Diagnosis and evaluation of cardiac sarcoidosis with FDG PET/CT and PET/MR

Introduction: 1. Review conventional diagnostic tools in cardiac sarcoidosis (CS). 2. Discuss advantages and disadvantages of ¹⁸F-fluorodeoxyglucose (FDG)-PET/CT and PET/MR in cardiac sarcoidosis and methods of optimizing clinical utility.

Methods: Sarcoidosis is a multisystem granulomatous inflammatory disease of unknown etiology, while cardiac sarcoidosis (CS) is a rare complication arising in only 5% of the patients with sarcoidosis. However, it can be life-threatening, with the potential to cause cardiac conduction disorder, systolic dysfunction, and sudden cardiac death. To date, the gold standard for definitive diagnosis of CS is by identification of non-caseating granulomas on endomyocardial biopsy (EMB). Nonetheless, EMB is an invasive test with low sensitivity due to the heterogeneous distribution of the disease in the heart. Echocardiogram is the first-line imaging used in patients with suspected CS and arrhythmia; however, its findings are nonspecific and lack the ability to detect subtle changes in CS. Cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) is another widely used imaging in the diagnosis of CS. Although CMR has the ability to detect active lesions and advanced fibrotic lesions, it has a limitation in the relatively low specificity to distinguish between active lesions and chronic fibrotic scars and is not feasible in patients with implantable cardiac devices. According to a joint procedural position statement by the Cardiovascular and Inflammation and Infection Committees of the European Association of Nuclear Medicine, the European Association of Cardiovascular Imaging, and the American Society of Nuclear Cardiology, CMR remains the preferred imaging modality to assess suspected CS in most cases. In cases in which CMR is contraindicated or shows abnormal findings, imaging with both FDG-PET/CT and radionuclide myocardial perfusion imaging (MPI) are recommended. FDG-PET/CT may serve as first-line imaging in cases of known systemic sarcoidosis since it allows for the evaluation of multiorgan involvement in addition to CS. Positive findings on PET imaging or positive findings on both CMR LGE and MPI with negative PET findings indicate that an implantable cardioverter defibrillator may be warranted.

Results: Recent studies have demonstrated an emerging role of FDG-PET in diagnosing CS and evaluating the response to the treatment. In active sarcoid lesions, activated macrophages have high glycolytic activity, resulting in high FDG uptake. Several studies have suggested the possibility of using FDG-PET to monitor disease activity of CS during corticosteroid treatment by showing diminishing FDG uptake in the myocardium during and after therapy. Because normal myocardial tissues utilize both free fatty acids and glucose as their main source of energy, false-positive FDG uptake is possible. Therefore, methods to minimize the physiological uptake of FDG in the normal myocardium are necessary to increase the specificity of FDG-PET. At present, fasting for at least 12 hours, following a low-carbohydrate diet for one day, and pre-administration of intravenous unfractionated heparin (UFH) have shown to reduce the physiological uptake of FDG in the heart effectively. Additionally, FDG has limited ability in penetrating fibrotic areas, and these lesions can be a focus of inducing ventricular arrhythmias in patients with CS; thus, the reduction in FDG uptake in the heart during steroid therapy should be interpreted cautiously.

Conclusions: By optimizing the preparation of patients, FDG-PET is expected to facilitate early diagnosis with favorable accuracy, especially in patients with intracardiac devices. Also, the combination of FDG-PET and CMR has a promising role in cardiac sarcoidosis by assessing many revealing characteristics of the myocardium.