The main triggering factor for onset of acute coronary syndromes (ACS) following a prolonged period of coronary atherosclerosis is the rupture of an atherosclerotic coronary plaque followed by localised coronary thrombosis and/or spasm.1 The major factors that predispose the rupture of a vulnerable plaque are a relatively large lipid core, a thin cap and an accumulated macrophage content. None of these determinants of plaque rupture is related to each other or to the severity of luminal stenosis.1 Plaque rupture typically occurs at milder stenoses with 40–60% diameter narrowing or less.2–6 These mild stenoses generally do not give rise to symptoms or ischaemia on treadmill testing.7–9
The degree of stenosis in focal plaque segments on coronary angiograms does not correlate with the risk of plaque rupture. Plaques that have developed more recently are lipid-laden, cause minor luminal narrowing and are more likely to rupture than older, hardened plaques with more severe luminal narrowing.10–12 Therefore, it is not surprising that 65% of stenoses associated with subsequent myocardial infarction have <50% luminal diameter narrowing and 85% have <70% diameter narrowing.2,10–12
Conventionally, non-invasive methods for the detection of coronary disease using stress treadmill testing, stress echocardiography and myocardial perfusion scans provide indirect means of diagnosing significant coronary disease where the coronary luminal diameter narrowing is >70%. They are unable to detect the vulnerable plaques that do not cause any significant functional stenoses but that account for the large numbers of patients who eventually develop ACS. Coronary computed tomography angiography (CCTA) is one of the newest modalities of coronary artery imaging and is having a major impact on the assessment of coronary artery disease.
CCTA is performed by imaging the coronary arteries with a multidetector CT (MDCT) scan. Multiple submillimetre detector elements mounted on a gantry with a subsecond gantry rotation time allow high-resolution axial images of the coronary arteries to be recorded while the patient holds his or her breath. A 16-channel MDCT scanner will have a lower volume coverage than a 64-channel MDCT scanner. Hence, the breath-holding duration for a 16 MDCT CCTA is between 20 and 25 seconds, and for a 64 MDCT CCTA it is between seven and 10 seconds.
Accuracy of Coronary Computed Tomography Angiography
With such a wide choice of non-invasive cardiac imaging modalities, it is important to assess each new modality on its own merits. CCTA must be able to demonstrate superior accuracy compared with current modalitites if it to be used routinely. Conventional non-invasive modalities for coronary artery assessment are performed to detect the likelihood of significant flow-limiting lesions, but provide no information as to the presence of vulnerable plaques and are unable to detect the presence of sub-clinical atherosclerosis that may predispose future cardiac events. The results of these tests may be influenced by gender, cardiac rhythm, inability to exercise and the number of vessels involved. Treadmill testing, stress echocardiography and myocardial perfusion scans have sensitivity/specificity/ accuracy of 68/77/73%, 85/84/87% and 89/80/89%, respectively.13
Many centres have demonstrated that CCTA has a high sensitivity and specificity for detection of coronary artery disease compared with invasive coronary angiography. In our centre, we were able to demonstrate a sensitivity of 99%, specificity of 98%, positive predictive value (PPV) of 94% and negative predictive value (NPV) of 99% for the detection of significant coronary artery stenoses.14–18 This compares very favourably with the other conventional modalities of non-invasive cardiac imaging. Hence, among the non-invasive tests CCTA has the highest specificity and sensitivity for non-invasive detection of coronary artery disease.
It is also consistent in most of the published papers that CCTA has a high NPV.14–18 The PPV of CCTA varies from centre to centre as different protocols and post-processing methods are used. Initially, there is a tendency towards overdiagnosis, as there is a learning curve for CCTA. However, with proper patient preparation, experience, optimal protocols and appropriate post-processing techniques, a high PPV is achievable.18
Comparison with Invasive Coronary Angiography
CCTA is increasingly being compared with invasive coronary angiography (ICA). Unlike CCTA, which is able to provide a 3D image of the coronary vessel, including the vessel wall and the presence of plaque, ICA is a ‘lumenography’, demonstrating only the lumen of the coronary artery without visualisation of the vessel wall or plaque.
The presence of a plaque in a coronary artery segment is inferred from the narrowing of that segment relative to a wider adjacent segment. Hence, plaques not visualised by ICA can be visualised by CCTA. A ‘normal’ angiogram by ICA assessment may be abnormal on CCTA as some of the plaques may not cause an obvious reduction in the lumen size. This is usually seen in bifurcation plaques or diffuse plaques.
The limitation of ICA as a lumenography is particularly apparent in diffuse coronary artery disease. Intravascular ultrasound (IVUS) has been able to demonstrate the presence of diffuse extensive coronary atherosclerosis in the absence of vessel stenoses on angiography.19–26 Compared with IVUS of the coronary arteries, the sensitivity of ICA for the diagnosis of diffuse coronary artery disease ranges from 7 to 43%, with a specificity of 95%.23,27–29 In addition, the diagnostic errors in visually interpreted coronary arteriograms, where vessel diameter narrowing is visually estimated, are well documented.30,31 Even cardiologists with extensive experience in coronary angiography commonly overestimate the severity of diameter narrowing by 30–60%.30 Hence, visual assessments of coronary angiograms severely underestimate mild or diffuse coronary artery disease and overestimate the severity of plaques that have >50% diameter stenosis. Therefore, ICA as the ‘gold standard’ for coronary artery disease has several limitations.
CCTA holds much potential as a highly accurate modality for assessment of coronary artery disease. Unlike ICA, which provides 2D imaging and is essentially a lumenography, CCTA provides 3D imaging and is able to visualise the coronary plaques and other cardiac structures. In addition, CCTA also has the advantages of being non-invasive, less costly and an outpatient procedure. In contrast to the known stroke and myocardial infarction risks of ICA, in the first 3,000 CCTAs performed in our centre there was no myocardial infarction, no stroke and no mortality risks.
However, CCTA has certain interpretative pitfalls resulting from artifacts. The artifacts may be due to respiratory (poor breath holding) or cardiac motion (e.g. sinus tachycardia, irregular rhythm), beam-hardening effects (caused by the presence of severe calcification, metallic stents or pacing wires), contrast-related artifacts (produced by the filling of adjacent chambers and coronary venous vessels) and post-processing artifacts (a common cause of overestimation of luminal stenosis is due to ‘partial volume effect’ during post-processing). In experienced centres using the 64-slice MDCT, CCTA may be comparable to ICA in terms of sensitivity and specificity for the detection of significant coronary artery disease for the large majority of patients, and is increasingly being used as the non-invasive tool of choice.18
Safety of Coronary Computed Tomography Angiography
The main risks of CCTA relate to the use of iodine-based contrast agents and potential risks arising from radiation exposure during the scan. Contrast risks are low. Post-marketing surveillance of one particular contrast agent, Ultravist (data from Schering), showed that there were 14 serious adverse drug reactions in 75,000 patients (<0.02%). Contrast risks are minimal and comparable for both CCTA and ICA for native coronary angiography. In the case of ICA of bypass grafts, the contrast load will be significantly higher compared with CCTA of bypass grafts. With the 64-slice MDCT, CCTA can be performed with as little as 50cc of iodinated contrast. The precautions to be taken for those with renal insufficiency are the same as in any examination that requires contrast agents. Most adverse contrast reactions present with rash, and in rare cases anaphylaxis can occur. In our centre’s experience, for our first 3,000 CCTA examinations there was only one case where adrenaline had to be given as a result of anaphylaxis. The patient did not go into shock and did not require hospitalisation.
The other main risk of CCTA is the risk of radiation exposure. In understanding the potential risks of radiation, it is important to understand the terminology. The term ‘radiation exposure’, which quantifies the ionisation in the air produced by X-ray photons, does not equate with the term ‘radiation dose’, which quantifies the amount of radiation absorbed by the patient’s body as a result of exposure to X-rays. Radiation dose assessment is important for decisions on the risk–benefit value of the CT examination and assessment of the effectiveness of measures for minimisation of radiation during CCTA. The fundamental radiation dose parameter in CT is the CT dose index (DI), which is a measured parameter.32 The effective dose (ED) is the main parameter that is used to compare the potential biological risk of X-ray examinations. It is commonly used to compare the different absorbed radiation doses and radiation risks of different X-ray examinations.33 Unlike the CTDI, which is a measured parameter, the ED is derived from the CTDI. The international system of units (SI) unit for measurement of ED is the sievert (Sv) or millisievert (mSv). The ED is calculated from the relative weighted radiation risks of each specific organ.33–35
Reduction in radiation dose during CCTA has been made possible using two different methods. The first method utilises the fact that, due to the elliptical axial section of the human body, the attenuation of the X-ray is less if the X-ray beam traverses in an anterior–posterior (AP) direction as opposed to a lateral direction.
Hence, less X-ray energy is required to produce a comparable image in an AP direction compared with an X-ray source in a lateral direction.36,37 The second method involves the optimisation of radiation exposure by electrocardiogram (ECG)-controlled tube current modulation during periods of the cardiac cycle where cardiac motion artifact is minimised (ventricular diastole).38–40 Reduction of the tube current output in systole when the likelihood of cardiac motion artifact is higher can result in dose reductions of 45–48%, depending on the patient’s heart rate.38
Many studies have been performed to analyse the radiation dose of CCTA. Some of the earlier studies had shown that the radiation dose from MDCT is approximately 4–7mSv and is comparable to that from uncomplicated conventional coronary angiography.40–43 In a study where the ICA was performed by different cardiologists, the average dose varied from 3.1mSv to 8.6mSv.44 In a more recent study, continuous scanning with the newer 64-slice CT scanner without using ECG-controlled tube current modulation resulted in an ED of 13.4mSv for men and 18.9mSv for women. With dose modulation, the ED was reduced to 7.45–8mSv for men and 10.25–11.3mSv for women. This study assumed an effective mAs of 880.16 In our centre, using the 64-slice CT scanner the tube current for CCTA studies is routinely set between 500 and 600mAs.
The increased radiation risk of CCTA is offset by the increased morbidity and mortality risks of ICA. In one prospective study that investigated the risk of stroke embolisation following ICA, asymptomatic new cerebral infarction detected using magnetic resonance imaging (MRI) following left cardiac catheterisation occurred in 15% of patients.45 Hence, invasive cardiac catheterisation carries a significant risk of embolic stroke – mainly ‘silent stroke’.
ICA carries a non-radiogenic risk of mortality of 0.11%, a major complication risk (excluding contrast reaction) of 1.3%, a radiogenic risk of mortality of 0.02%, an overall mortality risk of 0.13% (nearly two-fold higher than that of CCTA) and a major complication risk of 1.3%.46,47 These risks do not include contrast reactions and silent strokes. In comparison, CCTA carries no non-radiogenic risk of mortality and no major complication risk, and the radiogenic risk of mortality is 0.07%.47
Hence, with proper optimisation of the protocols and settings, the radiation risk of CCTA can be minimised and the overall mortality and morbidity risks of CCTA are favourably weighted towards CCTA compared with ICA. The main risk of CCTA is the radiation risk, and radiation protection of patients is necessary. Radiation protection of patients means that the justification for the radiological procedure is based on the premise that the potential benefit for the patient outweighs the potential risk of radiation. It also means that the ED for each procedure is calculated to assess the risk–benefit value of the CT examination and the effectiveness of the protocols and settings in minimising radiation risks.
CCTA can provide 3D visualisation of the coronary vessel wall structure, heart muscle, valves, pericardium and even ventricular contractility function. It has a higher sensitivity and specificity for the detection of coronary artery disease compared with conventional non-invasive tests. Its main disadvantage is its potential radiation risk. However, this is balanced by it being the only non-invasive cardiac imaging modality that is able to detect the sub-clinical plaques that may predispose to myocardial infarction and its ability to provide plaque characterisation. Hence, it can potentially play a role in the risk stratification of patients with cardiovascular risk factors and provide physicians with added information on treatment decisions.
In contrast to ICA, which visualises only the lumen of coronary arteries, CCTA holds the potential for a comprehensive examination of the heart using one single examination technique. In addition, it can provide information on plaque distribution and characteristics that cannot be obtained by ICA. The examination is easily reproducible and objective and has a very high NPV. In high-volume experienced centres, a high PPV is also attainable. CCTA may potentially provide an alternative for patients who have met the contraindications for ICA. In our centre, CCTA has replaced ICA as the investigation of choice for patients who are thought to have coronary artery disease. However, in some patients the presence of severe calcification can present significant diagnostic challenges. As technology advances, MDCT imaging of the coronary arteries will become more widely used and will grow in importance as a diagnostic tool for the management of coronary artery disease.