I want to first start by thanking all of you for attending today. This is a discussion, I should say, because we're gonna ask for questions from you all as well. A discussion titled, PSVT Reimagined, Addressing the Challenging Journey. And I want to thank the folks from Milestone Pharmaceuticals for sponsoring this session. My name's Todd Valines, and I'm going to get us started off. I am a cardiologist at the University of Virginia. You can go to the next slide. I'm a cardiologist at the University of Virginia, professor of medicine, and a vice chair for the clinical services at our division. And I'm really pleased to be joined by two just experts in the field who know so much about PSVT, both in the emergency room setting and in the longitudinal care setting as well. So I'll let each of them introduce themselves. My name is Kathy Wood. I'm from Emory University. A long, I guess, 18, 20 years, I guess, in EP with AFib and SVT patients. So it's really great to be here to talk about the journey that patients go through. I'm Charlie Pollack, a proud alumnus of Emory University. I am an emergency medicine physician in practice for nearly 40 years, which means I've seen a lot of PSVT. And I'm currently in an academic position at the University of Mississippi, and I'm very pleased to be here with you at HRS. Well, great. Well, we're gonna jump right into this. These are the faculty disclosures. We'll just let you all take a brief review of those. And obviously, today's session, big thanks to Milestone Pharmaceuticals for putting this together. So these are our agenda and objectives. And so I think first and foremost, we want this to be educational for all of you. We're going to walk through, really as a level setting, just review SVT, talk about the diagnostic approach, and really focus on the patient journey. And this is something, this is maybe a topic that we don't talk enough about. I know in my own clinical practice, this is a disease that takes up a huge proportion of my clinical care, clinical time. And so we're gonna talk about the current standards of care, impact of SVT, both the symptoms and the treatment on patient quality of life, and hopefully get your questions. You can submit your questions using the HRS app. And so we will get those. We'll also, I think, have a mic going around. We can ask some questions at the end. And again, the objectives here are really to learn something, to be educational, and hopefully accomplish that, focusing, again, on the patient journey and the unmet needs in the management of patients with SVT. So we'll start with a brief overview. And I think at this meeting in particular, I think most of you are probably, like me, clinically involved in the care of patients with SVT. But I think it's important to go back and quickly review the subtypes. And what do we mean when we use the terms like SVT or paroxysmal supraventricular tachycardia, or PSVT? And so I think we're gonna focus, during this presentation, on both avenodal and atrioventricular reciprocating tachycardias. So these reciprocating types of SVT that I think many of you are very familiar with. These make up the majority, about 90% of the clinically relevant SVTs. These are, of course, the SVTs that end up, many times, going for curative ablation, EP studies, and can be a challenge to diagnose. And of course, this slide just reminds us how important the resting EKG can be, as well as any monitoring, whether it be ECT monitoring or other monitoring that identifies the onset and offset of these rhythms. Of course, the majority of patients have avenodal reentrant tachycardia, about 60% of these. And as you know, that this involves a micro-reentrant pathway within the AV node. And in these patients, we don't see resting pre-excitation, or delta waves. A smaller proportion of patients will have atrioventricular reciprocating tachycardia. This is a macro-reentrant pathway, involving the AV node as part of the circuit, but with an accessory pathway located in really any location around the heart three-dimensionally. And in these patients, of course, we may see pre-excitation or delta waves at baseline. We're not gonna focus a lot of our discussion on atrial tachycardia. So, just from terminology, we know that focusing on AVNRT, this can present as typical or atypical forms. And it's important for us to kind of understand this. Most patients, over 80% of patients, have typical, or what we call slow-fast AVNRT, where conduction goes down the slow pathway, as you can see in the cartoon, and then back up the fast pathway. And so, having an EKG in this tachyarrhythmia can be very diagnostic, or at least suggestive, of the mechanism, particularly in these patients. And so, in most patients, you won't see any atrial activity. The P waves are hidden in the QRS complex. Or, you'll see it just after the QRS, either as a pseudo-S or pseudo-R-primed wave. And of course, if you're doing intracardiac electrograms, or intracardiac electrophysiology studies, we've shown here your ventricular to atrial conduction times are very short. Contrast this with atypical AVNRT. And so, this is minority of patients. And these patients will have, typically, conduction down the fast pathway, and retrograde up the slow pathway. And so, this looks different on EKG. And so, you may see a non-sinus appearing P wave before the QRS complex. Or, in a very uncommon scenario, what we call the slow-slow atypical AVNRT, these are patients who have two slow pathways involving their reentrant circuit. And so, again, getting an EKG when patients are in this tachycardia, particularly the onset and offset, can be very diagnostic. Contrast that with AVRT, or you may hear referred to as Wolff-Parkinson-White. These are patients that have a circuit I've already described using the AV node in a macro-reentrant circuit. We've shown this here, this cartoon, that most patients are what we call orthodromic. So, conduction goes down through the AV node, antegrade through the typical conduction system, and then retrograde through the accessory pathway. And so, this is the majority of AVRTs. This presents as a narrow complex tachycardia. We also know, rarely, patients can have antidromic AVRT, where this pathway is reversed. Conduction is down the accessory pathway, back up, retrograde through the typical conduction system. And in this scenario, patients can present with a wide complex tachycardia. And so, important to distinguish these to different etiologies. Of course, clinically, they'll present often very similarly. And both can be treated with ablation. Now, this is just a reminder. I think, finally, an appropriate recognition of many of the sex-based differences in cardiovascular medicine. And SVT is no exception. And so, it is a disease that affects more women than men. You can see here that about two-thirds of patients who come to clinical evaluation are women. And this is not, overall, an uncommon disease. I tell you, in my own clinical experience, I was just in clinic yesterday with a patient who we diagnosed with SVT, who had had years of palpitations, and frustrating symptoms. And her statement to me was just knowing what this is is so relieving. So, this is a common disease, and it affects middle-aged patients predominantly. And so, because these reentrant arrhythmias generally start with ectopy, we know that things that increase ectopy will increase the prevalence of these arrhythmias. And so, we know that patients who are sick or ill, of course, will often have more of these arrhythmias. Patients who are hyperthyroid or have electrolyte imbalances or hypoxia. But, of course, common things, just stimulants, reduced sleep, nicotine, marijuana products, either inadequate physical activity or extremes of physical activity, as well as a number of other medications that are commonly used. And so, there are numerous triggers. I think it's important to point out that even without these triggers, many patients have come in with SVT and say, why did I have this? I can't, I'm not doing any of these things. And so, this is one of the frustrating challenges with SVT. So, I wanna start with, by asking our esteemed panel, this very diverse panel who practice in very different settings than I do, how do you describe SVT to your patients? And what advice do you provide patients to help them minimize episodes? So, turn it over to the. So, I listened with interest to my friend, Todd, describing the slow, fast, slow, slow, fast, slow. Patients always just tell me fast, fast, fast, fast, fast. So, the typical description from the patient is often coupled with anxiety, which is understandable. But they're always describing palpitations. If you push them about it, they can tell you that they're regular, which is an important distinguishing characteristic, particularly if by the time you're seeing them, the SVT is resolved, which is not uncommon. And so, when I'm describing it to my patients and trying to put some medicine behind their description, the first thing I do is say, look, this is not a killer heart problem. You know, this gets very bothersome. It can be very symptomatic. It can make you rush to the ER. It can make us give you all sorts of medicine. But this is not gonna kill you. And immediately, you see them exhale and express a sigh of relief. I tell them that there's something abnormal in the rhythm of their heart that, without warning, and sometimes without provocation, sometimes with, that'll be based on what they've told me about how this episode started, just starts racing. And it's incredible, really, how long it can last, but it often stops spontaneously. Sometimes it lasts until they get to the emergency room. When you say advice to help them minimize episodes, if there does seem to be a precipitating factor, we try to hone in on that. But it's sort of like when a patient comes into the emergency department with hives. You know, eight times out of 10, they can't tell you what they did or what they were exposed to that caused it. We just know we can give an H2 blocker and make them better. So, an H1 blocker and an H2 blocker. With this, you know, we have, right now, our primary armamentarium is a blunt instrument, which is adenosine, which, if the patient's ever had it, will often tell you that I'd almost rather have another episode of SVT than have to get adenosine again. So, we talk about, again, trying to avoid precipitants if they can be identified. Depending on the dexterity and medical fluency of the patient, I may talk to them about vagal maneuvers, which can be something as simple as giving them a syringe to blow into the business end of, or telling them to bear down if they understand that. And, you know, we know from the literature that vagal maneuvers sometimes help, but usually they don't. But at least it gives them the sense that they're doing something. And so, really, it's avoidance, and remember when it happens, that yes, you need to seek care, but you're not gonna die from it. That's great. Kathy, any additional thoughts? I think the pictures that you showed, maybe not to that detail, but a diagram is really helpful so they can understand the circuit where it's coming from, and tell them that something that happens, that there's nothing, everything that they think they can trigger, that could be a trigger, is not consistent. And so, I think that calms them down, as well as what Charlie said, it's not gonna cause a heart attack, they're not gonna die. And so, I think that reassurance is pretty important at the beginning. Yeah, so education, empowering the patient, understanding their disease, and some reassurance as well, because this feels terrible, this is a disease that patients come in with and they feel like, they oftentimes do feel, could I be having a heart attack, will I die, could I have some serious complication. All right, great. So let's talk a little bit about the diagnostic approach and the patient's journey to diagnosis. We know that there's delays between symptom onset and definitive diagnosis, sometimes averaging two to four years, although I'll say that's on the short side. We've had many patients that have suffered for seven, 10, 15 years trying to get a diagnosis for the symptoms that they're having. So we know that two thirds of patients reported visiting the ER at least once before they received a diagnosis of SVT, but yet the rhythm broke, and so they weren't able to document what was going on, so they weren't able to receive a diagnosis. And one out of four patients, only one out of four patients received a diagnosis of SVT via the ED. And this is probably because of the multifactorial situation in that the tachycardia lasts a short period of time, the symptoms are very different between episodes as well as among patients. And so there's no uniform symptom presentation, so the patients aren't sure if this is the same thing that was happening before. And then up to 50% of patients, it's diagnosed in the literature, has been misdiagnosed as anxiety, panic disorder, and then patients are not taken seriously with their symptoms when they don't have documentation of the episode. I remember one patient that we had was so excited after seven years with two different primary care physicians not being believed with her symptoms, she was finally referred to a specialist, and she and her husband were so disappointed when they got to the specialist's office and realized it was the psychiatrist and not a cardiologist. So that was really disappointing. And then the wide array of symptoms that we mentioned can also confound the diagnosis, not only during the SVT, but also after the SVT episode is over. So we know palpitations are common, but there's so many other symptoms like chest pain, syncope, dizziness, diaphoresis, nausea, and vomiting. So there is a gambit of symptoms that makes these episodes difficult to pin down for patients, and as well as providers with no documentation. And then post-SVT, patients talk often about the length of the fatigue after the episode stops. It can be up to four days that they feel exhausted and incredibly fatigued. Some can't even go to work. And the dizziness and the polyuria happens, according to patients, a lot more often than is discussed in medical textbooks. So I was assigned this topic because I have a 15-year-old daughter, and I understand the intoxicating addictive power of electronic devices because of that. Here, we're talking about things like watches, consumable wearables. They're obviously small devices that can be implanted medically to detect abnormal rhythm as well. But more and more, we see patients coming in and say, hey, I had that funny feeling in my chest again, and I was wearing my watch, and here's what it looked like. Well, depending on how long that episode lasted, you may or may not be able to make catch-your-tails out of it, because it turns out, when you compare it to a 12-lead ECG, if the episode of SVT is less than 15 seconds, the typical Apple Watch, I don't want to endorse anything, you say I'm wristless, watchless, Fitbit, Garmin, typically won't capture it, or at least it won't give you a meaningful rhythm strip. If, on the other hand, it lasts longer than 60 seconds, then the sensitivity gets up to as high as 100%. So the cut point is at 15, but the longer it lasts between 15 and 60, the more likely it is to register and give you something that you might actually be able to interpret if you can query the device and get a download. So you see the, I wouldn't make too much out of this, this is a study of 52 patients, so the fact that there's varying sensitivity among the devices, I don't think that's a valid comparison. Just in general, you can say the consumer wearables may be helpful to you, may be something you want to suggest to your patient if their episodes tend to last longer. The thing is, though, patients whose episodes last longer are more likely to have the rhythm when they come to see you, so maybe it's not that important. You see that the agreement, the specificity between the wearable device and the 12-lead ECG is quite high for the Apple Watch and less high for the others. Again, I'm not drawing any conclusions from that, but in these 52 patients, if the episode lasted longer than 60 seconds, the Apple Watch seemed to be pretty helpful in terms of correlating with the 12-lead. Now, Todd said something earlier about the importance of the resting ECG. Well, as you might imagine, as you probably heard at a meeting like HRS, there are deep learning models that are being developed to evaluate resting ECGs and look for things like nascent AFib or SVT. How it works, I'm not really quite sure, but you see all the different parameters that you can measure there, and I'm sure there's a whole lot more than that, QT, PR, QRS, rate, P-wave, T-wave, R-wave, whether or not there's a bundle branch block in the new input to patient's age and gender. There are, I'm sure, many more parameters you put into the model, but looking at a database of ECGs in sinus rhythm from over 9,000 patients, they applied this deep learning model to it, and they say that they validated it for identifying an abnormal rhythm in about 4,000 patients. So that's pretty good, that's close to half. And so at this point, I'm sure you're all aware of how quickly AI is developing and moving forward. At this point, we can't say that it can be used to confirm the SVT if you've got that patient who comes in with a normal or relatively normal resting ECG, but they're describing symptoms that sound like SVT that resolved before they got there. But in the future, it may be helpful in doing just that, or at the very least, it may help us re-stratify a little bit the potential benefit of putting in a monitor or even just putting patients on a holter. So a lot of, like everything to do with AI, a lot of promise yet to be realized, but a lot of really smart people are working on it and apparently burning up a whole lot of energy doing that. So we'll see what happens with it in the field of SVT. So the patient journey from presentation to ED, obviously the patient journey for probably 99% of patients with SVT involves the emergency department at some point. But if we can confirm the diagnosis or we can set up some sort of monitoring process so that hopefully the diagnosis can be confirmed next time, and the patient ends up eventually seeing a cardiologist and maybe that cardiologist is an EP or not, and so he or she is not, maybe there's a referral to an EP. Both of you have talked about the fact that this can take a while. If some of that is the limitations of our system, some of it is the vagaries of the diagnosis. But let's take that first question separately because the second one's quite different. Todd, what, I mean, tell me what your typical patient journey looks like when you're dealing with a patient with SVT or PSVT versus one that's maybe more atypical. I mentioned the patient I just saw in clinic yesterday and she had been evaluated with six monitors over six years. And we eventually made a diagnosis using a wearable device which was helpful, not one of the ones that's shown there, but as was mentioned by Kathy, many of these patients, if you go back and say, tell me when these symptoms first started, they'll tell you the most interesting stories. And they may be unreferred to psychiatrists, many of these patients have been misdiagnosed as having asthma very frequently. In fact, many of them have been on chronic therapies for their asthma. And they don't understand, in many cases, how could all this testing be normal, right? They've had echocardiography, some of them have had stress tests if they're older and had chest pain with their symptoms. And some of them have had some pretty extensive evaluations for ischemic heart disease. So it's highly variable, but I will tell you, it's very, very much the exception that a patient has had a symptom and had a diagnosis shortly thereafter. And so they've been either misdiagnosed or they've thought, am I crazy? I keep, you know, they've been to the emergency room, they go to see people like you, and half the time they get to the emergency room and they get told, you know, your rhythm is normal, your EKG is normal, your labs are normal. They stay there for some period of time and then they're discharged home. And so they start even questioning whether they should go in and see doctors anymore. And so that's kind of been my experience. And so I think we can talk about the next step is once we've made a diagnosis, of course, we know that ablation is exceedingly effective and for many patients. But as we know that many of these patients, maybe their symptoms are not that frequent or they're not interested in ablation, or they'd like to have a medicine at home that could abort their events without having to go get experience with this drug adenosine that you mentioned, which is absolutely, if you've had that or had patients who've had that, they never ask for it again unless they're really an extremist. So I think there's this big unmet need about either an invasive procedure or the emergency room. We haven't had a lot in between to manage them. Yeah, I mean, suppressive oral therapy, pill in the pocket, that sort of thing, hasn't worked very well for SVT. But as you say, as of now, there's really nothing in between an ED visit after vagal maneuvers fail, if they're even attempted, and ablation, except for adenosine. And that's if you catch the rhythm in the act. Otherwise, it's just a quandary. Kathy, anything to add? No, I think that's exactly right. It's just such a long trajectory to get diagnosed that the actual diagnosis is sometimes almost like a treatment. They're so relieved that they finally got a diagnosis. It really can be a problematic journey for these patients. So our second question here refers to the development of AI. I don't think we're there yet, although, Todd, you're at a big academic center. Maybe you've had some experience with it. But what about wearable devices? Have either of you encountered a patient who comes in saying, look, I got it. It's here. I'm not making this up. Yeah, I mean, I tell people, insurance won't pay for 24-7 continuous monitoring. These are oftentimes episodes that are unpredictable and sometimes not that frequent. And so like I mentioned before, patients have often worn monitors for periods of time and not seen anything. And so I mean, I'm all about finding any way that I can capture this. And so patient wearables, despite the limitations, which we all know with some data quality, right? But if you can use them in a patient who knows how to use them, then many times it can be very diagnostic. Now, I will say that just like monitoring, for every 10 times that a patient says, hey, look at this on my watch, most of it's noise. And there's a lot of just either noise motion or just common things like ectopy or very brief atrial tachycardia, which we see quite a bit. But it is allowing us to extend our monitoring period beyond just the formal event monitor. So I think it is helpful. And I've had some patients, particularly using the newer generation watches and devices like CardioMobile, which those are expensive, though. And so talk about health equity, right? Not every patient can afford to go out and buy those devices. But I think we're just hitting the tip of the iceberg on the wearable devices. So I think that if you ask that question three or four years from now, we'll, I think, all have a lot more confidence I'm hoping in those devices. Anything to add, Kathy? No. I think that we'll see more in the future. The cardi is a great gadget. But so often, the episodes are so short, by the time they've reached for it, the episode is over. So it's been very frustrating for patients. OK, let's switch to talk about the impact on not only the patient, but the health care system. This was a nice paper by Nordblom and colleagues that looked at the different ways patients' lives are being affected by SVT, from the actual fatigue and physiological symptoms to the emotional component, the worry about the unpredictability and the fear of, when is this going to happen? Where will I be? How am I going to handle it when it occurs? And therefore, their existential or inhibited existence as they withdraw, essentially, from social engagements, they stop driving. There's many adjustments that patients have to make so that they're not put in the situation that this may occur when they're driving or doing social engagements. Or if they find that a glass of wine starts it, then they don't want to go out with friends because the glass of wine could be a trigger. And the barriers that they raise in participating in social activities is due a lot to the uncertainty and the unpredictability of the episode occurrence. And then they spend so much time in identifying triggers. What starts it? What can I do to stop it? What works? What doesn't work? And they spend so much effort. But whatever they find, it's not consistently the same answer every time. So it's really frustrating for patients. And then following the diagnosis of SVT, once they do get a diagnosis, they often experience increased health care utilization. This is a nice bar chart looking at two studies that used insurance claims databases. And the navy blue is pre-diagnosis. And the light teal bar color is post-diagnosis. And you'll see across the board that post-diagnosis has more health care utilization significantly than pre-diagnosis. And you'll also notice in this slide that women have higher utilization than men, which offers another example of the sex-based differences that Todd mentioned earlier. And this was a really unique study that went back and looked at time of diagnosis and went back three years. So if you look at the left of the slide, that's three years before diagnosis, two years, one year, the year of diagnosis, and then two years after and three years after the diagnosis. And you see in the middle, that tall bar is costs of expenditures after they were diagnosed with SVT. You'd think, oh, well, that's because they're all getting ablated. That's the very top color, $4,280. And the huge portion, the $8,463 representation there, is the inpatient, which includes ER visits. So you see these people are flailing. They're going back and forth to the ER. They're being admitted for tests. And it's really so difficult that they have to go through all this when they've already been diagnosed. So to turn it back to the panel, since SVT is considered non-life-threatening, which is what you hear often explained to patients, well, this isn't going to kill you, so they're supposed to be OK with that. But it can be life-altering. And the symptoms do interfere with patients' quality of life. Do you have anything about that patient you saw yesterday that could add to this? Yeah, well, I will tell you that many of these patients, the patient I saw yesterday was a new diagnosis. But many of these patients have become tethered. In fact, the patient I saw yesterday asked me, I'm planning on going on a vacation. I'm planning on going to a rural area. And is that safe? Can I do that? For many patients, and this was a new diagnosis, but many of these patients have changed their whole lives around this diagnosis, even though you tell them this is not life-threatening. If they've had a sustained episode that has lasted a few hours, you saw the symptomatology from that. And or they've been to an emergency room and someone like Charlie has treated them, they're very wary about being too far from an emergency room or from an ambulance system. So going somewhere out hiking, I hear this a lot. I can't go off of cell phone coverage. I can't go to remote areas. I can't take the trip of my lifetime. And so they become really tethered to the health care system, knowing that they really don't have much else that can treat an acute episode, because vagal maneuvers don't work, and they've got adenosine, but that requires an IV and an emergency room physician. And so that's really the big unmet need and what I often hear. And of course, the patient I mentioned yesterday asked that very question. OK, is this going to kill me? Can I go on my vacation? I plan next month. Now hers was actually hers was a cruise to Alaska. But trying to, if we had, I think, therapies to empower these patients, I think it would be a real win for patients and those like us who treat these patients and all of you. Yeah, I think, Charlie, this next question is for you about treatment of SVT patients in the ED. If we had something that patients could use at home that would keep them out of the ED, how would that affect your patient flow? Yeah, well, I've done emergency medicine for so long that I can remember when we used to be happy when our volume went up, because that meant we were justifying our existence. Now, we have enough patients. It was that way before the pandemic. It's certainly even worse during and after. So if there's something that can be done in the outpatient environment that reduces the demand on the ED, that's important to us. And I would say that the case of a broadly defined cardiac emergency, that applies to even more, because that requires the immediate activation of a team of people to try to figure out what's going on. So a patient comes to triage, either from private auto or walks it up the street, or comes in by ambulance. And they say, my heart's racing, and I feel like I can't catch my breath, which is a pretty typical description by patients with some variations of the theme in SVT. That's going to get everybody's attention. We have core measures that mandate that an ECG be taken as soon as possible and then handed to somebody who can interpret it, assuming they're still in the rhythm. Then the other priority is going to be to get that patient into a monitored bed. Takes two nurses to get in there. One gets an IV started, the other is bringing in the med cart, maybe the code cart, depending on what the patient's blood pressure is. If the patient's hypotensive, they may well get cardioverted. If they're not hypotensive, then we're going to be getting that line started so we can give them something, typically adenosine, often two doses of adenosine to get them to break. And for a variable amount of time, probably anywhere from 20 minutes to 60 minutes, that patient's consuming a disproportionate share of resources in the emergency department. The other thing that's of interest is that we always try to, when we know adenosine is going to be given, we try to get as many trainees into the patient's room as we can so they can watch the effect of the adenosine. I don't know how many of you have given adenosine. Probably most of you in the room have given it or seen it given. And it's fairly typical for the patient to have a sinus arrest or a sinus pause when the adenosine works, if it's given properly. Very important. It's not adenosine taught, but very important that it's got to be given, push with a 30 cc or so, push the saline behind it. Because if it kind of dribbles in, it gets deactivated before it even gets to the heart. Because adenosine, as you know, is a very short-acting natural compound. So what happens typically is that about three or four seconds after that push of the saline, the ECG that was going like this goes like that. The patient turns very pale, says, I'm dying, or what's happening? Typically, the medical student has to lean against the wall so he doesn't pass out. And we all know that in 10 or 15 seconds, it's going to either basically go back into SVT or will have broken. As I mentioned a moment ago, in my experience, I would say at least 50% of the time, at least 50% of the time, we'll give a second dose. And the patient, of course, then develops a huge sympathetic tone because they know it's going to happen again, which, in my opinion, just makes it that much harder to convert the patient the second time. Occasionally, the usual dose is 6 milligrams, so the second is 12. Occasionally, we go up to 18, and sometimes even that doesn't work. But the patient persists in that rhythm, and the blood pressure is stable, so our options become kind of limited. But again, to get back to the spirit of the question, that has then taken up a whole lot of resources in the emergency department. And so if there was something that patients could self-administer, I mean, this is not, they may not identify it as SVT, but if they get that feeling again that they've had before, and there's something they can take that has a better than, certainly better than 50%, maybe even better chance of aborting that rhythm before they have to dial 911 or get a family member to come take them to the emergency department, that's a win for everybody. It's a win for the patient. It's a win for the emergency department that's not being stressed by that. And it's a big win for society and health care costs, because those ambulance rides and those ED visits are expensive, and somebody's paying for that. If the patient's uninsured, all the taxpayers are paying for it. If the patient's got insurance, then all the members of that plan are paying for it. So it's something that we would love to impact if we could. That's a great point. Just go to you. Yeah, so let's review. We've talked a lot about the management of SVT. Let's actually look at the current guideline standard of care. And so this is just reviewing the acute management of narrow complex tachycardias in general. And so we can see on the left-hand side of patients come in, as Charlie mentioned. Fortunately, the majority of these patients are hemodynamically stable. If they weren't, they would undergo synchronized cardioversion. We talked about using vagal maneuvers. All of the US guidelines give vagal maneuvers a class one level of evidence B. And certainly, that's something that we can try. In fact, we can train patients to do this prior to their coming to the emergency room. But as we'll review in a moment, these are typically ineffective. And so adenosine is our go-to therapy. This is, again, a class one guideline-recommended therapy. Of course, the challenges with adenosine you just heard. And in fact, I just want to reiterate what Charlie said, two things. Number one is you've got to give this the right way. Shown here are the typical doses for drugs used to treat narrow complex tachycardias. Adenosine, again, because it's metabolized by red blood cells and endothelial cells all the way back to the heart, you need to get it to the heart rapidly. And so it is a bolus followed by a rapid flush. And you can give six milligrams. And then if that is not effective, 12 milligrams after about one to two minutes. And if you're giving this, by chance, in a hospitalized patient with a central line, you would cut those doses in half. And if that's not effective, even after redosing, then we're really in a group of patients that's really challenging to treat. And so we would use typical agents to try to block or slow conduction through the AV nodes, such as intravenous calcium channel blockers or beta blockers. And so just a second reminder, when you're giving adenosine, please record the EKG while you're doing that. This is extremely helpful. And sometimes we see this in the rush of the moment. You forget to do that. But that can be extremely diagnostic as well, in just the small case that this is not a reentrant SVT or reentrant narrow complex tachycardia. Now, we've kind of beat up on vagal maneuvers. And I think for good reason is that they have a real variable efficacy. And when they work, it's great. If you've ever done this and this works, the medical students in the room will say, oh my gosh, that was amazing. I've never seen someone rub on someone's neck and abort a rhythm. But this is, unfortunately, not a super effective therapy. Even in provider-assisted vagal maneuvers, less than 50% of patients will convert. And when you look at patient-performed vagal maneuvers, and this includes even modified Valsalva maneuvers, abysmal results, less than 10% conversion rates. And this is what's been seen in even recent contemporary prospective randomized clinical trials. Now, one of the biggest challenges in treating patients with SVT is that you see a patient who has maybe one or two episodes a year. And so do you put them on a chronic daily heart rate lowering medicine that is often accompanied by side effects, beta blockers, the patients aren't clamoring to take those every single day for the off chance that they go into SVT. Maybe they'll have less symptoms and lower heart rate. Well, what about giving it to them and saying, well, if you go into SVT, take this. And you can see the real challenge here. The peak effect of oral metoprolol or a short-acting calcium channel blocker is one to two hours. And so you're taking a medicine for a short-acting effect that's really not a short-acting therapy. And so we really do not have currently any adequate therapies that actually can be taken at the onset of symptoms. In fact, guidelines, US guidelines give it a 2B recommendation, so not a strong endorsement. And in fact, pill-in-the-pocket use of short-acting beta blockers, I say short-acting, or calcium channel blockers is not even discussed in ESC guidelines. And so we really, we talk about unmet needs in health care. This is a big one. It's either adenosine or not much else that really works. And that's a real challenge. And so talking about reducing health care utilization, if we had something we could empower patients with that had an effective termination rate that they could take with them and put in their pocket or put in their purse and take with them on vacation, I think that would be a huge win. So if we review specifically patients who are in the non-acute setting, how do we manage these patients? Well, we know that highly symptomatic patients who have ADNRT, who are willing to undergo ablation, that's a class one recommendation. That's a slow pathway catheter ablation. But we know that in certain parts of the country, certain parts of the world, that wait times for ablation are not short. Or we know that access to electrophysiologists can be not optimal in some parts of the country. And some patients aren't really sure they want to undergo ablation just yet. And so that's a group of patients where we have this dilemma of, do we put them on long-acting therapies or try to give them short-acting therapies? And so this is a real challenge. Of course, if patients are highly symptomatic and do not want to undergo ablation or have had failed ablation, we oftentimes are considering some fairly toxic drugs in the sense of class one antiarrhythmics or class three antiarrhythmics, among others. And so a challenge in that perspective. If we look at AVRT, again, very similar. If the patient is willing to undergo ablation, that is a class one recommendation. These are patients with pre-excitation. But again, in patients without access to ablation, unwilling to undergo ablation, or perhaps pathways that are at high risk for complications, conduction system complications for ablation, we often do manage these patients medically in that scenario. And so for the panel, what challenges do you face in treating acute episodes of SVT? And I think a couple of questions within this are addressing what do you think of our current treatment options, such as chronic meds and ablations? And then how do we approach shared decision-making when talking with patients about those options? Just while we're talking about acute treatment, I want to emphasize something you said a moment ago, which is to keep the monitor running and the paper running when you give adenosine. Because it's really cool when the patient goes flatline. It's also really cool when it turns out the patient's actually an atrial flutter. And you block the atrial ventricular conduction, so you see the little picket fence P waves. But a much slower, you increase the block, so a much slower QRS complex. And that is diagnostic. So often it's hard to distinguish between the two, particularly in the emergency department where we don't have very sophisticated monitoring methods. But the challenges with current treatment options, ablation, I think, first of all, it has to be made clear that it doesn't work for everybody. Can't always find the pathway or whatever you need to zap or whatever you do to it. And of course, patients with inadequate access, inadequate insurance coverage, concern about invasive procedures, all those patients are not going to benefit from ablation. The chronic meds, I think, really comes down to how often the patient's having episodes. If they're having them regularly, of course, that makes a better case for ablation if ablation is possible. But if you're having them regularly, then you can justify the side effects that come from having patients on long-term beta blockers, especially. Calcium blockers, a little bit less. But patients get a lot of chronic fatigue. They have sexual function problems. They have depression. I mean, these are not benign drugs, even at low doses. So the chronic meds, I think, are not very helpful. I don't know that I've ever seen a patient, I haven't seen that many, who have been prescribed pill-in-the-pocket for SVT. But of those, I don't think I've ever seen one for whom it worked. So I don't think that's really a legitimate option either. So I think there's a real gap here in terms of what we would like to be able to offer our patients that currently approved medications and strategies and guidelines and recommendations just don't cover well. Well said. such as a pill in the pocket, that would be fast acting, it would make a big difference, and I think give patients a lot more confidence. Yeah, and that term, fast acting, I think there's a different definition than what I use. You know, as an ER guy, we want everything to happen in a compressed time frame, but, you know, fast acting in a patient who's extremely symptomatic, very anxious, maybe experiencing chest pain, scared to death, which of course, again, just drives up their sympathetic tone and extends the symptoms. But, you know, waiting 15 minutes for something to work is really not very practical. Yeah, and even the doses that we would give in the pill in the pocket are often inadequate for reasonable rate control, and so they take two hours to work, and they're probably not at a dose that's sufficient for any meaningful, you know, AV conduction block. That's a real challenge. The other thing is, there's a secondary question about shared decision making. Of all of the strategies we're talking about that are currently available, I think pill in the pocket is probably the toughest one to get patients to understand, because, you know, they may be hesitant to treat themselves, thinking, well, maybe this isn't what I think it is, or then they get frustrated when it doesn't work in 15 or 20 minutes, so they take another dose. I think it's really a suboptimal way to approach this, and so if you're going to consider that for a patient, and maybe after what I've said here, you're maybe less likely to consider it, but if you're gonna consider that, it takes a lot of patient education, and ideally, you talk to the patient's family member as well, who's typically with them if this happens again, because it's a very imperfect solution. Yeah, I think you'd like a medicine that is rapid onset, well-tolerated, and doesn't last for 12 hours afterwards. Exactly. All right. Yeah. Let's talk a little bit about the impact of SVT treatment on the patient's quality of life. Thank you. You know, I'm happy with any slide that has ED in the title. It's a big issue for us. You see 140,000 ED visits in the U.S. in 2019, and that's just with the principal diagnosis of PSVT, and Todd already told you that, or maybe Ken, one of you told us that only a quarter of the patients are actually diagnosed in the emergency department, so the actual incidence is probably much higher, and, you know, we're in a weird time in healthcare in the U.S. Patients are generally trying to avoid going to the emergency department when they have something that happens to them that makes them anxious, and then they get more anxious about going to the emergency department. It just, you know, it's a cycle that's really all-consuming for these patients, and so we're going to be seeing more of these patients when they finally give up and say, well, this isn't getting better. I'm gonna have a heart attack, so then they go. Maybe by the time they get to the emergency department, the rhythm is spontaneously broken, and we may be able to suspect it enough, or maybe we see something on the watch where we can make it a secondary diagnosis, but any time it appears on the ICD-9, excuse me, I'm throwing my aids here, the ICD-10 list, any time you see PSVT there, you can be sure that if you look back in that patient's healthcare resource utilization record, you're going to see more than you might expect for a patient of that age, that gender, and that level of comorbidities because of the PSVT. All of that, of course, is associated with higher expenditures. Healthcare resource utilization means more money spent, and again, somebody's paying for that. It's a societal burden that we all bear, and so again, I think, and I've acknowledged my perspective, and Glenn's been in the emergency department a lot, but otherwise, we're probably the only two who've ever actually worked in the emergency department. It's an incredibly expensive venue of care, so to me, the biggest impact of a potentially self-administered medication for PSVT that could abort an ED visit is something that, to me, that's probably the biggest both patient outcome, patient quality of life, and also economic outcome, so we, again, I'll point out, I think this is a big gap in our current armamentarium. We've talked about this already. Ablation's great. It doesn't work for everybody, but it works probably for the majority of people who have a diagnosed PSVT if they can get it, so what does that mean? Well, they've gotta be someplace where it's offered, and that's much more common in urban environments than rural environments. It's gotta be someplace where the patient, from a sociocultural standpoint, is more willing to undergo an intervention like this, and then, of course, have the insurance coverage to do it. That means that African Americans and other racial minorities, patients without insurance or Medicaid are less likely to get it. Interestingly, probably not surprisingly, patients with Medicare or who have private insurance are more likely to undergo ablation, again, if the stars align and it's available to them. You see, in the bottom left-hand corner there, ablation procedures by region. That's, yeah, I think, reflecting... First of all, I would've expected the Northeast to be the highest. It's not for some reason, because I think they do more ablations in Boston than they do in every place else combined, but anyway, it's not there. Interestingly, in the South, in this time period, nearly half the procedures were performed in the South, and that is typically, if we're just looking at a healthcare access map of the US, that's typically where access is the most limited, so it's interesting to see that happening. I don't know that we can infer much out of that statistic because it's really a specific individual issue, whether or not ablation occurs, but probably the take-home message from this slide is in the bottom right. Access to basic cardiac EP care has, not ED, but EP, has decreased over the past decade, which disproportionately affects communities of racial minorities, lower socioeconomic status, and residents of non-metropolitan areas, all those things we pointed out in this slide. So it all lines up, and again, it calls for the need for something that the patient can potentially exercise him or herself and either limit or really eliminate the need for ablation. If these things don't happen very often and there's something reliable they can take without even having to go to the emergency department, then I think they're much less likely to get in that queue for ablation if they're even eligible for it. So, Kathy, patients right now, for the most part, are dependent on visits to the hospital that are unscheduled, and how do you see that impacting their quality of life? It's just so frustrating for patients because, as you've said so many times, they go to the emergency room and they're in the parking lot and the rhythm breaks, or they get in and they're seen and there's normal sinus rhythm. So it's a really frustrating experience for patients, but they are dependent because they don't have any other way to treat their SVT. I think that if there was something that patients could use that they could use at home that would work more effectively than vagal maneuvers at home, it would be huge help for the patients as well as the healthcare system. Yeah, I think that word dependency in the question is very important. These patients feel very frustrated. They feel, particularly if the diagnosis hasn't been made, they feel invalidated, unvalidated, I'm not sure what the right term is there, but they feel like people aren't believing them, which is something that clearly has a negative impact on quality of life. And so we see that a lot with PSVT, particularly before it's diagnosed. And I'll turn to my cardiologist colleague for that second question. If you were going to define the holy grail of PSVT therapy, something that could be self-administered, what do you think it would look like? Well, I mean, I think we've mentioned it earlier, empowering patients, filling this unmet need, and untethering people from emergency departments. And so you'd have to have a drug that people can take with them. It's gotta be portable. It's gotta be stable, right? So that they can throw it in their purse and not worry about it breaking or not working or being unable to be administered. It's gotta be rapid onset, right? It's gotta be the onset to symptom relief. We would want to be within seconds to minutes. And it's gotta be obviously safe to administer and hopefully not so unaffordable that only the most wealthy in the world can take it. So I think if you had that right now, there's nothing right now that's currently on the market that gets even close to that, right? You need an IV or an adenosine, or you're kind of stuck doing vagal maneuvers, which we know don't really work. And so I think that's an exciting, potential in this field, right? Quite frankly, having something that you could give the patients that have met all of those criteria. I can tell you, thinking about the prevalence of the disease that we talked about, this is a common disease. It's a challenging disease to diagnose because palpitations and chest pain are common symptoms that have varied causes. But when you make that diagnosis, yes, you look around here, ablation keeps getting better. That's exciting. But having better medical therapies, I think, is something we ought to, as a field, be really excited about, too, in addition to better ablation catheters. So I think that's really something that, if you think about, there's not been new therapies that I can think of for PSVT during my, really during my career outside of the ablation world. I remember when verapamil was exciting. Yeah, that's right, that's right. So I think we'll start to wrap it up here, and then we'll see if we have some questions chatted in from the group here. Bring it all together, and in conclusion, there's a huge opportunity to address the clinical burden of the disease of SVT. We've talked about how it's often misdiagnosed, and then the huge delays from symptom onset to diagnosis, which further delay access to treatment. SVT adversely impacts patients' psychological well-being and increases healthcare utilization, not only for them, but for society as a whole. The need for treatment in an ED or other hospital setting further adds to the burden of the disease and the way patients feel tethered to the healthcare system. New pharmacological therapies are needed for SVT, especially in patients for whom ablation is not an option. They are not, they're living in one of those rural areas where they don't access ablation as easily, and they maybe have to have some time to think about whether they wanna undergo an invasive procedure, or in cases where the ablation has been unsuccessful. I think we'll open it up now for question and answers from the audience. All right. So, if you have questions, please raise your hand or speak up, and we've got some microphones. We've also got the app, I think, if you have submitted any questions using the app. Hi, thanks very much. Full disclosure, my name's David Beruch. I work for Milestone as the chief medical officer. Thank you very much. That was wonderful. If I could ask a question of each of the three of you, and I'll go in this order, just for reading right to left. And if I may call you by your first name. Well, the ED comes first, so it makes sense. There you go. So, Charlie, after a patient comes in with a clearly inscribed on the EKG SVT, it terminates with adenosine, with all the drama you described, the side effects you described. What do you tell the patient at that point when you send him or her home? It's with what type of referral? It's with what type of prescription? What does the patient go out with that they haven't come in with? Yeah, I think it depends on whether or not this is the first time it's happened to them. If we're fortunate, I don't guess the patient is, but if we're fortunate, they described this happening multiple times before, but this is the first time it's actually been diagnosed, then all of these patients I'm gonna refer to cardiology. Depending on the insurance plan, they may have to go back through a PCP, but still to cardiology. Not EP specifically, but cardiology. But if the patient has had repeated such episodes, then I might consider discussing with them, and if I can get the PCP on the phone, the idea of putting them maybe on a low-dose beta blocker or something just until they can see the cardiologist. If this has never happened before, then I'm generally not going to think about starting any therapy. I'm just gonna do the referral, and I'll probably place a phone call to try to get the patient in sooner instead of later. Thanks very much. Kathy, you've written extensively and spoken extensively about the frustrations that both men and women, mainly women, but men and women face trying to get a distinct diagnosis. When I think about that, I used to be a practicing electrophysiologist. I put those kind of frustrations into a couple of different categories. One is, as you said, the tachycardia breaks just as they're walking into the ER. Number two, the second category is they see someone, they put a 24 or maybe a 48-hour holter on them, and guess what? They're symptom-free during that time. And the other category I term, it's not a pretty term, but kind of the term of patronization. It's sort of like, oh, it was just an anxiety attack. I'm there, it'll get better. What kind of stress are you undergoing? To what degree would you put other categories there? And number, is my first question. And the second question is, speaking as a patient advocate, if you had one bit of advice to give someone in that kind of circumstance, they have palpitations but no diagnosis, what's the one advice you'd give to a patient like that? Gosh, I guess I would, I'd probably get one of those cardiomobile devices if they haven't been diagnosed, and have them use it to document the rhythm. If they've had a documented episode, then I would say be very much aggressive and speak for yourself and demand to be referred. Because often it's OB doctors that first hear these stories. Other times it's primary care or the emergency room physician. But it takes a long time to get through that part of the puzzle before you get to see a cardiologist. So it's really frustrating. Patients go to so many different lengths to cover up, to appear normal. It's really frustrating for them. And I think I would have to tell them to have patience, but to pursue further treatment. Okay, thanks. I mean, what you mentioned is actually very intriguing, and that is specific patient education to OB-GYNs. Yeah. Because for all the reasons that we know, I mean, the state of pregnancy expands fluid, and causes all that. So that's actually a very interesting idea I hadn't thought about before. Um, Todd, when you see a patient, there are a couple of different options, as you guys have already outlined it. No need to repeat them. How do you help to guide a patient to medical therapy versus an ablation, versus let's say a portable treatment that isn't yet marketed? Yeah. How do you help to guide the patient, number one? And number two is, at what point do you refer, or excuse me, when you refer a patient to an electrophysiologist, is that because the decision to go for an ablation is almost a fait accompli, or do you refer a patient to an electrophysiologist to talk about options more? Yeah, as you know, I mean, great question. It's very individualized, right? And a lot of it will depend on some of the things Charlie mentioned. Symptom severity, symptom frequency being two big ones, and level of patient concern, right? Patients these days often have done their homework as well, and so they'll have read about procedures, read about ablations. But it is very individualized. I mean, obviously patients who are having recurrent, prolonged, highly symptomatic episodes, you know, those are people we're gonna, I'm gonna really push to see an electrophysiologist and strongly consider ablation. And of course, we do a lot of drawings, and a lot of diagrams, and we talk a lot about complication rates and success rates. And this is one of those really exciting areas in cardiology where you can potentially cure disease. And so I'm a big fan of ablation. And I, you know, tons of electrophysiologists in my institution that do great work. And so in those patients, that's a pretty easy referral. But, you know, many patients are skeptical. They're, they wanna avoid needles. They wanna avoid procedures. They've heard of some rare complications. And they know it's not 100% effective. And so in those patients, you know, that is where we talk about a lot of these medical therapies and I think we've had this, you know, unfortunate unmet need of not having an acute therapy for these patients. So it's really individualized. And, you know, in patients that are on the fence, I often will still refer them to EP because I said, you know, I've given you, you know, you know, what I can tell you, but, you know, just go hear more about the procedure from an actual person who's going to do the procedure. And then, you know, we want them to be fully informed before they say yes, no, or maybe. I also tell them that this isn't a decision you have to, you know, it's not like this is your only chance, right? You're gonna continue to see us in care. There's longitudinal care. And so if you don't want ablation today, you know, if you have recurrent events despite medical therapy, we can always reconsider ablation at that time. All right. Well, I think we're out of time. Are there other questions from the audience or burning questions? Or did anyone submit anything before we wrap up? Yep, we have a question here. Full disclosure also, an MSO is a milestone, but I guess when you talk about patients not being believed and possibly provider, lack of awareness among providers, how much do you think patient education or just overall disease state education to the patient population is gonna play a role in improved detection and diagnosis of SVT? I think it's really important, but you have to realize that the levels of medical literacy among our patients varies dramatically. There's certainly not gonna be one size fits all education for this. And yeah, I think that we've gotta pick our targets. You know, it would be great if our college professor patients understand the pathophysiology of AVNRT. It'd be great if our uneducated patients who don't have insurance just learn to recognize that, oh, that's my heart doing that funny thing again. I should probably go to the ER. If it's available, I should take a medication that I've been prescribed. So I think an informed patient is always a better patient, but that term informed patient really varies a lot across the population. We see with this disease and with every other. Yeah, I mean, you know, certainly we've come across a few patients who, you know, say my episode started when I drank this really, really, really, really cold smoothie or something like that. And so we know that, you know, there may be, you know, individualized triggers in patients like that. But in general, it's not a, you know, the triggers can vary widely across, you know, different patients. So it's, I don't, you know, the challenge I have, and I think Kathy mentioned this, is that, you know, some of these patients have tried to cut everything out of their life that causes this. They're almost doing, their quality of life has clearly suffered. And so I try to avoid too much over-prescription of triggers initially, unless it's really clear, right? And sometimes things get, you know, hey, I ate, you know, I ate vegetables that day, and so I'm going to stop eating vegetables, like, no, no, just don't do that, right? It happened after I exercised, so I'm going to stop exercising, so probably don't do that for now. So I think we have to be cautious in that scenario. There are some triggers, though, that are predictable, for example, a patient who occasionally uses marijuana, and almost every time he or she does, PSVT ensues. A patient who never has PSVT unless they've had three Red Bulls, you know, you can give some pretty concrete advice to patients like that. Yeah, we want them cutting out those non-healthy behaviors. I would agree that that's the minority of cases. We always stress, though, that whatever they identify, it's not consistent. Right. So when they cut out caffeinated coffee and only drink decaf, they still have an episode. When they stop drinking those ice-cold smoothies, they still have an episode. Then they get all frustrated again. And then they get frustrated. They thought they had it figured out. Yeah. So I think passing on that whatever they identify is not going to be consistent for every episode is helpful information to give them. I think we've got one last question back there. Thanks. Thanks for a great session. Really eye-opening. Kind of following up on the last question, you've mentioned several times that vagal maneuvers don't work. Don't often work. Don't often work. What is your take in general, though, on, say, vagal stimulation or autonomics, how So yeah, I mean, certainly maybe we'll get David's take as well. I mean, I think we showed you some triggers for this that are generally, if you look at that slide, it's predominantly things that increase sympathetic tone, acute illness, hypoxia, stimulants. I think in the majority of patients, we think that's probably where you see higher grades of avectopy, which going back to basic physiology is typically what initiates an episode of reentrant tachyarrhythmias. But there can be patients. We know there's vaguely driven atrial fibrillation in a minority of patients. And so there may be some patients where maybe they see this with sleep. In my experience, it's pretty rare for SVT. I don't know if others have had that experience. But I won't say that there aren't patients out there who don't have some episodes during episodes of higher vagal tone, perhaps. But it's generally not as common in my experience. I don't know, David, if you've got any comments on that. Sure, thanks, Doug. For the question, does the autonomic nervous system affect AFib and SVT? The answer is yes, profoundly. The next question is, can we use the autonomic nervous system, for example, a vagal maneuver, to help to treat? And the answer there is kind of, as Charlie already mentioned, kind of a dismal no. We've actually published on this. And the rates of vagal maneuvers being effective for SVT, for PSVT, in patients in whom a vagal maneuver has been trained, they've been trained to perform it, it's 4% to 6%. So it's pretty poor, even in those patients who've had a health care professional train them on how to do a vagal maneuver. So the answer to the question is, for all the reasons Todd just mentioned, the autonomic nervous system has a profound effect, particularly when patients are all revved up by their sympathetic nervous system. But unfortunately, there's not a lot of leverage there to use that to control them. Research has been done on, for example, vagal stimulation, tragal stimulation, stuff like that. There have been some intriguing results, actually mainly for heart failure and AFib. I haven't seen that much for SVT. So I would look at it as intriguing, but not yet ready for prime time. All right, well, I think with that, we'll close. The speakers will be around afterwards if you have any specific questions. But I want to thank you all for coming today. And again, thanks to the folks at Milestone for this really educational session. I really enjoyed it. Thank you.

paroxysmal supraventricular tachycardia

PSVT management

diagnostic challenges

adenosine treatment

self-administrable therapies

ablative procedures

oral medication

pharmacological developments

patient education

early detection