San Diego, and Heart Rhythm 2025. It's the 46th, and I think I was at 45, of these sessions for the Heart Rhythm Society. So apparently, if you haven't already done so, please download the HRS mobile app from your preferred app store. And this is how you can participate in these sessions. I'm Susan Etheridge, and I work at too many places to actually go through them all. And I am joined here by Dr. AJ Batra, who's the co-chair. And we have a great lineup of speakers, so welcome, everybody, and thank you for staying for this evening's session. Thank you, Susan. Welcome, everyone. And really excited to be, you know, I just can't wait to hear these talks, because they are such great topics, and such great speakers. So, you know, these are gonna be really challenging cases, and there's oftentimes not a right or a wrong answer. But we, I'm hoping that it'll stimulate enough questions and discussion. We've also asked our speakers to kind of engage the audience by putting in audience response questions in there with real cases. So hopefully, that'll give an opportunity to engage the audience. And what we are asking is for questions that you have, either send it to your app for the, to the chat, and we'll try to do the questions at the very end of the four talks. So with that, the first speaker's gonna be Dr. Christina Miyake, needs very little introduction, or no introduction. She is at University of Texas Children's Hospital. And Christina, take over. Thanks so much, and thanks to the organizers. All right. So, if you wanna go ahead and scan your QR code. All right. So my goal today is gonna be to quickly review the 2025 AHA AC guidelines for CPVT and competitive sports. I wanna give you a couple of practical tips and important points when talking to and managing your CPVT patients. I don't have a time to go into all the details, so just briefly, as you know, it's the most lethal of inheritable arrhythmia disorders. And arrhythmias are provoked by adrenaline. So I thought it was important to understand some of the treatment targets. So as a review, adrenaline binds to the beta receptor, and that triggers the defective ryanodine receptor that has a gain-of-function change to release massive amounts of calcium into the cytosol. So your treatment options are going to be to block that beta receptor, to block the ryanodine receptor with fluconide, to do a sympathetic denervation to take out the neural adrenaline input, and then ICD, if you do have arrhythmias. And as you know, there's some controversy in terms of electrical storm. So really important in terms of trying to decide which treatment option you wanna do for your patient. So let's look at the 2025. These are brand new AHA, ACC guidelines, and they talk specifically about CPVT. So here's what they say. And it's broken down into three different categories. You're either asymptomatic or symptomatic or previously symptomatic, and you're either phenotype positive or negative. So if you're asymptomatic and phenotype negative, no inducible ectopy on a burst exercise stress test, it's reasonable to let your patient play sports as long as you've had some discussion and you wanna discuss whether or not you wanna do prophylactic treatment. If you're asymptomatic and you're phenotype positive, then there's shared decision making, and you can optimize therapies until you get normalization of your burst exercise stress test. If you're previously symptomatic and phenotype positive, then the recommendation is combination beta blocker and flaconide, plus minus a sympathetic denervation and normalization of your exercise stress test before participation. Now what does normalization mean? Ideally, the definition was no ectopy. However, if you have bigeminy, that may be acceptable, but couplets or non-sustained VT requires treatment intensification. In addition, the guidelines recommend you have an emergency action plan in place. All right, so this is a case, and this is Gabby. She's my patient. She's a 15-year-old. She's a former three-sport varsity athlete, and she was diagnosed after multiple syncopal episodes, all during sports activities. So you can see her baseline on no antiarrhythmics. She has isolated PVCs and bigeminy and a single ventricular couplet. On treatment with dual therapy, she's got zero ectopy. So my question to you, would you allow Gabby to return? No reservations. You would, but you don't feel entirely comfortable. C, no, you would not. Want to answer? Okay, let's see. I don't see any responses. Anyone? It takes us. Okay. Hurry. All right, so most of you would allow sports, some don't. So let's go on, and let's keep talking. All right, so there really isn't any guidelines in terms of how do you actually do this. And I just want to tell you, this is just one approach I thought might be helpful. This is what I've been doing. But it's not a recommendation, it's not a guideline. And I typically will change management depending on what I learn from my own evidence. All right, so take this with kind of that viewpoint. The first thing I do is I always, always get a baseline phenotype. I want to know what your rhythm is without any anti-rhythmics. I'm gonna do a burst protocol exercise stress test and a Holter monitor. Now what if I don't see any ectopy? I'm gonna tell you, that's pretty rare. I've only had two patients do that. There's two things that are gonna come to mind when that happens. Number one, am I dealing with CRDS? And number two, was that exercise stress test done in the morning? Why do I ask myself that? Well, this was a paper written by Yuki Asaki. And what she showed is that cardiac arrests and VT events tended to occur more frequently in the afternoon hours. In addition, exercise stress tests were more positive in the afternoon and negative in the morning. Now granted, this was 80 patients. This was maybe a biased cohort. But I do take this into consideration. And if it's negative the first time and it was in the morning, I actually always run them in the afternoon and try again. I actually have had some positive results. All right, so going back, you've done your baseline phenotyping. I've started medications. This is the point in which I actually talk to the patients in a shared decision making process. To me this means, and I think the guidelines put this really nicely, there's two experts in the room. You're the expert and you need to make the decisions based on medical management about the clinical decisions that are gonna impact your patient and how they may respond. The other expert is your patient. And they're the expert in terms of their personal values and what's important to them in terms of participating in sports and their risk. So remember that as you're talking to your patients. The next thing I do, and this is my own personal and granted, it's very variable what you're gonna do. But I actually limit or restrict sports for the first year, at least six months. And the truth is, as you're getting your patient ready to go back to sports, there's several things you need to do anyways. And this is what's going on in that time. So number one, I always make sure that the family and the patient have CPR training. Number two, I make sure that that patient has a personal AED, even if they have an ICD. Number three is that I recommend, or I make sure that they have an emergency action plan and that their sports, their coaches, their school, and their trainers are aware of it. Number four, I just bring this up because I do this with every patient. I make sure that they think about their mental health and that they think about having a counselor. I always recommend them having a counselor for someone to talk to. All right, now your patient's ready. They wanna participate in sports. I'm always on dual therapy, flecainide plus natalol. My typical goal is about 1.5 mgs per kg per day of the natalol, and then flecainide. I actually go for a goal level of this moderate to moderate high, 0.6 to 0.8. And then my recommendation, here's what I do, is I recommend a loop recorder. And I use it during this time. I'm watching them. Are you compliant? Do you have any breakthrough rhythm? Remember, these are teenagers. To me, the risk is that they're non-compliant and they miss their medications. So this is kind of me saying, here, you're showing me you can do this, you're compliant. And so that's the next step. So let's go over, here's Gabby again. So she had her exercise stress test. As you know, no ectopy. She's on treatment. Her flecainide level is 0.3. I recommended she go up on it. And she's fully compliant with medications. This is a girl who never misses her medication. Her loop recorder is implanted. She's about ready to go, and I'm about ready to release her for sports. And she's at a high school basketball game. She's just watching it. She's not participating. And she's walking up the stairs. And that's what her loop recorder recorded. So this is why I do it. And again, her flecainide level was on the lower side. So imagine if she's actually playing sports. Okay, so you know why I put the loop recorder in. I follow them. Now I'm gonna go back, and I'm gonna do my whole tour and my birth stress testing again, and make sure, thank you, that, see how their response is. And my, again, this is personal, I go for zero ectopy. And why is that? These are for the competitive players. Here's my patient. This is Tommy. He was well-controlled. Never missed his doses previous, or listen to what he told me. He ran on a stress test, and he had single PVCs. Well, this was Tommy just a few months later. Tommy was running from his house. He just ran to the gym. He wasn't actually participating in sports, and he had a full-blown cardiac arrest. He missed his dose. At that point, I wasn't doing loop recorders. But again, I do worry, if you are having ectopy, and you are compliant and on your full medication, what happens when you miss that dose? So, I do look for zero ectopy if I have a competitive player. All right, so then, they pass that test. The next thing I do is I go back to that shared decision-making, you know, before I release them. And here's the deal that I have. This is my sports agreement. I say, you miss one dose, and that's five days. No practice, no competitive sports, nothing. You have to make that. That's, you know, it's agreement between us, but you need to be in control of this. So, that's where we go, and if they pass all this, then I go ahead and let them play. But, what else? You know, here's another patient not playing sports. The patient is, you can see, playing some football. But you can see in the middle, he's in a VT. This was a beautiful paper written by Dustin Nash and Molly Shaw, really helping us understand that your treatment needs to be targeted not just towards sports, but other adrenergic triggers. So, this is video gaming. What about this? This is my patient. This is kind of a routine. Watch, you can see there's atrial tach, bidirectional VT, classic for CPVT. But importantly, when you get your Holter monitor back, when is it occurring? That's one o'clock in the morning, all right? So, I'm gonna tell you that this is something I have a conversation with every single time my patients that are either going into the teenagers or they are teenagers, I talk about this with them. And I tell them, I'm really real. I understand this is real life. I understand what, and this is reality. So, I talk about this, I do my counseling, and I say, here's the deal. You miss one dose, you're not having no sex, no play. And so, that's just something I just wanna bring about. This is not sports activity, but it is activity that can be dangerous. In summary, this is a dangerous, lethal disease, whether it's competitive sports or other forms of play. Being an active participant in your patient's care is critical in knowing those triggers that can induce arrhythmias. Counseling and shared decision-making is key, and the information provided today is only one opinion. And with ongoing evidence-based data regarding how to manage our patients, I think in competitive sports will continue to help in the future. So, thank you. Again, we're gonna take questions at the end. So, the speakers are all staying up here. I'd like to introduce the second speaker, Dr. Joseph Otawa, who is at the University of Alberta in Edmonton, Canada. And in fact, from now forward, everyone is a Canadian. And Joe's gonna talk to us about, would my patient benefit from a sympathectomy? Good afternoon. Oops. Thank you to the organizers for the opportunity to present. There we go. As Susan mentioned, I'll be talking about sympathectomy. And as discussed with the chairs, I'll focus on the role of sympathectomy in patients with CPVT. Do you need to scan the QR code one more time? All right. And I'll be covering the listed objective for the presentation. So, I'll start with two cases, no secrets, both put forward for sympathectomy and trying to address the title of the talk, if there would be good candidates. So, the first case is that of a 19-year-old young man diagnosed at the age of 10 years, having presented with arrhythmic syncope during exercise. And the initial stress test showed polymorphic VT. His course was significant for recurrent syncope, despite very good medication compliance, as well as diagnoses of non-progressive skeletal myopathy and learning disabilities. At the time of his last few follow-ups, he was having ongoing polymorphic ventricular arrhythmias in the form of non-sustained VT, on optimal medical therapy, as well as frequent atrial tachycardias of really all forms. His therapy was high-dose Nadelol for his weight, 60 in the morning, 20 in the evening, but no flaconite. He had developed convulsive syncope of unclear etiology twice when flaconite was trialed as a child and a young adult, and no improvement in his arrhythmia burden. His genetic testing showed an RYR2, likely a pathogenic variant. His baseline ECG, bradycardia, but otherwise normal as expected, and his stress test showed some ugly polymorphic VT, despite the medical therapy, and atrial tachycardias during peak exercise and recovery. His Holters showed similar stuff, and as you note, he has ectopy and atrial tachycardia even during low heart rates or low adrenaline state. Because he was somewhat unusual, we discussed him with one of our colleagues, Wayne Chen, who is an RYR2 expert, and described the phenotype and sent him the details of the variant. He had a mouse model with a similar nearby variant, and he described it to my simple non-basic scientist brain as quite a leaky RYR2, a little bit different than the maybe typical CPVT RYR2 channel variant. He thought that this type of variant would result in an even lower threshold for SOICR or store overload-induced calcium release, so more pointy arrhythmias with adrenergic states, but also is unstable in the closed state with calcium release at baseline, hence the ventricular atrial arrhythmias during a low adrenergic state. Moving on to the second case, it's that of a 39-year-old diagnosed at the age of 14, having also presented with arrhythmic syncope during strenuous activity, and initial stress test showed monomorphic VT. His follow-up, or his course, was quite tumultuous. Recurrent syncope, medication side effect, and a period of non-compliance, although not in the recent follow-up. Eventually, unfortunately, an aborted cardiac arrest, ICD implant, multiple shocks for polymorphic VT and VF. Also, of course, not of course, but unfortunately, lead failure and requiring lead extraction. At the time of his last few follow-ups, he again was also having ongoing polymorphic ventricular arrhythmias with non-sustained VT and optimal medical therapy. And for him, that consisted of high-dose bisoprol, because despite trying different combination of Nadelol, he was having significant side effects on high doses, as well as flecainide, but only 50 BID GI symptoms and chest pain at higher dose. His genetic testing showed an RYR2 variant, but it was labeled as a VUS. Baseline ECG also normal, and stress test showed also an unsustained polymorphic VT and bidirectional ectopy. So they were both put forward for left cardiac sympathetic denervation. I know most people are familiar with it, but just to make sure we all know what I am referring to, I'll just briefly review that it's a surgical intervention, video-assisted in most centers, that involves resection of the left sympathetic chain from T1 to T4, along with all the side branches. Now, going back to our patients, if we look at the different guidelines, yes, we can fit them into the guidelines. They do meet some indication. But the main question is, would they benefit? Do we anticipate that they will benefit? Is our clinical acumen good enough to know if they will? And we'll come back to that question. I'll just quickly shift gears and talk about the outcomes of sympathectomy in patients with CPVT. Most of the literature is that of case series, and case reports. However, there is one multicenter study that was published in 2015 that I would like to review. And I also wanna share with you a preliminary data from an ongoing study looking at the impact of sympathectomy on patients with CPVT, combining the registry, the international and the pediatric CPVT registries. And I'll show them side by side just because of the limited time. So for the published multicenter study from 2015, they had only 63 patients. The majority were symptomatic. Median age at sympathectomy was 15 years, and follow-up was just over three years. Complications post-sympathectomy were not reported in details. In the combined registry study, the preliminary data suggests we will have about 165 patients, 75% are probands, majority symptomatic, similar number. Median age at sympathectomy also similar, about 15. We still don't have the details of the median follow-up. And complications, minor and major, were reported in up to 22% of patients. In terms of therapy, all patients, as expected, were on beta, almost all were on beta blockers. But the distribution of patients on NADLOL was different between the two datasets. A much larger proportion of patients were on flecainide in the combined registry, at 79%, compared to 24% in the previously published data. And half of the patients had ICDs. This is a high-risk group. In terms of the indications for sympathectomy, the published multicenter study had a lower proportion of patients with avoided cardiac arrest, but a much higher proportion of patients with ICDs. This chart is a simple visualization of the outcomes of patients in terms of major cardiac events before and after sympathectomy from the multicenter study. And as you can see, a large proportion of patients, some of them were asymptomatic before, showed improvement post, with 41 having no major cardiac events. However, 13 or 24 patients had at least one recurrence post-sympathectomy, including one sudden death and 10 ICD shocks. And when the authors looked at the subgroup of patients who had symptoms on optimal medical therapy before sympathectomy, 32% of them had recurrence. In the combined registry study, the preliminary data suggests that symptom recurrence post-sympathectomy is about 15%. We don't have the sub-analysis details yet, but to come. Now, when looking at stress test data, what we have so far is that there's improvement in ectopy in about 31%, but worse in 11, and unchanged in 51% of patients post-sympathectomy. And finally, in the published multicenter study, the authors looked at variables associated with non-responders, and only incomplete left cardiac sympathetic denervation was identified, but that was the explanation in only five patients. We don't have that data, but that's one of the main objectives of the combined registry study. And for the sake of completeness, I'll share with you the only report I could find on the role of sympathectomy in calcicrestion Q2 patients, CPVT patients, and it's a case report of only three, sorry, case series, including only three patients, and they found that there was no benefit in terms of ectopy reduction post-sympathectomy. So back to our cases, and then here we have, there should be an option to vote. Who thinks that the first patient, the 19-year-old with a ventricular and atrial arrhythmias, including arrhythmia in low adrenaline state, that leaky RYR2 will benefit from sympathectomy? Should that show up on the screen, or? You should go to the next slide, maybe, try that. Oh, next slide. I see, okay. Okay, 58 and 42. And what about the second patient? The 39-year-old with a border cardiac arrest, RYR2-VUS, and still having lots of arrhythmias on high-dose bisoprolone and flecainide. 88% all right nice so 58 if I recall well for the first one 88 for this one okay let's see so the first patient had an uncomplicated sympathectomy main complication was mind numbness and at initial few follow-ups he showed a favorable response surprisingly to the point that the escalation of his nadolol was initiated and this is his stress test this is a peak exercise showing only PVC's but no more non-sustained VT however he continued to have atrial arrhythmias the second patient had a few minor complications small pneumothorax isletosis that seems transient and neuropathic chest pain that's ongoing however at first few follow-ups it doesn't look very good and his medications have remained unchanged his stress test has continued to show a low threshold onset of ectopy and an unsustained VT during peak exercise unfortunately so in conclusion left cardiac sympathetic denervation can be an effective antiarrhythmic therapy for some patients with CPVT however depending on how you look at it 15 to 32 percent may continue to experience significant cardiac events and the long-term effectiveness of sympathectomy remains to be determined and we hope to answer that in the combined registry study more importantly identifying characteristics associated with suboptimal responders or non-responders is still evolving so the surgical technique has been flagged and that's a modifiable factor however phenotype and genotype may play a role however that association with outcome may not necessarily be as obvious as highlighted in the two cases I shared with you and finally there's a low risk of major surgical complications but there's a notable risk of minor surgical complication including neuropathic pain that can be quite bothersome to patients and would be important in counseling so I leave you with this question what is your level of trust in sympathectomy for a patient with a classic ROR to CPVT persistent complex ventricular ectopy on optimal beta blocker therapy no history for border cardiac arrest and it's kind of graded so is it should it be done now only if there's recurrent ventricular arrhythmia on beta blocker and flaconide or do they have to have a cardiac event or only if they meet indication for an ICD you don't like sympathectomy rarely never or you love sympathectomy it should have been done before the beta blocker All right. Great. Well, thank you very much. Thank you very much. Our next speaker, never fails to humor us, Dr. Shu Sanatani from Vancouver Children's. Thanks, Ajay. Thanks, Susan. You set the bar a bit high. I won't thank the organizers. I'll thank Cara and Doug for letting me have a talk so I could come to the meeting. I have a few disclosures, which I don't think are relevant to this. Okay, great. Yeah, sort of a weird, weird title, weird topic. And we're going to try and cover them all. So scan your QR code if you haven't already. There are a few seats in the front if any of you are going to stay for the whole thing. We're going to talk a bit about the difficult decisions and going to provide a suggestion of a management. So thinking back to what you learn in medical school, you learn important things like how the nerves leave your neck and innervate your forearm. We spent about six weeks on that. And then we do a little bit of pharmacology. We looked at a lot of slides of rheumatic fever. And we talked a lot about Ashkenazi Jews and Tay-Sachs disease and things like that. So I was well prepared for my electrophysiology career. But parents don't ask you about that. They don't ask you about Tay-Sachs ever. They ask things like, what do you think this rash is from? And then can he eat pizza? And then most of the questions, though, are in this format and often from the dentist's office and say, can I extract Johnny's teeth at this strip mall where I work? And I have no qualifications in any sort of resuscitative science. And usually you have to put your name down to vouch for that. And there's not usually a black and white answer to any of these things. You're sort of damned if you do, damned if you don't. Probably one of the most common questions I get asked is stimulants. And stimulants has been a real sort of growth industry because everyone's on them. And that little sort of tiny erratum that appeared on page 62 of circulation never really got read by anyone. So everyone still calls us and say, can I use stimulants? So we wanted to focus a little bit on this theoretical concept of could stimulants accelerate accessory pathway conduction in WPW and in theory make your WPW worse. I just want to acknowledge Diane Atkins who helped me with a talk on this many, many years ago. And having come just from a talk of great women in EP, nice to see that she was recognized with a Lifetime Achievement Award from the AHA. And this is just some of the slides that she sent me and I wanted to keep them in their original color. We always just had yellow on blue. And that was sort of it. But back at almost 20 years ago now, the alarm was sounded embarrassingly in Canada. Health Canada took the first reports of some concerns. And really this was before the concept of fake news. But this really was probably the fakest of news. So this was a pharmacist who reported via a sales rep that a 10-year-old had died suddenly who may or may not have been on Adderall. And it was three or four years ago and they were on a soccer field. No idea if they were actually playing. And this sort of made it to the FDA quality review. So I'm just going to ask the audience here and hopefully this works. So I have no concerns about a qualified professional prescribing stimulants. I do not authorize. My approach depends. And I have concerns, but usually go along with it. And then a lot of you I think will sit on the fence and say, I don't know, it depends. So no concerns. Well, that's good. It's a very, very educated audience here. So we thought we'd do some science. And some of you may recognize Aliyah Arslanova, who's in our audience and also the first winner of our Rising Star Award. And she has done a tremendous amount of work modeling accessory pathways using pluripotent stem cells. And she has gone above and beyond. This was supposed to be just sort of a little side gig. Like clinicians often will ask scientists, hey, can you answer this? And then they disappear for three or four years. And then they come back and say, I've written 1,000 pages on this. And you say, oh, never mind. That patient died. And so she set up a very sophisticated model where she developed stem cells and matured them into cardiomyocytes, and then very accurately titrated the doses of methylphenidate and tamoxifen, and caffeine, and isopryl. Caffeine and isopryl were, of course, controls. And then using this technology that she can explain to you has layers. And that is very sort of imperceptibly moving and recording things, both conduction velocity as well as repolarization. So we're not going to talk about repolarization today, because we're just focused on conduction velocity. Now, I went down a real rabbit hole, which was quite deep. And I asked myself, what are accessory pathways actually made of? And is there anyone in the audience that actually knows, like with certainty? I know a lot of males will say with confidence that they do. But this is actually very hard to figure out, because all the old papers when people actually did dissections of this, they didn't necessarily characterize the cell types. So Aaliyah, in her thoroughness, studied both atrial and ventricular myocytes. And they are very different in their properties and their behavior. But she studied the effects on both. Now, as you can see, though, there was really not much effect on conduction velocity. So all the stimulants really did not affect conduction velocity at all in either cell type. Isoproteranol did impact conduction. And I think there was a poster about isoproteranol in WPW today. Caffeine, at the dose that is typically consumed, also did not have much effect. So basically, the stimulants did not have a profound effect on conduction velocity. Now, I appreciate this is a model. But it really adds to already a large body of evidence that stimulants are safe in our patients. And I don't know that we would use this necessarily to justify an ablation in someone who may not want that. On the topic of stimulants, Mike Ackerman and his group did report that there were several cases of sudden cardiac arrest occurring in temporal proximity. And this came up a few years ago. There was a clever article about red bull or red herring. But this one actually sort of made the lay press. Doctors advise caution as energy drinks may trigger life-threatening cardiac arrhythmias. And Mike very eloquently added this. A myriad of potential agitators could have contributed, including sleep deprivation, dehydration, dieting and fasting, QT prolonged drugs, postpartum, those kind of things. So I really like that term, agitators. And I'm going to borrow it and take it for my own. And I'm going to apply that to this concept. So Christina mentioned video games. And we were part of a series that reported several young people who presented with cardiac arrest while playing video games. And it is really hard to tell if there is or isn't a signal there, especially because many of the people that play video games are in their room for hours. They don't necessarily eat or drink and they're just sort of in this very active state of brain activity without doing much else. So it's almost like we used to be in Zoom meetings during the early days of COVID. And so what we found, though, is a disproportionate number had CPVT. So usually we think of CPVT as maybe one fifth or one quarter as common as long QT, if that. But here the numbers were reversed. So definitely something about getting your brain involved and the autonomic stress. So Mike was not entirely convinced by our witchcraft science. And so he very assertively said, well, in our 3,000 patients, this has almost never happened. But he did sort of admit that it was reasonable to counsel people not to go for many hours without drinking or sleeping to play video games. So I think it's some of the lifestyle habits that accompany this and those agitators that may be contributing. Now, of course, you're all here for the answer that I promised this morning to the roller coaster question. Some of you participated in a survey this morning, sorry, last year in a survey about roller coasters. So we don't actually know. And I will express that this is not examining the g-force and things like that. So like your arms being ripped out of their sockets and things like that. This is just magnetic fields. And so MRI machines, of course, have giant magnetic field strength and we can navigate that. Amusement park rides are a complete unknown. And there are signs all over amusement parks saying people with heart conditions shouldn't ride these rides. Interestingly, so one of the questions we asked is do you rely on any published data guidelines or resources regarding your recommendations? And 80% do not. So I'm just sort of curious whether it's that little black ball that you shake and it tells you, you know, not today or is it sort of the wind or you just do what Ed Walsh told you to do. Like it's hard to know what exactly what logic you're applying here. And so and then this slide really interested me. I can see the underlying diagnosis and then whether they, you know, whether they're a good patient or sort of an unlikable one. I couldn't understand that the gender thing though, like that there, so there was gender gaps everywhere. So, you know, 3% of these poor people are being discriminated against on roller coaster rides. Now are very capable and willing scientists volunteer to go to an amusement park in this state. And they snuck in with these devices and then put them in epicardial and typical shoulder locations. And then they rode a lot of rides which they enjoyed. And then they tried, you know, popular ones and fast ones and accelerators one. And then, you know, by the end of it, they were pretty, pretty scienced out. The bottom line though, is that there is almost no important magnetic field strength, even in the ones that use the very modern linear induction motors. So even those magnetic fields are very minor. So you're probably going to come to more danger, you know, having a lot of magnets in the kindergarten than you are going on roller coaster rides. So I think roller coaster rides are back in the list. Really clinically insignificant. So what do we do with all these strange questions? So there's almost never data. So we, like everyone, you know, we look to our phones and say, well, you know, AI says, and then we talk and Christina has already shown this. We talk about the safety plan. We talk about medication compliance, listening to your body, have a buddy and really manage those autonomic agitators. What we've learned over the years in all these cases is there's almost always a reason that the cardiac breakthrough events happen. And it usually, it's often some sort of autonomic conflict. There may be a missed dose that just makes your autonomic nervous system a bit more unstable. There's often this adolescent phase of stress and certainly nutrition, sleep and hydration. So we're still, I think, you know, compelled to keep gathering data and these weird esoteric questions. So thank you very much. Thank you, Shu. I'd like to introduce our last speaker. It's Dr. Kirstie McIntyre who comes to us also from Canada from QE2 Health Sciences. Thank you, Kirstie. She's going to speak about, I have it here. Sorry, sorry, sorry. Stopping beta blockers in long QT syndrome. All right. Let's see if the slides feel like loading. Perfect. Thank you so much to the organizers and to all of you for staying now that Shu Sanitani has told us what to do about roller coasters. That was really helpful, but he is a tough act to follow. I have no relevant disclosures for this talk, but I am an adult electrophysiologist, I guess, in contrast to the rest of the group. If you haven't had the code, here it is again. All right. So our goals for this last talk of the afternoon is to challenge some longstanding paradigms in long QT syndrome management and to discuss when a beta blocker may not be needed in long QT syndrome management. So what exactly is the clinical spectrum of long QT syndrome? We've probably all seen this before, but there's quite a lot of clinical heterogeneity in the long QT syndrome patient population. We talk about prolongation of the QTC. We certainly spend a lot of time teaching our trainees how to measure the QTC, but some patients with long QT syndrome have a very normal appearing QTC, whereas others it can be quite dramatically prolonged. We have some patients who spend their entire life asymptomatic, whereas others may have syncope seizures or sudden death, and we fear the dreaded TORSAD, which some patients may never have. And a lot of this fear stems back to the early descriptions of long QT syndrome, where it was previously reported that untreated asymptomatic patients with genotype positive long QT syndrome had a very high event rate, and that sudden cardiac death before the age of 40 was pretty common. So this led to lots of fear about long QT syndrome. But more contemporary data suggests that things might not be so bleak. So from Mayo Clinic, we saw that the mortality rate was actually quite low, especially in patients who were appropriately diagnosed, risk stratified, and had an appropriate management plan put in place. So what do the guidelines tell us about long QT syndrome management? Well, they pretty much recommend beta blockers for everybody. So there's universal beta blocker therapy recommendations at various strengths. So class 1 recommendations for patients with phenotypically penetrant long QT syndrome and QTC values above 470, or if they've had previous symptoms or cardiac arrest, but even in our patients who are asymptomatic with more of a concealed phenotype. And we've talked a lot about NADLOL today, and it's still the preferred beta blocker for long QT syndrome management, along with propranolol. Do we like beta blockers? Well, we do. They work. They reduce event rates in patients with long QT syndrome. So what's the problem? Well, how many of us have treated patients with beta blockers? Do they love them? Not really. So we know that over time, there is a rate of non-adherence with beta blocker therapy, and they're not exactly devoid of side effects. So there's fatigue. There's decreased exercise capacity. There's unusual dreams. They complain because their hands are super cold, especially if they live in Canada, where we have winter. They gain weight. Their asthma is worse. Their sexual dysfunction. So beta blockers can be very well tolerated, but there are certainly patients who feel like we've made them zombies. We've ruined their life. Even though we may have saved their life, we've ruined their life with beta blockers. And previously, if you documented yourself to be non-adherent to beta blocker therapy or you were intolerant to beta blocker therapy, that equaled escalation of therapy to a defibrillator or to left cardiac sympathetic denervation. No beta blocker? Well, we've got to do something, right? Because we will sleep better at night if our patient is protected. When we think about long QT syndrome, we spend a lot of time thinking about our high risk patients, our symptomatic patients. But there is a lower risk cohort. So asymptomatic patients do have lower event rates. They do have lower mortality rates. So who is this low risk patient population? We know there's genetic heterogeneity in long QT syndrome. So it stands to reason that there's clinical heterogeneity as well. So should we really be using this one size fits all approach to long QT syndrome? Probably not. And in 2003, things looked pretty bleak, right? It seemed like everybody with long QT syndrome was destined to die before the age of 40, right? Just long enough to procreate, but then it was going to have a very bad outcome. But we have a growing recognition that there's this cohort of patients that we've identified through cascade family screening, who may have more of a concealed phenotype, who are asymptomatic, where maybe we don't need to worry quite so much about these terrible outcomes. So it leads to the question, are we over treating some patients with Long QT syndrome? Are we making them tired? Are we making them gain weight? Are we reducing their exercise capacity? Are we making their hands cold unnecessarily? So that led us to describe intentional non-therapy in Long QT syndrome. And we published this in 2020 in Heart Rhythm. So what exactly is intentional non-therapy? Well, it's not nothing. So it's institution of appropriate preventative measures. So avoidance of QT prolonging medications, making sure that if they have vomiting or diarrhea, that they have an action plan in place, preventing fevers, and not discharging them from clinical followup. So keeping an eye on those patients. What it's not is keeping our beta blockers zombies on beta blockers unnecessarily. It's not adding nixilatine. It's not denervating them unless they actually have an appropriate indication for denervation. It's not implanting an ICD as monotherapy for Long QT syndrome or implanting a pacemaker. So what happens when we go with a beta blocker-free strategy? Well, we looked at 661 patients with a diagnosis of Long QT syndrome. And of those, 55 asymptomatic patients were managed with an intentional non-therapy strategy. And it was a good split between men and women, about 50-50. And what we found is that patients tended to do well if our cohort included asymptomatic patients with lower QTC values who were older at the age of diagnosis. And the vast majority of our patients followed with this intentional non-therapy strategy had type 1 Long QT syndrome. And what happened? They didn't die. So none of the patients treated with an intentional non-therapy strategy experienced a Long QT syndrome-triggered event over over seven years of followup without a beta blocker. So when will I consider intentional non-therapy? They've gotta be asymptomatic. I prefer it if they have type 1 Long QT syndrome. I like it when they have more of a concealed phenotype. And I prefer them to be older age, which would include men over 18 or women post-menopause, reflecting the fact that we know that in general, pre-pubertal males have higher risk, but that tends to transition at puberty, whereas women post-puberty seem to be at higher risk. So this is my patient population where I will consider going beta blocker-free if they really can't handle beta blockers in their lives. So I think it's really important that we challenge old paradigms in Long QT syndrome management. And remember that there is this low-risk cohort in which a therapy without a beta blocker might be appropriate. That doesn't include our high-risk patients. You probably do need an intentional form of therapy, but you can't forget about the careful assessment and risk stratification in this patient population before you engage in this type of decision-making. And we can never forget the overarching principles of Long QT syndrome management, so avoidance of QT-prolonging drugs, for example. And here's some scenarios for you. So who would you consider for non-therapy? We've got an asymptomatic woman with Long QT type 2, QTC of 510. We have an asymptomatic 52-year-old man with type 1 Long QT syndrome, QTC of 460. Yeah, it's kind of a gimme, right? But it's worth having the conversation and thinking about with our patients. Thank you so much. So we'll take questions from the audience, but also questions from the computer if anybody has a question. Yeah, I think we have like 40 or 50 questions submitted already. Thank you very much. Yes, that's great. It's very engaging. You know, we can breeze through these and kind of some of them may be just yes, no kind of questions. Is that okay and we can alternate? So Christina, since you were the first speaker, a lot of them are directed for your talk. First question is, thank you for a wonderful talk. Appreciating the controversy, what is the opinion regarding the placement of an ICD for CPVT? Thanks, actually, I don't know if the question is in regards to sports or just in general. I think the most important thing is that it's really important that you take each individual patient into consideration in terms of that decision. For me, I do place ICDs. It's in patients who are non-compliant. So for example, I'm gonna try my best to get my patient through the early teenage child years. I do not put an ICD unless there's a, you know, they're having some event, but I've never had that specific problem unless they're a neurocardiac. That's what, a neurocardiac CPVT, I actually do put ICDs in. If you're a straightforward CPVT, ryanodine receptor, you don't have the neurologic phenotype, then I will try to get you through to the teenage years and then I'm gonna look for your compliance. So I have a patient, for example, and he kept having on his loop recorder multiple events. He would say, ah, I was doing my, I was drinking the other day, I forgot, but we spent the night at my friend's house, and then we sit down and we have a conversation and I say, listen, buddy, I'm really worried about you. I'm worried that you're going to forget one day and your mom's dead, your aunt's dead, you know, your grandma's dead, and they all died in their mid-20s, and you're 21, so you have that real conversation. So anyways, I think the point is it really is individualized. I absolutely will put them in, but it depends on that patient, and non-compliance is the most important thing, and I use those loop recorders in my practice to try to see if they are a compliant or non-compliant patient. I'm sorry this is so long. Well, I would take my bed of lockers if I was in the room with you. Scare me. What are you doing at night? Nothing. So this last question, the next question's to Kirstie. For the low-risk long QT patients that are concealed during resting ECG, do you have a cutoff during exercise that would remove them from that category? It's a great question. When we did the paper in the first place, the QTCs, when we talked about the lower values, was for your resting electrocardiogram. So it did not discriminate between what you did on the stress test. So some of the patients with exercise stress testing would have the characteristic profile of QTC prolongation in recovery, for example. So they don't have to be completely concealed. Great. Next question. Are clinicians still admitting teenagers to the hospital for five doses and up titrating flaconide? I don't admit teenagers. You probably do. We still do. Do you, Kirstie, admit adults for flaconide? Yeah, we don't. That's a good question, right? Should we be doing it? I called Prince. That's how I found out I didn't have to do it. So Joe, I think this is for you. What do you think is the value of a bilateral sympathetic denervation? Yeah, that's, I think, a very relevant point. The data on it is definitely limited, and there probably is also publication bias. There are some published cases and series where the patients benefit, but there may be many out there who don't benefit. However, there are some centers and some small series published out there whose primary approach is bilateral. And interestingly, they spare the stellate ganglion on both sides when they do that. The other relevant part to that argument is from limited experience with MIBG scans, so MIBG 1, 2, 3 scans, looking at cardiac innervation before and after sympathectomy. Sometimes, despite a surgically complete sympathectomy proven by a pathology specimen and side effect, ptosis, and all this stuff, there remains significant innervation of the heart. So some patients may have many more crossover fibers than we appreciate and would benefit from advancing to bilateral sympathectomy or primary approach with bilateral sympathectomy. Hi, Kara Motunaga from Stanford. Thank you very much for the talks. This one's for you, Joe. Kind of similar to what you were just talking about. Have you ever, or I'm curious, if you have other experiences or if you have thoughts on re-innervation. So let's say you do a cardiac sympathectomy and it seems very effective, and then maybe years down the line, you start to see signs of some arrhythmias again. So I have a four-year-old who presented with a cardiac arrest. We did, he was CPVT. We did a sympathectomy. He was clean, like no PVCs, no arrhythmias until he was about 12 years old, and I exercised him every year from the time he could do an exercise test, and nothing until he was about 12. He started showing some PVCs, and then, so I just escalated all of his medical therapy, but it was interesting, because he had just nothing for all those years, and then all of a sudden, he started showing. Another excellent kind of perspective on this. I don't have a personal experience with it, but I've looked into it a fair bit, because if you read the articles, and most of it, you know, led by Peter Schwartz, there's a strong argument describing that this is a pre-ganglionic denervation. There should not be re-innervation, but actually, there is enough data and literature that suggests that may not be the case. One of them is a cardiac surgical series where they looked at patients who have had, if I recall well, a mitral valve work and aortic arch work, and in the aortic arch surgery, you are more likely to damage the nerves than unlikely in the mitral valve repair, and they did MIBG scans before and after and showed that those who had arch work had some denervation, but that came back later on. So there is probably reason to suspect that yes, some patients may have re-innervation, whether it's that direct re-innervation from the left chain or take growth or innervation expansion or progression from the right chain, I'm not sure, but that theoretically can happen based on what's out there. Yeah. I'll just maybe make a comment as well. I'm sure people have heard me say when I was in medical school, the sympathetic nervous system and the parasympathetic nervous system were just like a seesaw that went up and down, and one went up, the other went down, and obviously, that's not true. There's co-activation, and I think 10 years from now, we'll also realize that just cutting some nerves doesn't totally fool your heart for a very long time, and there's a local autonomic nervous system that develops. We see it, of course, in our heart transplant patients who develop fairly good heart rate variability with the years out of transplant, so I think there's more to learn in this space. Yeah, I completely agree, and even when it comes to the actual diseases, I think I was telling Susan, you talk to these basic scientists, and you realize your kind of generic understanding of the Ryan Dean receptor and its malfunction is very superficial. They understand that there are different levels and there are different layers of the impact of the variances is different among its location along the receptor, and the phenotypes sometimes tell us or give us a hint, but I'm not sure we always read into it or are able to read into it. Okay, there's a couple of pacemaker and ICD questions probably towards you, Shu. One, why do you consider pacemaker dependence with no underlying rhythm during sensitivity testing when counseling for roller coasters? And I'll give you the second question, too. You can answer that. In CPVT patients and severe ADHD who have failed non-stimulant medications, would you consider clearing for stimulant therapy options? Sorry, could you say the first one again? If they're pacemaker dependent and roller coasters. Okay, so ignoring the sort of the other aspects, you know, the G-force and the bars and things like that, I don't think the magnetic field is impactful. I also think that our concept of pacemaker dependence is based on us trying for about 10 seconds in the hospital clinic to get an emerging rhythm, you know, faster than 30. But I think all of us have experience where, you know, an infant or a young child has fractured their lead two months before they come into clinic, and so almost everyone has an escape rhythm. It's just, you know, what does it take to emerge and things like that. Maybe a roller coaster. Perhaps. So the indication for pacing and all that doesn't make a difference to me. So you let them go on a roller coaster. What if they come to you and say, can you write a letter that I can go on a roller coaster? My letters are very standard, and I don't get into the weeds and the specifics. We're not super litiginous up there, so I can say things like, you know, treat like a normal child, no activity restrictions, no special precautions. And that's sort of our starting point. So yeah, we don't have a lot of people saying, you know, I need this letter for Disneyland or something. But, you know, like Make-A-Wish, for example, when these kids go on their wish trips, they will often ask, you know, are there restrictions on what they can do and things like that. So we do do some paperwork. And the second one, the CPVT and similar medications? Yeah, that's a harder question. We've had a couple of kids, and the reproducibility of the stress test is not 100% as we know. And so we're very encouraging of looking after their mental health. You know, I think several of us, Christina especially, are doing research in the space that shows if your mind is really scrambled, that's probably pro-arrhythmic. So we want to treat their mental health and their learning challenges and stuff optimally. But I have seen, you know, the stress test seems a little worse with the addition of the stimulants. Not enough data yet for signal or concern. I think it's something we're gonna look at. We're really kind of entering, you know, full feet, you know, jumping in with both feet and looking at the neurophenotype and that. So hopefully we'll have more answers in a year or so. Audience question. Hi, Rohan, Nationwide Children's. I'm gonna be brave and ask my question online, not anonymously. For a teenager with CPVT who has had a cardiac arrest and is now managed well on medications and has an ICD, would you then allow that patient to play sports if sports are literally his whole life? And follow-up question, if not, but he still wants to remain healthy because dad's a trainer or whatever, not that this is a specific situation. What sorts of gym activities do you feel are like specifically safer within the context of trying to lead a healthy lifestyle? I think that any of your, to be honest, I think any of your CPVT patients could potentially have an arrest. And, you know, sometimes we pick them up when they've just had syncope. So I would take that patient into consideration, but honestly, have a true, you know, heart-to-heart conversation with that person and say, are you willing to take the risk of having another event? That patient has an ICD, though, right, your patient? So my personal is yes. If they came to you and they say, I understand, Dr. Miyake, and this is what my patients say, I hear and understand what you're saying, I understand that sometimes the ICD is not protective and you have your other AED there, but I wanna do that, then yes, I would. I would, like all the other, you know, all the points that I made, really be on top of making sure that they don't have any rhythm and having them do exercise on your stress test and make sure that, you know, they're clean. What other, if they don't wanna do other activities, I don't know that I would have any specific limitations, to be honest. I let them go on the stress, I let them run, but I make them come in for the stress test to see that they're beta-blocked and they're not having any rhythm issues. So if you're gonna let them play on sports, I think you can let them go on the treadmills. The other alternative is to just tell them to keep their heart rate down, so that's the other approach I used to do before all this. Just keep your heart rate under, you know, 150. The truth is, they can't get their heart rate up, so it's usually under 120. And then the other thing, sorry, I always go, the other thing I do, it's really personal. Look at your patient, look at their stress test. Look to see what their peak heart rates are and then say, this is your goal. You wanna try to keep your heart rate under this if you're doing, and most of them won't, but. Sorry. I'd like to thank you all. I think our time is up and thank you very much for attending this excellent session. Thanks to our speakers, it was wonderful.

Heart Rhythm Society

CPVT

long QT syndrome

beta-blockers

flecainide

ICDs

sympathectomy

arrhythmia management

individualized patient care

cardiac conditions