IJCS | Volume 33, Nº4, July and August 2020

390 lymphocytic or viral myocarditis and from tuberculosis with necrotizing granulomas. Although frequent in the lungs, sarcoidosis may affect any organ. In addition, any part of the heart can be involved, particularly the basal septum, the lateral wall, the papillary muscle and the right ventricle. In an autopsy study of post-mortem diagnosis of CS, the scar was more frequently located in the interventricular septum, posterior left ventricle, right and anterior left ventricle and lateral left ventricle (in descending order of frequency). 16 Although a positive endomyocardial biopsy (EMB) is definitive for the diagnosis of CS, its sensitivity is around 30% due to the patchy involvement of the myocardium. 17 Clinical features CS has different types of manifestations, including clinically silent form, sudden cardiac death, conduction disturbances, ventricular arrhythmias and heart failure. 5,18-21 Other rare findings can be pericardial effusion or coronary involvement. 13,22 CS is the most malignant manifestation of sarcoidosis and 25% of the deaths are related to the cardiac form. 5 The extent of left systolic dysfunction has been pointed as the most significant independent predictor of mortality. Patients with severe left ventricular (LV) dysfunction with left ventricular ejection fraction (LVEF)< 30% at the time of presentation had a 10-y survival rate >80% in Japanese studies. 23 Also, the 10-year transplantation-free cardiac survival was 83% in a large population-based cohort. 6 Diagnosis The diagnosis of sarcoidosis requires three elements: 1) compatible clinical and radiographic manifestations; 2) exclusion of other diseases that may present similarly and 3) histopathologic detection of noncaseating granulomas. Multiple criteria have been proposed for diagnosing CS but the most commonly used are those by the Japanese Ministry of Health andWelfare (JMHW), revised in 2017 24 and those by the Heart Rhythm Society (HRS) published in 2014 25 ( Tables 1 and 2 ). Their basic difference is that the revised 2006 criteria did not mandate positive biopsies (either cardiac or extracardiac) for the clinical diagnosis of CS. Due to its patchy and mid-myocardial involvement, EMB has an elevated number of false-negative and there is an ongoing debate whether positive histology is required for the diagnosis. 26 New imaging techniques – positron emission tomography (PET), cardiac magnetic resonance imaging (MRI), electrocardiography, and electroanatomic voltage mapping – can increase the sensitivity of the EMB. 27 The JMHWdefines the presence of myocardial Gallium-67 uptake, a SPECT tracer, as a major criterion, due to its high specificity (despite its low sensitivity). However, this radiotracer causes a high radiation exposure to the patient (high half-life of 78h) and has a lower resolution than the PET. Cardiac MRI, perfusion studies and echocardiography findings are considered minor criteria. Both 18F-fluorodeoxyglucose (18F-FDG) PET and Gallium-67 are diagnostic but have also the potential role for monitoring disease activity and therapy response. The A Case Control Etiology of Sarcoidosis Study (ACCESS) is a sarcoidosis organ assessment instrument that categorizes SS clinical manifestations as: a) highly probable, as at least 90% likelihood of sarcoidosis causing this manifestation; b) probable: 50-90% likelihood of sarcoidosis causing this manifestation of c) possible: <50% of likelihood of sarcoidosis causing this manifestation. This instrument was developed by expert opinion and is useful for clinicians and researchers in establishing criteria for sarcoidosis organ involvement. 28 Diagnostic imaging tools Echocardiography Traditionally, transthoracic echocardiography is the initial imaging modality in patients with suspected CS, as for all types of cardiomyopathy. LV systolic and diastolic function can be easily assessed, as well as LV geometry, volumes, right ventricular (RV) performance and myocardial thinning or thickening. Echocardiography is able to identify some of the CS diagnostic criteria such as depressed LVEF, basal thinning of the interventricular septum and structural or wall motion abnormality. It is important to know that echocardiography is very operator-dependent, and despite a high specificity and a positive predictive value up to 92%, 29 its sensitivity is reduced, and a normal study cannot rule out the presence of CS. SPECT SPECT studies with 99m-Tc-perfusion agents or 201‑Tl are other diagnostic tools to evaluate the presence of scar at rest, as microvascular compression or fibrogranulomatous replacement of the myocardium Wiefels et al. 18F-FDG PET/CT and cardiac sarcoidosis Int J Cardiovasc Sci. 2020; 33(4):389-400 Review Article