Good evening, everybody. My name is Leon Menezes, and that's my very great pleasure to welcome you to this Nuclear Cardiology Around the World webinar that we're holding now in Europe. This is the third webinar we've held recently under the auspices of the American Society of Nuclear Cardiology, and we have flown from Latin America through to Asia and are now landing in Europe. I'm going to be hosting this evening's session with my co-chair, Marina Gianferra, who I will introduce to you in a minute. The format of these sessions has been one of case-based discussions centred around presentations from our faculty and then discussion. I'm not entirely sure what's going to happen because the questions and the points of interest that will be sparked are going to be led by this very eminent panel that we have convened, not just from Europe, but from America and Brazil and Singapore as well, so that we can discuss some of the patient problems that we can help solve using nuclear medicine techniques and others. So we're going to be discussing cases of infection and inflammation, the use of hybrid imaging, as I just alluded to, the increasing recognised burden of amyloid and then microvascular ischemia, and that will hopefully take us up to just around the hour mark and hopefully will give us food for thought about our practice when we return home to the clinic. Now, our panel is going to spark the discussion, as I say, but I also would really love if many of the attendees could chime in and you've got the Q&A button on there on the Zoom app to interject with questions, and we're going to be curating those questions and ones which get the most traction or pique someone's interest, we'll try and get to in the discussion. So if you hammer out those Q&A buttons, then hopefully we can respond to you in real time with your points and concerns. Now, as I say, this is the third time we're running this, and we're very pleased to have over, I think, last count, 250 people joining in on this webinar from all around the world, not just Europe. We want to hear what you thought about it so we can feed that back into our next offerings, and there will be an evaluation form for you to fill in. And again, if you do fill in the evaluation form, you can get a copy of all of our presentations on us receiving that. So that is your carrot to fill that out, but really we'd just like to hear what you thought. Also, for those of you who can look at more than one screen at once, Dominic Benz is on Twitter, sorry, on X, and will be live tweeting and amplifying our discussion on the internet here. And you can follow him at Dom C. Benz, all one word. And again, there may be a parallel discussion going on on Twitter as we go through this webinar. Okay, after I've spoken, it's now my great pleasure to introduce Larry Phillips. Larry is the current president of the American Society of Nuclear Cardiology and is joining us just to say a few words from his office in NYU Langone, where he's just about to be ejected and moving into a new department, but you won't see the mess his office is in. He's the director of nuclear cardiology at NYU Langone in New York, and as I say, is the president for this year of the society. So, Larry, I'm going to stop sharing and hand you the platform. Great, thank you so much. And yes, you will not be seeing my office right now, which is totally boxed up. I want to take a moment just to welcome everybody to today's webinar and to thank everybody who's participating in such a fantastic series. The American Society of Nucleic Cardiology is really an international society now. With over 5,000 members, a good 20% plus are from outside the United States with representatives from over 83 countries. Now, let me go back. Now, there's a lot of benefit to asking membership. Besides the collegiality of the community that we get to build together for nuclear cardiology, we want to make sure everyone's aware of membership benefits that go along, including the Journal of Nuclear Cardiology, which is now completely online. Webinars such as this one, newsletters, and a lot of online education resources to help, again, continually work to improve the quality of the care that we provide for our patients. There are a couple of educational programs I just want to mention that are coming up soon. Computer's going buggy when I move. The first is that we've been doing tremendous amount of education in the field of cardiac PET. As we get ready for ICNIC in Seville in less than two months, we are going to be having a PET intensive workshop to help people build their foundations in cardiac PET. You can use the QR codes in the upper right-hand corner of the screen for any of these programs. We also have a number of on-demand courses, including the nuclear cardiology knowledge base, as well as core curriculum, as well as PET. And I encourage people to take the opportunity to review these and to really join us in this learning environment. Our flagship program that'll be coming up is the ASNIC scientific meeting, which will be in September in Austin, Texas, which really promises to be both a tremendous educational experience, but also an ability for people to be together in the environment of Austin, Texas, where we have great food, good dancing. I was told no bull rides for me, but it should be a fantastic program. And so I just wanted to take the opportunity to welcome everybody to today's program and really to thank all of our speakers today for what I know is gonna be a fantastic program. So I'll stop sharing and hand it back to the team, Okay, great. Thank you very much, Larry. It's very nice to have the President of the Society here and also just emphasize the global reach of the Society and also tempt us with lion dancing and country and Western in Texas at the annual meeting. Righto, so shall we kick off with the cases in the presentation? So I'm delighted to have with us my co-chair today, Maria Gianferrera, who tells me that she's a cardiologist in Coimbra, but I think actually works for Visit Portugal, the Portuguese tourist board, from all the conversations I've had with her. She's the Deputy Director there of the Institute of Nuclear Sciences Applied to Health at Coimbra University, which is one of the oldest universities in Europe, and she's going to be discussing cases of inflection and inflammation. Leading off the discussion will have been Fabian Heierfeld. Fabian is the Director of Nuclear Cardiology in Georges Pompidou in Paris and a Professor in Medicine there at the University there. World-class expert in multimodality imaging and also, I believe, the Programme Chair for the ICNIC meeting in Seville, if I think not right. So I'm going to hand over to Maria Gianferrera and to Fabian to talk us through the first case. Thank you. Thank you very much, Leon, and thank you for the nice introduction and so it's my pleasure to be here and we are going to present the first case on inflammatory infectious disease of the heart and about infectious enocarditis. So are you seeing my slides OK? Perfect. So this is a case of a patient with 74 years old and he was admitted with heart failure in the ED department. So he has a prosthetic mechanic valve in aortic position implanted five years ago and he also had pneumonia last month, which implied hospital admission during three days. On admission, we have to emphasize that he has bilateral decreased pulmonary murmur and also a systolic-diastolic panfocal murmur. In admission, blood cultures were ordered and also echocardiography, transthoracic and also a transesophagic echocardiography and an X-ray. And you can see these are the images of the transesophagic echocardiography. You can see the aortic valve, the mechanical aortic valve, and you can see also a periprosthetic leaks surrounding this valve. We have in the X-ray a pulmonary effusion predominantly in the right side. So we have and the blood cultures were negative, persistently negative. So we have a patient without failure with a prosthetic valve, which is a predisposing condition for infectious endocarditis, one minor criteria. We have also periprosthetic leaks on the transesophagic and the transthoracic echo, which are major criteria for infectious endocarditis. And so one major and one minor criteria turns it possible to have this diagnosis, just possible. And according to the European Society of Cardiology guidelines published last year, whenever we have a possible diagnosis of infectious endocarditis, there's an indication when a to ask for other exams, namely, for instance, a PET-CT with FDG. That's what we've done. And we ask for a PET-CT with FDG for this patient. And you have the images of the PET-CT where you can see an increased uptake surrounding the aortic valve, the prosthetic aortic valve of FDG, which, of course, indicates inflammation versus infection surrounding this prosthetic valve. So the PET-CT allowed us to become from a possible diagnosis of endocarditis to a definite diagnosis of endocarditis. And that's what we have in the ASK guidelines, the last published guidelines of endocarditis. One indication for nucleic cardiology exams, namely PET-CT or SPECT-CT with white blood cells for patients with prosthetic valves or with devices, implanted devices in the heart. In this case, in particular, because of a refractory heart failure, surgery was performed, and this allowed the identification of the microorganism and, of course, to do targeted antibiotherapy. So thank you very much for your attention. And now the discussion, Professor Fabian Eiffelt. Thank you, Maria, for this very nice illustrative case of the role of FDG PET imaging in this patient that has a prosthetic valve and suspicion of prosthetic valve endocarditis. Maybe I will start asking you a first question for our audience who is not maybe familiar with the use of this FDG PET. It's which kind of criteria are you using to kind of define what is an abnormal FDG PET finding in this patient? Do you have specific criteria and how should we use them? Well, whenever we have a patient with a possible endocarditis, when we don't have a definite diagnosis of endocarditis made by blood cultures or echocardiography, we we use nuclear cardiology techniques, namely PET or SPECT. In my department, we usually do PET CT because we are able to. We have the possibility to use PET CT to diagnose these cases. But if PET CT is not possible or if we have a condition like, for instance, a very recent heart surgery, for instance, we have a prosthesis implanted less than three months ago. So we could use the SPECT CT with the white blood cells because they are even though the sensitivity is lower, the specificity is higher for infection. So our criteria is to use it if we have an implanted devices or a prosthetic valve. And whenever the diagnosis is not possible with the usual exams, that's blood culture and the echocardiography. Yeah, thank you. Maybe the fact that it's kind of focal and it's around the valve in this peripheral area is something it's very kind of making more suspicious of infection, because in some cases you can have a low kind of diffuse uptake in these valves. And I think this is important to kind of see on this case is that it's really the kind of this focal aspect and also that it's kind of associated with a lesion also on echo. It was exactly, if I understand well, was exactly at the same place where you have this parallel. So this is kind of also very making it suspicious of really an infection in this area. Yes. And if we don't have any questions, maybe I do. You have a question, Nathan? Yes, Fabian, and thanks for the presentation. One of our readers that she wants to know whether you could use technetium traces with SPECT if you don't have it available. Well, we can use it. White blood cells target, of course, with technician, but with SPECT CT. And as I told you before, it's a harder exam and it takes more time, a longer time. It's we have to take the blood from the patient. We have to to trace the white blood cells. And so it's not easy process, but we can do it. So the SPECT is always an alternative to the PET. It's more specific, but with a very much lower sensitivity than the PET CT. Can I maybe ask you another question? Did you look at other things in this FDG PET, except to the heart? Do you search for some other kind of information on this kind of exam when you do this kind of exam? Yes, this patient, in fact, he has in the X-ray like a lesion in the left lung. And it seems like something residual probably from the infection he had previously. But we look not only in the CT, but also in the PET CT. We looked for other, of course, other abnormalities. And it didn't show anything. So we were we were asked about it. So it was OK. Yeah, probably septic embolism would be a kind of a good thing. Yes, of course. Infection also in the spleen or of course, but it didn't show anything. Didn't show anything, which was good. I have two excellent questions from the audience as well. Firstly, do you use both the AC and the non-AC data? And secondly, from a very practical point of view, what is your preparation for the study, as opposed to doing a standard FDG oncology study? Well, these patients actually have to be prepared for this exam. We usually in our center, we usually do a preparation of 48 hours preparation. So the two days before the exam, these patients were not allowed to consume carbohydrates. So it's a diet based on proteins and fats, no carbohydrates. And that's usually what what we do before this exam. It's not easy to do that in outside the hospital when the patient came from home. It's not sometimes it's not very comfortable for the patient. And sometimes they came to the exam and they're not well prepared. But that's what we do. We want to really emphasize inflammation or infection in this case in these patients. So we want to emphasize FDG uptake besides the normal uptake from the myocardium. So we do this preparation for 48 hours before the exam. Yeah, I think this preparation is kind of reducing the FDG uptake in the myocardium are very important, but you look at the mitral valve or if you have a case of infection of a device because you're very close to the myocardium. So you need to really suppress well this FDG uptake in the myocardium. Possibly in this case, it's a bit higher than the myocardium. So even if you had another optimal suppression, you could still maybe identify the signal. But of course, it's better to prepare. I agree with you. It's better to do this diet for this kind of patients then. And the AC versus non-AC? I'm sorry, I didn't understand that, Nathan. Do you use the attenuation correction images or the non-AC images or both? We usually do the attenuation correction because we're doing PET CT. That's what we usually do, but I don't know if Fabian does anything else, but... I think it's important to look at both because you can have overcorrection in case of in this prosthetic valves and that can kind of on the attenuation correction, you can have like a digestion diffuse signal or kind of overcorrection of the attenuation. And it's also a good thing if you have a signal on the non-attenuation corrected images, this is kind of more in favor of an infection rather than of an artifact. So I think if you it's better to look at both. Often this non-attenuation correction images are really of lower quality. So it's more difficult. But if you have a signal on this one, I think it's you can be a bit more confident about the fact that it's not an artifact. Yeah, there's many great questions coming through, but just one last one, maybe. What about for patients who've had a recent surgery, the false positives and the false negatives? And do you use, say, white blood cells instead at that time? Yes, that's what we do. If the patient has a recent surgery, especially to implant a valve. Yes, we use PET CT instead of PET CT. Because, you know, in the in the recent days after the surgery, there is a lot of inflammation related with the surgery procedure. And an FDG just is an uptake by the inflammatory tissue. So we use SPECT with white blood cells instead of PET CT. Yes. Maybe I would just add just a few words, I think you can start with FDG PET because you can find a maybe alternate diagnosis with FDG PET with your whole body imaging. And if you have a if you have a question about an infection, it's worth to move to white blood cell SPECT or, say, Maria, because it's more specific and you know exactly where to look. So I think it's it's reasonable if you have both available to possibly start with FDG PET and in case of question, move to white blood cell SPECT, which, as Maria said, is much more kind of take more time. It's more complex. So I think you have to select a bit your patients that you refer to this kind of exams. Other questions will be answered in the chat group. OK. So. It's my pleasure to present now Professor Eiffel and Dr. Kaufman, who are going to present and discuss the second case on hybrid imaging. Professor Eiffel is the head of the nuclear medicine department of George Pompidou Hospital in Paris. And Professor Kaufman is the chair of nuclear medicine in University Hospital in Zurich. So welcome to both. And thank you very much for your presence. Thank you, Maria, for the introduction, I now move to the the speaker, our speaker, and I'm happy to discuss this case with Philip Kaufman. So we'll present you shortly this case. So this is a 70 year old gentleman. He was referred by his cardiologist to a department for myocardial perfusion scintigraphy, his cardiovascular risk factor, dyslipidemia dyslipidemia and high blood pressure. And he has just a history of fibrillation of paroxysmal atrial fibrillation. He's a very active gentleman. He's performing regularly intense mountain climbing in the French Alps. But he complained to his cardiologist about occasionally of shortness of breath when he was climbing steep slopes. The first step for me when I evaluate a patient that is referred to my department is I will try to evaluate the preclinical probability of this patient. And I show you here the ESC grid. You have different grids, but it's the one I use. And then in this case, he has dyspnea, he's more than 70, so we're about 32% of prevalence before starting any kind of test. So, I try always to, in this kind of patients, to perform exercise. And in this case, he performed a very good exercise with a workload of 10.2 meds over six minutes. He reached maximal heart rate, 102%. He was clinically negative, but ECG really positive with a two millimeter ST segment downstream on the ECG. And he complained during the exercise of moderate dyspnea at the peak of the physical exercise. To be noted, he had also a relatively high blood pressure that reached 240 millimeters of mercury at systole at the peak of the stress. Here, we performed then microepithelial scintigraphy with technetium radiolabeled tracer. It's on the CZT cardiac center camera. And here you can see the images of the stress and the rest, and also the bull's eye and the TID. We also perform, of course, gated acquisition of note on this gated acquisition. You can see, I gave you the values and he had a slight dilatation of the left ventricle, a drop also of the left ventricular ejection fraction after stress at 45% compared to 65% at rest. And so, if I summarize the finding on this case, the patient has symptoms. He has dyspnea, a positive stress ECG, high blood pressure during stress, a small reversible at the apex, only one segment, and a significant dilatation and dysfunction post-stress. While I was worried in this case of this patient, he had several red flags for me, suggesting balanced myocardiskemia. And I discussed with his cardiologist. She was not convinced that the patient had dyspnea at the peak of the stress. She was not convinced. She was thinking it could be due to the high blood pressure during the stress and she wanted to have, before referring the patient to invasive care, to have a Cori-CTA to look at Cori-CAD. Here are the images of the Cori-CTA. You can see that there are massive calcification of the proximal and mid-LAD that kind of hinder the precise kind of quantification of stenosis in this patient. And he had also probably then significant stenosis of the LAD and intermediate stenosis of the circumflex and the left main and the right coronary artery. Based on the Cori-CTA, he was referred to an invasive coronary angiography that confirmed high-grade stenosis of the LAD and also of the left circumflex and mid-grade stenosis, moderate stenosis of the right coronary artery. And he was treated by a PTCA plus stents of the LAD and the left circumflex. Before allowing him to do really intense climbing, his cardiologist referred him back for another test that he performed a few months later, and he did again reach a very high workload. But as you can see in this test, there is this perfusion defect that the apex disappeared and also the left ventricular dilatation and also the left ventricular dysfunction after stress disappeared on this follow-up test in this patient. So just to summarize, I think exercise-spec MPS is very important because you can really assess the symptoms, the presence of symptoms in the patient that will help you guide the discussion for treatments and also confirm the link between the symptoms and the presence of myocardial ischemia that could, if it's a cause of symptoms or not. I think Cori-CTA is also very useful because you can maybe improve your risk stratification of patient, identify high-grade stenosis of proximal segments of the coronary arteries, and also increase your specificity of aspect MPS in case of litigious cases. I believe there is a really added value of combining functional and anatomical imaging to guide patient treatment and improve the diagnostic performance of this test. And as the sentence for SNIC, I'm a patient-first imager. I try to combine this imaging to help patient care. Happy to discuss about this case with Philippe and with also the persons attending this very nice webinar. Thanks very much indeed, Fabien, for this wonderful case because I think it offers us the opportunity to discuss a number of points and maybe we cannot touch upon all of them, but I will start with one point. When we do non-invasive imaging for assessing a patient, they always tell us, yeah, you know, you should take care of the downstream resource utilization and not do too many tests. Now you end up with having two non-invasive tests. Then you have, and of course, let's say the ECG is another non-invasive test. At the end, you do an angio, you do a treatment, and then six months later, you do another imaging test, which I think is wonderful. But is there any criticism that there is too much of non-invasive assessment? Now, what triggered you, and people would have done the same, to do a perfusion scan in the first line and not a CT angio in the first line? Was that the age of the patient, probably? I think when you, I mean, we see so many different ways of practicing. So at the moment, I think it's a very good question. I think if you have symptoms, it's important to assess the symptoms of patient and probably in physiological conditions, because you can find many things that are not only choristenosis, like arrhythmia, in this case, high blood pressure during exercise, and really kind of link the symptoms with the perfusion of the myocardium. And I think if you look only at the anatomy, you might kind of make a short kind of conclusion about the relationship between what you see on coronary CTA and the symptoms, and end up by treating patients, overtreating also patients that have maybe stenosis that have nothing to do with the patient's symptoms. And this is, I think, it's more of concern to go until stenting if you have not clearly a link with, you know, what patient is complaining. At the end, what we want to do is really kind of help the patient kind of have less symptoms, live better. And I think this is important to make this link between the symptoms, the patient's symptoms, and also the what you find on imaging then. Absolutely. I mean, I couldn't agree more. But for example, if you would have done attenuation correction with a CT, and you would have seen a lot of calcification, would have guided that directly towards invasive coronary angiography, potentially? What do you think about that? Yes, I think in this case, when I have a really typical angina or positive stress ECG, I tend to do mostly coronary CTA, because I want to really exclude, I mean, if patients with not low to mid, moderate prevalence of CAD, I want to re-exclude the presence of a stenosis that could explain the symptom of the patient or the positive stress ECG. When I have more, in this case, a left ventricle dilatation, I think of balance ischemia versus, for example, cardiomyopathy or, you know, either dilated or hypertrophic, I think calcium scoring would be enough. If I see a diffuse calcium scoring plus this kind of signs of left ventricle dysfunction, I think for me would be enough to refer the patient for CAD, because I think there's a high risk of having an extensive CAD, and I think this would be enough in this patient. We also experience, we see relatively often that those who do a lot of sports, like this gentleman, they seem to have some kind of preconditioning or something, because they often tend to have very subtle signs of ischemia, and then the big surprise comes when they look at the anatomy. And here, I think the anatomy is really much more pronounced than the functional test. And along with this, if you would perform a hybrid picture with the two components, do you think that you will come to the conclusion that you need to stem both lesions? I would say probably, I feel respect. We missed some information about this balance ischemia, and I think what could be discussed also, if you have it, is to do a PET-MPI to have a better view of the extent of the perfusion, I mean, the decreased perfusion. I think what I've seen sometimes is what you see with SPECT is that you compare a signal, you have a reference signal, and if everywhere you have a lower signal, you might underestimate the extent of the perfusion defect. And what you can see is sometimes you have only a small perfusion defect, and in fact, it's the area where you have the lowest perfusion, but you may underestimate the extent of your perfusion defect. And I think my message is also very important is that you have to look, search for these signs of balanced myocardial ischemia, because it changed completely the prognostic of patient if you have an extensive perfusion defect. And that's one of the challenges that we have, I think, with SPECT is trying to really, for risk stratification, to really identify this high-risk patient. Probably, there is CTA that can help or calcium scoring, but possibly PET also. And this is, I think, an area where we have to think and see what is the best kind of algorithm to evaluate this kind of patients. I think I will give the word to Joao. He has his hands up, and you have a question, Joao. Thanks a lot. Yes. Thank you. Thank you, Philippe. Thank you, Philippe. It's a very interesting case, you know, with so many teaching points. I was amazed, Philippe, as you were, of this man's exercise capacity. You know, it's a 72-year-old man who's able to perform 10 mats. He reached 102% of his maximum predicted heart rate, which would be around 150. So if you multiply that by the blood pressure that he achieved, 240, you're going to end up with a double product of 36,000, which is really amazing. And that, to me, that goes along with a very small perfusion defect on SPECT. And it makes me wonder how much collateral flow this man has. And let's remind ourselves of the PROMIS trial, the randomized patients, to start with anatomy or to start with physiology. This certainly could be a PROMIS trial patient, the randomized 10,000 people. And at the end, when you go with anatomy, you end up having more revascularization, but the outcome is similar. Now, let's also, let's ask ourselves, could this be a schema trial patient that we learned so much from the schema trial? He would not even be considered for the schema trial because he wouldn't reach the schema threshold first. And if you look at the treadmill, he wouldn't also reach the criteria for severe ischemia to be randomized on the schema trial. He would be, however, refused based on anatomy because he has a 50% left main. But if you look at what his treatment was, he was not treated for a left main. He was treated for two other lesions. So it's really intriguing. And this reminds us also that although our evidence comes from randomized trials, such as PROMIS, such as schema, we do have to individualize management. And in this case, of course, I agree with the management based on the drop of ejection fraction on the CZT, which demonstrated that this could be underestimated perfusion deficit. So some points to take into consideration. Thanks for the comments. Maybe I can add another point is I think what we see is perfusion. I think perfusion is not ischemia. It's that in this case, it's a balance between consumption and what is, you know, the level of oxygen that you bring in this case, probably the consumption of the patient due to the high blood pressure is way higher than a normal patient. And I think that's what you capture with exercise. And then probably maybe with, let's say, not high-grade stenosis, he would maybe suffer more than a patient with high-grade stenosis because his level of consumption is really high. And I think what you capture with the stress ECG and with this Leventricus function is additional to what you see with perfusion. You see really the impact of ischemia on the heart. And I think this is what you have to really keep in mind when you analyze this test is that I try always to combine the results of the stress ECG with my aspects on the perfusion. I think this is the way you really improve your diagnostic performance and the information you provide to your cardiologists that refer patients, because I think both information are very complementary. And also what you get from CTAs and additional information is very useful also. Yes, thank you. Thanks a lot, Nathan. The hour is getting late, so there's lots of questions, particularly about using coronary calcium, which a lot of us will see this routinely, and we'll answer that in the chat. But I'll answer two very quick questions. Firstly, why Fabian was exercise used rather than adenosine in this sort of patient? And secondly, when you do an exercise with this patient, what is the minimum number of minutes of exercise you accept before you inject the radiopharmaceutical? So if a patient only exercises for two minutes or seven minutes, do you choose the number of minutes before you inject? So it's a very good question. I think I try always to start to do exercise in patients, because I think, like I said, it's something you can really capture a lot of information on the level of, you know, the symptoms, the level of the exercise, where the symptoms occur, other causes of symptoms. So I try always to do exercise if it's possible. And then I try to have symptom-limiting stress tests, exercise tests. It's like, as far as the patient can go, I go. And of course, my level, my threshold is always usually to try to reach 85% of maximum heart rate is the minimum and a certain level of exercise. That depending on the age of the patient, but it's usually I try in case I cannot reach one of both, like level of exercise or maximum, I mean, the 85% maximum heart rate, then I will do a complementary pharmacological test to be sure that I'm not, that I will detect high-grade stenosis then. Yeah, thanks a lot. I think we're running out of time. Just one comment, the ischemia, you pointed out that what we, what you look at is ischemia, what we see is perfusion. The ECG showed us ischemia and one could wonder why six months later you redo the perfusion scan, which showed only a sudden finding before rather than just doing ECG. But I think you've combined, of course, the two of them and you see the TID, which disappears. And so you're very complimentary. And so, and that's, I think is a very good way of really documenting that the treatment was successful. So I believe I hand over and thank you very much, Fabian, for this very illustrative case. Thank you very much. Okay. Fabian and Philip, thank you very much. And Joanne as well for your, your, your commentary on the case. I think that's fantastic. I just want, I'll just point out that I read, I read this week that France has the least rates of obesity in Europe and in the wider world. So that's maybe why Fabian's patients can exercise so, so well. That's not necessarily universal in other parts of the world. We're going to switch tack now to discuss a case of amyloidosis, and I'd like to welcome two presenters, Elisa Millan, who's a cardiologist from Triviso in Italy, and Emilia Jimenez-Heffernan, who's a cardiologist and nutriments physician in Huelva in Spain. And I think this is brilliant to have these two panelists to come and discuss the case, because amyloid is increasingly being recognised, but in some parts of the world, through the hereditary causes of amyloid, have had much greater experience with this disease and have been more switched on to it in the past. So I believe Elisa is going to introduce the case and Emilia will discuss and jump off on the conversation afterwards. Over to you. Thank you. Thank you very much. I'll try to continue to show you my desktop. Here I am. Good evening, everybody. And thank you for this invitation. And we are trying to present in the next few minutes this case of amyloidosis. The case is that of a man of 76-year-old man with hypertension and diabetes with previous left hemicolectomy for colon cancer. And he is in permanent arterial fibrillation in oral anticoagulant therapy. And in 2019, he received coronary angiography for chest pain, but no significant coronary artery disease was found. In 2022, he underwent an echocardiogram and the echo was suspected for infiltrative disease. In fact, there was a granular sparkling appearance. Left ventricular was markedly increased in parietal thickness. And he had preserved EF, normal kinetic of right ventricle and moderate aortic sterenosis. At that time, you can also see which was the ECG. As you can see, there is the atrial fibrillation we already know. And there was a poor progression of airwave in lead V1 until V3. We perform a scan with bone tracer. As you can see, we use HMDP, 99-amplification HMDP. And as you can see, there is the intensive uptake of the tracer in the heart, which is definitely higher in comparison to bone. And in fact, we reported a Perugini score of three. And we also perform a SPECT-CT with attenuation correction and scatter correction. And in these images, you can see a nicer definition of the uptake of the tracer all around the left ventricle, particularly in the septum with apical sparing. You can also see this apical sparing in the 3D as well as in the bullseye images. The laboratory's test show with serum-free light chain SA, troponin, BMTMP, and anti-proBNP were normal, normal serum electrophoresis. And about genetic tests, there was performed an abdominal Wohlfett pad biopsy, which was positive for the presence of amyloidosis deposit, but the genetic analysis was negative for panstereotein gene mutation. Therefore, the final diagnosis was that of cardiac ATTR wild type. In 2023, for a worsening of dyspnea, the patient received a new echocardiogram. And as you can see, there is a sclerotic calcification of the aortic valve, which was a tricuspid one. The valve is markedly hypomobile, and there is a severe stenosis. Left ventricle was within normal limits, but as you can see, there is an increased thickness in the septum, as well as in the posterior wall, and there is this granular, sparkling appearance of the myocardium. Moreover, you can see bilateral moderate dilation with a normal right ventricle. So the patient was submitted at a TAVR procedure, and in the post-procedure, he received the implantation of a pacemaker for a bradycardia, was an atrial fibrillation with significant poses. And as you can see, this was the images of the procedures of the TAVR. Therefore, at the end of this case, the take-home messages were that the dual pathologies of aortic stenosis and cardiac amyloidosis is quite common in older patients with aortic stenosis referred for possible TAVR. The second point is that cardiac amyloidosis in aortic stenosis is generally of ATTR type, but AL amyloidosis needs to be excluded of course. Last point is that TAVR should not be withheld in aortic stenosis patient with cardiac amyloidosis, and this procedure increase the prognosis of patients. Finally, I have some, I pointed some point of discussion to share with my discussant, Dr. Amelia Jimenez-Effernan, and the point of discussion are the choice of tracer for this type of scan. The discussion will also take into consideration if we can have some false negative scan and what to do in presence of equivocal scan. And also I will share with Amelia some ideas on the role of SPECT or SPECT-CT and about the possible role of following a patient with this kind of imaging. Thank you for the attention, and now I'd like to discuss all these things with Dr. Effernan. Thank you, Elisa, for this very interesting case of concomitant aortic stenosis and cardiac amyloidosis. Up to one in eight patients referred for TAVI, they are found to have cardiac amyloidosis. So this is very interesting. Regarding the tracer, in this case, you used HMDP, which is one of three possible tracers for this purpose, for cardiac amyloidosis, together with PYP, which is mainly used in the US, Canada, Japan, China, and Eastern Europe, and DPD, which is mainly used in Western Europe. All three are suitable tracers, but we must keep in mind the great heterogeneity of bone tracer tissue uptake that is related to multiple factors, the type of amyloidosis, the specific mutation, fibro composition, tissue involved, and also amyloid load and tissue cancerification, and of course, the tracer itself. And in this regard, we must remark that MDP should never be used for cardiac amyloidosis. This would be the fourth tracer, the fourth bone tracer, and should not be used because very frequently, I mean, it's unreliable. Very frequently, we can have falsely negative scans. So MDP should not be used. In fact, one of the cause of false negative scan can be the wrong choice of the tracer. Yes, certainly. So then we can also have false negative studies in LA amyloidosis, as you all know. LA amyloidosis can show any degree of uptake. So in presence of a negative scan, you cannot exclude it. And also with positive scans, we have to exclude it because sometimes AL amyloidosis can show very prominent uptake, even peritoneal three. We are gonna focus now on some mutations that persistently show false negative results. Having cardiac amyloidosis, the bone scan is negative. And this occurs in some TTR mutations, including the most frequent mutation worldwide, which is VAL50MET or VAL30MET in the early onset of disease group. This is a patient presenting with disease at the age of 50 or up to 50. So this is related to the type of fibrils, which are the type B amyloid fibrils, which are full length fibrils in opposition to type A fibrils, which are prevalent in the late onset disease and in the rest of the more frequent mutations, the more frequent mutations, because there are some mutations which are not VAL30MET that have false negative scans, but all the others are positive. Well, in those, the fibrils are type A, and these are a mixture of full length and truncated fibrils. So it seems that this mixture is important for the scan to be positive. So we shall never, never, we shall always acknowledge this fact when reporting a negative scan, if we have certain mutations or if it's the early onset disease patients. And then if we jump to the equivocal cases issue, well, our case depicts a very clear perigine myocardial uptake that even resembles a myocardial perfusion scan. But when we see perigine one uptake, we face uncertainty. Is it a truly negative study or is this reflecting early or incipient disease? If we suspect incipient disease, we can recommend a follow-up study in a few months or earlier if clinical signs or symptoms develop. But if suspicion is very strong, well, then endomyocardial biopsy may be necessary to exclude or confirm cardiac amyloidosis. These are tricky, they can be tricky cases, these perigine ones. Can we also suggest in presence of an equivocal scan to perform, if possible, in the center, SPECT or SPECT-CT? Yes, of course. SPECT is essential whenever perigine is more than zero. SPECT is essential because it's gonna help differentiate blood pool from true myocardial uptake and also to better delineate uptake when we see that it's very clear in the myocardium as in grade two and three perigine grade, but we want to better delineate it. We will see uptake is mainly in the perigine. Uptake is mainly in the basal segments of the myocardial walls and the apex will usually have little or no uptake. But also I would like to emphasize that SPECT-CT is even better than SPECT because sometimes in hypertrophied ventricles and elongated blood pool can be confused with true myocardial uptake. An enlarged right ventricle full of blood and the blood pool in the left ventricle that is surrounded by cold walls that are hypertrophied, well, that can resemble the anterolateral and inferior walls. And you can get the wrong impression that it's true myocardial uptake. Well, the CT component will clearly show you if it's actually blood pool or it's myocardial wall uptake. So those are very important. Yes. Yes. I have a couple of some great questions coming in the chat. It could be a whole other webinar for them. I'll choose a couple of some beauties. We noticed in this case there was some right ventricular uptake as well. We know in sarcoid imaging with FDG, right ventricular uptake implies a worse prognosis. Is that the same in amyloid imaging and looking at the extent of uptake in terms of worse prognosis? Elisa, do you want to take that? I haven't taken exactly the question. The right ventricular uptake. Does it compare to worse prognosis? Yes. Okay. The right ventricular uptake is a point. There are some studies, but it's not well delineated, but there are some study that the inclusion of the epics in the distribution of the tracer as well as the uptake in the right ventricle are prognostic favorable markers. Therefore, yes, there are some insight about this, even though it's not as well reported in the guideline for reporting these studies. We usually, in my center, we reported it. We used to report it. And maybe one last question as well, too. This is a very popular question. With respect to repeat scanning, particularly with patients getting drugs such as tefamidus, should we be doing repeat scanning and what are the implications? Okay. Well, there's a growing number of reports in the literature showing decreasing uptake of bone scan tracers in patients undergoing treatment with tefamidus and patisiran, and also with the drugs that remove the amyloid from the tissue, the antibodies. And the mechanism is not clear, but it seems to be related to the favorable effects of myocardial amyloid load and structure of treatment on this, and the effective reduction of serum TTR levels. And better than doing it visually, advanced spec CT quantification is also being explored as a mean of showing this more accurately. And yeah, there's a lot of work going on on this. And it seems to maybe have a role. And maybe four or five years back, we thought that the bone scan was always gonna be positive even if the patient responded to treatment, but it seems this is not the case. With these transformative therapies we have now that we didn't have four or five years ago. And with the new antibodies treatment, we also improved this, yeah, definitely. Well, thank you very much, you both. Certainly that amyloidosis will bring in the future many, many other informations in about the nuclear medicine techniques, including PET, of course. But it's time to move on to case four. And case four is on microvascular disease. And it's going to be presented. And it's my pleasure to present my co-chair, Professor Leon Menezes that runs nuclear cardiology at Bards Art Center. And this case will be discussed by Alicia Gemelli, leader of nuclear cardiology unit of the Fondazione Toscana in Pisa, and also a very prominent member of the European Society of Cardiology, namely of its cardiovascular imaging group. So, Leon and Alicia, that's your floor. Thank you. Excellent, thank you very much, Maria. I'm just gonna show two cases, quickly go through them as a jump off start. And I bring these here this evening because they demonstrate the issue that I have when I'm reading these scans as to what to say and how to lead the onward diagnosis, the onward management of the patients. So, this was a 70-year-old man. He had a run of non-sustained VT on a halter, in atrial fibrillation as well, and he also had a pause. So, they adjusted his beta blockers, but then sent him for a perfusion scan to see whether he had ischemia. That was all the information I had. Now, this is the scan. This is rubidium PET-CT, the standard display as we're used to for perfusion imaging. I haven't recorded this chap's BMI. These images are slightly noisy. I suspect he was on the bigger side. But looking at that, I thought, well, it doesn't look that impressive, allowing for the noise and the patchiness, therefore, in the uptake. Then I went to my bullseye images and different bullseyes to see, and the computer wasn't impressed either, certainly not on the scoring. So, I was still thinking, okay, this looks like a normal scan. And again, I don't believe in balancer ischemia, but that is the tenant of this little presentation, is if you're faced with two scans which are normal, maybe there is a global reduction in relative flow that I'm missing. And so, my review areas are then here with the ejection fraction. And on our software that we use, a small criticism of it, the key factor is the smallest thing on the screen. So, I'm just gonna mag up here on the ejection fraction. In blue is in rest, and in orange is the stress ejection fraction. And just for those people who don't have PET perfusion, we actually scan during the adenosine. So, this is a true vasodilator stress ejection fraction. And there's no change in the end diastolic volume, and the ejection fraction went up by a couple of points, but certainly didn't go down. So, I don't have any transient ischemic dilatation, and I've got some augmentation of stress, certainly no poor stress reserve. So, I'm not thinking balance ischemia on the basis. So, that's what I'm thinking. I'm gonna go with the normal scan readout here. But then we have the perfusion data, taking the first pass of the tracer, and modeling it with the one compartment model, and taking our relative perfusion images, which we see on the left-hand side, into now quantifiable images, which now have units. They're now parametric. So, we get stress and rest and reserve bullseyes. We get that done by segment by segment, and we get a pixel by pixel map on this particular software. Most of the literature and the work on this has been done, not on any of that, but simply on the global, or here, the total myocardial flow reserve, taking the whole, the ratio of the whole flow across the heart over stress over rest. And the ratio here is one and a half, which is at the very low limit of normal, and that then postulates that this patient has got severely reduced global flow reserve in the face of normal relative perfusion. So, I have to interpret this now as saying, is that there's something, that we need to do something else to determine what's going on, and to adjudicate the contribution of here, potential microvascular disease, or severe epicardial coronary disease, although I'm not thinking that from the other ancillary signs that even Fabian mentioned in his talk, or maybe possibly a combination of both. And in this patient, we decided to take him to the cath lab. He's a 70-year-old man in atrial fibrillation. CT scan, we didn't really favor. He was also quite a large gentleman, as I think I demonstrated. So, we went straight to the cath lab on him. But here, we see that he's got some coronary artery disease. His coronaries aren't perfect, as befits a 70-year-old, but there isn't any severe disease in either of his epicardial coronary arteries. And therefore, the cause of that severe reduction in the myocardial flow reserve has to be an element of microvascular ischemia. What I find slightly unsatisfactory about these cases is that I have to invoke another test, or invoke a probability of a finding. I can't be absolute about these things. And anyone who knows me knows me that I like to be quite categorical, and say this is what this is. But sometimes you do have to synthesize all the imaging that we can possibly get to come to an answer. The next case, one I can be categorical, so this pleases me. She's 73, also quite elderly. She's got chest pain on exertion, but she's already been to the cath lab, and those coronaries were unobstructed, maybe a mild to mild disease in the circumflex. And when we start doing this sort of service, reporting myocardial blood flows, there is actually a take-up from the conditions referring. And so the request says, is this myocardial ischemia? She's still got symptoms, but not explained by the extent of a coronary artery disease. So here's that angiogram from six months ago, and she's got really quite lovely coronaries. So when she's still symptomatic, this is why we go that way. And here's her rubidium scan. Quite a lot of gastric uptake and stress and rest here, overlapping the infralateral LV. Because of the ramp filter artifact, it's not so much of a readout problem. And the last case that Parthi showed on Twitter the other day, showing how rubidium doesn't really suffer from that. Again, pretty nice uptake throughout the LV. Maybe a mild fixed reduction in the apex, probably postulate that as apical thinning. Certainly there are no regional wall motion abnormalities in the apex and a history of infarction. Sorry, that's come out a little bit blurry. But again, zooming in onto the ejection fraction, just to see fantastic augmentation with stress, and certainly no change in the end diastolic volumes to any kind of ischemic dilatation. So no relative ischemia in the circumflex territory there, fixed apical reduction, apical thinning. Let's look at the myocardial blood flow. So we have shown you the normal perfusion, and here we have the bullseye maps. I'm just gonna zoom in on the numbers. And there, her global myocardial flow reserve is 1.2. So very much lower. And knowing that the Cori anatomy, that as we do in this case, we can say that this lady does have microvascular disease, and we've effectively diagnosed it with a combination of an invasive angiogram and a non-invasive test. And then therefore we can put on, well, one, give her a diagnostic label and potentially change her therapeutic management going forward. So two cases of severely reduced global myocardial flow reserve. One with the anatomy, one without the known anatomy. There is this differential between multivessel disease, microvascular disease, and a combination of the two. And in practice, you have to integrate coronary calcium of the CT, of dundal attenuation correction, an angiogram, be it a CT angiogram or an invasive angiogram, and those ancillary findings of triple-vestal disease as we work through the case to kind of make our best bet on the finding. Okay. What do you think of that, Alessia? So I think that these two cases are great cases. Congratulations, because we can speak a lot about the possibility to use PET for devaluation of ischemia. Because up to now, the only way that we have to evaluate absolute myocardial blood flow, that is the gold standard for devaluation of ischemia is with PET. Everyone is trying to find a cutoff and the possibility to evaluate quantitation in some way to use it for stratify and to evaluate also prognosis for patients. But PET is the only way that we have to evaluate absolute myocardial blood flow, because myocardial blood flow reserve is a sort of a ratio between rest and stress absolute myocardial blood flow. And the two cases that you presented are very interesting because they started from a different point of view. In the first case, you have a very, you have a low myocardial blood flow at rest and you have an increase after stress, even if it's not enough to have a maintained myocardial flow reserve. In the other cases, you have a normal rest absolute myocardial blood flow, but the increase after stress is very low. So these two cases probably are very different also in terms of answer of microcirculation abnormalities. So this is very interesting. Probably we should know something more about, for example, presence of risk factors like diabetes, hypercholesterolemia, because also in these cases, we can have a very important impact on microcirculatory abnormalities. What do you think? No, you're absolutely right. I just, the clinical history that I showed you is the clinical history that's presented to me when I'm reporting the scan. And so, yeah, sometimes you do have to go back through the electronic health record to exactly to find out, are they diabetic? Are they hypertensive? I can get the blood pressure details from the stressing, the pharmacological stress, or I can work out from their drug history what they might be. In neither of these two patients were diabetic, and I can't remember what hypertension off the top of my case. But yeah, it also, it is also, yeah, my eye goes to the ratio number at the end, but you do have to look at the actual, the denominator and the numerator to work out exactly what has happened here. You know, have we got adequate vasodilatation or not? Is that the one reason why these numbers are low? And again, is there actually a high rest flow artificially raising the, I've forgotten my maths, the denominator, which may make the ratio smaller, because then there may be corrections that you could apply to that in the calculation to adjust for that latent rest flow pressure thought to be due to hypertension. So absolutely, again, the more clinical information, the more you can feed into your interpretation. Yes, and I think that also there's, these results are very important because during the last ESC Congress, Mark Dweck, and I think that you know very well him, said that ischemia is just a consequence because the cause of ischemia and the cause of everything is plaque. I think that now we have the demonstration. It's not true because we can have ischemia also in absence of plaque. So I think that this is a very nice way to demonstrate that ischemia is not only the consequence of plaque, but ischemia is something that could be, and could be present standalone in some way, because it can depend by other factors, like for example, of course, microcirculation abnormalities. Nathan, please. Yes, thanks, Alicia, too. Some great questions coming through as well. Just, you talked about this correction, Leon, a little bit earlier on, and you did as well, Alicia. Do you want to spill this out, exactly what that correction is for those of the audience that aren't familiar with it? I'm laughing because it's one of these things where people get very exercised and angry in conferences, asking whether you can, you should, or you should not do this. But there's something called the rate pressure product correction. And what you do is you dial in the rest blood pressure and the resting pulse into the modelling of the blood flow. And you correct, if someone is hypertensive, or if their rest flow isn't near unity, you consider dialing that in. And it will, as I say, they're just the numerator in the software. Not all softwares are equal, and not all softwares make it quite as easy as that, but it's simply a mathematical correction. In most of the published literature, that correction hasn't been taken, so it hasn't been done. So some of our thresholds, absolute ranges, might be different had that correction been done. Could I also ask, is the concept of also splitting switch off to make sure that the adenosine is actually working? Do you use that in your practices? Oh yeah, well, sorry, yes. So I did mention, you know, one of the reasons for a very low number might be we've not actually stressed the patient, tend to use adenosine. This doesn't happen in regadenosome. But yeah, one of my colleagues, Charlotte Manastino, assistant cardiac MRI, absolutely it works in PET and in SPECT, slightly harder to see, is that during vasodilatation in the heart, there's vasoconstriction in the splanchnic circulation, so you get less uptake in the spleen. So I can tell without the labeling on the image, which is the stress or the rest scan, simply because the stress scan doesn't have the spleen lighting up with tracer, and it goes down on the stress, and it's avid on the rest scan. So that's a prerequisite to check. You know, my techs do that before the patient gets off the bed, have we stressed the patient? And again, my interpreter, when I'm reading the scan to check, I don't make a pass to myself to say, actually, we've never stressed this patient, and this is not myocardial vascular disease, this is just not, this is tea or coffee on board or something, yeah. And may I ask one last question? Yeah. I can ask one last question for Alicia as well too, and for Leon. We've been talking about fluperidaz for a long time, where do you think this is gonna fit in to our practices? Alicia, do you wanna? Oh, yes. So this is a very good question. I don't know if fluperidaz will be available soon, because I am older enough to say that we spoke about fluperidaz for a long time, but up to now we don't have it, but I think that if we will have the opportunity to use it, it will change the game. Because in some way, we can use it in a very user-friendly way, and we don't need to have cyclotron and everything that can reduce the availability of PET everywhere. And probably also the cost could be a little bit lower than rubidium. And this is my question also for Leon. Do you think that the use of rubidium can increase the role of PET rather than, for example, ammonia or water? I disagree with you that you've been, you're too old to seem to be disappointed by the story of fluperidaz. And I would say that certainly it's extraction fraction being very close to one makes it a very appealing tracer for use for the quantification purposes, because you don't have to introduce any corrections for that tail off at high flow rates. But then we have, yeah, we have to look at the market in that there is for perfusion imaging, and it's constrained. There was a very good review written in JNC looking at the worldwide penetration of PET for perfusion. I can speak to England, is that PET is driven by cancer provision, and that was why we had an increase in PET cameras. And then it's a case of muscling in on the scanner, trying to carve out time for cardiology patients. And the appeal for something like fluperidaz is that you can potentially order a unit test, which one or two, if you're a low volume practice and not have that commitment of a monthly rolling contract, say with a rubidium generator or the massive, well, I don't know massive, I don't know how much it is, but the commitment, like buying a puppy or buying an ammonia generator. So all of these are very big barriers to entry. And I think fluperidaz will make it easier because you can literally have a handful of cases. So yeah, if something like that does come to the market, I think it will be transformative. Although it won't, because it's 18F fluorine, it won't have the throughput advantages that we're seeing with ammonia and rubidium because these scans are half an hour appointments. So again, if you're a low volume center, maybe that might be not so much of a importance. Well, thank you very much to you all. And if there are no further questions, I think it's time to conclude this webinar. And I will be concluding it by thanking not only ASNIC, of course, to put it up, but also our faculty, everyone, and everyone that honors us with their presence. And I will express also my gratitude to all those assisting and organizing this event. Specially, I would like to thank Kelly and Dawn, of course, Nathan, Juan, Felix, everybody in ASNIC that helped us to put up this webinar, all the faculty and all of you that honor us with your presence. Don't forget to complete the webinar evaluation. And I hope to see you all very, very soon, of course, with ASNIC. Thank you very much. And have a nice evening. Bye-bye. Or a nice day, depending where you are. Bye-bye. Bye-bye. Bye.

echocardiogram

granular sparkling appearance

left ventricular parietal thickness

cardiac ATTR wild-type amyloidosis

tabri procedure

pacemaker implantation

exertional chest pain

coronary artery disease

Rubidium PET-CT

apical thinning

myocardial flow reserve