Good afternoon, everyone. Kudos to everyone for staying until late afternoon to learn about a very important topic, a series of topics. I'm Bob Eknazer from the University of Washington. And I'm Kelly Arps from the University of Michigan. We have a group of speakers going to talk about, obviously, very challenging substrates that we all take care of. They really span a wide range of the age spectrum, really, if you look at the topics we're going to discuss and pose a lot of complex clinical decision making for us. A couple of housekeeping things. If you don't already have the app, consider downloading it because your Q&A, your questions can be submitted via the app electronically. And there will be a mic Q&A afterwards at the very end. And then if you don't have the app, the QR code is also on the screen to scan to send questions. Excellent. So I'll introduce our first speaker, Dr. Matthew Brown, who's a heart failure specialist from Emory, who is here to teach us about amyloid. Thank you. All right. Well, thank you very much. I'm excited to be here. My name is Matthew Brown and I'm a heart failure fellow at Emory University. Very excited and honored to discuss the latest medical advances in cardiac amyloidosis and its impacts on arrhythmia care. Let's see. Oh, we have a QR code to scan. All right. Well, let's first talk about why this matters to you. Wow. Your experiences with this entity may have been riddled with cases like this end stage disease over the course of an era of just pure palliation. I'm excited to discuss advances in diagnostics for early recognition and novel treatments with survival benefits. As amyloidosis is a systemic disease, your role is vitally important as often first signs of cardiac involvement are with electrophysiologic manifestations rather than overt heart failure. These EP manifestations cover the full gambit with atrial arrhythmia burden quoted around 70 percent, high grade conduction disease occurring in about 10 percent, and ventricular arrhythmias with varying rates reported around 40 to 50 percent, largely driven by an NSBT, but all warranting thoughtful use of implantable devices. I hope I can also convince you that your help is not only needed in device management and arrhythmias, but also in having a high degree of clinical suspicion as you encounter these patients in the clinic and lab pre-diagnosis as early referral can now link them with earlier treatments and curb disease progression. Today we're going to walk through two recent consults I've had and along the way review cardiac amyloidosis diagnostic algorithms, explore amyloid light chain and transthyrene treatments, and then consider the EP implications. There's some audio response built in. We'll give it a whirl, see how it works. Let's jump right in. First, we're called about atrial flutter in a 54 gentleman with a recently diagnosed HF-PF in the setting of rapidly progressing kidney disease newly requiring intermittent HD. You go down and they're finishing up the bedside echocardiogram and you find preserved biventricular function, but severely concentric hypertrophy, reduced global longitudinal strain pattern with the cherry on top, apical sparing. You're already thinking amyloid and my question for you is what is the next best test to order in order to work up his cardiomyopathy? All right. Well, recommendations from the 2023 ACC expert consensus document. Whenever there's clinical suspicion for amyloid, it's important to then rule out hematologic markers. So testing with a combination of serum free light chain as well as serum and urine immunofixation is the next step. And it's important to note that it's no longer just SPEP and UPEP. They are not sensitive enough to rule out pair of proteins. You have to use the immunofixation. Some labs simply rely on a reflux and that can lead to very confusing diagnoses. All right. But this patient's hematologic tests are remarkably abnormal with capital light chain ratios well above the reference range by magnitudes. So we got hematology involved as we started down the light chain pathway. They performed a bone marrow biopsy and sure enough it was consistent with a plasma cell dyscrasia. Stain positive for Congo Red, which confirms light chain or AL, cardiac amyloidosis. And looking at his cardiac biomarkers, they were very elevated. So he was presenting at a very advanced stage of disease. That's exactly what we want to avoid. In regards to his atrial flutter, in light of this new diagnosis, you know rate control agents and restrictive cardiomyopathy don't mix. So you're really left with amiodarone. There's some controversial data out there about digoxin. We do introduce it as the data in regard to mixing with amyloid fibrils is not totally clear. And then finally, it's very important to anticoagulate these patients regardless of CHA2DS2-VASc. They have very high rates of intracardiac thrombi. And in regards to that, any sort of anticoagulation strategy, regardless of rhythm control strategy, needs to be preceded by cardiac imaging to rule out thrombus before attempting cardioversion, which is what we did initially. And we were able to get some more volume removal, get him to a more well-compensated state. And then our hematology group actually initiated chemotherapy. Unfortunately, he went right back into atrial flutter. So they were unable to continue with chemotherapy. However, talking with our EP colleagues, we decided to try CTI ablation. And this was successful. Now, this image shows data that I'm extrapolating from TTR, but in advanced stages, which he was well-considered, recurrence is very highly likely in both cardioversion at 30 days and then anticoagulation strategies as well. But we were fortunate to be able to continue his care. And in regard to chemotherapy, it's very important to consider advances over the past few years. Previously, again, this would have been a palliative case. But there's a variety of agents that have been used to target plasma cell sources for this light chain disease. And in 2021, a trial incorporated CD38-targeting monoclonal antibody called daratumumab and this reinvigorated therapy. It's a landmark trial called the Andromeda trial. And they used daratumumab in combination with the three-drug regimen cyclophosphamide, fortezumab, dexamethasone, also known as CyBOR-D, and had significant reduction in a composite endpoint of major organ deterioration, hematologic progression, and death, as well as a two-fold increase in hardened kidney responses. It's rare that you see such a difference in the survival curves or the composite endpoints of oncology studies. So thinking about this new combination now dubbed Dara-CyBOR-D, it was found to be superior to all prior chemo regimens and even rivaled that of stem cell therapy. Thinking about our patient with advanced stage cardiomyopathy, data has shown that this therapy is effective in all stages and even has some data to say that it's more effective at the advanced stages. So that is enough about light chain. I am a cardiologist, and I like to stick to the cardiology realm, but I do love the interdisciplinary working from working with hematology colleagues. But let's move on to our next case, which is actually provided by one of our electrophysiologists. They brought in a patient from a local hospital who needed an AFib ablation. It was an elective procedure for persistent AFib. He underwent a pulmonary vein isolation and a CTI ablation. And during the case, they noted that his HV interval was almost 80 milliseconds. In sinus rhythm, his EKG showed nearly 350 with low voltage, and he had a past medical of bilateral carpal tunnel releases. So we were very excited to get involved. We started with an echocardiogram, and sure enough, he had concentric hypertrophy, a calcified aortic valve, biatrial enlargement, all the classic findings of cardiac amyloidosis. And again, with that cherry on top, apical sparing pattern. We looked at his hematologic markers, which were normal, and then proceeded down what I like to call the cardiac route. Previously, we used to perform invasive endomyocardial biopsy here. Now, we've rolled out a nuclear medicine scan called the PYP scan or pyrophosphate, which is actually a bone tracer, but it's very specific and uptaken by transliridin. So it involves both planner and SPECT-CT imaging, and it's a quick test that can be done pretty reliably. We also did genetic testing to rule out any sort of variant disease. Alright, and these are the results of his scan, which was consistent with grade 2, with the highest grade being 3 uptake. And it's well differentiated as you scan through the SPECT-CT, that it's all uptaken in the endomyocardium, as opposed to the blood pool. So this was a great referral by our EP colleagues, and we managed to catch him at an intermediate stage, and we were able to initiate TTR-directed therapies, namely the stabilizer tefamidus. So over the past decade, there's been lots of therapies that have rolled out. We now have 3 FDA-approved treatments for cardiomyopathy. They're bolded here. Two are stabilizers, and one is a silencer. They each have mortality benefits, and there's also several exciting clinical trials ongoing. We'll zoom through this data, each showing mortality benefit. The first being tefamidus, which is an oral, once-daily medicine. The next being acirimidus, which is also a stabilizer and a twice-daily oral medication. And then the third and most recent FDA approval, which was just last month, is a small interfering RNA molecule, siRNA, that targets TTR production at the MRA level and prevents it from being formed at all. This is an infusion, or I'm sorry, a subcutaneous injection that's performed every 3 months. Two exciting studies involve recombinant, a monoclonal antibody that's capable of actually degradating amyloid fibrils from the myocardium, as evidenced by this PYP scan with serial reduction over 12 months. Finally, we have CRISPR-Cas9, which is a single injection that rapidly and durably reduces TTR levels. So getting back to our case, this patient was found to have new TTR and significant conduction disease. We decided to move forward with a CRTP, given a past medical of syncopal events. You may say, why jump straight to a CRTP? But data has shown that patients with cardiac amyloidosis progress to have more advanced conduction disease, as evidenced by the increase in ventricular pacing over time. We know that right ventricular pacing can often lead to cardiomyopathy. Alright, so this is the most controversial topic, ventricular arrhythmia, and in light of new therapies, the prior dogma of death by electromechanical dissociation and futility of ICDs has really been challenged. Here is an ICD interrogation or a pacer interrogation shortly after our patient went home, showing that he had a 28 second run of ET and collapsed at a restaurant. So he was brought back in and we decided I'm interested in finding out what you guys would recommend as the next step here. All right. That's what we did. We were very compelled. And this is a management approach that was suggested in a 2014 algorithm from Stanford. It really spurred a lot of interest in ventricular arrhythmia burden in this population. They focused primarily on AL. We have a large hereditary transtyrene cardiac amyloidosis population at our institution. And they also are unique in that they have reduced ejection fraction. So we published some data with our experience and showed that among the people with reduced ejection fraction, they have much higher rates of ventricular arrhythmia. This is largely driven by NSVT. But in those that did get implantable cardiac devices, they had substantial rates of appropriate therapy approaching 25%. It needs to be acknowledged that no trial has shown any mortality benefit of primary prevention ICDs and recommendations in both the ESC and HRS continue to be 2A, 2B. So that concludes my talk. Hopefully you learned something today. And I'll take any questions at the end. Thank you. Thank you very much. Our next speaker making his way up here is Dr. Cletus Constantinidis from the University of Utah. And he'll be speaking to us about arrhythmia management in ARVC and desmoplacian cardiomyopathy. Thank you, Kelly. I'm going to start here. Hi, everybody. Thank you for coming late. So today we're going to talk about ARVC and desmoplacian and how we manage VT in these patients. Okay, so ARVC is right ventricular cardiomyopathy, predominantly RV. And we make the diagnosis using the 2010 modified criteria. We have six different categories. And we can make indefinite borderline or possible diagnosis based on how many criteria you meet, major and minor criteria. We know that there's multiple genes that are responsible for the phenotype of ARVC. The main ones are the desmosomal genes. And the most common one is PKP2, which is about 80% of the known mutations of the patients have PKP2. We know that 40% of patients, about 40% of patients have gene elusive disease. So what is the substrate in ARVC? So the substrate starts around the valves, around the tricuspid valve, and extends more epically and more anterior and in the outflow tract region of the RV. You can see the aneurysms that can develop in these areas around the valves, around the tricuspid valve here and around the outflow tract. The disease starts from the epicardium and slowly extends into the endocardium. And there's about 20% of patients that you find only epicardial substrate. And one clue is when you do the study, you use unipolar voltage to try to identify a deeper scar. The initial studies show that, show very poor outcomes with endocardial only ablation, endocardial only ablation in the early 2000s. And those results were followed by three main studies that show that if you do endo-AB ablation in these patients, they actually do much better. First study, 2009, was 13 patients who failed endo-ablation. And they had 77% freedom from VT with a mean follow-up of 18 months. Second study, in Sergey, a couple years later, 49 patients that compare endo versus endo-AB ablation. And it was at least three years of follow-up. You can see there the recurrence rate was much lower when you did a combined procedure. And that was followed four years later. Sergey, two-thirds of the patients had endo-AB ablation, mean follow-up, two and a half years. You get about 70% freedom from ventricular arrhythmia. VT burden is significantly decreased with the endo-AB approach. And these patients use much less antiarrhythmic drugs after the ablation. Last year, a study came out from Penn. It was a 22-year experience. They had 74 patients that they did endo-only ablations. And follow-up was 6.6 years, long follow-up. Freedom from ventricular arrhythmias was 55%. But if you can get these patients non-inducible, they do much better. They have 75% freedom from ventricular arrhythmias. And they use less drugs after the ablation. And what was interesting about this study is that there were two predictors of VT free survival. One was non-inducibility at the end of the study. And the other one was patients with older than 45 years old, suggesting that maybe later when the substrate changes from epicardial towards more endocardial, you can get the circuits from the endocardial surface. And maybe it's reasonable to start in older patients with an endocardial approach. And then only if you can get them non-inducible, you go epicardially. How about antiarrhythmic drugs? We know that flecani works very well in ARVC patients. The first study on the left, they took 100 patients. 60 of them had VT prior to treatment. Median follow-up was four years. And as you can see there, the freedom from ventricular arrhythmias in one year is 96%. And in five years, it's 75%. And more importantly, some of the patients had EP studies. And they did EP studies on and off flecainide. And you can see how much difference you have in terms of inducibility during the EP study when they're on flecainide. And the other study on the right is a small case series of eight patients that most of them had prior ablation. They combined flecainide with sodalo. And there was a significant decrease in the VT burden in these patients. And it appeared to be safe. Currently, I think there's an ongoing clinical trial for flecainide in ARVC. But the field is moving more towards a genotype-specific arrhythmogenic cardiomyopathy diagnosis. As you can see here, there's some genes that cause predominantly an ARV phenotype. There is some genes that cause predominantly an LV phenotype. But there's a lot of overlap between these groups. And we learned that specific genes can have specific phenotypes. And the prototype for that is desmoplagin. So this is a seminal paper that came out a few years ago where they described 100, they looked at 107 patients with pathogenic desmoplagin mutations. And they compared them to patients with PK, platyplacophyllin, the most common ARVC gene. Almost all of them have truncated mutations. And you see that desmoplagin creates this unique cardiomyopathy that has a very specific scar pattern that is like a ring-like pattern in the mid-epicardial LV. And it has these episodes of inflammation where patients present with chest pain. They have positive troponins. You do coronaries, they're clean. And as you'll see later, these episodes are associated with a high risk of ventricular arrhythmia. What is interesting is that if you use the ARVC criteria, the 2010 modified criteria, they have very poor sensitivity. So you're going to miss a lot of patients with desmoplagin. So this year, the largest cohort of desmoplagin patients was published in the European Heart Journal where they looked at 800 patients with likely pathogenic or pathogenic desmoplagin variants. And they identified the clinical features that predict high risk of ventricular arrhythmias and heart failure in these patients. As you can see here, the number of PVCs, T-wave inversions, non-sustained VT, and EF less than 50%. They have very high burden of adverse events, about 4% per year for ventricular arrhythmias and about 2% for heart failure. And almost half of these ventricular arrhythmia episodes were really fast VTs. And the unique features of this disease predict bad outcomes. So if patients present with these episodes of inflammation, they are at high risk for having both ventricular arrhythmias and heart failure. And in contrast to the ARVC diseases that males usually have worse disease, female patients have higher rates of ventricular arrhythmias in desmoplagin. How about ablation? Ablation is tough in these people. This is a multicenter experience, multicenter, 20 patients. These patients have biventricular involvement. Many times they get the septum. You see it's around the outflow tracts, very tough areas, close to the coronaries, a lot of fat there, meet epicardial. A lot of patients need multiple procedures. Some patients need four procedures. But after you finish all the procedures, they do well. The freedom from ventricular arrhythmias, 19 out of 20 patients, median follow-up of 18 years. But of course, I'm going to talk about PFA. I think PFA is, I think it's going to be the future in these diseases. And one of the main reasons is that it doesn't, it's not limited by scar. In these diseases, we know that there's a lot of scar. There's a lot of scar in the meet epicardial layers. You can't get there with the ARF. This was a case report published this year from the Cleveland Clinic where they put the faropulse in the RVOT, and they were able to, it's very interesting, they were able to disarticulate the epicardial RV from the endocardial, from the meet endocardial layers with PFA, which means they terminated the VT. The entire heart was in sinus rhythm except for the epicardial region that was still in VT. They gave four pulses in the two configurations. So four flowers, four baskets. So what is our experience at the University of Utah? So we've done about eight VT cases with PFA. It's very powerful. So the first case I show you here is a patient with RV predominant sarcoidosis. Initially, they thought he had ARVC, so one of the mimickers of ARVC. So he had recurring VT. He's in his 50s. Recurring VT, despite antiarrhythmics, he had multiple VTs. So what we did, we had both endocardial and epicardial access. And we mapped epi, the first here on the left is a pre-PFA, is mapping epi bipolar voltage pre-PFA. And then on the right, post-endopFA, we delivered multiple lesions until we were able to get him non-inducible. And only after 36 applications were able to get him non-inducible. But you can see here that it penetrates all the way out into the epicardial layers. And on the right, you see the lesions that we delivered. It's not the entire RV. It looks scary. But we missed the mid and epical portions there. So this is the area that we delivered energy. And he's doing well. It's been three months now. He hasn't had any VT. The second case is a laminae in a patient in his 50s with very similar scar to desmoplagin. He had a ring-like scar pattern in the LV. The same story, he had recurrent VTs, despite antiarrhythmics, multiple VTs. We did 38 applications for him to get him non-inducible. Again, the same story. We had an epicardial access, pre-PFA bipolar voltage in the epicardium. And this is post-PFA, after endocardial PFA applications. And you can see that it goes through, even on the LV. It's not as impressive as the RV. But it went through, and he was non-inducible at the end of the procedure. And the reason why we chose to go with PFA also was that these patients have very poor outcomes with RF, the sarcoid and the laminae. So we said, why don't we try something new? And we couldn't find the diastolic circuit anywhere, endo or RV. That's all I have. Thank you. Really pleased to introduce my neighbor here at the table, my dear friend and my colleague at University of Washington, Dr. Neil Chatterjee, who's gonna teach us about sarcoidosis management. Thank you, Bhavik, for that nice, warm welcome. Really delighted to be here today. Thank you for joining the session. All right, so I've been given a pretty broad mandate to cover in 12 minutes, which is to discuss the diagnostic uncertainty and ventricular arrhythmias and cardiac sarcoids. I will do my best. I promise you that this will stay at a relatively high level, but happy to answer questions afterwards. So the talk will be organized with those two mandates in mind, the first being to discuss some concepts in the topic of diagnostic uncertainty in sarcoid. And I'll try to make the case to all of you that sarcoidosis is both overdiagnosed and underdiagnosed. And then in part two of the talk, we'll cover some topics pertaining to ventricular arrhythmias and cardiac sarcoid, and discuss some concepts in risk stratification, and then also just a couple of pearls with respect to invasive management. So what is the current path to cardiac sarcoid diagnosis? There are many consensus guidelines, including those from the HRS, those from the JMHW, and the WASOG. But if you organize all of these at a very high level, they effectively involve some combination of the following. So generally speaking, some confirmation of tissue, and specifically a biopsy of the endomyocardium, a range of clinical factors, including, for example, the presence of heart block, the presence of LB dysfunction, or more nonspecific findings like VT or PBCs. And then usually some confirmation by either PET scan or cardiac MRI of evidence of sarcoidosis. So in what context could sarcoid be underdiagnosed? Well, I would make the case to you that sarcoid or anything is underdiagnosed if you don't consider it as a possibility in key subgroups. So what are those key subgroups? Well, one key subgroup are patients who are relatively young who are presenting with heart block and that's something that most if not all of you are well aware of. There are at least two sizable observational cohort studies that show that anywhere from 25 to 30% of young patients presenting with a complete heart block will be ultimately diagnosed with cardiac sarcoid. What's another key subgroup? Well, non ischemic cardiomyopathy patients who also have VT. These data are from Rod Tung and colleagues now for more than 10 years ago in which they looked at 100 consecutive patients who had non ischemic cardiomyopathy and VT referred to UCLA there at the time. They got PET scans on everyone. Half of those patients had some abnormality on PET scan and ultimately about 20% of those patients were diagnosed with cardiac sarcoid. What's another key subgroup? Well, how about non ischemic cardiomyopathy and PVCs? So this question was answered in the Maverick study which was led by DJ Lacaretti and colleagues published in Cirque A&E in 2019. This was a large multicenter cohort of patients with PVCs, actually both normal and abnormal EF. The average EF in this cohort was about 47%. Also about 100 patients. Half of those patients had a positive PET scan actually like Rod's paper. Two thirds of these patients had outflow tracked sort of PVC morphology. So these were not necessarily non OT sort of subtypes of patients. And ultimately 12% of these patients were diagnosed with cardiac sarcoid. So to switch gears, we've talked about how sarcoid might be underdiagnosed if it's not considered in key subgroups. Well then conversely, how could sarcoid be overdiagnosed? And to highlight that point, I'll share with you just a case. So this is a 47 year old patient with a history of an out of hospital cardiac arrest. He had a normal coronary angiogram, had an echo that showed some mild left ventricular dysfunction and an EKG that had a left bundle. He had a cardiac MRI which was red. I would argue proactively by the radiologist as having or sort of being in keeping with cardiac sarcoid. There was extensive patchy LDE involving the basal to mid septum. Patient then had a PET scan which was PET positive. The positivity was only present in the heart which is I think a key point here. The patient ultimately had an ICD implanted, was diagnosed with isolated cardiac sarcoid and then started on steroids. Patient now comes back a year later. He now has complete heart block and shocks from his ICD for VT. And now somebody takes a family history and he says gosh you know my brother also has cardiac sarcoid which is sort of odd. And he has another PET scan because of the ICD shocks and it turns out that the PET positivity that was present a year ago is still there in spite of being on steroids for more than a year. So now the patient has a CRT upgrade. He gets treated with amiodarone. Somebody sends genetics and in fact he has a pathogenic variant for lamin. And I think this highlights a key point which is that genetic cardiomyopathy can masquerade as cardiac sarcoidosis. And this point was really highlighted by my esteemed chair here and colleague Dr. Nasr. This is a nice paper that he and his colleagues published in Jackie P a few years ago in which they took the total cohort of patients that they were seeing with cardiac sarcoid. They identified the subset of those patients who had isolated cardiac sarcoid and they managed to offer testing to the majority of that cohort. And they found that a third of those patients in fact did not have cardiac sarcoidosis but it actually had a pathogenic mutation either for example in lamin or TPM1 or in this case MYBPC3. Since that publication we've now expanded that cohort at UW in a much larger cohort of patients. So now 81 patients who had PET imaging and gene testing. And we found that about 16% of those patients in fact don't have isolated cardiac sarcoid but in fact have a genetic cardiomyopathy. So in terms of some pearls about diagnostic uncertainty on the principle of under diagnosis I would highlight it's important to consider sarcoid in key subgroups. So young people with heart block, non ischemic cardiomyopathy with either VT or PVCs. We can diagnose cardiac sarcoid in anywhere from one in 10 to one in four of those key subgroup patients. And on the point of over diagnosis I would really emphasize that not all PET positivity is sarcoid. That's a really, really, really important point. Not all PET positivity is sarcoid. Anywhere from 16 to 30% of those patients may in fact have a genetic cardiomyopathy. Be particularly suspicious if the FDG avidity is not going away. You're treating with steroids, you're treating with steroids the patient's still PET positive. You may in fact have the wrong diagnosis. To extend that point I would make the case that isolated cardiac sarcoid is really an exclusion, is a diagnosis of exclusion. So we should be biopsying early, either cardiac or non-cardiac sites. We should be taking a careful family history and offering these patients gene testing. All right, now to pivot to part two of this talk which are to cover some topics in risk stratification in cardiac sarcoidosis. So what are the current guidelines for sudden death risk stratification in sarcoid? I'm not going to read this table to you but there is a really nice document in the European Heart Journal from a few years ago that really summarizes guidelines from both the HRS as well as the AHA and then also guidelines from our colleagues in Europe at the ESC. And I'd like to really focus on these class two guidelines, in particular cardiac sarcoid presenting with heart block. I'd also like to cover some of the data related to the value of a cardiac MRI or PET scan as it pertains to risk stratification and then go through some of the data behind the value or lack thereof of an EP study in this context. So what is the risk of ventricular arrhythmias in patients with cardiac sarcoid presenting with heart block? This is a really, really nice study published in Cirque A&E from 2018 in which the authors took 300 patients with cardiac sarcoid. They found 143 of them who presented with high grade heart block. And then they stratified those patients by the magnitude of heart muscle dysfunction and the presence or absence of VT. And if you focus on the right side of the graphic, I would highlight that patients with cardiac sarcoid who have a normal EF and no history of VT, that 10% of those patients had some manifestation of sudden cardiac death over the next five years, which is substantial, I would argue. Of course, if you also had evidence of heart muscle dysfunction and or history of VT, that was in sort of even higher risk context. But the punchline here is that in patients with cardiac sarcoid presenting with high grade heart block, we should really be making the case to place an ICD, not a pacemaker, independent of the presence or absence of heart muscle dysfunction or the presence or absence of VT. So what is the role now of cardiac MRI and LGE in particular for risk stratification in sarcoid? This is a really nice study from Coleman and colleagues which was a meta-analysis that was looking at the prognostic role of LGE positivity in sarcoid. So the endpoint in this study was a composite of death and VT, and what the authors found was that in all comers, the presence of LGE positivity was associated with a tenfold higher odds of death or VT as compared to sarcoid patients who did not have LGE on their MRI. To me, I think the most intriguing part of the study is actually this point, which is to say that the prognostic value of LGE actually appeared to be the most potent for patients who had a normal EF. So the odds ratio for LGE positivity for bad outcomes in folks with an abnormal EF was actually sort of marginal, whereas most of the prognostic value were in patients who had a normal EF. Now, does the extent of LGE matter? The short answer is yes. This is also a really beautiful paper from Kazmirzak and colleagues published in Circa A&E in which they just looked at all of the guidelines for sarcoid, and they just said, what is the annual event rate for sudden death for each of these guidelines? And when they looked at LGE in particular, they found that using a cut point of 6% was valuable, if you will, right? So patients who had more than a 6% sort of myocardial mass burden of LGE by MRI were at a 12% per year risk of having a dangerous cardiac arrhythmia as compared to 2% per year if you just use sort of LGE positivity by itself. So LGE matters, and 6% appears to be a valuable cut point. What about the role of PET scans? So these are data from Ron Blankstein, as an old colleague from the Brigham, looking at the relationship between perfusion defects in FDG and outcomes in cardiac sarcoid, and the punchline here is that patients who are positive by FDG and or perfusion are at higher risk of VT. If you had a combination of those two things, you were at fourfold higher risk than if you did not have either. All right, so is an EP study helpful in sarcoid? Despite these making it into the guidelines, the data that they're based on, I would argue, is actually pretty scant. So the primary study that we all point to is this one paper published in 2011, which is a relatively small study of about 100 patients that did indeed show that patients who had a positive EP study were at higher risk of a composite endpoint of either VT or death. Although the authors, to their credit, make the case in the paper that the heart function of the patients who had a positive EP study was far lower than the LV function of the cohort that did not have a positive EP study. So in my mind, the finding of the study could have just been a story about patients with sarcoid who have low left ventricular function are at higher risk for bad outcomes, which I think is a sort of relatively intuitive point. Now, Will Sauer and colleagues, when he was in Colorado, extended these data and they focused specifically in patients with cardiac sarcoid and normal EF. And also, in this sort of relatively small study of about 100 patients, they did find that in normal EF sarcoid, the presence of a positive EP study was associated with a higher risk of VT over a follow-up of 120 months. But again, these numbers are small, right? Sort of seven patients in the positive EP study group. Okay, last couple slides in terms of sort of clinical pearls about sort of VT management and ablation in particular in sarcoid. The nicest paper that I would point all of you to is this sort of very nice study in JAMA cardiology in 2022, which is a large consortium paper, sort of multicenter, high-quality paper that looked at the impact of VT ablation in cardiac sarcoid and VT. And what they show, which is nicely shown in this graphic, is that the average number of ICD therapies goes from two in the month prior to ablation to zero in the month after ablation. I would really highlight here that 2 3rds of these patients were PET positive in the month prior to their ablation. So the mere presence of PET positivity is not a reason not to offer a patient an ablation. Okay, we often hear from our colleagues not in EP, oh gosh, the patient's PET positive, we should choose steroids, not ablation. Not true. Now, of course, there is a role to be thoughtful about the adjunctive role of steroids to ablation or other types of therapy in sarcoid, but it's worth emphasizing that the majority of our patients who present to the hospital with VT and sarcoid will be PET positive. I would also emphasize that half of these patients, either had VT transplant or death over the following two years after their VT ablation, and that if you were PET positive or had an LVEF less than 50%, your risk of that bad outcome was higher. Finally, these are nice data from the Brigham, Saurabh Kumar and colleagues, publishing their experience about ablation of VT and sarcoid. I would highlight here, which was actually nicely highlighted in the last talk, that sarcoid is a cardiomyopathy that not just involves the LV, but also the RV. So RV substrate is present in a third of these patients. When it's present in the RV, it tends to be more confluent. By comparison, when it's present in the LV, it tends to be more patchy. It's also worth considering, particularly in the setting of a positive PET scan, that there may be more than one underlying mechanism of VT in these patients, and VT-free survival was about 40% at one year over an average of about two procedures in this cohort. So some take-home points here with respect to sarcoid and risk stratification. It's important to consider the role of ICD therapy in key subgroups. So cardiac sarcoidosis presenting with heart block, and that's true regardless of the presence or absence of LV dysfunction or a history of VT. The drive-home point here is to say that it's important to make a diagnosis. So young person comes into the hospital with heart block, the impulse should not be just place a pacemaker and send them home. There's actual value in taking the time to obtain a diagnosis and to query, could this patient have cardiac sarcoid? Because the implications of that diagnosis matter in terms of the type of device we're choosing. The other point here is that doing an MRI can be helpful. The presence of LGE positivity matters, and a cut point of 6% appears to be a helpful cutoff. The role of EP study is really based on some small studies. It's not to say that it's not helpful, but it's important to sort of contextualize the data behind which we're offering a patient an EP study. And then the presence of a positive PET scan, either perfusion defect or positive FTG appears to be associated with bad outcomes. Finally, in terms of treatment of ventricular arrhythmias, VT ablation can be effective for our patients with sarcoid who are presenting with ICD therapies. Catheter ablation is a meaningful way to reduce the risk of ICD therapies in the future. Please note that two-thirds of these patients will be FTG avid, and that's not a reason not to consider a catheter procedure for these patients. And it was important to note as well that sarcoid is not just a left ventricular process but can involve the RV. Finally, for our patients with sarcoid presenting with VT and ICD shocks, if their PET scan shows FTG avidity and or their heart function is abnormal, that is a particularly high risk circumstance and we should be collaborating closely with our colleagues in heart failure to consider sort of alternative options. Thank you very much for your attention. Thank you. Thank you very much. And then last, we have Dr. Lohi Garg from the University of Colorado. And he's going to be speaking with us about arrhythmia management in hypertrophic cardiomyopathy. Thanks, Kelly. Thanks for having me. I'm gonna talk about arrhythmia management in hypertrophic cardiomyopathy and we'll try to keep it short because we're running a little behind on time. So as Neil said, you know, it's a big topic to cover in the 12 minutes that I was asked to talk about, but this is just the overview of the talk. Now we know that atrial fibrillation is very common in patients with hypertrophic cardiomyopathy, and if you look at the prevalence of atrial fibrillation in patients with hypertrophic cardiomyopathy, it's actually six-fold higher than normal population. The other thing we know about these patients who have hypertrophic cardiomyopathy is that one-fourth of these patients will develop atrial fibrillation during their lifetime, and the usual incidence is somewhere in between two to 4%. Now the risk of AF in patients with hypertrophic cardiomyopathy actually increases with age, as we know in general population, and most commonly occurs after 60 years of age, but it can occur in younger patient population, and one-third of patients who get diagnosed with atrial fibrillation are actually under the age of 50 years. Now there is no difference between the males and females, but if you look at the normal traditional risk factors for atrial fibrillation, these actually applies to patients with hypertrophic cardiomyopathy as well, and here we can see that patients who are obese and has a BMI greater than 30 are at much higher risk than patients who have a normal BMI, and similarly, if we look at patients who have an obstructive physiology versus a non-obstructive physiology, patients with obstructive hypertrophic cardiomyopathy are actually at much higher risk compared to non-obstructive physiology. Now if you look into the pathophysiology of AFib, it shares some of the traditional criterias that you get the diastolic dysfunction increase in the LVEDP, leading to left atrial enlargement and dysfunction. You do have genetic mutation that are involving the atrial muscles itself, leading to LA fibrosis, and then you have mitral valve abnormalities, left ventricular offload tract obstruction, which can all lead to mitral regurgitation, leading to increased risk of atrial fibrillation. Now as I said, this is just one of the cases that I actually did last week. We ablated her two years ago where we had normal voltage. We did PBI and posterior wall isolation, and she came back with an atypical flutter, and we performed ablation last week, and we noted that she had progressive atrial myopathy with very low amplitude signals along the whole anterior wall, and that progressed pretty rapidly. Within the two years, we have seen her in the clinic. Now AFib screening, as I said, the prevalence of AFib is very high in these patients, but the thing is that these patients are at risk for having high stroke risk if they develop atrial fibrillation. So based on that, the current guidelines is that patients who have risk factors for developing atrial fibrillation and have hypertrophic cardiomyopathy should actually be screened with halter monitor every six months to 12 months. And one of the risk scores that you can use to screen these patients is something called HCM-AF score. It takes into consideration four factors, including age of evaluation, age at initial HCM diagnosis, the left atrial dimension, and the heart failure symptoms. And based on what you get from these four factors, which is very easy to calculate in office, you can divide these patients into low-risk, intermediate, and high-risk patients. And what they looked into this paper is that if you have a high-risk patient and falls into the highest tertile, your risk for developing atrial fibrillation during follow-up is over 50%. And I will say that these patients should actually not be screened with just halter monitor every six to 12 months, but should be considered for an ILR implant for close monitoring of atrial fibrillation or use some of the wearable health technology like an Apple Watch or CardioMobile with regular screening in these patients. Now we all know that patients who have HCM, they should be anticoagulated, irrespective of their CHAD-VAS score, to reduce the risk of stroke because they can form not just left atrial appendage thrombus, but also left atrial thrombus. Now we see all these patients, they get primary prevention ICDs and they have a lot of subclinical atrial fibrillation. So in 2024 guidelines, we actually took a step forward and said, if you have SCAF over 24 hours, anticoagulation should be initiated, irrespective of their CHAD-VAS. But if it's under 24 hours, I think that really needs a discussion with the patient about the risk factors and do they want to be anticoagulated or not. Now a lot of discussion about left atrial appendage occlusion, actually these patients were excluded from all the trials and we have very limited data about left atrial appendage occlusion in patients with hypertrophic cardiomyopathy and stroke prevention, but we do have certain studies which is based on retrospective studies. I do want to highlight one study which was published two years ago. This is based out of a national readmission database where they looked at propensity matched and compared the patients who have hypertrophic cardiomyopathy and underwent left atrial appendage occlusion or patients who were treated with anticoagulation and what they noted is that the composite outcome of stroke, mortality, and TIA was much lower in patients who had left atrial appendage occlusion. Now rate versus rhythm control for AFib is another very interesting topic in patients with hypertrophic cardiomyopathy. We know that they have restrictive physiology of heart failure and rhythm control is actually key important in these patients in reducing the risk of heart failure as well as reducing the risk of inappropriate shocks if they have a defibrillator. However, rhythm control is not that easy in patients with hypertrophic cardiomyopathy and actually AAD can be very beneficial and effective in reducing the risk. Dasopiramide, we usually don't use that drug very frequently, but it's actually my workhorse for patients who have obstructive physiology and have obstructive hypertrophic cardiomyopathy and can be used due to negative ionotrophic effects and if you look at other class three agents, Sotilol, Tecosin, they are actually not that bad with efficacy at 30% or 50% at three years. I do try to restrict the utilization of amiodarone and keep it as a last resort in these patients if they have really bad heart failure related to atrial fibrillation. Now catheter ablation can be considered if they have drug refractory AF or as per patient preference and lastly, if they are going for a myomectomy or they are being considered for surgical intervention, concomitant surgical AF ablation with left atrial appendage occlusion with atrioclip should be considered. Now why ablation should not be offered as a first therapy, a lot of patients will say, I just wanna go for catheter ablation for HCM patients and I tell them that the outcomes aren't that great and if you look at some of the older literature with the RFA, the catheter ablation alone, freedom from recurrent AFib is only 50% at one year and 35% at three years, which is not great compared with general population, which is 75% and 50% in patient without HCM. But if you look at it, patient with HCM, if we do offer them multiple ablation, we can improve the outcomes and in conjunction with the antiarrhythmic drug therapy, we can actually achieve 70% success rate up to five years in keeping them in normal sinus rhythm with multiple ablation and continued AAD use after ablation. And then lastly, as I said, if they are going for myomectomy, surgical ablation at the time of myomectomy can actually result in 70% freedom from recurrent AFib at three years compared to only 30% with catheter ablation. Now lastly, all of us have been excited about PFA for last year or so. So this was a publication talking about results of PFA for hypertrophic cardiomyopathy. This came from our European colleagues, three academic centers from Switzerland, France. They looked at 109 patients with hypertrophic cardiomyopathy who had atrial fibrillation. It's a retrospective analysis, but 58% underwent PFA and 51 had thermal ablation with either cryo or RFA. Most of the patients do have PVR performed, but if you look at it with RFA and cryo, the extra PV ablation was only 18% compared to 62% in patients who underwent PFA. And when they looked at it over the 12-month follow-up, they noted that patients who underwent PFA actually did better in terms of recurrence of atrial fibrillation, with 72% freedom from atrial fibrillation compared to 50% with thermal energy. And when they subdivided into PVI and PVR+, they noted that the outcomes are still good with PVR+, with PFA technology. On the other hand, when they used the cryo balloon and they had PVR+, they had worse outcome with 10% freedom from atrial fibrillation, those small numbers. That was about atrial fibrillation. The other thing we really get concerned about in patients with hypertrophic cardiomyopathy is risk of sudden cardiac death and prevalence of ventricular arrhythmias. Now we know that the mortality rate in HCM is less than 1% annually. However, there are certain risk factors that increases the risk of sudden death. It could be 0.5% in low-risk. However, it could be as high as 6% in certain high-risk individual with hypertrophic cardiomyopathy. And these high-risk features include apical aneurysm, VF less than 50% with dilated LV, and extensive LGE on MRI as shown by Dr. Chatterjee for Salkward patients as well. Now when we look at these patients, if they have a primary prevention ICD, the intervention risk is less than 3.6% per year. On the other hand, if they have a documented therapy before, the risk of ICD intervention is as high as 10.6%. But a lot of concept is we think about that, oh, HCM patients have VF and that's why they need the therapies, however, when we looked at these patients who have hypertrophic cardiomyopathies and looked at what they received therapies for, VF is only present in 30 to 48%, and actually majority of these patients get monomorphic VT, which could be as high as 70% in these patients. Now I wanna showcase, this is a 57-year-old male, recurrent ICD shocks for monomorphic VT, was an amiodrone and maxillitine before coming into the hospital. And when we performed an echocardiogram, we noted that he has an LVF of 60%, has an apical HCM with an apical aneurysm with a mid-cavitary obstruction with gradient of 55 millimeters. Now you can see on the right side, you have a large apical aneurysm on the ventriculogram. This is in the RAL. And this was the VT that we induced in the lab. This was a right bundle, right superior V2 transition with a cycle length of 270. And when we mapped the endo, we noted that there was a lot of low amplitude, late potentials in the apical aneurysm on the endocardium. However, during the VT, there were no mid-diastolic components. So we actually went epi in this patient, and we noted that there were late signals at the very apical portion, and that was forming the diastolic corridor. And we performed ablation in the epi portion, and the patient was non-inducible. So what about apical aneurysm and ventricular arrhythmias? We know that apical aneurysm can occur in 2% of the HCM patients. However, they are disproportionately associated with high rates of adverse event. Actually, 25% incidence of sudden cardiac death, aborted cardiac arrest, or inappropriate ICD therapies in patients who have apical aneurysm. So I'm very careful in these patients who have mid-cavitory obstruction, even though they don't have the traditional septal hypertrophy, but if they have a mid-cavitory obstruction, I'm looking for apical aneurysm, because it probably adds the highest risk for these patients. And the event rate is actually very, very high in these patients, with 10.5% event rates, including progressive heart failure, death, and stroke risk. Now, this was the first report of catheter ablation for ventricular arrhythmias in hypertrophic cardiomyopathy. This was by Dr. Muntisha et al. back in 1997, and you can see that they have a catheter located at the neck of that apical aneurysm, and you have pre-diastolic potentials, and they terminated the ventricular tachycardia in 3.7 seconds. And this is all great, but you know what happened? They left the lab, next day patient had recurrent VT, and they performed resection of the whole aneurysm surgically with non-inducibility afterwards. So what are the outcomes in these patients? So this was the report back in 2011 from three different centers, or four different centers, looking at 10 patients with hypertrophic cardiomyopathy and monomorphic VT, and what we saw that two of them had apical hypertrophic cardiomyopathy, three of them had apical aneurysm. Mid-cavity obstruction was watched in three. And a lot of these patients required epi and endoablation. Actually, eight of the patients underwent epi and endoablation. One patient had end-only scar and one patient had no scar. But if you look at it, the most common location of scar in these patients was LV apex. And when they performed it, nine patients were non-inducible at the end of the procedure. One patient still had sustained VT and required surgical cryoablation for incessant VT. Actually, there is a case report about that patient. When they took that patient for surgical intervention, the VT was coming from the lateral wall and the lateral wall was two centimeter thick. So they had to resect the whole wall from the endocardium and then perform surgical cryoablation from the top to get to the VT. So it was a lot of mid-myocardial to epicardial scar. And then three patients had recurrent ICD therapies during the follow-up of 37 months. Based on this paper, we said, okay, maybe all these patients required endo and epiablation and we can't really get to the endocardial portion or epicardial portion or mid-myocardial portion of this VT. So they need an epicardial approach. However, our Japanese colleague actually performed ablation in patients who have only apical aneurysm. This is a paper from 2017, where they looked at 15 patients with LV apical aneurysms and performed endocardial ablation for these patients. And 12 of the 15 patients actually had non-inducibility after ablation being performed in the endocardium itself, despite having circuit on the epicardial or the mid-myocardial. There was one patient where they couldn't get successful ablation from the endocardium and required epicardial ablation. And when they looked at it, there were only two patients who had recurrence of VT during the follow-up of 12 months. And one patient underwent repeat catheter ablation during that 12 month with no recurrence. Suggesting that we can actually get to these patients which have LV apical aneurysm, we can ablate endocardially, especially close to the neck or sometimes deep into the tissue, and we can make this patient non-inducible without going epicardially. Now lastly, what are the outcomes in patients with non-left ventricular apical aneurysm-related VT? And this was a report from 2010. There were 22 patients with hypertrophic cardiomyopathy and drug refractory VT. And you can see most of these patients had substrate outside of that apical aneurysm. Only two patients had apical aneurysms. Most of these patients had low EF of less than 35% with mean EF of 34%. 82% of these patients had actually scar-related VT. And 60 of them were either coming from the apex or most commonly in the basal septum with 42%. And when they performed endocardial plus epicardial ablation, you can see endocardial RFCA was in nine patients or 41% patient, and epicardial ablation was required in 60% of these patients to make them non-inducible. And at 20 months follow-up, 73% of these patients had VT-free with no recurrence noted on device or therapy. So these are my conclusion. We know atrial fibrillation in common in patients with hypertrophic cardiomyopathy, and they should be anticoagulated with DOACs irrespective of CHAD-VASC. And rhythm control could be challenging. However, it's very feasible and can be performed successfully with more than one catheter ablation and antiarrhythmic drug therapy. Now, if you do notice an LV apical aneurysm, these patients are at high risk for developing monomorphic VT, and these circuits are often intramural or epicardial, and a combined epicardial and endocardial mapping and ablation should be considered if they have recurrent drug refractory VT. Thank you. Thank you, Dr. Barth. So Kelly and I decided we'll take advantage of the fact that there's no session following this one in this room to get some questions out. Are there any from the audience that care to use the mic? Because there are several in the Q&A online. Anyone in the audience have a question? All right, well, I have the first one, which I'm actually curious to hear. For Dr. Brown, but also everyone else, what's the role of left bundle branch area pacing in amyloidosis? Does your center try it? That's a great question. I think the data is, there's not enough data to really make a call. You know, it's left bundle branch area pacing is an evolving field, and I've learned a lot from our electrophysiologist at Emory and beyond. I'm really excited for it. I think it is another avenue, especially for our complicated heart failure patients outside of just amyloidosis. But I hope that there's amyloid patients in the trials so that we can try to construct some understanding of it. Neil, am I right? We asked, we had an ESPY research conference from an early pioneer of left bundle branch area pacing, and we asked if he tries it in amyloid, and even he said no. I'm not sure that's a definitive no, and there's obviously tools on the way, but I had the same question as someone here. Question for Dr. Konstantinidis. For ARVC with FLEC, are you comfortable using that without an ICD? Unless the patient doesn't want an ICD. We always offer an ICD. You offer FLEC and I to patients who don't necessarily meet criteria for ICD. That was the question, sorry. Depends. If they have documented, definitely ARVC, I would. I think it works. We don't know. Most of these people have ICDs, but I think I would. You haven't found it to be proarrhythmic as it was in the ischemic patients in the CASH trial? We haven't seen much, but we don't have a lot of these patients on FLEC and I without an ICD, so it's hard to say. Excellent. I'll take one of the questions for Dr. Chatterjee. They ask for young patients with heart block, how do you proceed with workup? And I'll add a little bit of my own thoughts. Many of these patients come in and they're in heart block and needing a temporary pacing wire, which can make it hard to get advanced imaging. How do you guys proceed with that? That's great. It's a great question. I mean, I think to answer the second question first, temp perms end up actually being a pretty viable way to be able to get cardiac MRIs in a safe manner. I mean, obviously TVPs are a contraindication in that setting. So in the right patient in whom there's a compelling indication to really pursue diagnosis, that's one approach. The other approach, I think it's really shepherded by Dr. Nasr and her group, is I think being relatively aggressive about biopsy. So PET imaging can obviously be accomplished with a temp wire in place. And if there's compelling, particularly septal involvement or non-cardiac involvement, then another avenue to diagnosis would either be a non-cardiac or extracardiac biopsy or a voltage-guided biopsy, which is something that we talk about often in our group. I think voltage-guided biopsies and biopsies in general for sarcoid is a topic in its own right. And the sensitivity, if you look at some of the kind of limited data in non-ischemic cardiopathy is only about 30 or 40%. So even voltage-guided biopsies are not perfect. But I think, generally speaking, I think those are some of the avenues we pursue in terms of PET scans, cardiac MRI, and then have biopsy early. You know, my follow-along is, can you tell the audience what Temperm is? Because I realize other institutions may not use our nomenclature. Oh, I see, yes, a semi-permanent pacing lead. So just a sort of externalized pacemaker, if you will. Thank you. Just carrying on with the same question. You know, clinically, you run into this situation where a young person with complete heart block, and you know, you do a CT scan, there's no sarcoid involvement. Extra cardiac sarcoidosis, you start thinking, is it primary or isolated cardiac sarcoidosis? Have had two instances, one where we just went ahead and gave him a pacemaker, and later we did a PET scan and MRI, and it was positive, and you know, became very hard to convince that patient to come back for getting upgraded to a device. In a second situation, this happened after the first case, and we decided, well, we can't get an MRI, we can't get a PET scan, and in-house PET scans are impossible to get, and you know, the amount of scheduling and other things that are required. So we used the so-called indeterminate EP study in the risk stratification, and it happened that the EP study was negative, so we gave a pacemaker, and later we did an MRI, and fortunately it was negative, so at least we felt better, but you know, that is a difficult situation that keeps coming back in the young with complete heart block. The second question I had as a follow-up is, you have a complete heart, you know there's extra cardiac sarcoidosis, and you come in with complete heart block, you give them an ICD, but they're complete heart block. Now the fair portion of these patients are going to develop pacing-induced LV dysfunction, and you don't know whether it is a progression of the sarcoid which is causing the LV dysfunction, or is it pacing-induced LV dysfunction. Would you not only give them an ICD from the get-go, but instead give them a CRT device from the get-go? And I have lied in one situation, and said visually EF is less than 50%, and given them a CRT, but I can't do that all the time. So I wanted your take on that, and how you approach that. Yeah, that's a great question. The first comment I think really highlights some of the challenges in the real world, when sort of caring for these patients. There is, you know I found as well, sort of clinical inertia once you've placed a pacemaker, and then you know somebody comes back, and is ultimately diagnosed with sarcoidosis, very difficult to then sort of repurpose that conversation, and guide them towards you know, ideally an RVPACES lead extraction, and ICD implementation. So I think even as challenging as perhaps the logistics can be, if they're overcomable, I think there's value in that, to prevent those longer term failure issues. The second question is a great one. I have to say I imagine there's probably a fair amount of practice heterogeneity in general, about the role of so-called prophylactic CRT, even in independent circling. You know I've had referrals from various places of folks with EFs of 52, 53% and in need of a pacemaker, and anticipated RV pacing more than 40% and so forth, and should we be putting in a CRT? And I think it's a good question. You know I think by the books, if somebody has a normal ejection fraction, I don't know if there's, we don't have much of a leg to stand on in terms of advocating for so-called prophylactic CRT. In terms of the development of an incident cardiopathy, you know I think your point's well taken. I think there's no way to really disentangle the pacing induced versus sarcoid mediated. I think in truth and in practice, we would offer that patient a CRT upgrade, and then obviously if their LVF did not improve, then it sort of favors that the likely mechanism is more sarcoid as opposed to pacing. Why I worry about it more is you know, these are patients you're making them immunosuppressed, you know because you're also putting them on immunosuppression, and then you bring them back for devices. And now you're making them high risk for CIED infection, and then you're lead extracting them, and then what, you know? Correct, yeah. So you started off with a problem, now you've made it even worse. So my own take would be I'd give them a CRT, and find a way to do it, whether it's reimbursed or not, I don't care. I think that question and that exchange highlights how complex the decision making is in all these groups of patients, and I think our speakers have helped us understand these challenges a lot better today, and I want to thank the four of you, on behalf of Kelly, my colleague, and co-moderator for your excellent talks today. Thank you.

cardiac conditions

innovative treatments

cardiac amyloidosis

monoclonal antibodies

electrophysiology

arrhythmias

ARVC

cardiac sarcoidosis

hypertrophic cardiomyopathy

ablation methods

advanced imaging