Infective endocarditis in the Netherlands:current epidemiological profile and mortality An analysis based on partial ESC EORP collected data

Introduction: Infective endocarditis (IE) is associated with a high in-hospital and long term mortality. Although progress has been made in diagnostic approach and management of IE, morbidity and mortality of IE remain high. In the latest European guidelines, the importance of the multi-modality imaging in diagnosis and follow up of IE is emphasized. Aim: The aim was to provide information regarding mortality and adverse events of IE, to determine IE characteristics and to assess current use of imaging in the diagnostic workup of IE. Methods: This is a prospective observational cohort study. We used data from the EURO-ENDO registry. Seven hospitals in the Netherlands have participated and included patients with IE between April 2016 and April 2018. Results: A total of 139 IE patients were included. Prosthetic valve endocarditis constituted 32.4% of the cases, cardiac device related IE 7.2% and aortic root prosthesis IE 3.6%. In-hospital mortality was 14.4% (20 patients) and one-year mortality was 21.6% (30 patients). The incidence of embolic events under treatment was 16.5%, while congestive heart failure or cardiogenic shock occurred in 15.1% of the patients. Transthoracic and transoesophageal echocardiography were performed most frequently (97.8%; 81.3%) and within 3 days after IE suspicion, followed by 18F‑fluorodeoxyglucose positron emission tomography/computed tomography (45.3%) within 6 days and multi-slice computed tomography (42.4%) within 7 days. Conclusion: We observed a high percentage of prosthetic valve endocarditis, rapid and extensive use of imaging and a relatively low in-hospital and one-year mortality of IE in the Netherlands. Limitations include possible selection bias

Added value of 18F-FDG-PET/CT and cardiac CTA in suspected transcatheter aortic valve endocarditis

Backgrounds: Transcatheter-implanted aortic valve infective endocarditis (TAVI-IE) is difficult to diagnose when relying on the Duke Criteria. Our aim was to assess the additional diagnostic value of 18F-fluorodeoxyglucose (18F-FDG) positron emission/computed tomography (PET/CT) and cardiac computed tomography angiography (CTA) in suspected TAVI-IE. Methods: A multicenter retrospective analysis was performed in all patients who underwent 18F-FDG-PET/CT and/or CTA with suspected TAVI-IE. Patients were first classified with Duke Criteria and after adding 18F-FDG-PET/CT and CTA, they were classified with European Society of Cardiology (ESC) criteria. The final diagnosis was determined by our Endocarditis Team based on ESC guideline recommendations. Results: Thirty patients with suspected TAVI-IE were included. 18F-FDG-PET/CT was performed in all patients and Cardiac CTA in 14/30. Using the Modified Duke Criteria, patients were classified as 3% rejected (1/30), 73% possible (22/30), and 23% definite (7/30) TAVI-IE. Adding 18F-FDG-PET/CT and CTA supported the reclassification of 10 of the 22 possible cases as “definite TAVI-IE” (5/22) or “rejected TAVI-IE” (5/22). This changed the final diagnosis to 20% rejected (6/30), 40% possible (12/30), and 40% definite (12/30) TAVI-IE. Conclusions: Addition of 18F-FDG-PET/CT and/or CTA changed the final diagnosis in 33% of patients and proved to be a valuable diagnostic tool in patients with suspected TAVI-IE

Normal imaging findings after ascending aorta prosthesis implantation on 18F-Fluorodeoxyglucose Positron Emission Tomography with computed tomography

Background: To diagnose abnormal 18F-Fluorodeoxyglucose (18F-FDG) uptake in suspected endocarditis after aortic root and/or ascending aorta prosthesis (ARAP) implantation, it is important to first establish the normal periprosthetic uptake on positron emission tomography with computed tomography (PET/CT). Methods: Patients with uncomplicated ARAP implantation were prospectively included and underwent 18F-FDG-PET/CT at either 12 (± 2) weeks (group 1) or 52 (± 8) weeks (group 2) after procedure. Uptake on three different locations of the prosthesis (“cranial anastomosis (CA),” “prosthetic heart valve (PHV),” “ascending aorta prosthesis (AAP)”) was scored visually (none/low/intermediate/high) and quantitatively (maximum standardized uptake value (SUVmax) and target-to-background ratio (SUVratio). Results: In total, 20 patients (group 1: n = 10, group 2: n = 10) (mean age 64±7 years, 70% male) were included. Both groups had similar visual uptake intensity for all measured areas (CA: mostly low-intermediate (16/20 (80%)), p = .17; PHV: low-intermediate (16/20 (80%)), p = .88; AAP: low-intermediate (19/20 (95%)), p = .48). SUVmax for CA was 5.6 [4.1-6.1] and 3.8 [3.1-5.9] (median [IQR], p = .19), and around PHV 5.0 [4.1-5.7] and 6.3 [4.6-7.1] (p = .11) for groups 1 and 2, respectively. SUVratio for CA was 2.8 [2.3-3.2] and 2.0 [1.7-2.6] (median [IQR], p = .07) and around PHV 2.5 [2.4-2.8] and 2.9 [2.3-3.5] (median [IQR], p = .26) for groups 1 and 2, respectively. Conclusion: No significant differences were observed between PET/CT findings at 3 months and 1 year after ARAP implantation, warranting caution in interpretation of PET/CT in the first year after implantation

Role of cardiac ct in infective endocarditis: Current evidence, opportunities, and challenges

Infective endocarditis (IE) can present with variable clinical and imaging findings and is associated with high morbidity and mortality. Substantial improvement of CT technology, most notably improved temporal and spatial resolution, has resulted in increased use of this modality in the evaluation of IE. The aim of this article is to review the potential role of cardiac CT in evaluating IE

18F-FDG/PET-CT imaging findings after sternotomy

Background: The clinical diagnosis of deep sternal wound infection (DSWI) is supported by imaging findings including 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT). To avoid misinterpretation due to normal post-surgery inflammation we assessed normal imaging findings in non-infected patients after sternotomy. Methods: This is a prospective cohort study including non-infectious patients with sternotomy. All patients underwent 18F-FDG-PET/CT at either 5 weeks (group 1), 12 weeks (group 2) or 52 weeks (group 3) post-surgery. 18F-FDG uptake was scored visually in five categories and assessed quantitatively. Results: A total of 44 patients were included. Sternal mean SUVmax was 7.34 (± 1.86), 5.22 (± 2.55) and 3.20 (± 1.80) in group 1, 2 and 3, respectively (p < 0.01). Sternal mean SUVmean was 3.84 (± 1.00), 2.69 (± 1.32) and 1.71 (± 0.98) in group 1, 2 and 3 (p < 0.01). All patients in group 1 had elevated uptake whereas group 2 and 3 showed 2/15 (13%) and 11/20 (55%) patients respectively with no elevated uptake. Group 3 still showed an elevated uptake pattern in in 9/20 (45%) and in 3/9 (33%) with a high-grade diffuse uptake pattern. Conclusion: This study shows significant lower sternal 18F-FDG at 55 weeks compared to 5 weeks post-sternotomy however elevated uptake patterns may persist

The impact of the multidisciplinary Endocarditis Team on the management of infective endocarditis

Background: In their latest guidelines for infective endocarditis (IE) (2015), the European Society of Cardiology (ESC) introduced the implementation of the Endocarditis Team (ET) to facilitate the management of IE. This study presents our experiences and the diagnostic and therapeutic impact of the ET on the management of IE. Methods: From 2016–2020, data of all patients with suspected IE referred to the ET were prospectively collected. The final diagnosis was defined by the ET as either rejected, possible or definite IE. Diagnostic impact was scored as any change in initial diagnosis, the frequency of additional diagnostic tests advised by the ET and any change in diagnosis after these tests. Therapeutic impact was scored as any change in antibiotic therapy or change from conservative to invasive therapy or vice versa. Results: A total of 321 patients (median age 67 [55–77] years, 71% male) were enrolled. The final diagnosis was rejected IE in 47 (15%), possible IE in 34 (11%) and definite IE in 240 (75%) patients. A change of initial diagnosis was seen in 53/321(17%) patients. Additional microbiological tests were advised in 69/321 (21%) patients, and additional imaging tests in 136/321 (42%) patients, which resulted in subsequent change in diagnosis in 23/321 (7%) patients. Any change in antibiotic treatment was advised in 135/321 (42%) patients, and change from initial conservative to additional surgical treatment in 15/321 (5%) patients. Conclusion: The ET had a clear impact on the therapeutic policy for patients with suspected IE and is useful in the management of this life-threatening disease. Broad implementation is warranted

Implementation of the 2015 European Society of Cardiology guidelines for the management of infective endocarditis in the Netherlands

Because the occurrence of infective endocarditis (IE) continues to be associated with high mortality, a working group was created by the Dutch Society of Cardiology to examine how the most recent European Society of Cardiology (ESC) guidelines for IE management could be implemented most effectively in the Netherlands. In order to investigate current Dutch IE practices, the working group conducted a country-wide survey. Based on the results obtained, it was concluded that most ESC recommendations could be endorsed, albeit with some adjustments. For instance, the suggested pre-operative screening and treatment of nasal carriers of Staphylococcus aureus as formulated in the ESC guideline was found to be dissimilar to current Dutch practice, and was therefore made less restrictive. The recently adapted ESC diagnostic criteria for IE were endorsed, while the practical employment of the relevant diagnostic techniques was simplified in an adapted flowchart. In addition, the presence of a multidisciplinary, so-called ‘endocarditis team’ in tertiary centres was proposed as a quality indicator. An adapted flowchart specifically tailored to Dutch practice for microbiological diagnostic purposes was constructed. Lastly, the working group recommended the Stichting Werkgroep Antibioticabeleid (SWAB; Dutch Working Party on Antibiotic Policy) guidelines for IE treatment instead of the antibiotic regimens proposed by the ESC

Added value of semi-quantitative analysis of [18F]FDG PET/CT for the diagnosis of device-related infections in patients with a left ventricular assist device

AIMS: Left ventricular assist devices (LVADs) improve quality of life and survival in patients with advanced heart failure, but device-related infections (DRIs) remain cumbersome. We evaluated the diagnostic capability of [18F]FDG PET/CT, factors affecting its accuracy, and the additive value of semi-quantitative analysis for the diagnosis of DRI. METHODS AND RESULTS: LVAD recipients undergoing [18F]FDG PET/CT between 2012 and 2020 for suspected DRI were retrospectively included. [18F]FDG PET/CT was performed and evaluated in accordance with EANM guidelines. The final diagnosis of DRI, based on multidisciplinary consensus and findings during surgery, whenever performed, was used as the reference for diagnosis. 41 patients were evaluated for 59 episodes of suspected DRI. The clinical evaluation established driveline infection in 32 (55%) episodes, central device infection in 6 (11%), and combined infection in 2 (4%). Visual analysis of [18F]FDG PET/CT achieved a sensitivity and specificity for driveline infections of 0.79 and 0.71, respectively, whereas semi-quantitative analysis achieved a sensitivity and specificity of 0.94 and 0.83, respectively. For central device component infection, visual analysis of [18F]FDG PET/CT achieved a sensitivity and specificity of 0.75 and 0.60, respectively. Semi-quantitative analysis using SUVratio achieved a sensitivity and specificity of 1.0 and 0.8, respectively. The increase of specificity for central component infection was statistically significant (P = 0.05). CONCLUSIONS: [18F]FDG PET/CT reliably predicts the presence of DRI in LVAD recipients. Semi-quantitative analysis may increase the specificity of [18F]FDG PET/CT for the analysis of central device component infection and should be considered in equivocal cases after visual analysis

Added value of 18F-FDG-PET/CT and cardiac CTA in suspected transcatheter aortic valve endocarditis

Backgrounds: Transcatheter-implanted aortic valve infective endocarditis (TAVI-IE) is difficult to diagnose when relying on the Duke Criteria. Our aim was to assess the additional diagnostic value of 18F-fluorodeoxyglucose (18F-FDG) positron emission/computed tomography (PET/CT) and cardiac computed tomography angiography (CTA) in suspected TAVI-IE. Methods: A multicenter retrospective analysis was performed in all patients who underwent 18F-FDG-PET/CT and/or CTA with suspected TAVI-IE. Patients were first classified with Duke Criteria and after adding 18F-FDG-PET/CT and CTA, they were classified with European Society of Cardiology (ESC) criteria. The final diagnosis was determined by our Endocarditis Team based on ESC guideline recommendations. Results: Thirty patients with suspected TAVI-IE were included. 18F-FDG-PET/CT was performed in all patients and Cardiac CTA in 14/30. Using the Modified Duke Criteria, patients were classified as 3% rejected (1/30), 73% possible (22/30), and 23% definite (7/30) TAVI-IE. Adding 18F-FDG-PET/CT and CTA supported the reclassification of 10 of the 22 possible cases as “definite TAVI-IE” (5/22) or “rejected TAVI-IE” (5/22). This changed the final diagnosis to 20% rejected (6/30), 40% possible (12/30), and 40% definite (12/30) TAVI-IE. Conclusions: Addition of 18F-FDG-PET/CT and/or CTA changed the final diagnosis in 33% of patients and proved to be a valuable diagnostic tool in patients with suspected TAVI-IE

Trained Immunity in Primary Sjögren’s Syndrome: Linking Type I Interferons to a Pro-Atherogenic Phenotype

Background: Trained immunity – or innate immune memory – can be described as the long-term reprogramming of innate immune cells towards a hyperresponsive state which involves intracellular metabolic changes. Trained immunity has been linked to atherosclerosis. A subgroup of patients with primary Sjögren’s syndrome (pSS) exhibits systemic type I interferon (IFN) pathway activation, indicating innate immune hyperactivation. Here, we studied the link between type I IFNs and trained immunity in an in vitro monocytic cell model and peripheral blood mononuclear cells (PBMCs) from pSS patients. Methods: The training stimuli heat killed Candida albicans, muramyl dipeptide, IFNβ, and patient serum were added to THP-1 cells for 24 hours, after which the cells were washed, rested for 48 hours and subsequently re-stimulated with LPS, Pam3Cys, poly I:C, IFNβ or oxLDL for 4-24 hours. PBMCs from pSS patients and healthy controls were stimulated with LPS, Pam3Cys, poly I:C or IFNβ for 0.5-24 hours. Results: Training with IFNβ induced elevated production of pro-atherogenic cytokines IL-6, TNFα and CCL2, differential cholesterol- and glycolysis-related gene expression, and increased glucose consumption and oxLDL uptake upon re-stimulation. Type I IFN production was increased in Candida albicans- and IFNβ-trained cells after LPS re-stimulation, but was reduced after poly I:C re-stimulation. Training with muramyl dipeptide and IFNβ, but not Candida albicans, affected the IFN-stimulated gene expression response to IFNβ re-stimulation. PBMCs from pSS patients consumed more glucose compared with healthy control PBMCs and tended to produce more TNFα and type I IFNs upon LPS stimulation, but less type I IFNs upon poly I:C stimulation. Conclusions: Type I IFN is a trainer inducing a trained immunity phenotype with pro-atherogenic properties in monocytes. Conversely, trained immunity also affects the production of type I IFNs and transcriptional response to type I IFN receptor re-stimulation. The phenotype of pSS PBMCs is consistent with trained immunity. This connection between type I IFN, trained immunity and cholesterol metabolism may have important implications for pSS and the pathogenesis of (subclinical) atherosclerosis in these patients