 7, 78%) also had a normal MPI. All patients with normal MSCT and normal invasive angiography but abnormal MPI had a mild fixed defect suggestive of attenuation artifacts.
An abnormal MSCT was noted in 49 patients (with 16 non-obstructive and 33 obstructive CAD) and invasive coronary angiography confirmed CAD in all patients. Interestingly, only 29 patients (59%) had an abnormal MPI.
Non-obstructive CAD on MSCT was observed in 16 patients (28%), and all had nonobstructive CAD on invasive angiography; of note, 6 patients (38%) had a normal MPI and 10 (62%) had an abnormal MPI.
Obstructive CAD (at least 1 significant stenosis) on MSCT was noted in 33 patients (57%), with 27 (82%) having obstructive CAD on invasive coronary angiography. An abnormal MPI was present in 16 patients (59%), whereas 11 patients (41%) had a normal MPI. Of interest, 2 of these patients had 3-vessel disease.
In a separate analysis, data obtained with 16-slice MSCT were compared with 64-slice data. With 16-slice MSCT, 19 of 21 patients (90%) were correctly diagnosed as compared to invasive coronary angiography, whereas correct diagnosis was obtained in 33 of 37 patients (89%) studied with 64-slice MSCT (p = NS).
This head-to-head comparison between noninvasive coronary angiography with MSCT and functional imaging by MPI in a large population with an intermediate likelihood of CAD reveals several findings. First, 55% of patients with an abnormal MSCT had normal MPI, indicating that only half of the observed lesions on MSCT may be of hemodynamic significance. Even among patients with obstructive CAD on MSCT, 50% had a normal MPI.
Conversely, patients with a normal MPI frequently (52%) exhibited an abnormal MSCT, indicating that a normal MPI does not exclude the presence of coronary atherosclerosis. In the subgroup of patients undergoing coronary angiography, similar results were obtained. These findings highlight the discrepancy between the 2 tests, namely, that atherosclerosis is not synonymous with ischemia, but also emphasize the complementary information that both tests provide.
Finally, this is a first attempt to apply MSCT in patients with an intermediate likelihood of CAD, including 44% of women. The MSCT findings correlated well with invasive coronary angiography, suggesting that the high accuracy of MSCT demonstrated previously in patients with a high likelihood of CAD also applies to patients with an intermediate likelihood of CAD.
Obstructive CAD versus hemodynamic significance
In the current study, a normal MPI was obtained in 55% of patients with an abnormal MSCT. Moreover, 50% of patients with obstructive CAD on MSCT had a normal MPI. The findings are in line with preliminary results by Hacker et al. (16), who compared MSCT and MPI in 25 patients with known or suspected CAD. These investigators showed that only 8 of 17 significant stenoses on MSCT (47%) were associated with abnormal perfusion on MPI.
These observations confirm that the severity of focal stenosis severity in itself is not sufficient to predict the hemodynamic significance of the coronary plaque burden. In our study, vessel-based analysis shows that only 39% of obstructed vessels have abnormal MPI, whereas 15% of non-obstructive vessels show perfusion abnormalities. In the latter situation, the additive effect of multiple mild stenoses in series eventually causes the perfusion defect (17). Similarly discrepant results have been reported when comparing invasive angiography with noninvasive imaging or invasive fractional flow reserve measurements. Salm et al. (18) showed that MPI was normal in 50% of angiographically significant lesions. In particular, lesions with an intermediate stenosis severity (defined as a percent diameter stenosis between 40% and 70%) vary in hemodynamic significance (18–20). To some extent, these discrepancies may be attributable to imperfect allocation of perfusion defects to corresponding coronary arteries owing to individual variations in coronary anatomy. Still, analysis on a vessel basis further emphasizes that only a moderate proportion of anatomically significant stenoses are of hemodynamic significance and result in abnormal perfusion in the corresponding vascular territory.
Atherosclerosis versus MPI findings
Alternatively, CAD was completely absent in only 48% of patients with normal MPI, of whom 52% had atherosclerosis on MSCT and 26% already exhibited obstructive CAD on MSCT. Thus, a normal MPI does not exclude CAD, and non-invasive coronary angiography with MSCT allows detection of CAD at a much earlier stage than does MPI. The relation between atherosclerosis detected by coronary calcifications and MPI was explored recently by Berman et al. (21) in 1,195 patients without known CAD who underwent electron beam computed tomography. The authors showed a poor relation between the presence of atherosclerosis on electron beam computed tomography and MPI results. Similar to the current results, a large proportion of patients with a normal MPI had atherosclerosis according to coronary artery calcium scoring, indicating again that a normal MPI does not exclude the presence of CAD.
The current observations have important clinical implications. With the introduction of MSCT and comparison to MPI, a paradigm shift occurs in the definition of CAD, displacing the emphasis from inducible ischemia to atherosclerosis. Based on the discrepancy between MSCT and MPI, one can argue that MSCT could be used as the first-line test. A normal MSCT excludes CAD, and the patient can be reassured. Alternatively, in the presence of atherosclerosis on MSCT, additional information is needed to define the hemodynamic significance of the observed lesions. This additional information could be provided by sequential MSCT and nuclear myocardial perfusion imaging using either positron emission tomography or SPECT. Patients with an abnormal MSCT but normal MPI have CAD. In those patients, aggressive medical therapy and risk factor modification should be considered (targeted primary prevention), whereas patients with an abnormal MSCT and an abnormal MPI should be referred for invasive angiography with potential revascularization.
MSCT in patients with an intermediate likelihood of CAD
As emphasized in a recent meta-analysis (22), the available MSCT studies have been performed in patients with known CAD or a high likelihood of CAD; in particular, pooling of 24 MSCT studies revealed a prevalence of significant stenoses on MSCT and invasive angiography of 65%. Pooled data from six 64-slice MSCT studies (including 363 patients) showed a sensitivity of 96% and a specificity of 92% to detect or exclude significant CAD (2–7). The current study was performed in patients with predominantly intermediate likelihood of CAD, yet the agreement between MSCT and invasive angiography remains excellent. All patients with normal MSCT had normal coronary arteries on invasive angiography, and all patients with obstructive or nonobstructive CAD on MSCT had CAD on invasive angiography. Only 6 of 33 (18%) patients with a significant stenosis on MSCT did not have a significant stenosis on invasive coronary angiography by visual estimation. These observations suggest that MSCT may be as accurate in patients with an intermediate likelihood of CAD as in patients with a high likelihood, although larger studies are clearly needed to confirm this finding.
In the present study, MSCT and MPI protocols were not uniform in all patients. For MSCT, scanners from 2 generations as well as manufacturers were used, whereas for MPI different tracers and stressors were applied. This, however, reflects the daily clinical routine and confers generalized applicability to our observations. Also, comparison of results obtained with either 16- or 64-slice MSCT did not show any significant differences.
Conventional coronary angiography was performed in approximately half of the patients included in the study and stenotic segments were not analyzed by quantitative angiography. However, the angiography was performed as considered clinically indicated and according to standard practice. Finally, despite the introduction of 64-slice MSCT, the technique still suffers from several important limitations, including limited diagnostic accuracy in case of extensive calcifications or elevated heart rates. Also, combination of MSCT with MPI and (potentially) conventional coronary angiography will result in a considerable radiation exposure.
Both MSCT and MPI provide different information on CAD, namely, atherosclerosis versus ischemia. How both techniques should be integrated in the clinical setting is not yet entirely clear, but the discrepant results provided by the 2 techniques underscore that MSCT and MPI provide complementary information.
Also, our study demonstrates that MSCT may be as accurate in patients with an intermediate likelihood of CAD as was previously reported in patients with a high likelihood of CAD.
This work was financially supported by the Netherlands Heart Foundation, the Hague, the Netherlands (grant 2002B105).
- Abbreviations and Acronyms
- coronary artery disease
- myocardial perfusion imaging
- multi-slice computed tomography
- single-photon emission computed tomography
- Received March 13, 2006.
- Revision received May 2, 2006.
- Accepted May 31, 2006.
- American College of Cardiology Foundation
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