Introduction
There are multiple aspects of imaging in the context of coronary artery disease. On the one hand, imaging is used to identify the presence of coronary artery stenoses, through two possible approaches. One approach is to visualize ischemia as the consequence of hemodynamically relevant coronary artery lesions. In clinical practice, this is most frequently done by stress echocardiography, stress cardiac magnetic resonance, or nuclear medicine techniques ( functional imaging ). The alternative approach is to directly visualize the coronary arteries and identify atherosclerotic lesions. Given the small dimensions and fast motion of the coronary vessels, this is technically challenging and requires a combination of high spatial resolution, high temporal resolution, and the ability to capture the entire complex course of the coronary artery tree. On the other hand, next to the mere identification of coronary artery disease, imaging fulfills other needs regarding management of patients, such as the assessment of left ventricular function or myocardial injury and viability.
Computed tomography (CT) and cardiac magnetic resonance (CMR) play an increasingly important role in the evaluation of patients with known or suspected coronary artery disease. The main application of CT in the context of chronic coronary artery disease is coronary CT angiography, that is, direct visualization of the coronary artery lumen to rule in or rule out coronary artery stenoses. Bypass grafts and stents can also be assessed but are significantly more challenging to evaluate than native coronary vessels. To some extent, CT can be used to characterize nonobstructive coronary atherosclerotic plaque. This may have applications in the context of risk stratification, but it is not yet a method with firmly established clinical applications. Other areas in which CT is used include the support of coronary interventions (in particular for chronic total coronary artery occlusions) and the identification of ischemia through myocardial perfusion imaging or simulation of the fractional flow reserve (FFR).
CMR is not used for visualization of the coronary arteries to the same extent as CT; rather, it is focused on imaging the myocardium. Late gadolinium enhancement imaging is a reliable, high-resolution technique to visualize and quantify myocardial scar and differentiate it from viable myocardial tissue, whereas stress CMR, typically after adenosine or dobutamine infusion, is an accurate method to identify myocardial ischemia.
Both methods complement each other regarding the assessment of patients with known or suspected chronic coronary artery disease. They have widespread clinical application and are firmly established in professional guidelines. Nevertheless, technical challenges exist that may impair image quality or lead to misinterpretation. Meticulous care in patient preparation and image acquisition, as well as sufficient expertise in interpretation, is therefore essential to maximize benefit to the patient.
Cardiac Computed Tomography
Imaging Protocols
Cardiac computed tomography is most frequently used to visualize the coronary artery lumen. The method is referred to as coronary CT angiography or coronary CTA . To achieve sufficient spatial and temporal resolution, high-end CT equipment and adequate imaging protocols must be used. Currently, 64-slice CT is considered the state of the art for coronary artery imaging. Newer technology, such as dual source CT or volume scanners that have wide detectors with 256 or 320 detector rows, provides further improved and more robust image quality.
Typical datasets for coronary artery visualization by CT consist of approximately 200–300 transaxial slices with a thickness of 0.5 mm to 0.75 mm ( Fig. 13.1 ). Data interpretation is based on interactive manipulation of these datasets using an image processing workstation, enhanced by post-processing tools such as maximum intensity projections and multiplanar reconstructions. Three-dimensional renderings, although impressive for visualization of the heart and coronary arteries, are not accurate for stenosis detection and play no role in data interpretation. Whereas many workstations provide prerendered reconstructions that are intended to show the coronary arteries over their entire course, readers should not rely on such automated post-processing tools alone. In fact, official recommendations mandate that the reader manipulate the original data and not rely on prerendered reconstructions of any kind.
There are some conditions for patients to be suitable for coronary CT angiography ( Box 13.1 ). Importantly, they include the ability to understand and follow breathhold commands, because even slight respiratory motion during data acquisition will cause substantial artifact. A regular and, preferably, low heart rate substantially improves image quality and reliability (optimally below 60 beats/min, even though this is not as strictly required for dual-source CT). To achieve a low heart rate, patients usually receive premedication with short-acting β-blockers, and nitrates are given to achieve coronary dilatation. For vascular enhancement during the scan, contrast agent is injected intravenously. Depending on scanner type and acquisition protocol, approximately 40 mL to 100 mL of iodinated contrast agent is used. Data acquisition can follow various principles, and the mode of data acquisition has profound implications regarding radiation exposure. Retrospectively electrocardiogram (ECG)-gated acquisition in helical mode (also called spiral mode ) provides for high and robust image quality and maximum flexibility to choose the cardiac phase during which images are reconstructed, including the ability to reconstruct functional datsasets throughout the entire cardiac cycle in order to assess wall motion (which, however, is not frequently necessary or clinically desired). Prospectively ECG-triggered axial acquisition is associated with substantially lower radiation exposure. Image quality is high, especially in patients with stable and low heart rates. Less flexibility to reconstruct data at different time instants in the cardiac cycle, as well as greater susceptibility to artifacts caused by arrhythmia, can be downsides of this acquisition mode but rarely affect individuals if they are well prepared. Overall, prospectively ECG-triggered axial acquisition is the preferred image acquisition mode in many experienced centers. Finally, prospectively ECG-triggered high-pitch helical or spiral acquisition, often referred to as flash acquisition, is an imaging mode that combines aspects of the former two techniques but can only be used on single source or dual-source CT systems with very wide detectors and only in patients with low and truly regular heart rates. It allows coverage of the volume of the heart within a very short time and maximizes efficacy of radiation use, so that it is associated with very low radiation exposure ( Fig. 13.2 ).
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Ability to follow breathhold commands and perform a breathhold of approximately 10 seconds
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Regular heart rate (sinus rhythm) < 65 beats/min, optimally < 60 beats/min
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Lack of severe obesity
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Ability to establish a sufficiently large peripheral venous access (cubital vein preferred)
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Absence of contraindications to radiation exposure and iodinated contrast media
The radiation exposure of coronary CTA (and cardiac CT in general) varies widely. When CT of the heart was first developed, use of radiation was not efficient and effective doses up to 25 mSv were not uncommon for standard acquisition protocols. With the use of improved data acquisition protocols, complemented by image reconstruction techniques that compensate for image noise, radiation exposure in the context of coronary CT angiography has been substantially reduced and typical values for effective radiation dose of contemporary CT protocols range between 1 and 5 mSv. In very strictly selected patient cohorts, it has even been reported that doses below 0.5 mSv and even below 0.1 mSv are possible, but image quality at this extreme end of the spectrum is not robust enough for routine clinical practice. Without going to the extreme and by using measures that are widely available, do not require special training, and are straightforward to implement, Chinnaiyan et al. reported a mean effective dose of 6.4 mSv across 15 centers routinely performing coronary CTA. In a 2014 multicenter trial, the average effective dose for coronary CT angiography was 3.2 mSv.
Accuracy of Coronary CT Angiography
Coronary CT angiography has high accuracy for the detection of coronary artery stenoses ( Figs. 13.3 and 13.4 ). Three multicenter trials assessed the accuracy of coronary CT angiography for the identification of coronary artery stenosis in comparison with invasive coronary angiography. Two trials performed in patients with suspected coronary artery disease using 64-slice CT have demonstrated sensitivities of 95% to 99% and specificities of 64% to 83%, as well as negative predictive values of 97% to 99% for the identification of individuals with at least one coronary artery stenosis. The positive predictive values were 64% and 86% in these two trials, which is due to a tendency to overestimate stenosis degree in coronary CTA, as well as the fact that image artifacts often result in false-positive interpretations. In a third multicenter study of 291 patients with 56% prevalence of coronary artery stenoses, as well as 20% of patients with previous myocardial infarction and 10% with prior revascularization, specificity was high (90%) and the resulting positive predictive value was 91%. However, this came at the cost of decreased sensitivity (85%) and negative predictive value (83%).
A 2016 meta-analysis summarized 30 clinical trials that evaluated the accuracy of coronary CTA performed with systems composed of 64 slices or greater in comparison with invasive angiography. A total of 3722 patients were included. The authors determined that, on average, 6.6% of studies were unevaluable. They also reported a pooled sensitivity of 95.6% and a specificity of 81.5% for systems with at least 64 detector rows. Of particular importance, the negative likelihood ratio was 0.022, rendering coronary artery stenoses extremely unlikely if coronary CTA is normal.
Accuracy values are not uniform across all patients. High heart rates, obesity, and extensive calcification negatively influence accuracy. Degraded images will lead to false-positive rather than false-negative findings. Specificity and positive predictive value will therefore be most affected. Along with patient factors that influence image quality, the accuracy of coronary CTA depends on pretest likelihood of disease. In an analysis of 254 patients referred to invasive angiography and also studied by CT, it was demonstrated that coronary CTA performs best in patients with a low to intermediate clinical likelihood of coronary artery stenoses (negative predictive value: 100% in both groups), while accuracy is substantially lower in high-risk patients ( Table 13.1 ).
| Pretest probability ∗ | n | Sensitivity | Specificity | Positive pred. value | Negative pred. value |
|---|---|---|---|---|---|
| High | 105 | 98% | 74% | 93% | 89% |
| Intermediate | 83 | 100% | 84% | 80% | 100% |
| Low | 66 | 100% | 93% | 75% | 100% |
Overall, the ability of coronary CTA to reliably rule out the presence of coronary artery stenoses and the fact that it performs best in situations of low to intermediate likelihood of disease indicate that coronary CTA is a clinically useful tool in symptomatic patients who do not have a high pretest likelihood of coronary artery disease but require further work-up to rule out significant coronary stenoses. A negative coronary CTA scan, if of high quality, will obviate the need for further testing. Indeed, several observational trials and registry reports with up to 35,000 patients clearly demonstrated that symptomatic patients, when coronary CTA is negative, have an extremely favorable clinical outcome even without further additional testing.
Randomized Clinical Outcome Trials Evaluating Coronary CTA
Two pivotal randomized clinical trials emphasize the fact that coronary CTA is a clinically useful tool that may be used for management decisions in patients with suspected chronic coronary artery disease. In the multicenter Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) trial, published in 2015, 10,003 patients with suspected coronary artery disease were randomized to either ischemia testing or coronary CTA as the initial test. After 2 years, outcome in terms of major cardiovascular adverse events or complications associated with testing was equal between the two groups. The rate of invasive coronary angiograms (12.2% vs 8.1%) and the rate of revascularizations (6.2% vs 3.2%, p < 0.001) were significantly higher if coronary CTA was used as the initial test. On the other hand, catheterization showing no obstructive lesions occurred significantly less frequently if coronary CTA had been used as the initial test (3.4% vs 4.3% of the population, p < 0.02). In summary, the trial demonstrated that there is no clinical risk to using coronary CTA as an anatomic test, as opposed to functional imaging, as a first diagnostic method in patients with suspected coronary artery disease.
The Scottish Computed Tomography of the Heart (SCOT-HEART) multicenter trial randomized 4146 patients with stable chest pain to receiving only functional testing or functional testing plus coronary CTA in the setting of suspected coronary artery disease. The additional information from coronary CTA to standard care changed planned management (15% vs 1%, p < 0.001) and treatment (23% vs 5%, p < 0.001) but did not affect 6-week symptom status ( p = 0.22) or the frequency of initial admissions ( p = 0.21) or subsequent hospital admissions for chest pain (11.9% vs 12.7%, p = 0.40) as compared to standard care alone. However, after 1.7 years of follow-up, the trial demonstrated that there was a trend toward lower event rates of fatal and nonfatal myocardial infarction by 38% ( p = 0.05) if ischemia testing was complemented by coronary CTA.
These two pivotal randomized imaging clinical outcome trials (PROMISE and SCOT-HEART) and several smaller trials demonstrated coronary CTA to have a proven role in management of patients with suspected chronic coronary artery disease. An overview of the PROMISE and SCOT-HEART trials is presented in Table 13.2 .
| Promise | Scot-Heart | |
|---|---|---|
| Patients | n = 10,003 patients | n = 4146 patients |
| Inclusion criteria |
|
|
| Methods | Functional stress testing ∗ versus coronary CTA | Usual care (ECG stress testing) versus usual care plus coronary CTA |
| Study endpoints | Death, nonfatal MI Hospitalization for unstable angina, Major procedural complications † | Certainty of diagnosis Angina due to CAD |
| Management |
| Increased preventive prescription |
| Outcome | No difference |
|
∗ Exercise treadmill, nuclear stress, or stress echocardiography.
† Major procedural complications: anaphylaxis, stroke, major bleeding, renal failure.
Imaging of Patients With Bypass Grafts and Stent
The follow-up of patients after previous revascularization is a frequent question in clinical cardiology. It needs to be taken into account that coronary CTA has relevant limitations in patients with previous coronary revascularization. Assessment of coronary artery stents ( Fig. 13.5 ) is often unreliable because the dense metal of the stents can cause artifacts that render the stent lumen unevaluable or create false-positive findings of stenosis. The ability to assess stents concerning in-stent restenosis depends on many factors. They include stent type and diameter, as well as the overall image quality. The analysis of large stents (eg, stents implanted in the left main coronary artery) may be possible by CT in most cases. In general, however, there is uncertainty about the accuracy of coronary CTA to detect and rule out in-stent stenosis. A meta-analysis reported that 20% of stents were unevaluable by CT, and sensitivity for stenosis detection was only 82% in evaluable stents. With the exception of large stents (≥ 3.0-mm diameter) in locations very amenable to CT imaging (eg, left main coronary artery), and if invasive coronary angiography is to be avoided, imaging of patients with previously implanted stents by coronary CTA should therefore not be routinely considered. Bioresorbable vascular scaffolds, on the other hand, are typically made of material that does not have the high attenuation of metal in CT imaging. No systematic evaluations have been performed, but imaging of the coronary lumen should not be impaired by these devices. CT may therefore be a useful method for the follow-up after percutaneous coronary intervention (PCI) performed with bioresorbable scaffolds ( Fig. 13.6 ).
Regarding the follow-up after bypass surgery, the accuracy of coronary CTA for the detection of bypass graft stenosis and occlusion is very high ( Fig. 13.7 ). However, assessing the native coronary arteries in patients after bypass surgery is typically difficult. The native vessels frequently have a small diameter and substantial calcification ( Fig. 13.8 ). Consequently, accuracy for detecting and ruling out stenoses in nongrafted and run-off vessels is relatively low, false-positive findings are frequent, and unevaluable segments impair the clinical utility of the test.
Coronary CTA and Ischemia
Coronary CTA, like invasive coronary angiography, is a purely morphologic imaging modality and cannot demonstrate the functional relevance of stenoses (ie, resulting ischemia). In fact, the correlation of CT results with the presence of ischemia is poor. Not surprisingly, coronary CTA is a better predictor of angiographic findings than of findings on nuclear perfusion imaging. A negative coronary CTA result is a reliable predictor to rule out the presence of coronary artery stenoses and the need for revascularization, and CT may therefore be used as a gatekeeper to avoid invasive coronary angiograms. Nevertheless, presence of a stenosis on coronary CTA does not mean that a hemodynamically relevant stenosis is present and revascularization should unconditionally be performed. Ischemia testing, whether noninvasive or as an FFR measurement in the context of invasive angiography, will typically be required before revascularization of a stenosis first detected in coronary CTA.
Several methods are under evaluation to improve the ability of coronary CTA to predict ischemia. To this effect, specific analysis methods, such as the transluminal attenuation gradient or CT-based determination of the fractional flow reserve (FFR-CT), are used. In particular, the latter receives widespread interest. Based on the anatomic CT dataset, computational fluid dynamics is applied to model the flow and resistance pattern under adenosine stress and to obtain the FFR value for all segments of the coronary artery tree ( Fig. 13.9 ). Initial publications show that FFR-CT is feasible as long as image quality is sufficient and that FFR-CT values correlate rather closely to invasively measured reference values. A large prospective cohort study (Prospective LongitudinAl Trial of FFR-CT: Outcome and Resource Impacts [PLATFORM]) including a total of 584 patients suggests that coronary CTA with FFR-CT may be an effective gatekeeper to invasive coronary angiography. In patients planned for invasive angiography as a work-up for chest pain, adding coronary CTA with FFR-CT before the planned angiogram resulted in a significantly lower rate of invasive coronary angiograms without obstructive coronary artery disease (direct angiography: 73.3% vs FFR-CT first: 12.4%, p < 0.0001). Patients were followed for 90 days, and the CT-based strategy was demonstrated to be safe, with low clinical event rates in both groups.
Imaging of Coronary Atherosclerotic Plaque
Coronary Calcification
Using cardiac CT, calcium deposits in the coronary arteries can be detected and quantified in low-radiation, nonenhanced image acquisition protocols ( Fig. 13.10 ). Tissue within the vessel wall with a CT number of 130 Hounsfield units (HU) or more is defined as calcified , and the amount of calcium is typically classified using the so-called “Agatston score,” which takes into account the area and the peak density of calcified lesions. In the general population, the coronary calcium score increases with age and, on average, is higher in men than in women. For the Agatston score, age- and gender-specific percentiles exist for various populations.
Coronary calcifications are always due to coronary atherosclerotic plaque, with the possible exception of medial coronary artery calcification seen in patients in renal failure. The amount of calcium roughly correlates to the overall plaque volume. Because coronary artery disease events are typically caused by plaque rupture and erosion, the amount of coronary calcium is associated with individual coronary artery disease risk. Coronary calcium allows for improved risk stratification in primary prevention and is more robust than other markers of risk, such as C-reactive protein or intima-media thickness. In asymptomatic individuals, the absence of coronary calcium is associated with very low (< 1% per year) risk of major cardiovascular events over the next 3 to 5 years, whereas an up to 11-fold relative risk increase of major cardiac events has been reported in asymptomatic subjects with extensive coronary calcification. Prospective large-scale studies, including the Multiethnic Study of Atherosclerosis (MESA) and the Heinz Nixdorf Recall Study, have convincingly demonstrated that coronary calcium measurement by CT has incremental prognostic information beyond assessment of traditional risk factors. The presence of coronary calcium will reclassify individuals who seem to be at low or intermediate risk based on traditional risk factors to a high-risk category, and that this may mandate more intense risk factor modification.
The correlation between calcium and stenosis is poor. Atherosclerotic lesions, and even stenosis, may be present even in the absence of calcium, especially in younger patients with recent onset of symptoms. The lack of calcium therefore does not reliably eliminate the possibility of coronary artery stenoses, particularly in young individuals and those with suspected acute coronary syndromes. Nevertheless, even substantial amounts of coronary calcium are not necessarily associated with the presence of hemodynamically relevant luminal narrowing. Frequently, very high calcium scores can be found in the absence of coronary stenoses. Therefore, the detection of coronary calcium, even in large amounts, should not prompt invasive coronary angiography in otherwise asymptomatic individuals.
In summary, the predictive value of coronary calcium concerning the occurrence of future cardiovascular disease events in asymptomatic individuals is widely accepted. A potential clinical role of coronary calcium for further risk stratification exists for individuals who are at intermediate risk as assessed by traditional risk factors. In patients at high or very low risk, coronary calcium imaging will usually not be indicated, because the result is unlikely to influence treatment decisions. Unselected screening or patient self-referral is not recommended.
Atherosclerotic Plaque in Coronary CTA
Next to the identification of stenoses, coronary CTA allows us to visualize—and, to a certain extent, to quantify and characterize—nonobstructive coronary atherosclerotic plaque ( Fig. 13.11 ). For risk stratification purposes, the analysis not only of calcified but also of noncalcified plaque components is a promising tool for refined assessment of individual event risk. In comparison to intravascular ultrasound (IVUS), accuracy for detecting noncalcified plaque has been reported to be approximately 80% to 90%, albeit in selected patients within small studies. Several trials and large registries have been able to demonstrate prognostic value of atherosclerotic lesions detected by coronary CT angiography both in symptomatic and asymptomatic individuals. In a landmark publication, Min et al. demonstrated increased overall mortality in patients with atherosclerotic lesions in more than five coronary artery segments. Ostrom et al. demonstrated increased mortality during long-term follow-up in patients with nonobstructive lesions in all three coronary arteries, or in patients who had obstructive lesions. An analysis of a clinical registry comprising more than 23,000 patients confirmed the prognostic value of coronary CTA, where the presence of coronary stenoses, but also the presence of nonobstructive plaque, was associated with an increased risk of mortality. However, the hazard ratio (HR) for nonobstructive plaque was relatively low (HR = 1.6; 95% confidence interval [CI] 1.2–2.2). Also, another analysis of the same registry was unable to demonstrate, for this mostly symptomatic patient group, an incremental prognostic value of contrast-enhanced coronary CTA over coronary calcium measurements.
