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Coronary Computed Tomography Angiography for the Assessment of Acute Chest Pain in the Emergency Department: Evidence, Guidelines, and Tips for Implementation

Ropp, Alan MD; Lin, Cheng T. MD; White, Charles S. MD

doi: 10.1097/RTI.0000000000000128
Symposium Review Articles
Free

Acute chest pain is an important clinical challenge and a major reason for presentation to the emergency department. Although multiple imaging techniques are available to assess such patients, considerable interest has focused on the use of coronary computed tomography (CT) angiography. Three recent multicenter trials have demonstrated the value of coronary CT angiography (CCTA) to diagnose patients with acute coronary syndrome (ACS) rapidly and accurately. Guidelines developed on the basis of these and other studies suggest that CCTA is optimally used in patients with low to intermediate risk for ACS. A related protocol, the triple rule-out scan, may be valuable if overlapping symptoms occur, particularly between those of ACS and pulmonary embolism. In developing a program to perform CCTA in the emergency room, it is important to work closely with emergency physicians and cardiologists to maximize appropriate use of this technique and to develop appropriate protocols that minimize radiation dose. Ongoing efforts to improve existing capabilities of CCTA include better characterization of coronary plaque and the use of CT fractional flow reserve and perfusion techniques.

Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD

The authors declare no conflicts of interest.

Correspondence to: Charles S. White, MD, Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, 22 South Greene St, Baltimore, MD 21201 (e-mail: cwhite@umm.edu).

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ACUTE CORONARY SYNDROME (ACS)

Acute chest pain poses a major clinical challenge and accounts for the primary reason for non–injury-related emergency department (ED) visits, totaling 5.5 million patients per year in the United States.1 ACS must be considered in any patient presenting with chest pain, although only 13% of patients are ultimately diagnosed with ACS.1 The annual prevalence of ACS is approximately 3 in 1000.2,3 The term ACS encompasses ST elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction (NSTEMI), and unstable angina (UA). The highest hospital mortality occurs with STEMI at approximately 7% compared with 3% to 5% for NSTEMI. At 6 months, both have similar mortality rates of 12% to 13%.4,5 Interestingly, patients with NSTEMI have twice the mortality rate at 4 years, presumably related to differences in patient profiles between the 2 categories.6 Patients presenting with NSTEMI tend to be older and have more comorbidities. ACS patients with abnormal electrocardiograms or biomarkers require hospital admission. The role of imaging is to noninvasively identify patients who may not need hospital admission by exclusion of significant coronary artery disease (CAD).

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HEALTH CARE EXPENDITURE AND UTILIZATION

As of 2010, the annual direct and indirect cost of heart disease in the United States was estimated at >$204 billion.7 Costs include hospital stays, ED visits, outpatient visits, home health care, medications, and lost productivity/mortality. ED visits and hospital stays related to heart disease totaled $73 billion, with $5.6 billion spent in the ED alone.7 Specifically, expenses related to ACS are estimated to cost $150 billion annually.7,8 In 2010, approximately 1,140,000 patients were discharged with ACS as their primary or secondary discharge diagnosis.7 ACS discharge estimates from 2009 were as high as 1,438,000. Clearly, the economic burden and hospital resource utilization of ACS remain significant, and advances to aid in appropriate triage and accurate diagnosis of these patients are in demand.

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DIAGNOSTIC CHALLENGE

Current diagnostic methods used in the evaluation of patients presenting with acute chest pain include biomarkers, electrocardiogram, and a choice of several imaging modalities, which include myocardial perfusion imaging (MPI), echocardiography, invasive coronary angiography (ICA), and coronary CT angiography (CCTA).9

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MPI

MPI uses radiopharmaceutical tracers that are actively taken up by myocytes. Areas with active blood flow display a normal perfusion pattern, whereas ischemic or infarcted myocardium demonstrates a perfusion defect when compared with normal myocardium. The negative predictive value (NPV) of MPI is nearly 100%, indicating that a negative examination essentially excludes ACS. When appropriate, MPI may also be used to determine ventricular function (eg, ejection fraction). Stress MPI is also useful for the detection of inducible ischemia and at-risk myocardium by demonstrating inducible perfusion defects and aids in decision making and determination of long-term management. An important disadvantage of MPI is that it requires patients to be removed from the monitored environment of the ED for an extended period of time, it does not assess many other causes of chest pain, and it delivers radiation doses ranging from 10 to 24 mSv.10

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ECHOCARDIOGRAPHY

Echocardiography directly visualizes the cardiac and valvular anatomy as well as assesses their function in real time. Acute myocardial ischemia manifests on echocardiography as regional wall motion abnormality corresponding to the diseased coronary artery territory. Either treadmill or pharmacologic stress echocardiography is often performed during the workup of ACS to aid in decision making and help determine long-term management. This allows for the evaluation of inducible myocardial ischemia, as evidenced either by angina or an inducible wall motion abnormality.

Although frequently incorporated into the workup of ACS, detection of ACS on echocardiography is limited by interobserver variability and technical difficulties encountered while obtaining a diagnostic study. In addition, patients with prior myocardial infarction often demonstrate false-positive results.11,12

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ICA

ICA is the current gold standard in the evaluation of ACS and can be used for therapeutic intervention. Direct injection of iodinated contrast material into the coronary artery allows for 2-dimensional visualization and quantification of any occlusion or stenosis. This procedure allows for both diagnostic assessment and immediate revascularization of hemodynamically significant stenosis with stents. Because it is an invasive procedure requiring mobilization of highly trained physicians and staff, ICA is typically reserved for patients at high pretest probability for ACS. In addition, the average radiation dose delivered during ICA is 8.5 mSv, with a range of 1.5 to 20.4 mSv.13

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CT SCANNING

Coronary calcium CT scans were developed with a goal to noninvasively risk stratify patients with coronary artery calcifications. The severity of calcification for each patient is quantitatively calculated using the Agatston score, a scoring system based on the quantity and Hounsfield Unit (HU) measurement of calcifications.14 Originally validated with electron-beam CT technology, calcium score scans can be performed on any multidetector CT (MDCT) scanner and have good sensitivity and NPV.15–17 However, it is well recognized that significant coronary artery stenosis depicted on CCTA occasionally occurs in the setting of a negative calcium score.18,19

CCTA has undergone rapid development due to advancements in MDCT technology. Modern CT scanners are now capable of imaging the coronary arteries with high spatial resolution (typically 0.5 to 0.625 mm) and speed (scan time typically <10 s and in some instances <1 s). After its widespread implementation, substantial evidence has accumulated over the last decade supporting the use of CCTA in the assessment of ED patients with atypical or nonspecific chest pain.

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EVIDENCE

A number of multicenter trials have compared the diagnostic accuracy of CCTA in symptomatic outpatients with chest pain with ICA as the gold standard, and found a high NPV of 83% to 99% for excluding significant CAD.20–22 There is also growing evidence supporting the use of CCTA in the evaluation of low-risk to intermediate-risk patients presenting with ACS. In this population, ACS can be excluded if the CCTA does not show significant CAD.

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Clinical Trials

Three large randomized multicenter trials comprising >3000 patients have assessed the use of CCTA in the setting of acute chest pain. The CT-STAT trial evaluated 699 patients randomized to either MPI or CCTA as the initial noninvasive test performed before ICA.23 The findings of the trial largely favored the use of CCTA in the evaluation of low-risk to intermediate-risk patients presenting with ACS.

A patient’s risk of mortality after presentation with ACS was determined by the Thrombolysis in Myocardial Infarction (TIMI) score.24 The patient initially underwent electrocardiography and administration of troponins to distinguish between STEMI, NSTEMI, and UA. If the patient was experiencing a STEMI, urgent revascularization was indicated. If they were experiencing a NSTEMI or UA, then they were triaged according to their TIMI score (Table 1). Each criterion in the TIMI score counted for 1 point and increased risk. Patients with a score of 4 or less were considered low to intermediate risk and possibly benefitted from CCTA before further workup or treatment.

TABLE 1

TABLE 1

The CT-STAT trial found several significant benefits to performing CCTA over MPI. These included a 54% reduction in time to diagnosis (2.9 vs. 6.3 h), a decrease in total ED cost of care by 38% ($2137 vs. $3458), and lower effective radiation dose (11.5 vs. 12.8 mSv), with minimal difference in major adverse cardiac events (MACE) (0.8% vs. 0.4%).23 However, given the relatively low specificity of CCTA (64% to 90%), the study confirmed that MPI is often required to confirm myocardial ischemia before proceeding to revascularization in some patient groups. Patients with 50% to 69% vessel stenosis on CCTA still require an MPI to prevent unnecessary invasive angiography.25

In addition to the CT-STAT trial, the ROMICAT II and ACRIN-PA have provided significant evidence supporting the use of CCTA in the workup of low-risk to intermediate-risk ACS patients.26 These trials most notably demonstrated the safety of negative CCTA as an indication for discharge from the ED with very low rates of major adverse cardiovascular events while reducing the time to diagnosis and total cost of care.26

The ROMICAT II trial consisted of 1000 patients from 9 different centers in the United States and concluded in 2012.27 Patients were randomized to either CCTA or standard ED evaluation. Among the most notable findings, 50% of patients evaluated with CCTA were discharged within 8.6 hours compared with 10% in the standard evaluation group. In patients found to have ACS, the length of stay was similar in both groups. There were no cases of undetected ACS in either group. More diagnostic testing was performed with significantly higher cumulative radiation exposure in the CCTA group. However, patients undergoing CCTA with an advanced 128-slice, dual-source CT scanner received lower radiation exposure (6.2 mSV compared with 4.7 mSv in the standard evaluation group). Total cost of care was similar in both groups. Overall, the CCTA group demonstrated a high NPV, at similar cost, but received higher doses of radiation.

The ACRIN-PA trial was a randomized controlled multicenter trial published in 2012.28 The study compared a CCTA-based evaluation with a standard ED rule out. A total of 1370 patients presenting with chest pain and a low to intermediate risk of ACS met study inclusion criteria. Patients in the CCTA group were more likely to be discharged (50% vs. 23%) and had a shorter length of stay. Coronary disease was more likely to be diagnosed, and there was no significant difference in the use of invasive angiography or the rate of revascularization between the groups. Patients in the CCTA group were less likely to have negative invasive angiography. However, there was no significant difference in the likelihood of repeat ED visit, hospitalization, or visits to the cardiologist office. Radiation exposure was not directly evaluated. However, the authors noted that improvements in imaging technology and technique allow the acquisition of high-quality studies with an average exposure typically less than nuclear MPI. The study concluded that using CCTA as the first imaging test for low-risk to intermediate-risk ACS patients allows safe discharge after a negative test with reduced length of stay. In addition, the authors suggested that earlier identification of coronary disease may allow the use of preventative therapies that may improve outcomes.

Follow-up data of patients discharged after negative CCTA were reassuring. A prospective study by Rubinshtein et al29 utilized CCTA to evaluate 58 patients with acute chest pain and found no MACE after 1 year. A study by Hollander et al30 examined 481 ED patients with negative CCTA results and demonstrated a very low (<1%) 1-year rate of cardiovascular events. Another study, reported by Schlett et al31 followed the 2-year outcomes of 368 patients from the initial ROMICAT trial to further evaluate the prognostic value of CCTA in ED patients. This study also found that CCTA can also be used to predict the risk for MACE in these patients. On the basis of this study, patients with the absence of CAD can be regarded as risk free for at least 2 years, whereas patients with CAD or regional wall motion abnormalities were associated with the highest risk for MACE.31 Further, the risk for 2-year MACE increased as the severity of CAD increased, as measured by CCTA criteria. These data demonstrate the value in using CCTA to stratify MACE risk and aid in clinical decision making.

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GUIDELINES

Recently, several organizations have published guidelines addressing the appropriate use of CCTA in symptomatic patients. Overall, CCTA is considered appropriate in the assessment of CAD in low-risk to intermediate-risk patients presenting with acute chest pain. Serum troponin and electrocardiography findings must also be either normal or equivocal in these patients. A dedicated CCTA protocol uses a scan range limited to the heart (Fig. 1). In cases of atypical chest pain wherein there is equal likelihood of CAD, pulmonary embolism (PE), and aortic dissection, a “triple rule-out” scan, a scan tailored to evaluate the entire chest, can be performed to evaluate for several life-threatening causes of chest pain (Fig. 2).

FIGURE 1

FIGURE 1

FIGURE 2

FIGURE 2

In 2010, a consensus document on appropriate use criteria for CCTA was created jointly by the American College of Cardiology Foundation, the Appropriate Use Criteria Task Force, the Society of Cardiovascular Computed Tomography, the American College of Radiology, the American Heart Association, the American Society of Echocardiography, the American Society of Nuclear Cardiology, the North American Society for Cardiovascular Imaging, the Society for Cardiovascular Angiography and Interventions, and the Society for Cardiovascular Magnetic Resonance.32 In this document, the appropriateness of CCTA was assessed for a number of clinical indications, with each indication classified as appropriate, inappropriate, or uncertain. CCTA was classified as appropriate in the emergent setting of acute symptoms with suspicion of ACS in a low-risk to intermediate-risk patient [defined by a <10% (low) or 10% to 20% (intermediate) 10-y absolute coronary heart disease risk].33

Four new category I Current Procedural Terminology codes were introduced in 2010 to report cardiac CT and CCTA examinations. Of the 4, 2 can be used in the setting of acute chest pain. Calcium CT (75571) and CCTA (75574) together add to the noninvasive diagnostic algorithm of acute chest pain workup.

In 2012, the ACR published appropriateness criteria in the clinical scenario of a patient with acute nonspecific chest pain at low probability of CAD and determined that CCTA is usually appropriate (rating: 7) in that specific clinical setting.34 In comparison, MPI and ICA were rated “may be appropriate” (rating: 6) and “usually not appropriate” (rating: 1), respectively. However, CCTA has a lower rating than both MPI and ICA when the suspicion for ACS is high.

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IMPLEMENTATION

CT-based Triage of Acute Chest Pain Patients

A consensus must be reached among emergency physicians, cardiologists, and radiologists regarding the evaluation of acute chest pain patients to mitigate overuse of CCTA in the ED. Developing a clear algorithm with well-defined clinical categories (negative, low risk, medium risk, high risk) that corresponds to imaging findings would help optimize patient management. For instance, we consider any patient with coronary stenosis >70% (>50% in the left main coronary artery) to be at high risk and requiring hospital admission (Fig. 3). Having a CT scanner capable of high-quality cardiac scans in close proximity to the ED allows for close patient monitoring and throughput. These patients often receive nitroglycerin and/or β-blocker, requiring the education and vigilance of the staff in potential drug complications (eg, hypotension, interaction of nitroglycerin with phosphodiesterase inhibitor). Diagnostic algorithms should also take into consideration a patient’s pretest probability of CAD. Otherwise healthy 25-year-old patients will have an extremely low pretest probability, and thus CCTA should be avoided in these patients, as it is extremely unlikely to provide any new useful information. Likewise, elderly patients with multiple risk factors for CAD, such as long-standing diabetes, should also be avoided. These patients are very likely to have extensive coronary artery calcifications, and it is doubtful that CCTA further clarifies the cause of their acute symptoms.

FIGURE 3

FIGURE 3

Patients whose CCTA studies demonstrate normal coronary arteries or nonsignificant stenosis (generally <50%) can be safely discharged from the ED. Cardiology consultation in an outpatient setting should be considered for patients with mild coronary stenosis. When moderate stenosis (50% to 70%) is found, the patient is admitted for observation and often undergoes further evaluation with MPI or diagnostic catheterization.

Although careful attention is paid to coronary assessment, a number of noncoronary pathologies can present in acutely symptomatic patients. Other causes of chest pain include pneumonia, PE, rib fracture, pneumothorax, aortic dissection, and pericardial disease. Therefore, reconstructions with full field of view to include the lung fields are often obtained to assess for causes of chest pain other than ACS.

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Scanner Technology

A variety of MDCT systems are tailored for coronary imaging. Wide-detector scanners include the 256-slice MDCT (Brilliance iCT; Philips Medical Systems) and 320-slice MDCT (Aquilion One; Toshiba Medical Systems), which cover 8 and 16 cm, respectively, thereby reducing misregistration or “slab” artifact. The 320-slice MDCT has a better spatial resolution at 0.5 mm and covers the whole heart, whereas the 256-slice scanner uses double Z-sampling and offers improved temporal resolution (0.27 s rotation time). Several dual-source 2×128-slice scanners (SOMATOM Definition Flash and Force, Siemens Medical System, GE Revolution, and other new scanners utilizing spectral CT currently in development) offer dual-energy acquisition in addition to improved temporal resolution (generally <0.28 s rotation time). The selection of MDCT therefore depends on institutional and imager preference. It should be noted that, although many advanced scanners and techniques are available to optimize CCTA, diagnostic studies generally can be obtained with using conventional scanners (64 slices and higher) located in close proximity to the ED.

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Protocols

Two scanning protocols are available in the ED setting: dedicated CCTA and a whole chest scan called “triple rule-out.” The triple rule-out protocol provides a global view of the major vasculature, enabling assessment for CAD, PE, and aortic dissection. This is achieved by using a single acquisition with a biphasic contrast injection (resulting in higher contrast volume) including full concentration intravenous contrast administered in the first phase, followed by a second phase of dilute contrast (50:50 with saline).35 With this protocol, the pulmonary vasculature, aorta, and coronary arteries are each adequately opacified during a single scan acquisition. The longitudinal extent of the scan is widened to that of a conventional chest CT, which results in a longer scan compared with dedicated CCTA. Studies have shown no significant difference in the image quality of the coronary arteries between the 2 protocols.35,36 One study showed that noncoronary reasons for chest pain were diagnosed in 11% of ED patients at low to moderate risk for ACS using a triple rule-out study.37 Use of a triple rule-out scan may be useful when the clinical signs and symptoms of PE and ACS overlap, presenting the clinician with similar pretest probabilities for both. Madder and colleagues found a poor diagnostic yield of triple rule-out for PE and aortic dissection; however, Schertler and colleagues suggested that utilizing an evidence-based method for developing a pretest probability for PE that includes Wells criteria and D-dimer improved the diagnostic yield of the triple rule-out. In cases in which both PE and ACS are considered equally likely, and with appropriate patient selection, the triple rule-out study may be superior to a CCTA given the improvement in the detection of PE.38,39

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Radiation Concern

The increasing use of CCTA has created considerable concern over the potential for radiation-induced malignancies due to medical imaging. To that end, radiation dose should be carefully monitored. Historically, CCTA studies have an average dose of 12 mSv.37,40 As the radiation dose is proportional to the square of the tube voltage, we routinely obtain diagnostic scans at a tube potential setting of 100 kV in patients with a body mass index of <40 kg/m2. When the body mass index is >40 kg/m2, an increased tube voltage of 120 kV is needed to preserve image quality. More recent advances have led to drastic reductions in radiation dose. Under ideal conditions and appropriate technique, submilliSievert scans are possible.41 The correct choice of scanning strategy is also important for limiting dosage. Approximately 80% dose reduction can be achieved by using prospective triggering rather than retrospective gating.28,42 In our experience, diagnostic triple rule-out scans can be achieved at an effective dose of 1.4 mSv by utilizing a high-pitch protocol.43 Nonetheless, use of a dedicated CCTA instead of a “triple rule-out” scan can also reduce the dose by a significant amount.44

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Iterative Reconstruction

Filtered back projection (FBP) was the obligatory algorithm for image reconstruction for many years, because processing algorithms were bottlenecked by inadequate computational power. More recently, computationally intense algorithms have been devised called iterative reconstruction. Iterative reconstruction utilizes a more advanced geometric model than filtered back projection and can provide similar image quality with up to 44% reduction in radiation dose (Fig. 4).45,46

FIGURE 4

FIGURE 4

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NEWER CONSIDERATIONS

Plaque Characterization

In addition to luminal assessment, CCTA is capable of characterizing plaques (ie, fatty, fibrous, or calcified) and identifying high-risk lesions. Motoyama et al47 found that plaques that demonstrated positive remodeling and low-attenuation (<30 HU) on CCTA were associated with a higher risk of subsequent development of ACS compared with those that did not. Madder et al48 showed good sensitivity (53% to 81%) and specificity (82% to 95%) using CCTA to identify evidence of plaque disruption (eg, plaque ulceration and intraplaque dye penetration) and also reported that these disrupted lesions were larger, more likely to be positively remodeled, and contained more low-attenuation plaque (<50 HU). In practice, we view noncalcified plaque and positive remodeling as a concerning finding that we report routinely.

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Fractional Flow Reserve (FFR)

FFR is a technique used during ICA to gauge the hemodynamic significance of specific coronary plaques by measuring pressure differences across a stenosis. When coronary angiographic findings are equivocal for significant stenoses, FFR is considered the gold standard for determining the need for treatment. The mean pressure in the coronary artery distal to the stenosis is divided by the aortic pressure during maximal vasodilation. FFR values of 0.8 to 1.0 are highly accurate for the absence of ischemia, whereas FFR<0.75 is associated with positive ischemic results that can benefit from revascularization (values between 0.75 and 0.8 represent indeterminate FFR results).49,50 Its analogue in CCTA (denoted FFRCT) attempts to provide a noninvasive calculation of FFRCT by applying computational fluid dynamics. The addition of FFRCT criteria (FFRCT≤80%) to CT criteria (stenosis ≥50%) was shown to improve detection of hemodynamically significant lesions as compared with CT criteria alone in the multicenter Determination of Fractional flow reserve by Anatomic Computed Tomographic Angiography (DeFACTO) trial.51 Further studies are necessary to determine whether routine application of FFRCT improves patient outcome as applied to the ED setting.

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CT Perfusion (CTP)

The potential for assessing myocardial perfusion on CT has generated much interest. Resting CT MPI cannot reliably exclude ACS, as reported in 1 study in which CTP detected only 3 of 9 patients with ACS.52 Adenosine stress CTP has showed more promise. Rochitte et al53 demonstrated that the combination of CTA and adenosine stress CTP (using a 320-slice scanner capable of volumetric scans) permitted accurate diagnosis of patients with hemodynamically significant CAD, using ICA and MPI as reference standards. It remains unclear whether CCTA/CTP has an incremental value over CCTA in the setting of low-risk to intermediate-risk patients with acute chest pain in the ED setting.

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CONCLUSIONS

Substantial evidence in the form of multiple large randomized controlled trials has validated the utility of CCTA to exclude ACS in low-risk to intermediate-risk ED patients. Imaging specialists are advised to work with ED physicians and cardiologists before implementation of a CT-based program in the ED. The balance between patient safety and diagnostic utility of CT must be evaluated in each clinical scenario to optimize patient care.

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Keywords:

acute chest pain; emergency department; coronary computed tomography angiography

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