Noninvasive coronary angiography with multislice computed tomography and myocardial perfusion imaging

Recently, multislice computed tomography (MSCT) has emerged as an alternative method for the noninvasive detection of coronary artery disease (CAD). Studies comparing this technique with conventional coronary angiography have shown that it allows detection of significant (≥ 50%) stenoses with high accuracy in patients with a high pretest likelihood of CAD. However, it is important to realize that in contrast to traditional first-line imaging techniques, such as myocardial perfusion imaging (MPI), MSCT is an anatomical imaging technique and cannot determine the hemodynamic consequences of coronary stenoses. In addition, the relative value of atherosclerosis detection with MSCT and ischemia testing with MPI has not been determined. To assess the benefits of the 2 imaging techniques, we performed a direct comparison between MSCT and MPI among subjects with predominantly an intermediate likelihood of CAD, as these patients represent the target population for noninvasive imaging.

Subjects and methods

A total of 114 subjects (64 men) with no previous history of CAD who presented to the outpatient clinic in Leiden, the Netherlands, and Aalst, Belgium, for assessment of chest pain were included in the study. All subjects underwent both MSCT and MPI (stress-rest gated single-photon emission computed tomography [SPECT]) within 1 month of each other. Based on the Diamond and Forrester method¹ the pretest likelihood of CAD was determined, resulting in low, intermediate, and high pretest likelihood in 7 (6%), 97 (85%), and 10 (9%) subjects, respectively. In a subset of 58 patients, conventional coronary angiography was also performed. Multislice computed tomography (16-slice, n = 28; 64-slice, n = 86) and conventional coronary angiography studies were evaluated for the presence of (1) no CAD, (2) nonobstructive CAD (< 50% luminal narrowing), and (3) obstructive CAD (≥ 50% luminal narrowing). We performed MPI studies with either technetium-99m tetrofosmin or technetium-99m sestamibi using symptom-limited bicycle exercise (n = 72) or pharmacologic (dipyridamole [Persantine], adenosine [Adenoscan], or dobutamine [Dobutrex]) stress (n = 42). Perfusion defects were determined from the stress images and were classified into 2 categories: ischemia (reversible defects, with a ≥ 10% increase in tracer uptake on the resting images) or scar tissue (irreversible defects). Standard statistical analyses were used.

Results

On MSCT, 41 (36%) subjects were shown to have normal coronary arteries. Nonobstructive CAD was identified in 33 (29%) subjects, and at least 1 significant (≥ 50%) luminal narrowing was seen in the remaining 40 (35%) subjects. With MPI, 77 (68%) subjects had a normal study. In the remaining 37 (32%) subjects, reversible defects (indicating ischemia) were observed in 28 subjects and fixed defects (indicating scar tissue) were seen in 12 subjects.

Among subjects with normal coronary arteries on MSCT, 37 (90%) showed normal perfusion on MPI. However, in subjects with CAD (regardless of severity) on MSCT, abnormal MPI scans were observed in 33 subjects (45%). Moreover, even in subjects with obstructive CAD on MSCT, myocardial perfusion was still normal in 20 subjects (50%), despite the presence of significant lesions (Figure 1). Conversely, most subjects with a normal MPI scan exhibited atherosclerosis (n = 40, 52%), and in 26% of these subjects, at least 1 significant stenosis was detected on MSCT (Figure 2).

Figure 1. Bar graph depicting the prevalence of normal and abnormal MPI

studies for no, nonobstructive, and obstructive CAD on MSCT. MPI indicates

myocardial perfusion imaging; CAD, coronary artery disease; MSCT,

multislice computed tomography.

Figure 2. Bar graph depicting the prevalence of no, nonobstructive, and

obstructive CAD on MSCT for normal and abnormal MPI studies. CAD

indicates coronary artery disease; MSCT, multislice computed tomography;

MPI, myocardial perfusion imaging.

Conventional coronary angiography was performed in 58 subjects, demonstrating the presence of CAD in 49 subjects (84%). Of these subjects, CAD was nonobstructive in 22, whereas at least 1 obstructive lesion was detected in 27 subjects. A normal MPI and MSCT study was obtained in 9 (100%) and 7 (78%) subjects, respectively, among the 9 subjects without CAD on conventional coronary angiography. The presence of CAD was detected by MSCT in 49 subjects (16 nonobstructive and 33 obstructive CAD) and confirmed by conventional coronary angiography in all subjects. Abnormal MPI, however, was observed in only 29 (59%) of these subjects. In all 16 subjects with nonobstructive CAD on MSCT, conventional angiography also showed nonobstructive disease; 10 (62%) of these subjects showed abnormal MPI. Finally, obstructive CAD was noted on MSCT in 33 subjects referred for conventional coronary angiography and was confirmed in 27 subjects (82%). In the latter group, MPI was normal in a considerable number of subjects (n = 11, 41%). Overall, agreement between MSCT and conventional coronary angiography was 90%.

Discussion

The results of our study showed that a distinct discrepancy exists between MSCT and MPI. An abnormal MSCT study frequently does not result in an abnormal MPI; even in subjects with obstructive CAD, ischemia was present in only half of these subjects. On the other hand, this also implies that a normal MPI study cannot guarantee the absence of considerable atherosclerosis, as CAD was ruled out in only 48% of subjects with normal MPI. In addition, a good agreement between MSCT and conventional coronary angiography was demonstrated in this particular patient population.

The discrepancy between MSCI and MPI was noted previously in a preliminary comparative study by Hacker and colleagues.² In a small, heterogeneous patient population, the authors observed hemodynamic consequences on MPI in only 23 of 43 (53%) significant stenoses shown on MSCT. Similar observations have been obtained comparing functional imaging with conventional coronary angiography. In particular, lesions with an intermediate stenosis severity (40%-70% luminal narrowing) may be problematic and may show a wide variation in hemodynamic relevance.³ Heller and colleagues evaluated the prevalence of abnormal MPI in intermediate lesions with an average of 59% ± 12% luminal narrowing on conventional coronary angiography.³ Similar to our study, ischemia was noted in only 48% of studied lesions. Thus, it is important to realize that an abnormal MSCT scan does not necessarily imply the presence of abnormal perfusion. Frequently, the detected lesions may be non-flow-limiting, and functional testing remains essential to determine the hemodynamic consequences of the MSCT abnormalities.

The observation that MSCT detects atherosclerosis before perfusion is compromised also has other implications, namely, that MSCT permits detection of CAD at an earlier stage compared with SPECT imaging. Indeed, although a normal MSCT scan was almost always associated with normal myocardial perfusion, a normal MPI scan was associated with normal MSCT in only 48% of subjects. Moreover, significant CAD was present in 26% of subjects, indicating that functional testing cannot reliably exclude the presence of CAD. Previous investigations correlating MPI to coronary calcium scores as a marker for atherosclerosis have reported similar observations. Berman and colleagues studied 1195 subjects without known CAD, revealing extensive coronary calcifications in a considerable proportion of patients with normal MPI.⁴

Thus, these observations indicate a current change in paradigm in the definition and detection of CAD. Because of the recent availability of noninvasive coronary imaging, visualization of atherosclerosis has become possible, thereby redirecting the emphasis from inducible ischemia to an earlier stage of CAD. As a result, the diagnostic algorithms in the clinical workup of patients with suspected CAD are likely to change with the incorporation of MSCT noninvasive coronary angiography. MSCT may be used as the first-line test when imaging is required. Because the observation of normal coronary arteries on MSCT excludes CAD with high certainty, patients with a normal MSCT scan may be reassured without the need for further testing or follow-up visits to the outpatient clinic. However, when MSCT demonstrates the presence of atherosclerosis, functional testing is still needed to determine subsequent management. In the event of a normal functional test, the patient has CAD but without compromised perfusion. In these patients, targeted secondary prevention by means of aggressive medical therapy and risk factor modification should be considered in combination with close monitoring. If the presence of ischemia is shown, however, referral for conventional coronary angiography and revascularization may be indicated. However, the benefits and cost effectiveness of such a strategy have not been proven.

A secondary observation was the fact also in patients with lower pretest likelihood of CAD, MSCT was accurate in detecting the presence of (significant) CAD. This is an important observation, as currently only limited data are available in this particular patient population. In contrast, the majority of data thus far have been obtained in patient populations with a high likelihood of CAD, as these studies were performed in patients already referred for conventional coronary angiography.

Conclusions

In this head-to-head comparison, a discrepancy between atherosclerosis testing with MSCT and functional testing with MPI was observed. Accordingly, these tests may be considered as providing complementary rather than redundant information. In addition, compared with conventional coronary angiography, MSCT was shown to be accurate in patients with an intermediate pretest likelihood of CAD.