Download PDF. Laurens E.
Department of Radiology and Nuclear Medicine L. Department of Cardiology L. Search for more papers by this author. Department of Medical Microbiology A. Department of Cardiology M. Department of Radiology and Nuclear Medicine E. Department of Radiology and Nuclear Medicine J. Cardiovascular Research Institute Maastricht J. Department of Internal Medicine C. Department of Cardiology P. Previous studies reporting a modest diagnostic accuracy may have been hampered by unstandardized image acquisition and assessment, and several confounders, as well.
Their scans were reassessed by 2 independent observers blinded to all clinical data, both visually and quantitatively on available European Association of Nuclear Medicine Research Ltd—standardized reconstructions.
Native Valve Endocarditis
Confounders were identified by use of a logistic regression model and subsequently excluded. Recent valve implantation was not a significant predictor of false-positive interpretations, but surgical adhesives used during implantation were. Low inflammatory activity at the time of imaging causes false-negative interpretations, whereas prior use of surgical adhesives causes false positives.
Abbreviations and acronyms
Previous studies reported widespread cutoffs for quantified FDG uptake because of a lack of standardization. Prior use of surgical adhesives may cause false-positive FDG uptake and needs to be taken into account.
Editorial, see p Echocardiography, as one of the mainstays of the modified Duke criteria, 2 can only visualize structural damage, and the sensitivity and specificity of these criteria, additionally including microbiological and clinical evidence of infection, are substantially lower in PVE than in native valve endocarditis.
Besides a visual evaluation, FDG uptake can also be measured semi quantitatively, and potential cutoffs for the maximum measured intensity around a PV standardized uptake value [SUV] max , and target-to-background ratios SUV ratio , as well, have been reported.
The study was approved and informed consent was waived by the local Medical Ethics Committees of all participating centers. The data, analytic methods, and study materials have been made available to other researchers for purposes of reproducing the results or replicating the procedure.
For all patients, at least 1 year of follow-up was available. No distinction was made between scans that were performed after first PV implantations or reimplantations. Demographic and clinical data of the included patients and technical data of the included scans were entered into a collaborative database.
To prevent possible confounding by follow-up scans during an active or after a previous endocarditis episode, only the first scan for suspicion of PVE was included in the analysis.
Infection Control and Sterilization
No patients had undergone both a scan for suspicion of PVE and one for another ie, oncological indication. Demographic data and the type of PVs and implantation dates, as well, were retrieved.
In case of multiple replacement surgeries of the same valve, the most recent valve implantation date was used. A history of diabetes mellitus and previous endocarditis was also noted. If multiple echocardiograms were available, abnormalities on transesophageal echocardiography were considered leading, and, in case of multiple transesophageal echocardiographies, the reported presence of abnormal findings on one would overrule their reported absence on another to ensure an accurate reference standard and modified Duke classification.
Evidence of cardiac device or lead infection was recorded, and results of blood cultures were scored as positive if at least 1 blood culture had been positive directly before or during the clinical admission, and the causative microorganism was recorded. Results of serology and polymerase chain reaction were recorded separately. Based on these data and clinical follow-up, the modified Duke classification 2 was calculated. In case of missing images or insufficient clinical data for a reliable final diagnosis, the scan was excluded from further analyses.
The modified Duke criteria were scored as well, 2 with the exception that echocardiographic findings unrelated to the PV were not included in the final diagnosis of PVE eg, vegetation on 1 of the native valves would not count as a major criterion in the final Duke classification regarding PVE , and data on minor Duke criteria eg, vascular or immunologic stigmata were often missing.
Group B streptococcal infections: guidance, data and analysis
Scans that were classified as being of poor quality were excluded from further analyses. Furthermore, the quality of myocardial FDG-uptake suppression was assessed by visually comparing the maximum intensity of FDG in the myocardium to the blood pool of the descending aorta and the liver, and classified as I, less than blood pool; II, equal to blood pool; III, less than liver but more than blood pool; IV, more than liver; and V, intense ie, similar to brain.
All images were analyzed on commercially available software Syngo. Based on both the attenuation-corrected and noncorrected images, both observers assessed the presence of any uptake around the PV and gave a final verdict on the abnormality of this uptake consistent with infection , taking known normal variations into account.
When there was a visual impression of unsuppressed myocardial FDG uptake within the automatically generated volume of interest, this area was manually removed from the measurement. This was measured within a spherical volume of interest with a maximum diameter of the lumen of the aorta excluding the vessel wall. For all semiquantitative analyses, the average of the measurements of the 2 observers was used.
Figure 1. B , Coronal view of a measurement of the mean SUV in the blood pool of the descending aorta using a small spherical volume of interest blue circle , drawn with particular care not to include the aortic wall. C , Combined sagittal view of both measurements. In case of multiple PVs, each valve was assessed and scored separately. Because the definition of case PVE versus control no PVE was set on a patient level rather than on a valve level, only the affected PV was included for the analyses of diagnostic performance and thresholds for SUV max and SUV ratio , to prevent erroneously classifying the scan as false-negative for the other valves.
Only the SUV max around the primary valve was included in the analysis. Scans that were not acquired on an EARL-accredited scanner or did not include an EARL-accredited reconstruction were not included in the semiquantitative analyses. The effect of possible confounders on the diagnostic accuracy was assessed by identification of statistically significant differences between patients with false-positive or false-negative interpretations and those with correctly interpreted scans using a logistic regression model including all demographic and clinical variables Table I in the online-only Data Supplement.
GUIDELINES & STATEMENTS
In particular, the effect of the previously described potential positive ie, recent valve implantation and surgical adhesives and negative ie, low inflammatory activity attributable to prolonged antibiotic therapy and isolated vegetation confounders was evaluated.
The effect of poor myocardial FDG-uptake suppression was evaluated both as a possible predictor of false-positive ie, uptake that mimics an infectious pattern and false-negative ie, diffuse myocardial uptake that masks an underlying infectious pattern scans. Subsequently, all patients or scans with statistically significant predictors of a negative or positive confounding effect were excluded to evaluate possible improvement of diagnostic accuracy.
For comparisons between groups, the Student t test or Mann-Whitney U test was used for normally distributed and nonparametric data, respectively. SPSS v Unless otherwise indicated, the interquartile range or CI is denoted in square brackets.
The interobserver agreement on quantitative analyses was evaluated by using an absolute-agreement 2-way mixed intraclass correlation coefficient.
Outcomes of the quantitative analyses were adjusted for the same confounders identified in the visual assessment through exclusion of the same scans. Figure 2. Inclusion and exclusion flowchart.
One hundred sixty scans were performed for suspicion of PVE, whereas 77 scans were acquired for other, mostly oncological indications. Clinical parameters including blood cultures and results of echocardiography at the time of these scans are listed in Table 1. Table 1.
The MV vegetation was deemed a remainder of previous endocarditis, whereas the pulmonary and tricuspid vegetation were later concluded to have probably been small thrombi. The 1 abscess found in a patient concluded not to have PVE was found to be a remainder of previous endocarditis before PHV implantation, because it had decreased in size in comparison with imaging before surgery. Four pre-existing paravalvular leakages were found in this control group. Overall image quality was good in and moderate in 76 scans.
Fourteen of these patients had a definite diagnosis of PVE according to the modified Duke criteria, whereas 7 had a possible PVE classification. As a measure of inflammatory activity, the average CRP at the time of PET imaging was lower in these 21 patients than in those with a true positive scan None of the other variables including leukocyte levels at the time of imaging were significant predictors of a false-negative scan, although longer intravenous antibiotic treatment was associated with lower inflammatory activity Spearman correlation coefficient of —0.
About group B streptococci
Three examples of scans affected by confounding factors. PVE was intraoperatively macroscopically and subsequently histopathologically confirmed.
In 3 of these patients, the surgical report of the PV implantation mentioned use of surgical adhesives ie, BioGlue [CryoLife Inc] , which was the only statistically significant predictor of a false-positive scan in the logistic regression model. The area of increased FDG uptake was consistent with the description of the area the surgical adhesive had been applied to in the surgical report of all 3 patients Figure 3B.
Neither the number of days since PV implantation, nor an implantation within 1 or 3 months, were significant predictors of a false-positive scan.
In the last patient in whom PVE was suspected who had a false-positive scan, and in the 1 patient with a false-positive scan that had been acquired for oncological indications, as well, myocardial FDG uptake had been classified by both observers as more than liver and intense, respectively, which may have hampered the visual assessment Figure 3C. Neither patient had been prepared by means of a low-carbohydrate diet.
Of the included scans, had an EARL-accredited reconstruction available for semi quantitative analyses: 55 in the PVE group and in the control groups.
Infectious endocarditis guideline 2015 pdf tax
Table 2. Figure 4. A total of 52 EARL-standardized scans 10 in the PVE group, 14 in the no-PVE after suspicion group, and 28 in the negative control group were affected by unsuppressed myocardial FDG uptake in such a way that 1 or both observers had indicated that this may have influenced their measurements.
However, excluding these scans from the analyses did not substantially change the average values in any of the groups.
In particular, 2 scans with very high values because of surgical adhesives were removed from the control group by this correction. Figure 5.
Diagnostic performance of the semiquantitative analyses of FDG uptake. Adjusted for confounders, a SUV ratio of 2.
Three of these 4 measurements had been done in oncological scans with intense myocardial uptake because of a lack of adequate patient preparation, which may have influenced these measurements. The fourth had a SUV ratio of 2. The 2-way mixed intraclass correlation coefficient of absolute agreement for single SUV max measurements 0. Excluding scans with unsuppressed myocardial FDG uptake that may have hampered these measurements increased interobserver reliability to excellent for both variables, with intraclass correlation coefficients of 0.
Whether initial or empirical antibiotic therapy should be ceased for diagnostic purposes, however, in case inflammatory parameters have already diminished without a certain diagnosis, remains questionable in light of the risks associated with unsuccessfully treated PVE. In our opinion, a pragmatic antibiotic treatment of a possible PVE is preferable over a PET-confirmed definite PVE that has to be reoperated because of the cessation of antibiotic therapy.
Surgical adhesives are known to be very FDG avid, with several case reports on patients who underwent lung surgery, aortic surgery, or heart valve surgery showing intense FDG uptake in areas where they had been applied, which can persist for several years if not indefinitely. They also referred to the same case report, but described no false positives that could have been attributed to PV implantation between 2 and 3 months before imaging.
Since the publication of this study and the update of the ESC guidelines, however, several studies that included patients scanned within 3 months of implantation, some even within 2 weeks, have explicitly described true-negative findings.