IJCS | Volume 33, Nº4, July and August 2020

394 pathway of glucose crossing the cellular membrane via glucose transporter (GLUT 1 and 3) and being phosphorylated by hexokinase inside the cell, where it gets trapped, and can be detected by PET imaging. 44,45 To improve the specificity in identifying pathological glucose uptake, background physiologic myocardial glucose metabolismmust be suppressed; to accomplish this, the patient needs to undergo a specific preparation including dietary manipulation with a high-fat, low‑carbohydrate diet, prolonged fasting, intravenous heparin or a combination of these approaches as described in the Joint SNMMI‑ASNC Expert Consensus Document on the Role of  18 F-FDG PET/CT in Cardiac Sarcoid Detection and Therapy Monitoring. 46 18F-FDG PET imaging is commonly performed concurrently with a PET or SPECT myocardial perfusion scan. 47 The combination of both perfusion defects and 18F-FDG uptake in multiple areas following a non‑coronary distribution makes the diagnosis more likely. Youssef et al., 48 in a meta-analysis, collected data from 164 patients and showed that PET had a pooled sensitivity of 89% and a pooled specificity of 83% in diagnosing CS. 48 A recent meta‑analysis by Kim et al., 49 had similar results, with a pooled sensitivity of 84% and a pooled specificity of 83%. The specificity increases with the correlation with extra-cardiac findings, seen in a 18F-FDG whole-body imaging, such as positive mediastinal and/or hilar lymphadenopathy. However, the presence of 18F-FDG uptake in a mismatch pattern with perfusion defect can also be seen in the presence of hibernating myocardium, and a careful differentiation must be made in patients with known ischemic cardiomyopathies. 32 It is important to keep in mind that 18F-FDG uptake is related to active inflammation within the myocardium, and the absence of uptake cannot rule out the presence of CS. 46 Indications for cardiac PET Diagnosis In the absence of histologic confirmation, PET is useful to investigate suspected CS; however, the diagnosis should not be based on PET findings alone but in combination with other methods including ECG, Holter and echocardiography. Some clinical scenarios in which cardiac PET may be useful have been previously described: 46 1) patients with histologic evidence of extra-cardiac sarcoidosis with an abnormal screening for CS, such as left bundle branch block or unexplained pathologic Q waves on ECG, regional wall motion abnormalities, wall aneurysm, basal septal thinning or LVEF </=50%, sustained or non-sustained ventricular tachycardia, LGE on MRI, unexplained palpitations or syncope; 2) patients with new onset of conduction disease, unexplained by other diagnosis, normally found in younger patients (<60 years old) with second or third degree atrioventricular block; or 3) patients with idiopathic sustained ventricular tachycardia. Monitoring response to therapy PET imaging is useful in monitoring patients who undergo immunosuppressive therapy as it has the capacity to quantify inflammatory state before and after treatment using the standardized uptake value (SUV), and therefore assess treatment response. 50 It can help in important decisions such as the duration or the intensity of the medication used and choosing the more appropriate immunosuppressive therapy. Patterns of uptake – visual interpretation 18F-FDG PET is normally acquired as a whole-body imaging and commonly uses computed tomography (CT) for attenuation-correction and anatomy correlation, and thereby has to be visualized using standard views (short-axis, sagittal and coronal views). 46 It is important to have an adequate alignment between PET and CT and to correlate the findings with the non-corrected images, in order to rule-out artifacts due to partial volume. There should also be a dedicated cardiac acquisition, normally visualized using the traditional cardiac imaging display, to compare with the perfusion imaging (PET or SPECT). Both images are generally normalized to the maximum counts per pixel of the image. The use of gated imaging can also add information such as LV volume, wall motion and systolic function. Both perfusion and 18F-FDG images should be interpreted simultaneously. A normal study should show a complete absence of 18F-FDG uptake in the myocardium and an absence of perfusion defect. 40 Another physiological or non- specific pattern is a focal and homogeneous 18F-FDG uptake in the lateral wall, without any perfusion defect. 46 Diffuse uptake is a non-specific finding and can be seen in both normal controls and patients with sarcoidosis. 40 Inflammation should be considered in the presence of focal or diffuse 18F-FDG uptake 40 ( Table 3 ). Wiefels et al. 18F-FDG PET/CT and cardiac sarcoidosis Int J Cardiovasc Sci. 2020; 33(4):389-400 Review Article

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