Comprehensive meta-analysis on [18F] FDG PET/CT and radiolabelled leukocyte SPECT–SPECT/CT imaging in infectious endocarditis and cardiovascular implantable electronic device infections

Background: The use of medical imaging has significantly increased over the past decade in all fields of medicine according to the advances in imaging technology. Cardiac infection represents an emblematic example where the use of nuclear molecular techniques is evolving as an important supplementary method for patients with suspected infection and diagnostic difficulties. Positron emission computed tomography (PET/CT) using fluor-18-fluorodeoxyglucose ([18F]FDG) and single-photon emission computed tomography (SPECT) using radiolabeled leukocyte (WBC) have been widely used in the diagnosis of infections. The aim of the present work is to provide a systematic review and meta-analysis of the published data on the use of hybrid nuclear medicine imaging [18F]FDG PET/CT and radiolabeled leukocyte SPECT in the diagnostic workup of patients with IE and CIED infection. Materials and methods: An English literature search was performed using the PubMed, Cochrane and Web of Science databases to identify articles. Studies were included if they assessed the diagnostic accuracy of [18F]FDG PET/CT and SPECT or SPECT/CT WBC in the diagnosis of possible infection, provided detailed criteria of a reference standard for diagnosis of infection, and provided sufficient data to determine sensitivity and specificity of [18F]FDG PET/CT and WBC SPECT–SPECT/CT. A first analysis was performed considering IE as endpoint and compared [18F]FDG PET/CT and WBC SPECT–SPECT/CT imaging. A second analysis considered CIED as endpoint was performed only on [18F]FDG PET imaging without a comparison with SPECT–SPECT/CT. Two additional analysis were performed, including (i) the sub-analysis of the manuscripts dealing with IE that were evaluated considering separately the ones dealing with NVE and PVE, (ii) the sub-analysis of the manuscripts for IE and CIED where patients underwent a specific preparation before undergoing [18F]FDG PET/CT scan. Results: The IE group included 14 [18F]FDG PET/CT and 3 SPECT/CT studies, while the CIED infection set comprised 13 [18F]FDG PET/CT and 1 SPECT/CT. For the subsequent sub-analysis within the group of IE studies, we included seven studies for NVE (all the ones with < 50% patients with native valve) and 11 studies for PVE (all patients with prosthetic valve or with > 50% patients with prosthetic valve). The sub-analysis, considering preparation protocols before [18F]FDG PET/CT scan, included 17 studies. [18F]FDG PET/CT had good specificity (89%) and lower sensitivity (71%), with high heterogeneity amongst studies. In the sub-analysis of 18 manuscripts dealing with NVE and PVE, sensitivity and specificity for NVE are 71 and 97%, respectively, while for PVE sensitivity and specificity were 83 and 92%. For WBC SPECT/CT, we found an overall sensitivity of 80% and specificity of 100%, even in the early post-intervention phase. When proper patients’ preparation is performed, sensitivity increased from 72 to 76% and specificity from 86 to 90%. Conclusions: [18F]FDG PET/CT and WBC SPECT/CT are useful for the diagnosis of IE and CIED infection. WBC SPECT–SPECT/CT appears to be slightly more specific than [18F]FDG PET/CT. On the other hand, [18F]FDG PET/CT has the advantage of being faster and very sensitive, with the great potential to allow an overall evaluation of the burden of the disease including clinically relevant extra-cardiac foci of infection, leading to timely and appropriate patients’ management.