Infectious endocarditis: Improving Diagnostic Performance in Native and Prosthetic Valve Infection with 18F-FDG PET/CT

Infectious endocarditis: Improving Diagnostic Performance in Native and Prosthetic Valve Infection with 18F-FDG PET/CT | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Original article Infectious endocarditis: Improving Diagnostic Performance in Native and Prosthetic Valve Infection with 18F-FDG PET/CT Ana Vera Marinho, José Paulo Almeida, Paula Soeiro, Rodolfo Silva, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-34097/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background 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. Methods: 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. Results: 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 SUVmax 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. Conclusions: 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. Cardiac & Cardiovascular Systems infective endocarditis 18F-FDG PET/CT Modified Duke criteria native valve endocarditis prothesis valve endocarditis Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction The diagnosis of infective endocarditis (IE) is a clinical challenge, due to a myriad of nonspecific clinical presentations, involvement of different microorganisms and patient characteristics. Despite ongoing advances in both diagnostic and therapeutic procedures, IE remains associated with a poor prognosis, with an in-hospital mortality of 14–22% and 1-year mortality of 40%(1)(2). Modified Duke criteria, the cornerstone of its diagnosis, is largely based in the presence of positive blood cultures and evidence of endocardial involvement on echocardiography. However, both transthoracic (TT) and transoesophageal echocardiography (TEE) miss IE sequelae in 30% of patients, especially, when intracardiac prosthetic material is implied (3). Therefore, the sensitivity and specificity of the modified Duke criteria is, approximately, 80% for native valve endocarditis (NVE) and lower values were found for prosthetic (PVE) or implantable cardiac electronic device (ICEDs), which leads to an erroneous diagnose in several patients (1). 18F-FDG PET/CT, combining the high sensitivity of 18F-FDG PET to detect inflammation with the high spatial resolution of cardiac CT to define structural damage, is evolving as an important additional method in difficult-to-diagnose cases and is able to provide functional data on the extent of IE. The added diagnostic value of 18F-FDG PET/CT has been demonstrated in patients suspected of PVE or infections related to defibrillators, pacemakers, or ventricular assist devices(4). For extracardiac infection, 18F-FDG PET/CT detects a significant number of clinically relevant foci in patients with known or suspected NVE or PVE (1)(5). In the most recent European Society of Cardiology (ESC) guidelines, 18F-FDG PET/CT has been included in the diagnostic algorithm PVE and also in the detection of embolic events for both NVE and PVE (6)(7). We aimed to evaluate the diagnostic performance of 18F-FDG PET in a cohort of patients with suspected IE referred to PET/CT in a tertiary care hospital. Methods Study population A retrospective study was performed at a tertiary center with 18F-FDG PET/CT and included all referred patients for this exam for suspected IE between May 2016 and June 2019. The choice to perform 18F-FDG PET/CT and the IE suspicion were based on the attending endocarditis team and did not follow a standardized protocol. Clinical, laboratory and microbiological data Baseline demographic characteristics of patients, including all relevant clinical data, were collected from hospital records at hospital admission. Laboratory data included basic renal and liver function test as well as hemogram. For microbiological data, all blood cultures with respective antibiotical sensitivity testing and, when applicable, serology, were recorded. Other imaging tests data Transthoracic echocardiography was performed in all patients and transesophageal echocardiography performed in 86.3%, and recorded images and reports were analyzed. Data was extracted regarding assessments of general cardiac parameters, including cavity dimensions and ventricular function, and specific endocarditis suggestive findings such as valve function, vegetations (shape, size, and number), and periannular complications (abscess, pseudoaneurysm, perivalvular leak). PET/CT Whole-body scans and dedicated cardiac bed images were obtained in a hybrid PET/CT scanner (Discovery ST, General ElectricsÒ). A [18F] FDG myocardial uptake suppression protocol, that included a 48h high-fat and low-carbohydrate diet and a fasting period of at least 12 hours, was used to optimize image quality and diagnostic accuracy. To further improve image quality 50 IU/kg of unfractionated heparin was administered, 15 minutes prior to radiotracer injection, in a few patients. Blood glucose levels were required to be less than 180 mg/dL during a period of approximately 60 min before the administration of the 18F-FDG. Attenuation corrected images were used to locate and examine the hypermetabolic foci. However, non-attenuation corrected images were also reviewed, particularly to assess hypermetabolic foci near metallic structures, mainly valvular prosthesis, medical devices and electrodes. Images were reviewed by both a nuclear medicine physician and a cardiologist with several years of experience in cardiac [18F] FDG PET/CT. Uptake intensity was measured by means of maximum Standardized Uptake Values (SUVmax) in patients with and without findings suggestive of infection. Uptake patterns were also noted. Cardiac and extra-cardiac findings were reported. Extra-cardiac findings included both those attributable to IE, such as embolic events, but also indicative of other pathologies, such as neoplasic lesions. Final diagnosis The final diagnosis of IE (gold standard) was established by consulting the final diagnosis attributed to the patient by the Endocarditis team at the time of hospital discharge or death, after being possession of clinical, microbiological, and imaging information as well as clinical response to treatment. Statistical analysis Continuous data are presented as the mean +/- SD. Categorical data are expressed as percentages. Sensitivity, specificity, positive and negative predictive values of DC at hospital admission, TOE echo and PET/ CT, in evaluation of NVE and PVE were estimated. Receiver-operating characteristic (ROC) curves were built to determine the cutoff values with the best sensitivity-specificity combination to detect infection considering a binary outcome (1=positive 0=negative). Continuous data was tested for normality with the Shapiro-Wilks test and the Student’s t or the Mann-Whitney test was applied to compare them as appropriate. Fisher exact test was used for nominal variables to assess differences between groups. In these analyses we used the final diagnosis of confirmed and the rejected NVE and PVE as the gold standard outcome. P values of less than 0.05 were considered statistically significant. Statistical analyses were performed using SPSS (version 23.0; SPSS Inc.). Results: Clinical and microbiological data and echocardiography findings In total, 82 patients (mean age of 61 +/- 19 years, 62% of male gender) were enrolled from May 2016 to June 2019. Baseline characteristics were summarized in Table 1 . Half of included patients had an implanted prosthetic valve (n=35), the majority of which biological (n=19) and in aortic position (n=27). Fever was present in most patients (n=64) ( Table 2 ), followed by heart failure symptoms and vascular occurrences. One patient presented with pacemaker pocket signs of infection. Staphylococcus aureus was identified in 19 cases and more than half of these were methicillin resistant (52.9%). Presence of vegetations was the most common echocardiographic finding (n=31), followed by moderate to severe regurgitation (n=14), presence of abscess, pseudoaneurysm (n=9) or fistulae (n=5). PET/CT findings Seventy patients (90.9%) were under antibiotic therapy before PET/CT with a mean interval between treatment initiation and PET/ CT of 20±14 days. PET/CT was positive for IE in 24 cases. The receiver-operating characteristic curve yielded an area under the curve of 0.91 (95% confidence interval, 0.88–0.96) for SUVmax. A SUVmax cutoff value of ≥3.1 identified positive cases with 88.9%% sensitivity and 70.0% specificity ( Figure 1 ). PET/ CT performance in IE of NVE and PVE diagnosis There were 6718F-FDG PET/CT concordant results with the final diagnosis of the endocarditis team, corresponding to a 96% of agreement, k = 0.91(p=0.04). PET/CT was positive in 1 patient without a final diagnosis of IE (false positive, 2.2%). Conversely, PET/CT was negative in 4 patients with a diagnosis IE (false negative, 5.7%). The sensitivity, specificity, positive, negative predictive values and area under the curve (95% confidence intervals) of DC at admission, echocardiogram and PET/CT in the diagnosis of IE are shown in Table 3 .The addition of PET/CT to the modified DC resulted in a substantial increase in diagnostic specificity (from 33.3% to 97.8%) with only a mild reduction in sensitivity (from 88.0% to 84.0%). The percentage of IE cases classified as “possible” was reduced from 58% to 4.3%. Concerning the subgroup of patients with intracardiac devices, PET/CT showed similar sensitivity to DC at admission but superior to echocardiography (89.5% vs 68.4%). PET/CT was also more specific than echocardiogram and DC at admission for diagnosis of device IE (90.0% vs 60.0% vs 51.0%). In this subgroup, PET/CT allowed reclassification, reducing from 67.4% of possible cases to 4.2 %. ( Figure 4 ) Extracardiac Findings: Additional Benefits of Whole-Body PET/CT PET/CT detected 4 cases of peripheral embolism, which were asymptomatic. In addition, PET/CT identified clinical important extracardiac findings in 34 patients, and provided an alternative diagnosis in 22 of the negative IE cases: other infection foci in 13 patients [pneumonia (n=3), Q fever (n=5), colon abscess/diverticulitis (n=1), spondylodiscitis (n=5),hepatic abscess (n=2), phlebitis (n=1), sternotomy infection (n=1)]; 1 patient with Takayasu´s arteritis exacerbation and 8 unsuspected neoplastic lesions [colon (n=1), kidney (n=1), testicle (n=1) and lymphoma (n=5)], (figure 2-5). Final Diagnosis and Patient Management The patients were followed during a mean of 14 +/- 10months. According to diagnosis gold standard defined for this study, IE was established in 22 patients and was rejected in 45 patients; 3 patients were classified as possible IE. Those patients with definitive diagnosis of IE, 11 were submitted to surgery or percutaneous extraction of leads or devices. The remaining patients were medically managed. The all-cause mortality was 17.1% (12 patients). Discussion: 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 influence 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(8). Partially this is due to health care–associated disease (9). In a large multicenter, multinational study, health care–associated infective endocarditis accounted for 34% of cases (10). Hemodialysis, non–hemodialysis intravascular catheters, and invasive procedures are often associated with the infection (11). Furthermore, the proportion of cases related with prosthetic valves and implantable cardiac devices is increasing(8). 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)(12). Patients with intracardiac devices or prosthetic valves are a special IE population with a clear predisposing factor, different epidemiological profile, and higher mortality. The traditional modified Duke criteria are difficult to use in these patients due to the challenging interpretation of lesions on echocardiography and several cases of suspected IE are left without a conclusive diagnosis(2). The scenario is even more problematic in case of suspected intracardiac devices/leads infection, in which patients frequently present with nonspecific clinical manifestations and both TT and TOE were limited in evaluation of cardiac right chambers. Consequently, these patients may be recurrently hospitalized for an inflammatory/infectious disorder of unknown origin despite detailed investigations. In the absence of proven lead infection, further clinical management including the removal of the system is postponed due to the known morbidity and mortality risks associated with the extraction procedure (0.5–2.0 %)(13). 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 depict embolic events and evaluate abnormal metabolic activity around the site of prosthetic valve implantation (14). 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% (15). 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 (5). 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(16). Evidence of its use in patients suspected of transcatheter-replaced aortic valves (TAVR) endocarditis is still limited to case reports, but may soon become relevant as the incidence of TAVR endocarditis has been increasing over the past decade and the mortality is high. 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(17). There are other valid reasons to consider both PET/CT even when the Modified Duke criteria have already been met, 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 guide treatment strategies(1).The presence of septic emboli is crucial for the correct management of patients with IE. Failure to identify metastatic infection complications may lead to early interruption of therapy, thus potentially triggering relapse and an unfavorable outcome.(18) Infectious embolism is not uncommon as it can appear in 20% to 50% of patients and could be asymptomatic and though difficult to recognize(13),(19),(20). 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. Tables Table 1 Baseline characteristics of study population BaselineCharacteristic Total (n=82) Age (years) 61 ± 19 Male gender 51 (62.2%) Symptoms - Fever 64 (83.1%) - Heartfailuresymptoms 11 (14.9%) - Vascular phenomena 9 (9.00%) - Pocketinfectionsigns 1 (1.3%) Past medical history: - Hypertension 50 (63.3%) - Diabetes 17 (21.8%) CardiacProsthesis/ Intracardiacdevice 48 (58.5%) Prosthesistype 35 (42.7%) - Bioprostheticvalve 19 (50.0%) - Mechanicalvalve 12 (31.6%) - Prosthesic ring 4 (10.5%) - Mitra clip 1 (2.60%) Localization - Aortic 27 (69.2) - Mitral 7 (17.9%) - Aortic + mitral 1 (2.6%) - Pulmonar 1 (2.6%) Time from implantation to PET (years) 4.7 ±6.6 IntracardiacDevices 18 (22.0%) - Pacemaker 13 (59.1%) - ICD/CRT 2 (9.10%) - Dacron tube 4 (18.2%) - Patch 1 (4.5%) Time from implantation to PET (years) 5.3 ±5.9 Table 2 Echocardiography, laboratory and PET/CT findings TT/ TOE Echocardiogram 80 (97.6%) - Moderate to severeregurgitation 14(18.7%) - Vegetations 31 (39.7%) - Abcess/Pseudoaneurism 9 (11.8%) - Fistule 5 (6.6%) C-reactive protein (mg/dl) 14.8 ±19 White blood cells x10E9/L 10.3 ±5.0 Bloodcultures /serology 75 (91.5%) - St aureurs 19 (43.2%) - Coagulase negative Staphylococci 3 (6.8%) - Oral streptococci 2 (4.5%) - Streptococcusbovisgroup 8 (18.2%) - Enterococcusspp. 2 (4.5%) - Gram negative bacilli 2 (4.5%) - Coxiella burnetii 5 (11.4%) Modified Duke criteria at admission - Definitive 13 (16.9%) - Possible 45 (58.4%) - Rejected 19 (24.7%) Metabolicactivity (PET/CT) - SUV max 3.3± 1.4 Peripheral embolism 4 (4.90%) Extracardiac findings 34 (41.0%) Table 3 Diagnostic Performance of the modified Duke criteria at admission, and PET/CT for native valve endocarditis Sensitivity Specificity PPV NPV AUC Modified DuKe Criteria 88.0 [(38.8–69.6) 33.3% [86.1-91.7] 33.3% [86.1-91.7] 33.3% [86.1-91.7] 0.60 (0.46 – 0.74) PET/CT 84.0%% [71.5-100.0] 97.8% [52.4-63.1] 87.5% [3.5-12.2] 83.3% [98.2-100.0] 0.83 (0.71-0.93) Table 4 Diagnostic Performance of the modified Duke criteria at admission and PET/CT for prosthesis and intracardiac device endocarditis Sensitivity Specificity PPV NPV AUC Modified Duke Criteria 89.5 [38.8–69.6] 15.8% [86.1-91.7] 51.5% [23.4-44.5] 51.0% [97.5-99.6] 0.52 (0.32 – 0.72) PET/CT 89.5%% [71.5-100.0] 94.7% [52.4-63.1] 94% [3.5-12.2] 90% [98.2-100.0] 0.85 (0.70-0.97) Limitations This was a single-center study with recognized limitations. Our sample size was insufficient to allow robust subgroup analyses such as the performance of PET/CT in mechanical vs biological prothesis or intracardiac devices vs prothesis. The gold standard for the diagnosis was the clinical judgment of the endocarditis team based on the results of diagnostic tests and the clinical follow-up of patient. Finally, in our study the time between the beginning of antibiotherapy and the PET/CT was longer than reported by other studies. Conclusions 18F-FDG PET/CT proved to be a useful diagnostic tool in patients with both suspected NVE and PVE with good sensitivity and excellent specificity, resulting in a significant decrease in the number of cases of possible EI. This significant diagnostic improvement, which could have an important impact on IE outcomes, merits further assessment in larger series. References: Gomes A, Glaudemans AWJM, Touw DJ, van Melle JP, Willems TP, Maass AH, et al. 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Nationwide trends in complications of infective endocarditis in United States from 1999 to 2014. J Am Coll Cardiol. 2019; Kestler M, Muñoz P, Rodríguez-Créixems M, Rotger A, Jimenez-Requena F, Mari A, et al. Role of 18F-FDG PET in patients with infectious endocarditis. J Nucl Med. 2014; Orvin K, Goldberg E, Bernstine H, Groshar D, Sagie A, Kornowski R, et al. The role of FDG-PET/CT imaging in early detection of extra-cardiac complications of infective endocarditis. Clin Microbiol Infect [Internet]. 2015;21(1):69–76. Available from: http://dx.doi.org/10.1016/j.cmi.2014.08.012 Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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EPE","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"M.J","middleName":"","lastName":"Ferreira","suffix":""}],"badges":[],"createdAt":"2020-06-08 20:06:46","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-34097/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-34097/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":1302950,"identity":"d0c4a988-4c3b-4dbf-a9da-7baf8607c872","added_by":"auto","created_at":"2020-06-10 21:16:48","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":13126,"visible":true,"origin":"","legend":"Maximum standardized uptake value (SUV max) receiver-operating characteristics (ROC) curve.\nA SUV max cutoff value of ≥3.1 identified positive cases with sensitivity of 88.9% and 70.0% of specificity.","description":"","filename":"Fig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-34097/v1/Fig1.jpg"},{"id":1302951,"identity":"e46c5c9d-f508-4452-a090-69c5887a0aa6","added_by":"auto","created_at":"2020-06-10 21:16:49","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":56049,"visible":true,"origin":"","legend":"18F-FDG-PET/CT Scanning Identifying inflammation in local of sternotomy","description":"","filename":"Fig2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-34097/v1/Fig2.jpg"},{"id":1302952,"identity":"1c5f5179-eb47-483c-b571-1109067d8ec1","added_by":"auto","created_at":"2020-06-10 21:16:49","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":41863,"visible":true,"origin":"","legend":"18F-FDG-PET/CT Scanning Identifying a mass in ascending colon with high metabolic activity","description":"","filename":"Fig3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-34097/v1/Fig3.jpg"},{"id":1302953,"identity":"0a7847f2-cb48-4c74-8b9e-bbb6b35e6083","added_by":"auto","created_at":"2020-06-10 21:16:49","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":66236,"visible":true,"origin":"","legend":"18F-FDG-PET/CT Scanning Identifying a mass in testicle","description":"","filename":"fig4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-34097/v1/fig4.jpg"},{"id":1302954,"identity":"de3c1d6a-b92e-43a2-b419-7602565d31db","added_by":"auto","created_at":"2020-06-10 21:16:49","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":62186,"visible":true,"origin":"","legend":"18F-FDG-PET/CT Scanning Identifying a hepatic abscess.","description":"","filename":"fig5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-34097/v1/fig5.jpg"},{"id":13539186,"identity":"37c7b82e-a250-418a-a84b-da931bd3f055","added_by":"auto","created_at":"2021-09-17 01:42:21","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":411154,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-34097/v1/11310ab3-12bc-45d9-b02e-48abf59a6625.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eInfectious endocarditis: Improving Diagnostic Performance in Native and Prosthetic Valve Infection with 18F-FDG PET/CT\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe diagnosis of infective endocarditis (IE) is a clinical challenge, due to a myriad of nonspecific clinical presentations, involvement of different microorganisms and patient characteristics. Despite ongoing advances in both diagnostic and therapeutic procedures, IE remains associated with a poor prognosis, with an in-hospital mortality of 14\u0026ndash;22% and 1-year mortality of 40%(1)(2). Modified Duke criteria, the cornerstone of its diagnosis, is largely based in the presence of positive blood cultures and evidence of endocardial involvement on echocardiography. However, both transthoracic (TT) and transoesophageal echocardiography (TEE) miss IE sequelae in 30% of patients, especially, when intracardiac prosthetic material is implied (3). Therefore, the sensitivity and specificity of the modified Duke criteria is, approximately, 80% for native valve endocarditis (NVE) and lower values were found for prosthetic (PVE) or implantable cardiac electronic\u0026nbsp; device (ICEDs), which leads to an erroneous diagnose in several patients (1).\u003c/p\u003e\n\u003cp\u003e18F-FDG PET/CT, combining the high sensitivity of 18F-FDG PET to detect inflammation with the high spatial resolution of cardiac CT to define structural damage, is evolving as an important additional method in difficult-to-diagnose cases and is able to provide functional data on the extent of IE. The added diagnostic value of 18F-FDG PET/CT has been demonstrated in patients suspected of PVE or infections related to defibrillators, pacemakers, or ventricular assist devices(4). For extracardiac infection, 18F-FDG PET/CT detects a significant number of clinically relevant foci in patients with known or suspected NVE or PVE (1)(5). In the most recent European Society of Cardiology\u0026nbsp; (ESC) guidelines, 18F-FDG PET/CT has been included in the diagnostic algorithm PVE and also in the detection of embolic events for both NVE and PVE (6)(7).\u003c/p\u003e\n\u003cp\u003eWe aimed to evaluate the diagnostic performance of 18F-FDG PET in a cohort of patients with suspected IE referred to PET/CT in a tertiary care hospital.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cem\u003eStudy population\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eA retrospective study was performed at a tertiary center with 18F-FDG PET/CT and included all referred patients for this exam for suspected IE between May 2016 and June 2019. The choice to perform 18F-FDG PET/CT and the IE suspicion were based on the attending endocarditis team and did not follow a standardized protocol.\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eClinical, laboratory and microbiological data\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eBaseline demographic characteristics of patients, including all relevant clinical data, were collected from hospital records at hospital admission.\u0026nbsp; Laboratory data included basic renal and liver function test as well as hemogram.\u0026nbsp; For microbiological data, all blood cultures with respective antibiotical sensitivity testing and, when applicable, serology, were recorded.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eOther imaging tests data\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eTransthoracic echocardiography was performed in all patients and transesophageal echocardiography performed in 86.3%, and recorded images and reports were analyzed. Data was extracted regarding assessments of general cardiac parameters, including cavity dimensions and ventricular function, and specific endocarditis suggestive findings such as valve function, vegetations (shape, size, and number), and periannular complications (abscess, pseudoaneurysm, perivalvular leak).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003ePET/CT \u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eWhole-body scans and dedicated cardiac bed images were obtained in a hybrid PET/CT scanner (Discovery ST, General Electrics\u0026Ograve;). A [18F] FDG myocardial uptake suppression protocol, that included a 48h high-fat and low-carbohydrate diet and a fasting period of at least 12 hours, was used to optimize image quality and diagnostic accuracy. To further improve image quality 50 IU/kg of unfractionated heparin was administered, 15 minutes prior to radiotracer injection, in a few patients. Blood glucose levels were required to be less than 180 mg/dL during a period of approximately 60 min before the administration of the 18F-FDG.\u003c/p\u003e\n\u003cp\u003eAttenuation corrected images were used to locate and examine the hypermetabolic foci. However, non-attenuation corrected images were also reviewed, particularly to assess hypermetabolic foci near metallic structures, mainly valvular prosthesis, medical devices and electrodes. Images were reviewed by both a nuclear medicine physician and a cardiologist with several years of experience in cardiac [18F] FDG PET/CT.\u003c/p\u003e\n\u003cp\u003eUptake intensity was measured by means of maximum Standardized Uptake Values (SUVmax) in patients with and without findings suggestive of infection. Uptake patterns were also noted. Cardiac and extra-cardiac findings were reported. Extra-cardiac findings included both those attributable to IE, such as embolic events, but also indicative of other pathologies, such as neoplasic lesions.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFinal diagnosis\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe final diagnosis of IE (gold standard) was established by consulting the final diagnosis attributed to the patient by the Endocarditis team at the time of hospital discharge or death, after being possession of clinical, microbiological, and imaging information as well as clinical response to treatment.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eStatistical analysis \u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eContinuous data are presented as the mean +/- SD. Categorical data are expressed as percentages. Sensitivity, specificity, positive and negative predictive values of DC at hospital admission, TOE echo and PET/ CT, in evaluation of NVE and PVE were estimated. Receiver-operating characteristic (ROC) curves were built to determine the cutoff values with the best sensitivity-specificity combination to detect infection considering a binary outcome (1=positive 0=negative). Continuous data was tested for normality with the Shapiro-Wilks test and the Student\u0026rsquo;s t or the Mann-Whitney test was applied to compare them as appropriate.\u0026nbsp; Fisher exact test was used for nominal variables to assess differences between groups. In these analyses we used the final diagnosis of confirmed and the rejected NVE and PVE as the gold standard outcome. P values of less than 0.05 were considered statistically significant. Statistical analyses were performed using SPSS (version 23.0; SPSS Inc.).\u003c/p\u003e"},{"header":"Results:","content":"\u003cp\u003e\u003cem\u003eClinical and microbiological data and echocardiography findings\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eIn total, 82 patients (mean age of 61 +/- 19 years, 62% of male gender) were enrolled from May 2016 to June 2019. Baseline characteristics were summarized in \u003cem\u003eTable 1\u003c/em\u003e.\u003c/p\u003e\n\u003cp\u003eHalf of included patients had an implanted prosthetic valve (n=35), the majority of which biological (n=19) and in aortic position (n=27).\u003c/p\u003e\n\u003cp\u003eFever was present in most patients (n=64) (\u003cem\u003eTable 2\u003c/em\u003e), followed by heart failure symptoms and vascular occurrences. One patient presented with pacemaker pocket signs of infection.\u0026nbsp; Staphylococcus aureus was identified in 19 cases and more than half of these were methicillin resistant (52.9%). Presence of vegetations was the most common echocardiographic finding (n=31), followed by moderate to severe regurgitation (n=14), presence of abscess, pseudoaneurysm (n=9) or fistulae (n=5).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003ePET/CT findings\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eSeventy patients (90.9%) were under antibiotic therapy before PET/CT with a mean interval between treatment initiation and PET/ CT of 20\u0026plusmn;14 days. PET/CT was positive for IE in 24 cases. The receiver-operating characteristic curve yielded an area under the curve of 0.91 (95% confidence interval, 0.88\u0026ndash;0.96) for SUVmax. A SUVmax cutoff value of \u0026ge;3.1 identified positive cases with 88.9%% sensitivity and 70.0% specificity (\u003cem\u003eFigure 1\u003c/em\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003ePET/ CT performance in IE of NVE and PVE diagnosis\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThere were 6718F-FDG PET/CT concordant results with the final diagnosis of the endocarditis team, corresponding to a 96% of agreement, k = 0.91(p=0.04).\u003c/p\u003e\n\u003cp\u003ePET/CT was positive in 1 patient without a final diagnosis of IE (false positive, 2.2%). Conversely, PET/CT was negative in 4 patients with a diagnosis IE (false negative, 5.7%).\u003c/p\u003e\n\u003cp\u003eThe sensitivity, specificity, positive, negative predictive values and area under the curve (95% confidence intervals) of DC at admission, echocardiogram and PET/CT in the diagnosis of IE are shown in \u003cem\u003eTable 3\u003c/em\u003e.The addition of PET/CT to the modified DC resulted in a substantial increase in diagnostic specificity (from 33.3% to 97.8%) with only a mild reduction in sensitivity (from 88.0% to 84.0%). The percentage of IE cases classified as \u0026ldquo;possible\u0026rdquo; was reduced from 58% to 4.3%.\u003c/p\u003e\n\u003cp\u003eConcerning the subgroup of patients with intracardiac devices, PET/CT showed similar sensitivity to DC at admission but superior to echocardiography (89.5% vs 68.4%). PET/CT was also more specific than echocardiogram and DC at admission for diagnosis of device IE (90.0% vs 60.0% vs 51.0%). In this subgroup, PET/CT allowed reclassification, reducing from 67.4% of possible cases to 4.2 %. (\u003cem\u003eFigure 4\u003c/em\u003e)\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eExtracardiac Findings: Additional Benefits of Whole-Body PET/CT\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003ePET/CT detected 4 cases of peripheral embolism, which were asymptomatic.\u0026nbsp; In addition, PET/CT identified clinical important extracardiac findings in 34 patients, and provided an alternative diagnosis in 22 of the negative IE cases: other infection foci in 13 patients [pneumonia (n=3), Q fever (n=5), colon abscess/diverticulitis (n=1),\u0026nbsp; spondylodiscitis (n=5),hepatic abscess (n=2), phlebitis (n=1), sternotomy infection (n=1)]; 1 patient with Takayasu\u0026acute;s arteritis exacerbation and 8 unsuspected neoplastic lesions [colon (n=1), kidney (n=1), testicle\u0026nbsp; (n=1) and lymphoma (n=5)], (figure 2-5).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFinal Diagnosis and Patient Management \u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe patients were followed during a mean of 14 +/- 10months. According to diagnosis gold standard defined for this study, IE was established in 22 patients and was rejected in 45 patients; 3 patients were classified as possible IE.\u0026nbsp; Those patients with definitive diagnosis of IE, 11 were submitted to surgery or percutaneous extraction of leads or devices. The remaining patients were medically managed. The all-cause mortality was 17.1% (12 patients).\u003c/p\u003e"},{"header":"Discussion:","content":"\u003cp\u003eOur 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 influence IE-related morbidity and mortality.\u003c/p\u003e\n\u003cp\u003eInfective 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(8). Partially this is due to health care\u0026ndash;associated disease (9). In a large multicenter, multinational study, health care\u0026ndash;associated infective endocarditis accounted for 34% of cases (10). Hemodialysis, non\u0026ndash;hemodialysis intravascular catheters, and invasive procedures are often associated with the infection (11). Furthermore, the proportion of cases related with prosthetic valves and implantable cardiac devices is increasing(8). 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)(12).\u003c/p\u003e\n\u003cp\u003ePatients with intracardiac devices or prosthetic valves are a special IE population with a clear predisposing factor, different epidemiological profile, and higher mortality. The traditional modified Duke criteria are difficult to use in these patients due to the challenging\u0026nbsp; interpretation of lesions on echocardiography and several cases of suspected IE are left without a conclusive diagnosis(2). The scenario is even more problematic in case of suspected intracardiac devices/leads infection, in which patients frequently present with nonspecific clinical manifestations and both TT and TOE were limited in evaluation of cardiac right chambers. Consequently, these patients may be recurrently hospitalized for an inflammatory/infectious disorder of unknown origin despite detailed investigations. In the absence of proven lead infection, further clinical management including the removal of the system is postponed due to the known morbidity and mortality risks associated with the extraction procedure (0.5\u0026ndash;2.0 %)(13).\u003c/p\u003e\n\u003cp\u003eThe 2015 ESC Guidelines on Endocarditis recommend using additional imaging modalities when echocardiography and blood cultures are inconclusive (i.e. result in a \u0026lsquo;possible\u0026rsquo; diagnosis of endocarditis, or a \u0026lsquo;rejected\u0026rsquo; 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 depict embolic events and evaluate abnormal metabolic activity around the site of prosthetic valve implantation (14).\u003c/p\u003e\n\u003cp\u003eIn 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.\u003c/p\u003e\n\u003cp\u003eIn 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% (15). 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 (5).\u0026nbsp; 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.\u003c/p\u003e\n\u003cp\u003eNo distinction between biological and mechanical prosthetic valves was made in our study. Roque \u003cem\u003eet al.,\u003c/em\u003e in a study evaluating metabolic patterns of captation after surgery, no differences between\u0026nbsp; biological or mechanical prothesis were\u0026nbsp; found(16). Evidence of its use in patients suspected of transcatheter-replaced aortic valves (TAVR) endocarditis is still limited to case reports, but may soon become relevant as the incidence of TAVR endocarditis has been increasing over the past decade and the mortality is high. In our cohort, 2 patients had TAVR endocarditis suspicion and 1 patient had a previous \u0026ldquo;mitraclip\u0026rdquo; implantation. In all cases, PET-FDG excluded the diagnosis.\u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe 4 false-negative cases, in our study, could be due previous antibiotherapy\u0026nbsp; 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(17).\u003c/p\u003e\n\u003cp\u003eThere are other valid reasons to consider both PET/CT even when the Modified Duke criteria have already been met, 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 guide treatment strategies(1).The presence of septic emboli is crucial for the correct management of patients with IE. Failure to identify metastatic infection complications may lead to early interruption of therapy, thus potentially triggering relapse and an unfavorable outcome.(18) Infectious embolism is not uncommon as it can appear in 20% to 50% of patients and could be asymptomatic and though difficult to recognize(13),(19),(20).\u0026nbsp;\u0026nbsp; 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.\u003c/p\u003e"},{"header":"Tables","content":"\u003ctable border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline characteristics of study population\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003ctd width=\"292\"\u003e\n\u003cp\u003eBaselineCharacteristic\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"222\"\u003e\n\u003cp\u003eTotal (n=82)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"292\"\u003e\n\u003cp\u003eAge (years)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"222\"\u003e\n\u003cp\u003e61 \u0026plusmn; 19\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"292\"\u003e\n\u003cp\u003eMale gender\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"222\"\u003e\n\u003cp\u003e51 (62.2%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"292\"\u003e\n\u003cp\u003eSymptoms\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"222\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"292\"\u003e\n\u003cp\u003e-\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; Fever\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"222\"\u003e\n\u003cp\u003e64 (83.1%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"292\"\u003e\n\u003cp\u003e-\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; Heartfailuresymptoms\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"222\"\u003e\n\u003cp\u003e11 (14.9%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"292\"\u003e\n\u003cp\u003e-\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; Vascular phenomena\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"222\"\u003e\n\u003cp\u003e9 (9.00%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"292\"\u003e\n\u003cp\u003e-\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; Pocketinfectionsigns\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"222\"\u003e\n\u003cp\u003e1 (1.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"292\"\u003e\n\u003cp\u003ePast medical history:\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"222\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"292\"\u003e\n\u003cp\u003e-\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; Hypertension\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"222\"\u003e\n\u003cp\u003e50 (63.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"292\"\u003e\n\u003cp\u003e-\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; Diabetes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"222\"\u003e\n\u003cp\u003e17 (21.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"292\"\u003e\n\u003cp\u003eCardiacProsthesis/ Intracardiacdevice\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"222\"\u003e\n\u003cp\u003e48 (58.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"292\"\u003e\n\u003cp\u003eProsthesistype\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"222\"\u003e\n\u003cp\u003e35 (42.7%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"292\"\u003e\n\u003cp\u003e-\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; Bioprostheticvalve\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"222\"\u003e\n\u003cp\u003e19 (50.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"292\"\u003e\n\u003cp\u003e-\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; Mechanicalvalve\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"222\"\u003e\n\u003cp\u003e12 (31.6%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"292\"\u003e\n\u003cp\u003e-\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; Prosthesic ring\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"222\"\u003e\n\u003cp\u003e4 (10.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"292\"\u003e\n\u003cp\u003e-\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; \u003cem\u003eMitra clip\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"222\"\u003e\n\u003cp\u003e1 (2.60%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"292\"\u003e\n\u003cp\u003eLocalization\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"222\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"292\"\u003e\n\u003cp\u003e-\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; Aortic\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"222\"\u003e\n\u003cp\u003e27 (69.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"292\"\u003e\n\u003cp\u003e-\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; Mitral\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"222\"\u003e\n\u003cp\u003e7 (17.9%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"292\"\u003e\n\u003cp\u003e-\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; Aortic + mitral\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"222\"\u003e\n\u003cp\u003e1 (2.6%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"292\"\u003e\n\u003cp\u003e-\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; Pulmonar\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"222\"\u003e\n\u003cp\u003e1 (2.6%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"292\"\u003e\n\u003cp\u003eTime from implantation to PET (years)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"222\"\u003e\n\u003cp\u003e4.7 \u0026plusmn;6.6\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"292\"\u003e\n\u003cp\u003eIntracardiacDevices\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"222\"\u003e\n\u003cp\u003e18 (22.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"292\"\u003e\n\u003cp\u003e-\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; Pacemaker\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"222\"\u003e\n\u003cp\u003e13 (59.1%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"292\"\u003e\n\u003cp\u003e-\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; ICD/CRT\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"222\"\u003e\n\u003cp\u003e2 (9.10%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"292\"\u003e\n\u003cp\u003e-\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; Dacron tube\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"222\"\u003e\n\u003cp\u003e4 (18.2%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"292\"\u003e\n\u003cp\u003e-\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; Patch\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"222\"\u003e\n\u003cp\u003e1 (4.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"292\"\u003e\n\u003cp\u003eTime from implantation to PET (years)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"222\"\u003e\n\u003cp\u003e5.3 \u0026plusmn;5.9\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" width=\"515\"\u003e\n \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eEchocardiography, laboratory and PET/CT findings\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd width=\"338\"\u003e\n\u003cp\u003eTT/ TOE Echocardiogram\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"177\"\u003e\n\u003cp\u003e80 (97.6%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"338\"\u003e\n\u003cp\u003e- Moderate to severeregurgitation\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"177\"\u003e\n\u003cp\u003e14(18.7%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"338\"\u003e\n\u003cp\u003e- Vegetations\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"177\"\u003e\n\u003cp\u003e31 (39.7%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"338\"\u003e\n\u003cp\u003e- Abcess/Pseudoaneurism\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"177\"\u003e\n\u003cp\u003e9 (11.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"338\"\u003e\n\u003cp\u003e- Fistule\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"177\"\u003e\n\u003cp\u003e5 (6.6%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"338\"\u003e\n\u003cp\u003eC-reactive protein (mg/dl)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"177\"\u003e\n\u003cp\u003e14.8 \u0026plusmn;19\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"338\"\u003e\n\u003cp\u003eWhite blood cells x10E9/L\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"177\"\u003e\n\u003cp\u003e10.3 \u0026plusmn;5.0\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"338\"\u003e\n\u003cp\u003eBloodcultures /serology\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"177\"\u003e\n\u003cp\u003e75 (91.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"338\"\u003e\n\u003cp\u003e- St\u003cem\u003eaureurs\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"177\"\u003e\n\u003cp\u003e19 (43.2%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"338\"\u003e\n\u003cp\u003e- Coagulase negative Staphylococci\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"177\"\u003e\n\u003cp\u003e3 (6.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"338\"\u003e\n\u003cp\u003e- Oral streptococci\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"177\"\u003e\n\u003cp\u003e\u0026nbsp;2 (4.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"338\"\u003e\n\u003cp\u003e- Streptococcusbovisgroup\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"177\"\u003e\n\u003cp\u003e8 (18.2%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"338\"\u003e\n\u003cp\u003e- Enterococcusspp.\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"177\"\u003e\n\u003cp\u003e2 (4.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"338\"\u003e\n\u003cp\u003e- Gram negative bacilli\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"177\"\u003e\n\u003cp\u003e2 (4.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"338\"\u003e\n\u003cp\u003e- Coxiella\u003cem\u003eburnetii\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"177\"\u003e\n\u003cp\u003e5 (11.4%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"338\"\u003e\n\u003cp\u003e\u003cstrong\u003eModified Duke criteria at admission\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"177\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"338\"\u003e\n\u003cp\u003e- Definitive\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"177\"\u003e\n\u003cp\u003e13 (16.9%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"338\"\u003e\n\u003cp\u003e- Possible\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"177\"\u003e\n\u003cp\u003e45 (58.4%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"338\"\u003e\n\u003cp\u003e- Rejected\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"177\"\u003e\n\u003cp\u003e19 (24.7%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"338\"\u003e\n\u003cp\u003e\u003cstrong\u003eMetabolicactivity (PET/CT)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"177\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"338\"\u003e\n\u003cp\u003e- SUV max\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"177\"\u003e\n\u003cp\u003e3.3\u0026plusmn; 1.4\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"338\"\u003e\n\u003cp\u003e\u003cstrong\u003ePeripheral embolism\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"177\"\u003e\n\u003cp\u003e4 (4.90%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"338\"\u003e\n\u003cp\u003e\u003cstrong\u003eExtracardiac findings\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"177\"\u003e\n\u003cp\u003e34 (41.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDiagnostic Performance of the modified Duke criteria at admission, and PET/CT for native valve endocarditis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd width=\"92\"\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003e\u003cstrong\u003eSensitivity\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e\u003cstrong\u003eSpecificity\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e\u003cstrong\u003ePPV\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e\u003cstrong\u003eNPV\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e\u003cstrong\u003eAUC\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"92\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eModified DuKe Criteria\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003e88.0\u003c/p\u003e\n\u003cp\u003e[(38.8\u0026ndash;69.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e33.3%\u003c/p\u003e\n\u003cp\u003e[86.1-91.7]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e33.3%\u003c/p\u003e\n\u003cp\u003e[86.1-91.7]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e33.3%\u003c/p\u003e\n\u003cp\u003e[86.1-91.7]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e0.60\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;(0.46 \u0026ndash; 0.74)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"92\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003ePET/CT\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003e84.0%%\u003c/p\u003e\n\u003cp\u003e[71.5-100.0]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e97.8%\u003c/p\u003e\n\u003cp\u003e[52.4-63.1]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e87.5%\u003c/p\u003e\n\u003cp\u003e[3.5-12.2]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e83.3%\u003c/p\u003e\n\u003cp\u003e[98.2-100.0]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e0.83\u003c/p\u003e\n\u003cp\u003e(0.71-0.93)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003ctable border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDiagnostic Performance of the modified Duke criteria at admission and PET/CT for prosthesis and intracardiac device endocarditis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd width=\"92\"\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003e\u003cstrong\u003eSensitivity\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e\u003cstrong\u003eSpecificity\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e\u003cstrong\u003ePPV\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e\u003cstrong\u003eNPV\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e\u003cstrong\u003eAUC\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"92\"\u003e\n\u003cp\u003e\u003cstrong\u003eModified Duke Criteria\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003e89.5\u003c/p\u003e\n\u003cp\u003e[38.8\u0026ndash;69.6]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e15.8%\u003c/p\u003e\n\u003cp\u003e[86.1-91.7]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e51.5%\u003c/p\u003e\n\u003cp\u003e[23.4-44.5]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e51.0%\u003c/p\u003e\n\u003cp\u003e[97.5-99.6]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e0.52\u003c/p\u003e\n\u003cp\u003e(0.32 \u0026ndash; 0.72)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"92\"\u003e\n\u003cp\u003e\u003cstrong\u003ePET/CT\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003e89.5%%\u003c/p\u003e\n\u003cp\u003e[71.5-100.0]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e94.7%\u003c/p\u003e\n\u003cp\u003e[52.4-63.1]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e94%\u003c/p\u003e\n\u003cp\u003e[3.5-12.2]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e90%\u003c/p\u003e\n\u003cp\u003e[98.2-100.0]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e0.85 (0.70-0.97)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"Limitations","content":"\u003cp\u003eThis was a single-center study with recognized limitations. Our sample size was insufficient to allow robust subgroup analyses such as the performance of PET/CT in mechanical vs biological prothesis or intracardiac devices vs prothesis. The gold standard for the diagnosis was the clinical judgment of the endocarditis team based on the results of diagnostic tests and the clinical follow-up of patient. Finally, in our study the time between the beginning of antibiotherapy and the PET/CT was longer than reported by other studies.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003e18F-FDG PET/CT proved to be a useful diagnostic tool in patients with both suspected NVE and PVE with good sensitivity and excellent specificity, resulting in a significant decrease in the number of cases of possible EI. This significant diagnostic improvement, which could have an important impact on IE outcomes, merits further assessment in larger series.\u003c/p\u003e"},{"header":"References:","content":"\u003col\u003e\n\u003cli\u003eGomes A, Glaudemans AWJM, Touw DJ, van Melle JP, Willems TP, Maass AH, et al. Diagnostic value of imaging in infective endocarditis: a systematic review. Lancet Infect Dis. 2017;17(1):e1\u0026ndash;14. Available from: http://dx.doi.org/10.1016/S1473-3099(16)30141-4\u003c/li\u003e\n\u003cli\u003eLancellotti P, Habib G, Oury C, Nchimi A. Positron Emission Tomography/Computed Tomography Imaging in Device Infective Endocarditis: Ready for Prime Time. Circulation. 2015;132(12):1076\u0026ndash;80.\u003c/li\u003e\n\u003cli\u003eHill EE, Herijgers P, Claus P, Vanderschueren S, Peetermans WE, Herregods MC. Abscess in infective endocarditis: The value of transesophageal echocardiography and outcome. A 5-year study. Am Heart J. 2007;\u003c/li\u003e\n\u003cli\u003eFowler VG, Miro JM, Hoen B, Cabell CH, Abrutyn E, Rubinstein E, et al. Staphylococcus aureus endocarditis: A consequence of medical progress. J Am Med Assoc. 2005;\u003c/li\u003e\n\u003cli\u003ePizzi MN, Roque A, Fern\u0026aacute;ndez-Hidalgo N, Cu\u0026eacute;llar-Calabria H, Ferreira-Gonz\u0026aacute;lez I, Gonz\u0026agrave;lez-Alujas MT, et al. Improving the Diagnosis of Infective Endocarditis in Prosthetic Valves and Intracardiac Devices with 18F-Fluordeoxyglucose Positron Emission Tomography/Computed Tomography Angiography: Initial Results at an Infective Endocarditis Referral Center. Circulation. 2015;132(12):1113\u0026ndash;26.\u003c/li\u003e\n\u003cli\u003eHabib G, Lancellotti P, Antunes MJ, Bongiorni MG, Casalta JP, Del Zotti F, et al. 2015 ESC Guidelines for the management of infective endocarditis: The Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Eur Heart J. 2015;\u003c/li\u003e\n\u003cli\u003eMillar BC, de Camargo RA, Alavi A, Moore JE. PET/Computed Tomography Evaluation of Infection of the Heart. PET Clin. 2019;\u003c/li\u003e\n\u003cli\u003eWang A, Gaca JG, Chu VH. Management Considerations in Infective Endocarditis A Review. 2018;(March).\u003c/li\u003e\n\u003cli\u003eToyoda N, Chikwe J, Itagaki S, Gelijns AC, Adams DH, Egorova NN. Trends in infective endocarditis in California and New York state, 1998-2013. JAMA - J Am Med Assoc. 2017;\u003c/li\u003e\n\u003cli\u003eAlmirante B, Tornos P, Pigrau C, Sambola A, Igual A, Pahissa A. Contemporary epidemiology and prognosis of health care-associated infective endocarditis. Chinese J Infect Chemother. 2009;9(4):296.\u003c/li\u003e\n\u003cli\u003eDelahaye F, M\u0026rsquo;Hammedi A, Guerpillon B, De Gevigney G, Boibieux A, Dauwalder O, et al. Systematic Search for Present and Potential Portals of Entry for Infective Endocarditis. J Am Coll Cardiol. 2016;\u003c/li\u003e\n\u003cli\u003eThuny F, Giorgi R, Habachi R, Ansaldi S, Le Dolley Y, Casalta JP, et al. Excess mortality and morbidity in patients surviving infective endocarditis. Am Heart J. 2012;\u003c/li\u003e\n\u003cli\u003eGranados U, Fuster D, Pericas JM, Llopis JL, Ninot S, Quintana E, et al. Diagnostic accuracy of 18F-FDG PET/CT in infective endocarditis and implantable cardiac electronic device infection: A cross-sectional study. J Nucl Med. 2016;57(11):1726\u0026ndash;32.\u003c/li\u003e\n\u003cli\u003eHabib G, Lancellotti P, Antunes MJ, Bongiorni MG, Casalta JP, Del Zotti F, et al. Ghid de management al endocarditei infecţioase 2015. Vol. 26, Revista Romana de Cardiologie. 2016. 343\u0026ndash;405 p.\u003c/li\u003e\n\u003cli\u003eMahmood M, Kendi AT, Ajmal S, Farid S, O\u0026rsquo;Horo JC, Chareonthaitawee P, et al. Meta-analysis of 18F-FDG PET/CT in the diagnosis of infective endocarditis. J Nucl Cardiol. 2019;26(3):922\u0026ndash;35.\u003c/li\u003e\n\u003cli\u003eRoque A, Pizzi MN, Fernandez-Hidalgo N, Cuellar-Calabria H, Rios R, Ferreira N, et al. 524918F-FDG-PET/CTA of prosthetic cardiac valves: postsurgical inflammatory patterns and its temporal evolution. Can we question the 3-month limit of the current guidelines? Eur Heart J. 2018;39(suppl_1):2019.\u003c/li\u003e\n\u003cli\u003eSwart LE, Scholtens AM, Tanis W, Nieman K, Bogers AJJC, Verzijlbergen FJ, et al. 18F-fluorodeoxyglucose positron emission/computed tomography and computed tomography angiography in prosthetic heart valve endocarditis: From guidelines to clinical practice. Vol. 39, European Heart Journal. 2018. p. 3739\u0026ndash;49.\u003c/li\u003e\n\u003cli\u003eShrivastav R, Ludhwani D, Kallur KR, Perimbeti S, Bandyopadhyay D, Jimenez RCO, et al. Nationwide trends in complications of infective endocarditis in United States from 1999 to 2014. J Am Coll Cardiol. 2019;\u003c/li\u003e\n\u003cli\u003eKestler M, Mu\u0026ntilde;oz P, Rodr\u0026iacute;guez-Cr\u0026eacute;ixems M, Rotger A, Jimenez-Requena F, Mari A, et al. Role of 18F-FDG PET in patients with infectious endocarditis. J Nucl Med. 2014;\u003c/li\u003e\n\u003cli\u003eOrvin K, Goldberg E, Bernstine H, Groshar D, Sagie A, Kornowski R, et al. The role of FDG-PET/CT imaging in early detection of extra-cardiac complications of infective endocarditis. Clin Microbiol Infect [Internet]. 2015;21(1):69\u0026ndash;76. Available from: http://dx.doi.org/10.1016/j.cmi.2014.08.012\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"infective endocarditis, 18F-FDG PET/CT, Modified Duke criteria, native valve endocarditis, prothesis valve endocarditis","lastPublishedDoi":"10.21203/rs.3.rs-34097/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-34097/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eThe 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.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eConsecutive 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.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e 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 SUVmax 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.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003e18F-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.\u0026nbsp;\u003c/p\u003e","manuscriptTitle":"Infectious endocarditis: Improving Diagnostic Performance in Native and Prosthetic Valve Infection with 18F-FDG PET/CT","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2020-06-10 21:16:48","doi":"10.21203/rs.3.rs-34097/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6f9e0a01-2317-4ce8-b563-630fe06461a0","owner":[],"postedDate":"June 10th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":117512,"name":"Cardiac \u0026 Cardiovascular Systems"}],"tags":[],"updatedAt":"2020-06-23T12:33:43+00:00","versionOfRecord":[],"versionCreatedAt":"2020-06-10 21:16:48","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-34097","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-34097","identity":"rs-34097","version":["v1"]},"buildId":"WrCJVZZCHTDjtuVLN7oU0","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}