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Okay. Can you stop sharing your screen for a brief second? Chris? Hi, folks. If you just joined us, Um, sorry for that weight. And thanks very much for waiting patiently for us. We just had some tech issues. Um, I couldn't hear Chris, but it's all sort of now. And hopefully you guys can hear me. Um, and hopefully enjoy today. Welcome back to those of you Haven't been here before. And for those who are new to this, I just want to give you a little idea as to what the purpose of this really is. Uh, the cardiac journal club is established. Really? To share the expert knowledge with people like crap from people like Chris Drive that interest in science and free. Allow us all to work that bit closer by collaborating, sharing that expert knowledge and allowing us to better serve the patients that we work for. Um, So how can you join tonight? Well, you'll you can join in with, uh, while you're not able to join in with video audio. What you can do is pop questions, right? We've got some pools that Chris has kindly prepared for us, and Chris has kindly offered to do a live Q and A with us right at the end. Um, now, who have we got to speak with us tonight? Well, we have Chris, who is deputy principal. Correct science scientists and clinical lead for devices at bars. Health. Um, he's a really great expert in all things devices. So it's going to be a really good talking about the the luxury of looking for Chris slides ahead of tonight, and they're looking really good. So without further ado, Chris, you can take center stage yet. Thank you very much. All right. I'm just going to show my slides and you'll see a little bit of inception, as you will see on the screen. And now we're off. So high Thanksgiving. So Christmas house, Um, we have the title of Hercules needs Zeus today because we're going to be looking at a combination of hypertrophic cardiomyopathy, implantable defibrillators, looking at a little bit of an update on practice for those that don't really know much about either of those topics and looking at some of the future. And, um, what's going on in the current space? Um, So, um, one of the some of the objectives that we want to sort of do today is just go over what I c D is what? Hypertrophic cardiomyopathy, shtm, how we select patients for either. For I see DS and or for HDL with I C d s. Um, maybe what? Some of the outcomes with HTM. And what is the what is the choice of the type of the device, which is where the real the future is for, um, these, uh, these patients. So, um, firstly, I wanted to just see if what people really knew about I C. D s. Um, so an implantable defibrillator. Um, does anyone just put in there? What do you think it's for? Um, Do we use it to make people jump? Do we use them to spend lots of money to make lots of money for corporations? Uh, do we do it to prevent sudden cardiac arrhythmia? Um, arrhythmic death. Do we do it to stop them going through airport scanners? Or do we do it to stop driving? Lawry's, um, just pop the answer in, And if you don't know, you don't know. Um, I'm gonna answer later, All right? So most pretty much everybody's gone to prevent some arrhythmic death. So that's helpful that you will know that at least, uh, but they do do all the rest of them. They do. Stop your driving. They do stop driving long as they do Stop. You go through airports, cancers they do cost a lot of money. Uh, and they don't have to make you jump if you do have an I c d therapy. Um, so, um, so preventing some sudden death. So this is an example of a trace? I needed to put a trace in here because I feel much more comfortable when I'm talking about electric grams more than necessarily talking about research. So I thought I'd put electrical in the staff to calm my nerves. So for those that don't know what an electrogram looks like, that is this top bit here. And this is an RV electrogram. Uh, and this is a far field electrogram. Uh, so we have a far field, the local RV, and then we have the markers and the markers actually mean for what the device is thinking and how it's interpreting this now for those I expect most people are involved in cardiology here will be able to recognize easily that this is a life threatening rhythm of ventricular fibrillation. Um, and the far field electrogram is the thing that you'll probably find most familiar because this looks more like an EKG. You can see a QRS and then a a T wave when the intracardiac is only looking at about half a centimeter is worth of myocardium. So you have don't really have a QRS. You have more of just a complete spot, a really fast spike, and then a smaller T wave. Um, and here we've got the near field. So the that's what's actually going on. The local RV myocardium is all over. The place is rapid. Um, and you can sit and be a lot faster than what's going on Global, uh, RV and the LV, which is that ventricular fibrillation that we see? Um, so by that we have the initiation, which is a of the with the PVC. Um, that's starting off the V V f. Then the patient is in sustained V F, point B and the device here where it's sort of the F market goes up. This patient in V. F. I need to do something about this. So I'm going to charge up my capacities. Um, and I'm gonna shock them. And the device that point see shocks them, and we see that the shock artifact and then the restoration of Sinus rhythm. So well done, this device patient has tried to die, and we have stopped them. So this is Zeus in action. Um, and if anyone's wondering how much it is about 800 volts, we talk about more, mostly in jewels about. So it's about 30 40 Jules, which is a bit lower than the sort of 200 joules you may use an external defibrillator, because internally, there's a lot less resistance if you're already in the heart. Um, now, I see DS used to be massive, And, uh, the first devices I see these that were implanted in the abdomen, uh, like small bricks. Uh, and then they gradually, over the sort of early two thousands got smaller and smaller. At this point in the 32 in the two thousands, they started to get implanted in the pectoral muscle. Um, at that point, then devices became much smaller, more commercially available. Uh, and then they got small up until probably about 2015. This is, uh, the most recent device sizes with the newer S I c d. Which we're going to talk about a little bit later. So we're going to go back in time to the early nineties for when I think most of us were infants. Um, so in the early nineties, what was needed for you to be to get one of these i C. D. S. At the time, these were implanted in the abdomen and they were big devices. Those big devices that we saw there to get a break in your abdomen. You need a surgeon? Um, uh, surgical implant you also needed, uh, would the indication for them, um, for this. So did you have to have a previous heart attacks and my cardio infarction? Did you need to have an ejection? Fraction of less than 25%. Did you have to have two consultants agree that you needed this time easy consultants with you? There was a lot less of them in the in the early nineties. Was did you need to previous resuscitated arrests? Or did you need to have an inherited cardiomyopathy? This one's a bit more challenging so just have a go. See what? You What do you think it would be? You don't. Obviously, I'm not testing where it's anonymous. So just put anything down that you think it could be so you can vote as well if you want them. Yeah, yeah. Thanks for coming in. Now. I'm surprised, actually, that people know this because I think it's quite it's quite amazing what? What was needed in the past. So, yeah, before, you actually needed to have survived to, um, cardiac arrests out in the community for you to get an I c D. Which is absolutely mental. Um, in my mind, because the fact that you survived one is a miracle to factor 52. Um, you should get a load of lottery tickets for that, because that is extremely unlikely. Um, so at the time I see DS were really hard to come by because they were so expensive. And because the criteria for them was so high now as the devices because it started to become smaller, there was more of an incentive and definitely from the industry to find out from more ways in which we could, uh, be using these devices. So one of the most important trials that came in, um, in the in the ninth in the late nineties was the added trial. Uh, so this was a comparison of anti arrhythmic drugs. This is a a sorry for secondary prevention. For those that don't know, Second prevention is just like if you had a cardiac arrest that counts as secondary prevention. Primary prevention is before you've had a cardiac arrest. So for people who have had a cardiac arrest, um, and resuscitated, um, from a called it near fatal or they've had a fatal arrhythmia. You were randomized to either received anti arrhythmic drug therapy and that anti arrhythmic drug therapy was amiodarone. Um, for those that don't use amiodarone, that is a class three anti arrhythmic, Um and, um, that can have this fantastic, um, stopping anti arrhythmias. But it has a very high risk profile for long term use in its, um, complications. And that can be due to the thyroid, the lungs, the eyes or skin, Uh, and the liver. You can kind of get scarring in all of them and, uh, irreversible damage to all of them particularly. And one of the quotes that I've always remember ever talk to patients about it. It's about a third of patients after three years. So that's quite a lot of people if you're going to have them on lifelong therapy. Anyway, this device, this trial nicely, nicely showed that the defibrillators had a mortality benefit over the drugs that they were tested against, which was this was the main driver to really the industry investing a huge amount into I C. D. S because they were expensive, Um, and also that they were kind of become more and more available to people who have survived ventricular arrhythmias. But this was, um, and this this is just an example of this. Try this. Try. This was a pretty well done, randomized controlled trial. But one of the things that they looked at was the factors, Uh, and the most common factor that were the sort of the hazards um, we're the ejection fraction being poor being, um, one of the most important hazards and having a less reduced ejection fraction was made. You do worse. Uh, that's something that is, um this was one of the first signs of this, um, that we end up, uh you know, talk about all the way through. Um, And if you had coronary artery disease, you generally did worse, Um, rather than all others. And there wasn't really that many, uh, that many others. It was a lot more coronary artery disease back then. So, yes. Um, if you had a A If you survived a sudden cardiac death due to an arrhythmia, you are pretty much a stone wall getting a defibrillator because of this trial. And there was a couple of other trials that were done as well. Which were the Scud have trial. Um, sorry. I just lost my, um, second screen. Um, with all my notes on it. Uh, yeah. Yeah. Uh, I do all this from memory. Um, Scott have trial. Uh, the cost trial. Uh, this was the Abbott trial for me. Do you need me to allow you to stop sharing and we shared if it's easier for you? Uh, no, it's fine. I'll bundle my way through and try and remember everything. So the it's all right, the randomized control trials. So just a little bit on randomized controlled trials. These are the second highest here when it comes to levels of evidence, um, below above multiple randomized controlled trials from systematic reviews on meta analysis, which are a group of randomized controlled trials which was performed. I haven't got that to show you, but there was, I think, a systematic review done of these secondary prevention randomized control trials. Um, and these are for the level of evidence we obviously start with in lab based studies that move on to animals and X editorials, An expert opinions, case reports. I do love the case report. I definitely think that case reports are, uh, something that if you're spying researcher to it's a great place to start with, uh, mainly because there's a lot less of evidence to collect. It's usually just one patient, but also, it can be the grounding for a lot of the future stuff that's done and that carries on with case series, case control, studies, can cohort studies. I don't need to read this to you, but I have, um, and randomized control trials for those that don't know are where you have a sample population that are round. I used to a new treatment or control treatment, and in this trial in these trials and the control treatment was drug therapy rather than the treatment the new treatment, which was the I c d therapy, Uh, and comparing the outcomes, but not just having a randomized controlled trial. These trials were actually tested to prove for superiority. Uh, and this is about the statistical power that you're using. So to say that you are using a trial to say that this is better than this, uh, that there are other trials to say that Well, this is as good as this and noninferiority say, Well, this is not worse than this, Uh, and this is sort of the way that we've transitioned, um, in I c d therapy over the years over the last 2030 years from superiority trials because we know now that patients need defibrillators in certain cohort. So in a second prevention trial, it would now be unethical for you to do a trial on with patients with I CVS because you know that that is the best therapy for them that has proven proven superiority by systematic review. So now the only trial you can really do for them is noninferiority studies, Um um, in those cohort of patients, because you need to be at least as good as what we've been able to prove already, and you can't really be. It's hard to prove it makes it a lot harder to prove much better. Superiority trials compared to these other trials need less less patients to be able to, uh, meet the statistical power as well. So some for some people, they can be a bit easier to run. Uh, and they're less costly. So the next most of the most primary, so the primary. And so this is the most cited randomized controlled trial on on defibrillators, and this is a massive trial, the magic to trial, which we pretty much use. Um, everyone uses pretty much everywhere. Uh, and this is the prophylactic indication for I C D. Patients with patients with my card infarction and reduced ejection fraction. So, as you could tell from the last last study, people looked at the patients who had the highest risk. So the people with reduced ejection fraction, which is quoted at 35 30 or 35% This study actually used the lower cut off of 25% and coronary artery disease and the previous myocardial infarction. So you took the highest risk patients and said, Well, should we put this in to protect them from this? Because we know that from secondary prevention, these guys at the highest risk of having a second a an event occurring. So this was a multi center. Our CT was massive across done across the world. It was an investigator lead, but sponsored by industry. And quite a lot of these drugs is quite a few of these that were done around the same time. We're done by different individual companies. They were all pretty much running similar fashion, multi center randomized. But some of them had different levels of low ejection fractions to try and get it right. So there was a blood test I think is 35%. Which is where a lot of our registry that built up on but this this trial was used 25% and found it after 20 months. Follow up. Um, that it was actually, um, stopped early. Uh, so this is where, um, something that I have not really seen in some other trials before, but because the boundary was met for effective therapy of the defibrillator, the trial was stopped. All the patients who were randomized to receive drugs were were stopped and given defibrillators because this was a more, uh, superior, um, effect from this trial. So I've talked about the so ischemic heart disease, and I c D is moving into sort of primary prevention. Um, primary prevention for patients with ischemic heart disease is very well, very well established. But what we found is that as devices and move forward, it's been interpreted differently and extrapolated differently, too. People with different conditions where it's a lot less incidents. Um, just like the cardiomyopathy, some particularly hypertrophic cardiomyopathy, where there's a lower incidents to be able to get the 2 1000 patient randomized in each arm. Trial is quite difficult when you're in coronary heart disease. It was possible, even, but you still have to go to 2030 different centers across the world to be able to make to achieve it. So I moved. I skip forward now to modern day from the two thousands to talk about the different types of I c. D. So the transvenous I c d was that is the traditional I c D. Uh, this is implanted up near the pectoral region where a pacemaker typically is. Uh, the lead is then fed down either the Catholic or auxiliary vein into the superior vena cava down into the right ventricle. And there's a a shock oil here. So imagine you're de fib. Paddles. You have one different paddle here. I've accidentally brought this back into the frame, and the device will shock between the can hear, um, and the coil, um, to be able to try and reset all the myocardial cells from ventricular fibrillation, which is the concept of defibrillation, which we can do a whole other, uh, session on how heart defibrillator and the theory behind it. Um, but so these transvenous devices These were the ones that were used in these randomized all of these randomized control trials, because the subcutaneous I said he hadn't even been invented. Um, this was first came in in the early 20 sort of 2010, 20 maybe 2013. The first implants were sort of done. Um, and this is a newer device that was invented by a physician, where they would put the counter the device down by on the on the rib on the rib wall and you would have the shot coil on the outside, and the device would sense the heart from the outside. So by using what they call it an S e C G rather than an e C G. But it's pretty much just looks like an e c g. So to be able to recognize what the heart rhythm is and to try and defibrillate it now that has its limitations compared to the transvenous device, because the transvenous devices in the heart, it can see from what is going on inside the heart from the local myocardium. So it's very reliable for the sensing when the subcutaneous I CD, when the reason why actually currently only one manufacturer has one commercially available is because it's been really hard to be able to manufacture a way to just see the BCG that you want and not see the muscle artifact and sore enough. People here have seen the CGs as soon as the patient lift your arms up, you can't see anything. So this is something that the, uh, the subcutaneous I see the manufacturer that got the Boston Scientific ended up buying them out and producing this and they're currently have a monopoly on this. I'm not going to talk about the wearable defibrillators. I don't know how much I believe in, uh, using them. I know there's, uh, the life vest I think it's called. Some people use these and think that there are sort of a bridge to transvenous device or a subcutaneous I C. D s. That's a more permanent solution. Now, hypertrophic cardiomyopathy is a heart condition where some people will be given defibrillators, which is where we'll tie these orders together. So for those that don't know normal heart and hopefully everybody's heart that dialed in now should have a normal ventricular size wall. So the muscle, just like when we were able to go to the gym and get big and just like Hercules, the hypertrophic cardiomyopathy. I've got big arms, and they've got really big, much really thick muscle. And I could probably ask Gavin to talk more about the different criteria to find how big all these areas are meant to be. But I don't personally know them. Uh, and the reason being is because I look at electrics rather than the pump. This is the biggest problem with having too much muscle, Um, and particularly if you end up having a scar is too much. Muscle can give you dispersion in your electrical current that's spreading around. So imagine it like a waterfall or channel of water that's going down the river. If I was to throw some water down the pipe that maybe this big, it would all be quite a streamlined in the way that it spreads and travels through. We've always to put it through the same amount of electricity through something much wider. It all spread out more, and you might get a little eddy currents that swirl around in different ways. It won't be as uniform streamlined, and that's what you can end up having happening in a simplistic way for in hypertrophic cardiomyopathy. So the HCM guidelines in 2014, which I'm proud to know some of these people that are produced this, UM, which was produced in 2014. And that hasn't been an updated version of this yet, and it's been quite a while. 78 years since this guidelines came out to talk about. I see she's using a risk stratification, uh, mechanism. So for secondary prevention patients, which I've already said that Pretty much a no brainer for giving an I c d. Uh, it says if you've had a sustained cardiac arrest and you've had and you've luckily survived and you or you've had sustained ventricular arrhythmia with a blackout or you felt dizzy So you had a hematoma. Compromise, which is pretty much is what we count as a secondary prevention. Um, and you're going to live longer than a year. You should get I c D. Um, And it's important about this longer than a year. There's a trial that I think it might have been. Actually, the magic trial, which looked, said, Actually, most of the benefit was in the after the 1st 99 months. And actually, what you find is if the discussion with the patient at this point is more, how would you like to die if you're gonna die within less than a year? Because I'm having an arrhythmic deck is that death is actually painless. If you don't have an I c d. You do, you're going to end up getting a lot of shots. But if you don't, it was actually you just Hey, Chris. Interesting part. Yeah, I just lost your brief There is okay, if you just back up a little tiny bit you were touching upon. Um uh, it's quite painful if you die from a rhythmic death. And then I just lost you, okay? Painful dying from an arrhythmia deck. So, um, definitely want to try and avoid that if we can. So patients who have a life expectancy of less than one year you'll have that consultants. We'll have that discussion with the patient to say, Would you like to die suddenly? Or would you just like to, um, also have the option of dying suddenly? Or would you like to have shocks that may keep your so in primary prevention? This is where, um, looking at the, um looking at the patient's history, looking at their echocardiogram in there and the ambulatory cg to try and come up with this risk or and this looks at their age when they their family history, unexplained syncope, um, lvot maximum thickness diameter, um, and non sustained ventricular tachycardia which, um, from try from the cohort studies that have been done non sustained V t, which is actually characterized as three beats now, three beats for me for me is. Actually I don't I wouldn't even obviously come as a CT scan was a triple it. But this was something that was looked at it, actually, quite a few different papers from cohort studies that were done that said at least three beats would be counted as non sustained V. T. So this thing is then put through the risk or calculator, which you can find online. If you're interested, just search, Hmm. Risk calculator. It comes up, and it looks at categorize people with low risk, intermediate risk and high risk. Um, and most of the time, it's the high risk and intermediate risk where patients will be counts, uh, joint discussion with the patient, whether they should opt for an I. C. D or not. Um, and then now recently has become the decision of what I see. D should be used. So in the guidelines, when it says that you should be looking at programming these devices, um so the ventricular fibrillation zone, which is the highest program zone that we use to program at least two 20 beats a minute. She's pretty fast, and actually, I find this almost contradictory in the guidelines. Because if you looked at the primary prevention that the guidelines for I CD programming that's done by the ear a group and hrs group, um um are saying that they should use, um, the zones of 200 beats a minute to 220 minutes not greater than 200. And this is actually quite fast. This isn't how I would program my I CD or people's. I see. I would aim for 200 zone, and then I would maybe tailor that on their age and maybe go higher if they're on the younger side. But devices work better. When all the randomized controlled trials that were done with the vice programming all looked at programming with zones of actually 200 or or less, only one of them actually looked at a zone with the lowest zone at 200 beats a minute, which this is suggesting, so that is probably not actually used in clinical practice that often, Um, but the subcutaneous I C. D. Is in the guidelines, and it said that it says, And this is a quote. The newly developed subcutaneous I C. D has FDA approval and to be considered who have no patients who have no pacing indication, as one thing I forgot to mention is the difference between the transvenous and the S I C. D is the S I C D has no ability to pace the heart and all transvenous devices workers, pacemakers as well. Um, and can also deliver painless 80 people therapy, which is called anti tachycardia pacing, which is basically, rather than having to shock them, you can pace them out of the arrhythmia painlessly. Uh, and everybody, I think would prefer to be terminated from a life threatening heartburn and painlessly than having to have a shot, which could be quite painful. So, um, what I really wanted to go through today and I realized I'm actually going really slowly, so I'm going to have to try to speed up. Uh, it's a randomized. And if you need to leave, I'm really sorry. You're fine. Don't worry about the time you're doing good. So the randomized control trials for S I c d. Now that this is the only, uh, only only trial that's been published for the subcutaneous I c. D. And, um so this was completed in 2020 we were one of the enrollment centers here. Apart, Um, and having personally done some of the implants and stuff, all this paper, this trial, I found it quite interesting, uh, to learn a little bit more about, um So the authors So the the lead author was based in, uh, in Amsterdam. Rain, rain eardrops, who is a very large He was one of the early adopters of S I C. D. From the original company that started making the S I C. D, which then was bought out by Boston Scientific. Uh, he's a proctor for breast practice. They have their center that have lots of people go over there. There are very large volume s I C D service. Um, we are one of the largest, with the largest in the UK, but I think they're even larger than us. And I think they're larger than even some of the American centers. So this trial, which was led by then, was in 39 centers across the European, and there was a big multi center trial that was funded by, um, Boston Scientific, who obviously make the device. So there may be, uh, an inherent bias towards the way this trial is, but we'll get into that a little bit more. The authors all completed disclosure for forms, and I've looked at. I looked through this and it was quite extensive because of the, um, sort of. The authors that were on this paper were quite high profile people. So we have lots of contradicting personal consultants fees, so lots of them are paid by lots of different companies, not just Boston. Scientific isn't just the Boston Scientific sponsored people. It's There's lots of different competing companies that don't have this technology. The detail, the protocol was, uh, I think it was really nicely, uh, published in the New England Journal of Medicine before the trial came out, and the full detail of it is there it was the same stuff that we got delivered to us here at bars as well. So it was very well structured in the way that it was published out and peer reviewed before the trial even started. Um, and within that, there is quote saying that the industry was not involved in the trial except for the funding, and I've definitely seen clips of and talks with rain. I'm not saying that this was their trial, that the Amsterdam groups trial design, uh, which I think is credit to them to definitely try and pull off this sort of trial. So the research question that they were asking was based on a non noninferiority principal, which actually could be not necessarily one of the weaknesses of this trial. But as I was saying, pretty much all of these patients were guideline guided. They should have an I c D. So this study wasn't based specifically for hypertrophic cardiomyopathy, which is why I wanted to talk about it a lot. So this is a study, Uh, so just explaining noninferiority trouble for those that don't know we're looking at whether this new treatment is not worse than the active treatment. So is an S I c D. Not worse than a trans venous I c D, um So device. And they were asking specifically about device related complications and inappropriate shocks. And this is one of the areas that I think is probably most controversial about this trial is that it wasn't looking about how successful it was, terminating the life threatening heart rhythms that we work, that we were actually trying to protect. And they say they they did that because it had an FDA approval. And there's already been a few efforts called the effortless and untouched registries that say that it is 99.9 or 99.7% successful at cardioverting ventricular fibrillation, which is in keeping with the transvenous population. But actually there hasn't been a trial that proved the noninferiority of, like treating the life threatening heart rhythms, which actually would have, I think, probably end needing a lot more statistical power. Um, a lot more patients. So I think that's why they opted for complications. Inappropriate shocks. Um, and maybe even there was an assumption already by the time that this trial that come over the S I C D worked, So why bother trying to look at why it worked? Which I think we can all probably say is is there's a definite limitation. Um, but one of the important things to think about with the complications and inappropriate shocks is it's actually both devices work very differently. So the transvenous devices are implanted in the pectoral muscle and fed through veins. When the S I C D is implanted bound by the ribs, and it's just under the skin. So some of the complications that you get with one device can't physically happen with the other one, Um, inappropriate shocks. One of the devices is incensing in the heart, and one of them is outside the heart. So they are sensing in complete their heart in completely different ways, which can mean, and it could mean that one of them is worse than the other. And the S I c D typically in the original version of the SED did have a higher inappropriate shocks. Great. So the Praetorian trial looking at the patient's election Um so sorry. My, uh, some of the bits aren't working here, but looking at the patient's baseline, so they randomized, uh, they had a statistical power of, I think not 0.9, um, and ended up with a group of cohort of about 400 in each arm. Um, and the way they calculated that power, I think, was actually quite good. They used the Scud have trial, which was one of the major randomized control trials, and looked at their complications are, um, to be able to say what the complication rate should they were expecting the the most patients were about the same age. And I think one of my limitations with this is this trial considering got published in The New England Journal of Medicine is there's no P values for any of this comparison. I think you can all notice that the P Value column is missing off the end. Which one would be quite helpful? And it may be just be because they all nonsignificant. But it would be nice to actually see that. Um, that's characteristic, I think, actually goes along the whole all of the, um, tables that produce for this trial. So they included, um importantly, Primary and secondary prevention patients, Uh, and actually a secondary prevention patients are a lot harder to come by. So there was only 20% of those patients, uh, sort of in each group. Um, excluding these patients where the need for pacing an ATP um, ATP therapy. So this is a GP therapy. The pain. This therapy is pretty much given for patients who are known to have V t that could be treated by it. So if you have a really fast ventricular, you black out for um, not debatable whether you need a TB. But if you have a rhythm that's more tolerated, you probably should have some ATP to treat it painlessly so you don't get the psychological effects you can get, which are quite detrimental with patients who have shocks. So, um, one of the other things that's important about the S I c. D. Because it senses from outside the heart, is you have to be able to test whether the patient is appropriate for the device or not. So there's extra tests involved, which can mean that you end up Taylor and tailoring towards patients that are more appropriate for the trial than, uh than necessarily others. And the can't be extrapolated out so you can find that this is a definite limit station and lots of people have done extra things. Looking at the appropriateness for the this sensing better test. Now, um, I'm going to go into that later. There's another comment to make about this, um, part of the trial. So the predictive variables. So the things that we're meant to be controlled with in the trial that do, um, that could actually be a compounding factors. And this one massive one, which is my one of my favorite things to talk about is I CD programming. So, um, the I C programming was meant to be locked in. Remember conducting this part of the trial? That was very strict protocol about what you were meant to program in your transvenous devices and in your subcutaneous i CT ones. Because if I said one of the devices with a rate of 1 71 with 2 50 the one with 1 70 is going to get a lot more to give a lot more therapy than the one with 2 to 50 patients election. So the different cohort of patients with regards to the different different card, uh, the cardiomyopathy that be ischemic or DCM or HCM. Or maybe you've actually got structural heart. And we can see from this cohort the vast majority of the had ischemic heart disease. There was a decent amount of nonischemic cardiomyopathy and sort of drink drugs and everything else. So it's really quite hard. I think two already sort of look at these patients and know whether it's beneficial or not. And for the, uh for the bit that we're going to look at later the hypertrophic cardiomyopathy, but 15 to 1 hour and seven in the other. Um, that's not really not enough to provide a decent conclusion for hypertrophic cardiomyopathy. So this trial is mainly looking at the scheme of cardio heart disease, which is most of the OCD stuff is definitely will benefit from so looking at the procedural characteristics and how these procedures were done, Uh, this was in the supplementary review, which actually is really helpful. And I found really, really enlightening. Um, and one of the things that is important here is the different types of devices that we used. So in the transvenous devices, we act have been looking at some of this and for the transvenous devices. You do get a mixture of, um, inappropriate shocks rate, which is one of the the outcome variables that we're looking at between the different manufacturers. And there's a sort of mismatch of all the different manufacturers that we're using. But we've also got a different lots of different three different generations of S I C. D. Now, the first generation of device here was is the oldest device and actually had a limitation in that it couldn't take some of the newer software that was developed an algorithm. So I'm going to discuss later. So we actually have a and the trial started whilst this stuff was being developed and new algorithms were coming in particular in the subcutaneous I c d. Which makes it actually quite hard to make this sort of trial because it was the start to have. The protocol was starting drafted in something like 2012, 2013 and wasn't published in 2028 years. Quite a lot happened. So one of the other main key difference is is that the use of general anesthesia is very high in the subcutaneous. I see GI Group and a lot less than the Transvenous. I see GI Group, which can be important towards the complications. Um, so there there were no numbers of some of the variables which I mentioned the ejection fraction, Uh, I think was fairly even across the two and the QRS duration. Um, they did look at some subgroup analysis for the primary endpoint of complications and inappropriate shocks. And, um, interestingly, this, um, found that there was quite a disparity across these um so the key things that actually looked s I c d maybe maybe better was female, but there was a much less of those in the, uh there's very few females within this. And actually, I see these. Typically, there's a It's a lot harder to men end up with a lot more ventricular reviews than women. It seems, uh, the younger you are you seem to help benefit towards Trans s I C D. Which is something that hypertrophic cardiomyopathy patients are more generally, um, we look at the the other diagnosis, but the different arrhythmias there's a bit of a more widespread, um e f of less than 35% trended towards transvenous. I cd better. Um, and PR interval. So, um, that was normal. Did better. Um, with an S I c didn't necessarily transvenous iced tea. And I think that may have some legs. Because of the way that the inappropriate therapies are generally with transvenous. I see these are due to arrhythmias that can conduct people have got normal 80 nodes. The S I C D is actually quite good. Um, that missing out the arrhythmias that are conducted through so remote monitoring now, this is one of the things that actually is, um, not really talked about in anywhere in the trial. Um, and actually, it's quite an important factor that I think they've missed out, and they would have missed out because it wasn't available for some of it. So try remote. Monitoring is basically where the patient has a little monitor that sits there, bedside that once a day sends through the information to whatever clinic there's following them up, and we'll give them information about their device. Now that's important for if there's any lead problems, if there's any procedural complications that, like leads moving or whether they've had any shocks. And it is a mortality benefit for patients to have remote monitoring, and it is a variable for the reduction of inappropriate and appropriate therapies. So you will have more therapy if you do not have remote monitoring. Now, this cohort here of patients does not have the ability to have remote monitoring. Every single one of these patients had remote monitoring and the trans venous I said er and for these patients, actually, trans remote monitoring came out maybe halfway through this trial for these patients, so the transvenous I C d s are gonna likely live more because they have remote monitoring and have less therapy because they are on on on remote monitoring. So the S I C D group is actually, uh, less as a disadvantage because of this. Um, this is something that I was produced in 2021. So this was produced this paper here that looked at the association between inappropriate shocks and remote monitoring. This is produced after this this trial, but it's really important for the future trials that we want to do. Um, one of the variables within this as well. So knowing that the TRANSVENOUS patients have got remote, monitoring is they actually had less appropriate therapy as well. So appropriate shocks not just, um And this would also be due to the fact that they have ATP. So patients with transvenous i STDs have less shocks, and we've I've already mentioned how shocks are not nice for patients can be traumatizing for them. So transvenous I c d could be better in that in that regard than than the s I c. D. But this wasn't powered to look at that. One of the author important factors was looking at whether how well the devices were programmed for the zones that from the protocol now remember doing this protocol and reading it and being told you have to run by the protocol now. There was actually quite a few of these patients that weren't programmed, particularly in the transvenous are. So these transvenous patients who were programmed with them zones. Actually, 17% of them weren't programmed within the right zones, which means that probably 17% of them were more likely to have an appropriate therapy than they should have done. And two of the inappropriate therapies, which they do mention this in the In the New England Journal paper to of the trans venous I. C. D patients. We should never have had inappropriate therapy if they were programmed how the Protocols said that they were. But the vast majority of this is still in the like lines, and there is going to be some discrepancy. And if you look at the programming that was done in this trial, it's actually quite different to the H. Some of the hrs consensus guidelines. And if you were to look at even the data, that's done across the US and Paul that looks at the I CD programming. Um, this programming is actually very modern, and there's probably still ahead of the curve for a lot of centers across the world. So it probably needs to be interpreted with, uh, sort of a pinch of salt. Almost that this s I C D groups probably under over. Overestimated. It's inappropriate shock. And obviously, we were trying. This is the control here. So we've sort of made the control worse with that. So the outcomes, um, the composite endpoints were banging on the same for if you looked at the complications of complications and inappropriate shocks. But what was expected from this trial is that the S I C D has less device related complications, and the transvenous device has more. And that is because you are putting things into veins. You are putting something in the heart that's moving, um, and you are going to get so you are more likely to have those issues and you can cause issues like tamponade. So there's two tampons in the transverse and which can be catastrophic. Very unlikely, but can be, uh, you can also cause the authorities. And, um, but the only thing that was higher in the sec the arm was bleeding and hemotomas. But that's because you're going to make a bigger scar for an S. I C is about double the size. Um, and I think there wasn't necessarily a guideline in this paper for how what you should do for your withholding, um, anti coagulation and blood thinners. But the S I C D did have higher, inappropriate shocks rate, which was expected. And as I said, there was two of these patients that shouldn't have had them. So 29 went, It went to 27. Who shouldn't have had inappropriate shocks, and there's some minor amount, But the S I C D had more inappropriate shocks, um, than the transvenous arm. So they sort of came out on a level pending. Um, now, what? The study only defined didn't decide before, but fine afterwards was unnecessary shocks. Uh, and this is something a concept that not many people have. Maybe understood. So, um, it's where you have an inappropriate shocks or an appropriate shock. So ventricular arrhythmia that's detected. But it's too slow, so the device shouldn't be seeing it but with the S I c D. It was actually double counting the arrhythmias. That was slow. So 120 beats a minute. The patient tolerated and then delivered, so they counted them actually as appropriate shocks. But they're actually kind of inappropriate because the way that the device detected it so there, appropriately inappropriate. So they re define that as unnecessary, which doesn't really count because you transvenous devices you can, but it's quite difficult to get an unnecessary shock. So, um, that's their quote there, which I don't need to redo something. I just said it, um, device related complications. I've already mentioned um, and the device complications. So these complications here that the SED group are possible Unless you really if you do the procedure really, really, really, really badly, you should never get a pneumothorax. You shouldn't be able to perforate the heart from outside the heart. And you shouldn't be able to cause tamponade when you're not never going anywhere near the pericardium or the heart. So these are these are always going to be zero, which I'll get onto with another trial. So, in conclusion, I think the trial, if you read the limitation section is actually quite conclusive. Oh, sorry, I think quite honest. I think that they were limited with their follow up because there's only so long that you can run this sort of trial, for they had a 48 month month target, which is actually quite long. Most of the early trials were actually done with a year or two year followup complication rate, which is a test to say that actually, the complication rate must actually isn't that bad, considering it's over a 48 month period. Um, they said that the device was not inferior and they actually extended the follow up. They have a Pretoria 60 which is pretty much running the device, uh, the follow up for another sort of a couple of years afterwards. So they said that the from this, that the device is non inferior, um, at, um, complications and inappropriate shocks, but doesn't actually talk about anything to do with how successful we are. Uh, we can see that they have more shocks, but we don't know how well the device cardioverted arrhythmias for, um, so I hope that that would have come up in there any of their product reports or there, Um, any events that have occurred during it, But there wasn't really any mention of that within the paper. So, um, I think that this trial is kind of what was expected. They were expected results. Um, it was pretty well sampled. There was a few patients that were lost to follow up a few patients that we have to cross over. A few patients actually opted for one type of device than the other. Once they were explained the trucks trial protocol and they did exclude those early, they increased the value of the amount of sample that they were doing after the followup duration. They weren't finding as many. Um, I think in their review of about halfway through the trial, they finally they weren't having as many complications. So they increased the study population to adapt to the power. There's good technique, uh, details. And, um, but one of the things that I think is, um, the technicalities of the way that the device has actually changed quite a lot since it started. So if you were to run this trial again, I think you get very, quite different results. Um, and that's questions whether it's actually valid now with the newer device. Uh, this also doesn't really talk about the cost of the trans venous device is expensive, but the SED is the most expensive. It's more expensive than all of them, So that could be maybe a factor for some health care models. So, um, I think it should be used as an option. And should I think that what consultants are doing is using it a fair decision making process with the patients, I think is a is a good idea and try not to pitch. This is a superior device because there's no proof that this is a superior device yet. Uh, and I think that it's probably going to be non inferior in most cohort. But the scheme that cohort was really what this trial has been able to prove. It doesn't have the power in all the, uh, any of the other cohorts to say that it is non inferior. Um, so I think this this is the first trial that was done in with this device, comparing it to the transverse device. So, uh, it's it's the most important one, which is why I'm talking about it. um, and it's important to think about the considerations. Um um that it can be used for some options. So now I move on to the cardiomyopathy. Uh, actually, the new features. So the extent of the S I c D since since this inception has now got a way of extending S I c D detection. So you can actually let arrhythmias apart? Uh, last for longer. They have a new band pass filter which we've been looking at here, which makes a massive difference to the way that the device and s I C. D. Has in inappropriate shocks. The way that we test the vector screening has done better. We used to have to do this manually with BCG and some calipers. And now the whereas a program that runs this. So it's a much more uniform way in a way that you can assess much more scientifically than necessarily me with my calipers trying to measure it, right? Um, and remote monitoring of fresh I see patients is now the norm. So I think you know, the S I c d cohort of this trial was run again, would have a much lower inappropriate shocks break which is the one of the major fall down. And even though it didn't mean to the power and statistical significance, I think you could edge towards more equality rather than just looking at noninferiority. So somebody, um when I had called the atlas try and produce a trial called the Atlas Trial, which isn't peer reviewed, uh, published journal yet, but this was an abstract presents that H. R s conference, which is a big heart rhythm conference this year. Um, and they found that with a randomized controlled trial of 500 patients that the S I C D was superior when it came to lead related complications that I just told you that from the related complications, you physically can't have some of these complications with the S I C D. But you can with the Tranxene this device. So this is pretty obvious. Um, someone's proved it with a superior power with a powered randomized controlled trial, which is, I think, great. The inclusion of this was 93 HTN patients. But there's no breakdown in the abstract about how this has affected the HDL patient, so I'm really interested in looking at this, but this is kind of what you'd expect. I expect that you're going to get less hemithorax and your cervix with the S I c d. Because you can't get it. Inappropriate shocks is the biggest problem with the S I c d. So this is the area I think that we should be looking at for the trials more and looking at whether it actually cardiovert amount of life threatening with algorithms. Um, so I'm probably going to skip this because there is not much to discuss about their safety, Uh, apart from they've had, um, surprisingly, some random things a bit more like heart attacks and strokes and deaths were more in the SICU group of transvenous group. So I'd like to see the details on that because there's none in the transvenous arm and 500 patients. That's, uh, surprising that there is at least one I can't remember. It was a 3 to 2 or 1 to 1 randomization. But maybe I'll come back and talk about the next time. Uh, you don't have to. Uh, So can Pretoria in trial be extrapolated for the HDL patients? So I already said that this was for only 22 htn patients were included. But it did show that the SED could be more beneficial to younger patients and thinking about this logically. Yes, I see, Uh, the more likely you are to, uh, have a complication, the longer you have leads inside your heart. Um, and one of the things that this trial didn't talk about was how extraction when you have a lead complication with the transvenous device can be catastrophic. And that's something that isn't there with the S I c d. Because you're not within the vasculature. Um, and I think now that remote monitoring is available, I think you could probably expect the numbers to be lower, but HCM in transvenous populations, and some are actually more likely to have inappropriate shocks in the scheme mix. So in the eight CM cohort, you probably have to expect more, um, in both groups, because they are younger and you are able to get their heart rate up faster. So, um, I've talked to you for quite a while about this. Um, now I've said here, what device would you have? Uh, I actually don't really want to ask that anymore. I want to ask what device would you give a HCM patient? Um, would you give them an S I c d Would you? Or if you were a patient with HTN, would you have a S I c d or transvenous? I see. So from this trial, are you? Do you Are you convinced, one way or the other? And there's some This is a review article that was done in the American Journal of Cardiology. I think, um, and it looked at it was just summarizing two, um, devices. So this is got that. I don't know if anyone can see the whole the whole start paying for this one guy. Sorry, I didn't create a pool for this one, so folks can read the message in their answer. On what? They think they would be a be that amazing. Personally, I was stuck. Uh, yeah, yeah, it's just some of the pros and cons. Um, and then you've alluded to quite well the limitations of the study so kind of on the fence. I think this is what's really difficult for the patients. And then when you're even looking at the when we're looking at the trial data, you're sort of like, Well, the SED has its advantages. The transvenous actually has its advantages. Um, I don't really know, uh, and I think that the no one's putting the chat. So I want to say what I what? I think that, um So I I think for particularly for SSI HTM patients. I think most of those are younger, and I think the s I c D probably has an advantage over that. But we do need a randomized control child to be able to prove that, um rather than me just going on, I probably expect that it was It will probably be better. Um, but the transvenous device, I think. And I think that what with the company are hoping to produce is an element of transvenous inside the heart principal with the outside the heart principal, where the device to you have basically have two devices where the devices communicate with each other. That will be the I think the real game changer in the I. C. D. Therapy, because the leaders devices that we have going on with pacemakers really are changing the way that we treat pacing. So I think there's a lot of for the future. Um about device therapy? Um, as a whole, Um uh, hypertrophic cardiomyopathy. I actually think that they're really needs to be a lot more. There's there's no randomized control trial out there for hypertrophic cardiomyopathy with any sort of cohort. Um, it's all based on registry data, and we're all quite worried about whether we should, um, whether any of these patients would die so we don't get sued, which apparently wasn't a big deal in the nineties. So now we need to, uh, make our make sure we've got really ethical, good, ethical grounding, uh, to this, um, which obviously wasn't there. But then, um so, yeah, if you'd like to take any comments if anyone wants a property message in the chat, if you want to have a look at this trial, this is the QR code. You can have a little search for it. The supplementary material, I think is there's so much in there, and actually they've produced other articles about subsets of the Pretoria trial is so much more they can talk about, um as well. Um, I'm hoping that we'll be able to add to the space, um, in the future with HCM. Uh, because I think these patients could be Some of the patients could benefit the best long term from it. Thank you very much. Thank you very much for that. If anyone has any questions, please put them in into the little box that you should see on the right side of your screen. And thank you very, very much for the timing today and thanks, Chris, for persevering for all those tech issues. You had somebody coming I/O of the room. Power was going out and we had some tech issues with managed to handle all that. That's pretty darn impressive. Question, I guess from me is, um and it's a difficult one because you touched upon it like, you know, you mentioned the two different main device types we have. There is one other one I was thinking about is what would we think about? So yeah, perfect. Thanks for bringing it up. And you mentioned maybe if it was a younger population, there's the from a trans venous. There's an increased risk of complications from, uh, we might have a lead field at certain points. Uh, what I was thinking about is a flat addition might be more tempted for the sub. Correct? Yeah. Subcutaneous I c d. Which one do you think might be more appropriate in that context on an athletic published in between the athletic? Uh, yeah. So athletic. This is really difficult for me because, um, and even, um, so professional more. We're seeing more athletes competing now with devices and we're seeing we're seeing a change in school of thought with HCM as well as it used to be. Especially the Thailand rules was disqualification from sport. But we're seeing more change your opinion on that not shared decision making, So it's going to be more and more of a question. Really? Yeah. I think that there's, um there's pros and cons for both. So you've got the for somebody sporty. Um, the TRANSVENOUS device, I think, is more reliable from a sensing perspective. So you are probably a little bit better off with the transvenous device. However, because you're athletic, you're actually more likely to get an inappropriate shock anyway because you get your heart rate up faster. Um, so the discriminators do struggle more. The faster you get in both devices. Um, so that becomes a challenge. Um, we also look at the position and depends on the sport. So some patients some patients can be actually stuck with They have a device up in the chest. So if you're a professional golfer, Um And you know, now we're looking for having a device up here. This is going to affect your swing because it's going to be in the way. So you're gonna have to have a device over on this side, or you can have an S I C D. That goes out the way. Um, the S I C D can affect your back muscles. Some people can find it quite uncomfortable, particularly on the back. But being able to see because it goes under the Latins door side on the around the left hand side. So if you're quite active in the top half, it's can be quite quite painful. If you have the device under the muscle, it actually can be quite discreet, and you can get kind of away with it. And you can still you can't really lift weights. Very. Some people patients do, but it's more likely to damage the leads. Um, so I think if I was, uh, I know that because it's published online that there are particular athletes that are out playing professional football that have transvenous I see these, um I know of a few patients that we have the athletes that have s I C D s. But I think most patients who are quite athletic probably will end up heading more towards the transvenous arm right now. Um, I probably would suggest there first one benefit, though I'm going to counteract my own argument. One benefit of the S I c d compared to a transvenous I c d is If you do the S I c d and you don't like it or it goes wrong, you can switch to a trans venous device easily. The other way around is not easy. Transvenous two s I C d is much harder than s. I see two transvenous so you could try an s I c d see how you get on, not try not to have any issues. And if you do have issues, you can switch to transvenous. No one wants to have two procedures, but you actually can do that and you don't have the risk of the vasculature. So maybe I'm convincing myself the other way. I want more evidence, actually got I want more evidence for the SED. There needs to be more. I want that inappropriate shocks rate to come down and then I'd feel more comfortable. Cool. Um, not as good as if it is a real debate. And that's interesting to get your take on it, I guess. Last question for me I will not know is, uh I guess where do you see future research going in this space? So I think we're going to end up looking at a proper randomized control trials in, uh, different subgroups. Um, it was really well highlighted in the paper. And whenever this was Victorian and all the other trials have presented that the S I C. D. Has been tested more in a cohort of patients who probably might not give it to as much, which is the ischemic that are generally older that are generally more likely to need, um, CRT defibrillators and more more complex, uh, have more complex issues that may require them to have a teepee and pacemakers. Um, so it needs to be tested more in the younger populations and in the cardiomyopathy, where Actually, it probably could be more beneficial, longer term. Um, the future, I think, will be that this is all going to change again. Um, so transmitters device has really changed in the last 5 10 years, But with the addition of lead list with the S I c D. That is where there will be a huge amount of research over the next 5, 10 years. When you see combinations and other companies are coming out with their own S I c. D is to try and compete with the current monopoly that is Boston's S I c D. And that will be. I think we'll we'll get a wealth of evidence because they will want to do trials to prove that their their product is good, which means that well as well have a lot more investment into this field. Because transvenous, I said, I haven't really had any investment since They all got loads of money to be able to implant them all comes much harder. Big big businesses. If you're trying to find the trial for a randomized controlled trial for 2000 patients, randomized, these devices cost between 20 to 50 grand. So you're doing 20 times 2000 Do the math. So that's a big trial. Trying to ask nice or, um, an HR or charity for that kind of money is pretty impossible. Which is why these device companies are mainly the people that fund it. Um, so, yeah. Is there any any questions on the chat? Uh, evidence, rather for s I c d for other conditions, like a RV. See? Very interesting. Um, A R V c I think could have, um, some really some real benefits apart from quite a lot of a R V C patients. Get right. Bundle branch block now. Right bundle, branch block. A real pain for the S I c D. To be able to sense appropriately. So if they have a right bundle branch block, you're pretty much you're not going to screen for it. Screen well, in it. Um, so quite a few of the ARB see patients do have that or they have a notching, and they're sort of an r s r and B one of the two, which can be not as helpful. Um, the ARB see, patients as well can actually tolerate their reviews. Quite well. Um, I've seen a lot of RBC patients through our BT service and device service and when they can tolerate their reviews. You kind of want to eat up here. You kind of want the ability to pace them out of it. Um and some of them don't. But a lot of them do have more and more thick arrhythmias that you can get out with that piece. So I'd be swaying slightly towards the Transvenous group. But that's anecdotal again. There's nothing else there that's really looked at the group. I think you would be perfectly safe. I think you would probably have just as little. Maybe just as many inappropriate shocks and lead complications would be less in the S I c d on the real power for for S I, C D and the ARB See group was when we start getting leaderless ATP when you have a concurrent device, that's when it really will change for patients with people with that sort of arrhythmia. Uh, that sort of cardiac condition, I think at the moment I think you're still you could go either way. I'd be heading towards Transvenous unless they're really young and you may want to go s I C D um, but, yeah, there isn't. I know we're doing a registry here because I pulled all the data for R L D C patients. Um, but there is a little There's a little out there. Cool. It's interesting. Thank you very much. Floor tonight. Um, appreciate your time a lot. I'm sure everyone else does, too. So what I'm gonna do is quickly poppin send a feedback for me to everyone needs to 10. Tonight. Um, if you guys could attack, provide any feedback from using or check sometime later to do so in addition to that will be uploading tonight's webinar so people can catch up with Chris permission, if that's okay. Cool. And if that's also okay, would be great to upload slides, but which would be, if that's possible, Chris. Yeah, um, and then that means if anybody in your department wasn't able to catch up tonight and watch it, they can catch up. Uh, time that works best for them. So thank you and enjoy the rest of your night, folks. Thank you. Sorry. I went on a bit long. Everybody. Thank you for staying on everybody. Thank you. Sorry. One by