Computed tomography in coronary imaging: current status

7 Computed tomography in coronary imaging: current status ARJUN NAIR AND ANAND DEVARAJ Recent technological advances have led to improvements in the use of computerised tomography for coronary imaging. In this article, the authors consider the common applications, technical aspects and limitations of coronary computerised tomography angiography. Coronary artery disease (CAD) remains a significant contributor to morbidity and mortality in the UK, causing an estimated 88236 deaths in 2008 and costing the UK economy around 9 billion a year, 1 in spite of major advances in preventive, diagnostic and therapeutic measures. The diagnosis of cardiac chest pain in the acute and non-acute settings can still pose a challenge. A robust clinical assessment remains integral to accurate diagnosis, but conventional risk factors can fail to identify one-third of deaths caused by CAD. 2 Conventional invasive coronary angiography is the gold standard in diagnostic evaluation, but is not without its risks. With such a burden of disease, a non-invasive but accurate and acceptable means of assessing the coronary arteries is desirable. Over the past decade, coronary computerised tomography angiography (CCTA) has undergone significant evolution as a non-invasive diagnostic modality capable of evaluating coronary artery calcification and stenoses, atherosclerotic plaque characterisation, and cardiac morphology. CT TECHNIQUE CT scanners have an x-ray source and detectors mounted at opposite ends in a rotating gantry, through which a patient is moved during the image acquisition (Figure 1). Coronary calcium scans are low-dose studies performed without administration of intravenous iodinated contrast. However, like conventional invasive angiography, CCTA requires intravenous contrast administration, followed by a correctly timed scan such that the density of contrast is optimised within the coronary arteries (Figure 2). Factors that may absolutely or relatively contraindicate intravenous contrast, such as renal impairment or severe allergic reactions, thus need to be considered when requesting CCTA. A typical CT cardiac examination usually involves a calcium scoring scan followed by a CCTA. CCTA requires that the heart is as stationary as possible during the acquisition. In the past, the greatest obstacle to obtaining CT cardiac imaging of good diagnostic quality was the inability of the CT scanner to perform the imaging sufficiently quickly such that the heart could be imaged while at rest, during diastole. This has been largely overcome through a variety of methods to modify patient or scanner parameters. For patients with heart rates between 60 and 90 beats per minute, the use of beta-blockers to reduce the heart rate ideally to less than 60 beats per minute has become the norm. The development of electrocardiographic (ECG) gating has meant that images of the Arjun Nair, MB ChB, MRCP, FRCR, Imaging Fellow, Department of Radiology, Royal Brompton Hospital, London; Anand Devaraj, MD, MRCP, FRCR, Consultant Radiologist, St George s Hospital, London

8 x-ray source Detector array Patient Direction of rotation Figure 1. General schematic of a CT scanner CT gantry heart can be obtained during a particular portion of diastole (typically 65 70 per cent of the RR interval). This can be performed through either prospective gating, where images are acquired only at the desired portion of the cardiac cycle, or retrospective gating, where images are acquired through the entire cycle, but only images from the desired fraction of the cycle are used in image Figure 2. Coronary CT angiographic appearance of a normal right coronary artery reconstruction. With recent CT scanner technology (either dual-source or wide-area detector CT), an acquisition of the entire heart is now possible during a single heartbeat. The temporal resolution of such CT scanners (83 milliseconds) is getting closer to that of conventional angiography (5 20 milliseconds). Generally, ECG gating requires a predictable heart rate; thus, arrhythmias are a potential problem in CCTA. Factors that may limit image quality in CCTA are listed in Box 1. CORONARY CALCIUM SCORING Atherosclerosis causes coronary artery calcification; the quantity of coronary calcium is therefore an indicator of the overall atherosclerotic plaque burden. On CT, calcium scoring is usually a simple process whereby each high-density focus of coronary calcium is identified on the non-contrastenhanced study, and then automatically summed to provide a total score, which takes into account the size and density of all the foci of calcification (Figure 3). The calcium score can be considered normal (0), mild (1 100), moderate (101 400) or severe (>400), with each category of severity correlated with a higher risk of coronary event. 3 This predictive ability of calcium scoring has previously been the subject of some debate, but it is currently accepted that calcium scoring has a defined role in the triage of stable chest pain. This has led to its incorporation into the NICE guideline on assessment and diagnosis of suspected cardiac chest pain. NICE recommends that individuals with an estimated cardiac risk between 10 and 29 per cent, based on clinical assessment, be referred for CT calcium scoring (Figure 4). 4 However, calcium scoring has a few limitations. The calcium score is an estimate of overall atherosclerotic plaque burden, but it cannot predict or localise coronary artery stenosis. Calcified plaques are associated with positive remodelling (expansion of the involved vessel lumen), and such eccentric calcified plaque does not significantly BOX 1. Factors affecting image quality in coronary CT angiography PATIENT FACTORS l Body mass index l Heart rate l Heart rhythm l Excessive respiratory motion l Presence of cardiac devices (eg pacemakers, metallic prosthetic valves) SCAN FACTORS l Number of detector rows l Number of x-ray tubes (single- versus dual-source) l CT gantry speed l CT reconstruction technique (eg statistical iterative reconstruction) l Intravenous iodinated contrast volume and timing of injection contribute to arterial luminal narrowing. Heavily calcified plaques can cause a blooming artefact on subsequent CCTA, resulting in an overestimated adjacent stenosis or even an uninterpretable study. Conversely, a calcium score of 0 does not totally exclude coronary artery stenosis. Moreover, the calcium score may be modified by age, sex and ethnicity. A recent retrospective study found that African- Americans had a significantly higher prevalence and extent of non-calcified plaque (64 versus 41 per cent) and lower prevalence and extent of calcified plaque (26 versus 45 per cent) compared to white patients, independent of risk factors. Both groups had a similar prevalence of coronary stenosis 50 per cent or greater. 5 CORONARY CT ANGIOGRAPHY Significant CAD can be defined on invasive coronary angiography as 50 per cent stenosis in the left main coronary artery, or 70 per cent stenosis of at least one major epicardial artery. 4 The severity and location of a coronary stenosis, as well as the composition and vulnerability of the plaque causing it are all important factors in determining the www.trendsinurology.com TRENDS IN UROLOGY & MEN S HEALTH SEPTEMBER/OCTOBER 2012

9 likelihood of progression to clinically significant CAD, and the type of intervention needed. The advantage that CCTA has over conventional invasive angiography lies in its ability to depict both a coronary stenosis and the culprit plaque simultaneously (Figure 5). However, because of its lower spatial and temporal resolution as compared to invasive coronary angiography, CCTA may overestimate the degree of stenosis. CCTA performed on newer types of CT scanner (64-slice or dual-source) provides sensitivities of up to 99 per cent, and excellent negative predictive values for significant CAD using invasive coronary angiography as the reference standard, ranging from 86 to 100 per cent. 6 With such high sensitivity and negative predictive values, CCTA is a useful test to rule out significant CAD, and so can obviate the need for more invasive testing for patients presenting with stable chest pain. Importantly, it allows invasive angiography to be reserved for patients more likely to benefit from it. If significant stenosis is suspected, the need for revascularisation with angioplasty or stent placement, for example, can be planned for in advance. These advantages have led to the recommendation by NICE for CCTA with 64-slice CT or above in patients with stable chest pain who have CT calcium scores of 1 400. A recent multi-society guideline from the USA similarly recommends using CCTA for non-acute angina assessment in (a) patients with intermediate risk of CAD with interpretable ECGs and who are able to exercise, or (b) patients with low- to intermediate-risk of CAD with uninterpretable ECGs or inability to exercise. 7 CCTA in acute chest pain Recent studies have focused on the role and cost-effectiveness of CCTA in the assessment of acute ischaemic chest pain. For example, a prospective study by Meijboom et al. of 104 patients with non-st elevation acute coronary syndrome who were either high- or low-risk demonstrated the role 64-slice CCTA can play in excluding significant CAD in this group of patients: CCTA had a sensitivity, specificity, positive predictive value and negative a predictive value of 100, 75, 96 and 100 per cent respectively, on a per-patient basis. 8 More recently, the Rule Out Myocardial Infarction using Computer Assisted Tomography (ROMICAT) trial showed that when there was no evidence of CAD on CCTA, CCTA provided a 100 per cent sensitivity and negative predictive value for acute coronary syndrome. The Coronary Computed Tomographic Angiography for Systematic Triage of Acute Chest Pain Patients to Treatment (CT-STAT) trial in the USA has Figure 3. Calcium scoring on CT. Foci of calcium (arrows in a) can be selected with a mouse-click and then summed to provide a total calcium score (b) shown that using CCTA in low-risk acute chest pain patients can reduce the time to diagnosis by 54 per cent, as compared to rest-stress myocardial perfusion imaging, and is also more cost-effective. These results illustrate a role for CCTA in excluding significant CAD in a low-risk population presenting with acute chest pain. Trials such as the ongoing Role of Cardiac CT in Rapid Access Chest Pain Clinics (RADICAL) trial will hopefully tell us if such costeffectiveness can be replicated in the UK. 9 Estimated likelihood of CAD = 10 29 per cent b CT calcium scoring 0 1 400 >400 Investigate other causes of chest pain 64-slice (or above) CT coronary angiography Invasive coronary angiography if appropriate, otherwise non-invasive functional imaging Figure 4. NICE recommendation for CT calcium scoring and CT coronary angiography in patients with stable chest pain 4

10 Figure 5. Mild to moderate stenosis of the proximal left anterior descending artery on CCTA, caused by a soft (non-calcified) plaque (arrow). Note the eccentric focus of calcification (arrowhead), which is not causing any stenosis Prognostic information from CCTA In addition to aiding diagnosis, the extent and severity of coronary stenosis on CCTA has proven prognostic value, independent of baseline risk factors. For instance, over a mean 16-month follow-up of patients undergoing CCTA, Pundziute et al. demonstrated that cardiac events were more likely when patients were grouped according to the status of their coronary arteries on CCTA, ranging from no events in patients with normal coronary arteries, to 77 per cent of events in patients with obstructive coronary disease in the left proximal coronary system. 10 Recently, an analysis of 23854 patients undergoing CCTA in the Coronary CT Angiography Evaluation for Clinical Outcomes: an International Multicenter Registry (CONFIRM) trial confirmed an increased risk of mortality in patients with both obstructive and non-obstructive CAD, and a lower mortality when CAD was absent. 11 Other roles of CCTA An expanded role for CCTA in the evaluation of other aspects of cardiac disease (Box 2) is the subject of ongoing investigation. 12 14 ISSUES IN CARDIAC CT Radiation exposure As in any examination involving radiation, the goal is to keep exposure as low as reasonably achievable while still obtaining images of diagnostic quality. The minimisation of radiation dose is an important consideration as the use of CT calcium scoring and CCTA become more widespread, because of the small but important risk of cancer after ionising radiation exposure. The lifetime attributable risk of cancer from an effective radiation dose of 10 millisieverts (msv) is small, in the order of 1 in 2000, 15 but varies with age and gender, and also cumulatively increases with multiple exposures. Radiation dose from CCTA can be comparable to and may even exceed that of invasive coronary angiography. 16,17 However, a variety of modern dose-reduction techniques are now available (Box 3), which can lead to effective doses that are even below 1mSv. 18 Extracardiac findings The incidental discovery of extracardiac findings such as pulmonary nodules (Figure 6) or mediastinal lymphadenopathy during cardiac CT is inevitable, because the volume of the patient scanned during the examination covers more than the cardiac structures alone. A review of 15 published series concluded that while extracardiac findings are common in cardiac CT, with a prevalence of 15 67 per cent, a smaller but still significant proportion of these findings (1.2 22.7 per cent) require further action. 19 Consequently, there are still diverging opinions on whether all cardiac CT examinations should be evaluated for these findings by using a maximum (as opposed to a restricted) field of view. 19,20 Any clinician requesting cardiac CT examinations should BOX 2. Other potential uses of coronary CT angiography l Plaque characterisation to identify culprit lesions in unstable angina l Evaluation of left ventricular function l Evaluation of myocardial perfusion l Assessment of coronary stents and grafts l Evaluation of congenital heart disease BOX 3. Dose-reduction techniques in coronary CT angiography l Overall reduction of tube potential l Anatomical-based tube current modulation l ECG-controlled tube current modulation l Prospective ECG gating ( step-andshoot ) l High-pitch spiral acquisition l Statistical iterative reconstruction thus be aware of the potential for incidental findings that may cause considerable anxiety to a patient, but nevertheless should not be dissuaded from requesting the investigation if there is a clear indication to do so. CONCLUSION The use of CT in coronary imaging has seen remarkable expansion as a result of improved technology. Multiple studies have shown how it can aid diagnosis and prognosis in patients with suspected ischaemic chest pain in both the non-acute and acute settings. Declaration of interests: none declared. REFERENCES 1. Scarborough P, Bhatnagar P, Wickramasinghe K, et al. Coronary heart disease statistics 2010. Oxford: British Heart Foundation, 2010. 2. Grover SA, Coupal L, Hu XP. Identifying adults at increased risk of coronary disease. How well do the current cholesterol guidelines work? JAMA 1995;274:801 6. www.trendsinurology.com TRENDS IN UROLOGY & MEN S HEALTH SEPTEMBER/OCTOBER 2012

11 KEY POINTS Coronary computerised tomography angiography (CCTA) has a useful role in ruling out significant coronary artery disease in patients with suspected ischaemic chest pain, but must be used in the right circumstances Increasingly, CCTA is also providing prognostic information Radiation exposure is an important consideration, but technological advances are helping to reduce the dose from CCTA Figure 6. Incidental pulmonary nodule (arrow) discovered on CT calcium scoring 3. Pletcher MJ, Tice JA, Pignone M, Browner WS. Using the coronary artery calcium score to predict coronary heart disease events: a systematic review and meta-analysis. Arch Intern Med 2004;164:1285 92. 4. National Institute for Health and Clinical Excellence. Chest pain of recent onset: assessment and diagnosis of recent onset chest pain or discomfort of suspected cardiac origin. Clinical Guideline 95. London: NICE, 2010. 5. Nance JW, Jr, Bamberg F, Schoepf UJ, et al. Coronary atherosclerosis in African American and white patients with acute chest pain: characterization with coronary CT angiography. Radiology 2011;260:373 80. 6. Mowatt G, Cook JA, Hillis GS, et al. 64-Slice computed tomography angiography in the diagnosis and assessment of coronary artery disease: systematic review and meta-analysis. Heart 2008;94:1386 93. 7. Taylor AJ, Cerqueira M, Hodgson JM, et al. ACCF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/S CMR 2010 appropriate use criteria for cardiac computed tomography. A report of the American College of Cardiology Foundation 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. 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