Article

Computed Tomographic Angiography and Nuclear Myocardial Perfusion Imaging—A Comparison in Detecting Significant Coronary Artery Disease

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The cost and the risk of invasive angiography have encouraged the development of new diagnostic methods that allow the coronary arteries to be visualized non-invasively. The last decade has seen great strides in the field of cardiac imaging, particularly in the ability of cardiac computed tomographic angiography (CTA) to visualize the coronary lumen with excellent diagnostic accuracy (see Table 1).1-2 Three papers with 64-row multi-detector CT (MDCT) demonstrate a sensitivity of 94% and specificity of 93%.1-2,29 This suggests that CTA can serve as an effective gate-keeper to aid a strategy of selective cardiac catheterization (see Figure 1). Being such a modality, CTA is now being increasingly used in clinical practice. As a result of having high spatial and improved temporal resolution, this imaging modality not only allows branches of the coronary artery to be evaluated but also allows simultaneous analysis of other cardiac structures, making it extremely useful for other cardiac applications.3-4 Moreover, coronary artery calcium (CAC) detected by computed tomography has been shown to be highly specific for atherosclerosis and has prognostic value, yielding valuable information for risk stratification, being both incremental and independent to traditional risk factors.5-9 The combination of CAC and CTA allows for accurate risk stratification to choose lipid-lowering targets.10 Other uses of CTA include calculation of ejection fraction, as well as assessment of global and regional wall motion evaluation.11

Myocardial perfusion imaging (MPI) is an established method for non-invasively assessing the functional significance of coronary stenoses and delivers valuable information for risk stratification. Patients with stable angina and normal MPI results have a low risk of death or fatal myocardial infarction (MI) and therefore no intervention is required for these patients.12-16 Even in patients with documented CAD, normal MPI results have been shown to have similar low event rates.17-18 MPI identifies myocardial perfusion defects, analyzing the functional relevance of coronary artery stenoses, and provides important information for clinical decision making.12 However, MPI performs less well in the setting of cardiomyopathy or left bundle branch block, and does not allow for the assessment of subclinical atherosclerosis, so treating physicians do not develop an accurate target of lipid-lowering therapy after a negative test. A negative test implies to many physicians and patients the presence of normal coronary arteries, but extensive subclinical atherosclerosis may also be present.

Comparison of CT and MPI

Several studies have compared CAC assessment with MPI for the diagnosis of CAD.19-22 The high sensitivity of CAC23 is offset against the lower specificity for obstructive disease, yielding similar diagnostic accuracy to MPI in all studies to date. CAC and CTA detection of CAD are not affected by left bundle branch block, abnormal perfusion patterns from a dilated ventricle, or breast/diaphragmatic artifacts.

In direct comparison studies, electron beam CT (EBCT) coronary calcium has been shown to be comparable to nuclear exercise testing in the detection of obstructive CAD.24-25 The accuracy of EBCT is not limited by concurrent medication, the patient's ability to exercise, baseline electrocardiogram (ECG) abnormalities or existing wall motion abnormalities. Negative studies would be less likely to undergo invasive angiography. More comparison work between modalities is clearly needed.

Data also support a complementary role for coronary calcium and myocardial perfusion study (MPS) measurements. A recent study of 1,195 patients who underwent CACP measure and MPS assessment demonstrated that CACP was the most powerful predictor of an ischemic nuclear test, and that <2% of all patients with CACP <100 had positive MPS studies.26

Recent ACC/ASNC appropriateness criteria support that a low score precludes the need for MPS assessment, and a high score would warrant further assessment.8 These appropriateness criteria suggest nuclear testing may generally be inappropriate in patients with calcium scores <100, as the probability of obstruction or abnormal scan is very low. For the remaining asymptomatics, a person with an Agatston score >400 may benefit from functional testing to detect occult ischemia. The use of functional testing is paramount to determining the need for revascularization, as functionally insignificant lesions do not benefit from revascularization.

Hacker et al12 compared CTA and MPI in the detection of hemodynamically relevant lesions of the coronary arteries. Twenty-five patients with suspected or known CAD were studied. ECG-gated MPI and 16-MDCT angiography were performed. Sensitivity, specificity, and negative (NPV) and positive predictive values (PPV) were 100%, 87%, 100%, and 29%, respectively, for the ability of CTA to detect reversible perfusion defects in the corresponding myocardial areas. The data is still very limited regarding the comparison of CTA with MPI.

In one small study, the authors compared the accuracy of CTA and CAC with MPI using conventional catheter angiography as the gold standard for assessing significant stenoses of the coronary arteries.27 In this study, CTA showed a sensitivity of 94%, specificity of 96%, PPV of 92% and NPV of 97%.CTA demonstrated significant higher sensitivity than MPI (95% versus 81%, p<0.05). CTA demonstrated significantly higher specificity than both MPI (89% versus 78%, p=0.04) and CAC (56%, p=0.002). CTA also performed better in a per vessel analysis (sensitivity 94%, specificity 96%) than both nuclear testing and CAC.The anatomic gold standard favors an anatomic test such as CTA. This study compared a well established tool for the detection of myocardial ischemia such as MPI with a technique that provides anatomical information of the epicardial coronary arteries (CTA). No matter how accurate CTA is compared with angiography, the two pieces of information obtained with these fundamentally different techniques are hard to compare. Both catheter angiography and CT angiography evaluate only anatomical abnormalities, while MPI looks at perfusion to the myocardium, which could be either a macrovascular or microvascular etiology. However, since revascularization is based upon angiography demonstrating an obstructive lesion, this limitation is widely accepted and a nuclear test demonstrating a perfusion defect in the absence of significant obstruction is considered a false positive test.

Prognosis

It has been suggested that MPI, due to prognostic information available, should remain the non-invasive gold standard for detection of CAD. Coronary artery calcium (CAC) detected by computed tomography (CT) has been shown to be highly specific for atherosclerosis and has prognostic value, yielding valuable information for risk stratification.5 There is evidence to show that elevated coronary calcium scores (CCS) are predictive of future cardiovascular events, both independently of and incrementally to conventional cardiovascular risk factors.5-10 Thus, a high calcium burden (score >100) would be indicative of a high risk of future cardiovascular event (>20% 10-year risk), and warrant more aggressive lipid-lowering therapy. This algorithm has been supported by the American Heart Association (AHA),10 National Cholesterol Education Panel (NCEP) and Screening for Heart Attack Prevention and Education (SHAPE) Task Force Guidelines.28 Extensive prognostic data exists for both coronary calcium scanning and MPI, so either test will yield important prognostic, in addition to diagnostic, information.

CTA has been shown to be accurate for determining the presence and severity of coronary artery disease (CAD), with an excellent short-term prognosis after negative test.29 One prognostic study of CTA, with a six-month follow-up in a group of 834 patients originally not referred for cardiac catheterization based on CTA results, demonstrated no cardiovascular deaths during six-month follow-up.30 However, there is vast prognostic information also available with CAC. The combination of CAC and CTA therefore affords similar depth of prognostic studies to MPI.5-7,9

CTA as a First-line Test

Multi-slice computed tomography (MSCT) coronary angiography allows non-invasive direct assessment of the presence of coronary artery stenoses. With an NPV exceeding 97%,1-3,29,31 it has a role in triage of patients with suspected CAD. Due to its high NPV, the consensus among most imaging experts is that MDCT may be used as a reliable filter before invasive coronary angiography in the assessment of symptomatic patients with intermediate risk of CAD and in patients with uninterpretable or equivocal stress tests.32 Thus, MSCT might be applied as a primary gatekeeper when pre-test probability is low, and a secondary gatekeeper in patients with mildly positive single-photon emission CT (SPECT) (or equivocal finding) prior to deciding whether to perform conventional coronary angiography in these patients.

MSCT already at present has the potential to reduce conventional coronary angiographies in patients with positive SPECT while maintaining a sufficiently high per-patient sensitivity. This way both procedural complications and healthcare costs of conventional coronary angiographies might be reduced in clinical routine with the use of MSCT as a secondary gatekeeper prior to conventional coronary angiography. A recent expert panel report suggested that MSCT coronary angiography might gain a role in patients with unequivocal stress test response but found no sufficient grounds to support the indication in patients with evidence of moderate to severe ischemia.32

A recent scientific statement from the AHA on cardiac CT concluded that "CT coronary angiography is reasonable for the assessment of obstructive disease in symptomatic patients, (Class IIa, Level of Evidence B)".10

Persons with high pre-test probability of CAD may be older and have more diabetes, renal failure or other conditions that predispose to increased levels of CAC. Severe calcifications (scores >1,000), higher heart rates, arrhythmias, and intracoronary stents can limit the analysis of the CTA study with MDCT.33 Higher levels of CAC clearly diminish the diagnostic accuracy of CTA, so limiting CTA to a lower pre-test probability population (as the first-line test) may prove most cost-effective and accurate. Future prospective trials should address the effect of this management approach on healthcare costs.

MPI as a First-line Test

There is ample evidence that functional testing has a well-defined role as a first test in the work-up of CAD. MPI using SPECT is the most commonly applied diagnostic imaging modality in patients with suspected CAD in the US with more than nine million procedures performed annually.34 With its fairly high sensitivity, SPECT reliably excludes significant disease and can serve as a gatekeeper for conventional coronary angiography35 to minimize the rate of normal invasive examinations.36 There are multiple noted appropriate clinical uses, with vast clinical data supporting its use. However, the PPV of SPECT is limited and in a considerable number of patients with suspected perfusion deficits, conventional coronary angiography shows no significant coronary stenoses. Furthermore, it is the most expensive of the commonly applied clinical tests for CAD (compared with exercise testing, functional testing with echocardiography, or CTA), and imparts the highest effective radiation doses to the patient.

Large studies demonstrate consistently lower diagnostic accuracies of MPI than has been reported with CTA, most likely due to the lower spatial resolution of MPI as well as the inherent differences between functional and anatomic data (using invasive angiography as a clinical gold standard).A meta-analysis37 was performed for determining the sensitivity and the specificity of exercise SPECT MPI and exercise echocardiography for the diagnosis of CAD, the reference standard being invasive coronary angiography. The two tests had similar sensitivities (85% and 87%), but the specificity was significantly lower (more false positives) with exercise MPI (77% versus 64%).

Radiation

MDCT scanners impart an effective radiation dose to the patient when used for coronary angiography of approximately 10-16 milliseiverts (mSV).38-40 The radiation exposure can be reduced by using dose modulation, limiting the number of images scanned and slowing the heart rate to reduce scanning the same area more than needed. With diligent and efficient use of 64-MDCT one might be able to reduce the effective radiation dose to 6-8mSv, a similar dose obtained with MPI using technetium, and lower than similar studies using either dual isotopes or thallium.41 It should be noted that nuclear imaging has similar radiation exposure doses for cardiac studies (8-12mSv).42 Specifically, technetium studies are on the lower end of this spectrum (6-8mSev on average) and thallium studies have been reported as high as 27mSv.43

For MDCT coronary angiography, dose modulation techniques reduce radiation exposures, and this technique should be employed whenever possible.44 The effects of dose reduction are more pronounced for lower heart rates. Also, using the lowest necessary mA during each study will help limit radiation exposures during these procedures. For MDCT, increased numbers of detectors will allow for better collimation and spatial reconstructions. Having more of the heart visualized simultaneously will also allow reductions in the contrast requirements and breath holding, further improving the methodology.

Low Dose CTA with SnapShot Cine Technology (GE Healthcare, Milwaukee, WI) allows dose reductions using prospective triggering, by obtaining a small phase range of data, then turning off the x-ray tube until the next acquisition (see Figure 2). This is significantly different to dose modulation, whereby radiation dose can be reduced but the X-ray tube remains on during the entire study.With SnapShot Cine Technology, CT angiograms have been obtained with as few as 0.95mSv, allowing a 70–80% dose reduction. Since only one phase is being obtained with this new methodology, no ejection fraction data is available but the radiation dose saving is significant. This may be especially useful in younger patients and children, where radiation exposures carry the most significance.

Multi-modality Testing with Both CTA and MPI

Currently available and an area of on-going clinical research is the application of hybrid positron emission tomography (PET)-CT and SPECT-CT scanners. This will allow the acquisition of metabolic and/or perfusion information as well as anatomic data including both coronary calcification and angiographic data. Some have advocated this dual modality testing, whereby both functional and anatomic testing would take place in given patients. The natural appeal is to determine both the presence of obstructive lesions and simultaneously whether these lesions are functionally significant, potentially benefiting from revascularization. The problems that exist include increasing radiation doses to the patient, as well as costs, without proven outcome benefit or accuracy of this multi-modality testing. Until further validation work with dual-testing is performed, this should be relegated to selective cases where the clinical management is unclear after either initial test. The AHA, in the most recent statement on Cardiac CT, has stated: "The incremental benefit of hybrid imaging strategies will need to be demonstrated prior to clinical implementation, as radiation exposure may be significant with dual nuclear/CT imaging. At this time there is no data supporting the use of hybrid scanning to assess cardiovascular risk or presence of obstructive disease (Class III, Level of Evidence C)."10

Conclusions

The ability to see both non-obstructive disease (targets of anti-atherosclerotic therapy) and stenotic disease (for revascularization) has certain advantages over functional testing (only allows for visualization of significant stenosis).However, the functional information garnered from an exercise test such as MPI is invaluable in determining the need for revascularization, so CTA and MPI are more complementary than competitive. In the appropriate clinical setting,CTA will be valuable to the clinical practice of medicine, making certain diagnostic dilemmas less problematic.

CTA is a robust imaging modality with a wide range of clinical applications, allowing simultaneous assessment of wall motion, calcified plaque and obstructive disease.11

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