Oluwadewa Fatundi from the Mayo Clinic to talk about hypertrophic obstructive cardiomyopathy contemporary strategies for sudden cardiac death risk assessment. Okay, good morning, everyone. My name is Badi Fatun. I'm one of the EP fellows at Mayo Clinic Arizona, thrilled and excited to be here to talk to you about this interesting topic. There's a QR code. And here's the outline for what we'll talk about. We'll start with a case, and then we'll discuss some epidemiology, look at the differences between the US and European guidelines, and then look at trends in sudden cardiac death risk stratification. So first case is a 29-year-old gentleman that was referred to cardiology after a routine PCP screening identified abnormal ECG findings. And you see T-wave inversions in the lateral and then the high lateral leads as well. The following day, playing basketball, he developed shortness of breath and chest pressure, and he tried to tough it out for two hours. However, he succumbed, ended up taking aspirin and then resting. And the following day, he presented to the ER with palpitations and then similar symptoms. Taking history, it was notable that he had a heart murmur since childhood and difficulty keeping up with his peers. And he was having more of these symptoms over the past two to three years. Family history, his immediate family is alive and well. However, on his maternal side, he does have uncles with heart disease that we don't know of. When he got to the emergency department, a coat stamina was activated due to these abnormal findings, his symptoms, and then his elevated non-high sense of each opponent. He had a cath that was negative and showed a pullback gradient. And then his EF was notable for an echo of or for septal thickness of 28 millimeters. So for a poll, I'll just click for the next one. Which one of the tests would be most helpful in a risk stratification? All right, a nice split down the middle. And then for the next test, next question, what patient wants to play basketball again tomorrow? So what testing should we do before doing shared decision making and counseling on when to return to play? All right. So we'll talk about that. So here's the epidemiology of HOCUM. The prevalence is about 1 in 500, and there are more people that are asymptomatic than are symptomatic. The incidence of cardiovascular death is approximately 1 to 2%, and today we'll focus on sudden cardiac death. And the most common recorded fatal arrhythmia is VF, but VT is also prominent. Patients tend to have more severe symptoms when they are younger. So here are the 2024 ACC guidelines that many of us are familiar with. So we're going to focus on primary prevention, so we'll skip the class one recommendation. And family history, massive LVA syphilis, 30 millimeters, unexplained syncope, apical aneurysm, and EF less than 50. Now one difference between the 2020 guidelines and 2024 guidelines is here you see the risk estimate to discuss shared decision making, and we'll see how that juxtaposes with the European guidelines. NSVT, we'll talk about it a little bit later, it is a 2A indication, and then LGE is a 2B. Some things that are notable for the ACC guidelines, disclaimer, I am a adult EP fellow, so I won't really talk about children, but I think one thing that I found notable is that the genotype status for risk stratification, and we'll talk about how that differs and where that fits into future risk stratification. So here are the European guidelines, and they are particularly heavy on risk scores. So really they're, the first line is you put all these variables in the risk score, and then low risk is less than 4%, high risk is essentially 6% or higher, and then in the intermediate you can use certain variables. One area where it differs from U.S. guidelines is the age, the outflow gradient, and then the left atrial diameter are not as tightly adhered to. So here are the differences in the risk calculators, and one thing of note that you'll see that the European guidelines, the apical aneurysms, and then the extensive LGE, they relegate that to more a 2B in the patients that are between 4% to 6%, whereas the, it's part of the AHA calculator. And then also here are the risk scores, this is the ESC risk calculator for kids, and then another primacy calculator for kids, and it was notable that this includes genotype in kids. A couple caveats about the ESC risk calculator is that it, this is directly from the guidelines, you can tell from the spelling of pediatric, but it shouldn't be used in pediatric patients and competitive athletes and then in patients with HOCUM or various syndromes. One thing that they did note that I thought was interesting is that the sample population, the, had very few individuals with massive hypertrophy, the LV hypertrophy greater than 35 millimeters. So just notes of caution. And here are some of those, here's some of what I described on the previous slide. So in intermediate individuals between either less than 4% or 4% to 6% in other areas of the guidelines, then it will bring in the LGE or the, or reduced EF. Apical aneurysms, it notes that in the U.S., in the U.S. guidelines, it's, it can be used as an independent risk factor for risk stratification, however, in the European, it still wants you to go through the score first before, before looking at that as a risk factor. Okay, so now we'll get to the meat of the talk. So we'll look at novel risk, novel ways of risk stratification. So there are about nine of them and we're just going to go through each of them one by one. So the first one is, the first one is a T1 time, which I thought was very interesting. So basically in diffuse fibrosis is not well seen in MRI or in LGE protocols. And so what T1 mapping does is it identifies patients with either elevated T1 time or extracellular volume in HOCUM patients and that can identify patients with diffuse myocardial fibrosis even if they don't have obvious LGE. And it was found to have a sensitivity and specificity of 84 and 76 percent. And diffuse fibrosis, it is associated with a non-sustained VT and aborted sudden cardiac death. And so here you see a T1 time greater than 440 in this population associated with increased risk of sudden cardiac death. MRI entropy is also another interesting finding. Essentially entropy is identifying tissue with heterogeneous fibrosis. And so it makes sense that a scar that is, a scar that has heterogeneous properties will increase your risk of sudden cardiac death. So here at MRI entropy, it was added to LGE and found to have an increased predictive risk. Genotype. So genotype is not exclusively used in the, well, at least in adults in the ACCHA guidelines or the ESC for that matter. Here they found that patients with genotype negative and positive, or genotype negative versus genotype positive HCM, they had an increased risk of sudden cardiac death if they were genotype positive. And common genes include myosin-binding protein C, myosin-heaving chain intraponin, and those had a commensurately increased risk. And so we'll talk about that towards the end of the talk. Here's some of our data. And so we looked at patients at the various risk factors. And we found that the greatest risk factor for sudden cardiac death in our population was mass hypertrophy. But shortly after that was degree of LGE. And so here you see that on the Kaplan-Meier curve, the lowest survival did have the greatest LGE. We do have some unpublished data looking at LGE more as a continuous variable. And sometimes LGE rates around 10% have been found to be additive. And that will be published here in the future. Global longitudinal strain. So strain identifies subclinical systolic dysfunction and a marker of increased hypertrophy and dysfunction and myocyte disarray. And so here, when they looked at different quartiles of strain, then they found patients with the worst strain were more likely to have a sudden cardiac death. Antiprobian P. And this also makes sense. So antiprobian P was associated with patients that had increased scar, increased fibrosis, increased fibroblast deposition. And so it was noted that, and many of these are retrospective studies, so hypothesis building, but noted that antiprobian P was associated with increased risk of sudden cardiac death. So various aspects of CPED. Here I'm highlighting the VCO2 slope, which looks at respiratory efficiency. And this is commonly used in heart failure literature, which is where this was found. But basically, if the higher the VCO2 slope, then the worse that patients do. Normal is 20 to 30. And in the heart failure transplant literature, 34 is significant. So here in this population of patients with HOCUM, then 31 was the notable finding. Atrial fibrillation, which I thought was interesting. This wasn't just associated with thrombosis, but it was also associated independent of this was, so on the left you see pure sudden cardiac death, and then here you see survival and non-cardiac death, including all-cause mortality. Just kind of briefly, patients before they went into VF on whole term monitoring or on ICD, often were in either sinus tachycardia or atrial fibrillation, likely due to short lung, short sequences. So they're ECG findings, but I see I'm running out of time here. And then just a quick, this was a group at Tufts that looked at AIECG, so that's on the horizon. Quickly, patients with, so athletes, this is the 2024 HRS guidelines, and it looked at genotype, and it did use genotype and phenotype in actual counseling of the patients. And so it's a class one indication to get genotype of athletes, and to try and both in terms of prognosis and in terms of counseling. And then in athletes, you should not offer them an ICD simply to placate them and try and progress, try and allow them to return to play. So back to our patient, so we had an emergency action plan until he got in his ICD. His MRI was 15% LGE, he was genotype positive, which isn't surprising given the reverse curve that was on his echo, and he did have some NSVT, so it was pretty black and white. So key points, there are emerging risk factors that can be additive to existing risk stratification findings. Risk stratification isn't a one-time thing, it's longitudinal and dynamic. And then a thorough evaluation should be, you should conduct a thorough evaluation based on the best available literature, and you shouldn't bargain with patients with ICDs. So that's all I have, and thank you to the directors. Well done. Thank you very much for the excellent talk about hypertrophic cardiomyopathy and risk stratification. So we have to go on. The next speaker will be Bharat Kantarina from Cardiovascular and Heart Rhythm, and he's talking about sudden cardiac death risk in amniodosis, bridging imaging, electrophysiology, and biomarkers. How do I go to my slides? Okay. Good morning. Thank you for inviting me to give a talk. I thought this was a core curriculum session. I don't have a poll question, but let's see what we can do. Nothing to disclose. So here is my email address and Twitter handle. Anyone want to reach out to me, I will forward the PDF of this presentation. Hypertrophic cardiomyopathy is responsible for some 20% of sudden cardiac death cases. Cardiac amniodosis is a form of infiltrative cardiomyopathy, and as such, it is a rare condition as causative etiology of sudden cardiac death overall. As for arrhythmogenesis, the mechanism, all these listed conditions may respond differently to different triggers in different situations, and yet, in literature, there lies a tendency to describe mechanistic hypothesis interchangeably, and even extrapolate clinical outcome data from one another. Dennis' trial evaluated the role of ICDs for sudden cardiac death prevention in patients with non-ischemic cardiomyopathy, heart failure, low EF. With similar 23% all-cause mortality, the primary endpoint of the trial, at a median follow-up of 5.5 years, the trial results indeed minimize the role of preventive ICDs in this group. There were less sudden cardiac death cases in ICD group, but the other secondary endpoint, cardiovascular deaths were comparable between the two groups. The results were similar across all subgroups, except age. In other words, the mortality was less seen in younger patients. Further analysis of Danish trial, using models to predict all-cause mortality, and the proportional risk of sudden versus non-sudden death, showed that in non-ischemic cardiomyopathy, only few select patients seemed to benefit from ICD implantation. Hence, the ESC rightly so downgraded their recommendations for prophylactic ICDs in non-ischemic cardiomyopathy from class one to class two A. Additionally, the landmark studies, which led to current guidelines recommendations, preceded the four pillars of guideline directed medical therapy, and thus, further questions the role of ICDs as primary prevention in current clinical practice situation. Please note, cardiac amyloidosis does not specifically appear in any of the sublists. As regard cardiac amyloidosis, we know, in addition to immunoglobulin monoclonal light chain AL amyloidosis, there is ATTR, which is from misfolded monomers of transthyretin, but there are additional other amyloidosis with different level of cardiac involvement and cardiac presentation. This is a patient of mine, while waiting for a routine check at PCP, sustained cardiac arrest. No symptoms, normally EF, no CAD, but of course, underwent secondary prevention ICD implantation, and subsequently, with extensive investigations, she turned out to have ATTR, and she is now on tefamides. Retrospectively, looking at all her chart data, we found that there were presence of fragmented QRS, even on the ECGs, two years before the index event of cardiac arrest. The presence of fragmented QRS have independent prognostic value, hazard ratios of 2.4 for mortality, at least in the AL amyloidosis, and in this study, the survival probabilities were better in the absence of fragmented QRS. Now, N-terminal probNP, but not troponin, was independently associated with the multi-fold higher risk of mortality in this case. Value or lack thereof of EP study for prognostic estimation in small studies, non-inducible VT showed no predictive value. Is the history of syncope and prolonged HV interval, they were found to be independent predictor of sudden cardiac death. In one meta-analysis of six studies that showed, this is a patient with ICD in amyloid. In this meta-analysis, non-sustained VT occurred in 51% of the cohorts. Study also showed that during mean follow-up of 18 months, only 18% of patients received appropriate ICD treatment. And non-sustained VT did not predict appropriate ICD therapy. Our patient had several appropriate shocks, all due to VF without any preceding warning PVCs or non-sustained VT. Furthermore, the biomarkers would always be abnormal and above the outside of the normal range. In small study, again, 31 patients from Stanford, non-sustained VT was found to occur in 74% of patients and there was no significant correlation between non-sustained VT and antiprobe BNP. What is the incidence of ventricular arrhythmia in patients with amyloidosis monitored with Holter? And in this study, the incidence was found to be 44%. Those patients with VT had significantly more severe LVH, more reduced LVEF, and large left atria. Again, note there was no difference in the biomarkers level between the two groups, with and without ventricular tachycardia. Left ventricular hypertrophy, left ventricular mass, and left ventricular dilatations were the predictors of VT occurrence with the area under the curve of 0.76 in the receptive-operative curve analysis. So the overall reported prevalence of ventricular arrhythmia and cardiac amyloidosis varies very widely. And partly because there is heterogeneity in the study design, subtype of cardiac amyloidosis examined, and the methodology of monitoring used in the study. But the prevalence was high in AL compared to ATTR. The ICD studies, which came with the later in timeline, biomarkers were also found to be predictor of ventricular arrhythmias. Coming to primary and secondary prevention ICD studies, all the studies were retrospective, small, and compared to one another used different amyloid types in the study. The primary prevention study, the criteria used were also very arbitrary adopted, included PVCs, non-sustained VT, non-postural syncope, and so forth. And additionally, in four studies, the criteria for primary preventions were not even specified. What is more important that in the ACC and the Heart Atom Society NCDR study, this study was quite insightful. There were 472 patients, 23% women, and primary prevention ICDs were implanted in 76% of the study cohort. What was impressive that when compared to the, over 2,300 patients with propensity-matched non-ischemic cardiomyopathy, the one-year mortality was significantly higher in amyloidosis, 27% versus 11% in control. The factors associated with death were syncope, ventricular tachycardia, cerebrovascular disease, diabetes, and impaired renal function. Likewise, in this meta-analysis of six studies in which 78% of the total cohort had primary prevention ICD implanted, no mortality benefit was seen over mean 30 months of follow-up. Additionally, three-fold higher odds of mortality were seen in patients with cardiac amyloidosis and ICD compared with non-ischemic cardiomyopathy and ICD. Coming to the biomarkers issue, the Mayo Clinic investigators developed a prognostic staging system based on N-terminal probe BNP and troponin T using a cutoff threshold value. Over four years, odds to survival was poor at hazard ratio of 3.6 in stage three in which both biomarkers were above cutoff values, cutoff values being 3,000 picograms per milliliter for N-terminal BNP and 0.05 nanogram per milliliter for troponin T. So stage three much higher compared to stage one in which both biomarkers would be below cutoff level. The UK National Amyloid Center used anti-probe BNP and EGFR, and again, with that staging system, the mortality with the high hazard ratio of 3.8 was observed in stage three. Subsequently, the UK National Amyloid Center extended their staging system, included any level of anti-probe BNP, about 10,000 nanograms per ml, irrespective of the EGFR to define a new stage, stage four. And the mortality in stage four, one year, mortality was 15-fold higher than stage one. So very high mortality. Coming to the imaging part, almost all patients nowadays get cardiac MRI and very detailed echocardiography. Points to note that these imaging studies help define amyloid burden based on specific functional and structural abnormalities. For example, at low cardiac amyloid burden, certain parameters such as LV mass, MAPSE, global strain, EE prime, would be abnormal. And likewise, in the high burden amyloid, the ejection fractions, both left and right ventricular ejection fractions, and enlargement of atria would occur. Recent meta-analysis of the CMR studies further strengthened the prognostic role of CMR. Both functional and tissue characterization parameters, functional meaning the global longitudinal strain, reduced EF, tissue characterization would be elevated extracellular volume, encroachment of late gandolinium enhancement, and they were associated with high mortality risk. In addition to tefamidase, there are new disease-modifying drugs such as the small interfering RNA drugs in clinical use, clinical practice. And there are registries, international registry, active participations for multiple centers, and hopefully they would provide unique opportunity to learn more about the effect of amyloid and specifically the effect on ventricular tachyarrhythmia as risk of sudden death, and would hopefully narrow the knowledge gap that exists currently. So in conclusion, ladies and gentlemen and chairs, the current guidelines of ICD implantation in non-ischemic cardiomyopathy are not applicable in cardiac amyloidosis. Mortality after ICD implantation is significantly higher in patients with cardiac amyloidosis. Careful patient selections and shared decision-making surrounding ICD implantation has to be a priority. Integrating multimodality imaging biomarkers, ECG, EP parameters may help formulate unique guidelines, unique for amyloid group for the primary prevention ICD, and clinical trials, registries may provide new opportunities to fill the current knowledge gap that exists in our understanding of cardiac amyloidosis. And I leave with the central graphic illustration, and I thank you for your attention. Thank you. Thank you very much for the excellent talk. We have time for one or two questions. Any questions from the floor audience? If not, I'm going to ask you. Let's assume you have, that's a personal case. There's a man, 45 years old, with a hereditary form of amyloidosis. He has severe heart failure and many storms of ventricular tachycardia and received an ICD. And his sister has the same gene as he has, but on imaging, there's nothing detected. No ventricular tachycardia, no heart failure, nothing. The only thing is she has a slight rise of COPI-BNT. What would you do with this girl, or let's say lady, it's also 38 years old, where her brother is 40 years old? So I think in this situation, one needs to think outside the usual norm and not follow the guidelines, but experience and sit down with the patient and family and have a real shared decision-making conversation. Someone who has a normal ejection fraction, no symptoms, but had strong family history, with the same gene, I would have a low threshold to put a defibrillator, rather than someone who has very high, as I mentioned, biomarkers and low EEF, and they would have a low survival anyway, and then perhaps a palliative kind of treatment for that situation. But for this young person, I would certainly consider ICD. And would you also do medical drug therapy, such as, for example, tafamidazine? Yes, there are a lot of data coming out that you are altering the natural history of cardiac amyloidosis, the amyloid burden goes down, even the atrial fibrillation studies. Yeah, this is one of the most Thank you. It's the same. Wonderful. Well, it gives me great pleasure to introduce Dr. Jordana Krohn, an old college classmate and friend, who will be speaking about sudden wrist stratification and device selection in cardiac sarcoid. Thank you so much for having me here. Thank you to my chair, Dr. Pellegrini and Dr. Jung. Great. I have no disclosures. So I'll be talking about wrist stratification in cardiac sarcoidosis. These are the key points that I'm going to give you data to understand about this patient population. Wrist stratification of cardiac sarcoidosis patients is critically important. CS patients with high degree AV block should receive an ICD, regardless of ejection fraction. Cardiac MR is predictive of ventricular arrhythmias. Both amount and pattern of late gadolinium enhancement are important. And finally, transvenous devices are generally the best option. So why is wrist stratification in cardiac sarcoidosis so important? It's so important because it's common. In this study of 351 cases of CS from Finland, they found that AV block was the most common first sign of CS, and it occurred in 42% of patients. This was followed by heart failure in 17% of patients. But worrisomely, fatal and aborted sudden cardiac death was present in 14% as a presenting manifestation of cardiac sarcoidosis. When we took another look at this data, you can see that AV block is most common, followed by heart failure, and then sudden death. And when we look at the modes of death, arrhythmic death is most common in 80%, more common than death from heart failure, post-transplant complications, or non-cardiac causes. I'd like to show these pathology slides because I think they help us understand why cardiac sarcoidosis is such an arrhythmogenic disease. Over here on the left, you can see the left ventricle with a septum. The brown areas are normal myocardium, and the white areas are sarcoidosis. Because sarcoidosis has a predilection for the interventricular septum, where the conduction system runs, it's very common to get all kinds of heart block, right bundles, left bundles, and any degree of heart block. When we look at the cuts on the right, we come from the base of the heart, showing sections down to the apex. You can see, again, the white areas are showing the sarcoidosis, and this is really a patchy disease. In this case, you can see involvement of the interventricular septum and also the right ventricle. Because of the haphazard nature, you can get very complex ventricular arrhythmia reentrance circuits in these patients. So let's take a look at the patients with AV block. In this case, they took a study population of 143 patients and broke them down by other risk factors. So on the far left here, we have lone AV block. So these were patients that had normal ejection fraction with AV block, either a second degree mobitz or a third degree AV block. In the middle category, patients had a mildly reduced ejection fraction of 30 to 50%. And then the highest risk category were those with a very low ejection fraction, less than 35%, or who had already had ventricular tachycardia. When we look at the outcomes on the right, not surprisingly, shown in red are the high risk patients, those who have a very reduced ejection fraction or had already had VT. Those patients had the highest cumulative incidence of sudden death or VT, and that's not surprising. But what is surprising is if we look at the patients with lone AV block shown in blue were the ones with a mildly reduced ejection fraction. These patients had similar outcomes, and they still had significant risk of sudden death and VT. And when we break that down to look at what that risk was, you can see here that patients with lone AV block and a normal ejection fraction had a five-year risk of sudden death or VT that was 24%. And I argue that that is a very significant risk in these fairly young patients with normal ejection fraction. So in addition to AV block being high risk in these patients, we also know that cardiac MR can help us risk stratify. So here's an image showing some late gadolinium enhancement, which is shown here in the white areas. You can see it here in the septum and the posterior wall. And on the right, you can see it again in the interventricular septum and also laterally. In the 2017 guidelines for ventricular arrhythmias, it was stated that for cardiac sarcoidosis patients with an EF greater than 35%, ICD implantation should be recommended in patients who had extensive myocardial scar by MRI or by PET scan. But the challenge was we really didn't define what is extensive scar. There were some studies that used a late gadolinium enhancement or LGE cutoff of 20% or 21%, but other studies that had a lower cutoff of 8%. So a very important study that was published this year really sought to look at what does extensive mean? What cutoff should we be using? This study was entitled MRI and the Assessment of the Risk of Sudden Death in Cardiac Sarcoidosis. What is extensive or significant late gadolinium enhancement? This was a nationwide survey where they had 305 patients with definite or probable cardiac sarcoidosis. And they used a model that broke the LV into 17 segments. And what they found was that both LGE mass and the number of LGE segments predicted sudden death or ventricular tachycardia. So when we look at the outcomes here, you can see, and I don't think I have an arrow here that's transmitting, but in this case they looked at the cumulative incidence of sudden death or VT. And the red line uses a cutoff of greater than or equal to 9.9% by mass. They also found that having six or more segments of LGE was also predictive. So the key conclusion from this critical trial is that LGE mass greater than or equal to 9.9% and greater than six segments, greater than or equal to six segments of LGE could stand for extensive or significant LGE. In addition to the amount of late gadolinium enhancement, we also know that location matters. This is a study we participated in with the University of Michigan many years ago. And you can see the red line shows patients, again these were patients with normal or near normal ejection fraction. The patients that had right ventricular involvement of late gadolinium enhancement are shown in red. And you can see that those patients had significantly worse survival probability compared to the patients that didn't have RV involvement shown in blue. So we know that RV involvement is also another risk factor that we can look for. A very important recent study looked at MRI phenotypes. In this study there were 504 patients with histologically proven sarcoidosis who underwent MRI for suspected cardiac involvement. They defined pathology frequent late gadolinium enhancement as features on gross pathology in patients who underwent autopsy or cardiac transplant. And these high risk patients had LV subepicardial involvement, LV multifocal involvement, septal involvement or RV free wall involvement. And what they found was that these patients that had this pathology frequent phenotype had worse outcomes. Over here on the left you can see the tan line, that top tan line is the pathology frequent patients. They had a higher cumulative incidence of arrhythmic endpoints and also on the right heart failure endpoints. So we know that it's not only amount of late gadolinium enhancement, but it's also location and pattern that's very important in these patients. I'm going to switch topics a little bit here and talk about device selection in these patients. In general, transvenous devices are generally preferred. An atrial lead should be considered if conduction disease is present or may develop as is very common in these patients. Subcutaneous ICDs have the advantage of lower lead related complications and infections. Remember, these patients are often immunosuppressed and so infection is something that we worry about a lot. However, subcutaneous ICDs cannot provide pacing or anti-tachycardia pacing. In our clinic, we do have several patients with subcutaneous ICDs and these are generally patients who've had a transvenous device removed for prior infection. There is no data on physiologic pacing, although we do have some patients in our clinic who have successful left bundle branch leads. When we look at some older data of ICD function in these patients, one study, the top one, was a 13-center study with centers from the United States, Canada, and India. These were other important studies from University of Pennsylvania and University of Colorado. And we see that this is a very arrhythmogenic disease. The annualized rate of appropriate therapy, either shock or ATP, ranged from 8 to 14%. We also see that adverse events were common in 15 to 17% of patients. A common question that comes up in these patients is what about CRT? In general, we should follow standard indications for patients with reduced ejection fraction less than or equal to 50% and high pacing burden in accordance with the block HF trial. In a recent study published this year in ESC Heart Failure, the authors looked at 100 patients with cardiac sarcoidosis who received CRT. The important things they found were that 70% of patients were responders to CRT. And importantly, you can see here on this graph, it's the higher dotted dashed green line. Patients that did have response to CRT had an improved long-term outcome and did very well. This follow-up is over 6,000 days. In terms of ICD programming, keep in mind that these tend to be middle-aged patients. They can frequently have atrial arrhythmias and up to 32%. And so I typically program for primary prevention patients high zones and long detection times according to the MADE IT RIT results. In a case series of 142 CS patients, 4 of 38 patients, or 10%, experienced delayed detection or under-detection of VT related to cycle length variability. So the authors of that small study encouraged turning off stability criteria unless the patients had known atrial fibrillation. And I think this instability of the VT circuit is likely due to ongoing inflammation. Finally, a word about wearable cardioverter defibrillators. This is from a retrospective review of 46 CS patients. In this study, the WCD was worn 23.6 hours each day. And 10 patients, or 22%, had a VT or VF episode. And the time to first shock is shown on this graph. The first shock was successful in 100% of patients. This data shows us that WCD is an option in a cardiac sarcoidosis patients who have a need for protection from ventricular arrhythmias, but do not have an acute need for pacing. So I'd like to leave you with these take-home points, that risk stratification of CS patients is critically important. Cardiac sarcoidosis patients who have high degree AV block should receive a defibrillator regardless of their ejection fraction. Like MR is predictive of ventricular arrhythmias, both amount and pattern of late gadolinium enhancement are very important. And finally, transvenous devices are generally the best option in these patients. So thank you again. And this is my email, if anybody has any questions. Thank you. I think we have a question or two that came in through the chat, but if anyone has other questions, please feel free to come up to the microphone. Oh, we have some questions in the audience. Yes? Feel free to step to the microphone right behind you. So just wanted to ask what age, AV block is very common, what age you would start screening for cardiac sarcoids, someone presenting with AV, advanced AV block into the hospital? Yeah, that's a great question. So the most recent guidelines recommend screening anybody 60 years old or younger if there's no other clear indication for the AV block. Again, that's just a recommendation. And so if you have somebody who's 61 and you're a little bit suspicious and there's really no other reason for AV block. But the guidelines say at least we should be screening patients 60 years old and younger. And while he's coming to the microphone, there was a question about left bundle area pacing for patients that need resynchronization therapy and how that might play in in a sarcoid patient per se. I think it's a really good question. So we know that the involvement of the septum is patchy, so it is possible that left bundle branch pacing will perform well in these patients. However, you know, we really, most of these patients get ICDs, and if their EF is fairly preserved, they might just get a dual chamber. So at this time, it's our practice to generally put in a dual chamber ICD. The patients that have left bundles are patients that came in, had heart block, and sarcoid was not diagnosed at that time, so they got a pacemaker. In those patients, if further studies like with a PET scan or biopsy then proved to be likely cardiac sarcoidosis, we would then upgrade them to an ICD and use that left bundle lead in a CRT device in the LV port. So I don't think it's been extensively studied. Now, of course, at the late-breaking clinical trial yesterday, there is a new lead, a new defibrillator lead that is being utilized in the left bundle branch area. And so that's something I think is very intriguing for this population. There's no data there yet, but, you know, more to come in the future. I think you addressed my question, but basically I've seen two populations of sarcoid phenotype, the arrhythmogenic phenotype and the heart block phenotype. And I've followed about a dozen or more throughout the years of my personal practice, and almost none of the ones with complete heart block end up with sudden death or ventricular arrhythmias. What guidelines do you propose? Because I think the paradigm is now shifting towards using more ICDs. What is your criteria for upgrade of the pacemaker to ICDs in those patients? Yeah, I think that's a good question, and it's a really great question, and there's not a lot of data. You know, although that experience of yours is that sort of one or the other, the data bears out that these patients that present with heart block do have ventricular arrhythmias, and we have seen that in our sarcoidosis center as well. It is my practice that if we have someone with a pacemaker that is then diagnosed with cardiac sarcoidosis, that I will upgrade them. I think the data is very strong that these patients should be protected with a defibrillator. I do have other colleagues at other centers that will do an EP study. I don't think there's great data in this area, but I do think that patients with heart block from sarcoidosis, you know, have been shown to have high risk of ventricular arrhythmias, and I do think that they should be upgraded. So great talk, Jordana. Along those lines, in the real world, it's very hard getting a cardiac MRI in somebody who comes into your hospital with heart block in a timely fashion. Along those lines, I've had at least one patient who came there, was a young patient. We ended up putting the pacemaker in, scratched my head, a few months later got the MRI, sarcoid, and within the year she had a cardiac arrest, resuscitated by her defibrillator. So the reality of the MRI, I think, is just a very difficult issue, and I don't know how you confront that. But the other issue I'd ask is, I've encountered a number of patients who have purely cardiac sarcoid without any evidence of extra cardiac sarcoid once we look for it. And do you think that those patients are different in terms of outcome and the like? Why is it that they're only presenting with that manifestation, and what are the implications? Okay. Thank you. So I'll tackle the first question first. It is very challenging. If patients come in with heart block, maybe they're in the ICU, maybe they have a temporary wire. Really, that's not a patient most of us can send down to MRI. In those cases, I will get a CAT scan. That's pretty safe to do and pretty quick. Look for any lymphadenopathy or obvious lung disease. It looks like sarcoidosis, we'll put it in an ICD. If not, we will put it in a pacemaker and then do a PET scan and then further work up and push it down the road a little bit. So I think you get the data that you can, and you treat the patient if they need to be acutely treated. Those are the patients where we've had left bundle leads in place, and then we upgrade them and keep that left bundle for physiologic pacing. That's a practice at our institution. The second question about isolated cardiac sarcoidosis is a great one and a challenging one to address. I think it's been controversial over the years because there's not a great definition for isolated cardiac sarcoidosis. I believe cardiac isolated CS is really quite rare. And the important thing is that, have we really looked for it elsewhere? To truly define isolated CS, patients really need to have a full body PET scan that does not show involvement of other organ systems. I think that's pretty rare, and whether it's truly a separate disease I think is up for discussion. I think isolated CS is rare and difficult to diagnose. Awesome. Thank you so much. Thank you. It's my great pleasure to introduce Enrico Amorati. He will be speaking about risk stratification and idiopathic inflammatory cardiomyopathy. Hello, everybody. It's a pleasure to be here in San Diego, and I really thank the organizer for this invitation. So I will focus my talk on myocarditis. We have already heard about inflammatory cardiomyopathy as cardiac sarcoidosis, and I have no relevant disclosure. So when we talk about myocarditis, have in mind that we are talking about a population with a median age between 30 and 40, with a male prevalence, around 60% to 80% of patients are males. And what about the incidence? The incidence is between 4 and 14 for 100,000 individuals per year. That means that in a town with 1 million inhabitants, we can expect 100 new cases of myocarditis per year. This is a retrospective registry we conducted, the Lombard Registry, including 443 patients, well characterized, median age of 34 years, 80% male, 94% with a cardiac magnetic resonance imaging that confirmed the diagnosis, and about 13% with biopsy. And if you're thinking about the 100 patients with a potential myocarditis per year, here you can see that three of them are going to die due to cardiac death or receiving a heart transplantation during the first month after the first diagnosis. And one more patient is going to experience a cardiac death or a heart transplant during the following five years. And if we focus our attention on ventricular arrhythmias presentation, have in mind that 6% to 10% can have a sudden cardiac death before hospitalization among the young patient with a sudden cardiac death. And this is based on post-mortem examination studies. If we look at the administrative studies looking at the patients that were hospitalized with a final diagnosis of myocarditis, the rate of cardiac arrest or ventricular fibrillation during hospitalization is 2.5. If we look at the sub-analysis we conducted in the Lombard Registry, 6% of patients presented with ventricular tachycardia or ventricular fibrillation at presentation. So out of 100 patients, every year you can have in a town with 1 million inhabitants, six of them can present with ventricular arrhythmias. And why ventricular arrhythmias? Because you can have different triggers behind. You can have the inflammatory trigger, or then you can have the residual interstitial fibrosis or scars that can induce potential ventricular arrhythmias or can evolve toward heart failure. So if I have in mind one marker of risk of future ventricular arrhythmias, I have in mind sustained ventricular tachycardia or ventricular fibrillation at the presentation or in the first days after admission due to acute myocarditis. Luckily, we should exclude those patients that presented with very severe heart failure. I mean, a patient with five of EF, even if he is going or she is going to experience a ventricular fibrillation, is not really the point. I'm thinking about patients with normal or nearly normal ejection fraction that experience ventricular arrhythmias. And above that, we can think about patients who do not present with ventricular arrhythmias, but have in mind that these markers that you can find on cardiac magnetic resonance imaging. Specific pattern of LG on cardiac magnetic resonance imaging, septal ringer-like or an extensive LG, or no edema on cardiac magnetic resonance imaging. This is based on eight studies that look at the risk of ventricular arrhythmias that were published in the last years. The characteristic of these studies is most of them look at a patient that were at higher risk since the beginning, because they had a ventricular presentation with ventricular arrhythmias, or there were patients that already had an ICD at the time of the discharge. I'm not going into the details of these studies, but five out of eight of them showed that sustained ventricular tachycardia was a risk marker for future episodes. This is based on more than 500 patients. And also the presence of septal fibrosis or extension, or a larger extension of fibrosis based on magnetic resonance imaging or electronatomic mapping, were found to be associated with the future risk. If we look at the study by Kanata looking at 200 patients, they reported that at the baseline, 9% has a presentation with arrhythmias, both ventricular and supraventricular arrhythmias. So we can find a figure that is similar to the 6% I mentioned before. And if we look at this study that I'm going to present in more details by Gentile, you can see this is a multicenter study, including 156 patients with ventricular arrhythmias at presentation, median age 44. And what is interesting here is that the ejection fraction at presentation was an average of 50%. And these patients experienced a new episode of ventricular arrhythmias after a median time of eight months, and it was 37% of them had a new episode. And if we look at the predictors are sustained ventricular tachycardia, LGE above or equal to, or no edema at the cardiac magnetic resonance imaging. And this is the 2020 ESCC guidelines for the management of patients with ventricular arrhythmias and their prevention of sudden cardiac death. So first of all, you have to refer to specialized center these few cases with myocarditis and ventricular arrhythmias. Why that? Because they can reach a final diagnosis, for instance, of cardiac sarcoidosis, specific histological diagnosis, or they can go in depth looking for a potential genetic background that I'm going to talk about later on. And what are the indication for a secondary prevention of sudden cardiac death in this population? Because you expect that it's something that can reverse. You expect that inflammation can reverse. And so the indication is if this occur during a chronic phase, I mean a sustained ventricular tachycardia, this is a good reason to implant a defibrillator. Or even if it's an hemodynamically tolerated sustained ventricular tachycardia, this is an indication to a base on the opinion of the expert. While if you have an acute ventricular arrhythmias that is hemodynamically not tolerated during the acute phase, the indication is a two-way C. And in my view, also in the case of acute phase, you can include in a high-risk population those that experience hemodynamically tolerated ventricular arrhythmias. And this is also based on another study that we conducted based on the Lombardy registry. And if you look at the population with the ventricular tachycardia at the baseline, that are just 15 patients out of 248 patients, and a risk of new ventricular arrhythmias or sudden cardiac death of 40% against 1% at five years of those without a ventricular arrhythmia at the presentation. So an hazard ratio of 42. So in my mind, all these patients, independently of the fact that you can think that is a potentially reversible fact that the inflammation should be implanted with a defibrillator. And if you look at the other mark, receptal LGE had another ratio of 20, or an EF below 50% had another ratio of 15. So what we can look at further is the genetic background. In particular, pathogenic or likely pathogenic mark desmoplakian variants. And to look at this patient, you have to take attention at the pattern of LGE, septal pattern, or otherwise patient with frequent burden of premature ventricular complexes beyond the acute phase, or patient with a recurrent myocarditis. This is a patient we admitted in the past, 33-year-old man, EF 41%, high level of troponin, and he experienced a stable sustained ventricular tachycardia during a left catheterization to rule out coronary artery disorder. We performed the cardiac magnetic resonance imaging. You see the ring-like edema and presence of LGE. And this patient experienced ventricular fibrillation just five days after the cardiac magnetic resonance imaging. And below, you can see the ECG of his sister. She had a new myocarditis at the first episode of myocarditis one year after his brother. We decided to perform at that time the genetics testing, and we found that both had a desmoplakian variant that was pathogenic. And after that, we decided to implant also the sister, and the sister experienced ventricular tachycardia that was recognized and treated by the defibrillator. So this is just some hints to look at patients with a potential genetic background with myocarditis, recurrence of myocarditis, or the presence of a family history for myocarditis, sudden cardiac death, cardiomyopathies, the presence of septal LGE. And these patients are at higher risk comparing with the patient with negative genetics for recurrence of myocarditis and for the risk of ventricular arrhythmias. And of course, a specific histology, the giant cell myocarditis are patients at super risk of arrhythmia. So based on this finished study, you have to consider to implant a defibrillator because they have a risk of 40% of sudden cardiac death or ventricular tachycardia after one year of follow-up. So this is my final slide. Consider to implant a defibrillator in case of sustained ventricular tachycardia at presentation. Specific histology like giant cell myocarditis in most of cases with cardiac sarcoidosis. Or you can decide case by case in case of cardiac sarcoidosis with a preserved ejection fraction. Or in patient, I haven't talked about them, but with ventricular arrhythmias in the context of immune checkpoints inhibitors that are these new anti-cancer treatment. And then you have to put a combination of risk factor when you're looking at patient without ventricular tachycardia, without at presentation, or without specific histology. But you have to put together all the pieces, looking at the genetic background, the pattern of LG on cardiac magnetic resonance imaging, or the burden of premature ventricular complexes. Thank you so much. So I think we have time for one question, and if anyone wants to pop up, please go ahead. No, likely no. Yes, I'm going to repeat your question. Genetic testing for everyone with an acute myocarditis, my reply at present is no, but you can look at these markers. If you have septal LG distribution, a ring-like distribution, if it is a girl, because there is a higher prevalence of males, so it is quite uncommon to have a 20-year-old girl with a myocarditis, unless it is within the context of a systemic autoimmune disorder. That's great. Actually, I have one quick question for you. Can you say a word about timing of implant, if somebody comes in and has an acute myocarditis, are you generally sending them out with a wearable defibrillator, or waiting for things to cool off before implanting a device, or do you go ahead and do that in the index hospitalization? To me, if they experience a ventricular tachycardia with, let's say, 40% of EF, they receive a defibrillator before discharge. I do not think that when you have a 40% of risk in the follow-up, a wearable defibrillator is an option. Thanks. Thank you for attending the session. Have a great rest of your day.

sudden cardiac death

hypertrophic obstructive cardiomyopathy

risk stratification

cardiac amyloidosis

cardiac sarcoidosis

ICDs

T1 mapping

genotype considerations

cardiac MRI

inflammatory cardiomyopathy