<jats:bold>Background </jats:bold>The diagnosis of infective endocarditis (IE) remains a clinical challenge. Diagnostic accuracy of the modified Duke criteria is suboptimal for native valve endocarditis (NVE) and even worse in the presence of prosthetic material-related infection (PVE). We aim to evaluate the diagnostic performance of 18F-FDG PET in patients with suspected IE referred to perform PET/CT.<jats:bold>Methods: </jats:bold>Consecutive patients with suspected IE, referred to perform PET/CT between May 2016 and June 2019 were included. Diagnostic performance of modified Duke criteria (mDC) and PET/ CT for IE for NVE and PVE was determined.<jats:bold>Results:</jats:bold> In total, 82 patients (mean age of 61 ± 19 years, 62% of male gender) were enrolled. There were 67 18F-FDG PET/CT concordant results with final diagnosis, corresponding to a 96% of agreement, k=0.91(p=0.04). A SUV max cutoff value of ≥3.1 identified positive cases with 88.9% sensitivity and 70.0% specificity. In patients with NVE, the addition of PET/CT to the mDC resulted in a reduction of the number of possible IE cases (from 58% to 4.3%). In patients with PVE/intracardiac devices, PET/CT allowed reclassification of 67.4% of possible cases to 4.2%. An alternative diagnosis was provided in 55.6% of the negative IE cases.<jats:bold>Conclusions:</jats:bold>18F-FDG PET/CT proved to be a useful diagnostic tool in patients with both suspected NVE and PVE with good sensitivity and specificity, resulting in a significant decrease of the number of possible endocarditis. Furthermore, it allowed the identification of the cause of clinical scenario in more than 50% of patients in which the diagnosis was excluded.
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