CT imaging techniques
Introduction
In patients presenting with heart failure (HF), assessment of underlying aetiology is critical for optimal management. To differentiate between ischaemic and nonischaemic dilated cardiomyopathy, invasive coronary angiography is frequently performed. This technique is currently still considered the gold standard in the detection of coronary artery disease (CAD). In addition to accurate assessment of the presence, location, and severity of coronary artery lesions, the technique also provides the opportunity for direct intervention. On the other hand, the technique carries a small but not negligible risk of complications, while in many patients no clinically relevant abnormalities will be observed. Patients presenting with unexplained dilated cardiomyopathy and a low to intermediate likelihood of CAD may therefore benefit from a noninvasive imaging approach.
To this end, anatomical imaging with CT techniques has been proposed. With this technology, high-resolution images of the coronary arteries are obtained. In addition, detailed information on cardiac structures, and to some extent also function, can be derived. The aim of the current chapter is to provide an overview of the various applications of CT technology that may be relevant in the setting of HF.
CT techniques
Two CT-based modalities have been used for noninvasive anatomical cardiac imaging: electron beam CT (EBCT) and multidetector row CT (MDCT). Both techniques allow assessment of coronary calcifications and, during the administration of contrast, noninvasive coronary angiography. Developments have been particularly rapid for MDCT; in combination with its widespread availability this technique has become the most commonly CT technique in clinical practice.
During MDCT a gantry containing an X-ray tube and a detector system rotates around the patient to acquire multiple images during a single rotation. While initial systems allowed acquisition of 4 slices per rotation, current systems consist of up to 320 detector rows with submillimetre slice thickness. In addition, temporal resolution has been improved by faster rotation times as well as the introduction of dual-source CT systems. Nevertheless, most systems still require a low and stable heart rate to obtain good image quality, and β-blocking medication is frequently administered prior to MDCT imaging for this purpose.
During the administration of a bolus of iodinated contrast agent, a three-dimensional dataset of the entire heart is obtained within a single breath-hold of less than 10 s. Data acquisition is synchronized to the ECG to allow reconstruction of motion-free images. At present, several acquisition techniques are available, which are specified in Table 22.1. During ECG-gated spiral acquisition, the patient is moved continuously through the gantry at a slow speed while images are continuously acquired. This approach allows retrospective reconstruction of high-resolution datasets at any desired interval of the cardiac cycle. To reduce radiation exposure, dose modulation can be applied.1 During dose modulation, the tube current is lowered during the phases that are expected not to be used for reconstruction of the coronary arteries. Although the images during these phases contain more noise and are of lower image quality, evaluation of noncoronary structures remains possible. More recently, prospective ECG-triggered, sequential scanning is increasingly applied.1,2 Rather than continuous rotation of the X-ray tube, data acquisition is triggered by the ECG at a preselected phase. The patient is moved to the next position between successive acquisitions. Since imaging is performed during a small proportion of the cardiac cycle, considerable reduction has been achieved using this scanning mode. Heart rate needs to be stable and slow, however, as no other phases can be reconstructed retrospectively.
Table 22.1 Acquisition protocols for noninvasive coronary angiography with MDCT
ECG | Table | LV function | Radiation dose | |
|---|---|---|---|---|
Retrospective ECG gating | Continuous movement | Yes | High | |
ECG-correlated tube modulation | Continuous movement | Yes | Moderate | |
Prospective ECG, triggering | Sequential movement | No | Low |
Diagnosis of coronary artery disease
Coronary calcium scoring
The presence of calcium in the coronary arteries is an accurate marker for CAD, as coronary calcifications occur exclusively in the presence of atherosclerosis. Moreover, coronary calcifications have high X-ray attenuation values, and are therefore easily recognized during CT imaging without contrast. Initially, data concerning coronary calcium have been obtained with EBCT. More recently, however, MDCT has become the most commonly applied technique for this purpose. An example of a patient with coronary calcium detected on MDCT is shown in Fig. 22.1. The traditional method to quantify coronary calcifications is the Agatston score.3 Using this method, a score that can vary from 0 to over 1000 is obtained, thereby providing an estimate of the total atherosclerotic burden in the coronary arteries. Importantly, the absence of any calcium implies a very low likelihood of clinically relevant CAD. Extensive coronary calcifications on the other hand have been demonstrated to be strongly related with a higher likelihood of significant stenoses. Presumably, coronary calcium scoring may therefore allow rapid differentiation between ischaemic and nonischaemic aetiology in patients presenting with HF of unknown origin. This concept was investigated by Budoff et al.4 in a cohort of 125 patients with reduced left ventricular ejection fraction (LVEF) and known coronary anatomy based on previous invasive coronary angiography. Coronary calcium scores as determined by EBCT were significantly higher in the 72 patients with ischaemic cardiomyopathy than in the 53 patients with nonischaemic cardiomyopathy (798 ± 899 vs 17 ± 51). Moreover, based on the presence of any calcium, 71 of 72 patients with ischaemic cardiomyopathy (sensitivity 99%) were correctly identified. However, the specificity of a calcium score of 0 was lower (83%) as a positive calcium score frequently occurred in the absence of significant stenosis. Indeed, despite the close correlation between the Agatston score and total atherosclerotic burden, a drawback remains the fact that the technique does not permit direct evaluation of the stenosis severity. High coronary calcium scores reflecting extensive calcifications can be observed in the absence of any luminal narrowing, whereas severe stenosis can be present at sites with minimal calcium. Accordingly, using a low calcium score to define a positive study will result in high sensitivity but low specificity for the presence of a significant stenosis. As illustrated in Table 22.2, specificity will improve when a higher threshold is used, but at the cost of sensitivity. Nonetheless, despite this limitation, coronary calcium scoring may represent a practical initial screening approach to determine whether an ischaemic origin is likely or not, thereby allowing more appropriate selection of further (invasive) evaluation. Interestingly, further research by the same investigators has suggested that coronary calcium scoring may be even a more accurate technique to distinguish ischaemic from nonischaemic cardiomyopathy than nuclear stress testing or resting echocardiography,5,6 although evidently more data are needed.
Table 22.2 Diagnostic accuracy of different EBCT coronary calcium scores to differentiate ischaemic and nonischaemic cardiomyopathy
Threshold value | Sensitivity (%) | Specificity (%) | PPV (%) | NPV (%) | Accuracy (%) |
|---|---|---|---|---|---|
〉0 | 99 | 83 | 89 | 98 | 92 |
≥50 | 92 | 91 | 93 | 89 | 97 |
≥80 | 90 | 92 | 94 | 88 | 97 |
≥220 | 72 | 100 | 100 | 73 | 84 |
NPV: negative predictive value, PPV: positive predictive value.
From Budoff MJ, Shavelle DM, Lamont DH, et al. Usefulness of electron beam computed tomography scanning for distinguishing ischemic from nonischemic cardiomyopathy. J Am Coll Cardiol 1998;32(5):1173–8, with permission.
Noninvasive coronary angiography
As compared to coronary calcium scoring, contrast-enhanced noninvasive coronary angiography has several important advantages, including assessment of stenosis severity as well as the detection of noncalcified plaque in addition to calcified lesions. Accordingly, the technique may provide a more detailed assessment of the presence and severity of CAD, and thus facilitate rapid diagnosis. To evaluate the presence of significant (≥50% coronary lumen reduction) stenosis on MDCT, dedicated workstations are typically used. These workstations allow in addition to manual scrolling through the axial images, interactive manipulation of the dataset, including processing of three-dimensional reconstructions, curved multiplanar reformats, and maximum intensity projections. A clinical example of a patient presenting with HF and evaluated by MDCT coronary angiography is shown in Fig. 22.2.
In the general population, the diagnostic accuracy of MDCT to detect significant stenosis has been studied extensively against invasive coronary angiography. Using 64-slice MDCT, which is currently the most frequently used system, sensitivities and specificities exceeding 90% have been reported.7 Moreover, negative predictive values are particularly high, indicating that the likelihood of CAD is very low for a normal MDCT angiogram. For this reason, MDCT may be an attractive tool to exclude significant CAD and thus avoid invasive coronary angiography in patients with a low to intermediate likelihood of having significant stenosis.8
However, particularly in the presence of extensive calcifications or motion artefacts, detected lesions are frequently overestimated on MDCT. As a result, somewhat lower positive predictive values have been reported. Although quantitative approaches that may improve accuracy are currently under development, these algorithms have not yet been fully validated. In addition, the information obtained by MDCT is restricted to anatomy and no information on the presence and extent of ischaemia is obtained. Indeed, the technique cannot differentiate between lesions that are haemodynamically relevant and those that are not. In many cases with abnormal findings on MDCT, additional evaluation is still needed to obtain a definite diagnosis and determine further management. As a result, the value of noninvasive coronary angiography with MDCT is limited in patients with a high clinical suspicion of having significant CAD. In these patients, direct evaluation with invasive coronary angiography remains preferable.
At present only limited studies have been performed dedicated to patients with HF. Andreini et al.9 studied 61 consecutive patients admitted with HF of unknown aetiology using 16-slice MDCT. For comparative purposes, 139 patients undergoing invasive coronary angiography for other clinical indications were also investigated with MDCT. Overall, the technical success rate of the procedure was 97%. Importantly, MDCT allowed correct classification of ischaemic versus nonischaemic cardiomyopathy in all patients. Also on a segmental level, diagnostic accuracy in HF patients was high with a sensitivity and specificity of respectively 99% and 96%. Interestingly, sensitivity and negative predictive values were higher in the HF population than in the control population, probably because of the lower prevalence of CAD in this population (27.8% in the HF group vs 70.5% in the control group). In addition, it is likely that the reduced cardiac and coronary motion in HF may also have had a favourable effect on image quality and diagnostic accuracy.
Similar findings were recently reported using 64-slice MDCT.10 In this study by Ghostine et al.,10 all patients with significant stenoses (diameter reduction ≥50%) in two or more vessels were classified as having ischaemic cardiomyopathy. However, by definition, patients with single-vessel disease were only classified as having ischaemic cardiomyopathy in the presence of left main or proximal left anterior descending coronary artery stenosis. Using these criteria, MDCT correctly identified 60 of 62 (97%) patients without and 28 of 31 (90%) with ischaemic origin of HF. Although the impact on the patient-based analysis was minimal, the presence of extensive calcifications was identified as a major cause of reduced image quality and incorrect diagnosis on segmental level. In this regard, a stepwise approach incorporating coronary calcium scoring and noninvasive coronary angiography, as proposed by Cornily et al.,11 may be particularly attractive. In their algorithm, coronary evaluation consisted of initial coronary calcium scoring followed by noninvasive coronary angiography in selected cases. Patients with a coronary calcium score of 1000 or higher were referred directly to invasive coronary angiography, based on the rationale not only that the performance of MDCT coronary angiography will be lower but also that many patients will have abnormal studies requiring further evaluation anyway. In the majority of patients, however, coronary calcium scores of less than 1000 were obtained. In these patients, MDCT was shown to accurately rule out CAD as the underlying cause of HF and thus avoid invasive coronary angiography in 21 of 27 (78%) patients. Although larger cohort studies are awaited, recently published guidelines for the diagnosis and treatment of patients with HF indicate that MDCT may indeed be considered to rule out underlying CAD noninvasively in patients with low to intermediate likelihood of significant CAD.12
Left ventricular dimensions and function
In addition to the coronary arteries, MDCT can also provide detailed information on chamber morphology and function. Importantly, datasets can be reformatted in any desired plane and, depending on the acquisition technique (see Table 22.1), reconstructed at multiple phases of the cardiac cycle. Typically, to assess left ventricular volumes and function, datasets are reformatted in the short- and long-axis orientation, as illustrated in Fig. 22.3. Subsequently, end-systolic and end-diastolic phases are determined by selecting the smallest and largest cross-sectional left ventricular cavity areas. The high contrast between the left ventricular cavity and the myocardium has facilitated the development of dedicated software algorithms that automatically detect endo- and epicardial borders. Consequently, end-diastolic and end-systolic volumes are derived to obtain LVEF.
Numerous studies have shown excellent correlations between MDCT and other imaging methods.13–15 Overall, because its temporal resolution is inferior to that of two-dimensional echocardiography and MRI, a tendency of MDCT to overestimate end-systolic volume and thus slightly underestimate LVEF has been observed. Nevertheless, Yamamuro et al.13 demonstrated that measurements between MDCT and MRI (the current gold standard for left ventricular function) were more closely related than measurements between two-dimensional echocardiography and MRI, suggesting that MDCT may be even more accurate than two-dimensional echocardiography in the evaluation of left ventricular function.
Displaying the images in ciné-loop format allows evaluation of segmental wall motion in addition to global function. Comparisons against two-dimensional echocardiography and MRI have revealed high accuracy of MDCT in identifying regional wall motion abnormalities. Amongst others, Mahnken et al.16 observed an agreement of 86% between 16-slice MDCT and MRI. Moreover, using newer 64-slice MDCT technology, Henneman et al.15 showed that 96% of segments were scored identically on 64-slice MDCT and two-dimensional echocardiography (κ = 0.82). Although patients with reduced left ventricular function were included in these investigations, only few studies have specifically focused on patients with HF. Butler et al.17 studied 25 patients with an LVEF of less than 45% who underwent both two-dimensional echocardiography and MDCT. In this cohort with reduced LVEF (average 36 ± 8% on two-dimensional echocardiography), MDCT was shown to provide comparable results to two-dimensional echocardiography for both global and regional function.
Although MDCT may allow reliable assessment of left ventricular function, routine use of MDCT for the sole purpose of functional assessment is not recommended considering the radiation and contrast risks involved. Indeed, echocardiography and MRI remain the preferred techniques, and MDCT is considered only in patients with either suboptimal images during echocardiography or contraindications for MRI. In general, therefore, MDCT function analysis is usually only performed in conjunction with MDCT imaging for other purposes such as noninvasive coronary angiography.
Myocardial infarction
A growing body of literature indicates that MDCT may allow assessment of the presence and extent of myocardial infarction. End-diastolic wall thickness can easily be determined on MDCT, and the presence of end-diastolic wall thickness of less than 6 mm has been shown to correlate with the presence of larger, transmural myocardial infarctions.18 Moreover, several investigations have confirmed that the observation of myocardial hypoenhancement reflects scar tissue. This concept, which dates back to experimental animal studies in the 1970s, is based on the kinetics of the contrast agent used for MDCT. As in MRI, MDCT imaging is performed during the administration of a bolus of contrast agent, reflecting first-pass perfusion. In both chronic and acute settings, the presence of hypoperfused areas on MDCT has been shown to correlate with triphenyltetrazolium chloride (TTC) staining as well as with the traditionally used imaging modalities. In a porcine model, Mahnken et al.19 showed that hypoenhanced areas visualized by MDCT were strongly correlated to areas of myocardial necrosis on TTC staining and delayed enhancement MRI, although the mean size of infarction was slightly larger on MDCT (19.3 ± 4.5% of the left ventricle vs 18.7 ± 5.7% and 17.2 ± 4.0% of the left ventricle with TTC and MRI, respectively). Similar findings have been reported in humans comparing MDCT to either MRI or gated single-photon emission computed tomography (SPECT).18,20,21 An example of early hypoenhancement on MDCT is shown in Fig. 22.4.
From Mahnken AH, Koos R, Katoh M, et al. Assessment of myocardial viability in reperfused acute myocardial infarction using 16-slice computed tomography in comparison to magnetic resonance imaging. J Am Coll Cardiol 2005;45(12):2042–7, with permission.
However, areas of decreased myocardial perfusion can represent either microvascular obstruction or areas of myocardial necrosis. Delayed enhancement imaging, which results in regional hyperenhancement of scar tissue similar to MRI, may possibly provide more accurate evaluation of myocardial infarction (see Fig. 22.4). Gerber et al.22 showed that a combined MDCT protocol of early hypoenhancement and delayed enhancement imaging 10 min after contrast injection allowed characterization of myocardial infarction with contrast patterns highly similar to MRI. Between MDCT and MRI, areas of early hypoenhancement and late hyperenhancement showed good agreement on segmental basis (92% and 82%, respectively). Importantly, also absolute sizes of early hypoenhanced and late hyperenhanced myocardium were highly correlated without significant differences between the two techniques. Moreover, the presence and extent of early hypoenhanced and late hyperenhanced myocardium on MDCT has been shown to accurately predict functional recovery after 3 months.23
Recently, le Polain de Waroux and colleagues24 applied a combined coronary angiography and late enhancement protocol with MDCT to determine the underlying aetiology of HF. For this purpose, 71 patients presenting with left ventricular dysfunction of unknown origin underwent comprehensive evaluation with MDCT in addition to delayed enhancement MRI and invasive coronary angiography. MDCT coronary angiography correctly identified all patients with significant CAD on invasive coronary angiography. However, in two additional patients the severity of stenosis was overestimated on MDCT because of the presence of extensive calcifications. Using the delayed enhancement images, 28 of 29 (96%) patients with either subendocardial or transmural infarction on MRI were correctly identified on MDCT. In three patients, the observation of delayed enhancement on MDCT was not confirmed on MRI, resulting in a specificity of 92%. Importantly, combination of the information on coronary arteries and delayed enhancement was shown to allow accurate classification of patients with HF of definite or probable ischaemic origin. As compared to invasive coronary angiography in combination with MRI, sensitivity and specificity of 97% and 92%, respectively, were shown for MDCT. As suggested by the authors, MDCT may become an attractive modality for comprehensive assessment of aetiology in a single, rapid examination. Additional advantages include the more widespread availability and lower costs of MDCT as compared to MRI and the fact that patients with metallic implants can be safely studied. Disadvantages, however, remain the need for potentially nephrotoxic contrast agent, radiation dose, and the at present still somewhat variable image quality.
Cardiac vein anatomy
An application that is receiving increasing interest is visualization of the cardiac veins with MDCT. In highly symptomatic HF patients with wide QRS complex and depressed left ventricular function, cardiac resynchronization therapy (CRT) has emerged as an attractive treatment option that can provide substantial symptomatic benefit and reduce mortality. However, the presence of a suitable cardiac vein is mandatory for successful transvenous implantation of the left ventricular pacing lead. In this context, MDCT may become an attractive noninvasive technique to identify the presence of a suitable vein and guide lead implantation (Fig. 22.5). Indeed, several studies have demonstrated the feasibility of MDCT for the depiction of cardiac venous anatomy.25,26 In addition, a good correlation with invasive venography has been demonstrated in patients referred for CRT implantation.27 Interestingly, a possible association between the variation in cardiac venous anatomy and the history of a myocardial infarction was identified by van de Veire et al.26 In 100 patients undergoing MDCT scanning, a left marginal vein was significantly less frequently observed in patients with a history of myocardial infarction, as compared with control patients and patients with CAD (27% vs 71% and 61%, respectively, p 〈 0.001).26 Since the lack of a left marginal vein may hamper the positioning of the left ventricular pacing lead during CRT implantation,28 preprocedural identification of patients in whom suitable branches are present is of critical importance. In this respect, MDCT may provide valuable information by noninvasively identifying patients who may be referred directly for an epicardial left ventricular lead placement using minimally invasive surgery.
Mitral valve geometry
HF patients with left ventricular systolic dysfunction (LVSD) frequently develop mitral regurgitation due to enlargement of the left ventricle leading to mitral valve annular dilatation and reduced leaflet coaptation. As the presence and severity of mitral regurgitation negatively affect prognosis, additional mitral valve surgery during coronary bypass grafting should be considered in patients with ischaemic HF and mitral regurgitation. For optimal planning of the surgical procedure, detailed information of the shape of the left ventricle, the geometry of the valve, and the severity of mitral regurgitation is needed. Echocardiography remains the preferred technique, but some aspects may be evaluated by MDCT. As recently demonstrated by Delgado and colleagues, the high spatial resolution of MDCT allows for detailed evaluation of mitral valve geometry and its interaction with the left ventricle.29 The authors showed that several variables that may be important in determining procedural strategy and success, including mitral valve annulus dimensions as well as mitral leaflet coaptation height and displacement of the papillary muscles, could be derived using this technique.
Moreover, the detailed visualization of cardiac anatomy may be of particular value in the setting of percutaneous mitral valve annuloplasty. During this procedure, the mitral annulus diameter is reduced by mean of a device inserted in the coronary sinus. The feasibility of this percutaneous procedure depends on the distance between the coronary sinus and the mitral annulus, and remodelling of the mitral annulus may be inefficient when the coronary sinus courses along the left atrial wall rather than along the mitral annulus. In addition, a course of the left circumflex coronary artery between the coronary sinus and the mitral valve annulus may be associated with risk of compression. In several investigations, MDCT has been applied to study the relation between the coronary sinus, mitral valve annulus and left circumflex, revealing a highly variable relation between these structures.30,31 Accordingly, MDCT may provide valuable information for the selection of potential candidates for percutaneous mitral annuloplasty and could identify patients in whom percutaneous transvenous mitral annuloplasty may not be feasible.
Summary and conclusion
During the past decade, the rapid technological development of MDCT has allowed noninvasive coronary angiography. Owing to its high negative predictive value, the technique is particularly accurate in ruling out (significant) CAD. Accordingly, use of MDCT coronary angiography may be a reasonable approach to visualize coronary anatomy in patients presenting with HF of unknown origin and in whom extensive CAD is not expected. In addition, the technique can provide high-resolution images of cardiac structure and function. As a consequence, MDCT may allow a comprehensive cardiac evaluation in a single examination. However, this additional information is associated with increased radiation and contrast burden; use of MDCT for the sole purpose of assessing myocardial structure and function should therefore be restricted to patients in whom other imaging modalities are not feasible.
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