Number 34, 2007
Picture my heart!

Perspectives of new imaging techniques for patients with known or suspected coronary artery disease

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Joanne D. Schuijf, Jeroen J. Bax
Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
Correspondence: Jeroen J. Bax, Department of Cardiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. Tel: +31 71 5262020; fax: +31 71 5266809; e-mail: jbax@knoware.nl

Functional imaging
The rationale underlying functional imaging is the detection of perfusion or wall motion abnormalities that occur under stress-induced conditions in patients who have physiologically relevant coronary artery lesions. Stress can be achieved using physical exercise or pharmacological stress.

Nuclear imaging: gated-single photon emission computed tomography
Myocardial perfusion imaging with single photon emission computed tomography (SPECT) (Figure 1) is the most commonly used and well documented technique in the assessment of patients with suspected or known coronary artery disease (CAD). The average sensitivity and specificity to detect significant CAD based on a pooled analysis of 79 studies in 8964 patients were found to be 86% and 74%, respectively [1]. Since the introduction of this technique in the early 1970s, the quality and accuracy of its images have improved substantially as a result of technical developments. In addition, the more recently introduced technetium tracers have enabled acquisition gated to the electrocardiogram, which has allowed simultaneous evaluation of ventricular function.

Echocardiography
In addition to SPECT, echocardiography is widely used to assess patients with suspected or known CAD, as it provides a comprehensive assessment of cardiac structure and function, while being completely non invasive and associated with little patient discomfort.
To date, studies comparing this technique and invasive coronary angiography have shown average weighted sensitivities and specificities, respectively, of 84% and 82% for exercise echocardiography (15 studies, n = 1849 patients) and 80% and 84% for dobutamine (28 studies, n = 2246 patients) [5].
Known disadvantages of echocardiography include the limited value in detecting single-vessel disease and, in contrast to SPECT, a lack of quantitative reporting algorithms. In addition, the technique is highly dependent on the expertise of both the operator and the interpreting cardiologist. Finally, difficulties are encountered in patients who are obese or have chronic obstructive pulmonary disease, because of the lack of an acoustic window.
With the aim of improving border delineation, ultrasound contrast agents are currently under investigation. In addition to improved image quality, administration of contrast offers another advantage, namely assessment of perfusion in addition to ventricular wall contractility [6]. Pooled analyses of the available preliminary studies suggest improved sensitivity (on average 89%) at the cost of reduced specificity (63%) [7]. To some extent, however, this reduced specificity may be attributable to the fact that experience is still limited, in addition to a current lack of image standardization.

Magnetic resonance imaging
Myocardial perfusion can also be evaluated with MRI. For this purpose, short-axis slices are acquired during the first pass of contrast agent in both resting and stress conditions. Relative perfusion defects are subsequently recognized as regions with little or reduced contrast agent. A pooled analysis of 17 studies of perfusion MRI, including 502 patients, revealed a weighted mean sensitivity of 84% and a specificity of 85% to detect obstructive CAD [7]. A particular advantage of the technique is the high spatial resolution, which allows distinction between subendocardial and transmural perfusion defects. In addition, wall motion can be assessed accurately; MRI is even considered as the gold standard for the evaluation of left ventricular volumes and ejection fraction.
Using inducible wall motion abnormalities during dobutamine infusion as the hallmark for obstructive CAD, MRI was found to have average weighted sensitivity and specificity of 89% and 84%, respectively, on the basis of 10 studies obtained in 654 patients [7]. The excellent contrast and resolution are particularly beneficial for patients with poor echocardiographic windows. Unfortunately, although the technique provides safe and reliable evaluation of CAD, it is still time-consuming, and limited to highly specialized centers.

Anatomical imaging
Functional imaging provides safe and accurate assessment of the presence of clinically relevant CAD, but atherosclerosis in the absence of flow-limiting lesions can not be evaluated. Accordingly, extensive research is being undertaken with the aim of developing non invasive methods of visualization of atherosclerosis. Initially, only assessment of coronary calcifications, which can serve as a marker for the presence and extent of the atherosclerotic burden, was possible. However, it is important to realize that no direct relationship exists between the extent of calcium and the severity of stenosis, and extensive coronary calcifications can be observed in the absence of obstructive CAD [8]. As a result, the technique, although sensitive, lacks specificity and appears to be more suited for risk stratification than for detection of obstructive CAD [9].
More recently, direct non invasive coronary angiography has become possible by means of MRI, electron beam computed tomography and multislice computed tomography (MSCT). Of these techniques, MSCT appears at present to be the most robust for non invasive coronary angiography.

Multislice computed tomography
Since the introduction, in 1998, of multislice scanning using four detector rows, the technique has undergone an extremely rapid development. Currently, 64-slice scanners are commercially available, allowing the acquisition of a 4-dimensional data set in a breath-hold of less than 10 s duration. To date, 11 studies of 64-slice MSCT, in 663 patients, have been published, revealing average weighted sensitivity and specificity of 91% and 96%, respectively [10–12]. Importantly, the negative predictive value was consistently high, ranging from 92% to 100%, indicating that a normal MSCT is associated with an extremely low likelihood of CAD. Accordingly, the technique may be most valuable to rule out CAD. An example of a normal MSCT coronary angiogram is provided in Figure 2.

Integration of functional and anatomical imaging
During recent decades, the role of non invasive imaging has increased enormously. Initially, first-line evaluation of CAD was performed by means of functional imaging techniques, and the presence or absence of ischemia served as gatekeeper for invasive coronary angiography. Whereas the initial functional techniques relied on either inducible perfusion or wall motion abnormalities, continuous development of the technology has enabled more comprehensive evaluation. Both nuclear imaging and echocardiography currently allow simultaneous assessment of both perfusion and function, thus enhancing their diagnostic accuracy. Similarly, MRI allows integrated assessment of both function and perfusion in a single examination.
The recent introduction of non invasive atherosclerosis imaging techniques has generated considerable interest in visualization of preclinical atherosclerosis, which could be used for more individualized identification of patients who may benefit from further testing and treatment. Although these techniques allow accurate exclusion of CAD, the precise meaning of a positive examination is currently unclear, as the presence of ischemia cannot be determined. Indeed, preliminary studies suggest a large discrepancy between stenotic lesions on MSCT and perfusion abnormalities on SPECT, with only 50% of lesions actually resulting in ischemia [13,14].
The current expectation is thus that integrated use of both anatomical and functional modalities may be most beneficial in the evaluation of CAD, and for this purpose hybrid or dual modality imaging techniques are currently being investigated. In addition, advanced software programs that allow retrospective fusing of images from different modalities are under development. However, from a practical point of view, sequential imaging may be preferred and cost-effective. A potential strategy in these patients may be first to evaluate the presence of atherosclerosis by means of coronary calcium scoring or non invasive coronary angiography. If no coronary atherosclerosis is demonstrated, the patient may be discharged from further investigation; in contrast, if atherosclerosis is observed, additional functional evaluation is needed to assess the presence and extent of myocardial ischemia (Figure 3). Subsequently, the decision between invasive angiography (and possibly intervention) and medical therapy in combination with aggressive risk-profile modification may be based on the further evaluations. Accordingly, the combination of both anatomical and functional information may allow superior evaluation of CAD, resulting in more individualized management and potentially improved outcome. However, it is important to realize that data supporting such algorithms are currently lacking, and large studies addressing the accuracy, safety, and cost-effectiveness of integrated imaging strategies are required.

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