Journal of Thoracic Imaging:
Coming of Age: Coronary Computed Tomography Angiography
Bastarrika, Gorka MD, PhD* †; Schoepf, U. Joseph MD, FAHA* ‡
*Department of Radiology and Radiological Science
‡Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston, SC
†Department of Radiology, Clínica Universidad de Navarra, Pamplona, Spain
Reprints: Gorka Bastarrika, MD, PhD, Department of Radiology, Clínica Universidad de Navarra, Avenida Pío XII, 36, 31008 Pamplona, Spain (e-mail: firstname.lastname@example.org).
Disclosures: Gorka Bastarrika receives support from General Electric, Medrad, and Siemens. U. Joseph Schoepf is a medical consultant for Bayer-Schering, Bracco, General Electric, Medrad, Siemens, and TeraRecon and receives research support from Bayer-Schering, Bracco, General Electric, Medrad, and Siemens.
Technical development has substantially improved diagnostic performance of coronary computed tomography angiography (CCTA). A large number of studies have addressed proof of concept, feasibility, and clinical robustness of this noninvasive diagnostic technique, and most have consistently described the ability of CCTA to reliably rule out significant coronary artery stenosis. Clinical evidence supports the significant role of CCTA in an increasing number of scenarios, including the detection of coronary disease in symptomatic patients who are at intermediate risk and evaluation of coronary revascularization procedures. After initial feasibility testing, the scientific evaluation of CCTA now points toward analyzing prognosis, outcome, and cost-effectiveness of this noninvasive diagnostic tool. In this article, appropriate clinical indications, diagnostic performance, current clinical applications, prognostic value, and cost-effectiveness of CCTA are reviewed.
Coronary heart disease is the leading cause of death in developed countries. It was the cause of 1 of every 5 deaths in the United States in 2005. In that year, 445,687 persons died of coronary heart disease (232,115 males and 213,572 females). In 2009, it was estimated that 785,000 Americans will have a new coronary attack and approximately 470,000 will have a recurrent attack.1 As a consequence, much effort has been devoted to investigating new techniques that may positively influence risk stratification, diagnosis and prognosis of coronary artery atherosclerosis, and coronary heart disease.
Being the standard or reference to assess coronary artery disease (CAD), diagnostic cardiac catheterization still has a nonnegligible rate of 1.3% of major complications and a 0.05% in-lab mortality rate.1 Recent progress in the technical advancement of multidetector computed tomography (MDCT) scanners has enabled rapid and noninvasive evaluation of the coronary vessels with high spatial resolution. Moreover, after the integration of the 64-row MDCT and later-generation systems, coronary CT angiography (CCTA) holds the promise to accurately detect and grade CAD, increasing the existing evidence that this technique may even replace diagnostic cardiac catheterization in diverse clinical settings. In this review, appropriate clinical indications of CCTA, diagnostic performance, current clinical applications, prognostic value, and cost-effectiveness of CCTA are identified.
APPROPRIATE CLINICAL INDICATIONS FOR CCTA
Given the limited evidence base to date, no solid guidelines exist for the use of CCTA in clinical routine. Actual indications reflect the consensus opinion of pertinent professionals in the field on the basis of a comprehensive review of numerous clinical studies. The first major attempt to define the appropriateness criteria for cardiac CT was published under the auspices of the American College of Cardiology Foundation together with key specialty and subspecialty societies,2 aiming at covering a variety of common and potential clinical scenarios. In this statement, CCTA was considered appropriate for the evaluation of (1) suspected coronary anomalies; (2) acute chest pain in individuals with intermediate pretest probability of CAD without ST-segment changes and negative myocardial biomarkers; (3) symptomatic chest pain in patients with equivocal or uninterpretable stress test; and (4) persons with intermediate pretest probability of CAD who are unable to exercise or have an uninterpretable electrocardiogram (ECG). A panel of experts on behalf of the European Society of Cardiology and the European Council of Nuclear Cardiology provided similar recommendations.3 More recently, and in line with those reports, the American Heart Association Committee on Cardiovascular Imaging and Intervention of the Council on Cardiovascular Radiology and Intervention and the Councils on Clinical Cardiology and Cardiovascular Disease in the Young published a clinical consensus statement on the use of magnetic resonance angiography and MDCT angiography for noninvasive coronary artery imaging.4 General statements about the use of CCTA are shown in Table 1. According to the consensus statement, the presence of coronary artery anomalies signifies a substantive indication for CCTA. This technique may also be indicated as a second-line test in symptomatic patients who are at intermediate risk for CAD after initial risk stratification, including patients with equivocal stress-test results. The document encourages continued research in CCTA to determine the potential of this modality to detect, characterize, and measure the atherosclerotic plaque burden, as well as its change over time or as the result of therapy, but specifically states that “neither CCTA nor magnetic resonance angiography should be used to screen for CAD in patients who have no signs or symptoms suggestive of CAD.”4
In the near future, the usefulness of CCTA for ruling out significant CAD may be translated into potential new clinical scenarios, including evaluation of individuals with unexplained left ventricular dysfunction,5 before cardiac valve surgery,6 or to detect cardiac allograft vasculopathy after cardiac transplantation.7 In the context of surgical intervention, CCTA may also be used for the assessment of complex congenital heart disease, including anomalies of the coronary circulation, great vessels, cardiac chambers, and valves; and for noninvasive coronary arterial mapping, including internal mammary artery assessment before repeat surgical revascularization.2 However, specific recommendations for the use of this technique are expected to change along with the development in scanner technology and the performance of further research in the cardiac field.
CURRENT ROLE OF CCTA IN CLINICAL PRACTICE
Detection of Coronary Artery Anomalies
The usefulness of CCTA in detecting anomalous coronary arteries has been reported consistently in the literature.8 With respect to conventional coronary angiography, CCTA has the potential advantage of showing an anomalous origin of the coronary arteries in cases in which the former can mistakenly diagnose vessel occlusion (Fig. 1) or even show an interarterial anomalous coronary course, which may induce a decrease in myocardial perfusion. CCTA could also be used to assess the precise course of a coronary artery so as to avoid vessel injury during surgical reimplantation.
Detection of Coronary Artery Stenosis
As a main goal, noninvasive CCTA is meant to replace conventional diagnostic coronary angiography for the detection of CAD. Initial studies of CCTA reported large proportions of nondiagnostic studies, mostly due to the fact that low spatial and temporal resolution MDCT systems were available at that time. This limitation was partially solved with the introduction of the 64-row MDCT generation in 2004. According to the latest studies, the overall performance of the 64-row CCTA for detecting coronary artery stenosis with respect to conventional coronary angiography on a patient-based analysis results in sensitivity, specificity, positive predictive values, and negative predictive values ranging from 85% to 100%, 64% to 100%, 64% to 100%, and 83% to 100%, respectively.9–16Table 2 shows per patient-based overall diagnostic performance of the 64-row CCTA with respect to conventional coronary angiography to detect coronary artery stenosis. Of note, the 2 available prospective multicenter trials reveal that CCTA is very sensitive for detecting overall significant CAD defined as coronary artery stenosis of ≥50%.11,12 In line with this, a recent systematic review assessed the accuracy of 64-row CCTA for the diagnosis of CAD in a total of 2045 patients. In this meta-analysis, for a significant coronary artery stenosis of ≥50%, CCTA had sensitivities of ≥90%, specificities of 88% to ≥90%, and positive and negative predictive values ranging from 69% to 93% and from 96% to 100%, respectively.17 Thus, 64-row CCTA is highly sensitive for patient-based detection of CAD and has a high negative predictive value.18 Improved temporal resolution of dual-source CT (DSCT) systems has significantly increased the number of evaluable coronary artery segments19–25 even in individuals with high resting heart rates, relegating to the past the need for prescan β-blocker medication (Table 3).26 Interestingly, in a recent study comparing the diagnostic accuracy of 64-row MDCT and DSCT coronary angiography performed on individuals with low heart rates, Baumuller et al27 observed that the higher temporal resolution of DSCT coronary angiography results in improved accuracy and specificity for the diagnosis of significant coronary artery stenosis on a per-segment level at a similar radiation dose but provides comparable diagnostic accuracy on a patient-based level, compared with 64-row MDCT coronary angiography. Hence, as extracted from the results, even after using high temporal resolution DSCT scanners, the number of false-positive results remains high, with a trend toward overestimating coronary artery stenosis, particularly in extensively calcified coronary segments.28 However, almost all studies match the high negative predictive value of CCTA, emphasizing the role of this noninvasive tool in reliably ruling out significant coronary artery stenosis. Therefore, CCTA should be used with the sole purpose of triaging symptomatic low-risk and intermediate-risk patients with suspected CAD before invasive diagnostic cardiac catheterization to avoid unnecessary invasive workups in patients with nondiseased coronary vessels.
The most recent technical innovation has led to the introduction of 256-row and 320-row single-source systems29 and of 128-row DSCT scanners.30,31 Preliminary results indicate that the use of volumetric scanners and high-pitch spiral acquisition (Fig. 2) possesses the potential to significantly reduce the amount of contrast agent and the radiation dose required compared with conventional CCTA, while maintaining high diagnostic accuracy. In contrast, renewed interest in prospectively ECG-triggered data acquisition has introduced the concept of low-dose CCTA. This technique comprises sequential image acquisition with the application of radiation only during a predetermined interval of the cardiac cycle (ordinarily diastole), thus significantly reducing the amount of radiation administered to patients (ie, 1 to 4 mSv) (Fig. 3). Recent reports emphasize that this technique CCTA to be performed at a significantly less radiation dose, without impairment in diagnostic accuracy.32,33
The noninvasiveness and increased availability of this technique have led to the exploration of using CCTA in other potential clinical scenarios, such as triage of patients presenting to the emergency department with acute chest pain,34 before valvular surgery (Fig. 4),6 or before noncardiac surgery.35
Imaging of Coronary Revascularization Procedures
Assessement of Bypass Patency
Even if early studies already showed the ability of single-slice CT systems to assess patency or occlusion of bypass grafts,36 the use of MDCT systems significantly improved the accuracy of this noninvasive technique to determine the state of surgical revascularization procedures, with reported sensitivity and specificity values of 97% and 98%, respectively, for the assessment of bypass occlusion using the 4-row MDCT systems37 and next to perfect values for the 16-row MDCT scanners.38 Those values slightly decreased when bypass graft stenosis was determined with the early generation MDCT scanners. The performance of initial MDCT systems was significantly higher for the assessment of bypass status than for determining the patency of the native coronary arteries. The main reason for this discrepancy relies on the fact that bypass grafts are larger in diameter and move much less and slower than native coronary vessels, thus facilitating their visualization. Given the high performance of early MDCT scanners, the introduction of late-generation 64-row CCTA did not result in a significant impact in evaluating surgical revascularization procedures (Table 4).39–46 In a recent systematic review comparing the performance of 8-row, 16-row, and 64-row MDCT for the evaluation of coronary bypass grafts with respect to conventional coronary angiography, the investigating authors found a pooled sensitivity of 97.6% and specificity of 98.5% for assessing occlusion, and sensitivity and specificity values of 88.7% and 97.4% for depicting stenosis, respectively (Fig. 5).47
Potential drawbacks of CCTA to comprehensively assess individuals with previous bypass surgery rely on the type of graft, as imaging of arterial grafts is more challenging than visualizing venous grafts because of their smaller caliber and artifacts caused by metallic clips, and the small size and extensive calcification of the native coronary arteries located distal to the anastomosis. Faster scanners with more spatial resolution may partially solve this limitation.48
Planning of Cardiac Surgery
There is increasing benefit in surgical planning of coronary revascularization procedures when 3-dimensional cross-sectional techniques are used before surgery. In contrast to conventional invasive coronary angiography, CCTA has the ability to accurately assess the location and status of possibly occluded grafts, and it is outstanding in showing the diameter and course of the native coronary vessels. Indeed, the volumetric nature of acquired data can easily show general cardiothoracic morphology and the relationship of vessels of interest with adjacent anatomical structures; in cases of reintervention, CT can accurately determine the site, location, course, and anatomical landmarks of earlier grafts and ascertain the patency of vessels of potential interest for the reintervention.49 Moreover, CCTA perfectly delineates the presence, location, and extent of coronary artery calcification, which adds significant clinical value with respect to cardiac catheterization in selecting the most suitable site for bypass anastomosis.
Assessment of Stent Patency
The increasing use of coronary stent implantation to treat CAD requiring revascularization, especially with the newly introduced drug-eluting stents, has invigorated the need for defining the precise role of CCTA for determining stent patency and in-stent restenosis. Since stent patency or occlusion may be indirectly inferred by showing the presence or absence of intravenous contrast material in the distal segments of the stented vessel,50 assessment of in-stent restenosis by means of CCTA remains a challenge even with the newest CT scanners.51,52 The main limiting factors for in-stent assessability are stent composition and diameter. Beam hardening and streak artifacts caused by metallic stent struts significantly impair the visualization of the vessel lumen,53 whereas the assessment of stents of small diameter (ie, 3 mm or smaller) has substantial limitations.54 Performance of 64-slice MDCT55–65 and DSCT54,66,67 CCTA for the detection of in-stent stenosis in assessable stents with respect to conventional coronary angiography is shown in Table 5. Therefore, for clinical diagnostic purposes, it seems reasonable to confine the use of CCTA to assess the patency of large diameter stents (Fig. 6).
PROGNOSTIC VALUE OF CCTA
In a healthcare environment relying on evidence-based medicine and cost-effectiveness, patient outcome and prognosis should be the final and main step in the evaluation process of any newly installed diagnostic technique. In this sense, an increasing number of ongoing studies are being developed to determine the prognostic value of CCTA in symptomatic patients with chest pain and suspected or known CAD. After a mean follow-up of 78 months of a cohort of 2538 consecutive patients who underwent CCTA by electron beam CT, Ostrom et al68 observed that the burden of angiographic disease detected by CCTA provided both independent and incremental value in predicting all-cause mortality in symptomatic patients independent of age, sex, conventional risk factors, and coronary artery calcification. Min et al69 analyzed the association between extent and severity of CAD defined by CCTA and all-cause death in a consecutive cohort of 1127 symptomatic patients 45 years of age or older with similar results. These investigators concluded that CCTA could identify increased risk for all-cause death, whereas a negative CCTA study showed an extremely low risk for death. Hence, in symptomatic individuals with an intermediate likelihood of CAD referred for CCTA, normal coronary arteries or nonobstructive CAD carries an excellent prognosis, whereas the finding of obstructive CAD identifies patients at a higher risk of subsequent myocardial infarction.70–72 In line with this, diverse follow-up studies also reveal that CCTA safely rules out CAD in patients with suspected disease,73,74 effectively triaging symptomatic patients for conventional coronary angiography. From a slightly different point of view, Hadamitzky et al75 compared the observed rate of all cardiac events with the event rate predicted by the Framingham risk score in 1256 consecutive patients with suspected CAD who underwent 64-row CCTA during the 18-month follow-up period. Interestingly, these investigators observed that in their patient population, the rate of all cardiac events in patients without obstructive CAD was significantly lower than predicted by the Framingham risk score. Thus, all these studies agree that there is evidence that the extent and severity of CAD defined at CCTA predicts all-cause mortality, whereas patients with a normal CCTA have an excellent prognosis (Fig. 7).
COST-EFFECTIVENESS OF CCTA
After almost 2 decades of feasibility testing, cost-effectiveness results of CCTA with respect to clinically established diagnostic modalities are now becoming available. Initial reports suggested that CCTA is the most cost-effective approach for individuals with low and intermediate pretest likelihood of CAD, whereas for patients with a pretest probability of CAD greater than 60%, conventional coronary angiography remains more cost-effective.76 In a recent systematic review, Mowatt et al77 analyzed the clinical effectiveness and cost-effectiveness of 64-row or higher CCTA as an alternative to conventional catheterization in the CAD scenario and concluded that in this clinical setting, 64-row CCTA seems to be superior to myocardial perfusion scintigraphy. In terms of cost, these investigators described CCTA to be a short-term and probably a long-term cost-effective replacement for myocardial perfusion scintigraphy in diagnosing CAD.77 A negative CCTA for CAD should avoid the costs of unnecessary catheterizations, thus resulting in overall cost savings in the diagnostic process of CAD.
FUTURE OUTLOOK: IMPLICATIONS OF CCTA ON PATIENT MANAGEMENT
As discussed, particularly when performed with the newest technology, CCTA provides accurate and reliable information regarding CAD. This technique allows noninvasive assessment of the extent of CAD. The cornerstone of CCTA is based, however, on its high negative predictive value, which allows for significant coronary artery stenosis to be ruled out in the majority of individuals. Limitations regarding insufficient spatial and temporal resolution of the MDCT scanners may cause false-positive findings, directly influencing patient management. Thus, CCTA should be used in the appropriate clinical scenario and should be prevented from indiscriminate use to invigorate its adequate role in the diagnostic workup of patients with suspicion of CAD. Because CCTA has so far been an anatomic modality, it hardly provides information about the functional significance of stenosis severity. The presence of significant coronary artery stenosis does not necessarily translate into myocardial ischemia,78 a fact that supports the need for diagnostic tools that combine morphologic and functional information. Furthermore, because CCTA provides a significant amount of information that was not readily available before the development of CCTA, such as coronary artery plaque composition or detection of significant coronary artery stenosis in individuals with noncardiac origin atypical chest pain, determination of the prognostic significance of these findings requires further research. Finally, CCTA may serve as guidance for percutaneous interventional procedures, as this noninvasive technique may influence the decision-making of individuals who may benefit from percutaneous therapy or rather undergo elective bypass surgery.79,80
The availability, ease of use, and accuracy of CCTA has substantially improved in the last decade. This technique has shown its usefulness in a number of clinical scenarios in individuals with known or suspected CAD. Particularly, its ability to confidently rule out significant coronary artery stenosis has been consistently recognized. The clinical use of CCTA in the context of surgical revascularization is indubitable, whereas its role in addressing coronary artery stent patency requires further technical refinement. Ongoing research points toward the comprehensive assessment of CAD, including integrative morphologic and functional evaluation of the myocardium and coronary vessels. Most recent reports emphasize the prognostic value and cost-effectiveness of CCTA. Hence, CCTA may emerge as one of the most important clinical tools in the assessment of CAD, but further research is warranted.
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tomography scanners; x-ray computed; coronary vessels; angiography; coronary artery disease
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