Hello, my name is Gabriel Grossman. I work in Brazil, Hospital Mônios de Vento in Porto Alegre. And I'm very glad to participate in this very important program. I would like to thank ESNEC for the invitation. And my module is Infection PET Imaging with F18 FDG. This is my disclosure. So the learning objectives of this lecture is to define the clinical value and indications for infection imaging with 18F FDG. Describe patient's preparation and image acquisition of infection imaging with FDG. And identify the important components of interpreting infection imaging with FDG. So the indications, the most important indications of infection PET imaging with FDG is to evaluate endocarditis of prosthetic balls and also devices and leads. And we know that approximately 20% of infective endocarditis patients have no, have intracardiac devices or prosthetic balls. And the use of the traditional modified dual criteria is limited in this patient. So it's important the development of new diagnostic tools in this clinical scenario. So it's well known that modified dual criteria has a low diagnostic accuracy for early diagnosis in clinical practice. And also we know that prosthetic ball endocarditis and pacemaker or defibrillator infection, when we perform echocardiography, echocardiography can be normal or inconclusive in up to 30% of cases. So it's important to know that recent advances in imaging techniques can help in the evaluation of these patients, such as CT scan, MR, radio label, local site, SPECT-CT, and FDG PET-CT. So PET-F18-FDG is a potentially useful technique for evaluation of infective endocarditis, but it's important to know that adequate patient preparation is very important to have a very good result of the study. Inflammatory leukocytes express a high density of glucose transporters and are highly metabolically active. And this is the reason that we can see hotspots in infective endocarditis. And the recent studies have reported encouraging results in patients with endocardiac devices and prosthetic balls. Also PET-CT allows diagnosis of embolic events. So these are some literature examples of how can we see an infective endocarditis of an aortic tube. We can see these hotspots around the tube. So this is an endocarditis of the aortic tube that can be seen in PET-CT study. Also we can see endocarditis, infective endocarditis in prosthetic balls, and we can see this hotspot around the valve. And in patients with suspicious infective endocarditis of ICD or pacemaker, PET-CT can be very helpful. We can see, for example, the hotspot around the pocket or in the lids. And this study published in Circulation in 2015 was very important to show how PET-CT can help in this group of patients. It was a study that evaluated 92 patients admitted with suspected prosthetic valve or cardiac device infective endocarditis. And so we can see here that after the use of the criteria, 54% of the patients had possible diagnosis. So after the use and after the PET-CT study, this possible diagnosis decreased from 54% to 5%. So this was one of the first studies showing the use of PET-CT in this clinical scenario. And this is exactly how PET-CT can be useful. PET-CT can decrease the number of equivocal studies and equivocal diagnosis in infective endocarditis when the echo and the clinical scenario of the patient is unconclusive. So in this study, the positive predictive value was 92% and the negative predictive value was 88%, so very good results. And after this, other studies started to be published evaluating the diagnostic accuracy in prosthetic and also in native valves. And we know that the relatively low sensitivity for the diagnosis of native valve endocarditis may be explained by the lower predominance of polymorphonuclears cells and increased fibrosis in native valves. And also we can see smaller vegetations than in prosthetic valves. And these results, all these results in a reduced inflammatory response and this affect the diagnostic accuracy of PET-CT in native valves. But when the result, the study is positive, it can help. So in this study published a few years ago, we can see that PET-CT can increase the number of definite studies, definite diagnosis of infective endocarditis from 10 to 18 patients. And also in last year, published in JNC, there is another study showing that even with native valves, PET-CT can be helpful. So in this study, the number of definite studies increased after the use of PET-CT. The diagnostic accuracy is very good with an area under the curve around 0.86. So it's a very good method to evaluate patients with infective endocarditis suspected in prosthetic valves. So there are some systematic literature review and meta-analysis evaluating the use of PET-CT in this scenario. This meta-analysis published in 2018, a pulse sensitivity of 81% and a specificity of 85%. And when we evaluate the diagnostic performance of semi-quantitative analysis of FDG using the standard uptake value, we can see that when you use the SUV maximum of around 4.2, the sensitivity is 60% and the specificity is 91%. But when we use the ratio, the SUV ratio, the sensitivity increased to 75% and the specificity is around 86%. So maybe the SUV ratio can be better too than SUV max to evaluate in a semi-quantitative analysis these patients. There is another meta-analysis published in 2019 that evaluated 13 studies with more than 500 patients showing also very good sensitivity of 77% and a specificity of 78%. And the sensitivity increased a little bit when only involved prostheses were evaluated. So we can reclassify patients with suspected TAVI and infective endocarditis when we use just the modified criteria. We had in this study published in 2019, we had just seven patients with definite diagnosis and after the use of PET-CT, it increased to 12 patients. So I know that it's a very small study, but it shows the potential usefulness of the PET-CT in this clinical scenario. And this is another example of the literature showing a hot spot in the device confirming the infection of the device. So there are another tools when we use PET-CT for evaluation of infective endocarditis and we can evaluate in a PET-CT study the bone marrow or the spleen hypermetabolism. And these are findings that are very frequent in patients with definite infective endocarditis. And in this study of last year, patients with infective endocarditis has not just the hot spot in the cardiac evaluation, but also a positive bone marrow hypermetabolism or spleen metabolism in 97% of the patients. So PET-CT is not just important for diagnosis, it's important for prognosis also. This is a very nice study published in 2019, evaluating the prognostic information of PET-CT. And in this study, patients with moderate to intense FDG studies show more primary endpoints in hospital death, acute cardiac insufficiency, one-year death, recurrence, respitalization, or neoembolic events. So when the patient has a moderate to intense FDG study, the primary endpoint was more frequent in this group of patients. So for all this data that I showed you, in 2015, the European Society of Cardiology guidelines were published, including PET-CT as imaging criteria for infective endocarditis. And also as a minor criteria, the vascular phenomenon, septic emboli can be a minor criteria for the diagnosis of infective endocarditis. So when we see this, the flowchart of these patients, yes, guidelines recommend that when the patient has possible diagnosis or the diagnosis is rejected and the patient has prosthetic valve, we can use the PET-CT to reclassify the patient as definite, possible, or reject infective endocarditis. When we compare the do criteria with the ask criteria, we can see that the ask criteria has a higher sensitivity, but a lower specificity for the diagnosis of infective endocarditis. So, as I said before, the PET patient preparation is very important because heart takes up F18-FDG. So it's important to fasting at least for 12 hours and a 24 low carbohydrate diet. This will reduce the amount of glucose available for myocardial metabolism, making free fatty acids, the predominant cardiac energy source. We can do also intravenous heparin injection to do this shift. And so we want to suppress the uptake of FDG from the heart, of the heart. So FDG is injected 60 minutes prior to the image acquisition, and we do always a whole body acquisition to evaluate for septic embolite. So this is an example in the left of a bad preparation. So we can see that the heart takes up the radiotracer, and we want this preparation with a total suppression of the F18-FDG uptake of the myocardium. So we want this kind of preparation. And also the whole body acquisition is very important because we can see when we do a whole body acquisition, a septic embolite, as in this example, we can see in the muscle, in the bone. So it's very important to do a whole body acquisition when we evaluate these patients. CT angiography is required, so co-registration on one integrated scanner with breathing and acid-gated PET is preferred. But when we can't do this, we can separate, do a separate scan with post hoc fusion and a high-end dedicated CT scanner is possible. The total radiation dose is 5 to 15 millisieverts for the PET-CT study, and the CT radiation is 5 to 10 millisieverts. So the image interpretation and reporting, we can do a qualitative assessment. As I showed you before, we use seeing bright or hot spots, and we do this visual analysis with attenuation and non-attenuation corrected images. And we need to be aware of different patterns of uptake. And as I showed you before, we can do quantitative assessment using the SUV maximum and the SUV ratio, but there are no standardized parameters for this kind of assessment. It's important to know the confounding factors. Recent procedure can cause an inflammatory response and low uptake of the radio tracer, usually. Inadequate suppression of myocardial glucose metabolism, as I showed you before, is a very important confounding factor, as well as artifacts, acquisition artifacts. One another important confounding factor is a prolonged antibiotic therapy, usually more than two weeks, that can cause a false negative in these patients, and also isolate small or mobile vegetation that we cannot see in PET-CT studies. So these are the uptake patterns. In the left, usually when it's a very acute infective endocarditis, a very hot, important hot spot around, in this case, a valve, or not so high uptake, but uptake around the valve, but we can see also a focal uptake. Usually when there is a recent procedure, we can see a diffuse low uptake, as in this case, and this is not a positive study for infective endocarditis. So I brought some cases of my institution to show you. This is one of the first cases that we did. It was a male, a 66-year-old male with hypertension and T-cell lymphoma. He had aortic stenosis and a biologic prosthetic valve in 2003 and 15, and he was admitted in April 2016 due to fever. So the echo was done first, and it showed no vegetations, no abscess, and the valve was good with normal function, but the blood culture was positive for Staphylococcus aureus. So the next step was a PET-CT, and the PET-CT was positive with a hot spot around the valve. We can see here. And after a month, the echo was repeated, and it showed an abscess. We can see here in these images, also in the 3D that I will show you. So the patient has a perivalve abscess and leak. He had a new prosthetic valve and was discharged from the hospital in a very nice, very good condition. So the teaching point of this first case is that PET-CT demonstrated infection before morphological abnormalities. This is the second case, a 55-year-old male with diabetes and an oncologic surgery in 2011, and he had a bioprosthetic tricuspid valve and pacemaker in 2015. So he started with signs of a pacemaker pocket infection with no response to antibiotics. He had an echo and a culture that was negative, and the surgeon decided to order a PET-CT. So the PET-CT showed this hot spot in the pocket that was expected, but the leads were negative for infection. We didn't see any hot spot that we could classify as positive for infection. So in this case, the PET-CT was negative. So leads were not infected. He used antibiotics for 14 days and a new pacemaker device. And the teaching point in this case is that a futile thoracotomy was not performed because PET-CT was negative. So PET-CT is important when it's positive and also when it's negative as was shown in this case. So the third case, it's a male, a 71-year-old male with chronic kidney disease, heart failure, and an ICD, and he had an orthopedic surgery and had an infection in the wound and fever. Started with antibiotics. He had leukocytosis and high CPR, and he had a transesophageal echo with no vegetations. So the physician ordered a PET-CT, and this is the PET-CT. The PET-CT evaluated the leads, and the leads were clear. We didn't see any hot spot, important hot spot. So we can see here that the leads were negative for infection. So echo was repeated after one week and demonstrated a small vegetation in one lead. So the teaching point here is that prolonged antibiotic, as in this case, can cause PET-CT false negatives. This is a very important information that we need to know. So here, the echo of the patient with the infection. And this is the last case, a 68-year-old male with a bioprosthetic artery valve in 2018. Started with fever and sweating, and the echo showed no vegetations. So the patient was in the ICU for a week, and the echo showed no vegetations in the lead. Showed no vegetations. So this is the PET that was done after the echo because the probability of infective endocarditis was high and the echo was negative. And we can see a very nice image here of a hotspot around the valve confirming the diagnosis of infective endocarditis. So the teaching point here is that PET-CT demonstrated infection before morphological abnormalities. And this is the most important, one of the most important things of PET-CT that we can see with PET-CT infection before the morphological abnormalities that are needed to be seen in the echocardiogram. So this is a very nice registry that was done in several countries in Europe. And this study show a lot of very nice information. I just brought this slide, just want to show this slide because of course echo is the method that we should start in the evaluation of patients with suspected infective endocarditis. But we can see here that PET-CT and mainly in prosthetic valve, infective endocarditis can be very help, sorry, can be very helpful. And after doing echo, if we need to confirm the diagnosis, we can use the PET-CT to evaluate with more information to this patient. So in summary, when we have a possible prosthetic valve endocarditis, PET-CT can be very useful to reclassify the patients. And we need to know if the patient is using two weeks of antibiotics or more to do a good interpretation of the study. And even when the diagnosis is confirmed with a definite prosthetic valve endocarditis, we should consider the F18-FDG PET-CT if there is suspicion of septic emboli or metastatic infection, because we do a whole body study. So the take home points here is that the F18-FDG accumulates at the sites of infection, but we need, and it's very important, an adequate patient preparation. There is a reduction in the rate of misdiagnosis infective endocarditis classified in the possible category using the due criteria. We can detect peripheral embolic and metastatic infectious events, because PET-CT is a whole body study. But we need to have caution with patients who have recently undergone cardiac surgery as a postoperative inflammatory response may result in a nonspecific FDG uptake. And also we need to have caution in patients with more than two weeks of antibiotics. Thank you very much.

infection PET imaging

endocarditis

diagnostic criteria

PET-CT

prosthetic valves

equivocal diagnoses