VIEWPOINT AND COMMENTARY
Coronary Angiography by Computed Tomography
Coronary Imaging Evolves
Gilbert L. Raff, MD, FACC*,* and
James A. Goldstein, MD, FACC
* Ministrelli Center for Advanced Cardiovascular Imaging, Cardiology Division, William Beaumont Hospital, Royal Oak, Michigan.
Cardiology Research and Education, Cardiology Division, William Beaumont Hospital, Royal Oak, Michigan.
Manuscript received October 27, 2006;
revised manuscript received January 19, 2007,
accepted January 28, 2007.
* Reprint requests and correspondence: Dr. Gilbert L. Raff, Director, Ministrelli Center For Advanced Cardiovascular Imaging, Cardiology Division, William Beaumont Hospital, 3601 West 13 Mile Road, Royal Oak, Michigan 48073. (Email: graff{at}beaumont.edu).
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Abstract
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Rapid technological advances have facilitated high-resolution noninvasive coronary angiography using multislice computed tomography. Appropriateness guidelines recently have been published in the Journal of the American College of Cardiology and endorsed by several imaging specialty societies. Clinical studies are now available supporting the use of this method in selected diagnostic situations, particularly when the exclusion of coronary artery disease is of paramount clinical concern.
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Abbreviations and Acronyms
| | CCTA = coronary computed tomography angiography | | CT = computed tomography |
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Computed tomography (CT) has evolved over the past 25 years into a powerful cardiac imaging tool. Initially, spatial and temporal resolution limited its applicability, and CT was most helpful in assessing pericardial thickness (1). Fifteen years ago, electron-beam CT was introduced, and its major clinical use has been to quantify coronary calcium as a surrogate marker for the presence of coronary atherosclerosis (2). Beginning with the introduction of 4-slice spiral CT systems in 2000, rapid and revolutionary technological advances in the spatial and temporal resolution of multislice CT have facilitated practical coronary computed tomography angiography (CCTA) (3). The ability to image the coronary arteries without invasive catheterization has captured the imagination of physicians, patients, and the press. However, CCTA is also the subject of controversy, with detractors concerned that this technology will add nothing but cost to the diagnosis of coronary disease (4). The introduction of a novel medical technique is often heralded by overly optimistic predictions of its potential, therefore caution must be used before widely applying this imaging innovation. Clearly, the role of CCTA must be defined not by opinion, but rather by high-quality scientific studies that establish the strengths, limitations, and costs to society of this imaging tool. Fortunately, the "early returns" for CCTA are encouraging. This article reviews the present scientific data regarding the applications of CCTA for a variety of clinical scenarios, including: 1) accurate delineation of the presence, extent, and severity of atherosclerosis; 2) use in evaluation of acute chest pain syndromes; 3) adjudication of inconclusive stress test results; 4) preoperative delineation of coronary anatomy in patients undergoing cardiac surgery and general surgical clearance.
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The Unique Data Provided by CCTA
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As with "lumenograms" produced by invasive angiography, CCTA provides anatomical data regarding the coronary lumen and the presence of stenoses. However, as with invasive coronary angiography, such anatomical data alone do not necessarily provide insight regarding the physiological impact of a given lesion on coronary blood flow; therefore, the significance of intermediate severity lesions (25% to 75%) requires physiological testing. However, CCTA does provide data not available from invasive angiography alone. Analogous to intravascular ultrasound, CCTA provides striking images of the vessel wall and insights regarding the presence, extent, and character of intramural plaque, which is consistently underappreciated by images of its impact on the lumen only. The 3-dimensional data provided by CCTA also facilitate delineation of the course of anomalous coronary vessels and other congenital anomalies. A CCTA also can evaluate other cardiac anatomy, including atria, ventricles, valves, pericardium, great vessels, feeding tributary veins, the coronary venous system, and other structures within the thoracic cavity, notably the pulmonary vasculature and parenchyma (1,5,6).
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Accuracy of CCTA Versus Invasive Angiography
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There are now abundant data establishing the accuracy of CCTA for detecting the presence and severity of coronary atherosclerosis. Numerous studies including in aggregate more than 2,000 patients have directly compared CCTA with invasive angiography (7–35). These studies must be considered according to whether they used older 16-slice versus newer 64-slice scanners. Analysis of studies with 16-slice scanners (11 reports in 885 subjects) shows that using a per-patient analysis, considering a binary cutoff of any lesion 
50% as positive, the average sensitivity and specificity weighted by the number of subjects in each study are 96% and 76%, respectively (7–17). A comparable analysis for 64-slice scanners (7 studies in 444 patients) confirms greater accuracy, with reported sensitivity and specificity of 98% and 93%, respectively (18–24). Combining all 18 studies (1,329 patients) with available per-patient analyses, the subject-weighted mean sensitivity and specificity are 97% and 84%. There are important limitations pertinent to the methods of these studies, including inclusion only of patients previously scheduled for invasive angiography, thereby creating a potential selection bias toward patients likely to harbor disease, as reflected in the high incidence of true disease (mean 53%) in study subjects. According to the Bayes theorem, this bias might tend to increase the measured sensitivity and decrease the measured negative predictive value of CCTA. However, it is impressive that even with this bias, the average subject-weighted negative predictive value in these 18 studies is 97%. These data lead to the hypothesis that a normal CCTA may obviate the need for invasive angiography in properly selected clinical circumstances. The comparative capability of CCTA for quantitative analysis of coronary lesion severity has also been studied (19,20,31). Generally good correlation values with invasive angiography were found (average Pearson correlation, r = 0.72), but with considerable standard deviation, which presently limits its quantitative accuracy.
In summary, CCTA has a notably high sensitivity and negative predictive value for the detection of coronary disease. It may be uniquely suited to clinical situations in which the exclusion of coronary disease is of paramount concern.
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Clinical Applications of CCTA
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Evaluation of acute chest pain.
More than 6 million patients annually present to emergency departments with complaints of chest pain suspicious for acute coronary ischemia (36). Studies have reported that 2% to 8% of patients with acute coronary syndromes are misdiagnosed and inappropriately discharged (36–38). However, only a minority of patients whose initial electrocardiograms and cardiac studies are normal actually suffer from an acute coronary syndrome. In spite of this, because the consequences of diagnostic failure are so serious in both medical and malpractice terms, it is common practice to evaluate nearly all such patients using time-consuming and resource-intensive "rule-out myocardial infarction" protocols using serial electrocardiograms, cardiac enzymes, and stress-imaging modalities (39,40). This approach, which is often not definitive, incurs an estimated cost of $10 to $12 billion annually in this country alone (36,40). A CCTA, by virtue of its ability to rapidly exclude clinically significant coronary artery disease, has the potential to more efficiently diagnose and triage such patients.
We recently reported the results of a randomized trial of low-risk acute chest pain patients evaluated by either early CCTA or a standard diagnostic protocol (41). Patients randomized to immediate CCTA were eligible for discharge with normal or minimally abnormal results (<25%), patients with severe stenosis (>70%) were referred for immediate invasive angiography, whereas patients with intermediate-grade stenosis underwent additional stress testing. The 2 groups were compared for safety, diagnostic accuracy, and efficiency. Among patients randomized to CCTA, 75% had decisive triage by CCTA alone (67% immediately discharged and 8% referred for immediate catheterization, which revealed significant disease in 7 of 8 cases). Importantly, of those discharged immediately, no patient had a major adverse cardiac event or a subsequent diagnosis of coronary artery disease over the next 6 months. Overall, the diagnostic accuracy of CCTA was 94%, and the negative predictive value was 100%. Diagnostic efficiency, defined as time from randomization to definitive diagnosis, showed that the CCTA approach was more rapid (3.4 vs. 15.0 h) and reduced costs. These randomized data are consistent with prior observational studies (5,6,42,43), and these encouraging results have now spurred multicenter trials investigating this approach.
Evaluation of patients with inconclusive stress test results.
Although stress testing is a useful and widely applicable technique, it has substantial limitations in establishing a definitive diagnosis of coronary disease because of a significant incidence of false-positive and false-negative results. Ultimately, some patients require invasive angiography to definitively establish the presence or absence of coronary atherosclerosis. A noninvasive alternative to adjudicate these diagnostic dilemmas is now offered by CCTA. In a retrospective study of 1,053 patients who underwent CCTA for diagnosis after equivocal stress test results, Lesser et al. (44) reported encouraging results, with only 17% of cases requiring invasive angiography over 6 months. Prospective trials are now underway.
A recent study comparing CCTA and nuclear myocardial perfusion imaging as initial diagnostic approaches in patients with undiagnosed chest pain showed that CCTA had better accuracy in predicting invasive angiographic results (45). Among 16 patients with nonobstructive CCTAs going to catheterization, nuclear stress imaging was abnormal in 10 cases, yet none of these patients had obstructive disease on invasive study. The investigators made the point that for some subsets of patients, CCTA may be a better initial choice because it has fewer false-positive results and can therefore triage low-risk patients more reliably.
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Preoperative Evaluation of Patients Before Cardiac and General Surgery
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Recently, 4 studies encompassing 205 patients have compared CCTA with invasive coronary angiography before cardiac valve surgery (16,17,23,35). The studies reported sensitivities ranging from 81% to 100%, specificities from 80% to 92%, and negative predictive values from 98% to 100%. In one study, 64% of patients could have avoided invasive angiography because CCTA showed no significant coronary stenoses (16). It is logical to expect that this approach can be extended to preoperative evaluation of other high-risk groups, such as patients scheduled to undergo aortic aneurysmectomy, major abdominal surgery, or carotid endarterectomy. Together with research reports in the areas of acute chest pain and inconclusive stress tests, these results point toward the encouraging conclusion that in appropriately selected clinical situations, CCTA can reduce the need for invasive angiography.
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Limitations of CCTA
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It is important to emphasize the present limitations of CCTA. A CCTA may not provide technically adequate images of all segments in all arteries in every patient. This may be related to obesity, fast or irregular heart rates, or respiratory motion. As emphasized, a major limitation is that CCTA presently provides data regarding anatomical lesions only, not their physiological impact on coronary blood flow. Future advances may facilitate combined anatomic and perfusion imaging by CCTA (46). Extensive coronary calcium obscures the lumen and may substantially limit analysis of segments or even entire arteries by CCTA. Thus, this technique may be of limited application in patients with a high likelihood of significant coronary calcification, such as the elderly or in patients with prior calcium scores >1,000 Agatston units (16,17). Similarly, CCTA also has technical limitations for assessment of in-stent stenoses (3). Although CCTA reliably can determine the patency of stents, detecting in-stent stenosis is challenging. However, several recent studies using the latest-generation scanners and specialized image reconstructions report encouraging results in analysis of stents >2.5 mm (45,47–49). In spite of this, technical limitations singly or in combination may prevent the confident exclusion of hemodynamically important segmental stenoses.
Based on the clinical evidence at hand, what conclusions may be drawn regarding established versus evolving applications for CCTA?.
Taken together, the data reviewed provide a reasonable basis on which to conclude that CCTA already has a valid role in appropriately chosen clinical circumstances and should not be regarded as a purely investigational tool. When the results show normal coronary vessels, CCTA is particularly powerful clinically. The ability to definitively and noninvasively determine the presence or absence of coronary atherosclerosis is extremely helpful in an expanding array of clinical scenarios. This view is reflected in guidelines now jointly endorsed by numerous professional societies, including the American College of Cardiology Foundation, American College of Radiology, Society of Cardiovascular Computed Tomography, American Society of Nuclear Cardiology, North American Society for Cardiac Imaging, Society for Cardiovascular Magnetic Resonance, Society for Cardiovascular Angiography and Interventions, and Society of Interventional Radiology (50). Nevertheless, overenthusiasm for new technologies may lead to their overuse, and financial incentives may lead to their abuse. Therefore, it is essential that evidence-based clinical science be applied to firmly establish the optimal applications for CCTA. In this regard, it is noteworthy that efforts are being made by physicians and insurance carriers to introduce CCTA into clinical practice in a rational and responsible manner. The Advanced Cardiovascular Imaging Consortium is a collaborative quality initiative between participating hospital centers and Blue Cross Blue Shield/Blue Care Network of Michigan (51). Information regarding indications for CCTA, patient characteristics, technique, interpretation, and subsequent clinical events is collected by each center and collated by the coordinating center. Participating sites receive a quarterly report allowing them to compare their performance with that of the group as a whole with regard to important metrics, such as the average number of subsequent diagnostic and interventional procedures performed on patients with normal CCTA findings. If our thesis is correct, the proportion of such events should be low.
In summary, at this point we should not judge CCTA as either an overrated investigational procedure or the universal answer for the diagnosis of coronary disease. It is a powerful tool; let us use it wisely.
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Footnotes
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Supported by Siemens Medical Solutions, Berlex Pharmaceuticals, and Blue Cross Blue Shield of Michigan.
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Abstract
The Unique Data Provided...
