which is required, and then Aarti will start. My name is Seshadri Balaji. I'm one of the chairs. I'm from Portland, Oregon. So, welcome to San Diego and Heart Rhythm 2025. If you haven't already done so, download the HRS 2025 mobile app, and you can participate in live Q&A. We'll put up the QR code in a minute, which is also something you can use to send in your questions. When you're using the mobile app, log in with your HRS credentials. Please note that visual reproduction of Heart Rhythm 2025, either by video or still photography, is strictly prohibited. Okay. Aarti. All right. Welcome, everybody. We're really pleased that we have such a full audience, even this late in HRS, so welcome. My name is Aarti Dalal. I'm an electrophysiologist at Vanderbilt University Medical Center. Today's session is let's talk about the risk, baby. We are changing the order of our talks just a little bit, just because of travel plans. So, it is my honor to invite our first speaker, Dr. Douglas Darden. He's the director of sports cardiology at Kansas City Heart Rhythm Institute. And he will be speaking about the risk of sudden death with exercise and inherited channelopathies. Are exercise restrictions a thing of the past? Dr. Darden. Well, thanks, guys, and thanks for showing up to one of the last sessions of the conference. So, this talk is interesting. Exercise used to be really just terrible if you had genetic heart disease, especially before 2015. The data has changed quite a bit. It's matured and evolved, as well as our approach to exercise, too, in these individuals. So, what do I mean by that? Prior to 2015, if you had any genetic heart disease, if you had an ICD, that was automatic disqualification. But things began to change. 2015, this concept of shared decision-making came into play. We began tailoring risk assessment and therapeutic plans to the individual. And then, fast forward to 2024, the Heart Rhythm Society Expert Consistence Statement on arrhythmias in athletes. This was led by Dr. Lampert and Dr. Eugene Chung. I was fortunate enough to be part of this. We elaborated more on this shared decision-making topic and also touched upon return to play with select athletes, particularly when you appropriately risk stratified, the arrhythmogenic substrate was treated, patient was free from recent arrhythmia, and they're on stable medication regimen. So, a lot of times, when we think about sports cardiology athletes, we think of professional athletes, College One Division athletes. But really, with regard to genetic arrhythmias, it's anybody that puts a premium on physical activity. So, tactical athletes, weekend warriors, recreational athletes, all of these patients have somewhat of the same goal, and we approach care quite similarly among these. As we go through this talk, I'll walk through specific conditions, specific strategies. We'll talk about how we risk stratify, also elaborate on this concept of shared decision-making. And then, when there is available evidence, I'm going to talk about that and how that can guide us when we talk about risk assessment with regard to exercise. So, shared decision-making, isn't it just good medicine? I hear that quite a bit in some of these presentations, and it's not really anything goes, quote, anything goes. It's really a structured, collaborative, well-documented discussion. It evaluates risk, it optimizes therapy, you're setting safety plans, and it's not just for the patient and you, it's for coaches and the school systems, for example. And re-evaluation, which I'll bring up a little bit too, is key with this. So, you really have to know the literature well, you have to know the gaps within the literature, and use the available tools to help risk stratify, to determine the best course of action. There may be some pediatric EPs here, and I think shared decision-making with pediatric EP is even more complicated. I'm an adult EP, I see some kind of late teenagers and whatnot. But a lot of the data we have, we extrapolate from the adult population to the pediatric population. Disease phenotypes may emerge later in life too, so again, it goes back to that serial evaluation. And shared decision-making is more complex, you're not just dealing with the patient in front of you, you have to really involve the parents along with this discussion too. And these decisions that may be determined early in life have long-term implications. So, I just saw this patient a couple months ago now, two, three months ago. I saw him at age 21. At age 11, he was diagnosed with hypertrophic cardiomyopathy because he was blowing up a balloon and passed out from that. Septum measured about 1.4 centimeters. Since he blew up a balloon and he passed out, hypertrophic cardiomyopathy, got an ICD. At that point, he was told to never exercise, they pulled him from gym class, can never participate in any sports. He lit his device at ERI and he came in with an inappropriate shock, that's how I met him. After a long discussion, severe PTSD from this, horrible anxiety, probably long-standing depression from just lack of any type of physical activity too, we decided to basically replace his device but leave off his tachytherapies to just continue discussing this concept of shared decision-making. So, thinking back, I really wondered if we had the data that we have now, a couple of decades ago or a decade ago, whether or not this would be a different discussion we're having in current day. So, as we go through some condition-specific strategies, so my talk was really on channelopathies. I'll mention a few of these channelopathies. The first and most common one that we'll see is long QT syndrome. It's quite common, one in 2,000 people have this and up to 40% of people may actually have a normal QT on their resting 12 week. When you look at QT cutoffs, about 460 is what we are considering as at least screening for if you're pre-puberty and then for males and females after puberty, about 470, 480. And the genotype matters too, especially with regard to trigger. So, long QT type one, the most common. We often think of that as the one closely linked to exercise, especially swimming. Long QT type two is when startled, it can happen in the postpartum phase, therefore more of a female predominant. Long QT type three happens more at rest and sleep and has more of an adult onset. If you look to the right, you can see the different repolarization changes that help you determine also what type of genotype you may have. And so, going a little bit further into the risk stratification of this, the longer the QT interval is, the higher risk of any adverse events, especially when you hit 500, 550. The genotype matters, three, little higher risk than two, a little higher risk than one. Males are at higher risk pre-puberty, females higher risk post-puberty. But the good thing about long QT is that you can manage it very well with low event rate. Beta blockers, cornerstone of therapy, particularly non-selective beta blockers and analog. Don't forget about myxilatine for long QT type three. ICDs are most commonly going to be in those who have needed it for secondary prevention. Only a few get it for primary. And then don't forget about cardiac sympathetic denervation if you cannot tolerate medications or still have breakthrough events. When we look at the data for return to play exercise, the strongest data for any inherited channelopathy is for long QT syndrome. The Mayo Clinic published their series. Martinez published in Jack last year or so looking at elite athletes. Select group of those had long QT. And then most recently, the Live Long QT Registry led by Dr. Rachel Lampert looked at over 1,000 patients with long QT syndrome. No difference in adverse events between those with vigorous activity compared to those with moderate activity. So really, you can return to play. You can return to activity if you have long QT syndrome. But it has to be appropriately modified or appropriately treated with medical therapy, for example. And keep in mind, the risk is still not zero. I'll elaborate a little bit more on this too. But an emergency action plan needs to be in place. You're not just done after returning these patients to play. CPVT, this is one of the most malignant inherited channelopathies we have. It's an exercise-induced ventricular arrhythmia syndrome, most commonly due to mutations with riodidine. And when we think about therapy, universally, most of these patients should be on NADLOL, again, non-selective beta-blockade. Flaconide is often added, especially if you have breakthrough events still with ventricular ectopy. So most patients are on dual therapy. And sympathetic denervation can play a role. ICD is tricky in this population because these patients, you really have to emphasize appropriate medical therapy. If a patient gets shocked with CPVT, that can really provoke an adrenergic storm, essentially lead to more shock. So have to be on maximal medical therapy. And this is a little bit of a tangent, but something interesting, something that I came across last year. We often think of CPVT as autosomal dominant inheritance channelopathy, but there's emerging data showing that heterozygotes, may be at somewhat of a risk too. I came across one last year, and then recently, Jackie P. K-series published with heterozygotes and the risk of CPVT. So this benign type heterozygous issue may be something we need to look into a little bit further. So essentially, I bring that up because we should have a very low threshold for genetic testing, if you have somebody with exertional symptoms, especially with ventricular ectopy with exertion. Exercise and CPVT, little bit complicated. We're not dealing with a lot of strong data behind this. The strongest is from Mayo Clinic, just evaluating 21 athletes who returned to play, who were diagnosed with CPVT. Zero deaths, and when you look at those who actually got shocked or had an event rate, it's usually those that were, it was happening usually without exercise, or if the patient was non-compliant with their medical therapy. So all goes back to ensuring that you're really emphasizing medical therapy. And one important piece that I didn't talk about yet, but an exercise treadmill test can be quite helpful. I mean, very helpful, especially with CPVT. That should be non-negotiable. These patients should really have complete suppression of ventricular ectopy with medical therapy before you allow them to return to play. Brugada, this is a different kind of risk. This isn't really an exercise-induced arrhythmia. You're more likely to have ventricular arrhythmias at rest, or sometimes in recovery from exercise. So if you do have refractory ventricular arrhythmias, quinidine is the drug of choice for this, but usually exercise is quite safe with brugada, but you have to think more about avoidance. So you want to avoid fever, you want to stay hydrated, avoid any type of overheating with exercise, for example. This isn't a channelopathy, but I wanted to mention this too. Hypertrophic cardiomyopathy. This is one of the leading causes of sending cardiac death in athletes. We can appropriately risk stratify this, massive LV septum, late gadolinium enhancement, ventricular arrhythmias and whatnot. And again, that whole reevaluation concept, especially for pediatric diagnoses of hypertrophic cardiomyopathy is something that you want to serially keep in mind and keep evaluating. A few things too, hypertrophic cardiomyopathy is very heterogeneous. There are certain subtypes that carry a very high risk. Dannon disease, for example, PRK2, Fabry disease. When I was here at UCSD for fellowship, we were a pretty strong center for Dannon disease. One of the gene therapies studies was just published this year. But when I was looking through all of these ECGs, a lot of these patients have pre-excitation. So we often think of that as a fascicular ventricular pathway, but even with Dannon disease, a lot of these patients may have malignant extranodal pathways too. So if you have severe LVH in your youth, pre-excitation, you have to think about more of these serious types of hypertrophic cardiomyopathies. Hypertrophic cardiomyopathy, when we think about return to play, used to be universal restriction, but things have been changing quite a bit. Genotype obviously plays a role in this, but phenotype even more so, right? If you're genotype positive, phenotype negative, you don't need to restrict these patients from activity. Just keep an eye on them. Phenotype positive though, again, it's not a binary situation. It can be possible to return to play. There's observational data, the LIV hypertrophic cardiomyopathy study, registry data, over 1,000 patients, nearly 2,000 show no excess events with vigorous activity too. And again, the Martinez study, select group of those patients had hypertrophic cardiomyopathy, low event rate. However, we do have to recognize that observational studies have limitations. Not all athletes with hypertrophic cardiomyopathy are well-represented. So we have to have continued efforts to do more prospective evaluation of these patients. And inform patients that these studies may not actually apply to them too. But the background or the conclusion from that is exercise is really not universally restricted if you do have hypertrophic cardiomyopathy. Few things about ICDs in athletes. Now, ICDs in athletes, you're already basically by default, the highest risk. There's strong data from Rachel Lampert's ICD sports registry, evaluating about 400, 500 patients who have an ICD, followed them for a few years. No deaths, very few event rates, but it really speaks to appropriate medical therapy, appropriate risk stratification, appropriate ICD programming. Gotta remember that the ICD is there as backup, it's preventing sudden cardiac death, but it's not preventing the arrhythmia from happening in the first place. Now, a few other things too. I mentioned this earlier. Once you have somebody exercising, if they have an inherited channelopathy or genetic heart disease, you're not done, you're not out of the woods yet. You really have to take into account this concept of an emergency action plan. So you have to ensure that people are well-trained in CPR, they can recognize it, they know where the AED is, they know how to use it. So we looked into this a little bit. There's still a lot we can improve from this. Our group at KCHRI, we looked at all of the different mandates across the United States. We found quite a bit of variability with this. Specifically, there's significant lack of hands-on training, even AED training, and then very few states mandate any type of refresher courses. We surveyed about 2,400 high school students. Not all of them had training, 86% of them did though, but only about half of them felt comfortable using an AED, and almost all of them want further training. So there's a huge opportunity for that. This always fascinates me. We think of sudden cardiac death in athletes, the most common cause, typically the teaching was hypertrophic cardiomyopathy, but that's not the case. Study after study shows that it's mostly sudden unexplained death, or most commonly, sudden unexplained death, or sudden arrhythmic death syndrome. How do we improve that? Are we missing undiscovered genes right now? Can screening help with that? There's a lot we don't know about that. And then this concept of shared decision-making and emergency action planning, and oftentimes personalized emergency action planning too. There's no standard process for this. There's no type of pathway that we can give to providers to help guide us with this, but that would be one way that we can ensure that we're achieving the best outcomes for these patients who are considered high risk. So a few conclusions. Just because you have a diagnosis of some inherited genetic arrhythmia syndrome, for example, it doesn't automatically make you high risk. You have to risk stratify to use the tools that we have. Return to play depends on many different factors. Substrate needs to be treated. No recent ventricular arrhythmias. Compliance with medications. And once you return to play, have to really outline an emergency action plan. With that, thank you all for your attention. Thanks. So Doug has to leave right after this talk. So if anyone has questions for him, if you want to come up now, and while you're coming up to the mic, we have one that is coming through the online Q&A. So essentially, Doug, what the person is asking is, so there's a lot of data about exercise ICDs and safety of ICDs. Do you have a preference when you're, when you are speaking with your patients, transvenous versus sub-Q ICDs? Yeah, that's, especially if you're a pediatric athlete, you want to really take into account the long-term impact of transvenous leaves. So subcutaneous ICDs are quite common. We don't have good data for long-term outcomes with that, but what's going to be really interesting is the EVICD, smaller device profile, maybe a safety profile, or better safety profile with the leaves too. And do you base your decision based on the sports or the activity that they're going to do? Yes, yes. And so I don't see pediatric athletes, right? But especially I try to minimize any type of transvenous device if they don't need it, especially when somebody is relatively young. Yeah. Yes, please. Thank you for a nice overview. How do you approach patients who have long QT but with negative genetic testing, and they don't respond to beta-blockers, fluconide, et cetera? I actually have one patient who had really huge number of appropriate shocks despite maximal beta-blockers, fluconide, and the negative test for long QTs, other channelopathies, but she did well with sympathectomy despite I didn't know the mechanism. So how do you approach such population? That's a great question. I mean, that is the exact appropriate pathway I would follow too. It makes me wonder though if we are missing some unknown variants that we're not picking up on a routine genetic test too. All of it, yeah. Yeah, that seems very appropriate though. I mean, do you take the clinical scenario, whether is it adrenergic type, non-adrenergic type? Does it sometimes worsen the scenario if we do empiric sympathectomy? That's a great question. I don't know the data behind that, but yeah, that would have to be a strong consideration too. That is a really good point. Okay, one last question. Xander? Yeah, thank you for your talk. So I take care of, like a lot of us, I take care of both children and adults. And so one of the things I struggle with when I'm coming up with a return to play protocol or an action plan for whether that be a school or a team or maybe a college or a university, I don't have any professionals, but I wanted to see what level of detail do you provide in those action plans for the teams, for the universities and things? And do you keep them kind of more broad and say call 911 and have an AED? Or do you go into details like this is gonna happen and what level of detail are you providing in these action plans? Yeah, it varies from athlete to athlete, but usually try to be quite detailed if you're competing somewhat competitively. So it's something that most recently I had to basically write out somewhat of a document that implied that the coach was trained with CPR, they knew where the AED was. It was a young woman with Long QT syndrome. And she actually had her own AED, too. But no events, just managed well, medical therapy. But it is quite detailed. And that was somewhat required by the school, too. So to answer your question a little bit more detailed, though, I think it was published in Circulation or Circulation A&E. Rachel Lampert was the senior on this. It was kind of a research letter slash opinion piece. And they were mentioning this concept of a more standardized process for return to play and shared decision making. And they kind of had this templated note that they were using. I don't know if they use it routinely or if it was just an example. But I saw that a couple of weeks ago. And I thought that was very, very useful. So that could be helpful in that situation. Excellent. Thank you. Thank you, Doug, hope you got your flight. Thank you. Next speaker is Zelia Koyak from Amsterdam. And many of you know her papers. She has a longstanding interest in arrhythmias in adult congenital heart disease and risk factors for sudden death in the adult congenital heart population. So it's very appropriate that she gives this talk on risk calculation for sudden death in congenital heart disease patients. How useful are they? Thank you. Thank you for having me here today. I'm just trying to, I think I have to close this presentation, right? So do I just click it away? And while she's bringing it up, we'll have Dr. Koyak's questions at the end of the session. OK, and now I need to wait. Yeah. OK, thank you. Thanks again for the introduction. Excuse me. What's this one? Maybe you can use this. I can use that? Yeah. Thank you. Yeah. All right, okay. I don't have any relevant disclosures and I would like to start the presentation with a case. This was a 65 years old lady. She visited us in our outpatient department in 2016. She was known to have congenitally corrected transposition of the great arteries. And in 1997, we implanted a dual chamber pacemaker for complete heart block. She was also known to have atrial tachycardias, was in near class two and medication wise, she used Sotalol and Valsartan back in that time. We assessed her ejection fraction with CT scans and her pacemaker wasn't MRI compatible. And as you can see throughout the years, her ejection fraction was quite stable around 35%. Her pulmonary ejection fraction was above 40% and her coronary arteries were normal. On the right side, you see at the top, her ECG during the outpatient visit, which show the sinus rhythm with a ventricle paste, cure restoration of 136 milliseconds. And at the bottom, I found an older ECG showing her intrinsic rhythm with her complete heart block and a cure restoration of 125 milliseconds. So between 2012 and 2016, her pacemaker integration showed very regularly non-sustained VTs up to 23 beats with a rate of 200 beats per minute. She was completely asymptomatic of these episodes. And the questions I will try to address during this presentation today is, one, should we implant an ICD for primary prevention? I'm really curious what the audience would do. Maybe the people who think we should implant an ICD could raise their hands. One, two, only two, okay. My colleagues from Amsterdam, thank you. The second question, what do the guidelines recommend? And the third question would be, what's the risk of sudden cardiac death according to the available risk scores models today? So let's see what we have. Before I try to answer the questions, a little bit background information. Sudden cardiac death is one of the leading causes of death in ACHD population with prevalence between 15 up to 40% in different nationwide studies. However, the actual incidence is quite low. It has been reported to be between 0.2 up to 2.7 per 1,000 patient years in different cohorts. The sudden cardiac death incidence is logically highest in mid-30s in patients with complex defects such as Eisenmenger syndrome, transposition of the great arteries, and tetralogy of Fallot. And at an older age, after 50s, in those patients with simple forms of congenital heart defects. There are some new data available suggesting, for example, that patients with ASDs might have AV conduction disorders because of NKX 2.5 mutations. So maybe genetics plays a role in those simple defects as well, which can cause sudden cardiac death. What about ICD therapy? It seems to be quite effective in the ACHD population. This was a beautiful systematic review published in 2016, showing that appropriate shocks occurred in 22% of the patients with a primary prevention indication for ICD over a mean follow-up duration of 3.6 years. And the recipients of the ICDs were mainly had tetralogy of Fallot or transposition of the great arteries, most of the cases. The primary prevention indication was 36%. Unfortunately, the prevalence of inappropriate shocks was also quite high, around 22%. And the major cause of complications was lead failure or dislodgement. You might resolve that issue with an SICD, for example. And this is a beautiful French study which has been published two years ago where they compared congenital heart disease, patients with congenital heart disease and an SICD with patients with an SICD without congenital heart defects. So they included around 100 patients. The majority had tetralogy of Fallot, transposition of the great arteries or a univentricular heart. And they compared those patients, 100 patients with almost 5,000 patients without any congenital defects. And during a follow-up duration of 1.9 years, they found that 15.8% of the ACHD population had an appropriate shock which was twice as high as for the other group. And there was no lead dysfunction. So this might be a solution for some of the patients who do not need Bradypacing. This table gives a summary of the ICD recommendations according to various European and North American guidelines. And the red box here shows the level of recommendation. And there are two things quite remarkable here. The first one is that the level of recommendation differs between the different guidelines from class 1 to 1A to 1, sorry, to 2A to 2B. And the indications for ICD seem to be extracted from acquired heart disease, except for tetalogy of Fallot and transposition of the great arteries. So this was another interesting study which was published in 2016. What they did here was applying the ICD indications according to the guidelines to an ACHD population who had proven or perceived arrhythmic death. And they found that according to the consensus statement which was published in 2013 back in that time, they found that according to that guideline, only 41% of the sudden cardiac death cases would have an indication for primary prevention. And the ECC guidelines did even worse. They only identified 35% of these sudden cardiac death cases and even 14% of the controls. And we see here the ROC curves for both guidelines showing an AUC of 0.6, which is actually quite moderate or poor. Risk Score Model 1 was developed in Amsterdam. It was a Dutch study called Prevention ACHD. So I will, by the way, discuss two risk score models. So this is number one. So in this study, they developed a point-based risk score model where you could actually calculate the annual risk of sudden cardiac death for a specific patient. And the risk factors were driven from a retrospective multicenter case control study which had been published earlier. And those risk scores or risk factors were coronary artery disease, NIA class 2 or 3, SVTs, systemic ejection fraction below 40%, subpulmonary ejection fraction below 40%, acute restoration above 120 milliseconds, and acute heat dispersion of more than 70 milliseconds together with the a priori risk for sudden cardiac death, which differed in various underlying defects. So the more severe your congenital defect is, the higher the a priori risk is for sudden cardiac death. And afterwards, the risk score model was validated, so it was validated initially retrospectively, externally, and afterwards prospectively. This is the main result of the risk score model. So basically what we see here is that around 800 patients, ACHD patients, had been categorized into high-risk versus low-risk sudden cardiac death, and the definition for high-risk sudden cardiac death was 3%, which is the red line here. The primary outcome of the study was sudden cardiac death or VTVF or an appropriate ICD shock. The secondary outcome was sudden cardiac death only. And after a follow-up duration, 92% of the high-risk group was free of the primary outcome. So when we apply this risk score model to our patient, case X, which I discussed earlier, the patient would score four points. So she would score one point for heart failure symptoms, one point for SVT, one point for an impaired systemic ventricular ejection fraction below 40%, and a QRS duration above 120 milliseconds. And if you look at the table on the right side, when you go to the top, I'm not sure if I can point it, but she would score four points, what you see on top. And if you go to her underlying defect, which is a congenitally-corrected transposition of the great arteries, she would score an annual risk of sudden cardiac death of 4%. The second risk score model is, regarding the methodology, quite similar to risk score model one, but there were two main differences. The first difference is that this study hasn't been prospectively validated yet, so it was only a retrospective validation of the model. And they found slightly different risk factors as well. So in this risk score model, the age, the gender, unexplained syncope, and non-sustained VTs was also considered as an additional risk factor for sudden cardiac death. And with this risk score model, you are able to calculate the five-year sudden cardiac death risk in a specific patient. So they have also an online calculator for the risk score model, so when we fill that form out for our patient, she would score a five-year risk of sudden cardiac death of 6.6%. So to the second question, I will answer that now. So according to the guidelines, our patient would have a class one indication for an ICD, and according to the PACES-HRS consensus statement in 2014 and the ERA guidelines 2018. According to the ECC guidelines published in 2020, she would have a class two A indication, and according to the HRS guidelines published in 2017, she would have a class two B recommendation for an ICD. And when we look at the risk score models, our own risk score model would give her 4% annual risk of sudden cardiac death, and the Spanish risk score model would score her five-years risk of sudden cardiac death 6.6%. So there is some variety, as you can see. So what happened to our patient? Back in that time, we hadn't published the risk score model yet, but we had the data available, so our decision making back in that time was based on our own model, and we did an upgrade of her pacemaker to an ICD for primary prevention. In 2022, she called our outpatient clinic, and she told us that she had a dizzy spell while she was driving her car on the highway with her best friend sitting next to her. She hadn't felt any shock. So we remotely checked her ICD, and here you can see the opposite, which showed an appropriate shock for ventricular fibrillation. So in summary, we can say that the available risk score models are useful to identify the ACHD patients at high risk of sudden cardiac death for VTVF, who may benefit from primary prevention ICD implantation. They seem to have a greater accuracy in assessing sudden cardiac death or VTVF risk compared to existing ICD guidelines. The high-risk features common to both scores include a systolic dysfunction of the systemic or subpulmonary ventricle, white QRS complex, and ischemic heart disease. Both risk score models have their limitation. The prevention ACHD was a single-center study which few events and the follow-up duration was only two years, and the Spanish risk score model needs prospective validation. And for the future, comparison of both models in large prospective studies would be a bit of a longer follow-up is very desirable. So I hope that in the future there will be some research publication about this topic again. And I would like to thank our pacemaker technician, Michael Zumbrink, for providing this case for today. Thank you for your attention. Thank you. Thank you, Dr. Crock, that was a fantastic presentation. Next it's my pleasure to introduce David Spahr. He's the director of the EP Lab at Cincinnati Children's Hospital, and he will be speaking today about assessment of sudden death risk in pediatric dilated cardiomyopathy with LVEF less than 35%. Dr. Spahr. Thank you. I wanted to thank Heart Rhythm for inviting me to this talk as well. Did you say your patient did not feel that shock while she was driving her car? She didn't feel the shock. We all need patients like that, I think, and make them create a lot less stress. So this is a talk I was invited to give. We're going to review the assessment of sudden death risk in pediatric dilated cardiomyopathy with LVE ejection fraction less than 35%. I wanted to briefly discuss the adult non-ischemic risk factors with this group, the risk factors for sudden death and recommendations, and then we'll get into the pediatric risk factors and then future directions. Just in brief, dilated cardiomyopathy is a myocardial disorder. It's characterized by ventricular dilation and systolic dysfunction. The prevalence is about 1 per 100,000 patients, a little bit higher in younger populations. We'll review this a little bit later, but the mortality and transplant rates are very high, but sudden cardiac death is quite low. Dilated cardiomyopathy accounts for about half of all pediatric cardiomyopathies, and these are the major etiologies. We are going to lump these all together. I will not talk about myocarditis because I think it has a separate risk factor. We are going to talk about transition to adult non-ischemic cardiomyopathy. This will be a review for many of the people in the room, and at our program, we say this for the fellows when we talk about old information that they should know, but just to review, two studies for non-ischemic cardiomyopathy patients, both SCUD-HEFT and DEFINITE. Initially SCUD-HEFT had about 800 non-ischemic cardiomyopathy patients. In this study, total mortality over five years was 27% in placebo versus 21% in the ICD group, a trend towards significance. The definite trial included non-ischemics with LV ejection fraction less than 36% in PVCs. And this study did show a reduction in sudden cardiac death with a trend towards all-cause mortality reduction. More recently, the Danish study, which focused on non-ischemic cardiomyopathy patients less than 35%, did show ICDs had reduction in sudden cardiac death from 8% to 4% over five years. There was no overall change in mortality besides when they did secondary analysis in younger patients less than 70 years of age. Of note, this study is not generalizable with patients without CRT because in both groups there was about 60% CRT in both arms. But you can see in this figure there was a meta-analysis demonstrating a 24% risk reduction in mortality, ICD versus medical management excluding CRT. And this has led to the adult non-ischemic primary prevention guidelines of LV ejection fraction less than 35% on goal-directed medical therapy, survival greater than a year, class one indication. For those patients without class one heart failure symptoms, the data is less known. These patients were not included in Scott Hafter, Danish. The definite trial only had 20% class one, which is why the recommendation is only a 2B for ICD. In regards to secondary prevention, these randomized controlled trials for survivors of sudden cardiac arrest had a total of about 300 non-ischemic cardiomyopathy patients, which was about 15% of the entire study population. And the pooled analysis had a 31% reduction in mortality with ICD alone. In patients who had sustained VT, that was associated with mortality similar to those with unstable VT, and these are markers for lethal arrhythmias, also a class one indication. And then lastly, symptoms of what's concerning for ventricular arrhythmia, such as arrhythmogenic syncope, there are observational studies with high mortality and ICD shocks. It's important to note that syncope is not always related to arrhythmogenic syncope. In the MATED-RIT trial, only 39% actually had arrhythmogenic syncope, and this may be an indicator for end-stage cardiomyopathy and poor prognosis. For those patients where suspected syncope is arrhythmogenic, some patients underwent an EP study. Two studies demonstrated that inducible VT and VF was associated with ICD shock, and a sub-study of the DEFINITE trial demonstrated inducible VT and VF associated with ICD therapy. So this is the foundation, and our recommendations are very similar. So I'm going to transition to pediatric non-ischemic dilated cardiomyopathy now. So as I said, the annual incidence of sudden cardiac death is very low. It's less than other pediatric cardiomyopathies. It's less than adult non-ischemic cardiomyopathy. The low incidence of events makes it difficult to establish risk factors to guide recommendation for ICD. There's no clear evidence that ICDs for primary prevention improve survival. And as I showed, there's a lot of different types of dilated cardiomyopathy, so the phenotypes may overlap with other cardiomyopathy end results and variable risk for sudden cardiac death. This is from the PCMR registry, which I'll talk to you a little bit about in the next slide. But it's important to note that the mortality or transplant rates are quite high. So 40% undergo heart transplant or die within two years of initial diagnosis, and the one-in-five-year rates of death in heart transplant are 31% and 46% respectively. The PCMR or Pediatric Cardiomyopathy Registry was a large registry over 20 years. That included 1,800 children with dilated cardiomyopathy. Of those 1,800, 280 total deaths, of those 280 total deaths, there was 35 sudden. The five-year incidence rates of death was 2.4% for sudden cardiac death. It's quite low. This figure actually demonstrates freedom from total events, death and transplant, and you can see this is sudden cardiac death remains quite low. At the time of presentation, they created risk factors for sudden cardiac death, which included LV end-diastolic posterior wall thickness, age of diagnosis being younger, and use of antiarrhythmic medications. Unfortunately, ICD, ECG, and Holter data were not used in the analysis. They also created a PCMR regression tree looking at risk factors available at follow-up. The patients who had an LV end-diastolic dimension greater than 2.6, younger patients less than 14, and this finding of LV posterior wall thickness to end-diastolic dimension ratio, which is an index of ventricular remodeling, meaning thinner is worse, had a sudden cardiac death risk incidence of 4%. This is another study that's used for our guidelines, I think the other largest cardiomyopathy registry from Australia. It's a longitudinal cohort study that diagnosed children less than 10 years of age, which included 300 patients with dilated cardiomyopathy. Of that, only 5.5% experienced sudden cardiac death with a cumulative incidence of sudden cardiac death of 5%, which was lower than other cardiomyopathies seen in the study. Risk factors in this group included older age of diagnosis, though they were diagnosed under the age of 10, so 8.6, a positive family history of cardiomyopathy, and then findings of LV dysfunction, including LV end-diastolic dimension Z-score of 5, shortening fraction Z-score of minus 9. If there was recovery function, there was no sudden cardiac death seen. We are limited. We do not have a lot of studies that have yes-no ICDs with cardiomyopathy, pediatric dilated cardiomyopathy. This was a nice study reviewing a large database from patients awaiting transplant. Of the 5,000 subjects, about 16,000 had dilated cardiomyopathy. Of those, 11% had an ICD at the time of the study. What they found is that dilated cardiomyopathy was associated with a lower sudden cardiac death risk, and ICDs were not associated with decreased sudden cardiac death. So in the ICD group, the incidence was 0% versus non-ICD group, which was 2.2%, which had a negative P value of 0.6. That leads to our guidelines from 2021. Class 1 indications are very similar to the adults, survivors of sudden cardiac arrest who've experienced sustained VT, or due to—sorry, I'll rephrase that—survivors of sudden cardiac arrest or who have experienced sustained VT. And then the Class 2b indications are similar as well, where ICD can be considered in patients with non-ischemic dilated cardiomyopathy and syncope, or an LV ejection fraction less than or equal to 35%. So the rest of the talk, I was going to move—discuss a little bit some future directions, other factors that we may look into over time. Cardiac MRI in adults with non-ischemic dilated cardiomyopathy have been helpful to evaluate for myocardial infiltrative processes and evidence of scar. They've been shown to be associated with ventricular arrhythmias and a substrate for VT ablation based on typical anatomical locations. Delayed hyper-enhancement has also been associated with worse outcome in sudden cardiac death. There's been meta-analysis with increased mortality, heart failure admissions, and sudden cardiac death. Also annual sudden cardiac death or aborted sudden cardiac death was 6% in those with LGE positive compared to only 1.2% in LGE negative. And there's ongoing adult trials looking at cardiac MRI and outcome. Next, genotype and risk of sudden cardiac death. This was an adult review of almost 500 patients with dilated cardiomyopathy. About a third of them had either likely or pathogenic mutations. You can see the mutations in the slide. Sudden cardiac death, VT or VF, and variant positive patients trended towards a significance which you can see in this figure. And then specific genotypes such as laminopathy have the highest risk of sudden cardiac death, VT or VF, which you can see in this figure here. Lastly, I'm going to talk about goal-directed medical therapy. In adults, goal-directed medical therapy with these four pillars of therapy have demonstrated reduction of mortality. Unfortunately, only used in about less than one in five adults, but has been shown to increase mean survival by six years. Improved LV function has also been shown to decrease risk of sudden death. And we need future trials of the current medical therapy to allow us to understand what the true risk of either mortality and sudden cardiac death is with appropriate therapy. So finally, these are a bunch of pediatric and adult risks that we went over, including clinical risk, imaging of echo and MRI, some electrophysiology markers I didn't include, but there are single studies that look at QRS duration and QRS fractionation that do show risk of sudden death. I think it's unclear regarding non-sustained VT. EP studies we also demonstrated. Genetics and goal-directed medical therapy. I think the future directions are if we can better risk stratify. Obviously we're trying to stratify a very low risk compared to actually what we saw with the other study of annual risk of four to six percent. We're talking about probably a 0.3 percent risk per year. If we could better understand individual risk, that would be really helpful for shared decision making for primary prevention ICD therapy. Thank you very much. Thank you. Any questions? Well, while people are sending questions through the portal, I have a question for David. Do you routinely employ cardiac MRI in your dilated cardiomyopathy population? Do you use quantified MRI, et cetera, in your center? Is this on? Yeah. For full disclosure, I don't primarily see the cardiomyopathy patients myself. I do think they utilize cardiac MRI quite frequently, though. I think it's rare that we're using LGE as a direct indication for ICD, but I think what we have in pediatric cardiomyopathy is we use all these risk factors that don't actually exist and put them together. If you had a patient who had LGE positive and non-sustained VT, that probably could push us over the edge of ICD. I do think that's an area, though, that would warrant further research, though, and is something that we should investigate as a pediatric group. Is there anybody in the audience using that in your center? Are they routinely doing MRIs in all dilated cardiomyopathies? I guess many people here are pediatric EPs. Do you get referrals after an MRI or not at all? I see Carolina shaking her head. No? Okay. Yeah. All right. So we have some questions here online, and I sort of pose it to both of you, but Dr. Koyek, I think these might also be directed towards you, so it's sort of, I guess, twofold. So considering the sudden cardiac risk scores mentioned, are EP studies mandatory to indicate an ICD as indicated? And then, I guess, the second part, and maybe both of you can answer this, how much of a risk of sudden cardiac death is required before an ICD might be implanted versus drugs only? So what is that number? Very interesting questions. About performing an EP study, we know that Paul Kyrie, he has published a few studies where positive EP study in Tetralogy of Fallot patient was very predictive for sudden cardiac death. So in Tetralogy of Fallot, it is actually being used for risk stratifications. But I also know that, I'm not sure if everyone knows, but Professor Zeppenfeld in the Netherlands, she does a lot of VT ablations in patients with Tetralogy of Fallot. And some of her studies and her ideas are more like, if you do the EP study, if you are able to ablate the substrate in the RVOT in Fallot patients with a good LV ejection fraction, you don't necessarily need to implant an ICD. So her studies are very suggestive for that. Regarding the other defects, I'm not sure. I think the data is very, very limited. We don't standard perform an EPS in our congenital cases. So I don't have the answer for the other defects in adults. And the second question, what is being considered as high risk? So in our own investigation group, we considered an annual risk of 3% as a high risk because of the relatively young population. So when you look at the mean age of ICD implantation, most patients are in their 30s. So they are very young. So I think the threshold for implanting an ICD should be a little bit lower than acquired heart disease. In acquired heart disease or in inherited diseases, the threshold is around 5%. But our group, we thought 3% is high enough if you look at their age. Yeah. That's interesting because in the HCM literature, as you know, 6% over five years is considered high risk. Whereas you're quoting something like 15% over five years. So it's, I mean, none of us know the real truth. Here is another interesting question from the audience. What are the panelists or the audience doing with non-sustained VT in pacemaker logs? We see this so often and don't know what to do with it. What was it? Non-sustained VT in? Yeah. During routine pacemaker logs. Oh, right. And device interrogations. So in our own risk score model, non-sustained VTs didn't come out as a risk factor for sudden cardiac death. So when we consider an ICD for primary prevention in our own population, we don't do nothing with that. Do anybody in the audience, do you want to comment on how you might treat that differently? This should be interactive. We want you to participate, friends. I guess a similar question would be if you see non-sustained VT on routine monitoring in a dilated cardiomyopathy patient. I think if they are not, so I suddenly remembered that I published a study a long time ago where we actually, it was a technology of a low population where we actually looked at the non-sustained VTs and we found out that if they were completely asymptomatic, that the risk of sudden cardiac death was low in that population. But if they were symptomatic, that meant something. It's like if you have very fast non-sustained VTs and patients get disease spell or collapse because of that, you consider an ICD as well, right? So I think the symptomology plays an important role. Yeah. Fantastic. We've got two minutes. Oh, go ahead. The risk question from before is interesting as well because based on the sudden cardiac death risk, it's about 0.3% per year. And our recommendations are the same as adult dilated cardiomyopathy. So it's quite low and it's unclear what the benefits may be. We have two minutes left in our session. Any final comments or questions? Does anybody in the audience do EP studies in complex congenital heart disease patients to stratify? Andy? Do you want to come to a microphone? No? Would you, do you mean like a standalone or what if they had syncope or unknown like loop recorder versus an EP study? Yeah. I mean, I do EP studies that aim to see if I can ablate intents most often. And then if they're positive, depending, I use Paul's risk score and if, depending where they score, if we're successful, we wait and retest again six months later. If we're unsuccessful or if they have, you know, whatever the case may be, then they would be a candidate for ICD. And is that in a tetalogy of fallot patient or every? For TETs. For TETs. Only for fallot? Yeah. But TETs, you know, I feel like we, we have at least some kind of guidance on tetalogy. The patients who I struggle the most are the mustards, sennings, and the fontans. Yeah. Paul also did a study which hit me pretty hard that showed mustards were dying more of atrial arrhythmias than ventricular arrhythmias and beta blockers were highly protective. So I take that to heart as well. So I don't know what to do in a lot of the patients and still, I think a little bit of a black box as to how strong the models are and where to go. So I want to find out more. Thank you, Andy. Well, thank you everybody. This has been a great session. Thanks for staying till this, this late. Thank you.

Heart Rhythm 2025

genetic heart diseases

sudden cardiac death

congenital heart defects

dilated cardiomyopathy

channelopathies

risk assessment

ICD implantation

cardiac MRI

personalized care