Good morning. Welcome to this session. My name is Zavindra Mehta. I'm from Mount Sinai Morningside. And my co-chair is Dr. Erdan Esrari. Both of us would be chairing this session. It seems to be an exciting session in terms of so much has happened in hypertrophic cardiomyopathy. The session is about a contemporary look at arrhythmia risk and treatment. In addition, we would have a talk about exercise management in patients with hypertrophic cardiomyopathy. This is an ever-changing, exciting field. And I'll go on to you. I'm Ray Esrari. I'm from Auburn, New York. I did my fellowship at Yale and just here with Dr. Mehta talking about hypertrophic cardiomyopathy and arrhythmias. Thank you all for attending this session. Just as a preamble, we'll ask you to please download the app if you haven't already. There should be a QR code on the screen. I don't see it there. But that's the way you could ask questions during the session. And then we'll get a load out of it on our iPad. With that said, we'd like to introduce the first speaker. Our first speaker is Dr. Michael Kim who's from Creighton University Hospital. He will be talking about atrial fibrillation, ablation, and hypertrophic cardiomyopathy should the outcome temper our enthusiasm. Dr. Kim. Drs. Obisere, Mehta, fellow panelists, colleagues, I've been asked to present on the outcomes in atrial fibrillation ablation and hypertrophic cardiomyopathy. I hope this presentation will provide value to you, your patients, and your practice. Well, I guess I can't get it to move here. There we go. Atrial fibrillation is the most common sustained arrhythmia. It is even more prevalent in the population of hypertrophic cardiomyopathy, perhaps fourfold. About 25, if not 30%, of hypertrophic patients will eventually develop atrial fibrillation. It is often very poorly tolerated and more likely to be symptomatic than those in the general AF population in terms of averages. It represents a marker in this population of risk for advanced cardiomyopathy and is associated with negative cardiovascular outcomes. In this population, there is a high risk of stroke independent of CHADS-VASc scores. If we look at catheter ablation of AFib, we know that this is a proven treatment, both as a primary and secondary options in our general AF population. In addition, early rhythm control, including with AFib ablation, has been shown to improve cardiovascular outcomes such as CV death, stroke, heart failure endpoints in a population with at-risk markers. However, in hypertrophic cardiomyopathy, unfortunately, limited data exists regarding the efficacy and outcomes of AF ablation. Furthermore, there are no prospective randomized controlled studies in this population for ablation, rate versus rhythm, or ablation versus anti-rhythmic drugs. So, until recently, we kind of went on officially, I guess one of these, expert consensus statements, this is 2017, that we were advised to use similar indications for catheter ablation in hypertrophic cardiomyopathy as in the general AF population. This was officially rated as a class 2A recommendation. If we look at the data, including to present, there really are no demonstrable hard cardiovascular outcomes benefits for ablation in hypertrophic cardiomyopathy. And hard outcomes are gonna be, as you know, mortality, stroke, heart failure. There have been significant new and updated data over the past few years, including in 2023 alone, there were three meta-analyses presented by Ezzedine and colleagues, Faraz and colleagues, and Lateef and colleagues. So, what do we know? If I did my math right, perhaps there are about 2,500 patients, maybe 3,000 if you call all the observational studies, cohort analysis, studies that made up the meta-analyses to look at hypertrophic cardiomyopathy and atrial fibrillation ablation. The success rates of AFib ablation is significantly lower. Single procedure success rates probably are under 40%. It will get better if you have redo procedures. It will be better in paroxysmal AFib, but it will not be as good as what you see in the general AF population. Many of the patients with hypertrophic cardiomyopathy are gonna need repeat procedures. In the literature, about a third have a redo, and many of them will have concurrent anti-arrhythmic drug therapy, about 40%. Although there are conflicting reports, including some recently, it is generally felt to be comparable safety for the procedure. Of note, the ablation reports in hypertrophic cardiomyopathy are not early, okay? So, generally, time to first ablation is more than three years, and some reports nearly up to six years. So, one of these meta-analyses, I was fortunate to take part with my colleagues from Baylor in Houston, University of Nebraska, Mercy One in Iowa, and we looked at 1,183 patients, 19 studies. So, what's new is, for these studies, we looked at pre and post New York Heart Association class improvement. As you can see in this forest plot, things did get better. They got significantly better, but this is only 223 patients. This is a study from 2024 in Italy by Pieri and colleagues, and I like this study because it's a new way of looking at the data. This is a propensity analysis where they matched one-to-one patients with hypertrophic cardiomyopathy to ablation or medical therapy. The strength of this is almost five years of follow-up, and they looked at hard cardiovascular outcomes endpoints, and once again, unfortunately, they didn't find any benefit in terms of looking at whether it's a primary composite, a secondary composite, stroke. There was no difference in mortality endpoints, time to, you know, reaching transplant, heart failure endpoints, stroke, et cetera. However, the ablation group did have less recurrence, 64 versus 84%, and they did have less progression to permanent AF, 20 versus 34%. Another recent study to highlight is Aluwalia and colleagues where they took a population with cardiac implantable electronic devices, only 81 patients, but they looked at AFib burden and ablation, and they found a significant correlation where the reduction in AF burden as demonstrated by these implantable devices significantly correlates with the reduction in implantable devices significantly correlated with improvement in symptoms with a median follow-up of about three years. So I'm gonna go to the Wayback Machine. So you see 2007 there, okay, and this is non-hypertrophic cardiomyopathy, and the Wayback Machine says, a statement in there that the primary justification for an AF ablation procedure is the presence of symptomatic AF with a goal of improving a patient's quality of life. I think you should think about this, and this should resonate when you start thinking about hypertrophic cardiomyopathy. So officially, 2024, there's been some updated expert consensus statements based on a lot of the data that I've presented, but not all of it, because just the time cutoffs, and I think it's worth looking at because it hits all the points. Catheter ablation of AF is reasonable in patients with hypertrophic cardiomyopathy. After careful consideration of anticipated clinical benefit, associated risk of procedural complications, and the potential need for more than one procedure. So in conclusion, we need more data. Randomized data would be great, and including data in early rhythm control strategies. That said, these softer treatment targets, symptoms, quality of life, functional capacity, and hypertrophic cardiomyopathy are reasonable patient-centered outcomes, and they can drive treatment and ablation strategies. So these softer endpoints, symptoms, functional capacity, are of tremendous importance to our patients. So is a treatment target of feeling better a good one? Yes, it can be. Let's see the outcomes be your guide. Thank you. We move on to another challenging treatment option, which is arrhythmias coming from the ventricle and hypertrophic cardiomyopathy. The next talk is labeled catheter ablation for ventricular tachycardias in hypertrophic cardiomyopathy. I invite Dr. Asim Sharma to give the talk. Dr. Sharma is from Cleveland University Hospital. All right, well, thank you, Dr. Mehta, Dr. Obasare, and thanks for everyone for being here today. So the title of my talk is Ventricular Tachycardia Ablation and Hypertrophic Cardiomyopathy. The goals of my talk today are going to be threefold. One, I want to discuss some of the indications for VT ablation and hypertrophic cardiomyopathy, discuss some of the challenges that are associated with VT ablation in the HCM substrate, and spend some time sharing some examples of challenging cases and techniques that can be used in increased success in these patients. So the 2024 guidelines for HCM recommend the use of antiarrhythmic drug therapy in patients who have sustained ventricular arrhythmias or recurrent ICD shocks. And antiarrhythmic drugs include amiodarone, dofetilide, maxillitine, or sotolol. And in patients who continue to have recurrent sustained ventricular arrhythmias or who have recurrent ICD shocks in those patients, catheter ablation has a 2A recommendation. So similar indications for other conditions for which you would bring patients for catheter ablation. Unfortunately, there is limited long-term data, long-term outcomes following VT ablation in hypertrophic cardiomyopathy. Mostly we have retrospective studies and pooled analyses suggest a success rate of freedom from ICD shocks of about 70% at one year. So very similar to other non-ischemic substrates, though perhaps maybe slightly more difficult. And patients often, these patients, hypertrophic patients, often need continued antiarrhythmic drug therapy, even repeat ablations in some cases to fully address the ventricular substrate. So what exactly makes ablation challenging in these patients? Well, for one, they have hypertrophic, thick myocardium, and we're limited by the inherent limitations of radiofrequency in terms of depth, and there may not be enough penetration to fully reach the substrate. These patients often have mid-myocardial and epicardial substrate, and accessing and mapping these areas and ablating there can be challenging. There can be cavitary obliteration during systole that makes manipulation of catheters difficult in the ventricle. It can increase the risk of steam pops. And then there's apical aneurysms that many patients have, and thin-walled aneurysms where there can be an increased risk of perforation in those areas. So when we're considering bringing somebody in for VT ablation with hypertrophic cardiomyopathy, I think for any patient, even non-hypertrophic patients, you really want to consider what the substrate is. And preoperative imaging, either with cardiac MRI or CT scan, as well as detailed analysis of the defibrillators and EKGs is very important. And I found that these patients typically fall into three main categories. And one is your patients with apical scar, apical aneurysmal substrate, then patients with septal scar, intramural substrate. And then there can be these patients that, like other non-ischemic cardiomyopathies, have this patchy, mid-epicardial, diffuse LGE. And as time progresses and they become this burnt-out HCM, there can be very diffuse, confluent LGE with subendocardial sparing. And in those patients, it can be sometimes difficult to really pinpoint, based on imaging, where the substrate actually is. So I'll show some examples of these cases. So this first case is a patient with apical aneurysm. You can see the MRI on the left that shows cavitary obliteration during systole. There's an apical aneurysm. And on the right, you can see significant LGE in that apical aneurysm. And so this patient, of course, had apical VT arising from that apical aneurysm. And the typical strategy for these patients is to try to isolate the apex, where the VT is coming from. Oftentimes, you can accomplish this by ablating along the neck of the aneurysm. But it can be difficult, especially in cases like this, where there's cavitary obliteration that the ablation catheter can get squeezed during ablation, can increase temperature during this time. There can be risks of steam pops there. And so temperature-controlled ablation, such as with the QDOT catheter, is very actually helpful here, increases safety. And you can see an example of one lesion here, where, during systole, temperature rises, and power is correspondingly decreased during that time, and that helps to avoid the risk of steam pop. Active ice guidance is very helpful here, ice catheter and the RV watching to navigate around the cavitary obliteration. And epicardial ablation is oftentimes needed in these patients to fully isolate that neck of the aneurysm. In some studies, up to 60% of these patients will need epicardial ablation. So that's something that you should always be prepared for in these cases. In this particular patient, we didn't have to go epicardial. So the pre-map multipolar voltage is on the left. And on the right, we were able to isolate the apex from the endocardium. Now moving to more intramural substrate in the septum, here I think pre-procedural imaging is very helpful, and especially image integration into the ablation procedure. So I use InHeart. Adas is also a company that does a very similar thing. And this is an example of InHeart highlighting on a late iodine-enhanced CT scan where the intramural substrate is. And here's a 3D model of it on the right side. And using that imaging, we can integrate that during our procedure. And this really helps in terms of reducing time to map the VT where we can put the scar right on our CARDO map and target those areas. And to get deep into these lesions can sometimes be very difficult. Half-normal saline may need to be used on both sides. In this particular case, I had to use bipolar ablation with one catheter in the right ventral ventricle, one through the aorta in the left ventricle. And we're able to, with the imaging, target the areas that we needed to go and penetrate deep into that substrate. Finally, these patients with kind of more end-stage hypertrophic cardiomyopathy can have diffuse LGE. And this is an example of an MRI of a patient who has very diffuse LGE, especially from the mid-LV to the apex. And as classically described, there's sub-endocardial sparing. So functional mapping can actually be quite helpful here, ILAM mapping, to narrow down areas of interest when you have so much area of scar here. Of course, we always look at the EKG. And here we had a really nice EKG of an inferolateral apical scar, apical VT. And this is actually the map of the patient. You can see the endocardial voltage was completely normal. But ILAM mapping identified an area of isochronal crowding in the inferolateral apex. PACE mapping here gave us a very good match to the clinical VT. And ablating here made the VT non-inducible. So looking beyond radiofrequency ablation, I think this wouldn't be a talk at HRS 2025 without mentioning pulse field ablation. There is some data talking about the use of pulse field ablation in atrial fibrillation ablation in HCM. And there has been some association with improved outcomes. And obviously, pulse field ablation is scar agnostic, and there is a potential for deeper and more consistent lesions in this hypertrophic substrate with pulse field ablation. So I think more research is definitely needed, but this may be a promising energy technique for these patients. Additionally, outside of pulse field, sometimes, especially in these intramural substrates, coronary venous ethanol and radiation therapy for refractory cases can be helpful to access some of these substrates. So in conclusion, hypertrophic cardiomyopathy is a very challenging substrate for VT ablation. And you really have to use all your tricks in terms of mapping and ablation to really successfully ablate in these patients. Epicardial access, bipolar ablation, low ionic irrigants, and ethanol ablation are all techniques that may need to be employed. And the approach should really be tailored to the exact location of substrate, so pre-procedural imaging and workup is very helpful here to streamline the procedure. And looking towards the future, PFA may provide a significant advantage to RF in these patients, but more research is needed. Thank you. Thank you, Dr. Sharma. We would like to now invite Dr. Zakari from the Auburn Heart Institute of America to give his talk on arrhythmias in Holcombe and medical management. Hello. Thank you, everybody, for attending. Thanks, Dr. Mehta, Dr. Obasare, for inviting me. And this is a brief talk on the antiarrhythmic medical management in Hocum. And I also am from the Auburn Hearts and Vascular Institute of America in Auburn, New York. I hope you can see the text there. Basically, the overview, Hocum is a very common multigenetic process, affects at least genotypically 1 in 500 individuals, and is characterized by the abnormal thickening of the myocardium and also a higher prevalence of arrhythmias. And so, like we heard, atrial fibrillation and VT are very common. And overall, requires a unique approach to managing and monitoring for any arrhythmia. And this is just a brief picture on what the Hocum looks like. And we'll see that it's important as opposed to other types of cardiomyopathy in terms of managing and monitoring. So to identify and screen for arrhythmias, an annual EKG is required. And screening for any kind of arrhythmic disease is of paramount importance. And we want to monitor very closely when any new symptoms arise. And implanted loops and event monitors are indicated for recurrent symptoms. And as Dr. Kim was talking, the AFib is very common, complication in Hocum. It's poorly tolerated for several reasons. Diastolic dysfunction, lack of atrial filling, afloatrack obstruction. And it's obviously very important these days to aggressively treat and manage AFib in Hocum patients. So we have the primary goal is to maintain sinus rhythm. So at all costs, we start with antiarrhythmics, beta blockers, calcium channel blockers for fib. And then for any VT arrhythmias, Amio, NorPace, Sotalol, things of that nature. And rate control, if rhythm control fails, is the next most appropriate step. And emerging data on AFib ablation for poor antiarrhythmic candidates, refractory symptoms. And as Dr. Kim said, that may require redo fib ablations due to possibly non-pulmonary vein triggers and poor substrate in the atrium. And then, of course, there's AV node ablation and pacing when all else fails. What about non-sustained VT? That's very common in Hocum. It's associated with an increased risk of sudden cardiac death. Just touching on this to indicate that it's unclear exactly what to do with non-sustained VT. It's a 2B recommendation for ICD therapy. And not part of my talk today, but as we know there are established risk factors for high risk ICD requiring Hocum. And just to highlight up here, one of those is sustained VT and then there's another one that kind of disappeared there. That's non-sustained VT on a monitor. That's considered a high risk for sudden cardiac death. So we do want to look for non-sustained VT, but we don't exactly know the best treatment plan for that. Advanced imaging, just quickly, the TE can be challenging to look for clots in the appendage and we prefer CT for the morphology of the appendage and also for looking for thrombus. And just to reiterate, the cardiac MRI with delayed enhancement can be very important in identifying arrhythmia substrate and also initially, for example, to rule out other infiltrative or inflammatory cardiomyopathy. So you might have a patient who has VT, you know, they've already had a device and for a long time and we don't exactly know that it's Hocum. So that will show up on an MRI and it also helps for mapping for future ablation. Real quick, the EP studies, just to point out that there's not a very clear role for any EP studies in diagnosing Hocum or treating arrhythmias. It's not routinely recommended and it doesn't really lead to any prognostic value. And to finish up, we have a emerging data on Mavacamtin, also called Camzeos or Camzaios, not sure exactly. It's a cardiac myosin inhibitor and there's emerging data for its effects on reducing the burden of atrial fibrillation, mitigating ventricular arrhythmias and then also rhythm stabilization by reverse remodeling. And that is data that came out a few years ago in the Lancet. And just to summarize that study, a-fib reduction can improve diastolic function and reduce left atrial size that can potentially lower the risk of developing a-fib and mitigating ventricular arrhythmias by decreasing the amount of myocardial fibrosis. And then further reverse remodeling can stabilize the rhythm by structural remodeling and potentially create a more stable cardiac environment and reduce the incidence of ventricular arrhythmias in HOCUM. So the data is still ongoing with that. Just to sort of explain that a little more. So the HOCUM patients are at increased risk for VT and sudden death. And the thought is that if Mavacamptin can reduce myocardial fibrosis, which is a key arrhythmogenic substrate, then it can decrease VT incidence. But there's ongoing studies needed to determine if there's any role in risk stratifying these patients or is this a potential medical therapy as an adjunct to ICD therapy. And then importantly, rhythm stabilization. So reverse remodeling, the myofibrils are disarrayed in HOCUM. And if there's a cardiac myosin inhibitor that can sort of remodel that process, it may lead to normalizing wall thickness, reducing stiffness, which is also important for atrial arrhythmias, and overall create a more electrically stable cardiac environment. So it sounds very promising, but the two trials so far show that there's a benefit on exercise capacity and symptoms from LVOT obstruction, but they also hint at a possible arrhythmic benefit. And like we said, reverse remodeling to decrease the incidence of potential VT. And we would hope that there's future trials that would be able to measure the arrhythmia incidence as a primary or secondary outcome. And for that, most likely, we'd want to use implanted loop recorders to track the burden, for example, before and after cardiac myosin inhibitors. So overall, HOCUM is a complex patient population, and there's needed to have a multifaceted approach and individualized treatment plan, which involves, importantly, antiarrhythmics, anticoagulation, which, as Dr. Kim was saying, patients should be anticoagulated irrespective of their CHA2DS2-VASc score, and monitoring. So apologies for the AI-generated summary there, but basically screening, treatment, team-based approach, and target outcomes and quality of life. And just to summarize, take-home points would be the importance of rhythm control, anticoagulation requirements, rate control strategies, and long-term monitoring are important. Thank you. Thank you, Dr. Zachary. That was a good summary. Next, we come on to a very common problem which all clinical cardiologists face. It's the contemporary risk stratification and ICD indications for hypertrophic cardiomyopathy. I invite Dr. Ethan Rowan from Leahy Clinic Medical Center to deliver this talk. I look forward to it. Great, thanks so much for having me. These are my disclosures. I think my most pertinent one is I am not an electrophysiologist, but know a little bit about hypertrophic cardiomyopathy. So HCM, disease characterized by myocardial hypertrophy. That being said, it's some of the other pathologic features which we think really drives ventricular tachyarrhythmias in this disease, including myocyte disarray, myocardial ischemia, which is in part from the hypertrophy, but also by abnormal arterials, high LV systolic pressures, and scar, all of which in an individual patient can contribute to generating VT or VF. About 6% of all HCM patients have ventricular tachyarrhythmias. And the key question here is how do we identify those individuals who are at higher risk? And in 2025, we have what has become a pretty mature risk stratification algorithm where we look for major risk markers, and if someone has one or more of those major risk markers, it's a scenario where we start thinking about high risk and reasonable to start considering a primary prevention ICD. Sudden death risk in individuals over the age of 60 is actually quite low, even in the setting of major risk markers, so we're really thinking about this for younger individuals. And what are those major risk markers? They include family history of sudden death, unexplained syncope, massive LV hypertrophy over 30 millimeters in thickness, apical aneurysms, extensive LGE, end stage with EF of less than 50%, and NSVT. Notably, on a population level, those individuals with HCM who have identified sarcomere gene mutations do appear to have higher sudden death risk. On an individual patient level, that amount of risk is actually minimal, and therefore is not part of the risk stratification algorithm. I'm gonna focus on a few of the newer risk markers, apical aneurysms, extensive LGE, and systolic dysfunction in HCM, and also talk about what I think is a change in thoughts as it relates to NSVT. Let's start with apical aneurysms in HCM, thin-walled, achinetic aneurysms at the apex. This is also with transmural scarring at the apex, often missed by transthoracic echo, identified reliability with CMR and contrast echo. These individuals are at high risk for sudden death events, event rates are almost 5% per year, and so presence of aneurysm alone is enough for ICD consideration. This is the only risk marker where risk persists over the age of 60, so also is a major risk marker for those individuals who are older in age, and high risk for recurrent ventricular tachyarrhythmias in a substrate which can be ablated if they are having recurrent arrhythmias. We recently presented data which is from a multicenter cohort of, and the largest cohort of HCM patients with LD apical aneurysms, which I presented at ACC, and I think one novel and important realization is that when the aneurysm size is very small, under 10 millimeters, risk for sudden death in those individuals is quite low, only 0.2% per year, consistent with other low-risk phenotypes in this disease, but when the aneurysm size is higher than that, over 10 millimeters, particularly high risk for ventricular arrhythmias with incremental increase with size. So in those patients with very small aneurysms, I think it's reasonable to continue surveillance as opposed to move forward with ICD implant based on this data, but obviously looking for change in size of the aneurysm over time. How about LGE, Lake Island Enhancement, Senon Cardiac MRI, very common in HCM. Almost 70% of patients have some LGE. As you see in these examples, extraordinarily heterogeneous in the location and extent, and when we think about LGE and risk stratification in HCM, it's less about presence and much more about amount, and when the amount increases, as you can see in this slide, incremental increase in risk, we've identified 15% or more as the cut point that we use. It is a 2B indication as opposed to the other major risk markers, which are 2A, and the reason for that is quantification of LGE can be challenging. So you really wanna make sure that the amount of LGE really matches up with the quantification visually. How about systolic dysfunction in HCM? Note, in HCM, ejection fraction is typically hyperdynamic. Average ejection fraction is over 70%. So we consider systolic dysfunction in HCM when the EF drops to less than 50%. You can see here and compare it to patients with ejection fractions higher than 50%. Those patients with lower EFs, high risk for both heart failure, mortality, and all-cause mortality, but also sudden death events, and notably, risk for sudden death events is equivalent in those HCM patients with EF of 35 to 50% versus those less than 35%. So risk marker for us, systolic dysfunction is under 50% in this disease. Do these newer risk markers matter? And we looked at this in a multicenter cohort of HCM patients, 162 of whom had appropriate ICD therapy. And in those patients with appropriate ICD therapy, these newer risk markers account for 30% of all patients with events. Notably, these newer risk markers are not part of the ESC risk score, and that's probably the reason that the ESC risk score, in part, has much lower sensitivity than the risk markers that AHA and ACC endorse, but are nonetheless quite important in terms of risk stratification. How about NSVT on monitoring? I think, in general, in cardiology, the movement has been away from 24 or 48-hour monitoring and more towards extended monitoring for patients. And to this purpose, when you look at prevalence of NSVT, as we did here in 240 consecutive HCM patients, almost 50% of patients have NSVT over two weeks of monitoring, as compared to only about 20% who have NSVT over 48 hours. So very common to see this. So should we be doing two-week monitors or more in these patients? And I'm gonna talk about what defines high-risk NSVT in the next slide, but you can see here that two-thirds of HCM patients with higher-risk NSVT characteristics did not have any NSVT in the first 48 hours. And so you are missing higher-risk NSVT episodes when you do monitoring for less than 48-hour periods. But at the same time, 50% of patients having NSVT makes it hard to say that this would be, in itself, a risk marker. And based on data from Mark Link and all, we know that these higher-risk features do correlate to sudden death events in HCM, meaning frequent episodes, longer durations of NSVT, and faster runs of NSVT, while shorter, isolated bursts of NSVT on monitoring is much less certain. And so that's really the way I think about risk stratifications as it relates to NSVT and HCM, putting more weight on those characteristics. I mentioned some limited sensitivity as it relates to ESC HCM risk score, but how about the ACC AHA risk markers? And this is data from our center, over 2,000 HCM patients. You can see the patients who were high-risk, who underwent implanted ICD, 16% of them had subsequent ICD interventions for VTVF, while those patients who are low-risk, did not have those risk markers. Sudden death risk is quite low, only 0.3% of those patients had events. And I like to think that this risk stratification algorithm is in part responsible for what we showed here, which is a decrease in actual sudden death rates in HCM over time. Thank you very much. Thank you. Thank you, Dr. Rowan. At this time, we'd like to invite Dr. Lampert from Yale University. She's gonna discuss exercise and sports in hypertrophic cardiomyopathy. Can everyone play? This is a very contemporary topic, so we're excited to hear from her. How do I get to my thing here? I don't have a mouse. I'm sorry, I don't seem to have a, I don't seem to be able to drive anything here. Oh, maybe I need to escape. Do I need to escape? Yeah, I can't, I'm not. Oh, there it is. So patients with hypertrophic cardiomyopathy exercise less than the general population. They're more likely to be overweight or obese. Two-thirds of them have purposely reduced their exercise after diagnosis. And for most patients, this has had a negative emotional impact. Less than half of HCM patients meet even the minimal recommended guidelines from the AHA for exercise. In this early study from Dr. Amon's group, he put 100, their group put 182 HCM patients who are minimally symptomatic on a CPET as part of a study of predictors of mortality. They found that peak VO2 was, along with the gradient, were the strongest predictors of survival. Now, this might be an association. Those HCM patients with less severe disease have higher physical fitness, and that's why they're living longer. But it's also possible that perhaps, as in the general population, this could be a modifiable risk factor. So the first study to really evaluate can we modify maximal VO2 or physical fitness in HCM patients was the RESET study that randomized 136 patients to moderate-intensity exercise training, a home-based program versus usual care, for 16 weeks. They found an improvement in peak VO2 consumption consistent with an increase in physical fitness. During this timeframe, there were no arrhythmias, and there were no changes for better or worse in echo parameters. A similar study randomized HCM patients to a high-intensity versus a moderate-intensity training program. In that study, both improved their VO2 max. There was no difference from the high and the moderate-intensity training groups. Similarly, there was no signal for harm with no arrhythmias and minimal echo changes that were not relevant. So based on these data, the recent 2024 AHA-ACC guideline for the management of HCM now gives a class one recommendation that patients with hypertrophic cardiomyopathy should perform mild to moderate-intensity recreational exercise to improve fitness, functioning, quality of life, overall health. But I think it's tempting to extrapolate, could this actually improve mortality as it does in the general population? And I think this is really an important avenue for future research, and I'm hoping by the time of the next guidelines, they'll be able to have improved longevity as well. Now what about competitive sports, a more complicated question? So historically, athletes who have hypertrophic cardiomyopathy have been restricted from sports, starting with the first Bethesda guideline for competitive sports in 1985. And basically, patients with HCM, no way, no how, maybe 1A sports. Sports are classified based on dynamic and static challenge, and 1A are the least dynamically static, basically golf, bowling, riflery, things you didn't even know were actually sports. And this guideline has continued through 2015, really no way, no how. Now what was the rationale for these restrictions through 2015? So sudden death in young people, and in athletes and other young people, is obviously a tragic event. Now what proportion of sudden death in athletes is due to HCM has varied based on studies. The original registry of athletes with sudden death, Dr. Barry Marin's registry, showed that about a third of these events were due to hypertrophic cardiomyopathy. Later studies that use slightly different methodology have found that number to be lower. I think that the question of what that actual number is is not all that relevant. Basically, the bottom line is that HCM is among the causes of sudden death in athletes. It's highly, it's the most prevalent of the genetic diseases that do kill young people, and so it's not surprising that it's highly prevalent in this group as well. Now, there was a thought at some, early on, that when sudden death in athletes happen, it's always during exercise. Again, from the same registry of an early report of 134 athletes, 90% of these happened during exercise. But I think we have to dive a little bit deeper into the methodology to understand that number. This was a registry that used voluntary reporting and media reports, and when the athlete dies on the field, it gets in the media, and when they die at home, it doesn't get in the media. And even pathology, pathologists were also submitting reports to this, and even the pathologist, if the athlete dies on the field, is gonna report it, and if they die in their sleep, that pathologist doesn't know that that person was actually the quarterback. So I think that statistic is something we need to think about in that sense. But most importantly, all of these data are series of sudden deaths and sudden cardiac arrests in patients who weren't diagnosed, and so they don't really apply to the patient in front of us who has HCM and wants to go back to play. So what do we know about the risk of exercise in the diagnosed risk-assessed patient with HCM? So as we've just heard from Dr. Rowan, our risk assessment in HCM is pretty good. In this study from his and Marty Marin's group, this was an early study looking at the risk-predictive value of LGE or SCAR, they found that of their 1,300 patients that they followed for this period, that there were 37 sudden deaths. Of these, 21 had no traditional risk factors, and then there were eight who had no traditional risk factors nor MR predictors, leaving a rate of 0.6% for a sudden death for those with no identifiable risk factors. So the question that we need to answer is does exercise increase the risk of that 0.6% in people that wouldn't otherwise be identified as high risk in getting an ICD? So what data do we have for the athlete who's diagnosed with hypertrophic cardiomyopathy? So first of all, it's important to understand that restriction from sports is not benign, and this was a focus of our recent HRS Expert Consensus Statement on arrhythmias in the athlete. Organized sports lead children not only to be more physically fit, but children participating in sports do better in school, engage in less risky behaviors. Sports builds all those qualities we really want our kids to have, and so restriction is not benign. So what about play, what is the data on that? So we have a couple sources of data on athletes with HCM who have returned to play. So there's a couple of series, this one is from Italy, of 88 athletes, these were all young adults, who were followed for seven years after their diagnosis. 61 of them had stopped exercising, 27 continued. There were two arrests in this group later on, unrelated to sports, and there were no differences in the risk of event between those who had gone back to play and those who had not. This is another retrospective series from the Sharma Group in England that looked at 53 athletes with HCM, again, young adults, about half of these were professional, mostly soccer players, and these were non-obstructive cardiomyopathy patients, and there were no deaths or sustained events in these athletes who had gone back to play. Now the most recent series, Return to Play for Elite Athletes with Genetic Heart Diseases, looked retrospectively at 76 high-level athletes, these were NCAA Division I or professional, who had returned to play, and about half of these had HCM. Overall, there were three breakthrough arrhythmic events, none of them occurred during sports, and there were no deaths or adverse events. We also have a subgroup of prospective series, this is our ICD Sports Registry that enrolled 440 athletes with ICDs who were continuing to play, of those, 75 had HCM. There were no deaths or cardiac arrests related to sports in the whole group, so obviously there were none in the HCM patients either. There was one electrical storm in an athlete who had HCM, which occurred, it was a teenager who was at a party, and none were occurring during exercise. We also now have data from a Prospective Comparative Registry, this was our Live HCM study, that enrolled 1,660 HCM patients, and about half of whom were vigorous exercisers and half were not. Looking at an endpoint of death, arrest, appropriate ICD shock, or syncopal arrhythmia, we found that the non-vigorous and the vigorous were essentially identical in that risk. We looked at the most active group, age 14 to 22, corresponding to a high school or college career, who were phenotypically positive. Among these were 42 varsity athletes, 45 vigorous athletes, but not varsity, and 91 non-vigorous people, and the findings were similar. This is too small for meaningful statistics, but there was no signal, again, here. So based on these data, the 2024 guideline for HCM gave sports, vigorous sports, a 2B recommendation or something that may be considered. Now our HRS statement that came out later that year gave this a 2A recommendation or something that is reasonable. The most recent statement is the AHA ACC sports-focused statement that split the difference and said reasonable to consider. So what does it all mean? And I think it's really, the most important is to recognize the similarities amongst all three of these documents that really focus on concepts of expert assessment. If that patient needs an ICD, you wanna make sure they get one, shared decision-making, and emergency action planning. So a couple unanswered questions. Sports and progression of disease, we don't really know that you can hypothesize risks, you can hypothesize benefits. The only, there's an animal study that showed a benefit of vigorous exercise in a specific transgenic murine model. The human data are really too short to be valuable. We have reset in some similar studies, but they were really less than a year, and so we can't really say much about the progression of disease. Another unanswered question relating to the title of this, can everyone play, I think is the question of left ventricular outflow tract obstruction. So data conflict on the role of obstruction in predicting sudden cardiac death. It appears in the European calculator, it does not appear in the US guidelines. We know that we have, for the symptomatic athlete, we now have excellent treatment, and obviously anyone with symptomatic obstructive HCM should be on a cardiac myosin inhibitor. But what about the asymptomatic athlete? And it's pretty common that you put a patient with HCM on a treadmill, they may develop a gradient they didn't have before. Whether this patient should be treated or not is a question of debate, and I think an important avenue for future research. If, so we still have a lot of room to go. There's an ongoing registry called the Outcomes Registry for Cardiac Conditions in Athletes. Patients can self-enroll in this. So if anyone in the audience has an HCM patient participating in vigorous sports, college, professional, or high school, they can self-enroll in this. Just, you can't have a talk about sports participation for athletes with cardiovascular disease without focusing a little bit on shared decision-making. And this is something that is a topic of an hour lecture in itself, but basically we've moved away from telling our athletes, yes, you can, no, you can't, to really a focus on that conversation. And finally, I wanna end with two cases. The top case is an athlete who, a basketball player, who had a cardiac arrest on national TV. I don't know this person's diagnosis, but everybody has seen this. Another case not on national news or on YouTube, a case I happen to know about, was an athlete who was diagnosed with HCM on screening and was removed from the team. Later that year, that person had a cardiac arrest at his after-school job, which he had gotten because he was no longer on the team. Luckily, he was resuscitated successfully. And I think what these two cases demonstrate is that if you take the player off the field, you can sleep well knowing that he or she won't die on the field. And I think that's really an approach to have in the back of our minds as we're doing this evaluation. Thank you. Thank you, Dr. Lampert. I think I'm gonna jump on to a few audience questions. The first one is for Dr. Kim. Do you routinely continue anticoagulation following ablation given the risk of recurrence and success rate in these patients? In hypertrophic cardiomyopathy, since stroke risk is independent of CHADS-VASC, I think that area, I think you're gonna see some variation out in the real world. But I would advocate that you continue anticoagulation. Second question, obviously, is also about AFib. Again, Dr. Kim, when do you switch from AF ablation strategy to AV nodal ablation strategy in terms of number of attempts, substrate change approach used for ablation? Yes. This is a difficult question. Our hypertrophic patients are generally younger. They're very symptomatic. I think you're gonna try a lot. I don't wanna put a number to multiple procedures. I guess it would depend on what you're actually going after and what drugs you have tried in combination with ablation and the rate control. So I don't have a great answer for that, being honest. I think you wanna try and use AV nodal ablation kind of as a last-ditch effort to try to palliate or alleviate symptoms. I think I might just add a comment that AV nodal ablation in hypertrophic is not a good solution related to the diastolic dysfunction and at least in my practice, I try to maintain sinus rhythm as long as I can. And obviously, AF strategies are changing every three, four years. You have a new tool in your armamentarium to see if you can keep this patient in sinus rhythm. That's a great point. I personally have never done an AV nodal ablation in a hypertrophic cardiomyopathy patient. So that gives some perspective. Thank you, yeah. Thank you. The next questions are for Dr. Sharma and Dr. Rowan regarding the quantification of LGE stratification. What is the cutoff method, cutoff point you guys recommend? Is it greater than 15%? Yeah, so it's around 15%. It's a clear incremental increase. To say that 14% is not enough for an individual patient to start thinking and at least having a shared decision-making conversation about a device is not true. That it's just like a wall thickness of 29 millimeters. It's the same thing. You have to start thinking about risk for that patient and talking to that patient about risk. I think the challenge is quantification. Most of the studies use six standard deviation or manual thresholding, but there are limitations with those approaches. And again, you really wanna make sure that that quantification is done by someone who's experienced with it or really matches up what you're seeing visually. And I'll just add, I agree with all that and to remember that this is not a static risk and to, if a patient doesn't have as much LGE initially, to consider repeating the MRIs in a few years, depending on the development of other risk factors as well. I think I'll just stay on with Dr. Sharma. This is a very interesting question for EP. Is substrate modification without VT induction reasonable as a first-time VT ablation in hypertrophic cardiomyopathy? Obviously, you're comparing it with ischemic. Yeah, I think it definitely depends on where the substrate is. And as showed, there's multiple different substrates in these patients. I think that induction of VT, at least at the beginning of the case with non-invasive program stimulation is part of my practice. I think it adds a lot to know, to have a target in terms of the VT and pace mapping. But I think in some of these apical aneurysm cases, if you really know that it's an apical VT, a substrate-based approach may work. But I always think that some of this, some electrophysiological induction is very helpful. And most of the time, these patients do tolerate the VT relatively well, better than a lot of the other non-ischemic substrates are usually younger, lower risk. So I often do still do stimulation. Thank you. I had a quick question for Dr. Lampert and Dr. Zakari. What is the role of implantable loop recorders in athletes? I would not put in a loop recorder in someone just because they're an athlete. I think if you have symptoms that are questionable, that's really the indication for a loop recorder that I would use. So in HCM, I mean, certainly like near syncope is pretty common for all different reasons, and that's a good reason to put in a loop. But I wouldn't routinely do one just because someone's an athlete. Go ahead, I think there's a question from the audience, yeah? Nick Peters from Imperial College London, England. I mean, I'm interested in the panel's view. Isn't it extraordinary that when we're talking about arrhythmic risk, the scoring system uses factors that are anything but electrophysiological? And I do find it extraordinary in the age of the deep insights we now have from detailed mapping, from AI as applied to surface ECG, for example, that we are still not invoking electrophysiology or any electrophysiological parameter in risk estimation. And is it because we operate in silos, and generally speaking, doctors with an interest in hypertrophic cardiomyopathy are not electrophysiologists? Is it because the implication of better defining arrhythmic risk would mean that we don't put ICDs in some patients that we would otherwise have done, and no one's got an appetite for doing that? Or is it something else? But I do find it extraordinary, and if you arrived on this planet from Alpha Centauri, you would say, how is it that there's no electrophysiology at all in risk assessment of arrhythmic risk? I would put a question back to say that most of the patients, as an EP in general, all of the patients we risk assess, post-MI, not cardiomyopathy, standard heart failure patients, we don't use electrical characteristics either. So far, what we have are clinical characteristics that predict sudden death. And I think certainly it's exciting to think about there might be, can we find something in that EKG with AI that we're not seeing with our naked eye that's gonna be a great predictor? But I think right now, I don't think we have those parameters. Or for anyone. We need to be up for the fight to look. And actually, history is peppered with attempts to do so. And I do know some work that's been done, okay, along the way, looking at electrogram fractionation, that did identify and segregated very well with arrhythmic outcome. But these things don't seem to have been accepted into the guidelines. And I'm really asking you, why not? I would give one answer, which I think that when we think about, again, going back to the standard heart failure population, I mean, we've looked at so many factors, T-wave alternance, signal average, EKG, T-wave distribution, so many different ways to look. And so far, we haven't found anything that actually guides therapy. So I totally agree with you. I think if we can find some electrical predictors, it'll be great. And if AI helps, that'll be super. But I don't think there's ever been an electrical predictor that said, if we treat this person versus not treating them, we're actually gonna help save their lives, as opposed to just, yeah. So I think it's a great wave of the future, but I don't think we have the data to support that right now. And we don't know what we don't know, and we won't know it until we look. Yeah, we should look. And there are ongoing studies, Rick Carrick in the audience over there, trying to answer that question, using AI EKG to risk predict HCM patients. I have another question for Dr. Owen. There is some pediatric and young adult study showing that LV obstruction may be protective for sudden death. How can that be explained? I'm sure that makes you smile, so I presume you know the answer. You don't know what you don't know, and then that is definitely an answer, which I think is kind of unclear to me. You know, when I was talking about risk stratification, let me just be clear, that was adult and young adult patients, not pediatric patients. Pediatric patients, there are a number of risk tools out there trying to risk stratify them. We only see, we see adolescents. For adolescents, our practice is still using the major risk markers, which does not include outflow obstruction. But you're right, the pediatric patients, those risk models do have outflow obstruction being associated with decrease in risk, and I'm not sure pathophysiologically I understand that. Well, thank you to all our speakers and audience for attending this excellent session. Enjoy the rest of HRS 2025.

hypertrophic cardiomyopathy

arrhythmia risk

exercise management

ICD indications

AF ablation

ventricular tachycardia

antiarrhythmic management

risk stratification

exercise guidelines

treatment strategies