Our study finds that the use of PET/CT adds further diagnostic information to classical DC in patients with suspected IE, particularly those with prosthetic valves and intracardiac devices. This may have a significant effect on the choice of an appropriate strategy and therefore impacts IE-related morbidity and mortality.
Infective endocarditis is more common now than in the past, with its incidence increasing from 9.3 per 100 000 population in 1998 to 15 per 100 000 in 2011(9). Partially this is due to health care–associated disease (10). In a large multicenter, multinational study, health care–associated infective endocarditis accounted for 34% of cases (11). Hemodialysis, non–hemodialysis intravascular catheters, and invasive procedures are often associated with the infection (12). Furthermore, the proportion of cases related with prosthetic valves and implantable cardiac devices is increasing(9). Despite major advances in diagnostic and therapeutic procedures, the prognosis is poor with a 1-year mortality approaching 30% and high complication rates at long term(1)(13).
Patients with intracardiac devices or prosthetic valves are challenging IE population because of frequent atypical presentation, different epidemiological profile (more prevalence of MRSA, fungi and multirresistent agents), and higher incidence of perivalvular extension and complications and increased mortality. The traditional modified Duke criteria are difficult to use in these patients due to the challenging interpretation of lesions on echocardiography and a negative study did not exclude the diagnosis. several cases of suspected IE are left without a conclusive diagnosis (2). The scenario is even more problematic in case of suspected ICEDs infection, in which patients frequently present with nonspecific clinical manifestations and both TT and TOE were limited in evaluation of cardiac right chambers.. Intracardiac echo was recently found to be feasible and effective and showed superior sensitivity for detection of vegetations in cardiac devices. However a complete normal echocardiographic examination does not rule out (14). Consequently, these patients may be recurrently hospitalized for an inflammatory/infectious disorder of unknown origin despite detailed investigations.
According ESC guidelines, complete hardware removal should be considered on the basis of occult infection, however in the absence of proven lead infection, further clinical management including the removal of the system is frequently postponed which can result in recurrences and significant mobility and mortality (3)(15).
The 2015 ESC Guidelines on Endocarditis recommend using additional imaging modalities when echocardiography and blood cultures are inconclusive (i.e. result in a ‘possible’ diagnosis of endocarditis, or a ‘rejected’ diagnosis with persisting high suspicion). Three techniques may be employed: CTA to depict perivalvular complications, cerebral magnetic resonance imaging (MRI), and/or whole-body SPECT/CT or PET/ CT to evaluate the presence of abnormal metabolic activity around the prosthetic valve and exclude embolic events (16).
In a cohort of patients with suspected IE referred to PET/CT in a tertiary care hospital the its diagnostic performance was evaluated. Comparing with modified DC the use of PET increased significatively the specificity for the diagnosis of IE from 33 to 98% in NVE and from 15.8 to 94.5% in PVE with similar sensitivity. In a metanalysis, Maryam Mahmood et al including 13 studies involving 573 patients showed, a pooled sensitivity of PET/CT for diagnosis of IE of 76.8% and the pooled specificity was 77.9%. Diagnostic accuracy was improved for PVE with sensitivity of 80.5% and specificity of 73.1% (17). However, some of these studies included initially rejected patients by modified Duke criteria, probably making less cost-effective the indication of 18F-FDG PET/CT in suspected IE (6). Our study did not include initially rejected IE patients by modified Duke criteria showing a high specificity in all the indications in which 18F-FDG PET/CT was performed. Furthermore, the results of this study indicate that substantial benefits can be obtained by including PET/CT in the diagnostic workup of patients with both native and with prosthetic valves/ intracardiac devices suspected IE.
No distinction between biological and mechanical prosthetic valves was made in our study. Roque et al., in a study evaluating metabolic patterns of captation after surgery, no differences between biological or mechanical prothesis were found(18). Evidence of its use in patients suspected of transcatheter-replaced aortic valves (TAVR) endocarditis is still limited to case reports, but the exponential growing rates of TAVR implantation in last years coupled with its implantion in older population with several comorbilities, increasing rates of TAVR endocarditis were expected. In our cohort, 2 patients had TAVR endocarditis suspicion and 1 patient had a previous “mitraclip” implantation. In all cases, PET-FDG excluded the diagnosis.
The 4 false-negative cases, in our study, could be due previous antibiotherapy before PET/CT; and presence of small lesions below the metabolic/spatial resolution of PET/CT. In fact, both false negative and false positive results have been reported in previous studies. False negative results might be due to prior administration of antimicrobial therapy, small size of vegetations, and elevated blood glucose concentration. False positive results might be a result of recent cardiac procedures and inadequate patient preparation(19).
Even when criteria for definitive IE category diagnosis was established by use Modified Duke criteria, there are other valid reasons to consider both PET/CT which include: evaluation of involvement of other valves or cardiac implanted electronic devices, identification of port of entry, identification of other foci of infection or other cause for clinical picture, all of which may change the treatment strategy(1). The presence of septic emboli is crucial for the correct management of patients with IE. Asymptomatic metastatic foci is present has been identified in up 20–50% of patients, mainly spleen (15),(20),(21). Failure to identify metastatic infection complications may lead to early interruption of therapy, thus potentially triggering relapse and an unfavorable outcome (22). In our cohort, PET/CT identified cases of clinically unsuspected septic embolism and clinical important extracardiac findings. It also provided an alternative or additional diagnosis in more than half of the negative cases, including 13 cases of neoplasm previous unknown.