The PET/ Control study: repeat PET-CT scans in the follow up of non-operated patients with prosthetic valve endocarditis.

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Cristiane Lamas, Mary Philip, Titouan Runet, Laetitia Tessonnier, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9313376/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 Purpose : Our aim is to describe our real-life experience in the follow- up of patients with prosthetic valve endocarditis (PVE) who were treated conservatively and compare the features of those who had 18-fluorine-fluorodeoxyglucose positron emission tomography coupled with computed tomography (PET-CT) follow-up to those without PET-CT follow-up. Methods : We performed a post hoc analysis of cardiac PET CT scan results of adult patients with definite PVE, prospectively included at a cardiology referral center. Patients treated conservatively with PET-CT follow-up (group 1) were compared to those without PET-CT follow-up (group 2). Statistics were performed with Jamovi 2.6.13. Results : Patients who had PET CTRL had higher Euroscore II (19 vs 13.2, p=0.008), more pacemakers (21.2% vs 0, p < 0.001), more spondylodiscitis (21.2% vs 10.9% p NS) and more enterococci (26.9% vs 14.5%, p NS). Surgery was indicated for 50.0% of group 1, vs 36.4% of group 2(p NS). Prolonged antibiotic treatment was given for 42/52(80.8%) of the PET CTRL group vs 5/55(9%) (p< 0.00001, OR 0.024, 95%CI 0.008- 0.075). Follow up PET CT was helpful in stopping or continuing antimicrobials for 25/42 (59.5%). There were no hospitalizations due to IE relapses in either group over the period of 1 year. Death at 1 year was seen in 6.3% vs 16.3% (p NS). Conclusion : Sequential PET-CT was mainly used to guide the duration of antimicrobial therapy, especially in patients with PVE with more complex or severe profiles. PET-CT may complement clinical and biological assessment in selected inoperable patients with PVE. Infectious Diseases prosthetic valve endocarditis 18 F FDG PET/CT antibiotic therapy Introduction Several observational series have reported the diagnostic value of 18-fluorine-fluorodeoxyglucose positron emission tomography coupled with computed tomography (18F-FDG-PET/CT, or simply PET CT) in patients with prosthetic valve endocarditis (PVE) [ 1 ]. An increased contrast uptake has been proposed as a major criterion when the prosthesis has been inserted for more than 3 months [ 2 ], and more recently as a minor criterion if implanted less than one month before the infective endocarditis (IE) episode [ 3 ]. Infective endocarditis increasingly affects an older population with significant comorbidities and high surgical risk [ 4 – 6 ]. Prosthetic valve endocarditis is a particularly difficult- to- treat infection, with higher mortality rates, and patients with PVE tend to be older and carry a higher burden of comorbidities [ 4 – 6 ]. Therefore, it is not unusual, in clinical practice, to manage inoperable patients with PVE, most often due to their very high surgical risk, and less frequently because of technical challenges or refusal of surgery by the patient or family. PET CT has been shown to be useful in the follow-up of patients treated conservatively, potentially indicating persistent infection and risk of relapse [ 7 – 10 ]. Our aim is to describe our real-life experience in the follow- up of patients with PVE who were treated conservatively and compare the features of those who had PET-CT follow-up to those without PET-CT follow-up. Methods Study design We performed a post hoc analysis of cardiac PET CT scan results of adult patients with definite PVE, prospectively included at a cardiology referral center in Marseille, France, in the period of January 2019 to February 2024. Cases were defined by the Duke modified criteria [ 11 ]and the ESC 2015 criteria [ 2 ]. Study variables included were demographic, clinical, comorbidities, echocardiographic, complications and in-hospital mortality. In the study site, cardiac PET CT scans are performed routinely for all IE patients at entry, and radiologists experienced in cardiac PET CT in endocarditis interpret them. Follow up visits are done by infectious diseases physicians and cardiologists at 1, 3, 6 and 12 months, and TTE with or without TEE are performed on the same day. Institutional protocols have been described in detail elsewhere [ 12 ]. Follow up PET CT is done on demand by the expert infectious diseases physicians on site. Definitions Prolonged antibiotic therapy was defined as any antimicrobial continued beyond the standard treatment duration for infective endocarditis, defined as per guidelines [ 2 , 4 , 6 ]. Relapse was defined as a second episode of IE caused by the same microorganism and reinfection as a second episode of IE caused by a different microorganism [ 2 ]. Statistical analysis Frequencies, means with standard deviations, or medians with interquartile ranges were reported according to data distribution, assessed by the Kolmogorov-Smirnov test. Patients treated conservatively with PET-CT follow-up (group 1) were compared to those without PET-CT follow-up (group 2). Student’s t-test was used to compare normally distributed continuous variables and the Mann Whitney test for non-normal ones. The chi square test and Fisher’s exact test, when indicated, were used to calculate differences in dichotomic variables. Statistical analyses were performed with Jamovi version 2.6.13. Ethics The study was approved by the health data access portal, PADS, under number PADS-DRKDPX. No patients objected to their data being collected during the study period. Results We included 200 patients with PVE from January 2019 to February 2024; 27(13.5%) died during hospitalization, 67(22.35%) underwent surgery and survived. Although systematic PET/CT is part of patient care, it was performed in 158(79%) cases. Reasons for not performing PET CT were clinical instability in 17/42 (40.4%), decompensated diabetes, inadequate dietetic preparation, claustrophobia, peripheral venous access failure and patient refusal. Therefore, we analyzed 106 patients, all of whom were treated conservatively for PVE. Of these, 52 belonged to group 1, which were those who had a follow up outpatient PET scan, described as the PET/CTRL group, and 55 to group 2 (those who were followed up at outpatients but did not have a PET CT demanded). For both groups, mean age was 70.1 ± 14.8 years, and 69.2% were male. Left-sided PVE affected 97.2%, and right-sided 10.3%. Previous IE had occurred in 20.6%. Comorbidities were frequent: diabetes in 22.4%, coronary artery disease 21.5%, cancer in 15.9%, chronic renal failure in 12.1%, COPD in 9.3%; active intravenous drug use was present in 6.5%. Median Euroscore II was 15.6[IQR 9.78–27.8]. PVE was community acquired in 76.6%. A bivariate analysis comparing the 2 groups is presented in Table 1 . Table 1 Comparison of selected variables in patients with prosthetic valve endocarditis treated conservatively, with PET CT follow-up (PET control group, or group 1) and those without PET CT follow-up (group 2). Selected Variables Group 1 (n = 52) Group 2 (n = 55) Odds ratio 95% Confidence interval P value Age(mean ± SD) 71.1 ± 13.29 69.1 ± 16.20 0.495 Male gender 38(73.1%) 36(65.5%) 0.394 On oral antimicrobials 42(80.8%) 5(9%) 0.024 0.008–0.075 p < 0.00001 Left-side IE 50(96.2%) 54(98.2%) 0.525 Right-side IE 10(19.2%) 1(1.8%) 0.0778 0.00957- 0.632 0.003* Previous IE 13(25.0%) 9(16.4%) 0.269 Previous CAD 13(25.0%) 10(18.2%) 0.391 Atrial fibrillation 23(44.2%) 24(43.6%) 0.951 Congenital heart disease 2(3.8%) 3(5.5%) 0.694* Presence of pacemaker 11(21.2%) 7(12.7%) 0.244 Presence of ICD 4(7.7%) 1(1.8%) 0.197* Intravenous drug use 1(1.9%) 6(10.9%) 0.114* Diabetes 10(19.2% ) 14(25.5%) 0.440 Cerebrovascular disease 5(9.6%) 6(10.9%) 0.826 COPD 3(5.8% ) 7(12.7%) 0.322 Chronic renal failure 4(7.7%) 9(16.4%) 0.239 On hemodialysis 1(1.9% ) 0.0% 0.486 Solid organ or hematologic malignancy 7(13.5%) 10(18.2%) 0.504 Nosocomial IE 5(9.6%) 11(20.0%) 0.132 Healthcare-related NNIE 2(3.8%) 2(3.6%) 1.000 IVDU related IE 1(1.9%) 5(9.1%) 0.206 HF secondary to IE 15(28.8%) 15(27.3%) 0.856 Cardiogenic shock 0 4(7.3%) 0.119 Septic shock 4(7.7%) 7(12.7%) 0.528 Third degree AV block 3(5.8%) 1(1.8%) 0.354 Aortic involvement 39(75.0%) 40(72.7%) 0.789 TAVI 6(11.5%) 16(29.1%) 3.15 1.12–8.82 0.025 Mitral involvement 17(32.7%) 22(40.0%) 0.432 Intracardiac device involvement 21.2% 0.0% 0.0325** 0.00186- 0.568 < .001 Perivalvular aortic abscess 6(11.5%) 6(10.9%) 0.918 Paravalvular leak 7(13.5%) 14(25.5%) 0.118 LV ejection fraction (median, [IQR]) 60.0[50.00 -62.8] 60.0 [50.00- 60.5] 0.393 #PASP (mean ± SD) 37.0 ± 14.42 37.0 ± 14.07 0.977 Embolism 32(61.5%) 25(45.5%) 0.122 CNS embolism 13(25.0%) 12(21.8%) 0.697 Spondylodiscitis 11(21.2%) 6(10.9%) 0.147 Positive blood cultures 41(78.8%) 48(87.3%) 0.244 S.aureus etiology 7(13.5%) 8(14.5%) 0.872 Enterococcal etiology 14(26.9%) 8(14.5%) 0.113 Surgical indication 26(50.0%) 20(36.4%) 0.154 Euroscore II (median,IQR) 19[10.9–29.9] 13.2[7.2–25.9] 0.088 Death at 1 year FU 3/48(6.3%) 8/49(16.3%) 0.199* *Fisher’s Exact test; ** Haldane-Anscombe correction applied;#=9 missing values for group 1 and 7 missing values for group 2 in PASP; IE=infective endocarditis; SD=standard deviation; CAD=coronary heart disease; ICD=implanted cardiac defibrillator; COPD=chronic obstructive pulmonary disease; NNIE = non nosocomial infective endocarditis; IVDU=intravenous drug use; HF=heart failure; AV=atrioventricular; LV=left ventricular; PASP= pulmonary artery systolic pressure; CNS=central nervous system; FU=follow up Comparison of the 2 groups showed no differences in age or comorbidities. Euroscore II was 19[IQR 10.9–29.9] for G1 and 13.2[IQR 7.2–25.9] for G2 (p = 0.008). We found significant differences between groups for right-sided PVE, which occurred in 19.2% for group 1 and 1.8% for group 2 (p = 0.003). Pacemakers were present in 21.2% of the PET-CTRL group vs none in group 2 (p < 0.001). TAVI was less frequent in group 1 (11.5% vs 29.1%, p = 0.025). Spondylodiscitis was more frequent in group 1, occurring in 21.2% vs 10.9% of group 2, though with no statistical difference (NS). Furthermore, enterococci were the causative microorganisms in 26.9% of group 1, vs 14.5% in group 2 (NS). Surgery was indicated for 50.0% of group 1, vs 36.4% of group 2(NS). Prolonged antibiotic treatment was given for 42/52(80.8%) of the PET CTRL group and 5/55(9%) of group 2(p < 0.00001, OR 0.024, 95%CI 0.008–0.075). Follow up PET CT was found to be helpful in stopping or continuing antimicrobials for 25/42 (59.5%) of patients and unhelpful in 9/42(21.4%); antimicrobials were stopped due to toxicity in one patient. For 7(17%) patients it was not clear whether follow up PET CT was useful regarding therapy. Oral suppression was prescribed for 28 patients, most of which (22/28, 78.6%) consisted of amoxycillin 3 g/day. There were no hospitalizations due to IE relapses in either group over the period of 1 year. Death at 1 year was seen in 6.3% of group 1 vs 16.3% of group 2 (NS), for 48 and 49 patients in whom the data were available, respectively. Discussion Our study describes a real-life experience on the follow-up of patients with PVE who were treated conservatively, comparing the group who had sequential cardiac PET CT as part of their care to those who did not. PET CT was mainly used as a tool to evaluate the right timing for stopping antimicrobials, as 81% of the patients were on oral antibiotics in the PET CTRL group. Besides they had significantly more often concomitant intracardiac device infection and right-side IE. Although not statistically significant, patients in the PET CTRL group had proportionately more enterococcal infections and spondylodiscitis, and a higher Euroscore. The proposal for a potential role of follow up PET CT in the management of prosthetic valve endocarditis was published several years ago [ 8 ], albeit limited by technical issues at that time. Ouk et al . showed that all recurrences (12%) happened in patients with persistent abnormal prosthetic uptake at the second 18F-FDG-PET/CT and highlighted the potential value of investigating the evolution of spleen and bone-marrow uptake. Other studies have dealt with the potential utility of cardiac PET CT in conservatively treated patients with PVE. A study in France, between 2013 and 2019, of patients who were not treated with surgery, and who had at least two 18F-FDG- PET/CT examinations during their medical management reported that on their first follow-up 18F-FDG-PET/CT, 21 of 36 (58%) patients still had heterogeneous prosthesis uptake, indicating persistent active endocarditis [ 9 ]. Besides, they found that bone marrow and spleen hypermetabolism were still present in 4/6 patients whose IE recurred, indicating their prognostic value. Furthermore, Regis and colleagues studied 62 patients (42 of whom, or 68%, had prosthetic valve IE) who underwent an end- of- treatment FDG-PET/CT for non-operated IE [ 10 ]. The follow up PET CT was performed between 30 and 180 days of initiating antibiotic therapy. They found statistically significant differences in the proportion of positive scans in the last vs the first scan (53% vs. 77%), and more importantly, they also found that the relapse rate was significantly lower in negative (0/29) than in positive (7/33) end of treatment FDG-PET scans. We did not consistently have a measure of the Standardized Uptake Value (SUV) in the PET CT results, and different radiologists interpreted the exams over time. On the other hand, we had no relapses of IE in patients with PVE treated conservatively at our site, possibly due to the combined expert follow up by infectious diseases physicians and cardiologists, and the frequent use of PET scan and echocardiography to guide duration of therapy. Regarding long-term antibiotic therapy in patients with surgical indications who are not operated on, few studies, all of which were retrospective, have addressed this issue. The common scenario is of elderly patients with a high burden of comorbidities, in whom valve surgery or even device extraction is deemed too risky [ 13 – 15 ]. The first, a multicenter Spanish study of 32 adult patients presenting with IE between 2011 and 2019, with a median age of 72 years, had nearly two thirds with PVE [ 13 ]. In this series, in which fungal IE was excluded, four patients presented a relapse (12.5%) and 4 (12.5%) had an IE related death between 2 months and 3 years. PET CT was used in 12/32(37.5%) cases, and in 9/12 cases it was used to stop antibiotics; noteworthily, in none of those patients in whom PET was used as a tool to guide antibiotic therapy was there a relapse on follow up, similarly to our findings. A second study, in Strasbourg, France, in the years 2020–2023, evaluated 22 patients received long term antibiotic therapy; they had a mean age of 77 years, 14(63.6%) had PVE (of which 9 TAVIs) and 6(27.3%) had cardiac device IE [ 14 ]. Twenty patients (91%) had an indication of surgical IE management or CIED removal, but none underwent these procedures. No relapses were noted at 1 year follow up, but mortality was 25% in 1 year[ 14 ]. This paper does not discuss any role of PET CT use for judging termination of suppressive therapy[ 14 ]. Finally, a study on 42 patients, from Paris, France, in the years 2016–2022, of which 64% had prosthetic valves (of which 5 were TAVIs), 31% cardiac implantable electronic devices and 26% both, evaluated suppressive antimicrobial treatment [ 15 ]. An initial PET CT was done in 38/42 (90%), and increased uptake was seen in 81% of cases (31/38). Of the patients in this group, 64% (20/31) underwent a second round of imaging at the end of curative treatment, and 35% (7/20) still had pathological fixation on the IE site [ 15 ]. Similarly to our study, enterococcus was often a causative microorganism (36%) and amoxicillin was often used as suppressive therapy (45%). However, drug adverse events were relatively frequent, albeit minor (12%), as were relapses/ reinfections (12% for both); 15.7% of patients died at 1 year. Interestingly, the death rate was like that of our group of patients who did not have follow up PET CT, which was 16.3% [ 15 ]. In summary, our study showed that sequential PET CT was helpful in the management of inoperable patients, guiding the duration of suppressive therapy. The PET CTRL scans, when showing a decreased uptake, taken together with other parameters, such as the overall clinical conditions of the patients, as well as inflammatory markers (C reactive protein levels and rheumatoid factor), were taken as a sign of resolution of the infective process. There were no relapses in either group and the mortality rates were not different statistically, despite the fact patients more often had enterococcal endocarditis, a difficult to treat and more often relapsing microorganism. Limitations Our study has several limitations. First, it is a retrospective post hoc analysis from a single tertiary referral center, which may limit the generalizability of our findings. Second, the decision to perform follow-up PET/CT scans was not standardized but rather based on physician judgment, introducing a potential selection bias. Third, the sample size, especially in the subgroup of patients undergoing repeat PET/CT, was relatively small, limiting the power to detect differences in outcomes such as relapse or mortality. Finally, the relatively short follow-up period prevents any firm conclusions on the prognostic value of repeat PET/CT. Larger, multicenter prospective studies are needed to confirm these findings and to define standardized protocols for the use of PET/CT in the follow-up of prosthetic valve endocarditis. Conclusions In this real-life cohort of prosthetic valve endocarditis managed without surgery, sequential PET-CT was mainly used to guide the duration of antimicrobial therapy, especially in patients with more complex or severe profiles. Outcomes in one year were comparable whether patients did or did not have PET-CT follow-up, but the study was not powered to assess relapse or mortality. PET-CT may therefore complement clinical and biological assessment in selected inoperable patients, while larger prospective studies are needed to define its prognostic value and optimal role. Declarations Competing interests The authors have no relevant financial or non-financial interests to disclose. Ethics approval This study was approved by the health data access portal, PADS, under number PADS-DRKDPX. Consent to participate No patients objected to their data being collected during the study period. Consent to publish Patients’ individual data are not present in the study and therefore there are confidentiality issues involved. Funding Dr. Lamas was supported by the Brazilian Ministry of Health, via her institutions ( Instituto Nacional de Cardiologia and Instituto Nacional de INfectologia Evandro Chagas, Fiocruz, Rio de Janeiro), to develop the project on the role of PET CT in patients with prosthetic valve endocarditis. Author Contributions All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Cristiane Lamas, Mary Philip, Titouan Runet, Laetitia Tessonier, Sandrine Hubert, Florent Arregle, Gilbert Habib, Marcelo Correia et Frederique Gouriet. The first draft of the manuscript was written by Cristiane Lamas and all authors commented on previous versions of the manuscript. All authors read and approved of the final manuscript. Acknowledgments: We thank Dr. Jean Paul Casalta for his role in patient care, being part of the Endocarditis Team at La Timone. Data Availability The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request, depending on institutional approval. References Bayer AS, Chambers HF (2021) Prosthetic Valve Endocarditis Diagnosis and Management- New Paradigm Shift Narratives. Clin Infect Dis 72(10):1687–1692. 10.1093/cid/ciab036 Habib G, Lancellotti P, Antunes MJ, Bongiorni MG, Casalta J-P, Del Zotti F et al (2015) 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)Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM). 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Infect Dis Now 54(3):104867. 10.1016/j.idnow.2024.104867 Beaumont AL, Mestre F, Decaux S, Bertin C, Duval X, Iung B, Rouzet F, Grall N, Para M, Thy M, Deconinck L (2024) Long-term Oral Suppressive Antimicrobial Therapy in Infective Endocarditis (SATIE Study): An Observational Study. Open Forum Infect Dis 11(5):ofae194. 10.1093/ofid/ofae194 Additional Declarations The authors declare no competing interests. Supplementary Files GraphicAbstract.png Graphic abstract of the PET/ Control study: repeat PET-CT scans in the follow up of non-operated patients with prosthetic valve endocarditis 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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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9313376","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":617186176,"identity":"e9f2a3d1-bbb7-4457-b48d-0ce59227aee5","order_by":0,"name":"Cristiane Lamas","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABA0lEQVRIiWNgGAWjYFACxgYGBgMgzQ7m2YBEGg8Q1HIApIUZzEsDixDQAgRgFRAthxECuAD/7MPNnz8U2OXxMzM/3fDjz3m7te2HgbbU2ETj0iJxLrFN4oBBcrFkM5vZzd6228nbziQCtRxLy23AocWAh7EN6BfmxA2HGcxu8DbcTjY7ANTC2HAYn5bmDwcM6hP3H2b/dvPPn3PJZucfEtTSAHTY4cQNzDxmt3nYDtiZ3SBgi8QZxjaJMwbHE2cc5im7LduWnGB2A2hLAh6/8PewP/5Q8ac6sb+9fdvNN3/s7M3Opz988KHGBqcWDJAIVplArHIQsCdF8SgYBaNgFIwMAAAKdGaWlhSHugAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0002-5561-999X","institution":"Instituto Nacional de Cardiologia","correspondingAuthor":true,"prefix":"","firstName":"Cristiane","middleName":"","lastName":"Lamas","suffix":""},{"id":617186177,"identity":"47cfa8f2-a28d-4c41-9f93-f85f83b4537b","order_by":1,"name":"Mary Philip","email":"","orcid":"","institution":"Cardiology Department, La Timone Hospital","correspondingAuthor":false,"prefix":"","firstName":"Mary","middleName":"","lastName":"Philip","suffix":""},{"id":617186178,"identity":"e33d6559-9cdf-4c1b-af9b-1f0e6ba0eef8","order_by":2,"name":"Titouan Runet","email":"","orcid":"","institution":"Cardiology Department, La Timone Hospital","correspondingAuthor":false,"prefix":"","firstName":"Titouan","middleName":"","lastName":"Runet","suffix":""},{"id":617186179,"identity":"5f159290-f2e9-47f7-b346-d01d0c05abdf","order_by":3,"name":"Laetitia Tessonnier","email":"","orcid":"","institution":"Radiology Department, La Timone Hospital","correspondingAuthor":false,"prefix":"","firstName":"Laetitia","middleName":"","lastName":"Tessonnier","suffix":""},{"id":617186180,"identity":"a4e274de-77de-4908-99c4-81a2255ca448","order_by":4,"name":"Marcelo Goulart Correia","email":"","orcid":"","institution":"Instituto Nacional de Cardiologia","correspondingAuthor":false,"prefix":"","firstName":"Marcelo","middleName":"Goulart","lastName":"Correia","suffix":""},{"id":617186181,"identity":"5ae2d86a-3245-4145-8c79-45af04d2746e","order_by":5,"name":"Sandrine Hubert","email":"","orcid":"","institution":"Cardiology Department, La Timone Hospital","correspondingAuthor":false,"prefix":"","firstName":"Sandrine","middleName":"","lastName":"Hubert","suffix":""},{"id":617186182,"identity":"c2f49525-0f21-49e0-b189-d93abf14f644","order_by":6,"name":"Florent Arregle","email":"","orcid":"","institution":"Cardiology Department, La Timone Hospital","correspondingAuthor":false,"prefix":"","firstName":"Florent","middleName":"","lastName":"Arregle","suffix":""},{"id":617186183,"identity":"6c9724a2-58f8-49b0-8e5a-ce976e0656be","order_by":7,"name":"Gilbert Habib","email":"","orcid":"","institution":"Cardiology Department, La Timone Hospital","correspondingAuthor":false,"prefix":"","firstName":"Gilbert","middleName":"","lastName":"Habib","suffix":""},{"id":617186184,"identity":"8144e36c-cec0-43a4-8e0a-14ac2992242d","order_by":8,"name":"Frédérique Gouriet","email":"","orcid":"","institution":"Institut Mediterrannée Infection","correspondingAuthor":false,"prefix":"","firstName":"Frédérique","middleName":"","lastName":"Gouriet","suffix":""}],"badges":[],"createdAt":"2026-04-03 13:32:08","currentVersionCode":1,"declarations":{"humanSubjects":true,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":true,"humanSubjectConsent":true,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-9313376/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9313376/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107868459,"identity":"7f553d89-843a-4aa5-a26b-5c7e9c23ec46","added_by":"auto","created_at":"2026-04-27 07:17:45","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":321206,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9313376/v1/6fafc89a-c840-4753-9c0d-dc21ce28cbe5.pdf"},{"id":106201374,"identity":"41ef0c5f-b3ae-438c-9411-210c7214a40f","added_by":"auto","created_at":"2026-04-06 03:13:32","extension":"png","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":2744712,"visible":true,"origin":"","legend":"\u003cp\u003eGraphic abstract of th\u003cstrong\u003ee PET/ Control study: repeat PET-CT scans in the follow up of non-operated patients with prosthetic valve endocarditis\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"GraphicAbstract.png","url":"https://assets-eu.researchsquare.com/files/rs-9313376/v1/b3e4e96df0c540e4bd1f6728.png"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eThe PET/ Control study: repeat PET-CT scans in the follow up of non-operated patients with prosthetic valve endocarditis.\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSeveral observational series have reported the diagnostic value of 18-fluorine-fluorodeoxyglucose positron emission tomography coupled with computed tomography (18F-FDG-PET/CT, or simply PET CT) in patients with prosthetic valve endocarditis (PVE) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. An increased contrast uptake has been proposed as a major criterion when the prosthesis has been inserted for more than 3 months [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], and more recently as a minor criterion if implanted less than one month before the infective endocarditis (IE) episode [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Infective endocarditis increasingly affects an older population with significant comorbidities and high surgical risk [\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Prosthetic valve endocarditis is a particularly difficult- to- treat infection, with higher mortality rates, and patients with PVE tend to be older and carry a higher burden of comorbidities [\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Therefore, it is not unusual, in clinical practice, to manage inoperable patients with PVE, most often due to their very high surgical risk, and less frequently because of technical challenges or refusal of surgery by the patient or family. PET CT has been shown to be useful in the follow-up of patients treated conservatively, potentially indicating persistent infection and risk of relapse [\u003cspan additionalcitationids=\"CR8 CR9\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOur aim is to describe our real-life experience in the follow- up of patients with PVE who were treated conservatively and compare the features of those who had PET-CT follow-up to those without PET-CT follow-up.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eStudy design\u003c/p\u003e \u003cp\u003eWe performed a \u003cem\u003epost hoc\u003c/em\u003e analysis of cardiac PET CT scan results of adult patients with definite PVE, prospectively included at a cardiology referral center in Marseille, France, in the period of January 2019 to February 2024. Cases were defined by the Duke modified criteria [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]and the ESC 2015 criteria [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eStudy variables included were demographic, clinical, comorbidities, echocardiographic, complications and in-hospital mortality.\u003c/p\u003e \u003cp\u003eIn the study site, cardiac PET CT scans are performed routinely for all IE patients at entry, and radiologists experienced in cardiac PET CT in endocarditis interpret them. Follow up visits are done by infectious diseases physicians and cardiologists at 1, 3, 6 and 12 months, and TTE with or without TEE are performed on the same day. Institutional protocols have been described in detail elsewhere [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Follow up PET CT is done on demand by the expert infectious diseases physicians on site.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eDefinitions\u003c/strong\u003e \u003cp\u003eProlonged antibiotic therapy was defined as any antimicrobial continued beyond the standard treatment duration for infective endocarditis, defined as per guidelines [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003c/p\u003e \u003cp\u003eRelapse was defined as a second episode of IE caused by the same microorganism and reinfection as a second episode of IE caused by a different microorganism [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eFrequencies, means with standard deviations, or medians with interquartile ranges were reported according to data distribution, assessed by the Kolmogorov-Smirnov test. Patients treated conservatively with PET-CT follow-up (group 1) were compared to those without PET-CT follow-up (group 2). Student\u0026rsquo;s t-test was used to compare normally distributed continuous variables and the Mann Whitney test for non-normal ones. The chi square test and Fisher\u0026rsquo;s exact test, when indicated, were used to calculate differences in dichotomic variables. Statistical analyses were performed with Jamovi version 2.6.13.\u003c/p\u003e \u003cp\u003eEthics\u003c/p\u003e \u003cp\u003eThe study was approved by the health data access portal, PADS, under number PADS-DRKDPX. No patients objected to their data being collected during the study period.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eWe included 200 patients with PVE from January 2019 to February 2024; 27(13.5%) died during hospitalization, 67(22.35%) underwent surgery and survived. Although systematic PET/CT is part of patient care, it was performed in 158(79%) cases. Reasons for not performing PET CT were clinical instability in 17/42 (40.4%), decompensated diabetes, inadequate dietetic preparation, claustrophobia, peripheral venous access failure and patient refusal. Therefore, we analyzed 106 patients, all of whom were treated conservatively for PVE. Of these, 52 belonged to group 1, which were those who had a follow up outpatient PET scan, described as the PET/CTRL group, and 55 to group 2 (those who were followed up at outpatients but did not have a PET CT demanded). For both groups, mean age was 70.1\u0026thinsp;\u0026plusmn;\u0026thinsp;14.8 years, and 69.2% were male. Left-sided PVE affected 97.2%, and right-sided 10.3%. Previous IE had occurred in 20.6%. Comorbidities were frequent: diabetes in 22.4%, coronary artery disease 21.5%, cancer in 15.9%, chronic renal failure in 12.1%, COPD in 9.3%; active intravenous drug use was present in 6.5%. Median Euroscore II was 15.6[IQR 9.78\u0026ndash;27.8]. PVE was community acquired in 76.6%.\u003c/p\u003e \u003cp\u003eA bivariate analysis comparing the 2 groups is presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of selected variables in patients with prosthetic valve endocarditis treated conservatively, with PET CT follow-up (PET control group, or group 1) and those without PET CT follow-up (group 2).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSelected Variables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGroup 1\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;52)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGroup 2\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;55)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eOdds ratio\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e95% Confidence interval\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge(mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e71.1\u0026thinsp;\u0026plusmn;\u0026thinsp;13.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e69.1\u0026thinsp;\u0026plusmn;\u0026thinsp;16.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.495\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale gender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38(73.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36(65.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.394\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOn oral antimicrobials\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42(80.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5(9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.024\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.008\u0026ndash;0.075\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.00001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeft-side IE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50(96.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54(98.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.525\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRight-side IE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10(19.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(1.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.0778\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.00957- 0.632\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.003*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrevious IE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13(25.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9(16.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.269\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrevious CAD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13(25.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10(18.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.391\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAtrial fibrillation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23(44.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24(43.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.951\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCongenital heart disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(3.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(5.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.694*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresence of pacemaker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11(21.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7(12.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.244\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresence of ICD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4(7.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(1.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.197*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntravenous drug use\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(1.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6(10.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.114*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10(19.2% )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14(25.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.440\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCerebrovascular disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5(9.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6(10.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.826\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCOPD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3(5.8% )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7(12.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.322\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic renal failure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4(7.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9(16.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.239\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOn hemodialysis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(1.9% )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.486\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSolid organ or hematologic malignancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7(13.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10(18.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.504\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNosocomial IE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5(9.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11(20.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.132\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHealthcare-related NNIE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(3.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2(3.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIVDU related IE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(1.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5(9.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.206\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHF secondary to IE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15(28.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15(27.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.856\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCardiogenic shock\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4(7.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.119\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSeptic shock\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4(7.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7(12.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.528\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThird degree AV block\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3(5.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(1.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.354\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAortic involvement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39(75.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40(72.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.789\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTAVI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6(11.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16(29.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e3.15\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e1.12\u0026ndash;8.82\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.025\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMitral involvement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17(32.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22(40.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.432\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntracardiac device involvement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21.2%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.0325**\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.00186- 0.568\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePerivalvular aortic abscess\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6(11.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6(10.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.918\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParavalvular leak\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7(13.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14(25.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.118\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLV ejection fraction (median, [IQR])\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60.0[50.00 -62.8]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60.0 [50.00- 60.5]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.393\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#PASP (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37.0\u0026thinsp;\u0026plusmn;\u0026thinsp;14.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37.0\u0026thinsp;\u0026plusmn;\u0026thinsp;14.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.977\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEmbolism\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32(61.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25(45.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.122\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCNS embolism\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13(25.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12(21.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.697\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpondylodiscitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11(21.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6(10.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.147\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive blood cultures\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41(78.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48(87.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.244\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eS.aureus\u003c/em\u003e etiology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7(13.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8(14.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.872\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEnterococcal etiology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14(26.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8(14.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.113\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgical indication\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26(50.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20(36.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.154\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEuroscore II (median,IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19[10.9\u0026ndash;29.9]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.2[7.2\u0026ndash;25.9]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.088\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeath at 1 year FU\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3/48(6.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8/49(16.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.199*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e*Fisher\u0026rsquo;s Exact test; ** Haldane-Anscombe correction applied;#=9 missing values for group 1 and 7 missing values for group 2 in PASP; IE=infective endocarditis; SD=standard deviation; CAD=coronary heart disease; ICD=implanted cardiac defibrillator; COPD=chronic obstructive pulmonary disease; NNIE\u0026thinsp;=\u0026thinsp;non nosocomial infective endocarditis; IVDU=intravenous drug use; HF=heart failure; AV=atrioventricular; LV=left ventricular; PASP= pulmonary artery systolic pressure; CNS=central nervous system; FU=follow up\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eComparison of the 2 groups showed no differences in age or comorbidities. Euroscore II was 19[IQR 10.9\u0026ndash;29.9] for G1 and 13.2[IQR 7.2\u0026ndash;25.9] for G2 (p\u0026thinsp;=\u0026thinsp;0.008). We found significant differences between groups for right-sided PVE, which occurred in 19.2% for group 1 and 1.8% for group 2 (p\u0026thinsp;=\u0026thinsp;0.003). Pacemakers were present in 21.2% of the PET-CTRL group vs none in group 2 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). TAVI was less frequent in group 1 (11.5% vs 29.1%, p\u0026thinsp;=\u0026thinsp;0.025). Spondylodiscitis was more frequent in group 1, occurring in 21.2% vs 10.9% of group 2, though with no statistical difference (NS). Furthermore, enterococci were the causative microorganisms in 26.9% of group 1, vs 14.5% in group 2 (NS). Surgery was indicated for 50.0% of group 1, vs 36.4% of group 2(NS).\u003c/p\u003e \u003cp\u003eProlonged antibiotic treatment was given for 42/52(80.8%) of the PET CTRL group and 5/55(9%) of group 2(p\u0026thinsp;\u0026lt;\u0026thinsp;0.00001, OR 0.024, 95%CI 0.008\u0026ndash;0.075). Follow up PET CT was found to be helpful in stopping or continuing antimicrobials for 25/42 (59.5%) of patients and unhelpful in 9/42(21.4%); antimicrobials were stopped due to toxicity in one patient. For 7(17%) patients it was not clear whether follow up PET CT was useful regarding therapy. Oral suppression was prescribed for 28 patients, most of which (22/28, 78.6%) consisted of amoxycillin 3 g/day.\u003c/p\u003e \u003cp\u003eThere were no hospitalizations due to IE relapses in either group over the period of 1 year. Death at 1 year was seen in 6.3% of group 1 vs 16.3% of group 2 (NS), for 48 and 49 patients in whom the data were available, respectively.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur study describes a real-life experience on the follow-up of patients with PVE who were treated conservatively, comparing the group who had sequential cardiac PET CT as part of their care to those who did not. PET CT was mainly used as a tool to evaluate the right timing for stopping antimicrobials, as 81% of the patients were on oral antibiotics in the PET CTRL group. Besides they had significantly more often concomitant intracardiac device infection and right-side IE. Although not statistically significant, patients in the PET CTRL group had proportionately more enterococcal infections and spondylodiscitis, and a higher Euroscore.\u003c/p\u003e \u003cp\u003eThe proposal for a potential role of follow up PET CT in the management of prosthetic valve endocarditis was published several years ago [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], albeit limited by technical issues at that time. Ouk \u003cem\u003eet al\u003c/em\u003e. showed that all recurrences (12%) happened in patients with persistent abnormal prosthetic uptake at the second 18F-FDG-PET/CT and highlighted the potential value of investigating the evolution of spleen and bone-marrow uptake.\u003c/p\u003e \u003cp\u003eOther studies have dealt with the potential utility of cardiac PET CT in conservatively treated patients with PVE. A study in France, between 2013 and 2019, of patients who were not treated with surgery, and who had at least two 18F-FDG- PET/CT examinations during their medical management reported that on their first follow-up 18F-FDG-PET/CT, 21 of 36 (58%) patients still had heterogeneous prosthesis uptake, indicating persistent active endocarditis [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Besides, they found that bone marrow and spleen hypermetabolism were still present in 4/6 patients whose IE recurred, indicating their prognostic value. Furthermore, Regis and colleagues studied 62 patients (42 of whom, or 68%, had prosthetic valve IE) who underwent an end- of- treatment FDG-PET/CT for non-operated IE [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The follow up PET CT was performed between 30 and 180 days of initiating antibiotic therapy. They found statistically significant differences in the proportion of positive scans in the last vs the first scan (53% vs. 77%), and more importantly, they also found that the relapse rate was significantly lower in negative (0/29) than in positive (7/33) end of treatment FDG-PET scans. We did not consistently have a measure of the Standardized Uptake Value (SUV) in the PET CT results, and different radiologists interpreted the exams over time. On the other hand, we had no relapses of IE in patients with PVE treated conservatively at our site, possibly due to the combined expert follow up by infectious diseases physicians and cardiologists, and the frequent use of PET scan and echocardiography to guide duration of therapy.\u003c/p\u003e \u003cp\u003eRegarding long-term antibiotic therapy in patients with surgical indications who are not operated on, few studies, all of which were retrospective, have addressed this issue. The common scenario is of elderly patients with a high burden of comorbidities, in whom valve surgery or even device extraction is deemed too risky [\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The first, a multicenter Spanish study of 32 adult patients presenting with IE between 2011 and 2019, with a median age of 72 years, had nearly two thirds with PVE [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. In this series, in which fungal IE was excluded, four patients presented a relapse (12.5%) and 4 (12.5%) had an IE related death between 2 months and 3 years. PET CT was used in 12/32(37.5%) cases, and in 9/12 cases it was used to stop antibiotics; noteworthily, in none of those patients in whom PET was used as a tool to guide antibiotic therapy was there a relapse on follow up, similarly to our findings. A second study, in Strasbourg, France, in the years 2020\u0026ndash;2023, evaluated 22 patients received long term antibiotic therapy; they had a mean age of 77 years, 14(63.6%) had PVE (of which 9 TAVIs) and 6(27.3%) had cardiac device IE [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Twenty patients (91%) had an indication of surgical IE management or CIED removal, but none underwent these procedures. No relapses were noted at 1 year follow up, but mortality was 25% in 1 year[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. This paper does not discuss any role of PET CT use for judging termination of suppressive therapy[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Finally, a study on 42 patients, from Paris, France, in the years 2016\u0026ndash;2022, of which 64% had prosthetic valves (of which 5 were TAVIs), 31% cardiac implantable electronic devices and 26% both, evaluated suppressive antimicrobial treatment [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. An initial PET CT was done in 38/42 (90%), and increased uptake was seen in 81% of cases (31/38). Of the patients in this group, 64% (20/31) underwent a second round of imaging at the end of curative treatment, and 35% (7/20) still had pathological fixation on the IE site [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Similarly to our study, enterococcus was often a causative microorganism (36%) and amoxicillin was often used as suppressive therapy (45%). However, drug adverse events were relatively frequent, albeit minor (12%), as were relapses/ reinfections (12% for both); 15.7% of patients died at 1 year. Interestingly, the death rate was like that of our group of patients who did not have follow up PET CT, which was 16.3% [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn summary, our study showed that sequential PET CT was helpful in the management of inoperable patients, guiding the duration of suppressive therapy. The PET CTRL scans, when showing a decreased uptake, taken together with other parameters, such as the overall clinical conditions of the patients, as well as inflammatory markers (C reactive protein levels and rheumatoid factor), were taken as a sign of resolution of the infective process. There were no relapses in either group and the mortality rates were not different statistically, despite the fact patients more often had enterococcal endocarditis, a difficult to treat and more often relapsing microorganism.\u003c/p\u003e\n\u003ch3\u003eLimitations\u003c/h3\u003e\n\u003cp\u003eOur study has several limitations. First, it is a retrospective \u003cem\u003epost hoc\u003c/em\u003e analysis from a single tertiary referral center, which may limit the generalizability of our findings. Second, the decision to perform follow-up PET/CT scans was not standardized but rather based on physician judgment, introducing a potential selection bias. Third, the sample size, especially in the subgroup of patients undergoing repeat PET/CT, was relatively small, limiting the power to detect differences in outcomes such as relapse or mortality. Finally, the relatively short follow-up period prevents any firm conclusions on the prognostic value of repeat PET/CT. Larger, multicenter prospective studies are needed to confirm these findings and to define standardized protocols for the use of PET/CT in the follow-up of prosthetic valve endocarditis.\u003c/p\u003e "},{"header":"Conclusions","content":"\u003cp\u003eIn this real-life cohort of prosthetic valve endocarditis managed without surgery, sequential PET-CT was mainly used to guide the duration of antimicrobial therapy, especially in patients with more complex or severe profiles. Outcomes in one year were comparable whether patients did or did not have PET-CT follow-up, but the study was not powered to assess relapse or mortality. PET-CT may therefore complement clinical and biological assessment in selected inoperable patients, while larger prospective studies are needed to define its prognostic value and optimal role.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eCompeting interests\u003c/h2\u003e\n\u003cp\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003ch2\u003eEthics approval\u003c/h2\u003e\n\u003cp\u003eThis study was approved by the health data access portal, PADS, under number PADS-DRKDPX.\u003c/p\u003e\n\u003ch2\u003eConsent to participate\u003c/h2\u003e\n\u003cp\u003eNo patients objected to their data being collected during the study period.\u003c/p\u003e\n\u003ch2\u003eConsent to publish\u003c/h2\u003e\n\u003cp\u003ePatients\u0026rsquo; individual data are not present in the study and therefore there are confidentiality issues involved.\u003c/p\u003e\n\u003ch2\u003eFunding\u003c/h2\u003e\n\u003cp\u003eDr. Lamas was supported by the Brazilian Ministry of Health, via her institutions ( Instituto Nacional de Cardiologia and Instituto Nacional de INfectologia Evandro Chagas, Fiocruz, Rio de Janeiro), to develop the project on the role of PET CT in patients with prosthetic valve endocarditis.\u003c/p\u003e\n\u003ch2\u003eAuthor Contributions\u003c/h2\u003e\n\u003cp\u003eAll authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Cristiane Lamas, Mary Philip, Titouan Runet, Laetitia Tessonier, Sandrine Hubert, Florent Arregle, Gilbert Habib, Marcelo Correia et Frederique Gouriet. The first draft of the manuscript was written by Cristiane Lamas and all authors commented on previous versions of the manuscript. All authors read and approved of the final manuscript.\u003c/p\u003e\n\u003ch2\u003eAcknowledgments:\u003c/h2\u003e\n\u003cp\u003eWe thank Dr. Jean Paul Casalta for his role in patient care, being part of the Endocarditis Team at La Timone.\u003c/p\u003e\n\u003ch2\u003eData Availability\u003c/h2\u003e\n\u003cp\u003eThe datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request, depending on institutional approval.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBayer AS, Chambers HF (2021) Prosthetic Valve Endocarditis Diagnosis and Management- New Paradigm Shift Narratives. 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Open Forum Infect Dis 11(5):ofae194. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/ofid/ofae194\u003c/span\u003e\u003cspan address=\"10.1093/ofid/ofae194\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[{"identity":"368c5b15-6679-45a4-853a-3ebb94448973","identifier":"10.13039/501100006506","name":"Ministério da Saúde","awardNumber":"Instituto Nacional de Cardiologia and Instituto Nacional de Infectologia Evandro Chagas, Fiocruz","order_by":0}],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Institut Mediterranée Infection","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":"prosthetic valve endocarditis, 18 F FDG PET/CT, antibiotic therapy","lastPublishedDoi":"10.21203/rs.3.rs-9313376/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9313376/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose\u003c/strong\u003e: Our aim is to describe our real-life experience in the follow- up of patients with prosthetic valve endocarditis (PVE) who were treated conservatively and compare the features of those who had 18-fluorine-fluorodeoxyglucose positron emission tomography coupled with computed tomography (PET-CT) follow-up to those without PET-CT follow-up.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: We performed a \u003cem\u003epost hoc\u003c/em\u003e analysis of cardiac PET CT scan results of adult patients with definite PVE, prospectively included at a cardiology referral center. Patients treated conservatively with PET-CT follow-up (group 1) were compared to those without PET-CT follow-up (group 2). Statistics were performed with Jamovi 2.6.13.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: Patients who had PET CTRL had higher Euroscore II (19 vs 13.2, p=0.008), more pacemakers (21.2% vs 0, p \u0026lt; 0.001), more spondylodiscitis (21.2% vs 10.9% p NS) and more enterococci (26.9% vs 14.5%, p NS). Surgery was indicated for 50.0% of group 1, vs 36.4% of group 2(p NS). Prolonged antibiotic treatment was given for 42/52(80.8%) of the PET CTRL group vs 5/55(9%) (p\u0026lt; 0.00001, OR 0.024, 95%CI 0.008- 0.075). Follow up PET CT was helpful in stopping or continuing antimicrobials for 25/42 (59.5%). There were no hospitalizations due to IE relapses in either group over the period of 1 year. Death at 1 year was seen in 6.3% vs 16.3% (p NS).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: Sequential PET-CT was mainly used to guide the duration of antimicrobial therapy, especially in patients with PVE with more complex or severe profiles. PET-CT may complement clinical and biological assessment in selected inoperable patients with PVE.\u003c/p\u003e","manuscriptTitle":"The PET/ Control study: repeat PET-CT scans in the follow up of non-operated patients with prosthetic valve endocarditis.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-06 03:13:28","doi":"10.21203/rs.3.rs-9313376/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":"4dc6cc19-7dcd-41b5-a794-97032b9cdaa9","owner":[],"postedDate":"April 6th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":65683273,"name":"Infectious Diseases"}],"tags":[],"updatedAt":"2026-04-06T03:13:28+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-06 03:13:28","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9313376","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9313376","identity":"rs-9313376","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}