Cardiac imaging in patients with suspected coronary artery disease.

Cardiac imaging has contributed substantially to the understanding of CHD. It has become a cornerstone of diagnostics and management. However, the benefits of imaging must always be weighed against the costs and any risks. Essential here is the right modality for the corresponding question.

The differential diagnosis in patients with thoracic complaints is extensive, ranging from benign entities to potentially life-threatening conditions. In Switzerland, a good 3% of visits to the general practitioner are due to thoracic complaints, and one in five patients with such complaints is referred to a specialist before a diagnosis is made [1]. Since coronary artery disease (CAD), in particular, is a potentially threatening cause with corresponding morbidity and mortality, there is a great demand for efficient and non-invasive diagnostic modalities to exclude or treat it. Evidence of such. In this environment, imaging modalities in particular have developed rapidly in recent years, driven by substantial technological evolutions. However, precisely because of the increasingly frequent use of these modalities, questions also arise regarding the associated costs, the potential risks for patients, and, last but not least, the appropriate application in everyday clinical practice [2].

Imaging modalities

Stress echocardiography: stress echocardiography is based on the detection of ischemia-induced wall motion abnormalities that can be provoked with physical or pharmacological stress. With the use of dobutamine, stress echocardiography can be further used to provide an indication of myocardial viability [3]. Recent developments such as “strain imaging” and 3D echocardiography have the potential to further improve the diagnostic accuracy of stress echocardiography. The main limitation of the method is especially the dependence on the examiner and sound quality (e.g. in obesity, emphysema, funnel chest, etc.).

Cardiac CT: Cardiac CT allows an anatomic/morphologic assessment of the heart and in particular also of the coronaries, comparable to the information that invasive coronary angiography can provide. In the context of CHD, the strength of the method lies particularly in its ability to exclude CHD due to its excellent sensitivity and near-perfect negative predictive value in patients with low pretest probability. [4,5] (Fig. 1 and tab. 1). The specificity, on the other hand, is rather moderate, since CT leads to an overestimation of the degree of stenosis. The prognostic value of cardiac CT has been demonstrated in several trials and large multinational registries [6].

It is worth mentioning that the technology has made immense technological progress in recent years, which in the meantime allows acquiring high-resolution images with very low radiation exposure. The average radiation exposure is in the range of 2-5 millisieverts (mSv) [7]; in specialized centers, average values of well below 1 mSv are now routine [8]. The limitation of the method is especially the necessary patient selection. Thus, in patients with marked or absolute arrhythmias, the coronaries can be examined only to a limited extent, depending on the type of scanner. Furthermore, the usual contraindications for contrast-enhanced CT examinations apply, namely iodine allergy and severe renal insufficiency.

Single Photon Emission Computed Tomography (SPECT): Myocardial perfusion SPECT is based on the principle of perfusion-dependent tracer uptake into viable myocytes and detection of γ-radiation ultimately emitted during radionuclide decay. Today, mainly 99m-technetium-based tracers are used, such as sestamibi or tetrofosmin, as they allow better image quality at lower radiation exposure in contrast to 201-thallium (Fig. 2). The latter could be significantly reduced, especially with the introduction of modern detectors, and is in the range of 2-5 mSv [9].

Loading can be done physically or by intravenous administration of dobutamine or adenosine. Finally, perfusion deficits induced by exercise or already existing at rest allow the detection of ischemia or ischaemia. Myocardial scars and thus the detection of CHD with high diagnostic accuracy [10]. Simultaneous ECG triggering also allows for left ventricular volumes and contractility to be assessed. In contrast to other modalities, SPECT has data on its prognostic value for many tens of thousands of patients, underscoring the role of this method also for risk stratification of patients with CHD [11,12].

Positron emission tomography (PET): Like SPECT, PET examination is also based on the detection of radioactive decay. However, the methods differ fundamentally with respect to the type of radionuclides used: While radionuclides with γ-decay and relatively long half-lives (e.g., 6 h for 99m-technetium) are used, those used in myocardial perfusion PET are those with β+-decay and comparatively short half-life (e.g., 10 min for 13N-ammonia), which implies the availability of a cyclotron for their immediate on-site production; an exception is 82-rubidium, which can be produced with a generator. The resolution of PET is significantly better than that of SPECT and the attenuation correction is more robust, resulting in PET offering some of the highest diagnostic value of all imaging methods (Table 1) [13]. In addition, PET allows absolute quantification of myocardial blood flow in ml/min/g (Fig. 3), which improves detection of any balanced coronary three-vessel disease or microcirculatory dysfunction [14]. The prognostic value of myocardial perfusion imaging with PET has been demonstrated in several large studies [15–17]. The radiation exposure of a 13N-ammonia myocardial perfusion study is 1-3 mSv.

Magnetic resonance imaging (MRI): Cardiac MRI not only provides excellent information on cardiac function and morphology, but also allows qualitative information on myocardial perfusion with good diagnostic accuracy by image acquisition during application of gadolinium-containing contrast medium at rest and under pharmacological stimulation with adenosine (Fig. 4 and Table 1) [13,18]. When dobutamine is used as a stressor, additional ischemia-induced wall motion abnormalities can be detected. Finally, tissue characterization can be performed using late-gadolinium enhancement (LGE) imaging. In the context of CHD, this is particularly true for the detection of infarct scars and, conversely, for the detection of viable myocardium. Contraindications for cardiac MRI are mainly metal implants (including most of the implanted pacemakers or CRT and ICD devices), severe renal insufficiency and claustrophobia. Arrhythmias and limited cooperation in breath holding also affect image quality.

Hybrid Imaging: Hybrid imaging describes the integration and fusion of multimodal imaging with co-registration. Currently, the greatest clinical benefit is obtained by combining anatomic/morphologic and functional information, e.g., combining cardiac CT with myocardial perfusion SPECT or PET. This allows simultaneous assessment of the severity of stenoses and their hemodynamic relevance as well as visualization of the affected supply area (Fig. 5). A number of smaller studies have demonstrated the diagnostic superiority of hybrid imaging using SPECT and PET/CT over the individual modalities alone [19] as well as their prognostic value [20,21].

Differential use of methods for the diagnosis of CHD

Pretest probability and Bayes’ theorem: Sensitivity and specificity are the terms usually used to determine diagnostic accuracy. However, both are per se inadequate to describe how the accuracy of the method fares in a real clinical setting. In abstract form, Bayes’ theorem formulates in this situation how the pretest probability for a disease is related to the sensitivity resp. Specificity of a given examination method interacts. Thus, pathologic examinations are often false positive in patients with very low pretest probability, whereas normal workups are often false negative in patients with high pretest probability. In terms of imaging modalities for the evaluation of CHD, this means that their diagnostic value is highest with a moderate pretest probability of 15-85%. Among symptomatic patients, these are those with atypical angina and middle-aged female patients with typical angina (Table 13 in reference [13]). These patients should primarily undergo noninvasive imaging [13].

Comparison of modalities and recommendations: Attempts to compare the diagnostic accuracy of the different methods are limited in many cases by the different surrogate markers for ischemia of the different modalities (eg, anatomic/morphologic assessment by CT, wall motion abnormalities by stress echocardiography, and perfusion imaging by PET, SPECT, or MRI) and by the different local expertise for one modality. It is therefore not surprising that the reported values for sensitivity and specificity show a wide spread and overlap considerably in some cases (Tab. 1) . While there are individual studies that suggest a superiority of individual modalities [22,23]published, partly pooled data rather lead to the assumption that the real differences are probably smaller than assumed. [24,25]. However, there is consensus on the recommendation of the current ESC guidelines that the diagnostic accuracy of imaging is superior to that of the stress electrocardiogram and should therefore be preferred to the latter whenever available [13]. Figure 6 provides an overview of the imaging strategy recommended by the ESC for suspected CHD. It should be noted that differential imaging plays a particularly important role in this context: Table 2 is intended to provide a concluding guide here.

Take-Home Messages

Cardiac imaging has contributed substantially to our understanding of CHD and has become a cornerstone of diagnostic and
Management of CHD developed.
Current guidelines recommend noninvasive imaging in stable patients whenever local expertise is available.
At the same time, it is always important to carefully assess the benefits of imaging versus the associated costs and any risks. It is essential to choose the right modality for the appropriate problem in the right patient depending on the patient’s clinical characteristics and comorbidities as well as local expertise.

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