Dr. Douglas N. Gibson discusses stroke prevention strategies for patients with atrial fibrillation as well as currently available antiarrhythmic drug therapy options.
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All right. Welcome back, everybody. We're gonna shift gears a little bit. We're gonna talk more about specifically about arrhythmias and device therapy. And the device therapy will tackle both arrhythmias and overlap into the heart failure arena. So this is part of why we do the conferences, heart failure and arrhythmias because a lot of what we do on the arrhythmia side and device therapy side directly relates to heart failure. So I'm gonna I'm gonna start us off with a talk about atrial fibrillation and these air 30 minute talk, so it's gonna be a little tough. Thio cover all of a tribulation in 30 minutes, I'm gonna focus on specific updates and advances in the field and things that I think should be highlighted in the current era. So let's see if we can get myself to take control. All right, here's my disclosures. And so here here's the basic playbook. I mean, this is sort of what goes through my head as I evaluate patients with arrhythmias. First of all, to big things to think about, actually, let me step back for a minute. Risk factor modification. That should be part of everything. Eso really as were evaluating patients, and they have been identified as a diagnosis. With the diagnosis with atrial fibrillation, we immediately start thinking about blood pressure, control and sleep apnea, valve disease and heart failure. Basically everything. All of the modifiable risk factors that we could get after we get after. But immediately after that, we start thinking about stroke prevention and symptom management. I'm gonna follow this outline pretty pretty close. We're gonna start with stroke prevention and going to symptom management. Um so obviously one of the first things we do is calculate the chads vast score and think about Orlando coagulation. If they're not good candidates for Linda Coagulation for any reason, we think about the actual appendage closure. So obviously the Newark drugs air great. There's, um, practical considerations with using these drugs and abroad population of cardiology patients. Often a lot of patients with a defibrillation will have coronary artery disease, and you end up having to use these drugs in patients that undergo stenting procedures. And the question comes up as to whether that we should be doing triple therapy. Obviously, triple therapy will increase your risk of bleeding. And so we've been asking the question here for a few years now. How best to manage these patients. So this is one of the original trials here with rival rocks. Even that showed that this modified dozing associated with triple therapy so reduced the rival rock band in the early Postant phase was perhaps a good way to play it in terms of being able to reduce risk, Keeping an eye on my time here a little bit, Um, so obviously a big, bigger trial that was done recently. And these air in patients undergoing PC I with a tribulation, You getting past original procedure that you randomized three approaches? Obviously, this is the interesting approach. Just double therapy with Plavix or or another 23 a hitter. So not to be three bay, but a Plavix light drug associate with rock arrival. Roxanne. So can you do double therapy versus triple therapy? And the triple therapy that were randomized against double therapy were reduced. Those rival rocks ban Plavix and aspirin or warfarin, Plavix and aspirin. So there was a nursing trial, 17 results, and basically what it showed here is pretty much what you would expect in terms of bleeding warfarin with triple therapy including warfarin, had a fairly high bleeding risk rate. Rival rocks Dan reduced ghostwriter rocks down with aspirin and Plavix. Significant reduction. Significantly reduced event rate in terms of the bleeding risk on, obviously, the double dual therapy had again reduced rate of bleeding. So double therapy is kind of coming out in a couple of different travels here, including this one as the preferred way to manage these patients and probably seeing that in your clinical practices as well. Yeah, what about do you do you pay a penalty in terms of ischemic events? You know, the patients have stent thrombosis or strokes as a result of modifying this therapy, and you can see here pretty comparable events. There were significant differences, uh, being the double therapy and the various forms of triple therapy, all the numbers of pretty close in terms of ischemic events. So it looks like a good way to go. I think you're going to see that gaining steam going forward. Obviously, with our interventionist, there are some high risk patients with left knee and stenting, a big burden of promise and relatively low risk of bleeding. Way will still see some triple therapy, so these decisions Air individualized. But in general, I think the field is moving towards double therapy. Obviously, uh, eloquence is, uh, thinking along the same line. So keep an eye out for the published results of this Augustus trial. So this again, it is a trial, and this included a acute coronary syndrome or PC. I and these patients were randomized. Everything got a Plavix like drug, But then you've got randomized to warfarin with triple therapy. So warfarin, Plavix and aspirin or just warfarin and Plavix on the pick sedan arm again. You a randomized to triple therapy, including aspirin or double therapy with just picks, a band and and, uh, and plastic. So again, the results of pretty much what you'd expect in terms of bleeding events um, the warfarin are with triple therapy was the highest picks a band triple therapy. Next in line. And look down here. I think this is the interesting. When the green line bleeding risk is dramatically reduced. Eso again Basically what we would expect in terms of safety being it improved the results on the ischemic side or a bit complex. I didn't They're a little bit more than what I could show here recently, but it looks like you don't pay a big cost or big penalty on the ischemic side. In these patients seem to do well in terms of ischemic events. We will be able to dig into the results on the scheme. Excited, making sure we don't increase the risk of things like stem thrombosis going forward. And these results come from presentations. I haven't seen the formal publication on this one. You have to keep your eye out for that as well. Um, we now have reversal agents from no X on decks, and that is the big one. This is factor 10 A. It's got a binding site where things is a pro quagga clotting factor. And this is a binding site where eloquence or Xarelto would bind to it s so that's how that works is, uh, binds here in activates the clotting factor a blood thinner. So this is the molecule is basically a decoy. It serves as a decoy, and the eloquence, molecule or drill toe molecule will bind right here. Basically, this decoy molecule sucks up the drug and the gates, its effect. So there's two doses of this. There's a low dose and basically the way you can remember this is if you using the reduced those rocks band or pixel van, you use the lower dozing graduated I have listed here when it comes to the higher dose of Xarelto R l acquis. Uh, if the dose is more than eight, if you're thinking of reversing the patient more than eight hours after their dose, then you go the low dose dozing regiment. So that that in my mind, fairly easy to remember. Low dose gets the low dose. If you're using high dose of an organic coagulant, it's more than eight hours after that dose, you can use the low dose of it index in it. So high dose. Obviously, if you're using the high doses of these drugs, then you get the high dose. And here's the high dose regimen. Eso And this is, uh this is basically what the blood clotting looks like if you will think of this as drug effect. So here's the end of the bullets of indexing it here and you can see the anticoagulant effect drops very sharply. And the doctor bandits works for Dr Van Aziz. Well, and so we have some data about efficacy here, and you can see in terms of bleeding events you have about, you know adequate treatment of those bleeding events are adequate reversal bleeding clinically in about 75 greater than 75% of patients. So it doesn't matter which drug doesn't matter your sex wherever you're bleeding. Waas you get pretty good results clinically from giving this reversal drug. We also use some some of the reversal drugs captivating clotting factors case Sentras, one that we have utilized in the lab for acute complications as well. But Adex notices clearly the choice. So do it's a great I prescribed a lot more docks. I do appendage closure, but clearly we're not covering all patients that need protection against stroke. With no accident, it's There's multiple reasons for that, some of which, perhaps, has to do with with educating clinicians and patients. But a fair chunk of this is concerned over harm There. We see a lot of patients that are just aren't great candidates for these medications, and as a result, patients are going untreated. So several big pop studies looking at this and wanted to take a look at here is This is a 95,000 patients from Jammeh and these air post ischemic stroke patients, and 83% of them were not covered with Orlando coagulation. When they, you know, these patients that should have been on therapeutic Orlando coagulation and work. Ah, lot of half dozing of dough ax goes on in clinical practice. I think clinicians and patients were trying to make themselves feel a little bit better about, you know, I'm gonna give this patient of drug, perhaps give them some partial coverage, but the bottom line is they looked at that and reduce dozing of dough. Ax does not cover you for stroke. I mean, you're taking some written, quite increased risk of bleeding. That's what's bleeding. But you basically do not get protected in a stroke. So that's something else that needs to be communicated is you're not doing patient any good in terms of stroke protection would reduce those direct. Yeah, so So the on the left actually kind of closure side of the story. There's a new device here called The Watchman Flex. It just went through many trials, got FDA approved this year, so the old watchman had an open back then with sharp prongs back here, uh, it was only covered with fabric. Half what they did with the new one is they. So did all these problems together? No, There's no sharp pieces sticking out the back anymore that will result in less of a risk of perforation. There are two rows of anchors now for better stability and greater fabric covering, and that, should that is proven to help a better stealing one of the biggest nuisances Thio appendage closure was the risk of a device related thrombosis, or thrombosis, occurring on the face of the device network. It's all mostly related to have threaded inserts used to stick up above the face of the device right here in the lower right image. They now counter sunk that threaded insert, and as a result of that in the published the recent published I E. The result, the risk of device related thrombosis was cutting than more than half. Okay, so, safety wise, this device is nice. It's got a close back in, which allows you to readjust the positioning, uh, without having to worry about perforation in the back of the pennant are worrying less about perforation of the back of the pendant. Yes, that still can occur, but should translate into significant improvements and safety. We just make sure I could get that slide to switch. So I think there may be a little difference in my videos ability to play. But you condone devices deployed. We then tug on it to make sure it's well anchored into place. And then we shoot some contrast in at the end to make sure that we like the position of the closure. So I assume that videos played all the way through. That would be the tug test. There are my screen. There's the and geographic image there at the end. So so what does all this One of the studies show procedure events were extremely low, so improve safety. This this to me was a fairly significant or exciting, and that used to have a leak rate around the face of the washing of the older watching about 25% at one year 100% of appendages were closed with the new watching flex. It's a big improvement and probably matters in terms of stroke risk reduction over time procedure, sex success should go up we should be able to wear what we are able to treat. A wider variety of anatomy is more shallow appendages, wider appendages. Ondas result. We are able to get patients off of Orlando. Coagulation is with comparable stroke risk and dramatically less bleeding risks. And that's what previous studies and showed. So now most of the original watchman trials were compared with warfarin on those important study at a Prague doctor Ready in New York conducted this with some European investigators, and this was a trial comparing watchman and other versions of appendix closure to know X. It was a composite in point here, the point stroke, systemic embolism, bleeding, cardiovascular death or obviously procedure related complications. The results were interesting. Basically, the watchman, uh, was proven to be non inferior, to know x so you can see here these are the event rates, the pen ish closures in red. No act is in blue. You see the curve start to diverge and basically concluded that it was not inferior to, you know, act therapy. Appendage closure was so very important. Trial on it. It shows that no, actually, definitely better drugs and war friend. One of the interesting things in this trial is that this is this is three year follow up data that was presented. The study is planned for five years, and there wasn't a reduction and bleeding in the left conditional pending closure arm compared to the no act which speaks to the fact that no act drugs or better, they're very acceptable drugs for patients that relatively low risk of bleeding Definitely safer what we expect to happen over time Way will have less waiting in the in the watchman arm and over. Probably the next interim analysis will have significant reductions in bleeding with the attendant closure arm compared to the new economy. So we got through the stroke prevention side. Now we're gonna take a look at symptom management here, and basically we have basically a few options for symptom management. Can rape control with drugs or even own ablation pacemaker. We have entering the drugs and we have ablation. There are some surgical options which I don't have a lot of time to get into. But terms of advances in mapping an ablation way now have better catheter. These air multi electrode catheters that will take large volumes of data from all over the inside of the heart that could be done in Sinus rhythm. Looking at the health of the chamber can be done in each defibrillation. Rachel flutter. So it provides is very high density mapping. This is something called the H D grid Catheter. With this catheter does well is as an electrical wave front approaches it, it will record that electrical wave front in two directions across this bipolar across. This by poll, it will help us capture election fantasy that weren't previously seeing. So this is the reason this is an example of a map that was made with that catheter. This is the right atrium over here. This is the left atrium over here. This patient was in left atrial flutter, and you can see that flutter circuit revolves right around the front of the left atrium here. And so what we do, what that allows us to do is look for the isthmus. So watch right in here. You'll see that entire electrical wavefront crowd right through there. And then this is the mitral valve. Annual is going around here, and we wear a blade from the metro analysts up to this fixed obstacle up here, which was a small region of scarring. So very precise mapping of these arrhythmias. This is an example using the card Oh, system on. Here's a again, a fixed obstacle. And you can see this electrical wave front again. Left atrial flutter rotating around that fixed obstacle. You have these air little vectors and they're based on the size of the Electra grams in the direction and really gives us a very precise map of how these roommates go around around the left nature, the Holy Grail for ablation, or the thing that we need to do the most work on and get better tools and technology understanding of his persistent atrial fibrillation. I think the most exciting development along these lines comes from a company here in Carlsbad called the cutest s. So this is a map. This this catheter does not touch the inside of the heart looks like olive shaped structure system built chamber. It will send out electric ultrasound beams in all directions. Uh, collect data when the ultrasound beams, air bound, bounced off cardiac tissue and create a three dimensional model just with ultrasound, for exciting thing is that it uses ah Siris of electro grams that can record the electrical wave fronts traveling through a left atrium. And this is a map made during a tribulation. We haven't done a whole lot of mapping during a defibrillation because we just haven't had the tools to sort out that complicated electrical chaos that goes on there on DSO This. What we see here is something that we're referring to is a D cell zone. And so just watch this map from and these air these airway front spreading through the hard. They're very irregular, erratic, and you can see the all enter into this area, and some of them will rotate around it. Some of them will come in and squeeze into this area, slow down and then break out. So what this tells us is there's something about this site that's anchoring or driving or important to that agent tribulation mechanism. You have consistently abnormal spot there. There's at least one paper that shows by targeting those thoughts, you get better success rates for a relation of your persistent A food patients. So more study to come on that, but the first time we've been able to begin with the practical tool there's a research tools to do this, perhaps better. But this is a practical, practical tool that's available now where we can start mapping persistent agent tribulation. So the most exciting thing in the field right now is something called post field of Elation. It's a new way to a blade. Abnormal heart muscle. Basically what? This is very high voltage. Very short duration pulse is that it does not destroy tissue with heat. These these air nanoseconds or microseconds pulses delivered in the sequence. And what it does is it reorganizes. The cell membrane allows courts to form in the cell membrane, uh, the cell for energy to generate 80 p. It needs that trans membrane, a logical Grady into drive that energy production processes. So when you open up that poor in the membrane, what also into flow in dancing to flow out, you just disrupt that entire Grady in the Cell just dies by a pop apoptosis. Cardiac cells are extremely sensitive because they're very. They're very energy intensive cells that use a lot of energy, basically all the time. On def, you disrupt their ability to make energy. You cause them thio diet, if you will so it's a very it's a very clean way to kill. Abnormal heart muscle is very effective. So a couple of important publications that came out and Jack here recently looking at paroxysmal atrial fib relation, you get very high success rates. Very durable success rates upon Rick on repeat napping when what they did is they performed inflation procedure. They took a look and everybody in three months later on and these ablation regions very durable. One of the big challenges that we've had is we can oblate things. They look like they're destroyed to us, but is the heart heals the electrical, the tissue can recover. This technology perhaps has the opportunity to ensure that what we have laid stays avoided and so you can see success rate for paroxysmal atrial fibrillation in the study was up around 80 87%. Also being studied in persistent a defibrillation where in general, we have to blame or abnormal horror from us. Um and so look, look at these numbers. For example, 82 of 85 pulmonary veins were they remained successfully a bladed at the end of three months. We e don't think I know we just haven't seen any tool that that that is that effective? Uh, we also target the poster wall in nature tribulation and basically every bit of every one of these patients were targeted. The poster while the poster wall remained isolated three months now, those air small numbers of patients I don't think the number will hold up. Over time, we'll have some poster walls, every connect. But we have not seen numbers like this. The Mawr exciting thing about this, I think in terms of obviously success is important. But safety is more important. You cannot damage the esophagus with the levels of energy it takes to kill cardiac tissue. So when we've tried this, we've been right on top of the esophagus, firing these tools off, and you just cannot damage the software. You probably can't. You want very high on your energy. But we haven't found that threshold yet. Likewise, you can't damage the frantic nerve. And you can't cause pulmonary vein stenosis. I'd say Kante, meaning that, you know, based on studies. So far we have not seen it. And there's a mechanistic reasons to think that it just won't happen. This is an example of the ablation. Catherine the ablation. Legions air. Very interesting. They're very sharply demarcated. In other words, where of that high voltage electrical field goal goes on one side of it? Tissues did. On the other side of that threshold, the tissues live interestingly as well. Where the ablation region takes place on Lee, the cardiac cells are touched. It looks like a smart bomb went off. Blood vessels were left intact, nerves were left intact. Everything else is left intact. Just heart muscle cells look like like a ghost town. There's just none of them. Eso Very interesting way to kill tissue. That's an example of a map that was performed following ablation. The results are immediate. Soon as you're fired and it takes very little time and you're talking about in relation reason that is done in under a second. So increased safety increase speed increased success. Uh, they reasonably very excited about all of that stuff. So let me see how much time e a few minutes so way always get in the course evaluations. Um, everybody's interested in practical considerations related to answer with drugs, so it's pretty good example of the drugs and how I personally use them. There's a couple different differences here that I will go over. So you're looking at somebody with paroxysmal a fibber persistent a fib, and they need a drug to control the arrhythmia. So we've divided this table up into columns. So no structure, disease, corner disease, heart failure, and l ph or hypertrophic cardiomyopathy. So first line therapy in a patient with a normal heart would be things like fleck and I'd path known Trinitron or so long, I think, in my practice during Veteran is probably moved up to the top just because of safety issues. Um, by my biggest concern about Dr Jeanette, Iran is a It doesn't appear to be as effective as something like open on reflection. I'd but very safe. Andi. I don't have to worry about Dangerous released with that one. So I often times find myself trying that first I need to drive this little more successful in that patient group of somebody's more persistent. You know, they've already failed. Turn it around and I'll choose Fleck A night of passion own. I'll go over some details of those two drugs a little bit later. Corner artery disease. I'm using a lot of the metro in a lot of soda. Lol, um, you're a is usually at the bottom of my list and a lot of people like camera because of safety. I'm pretty comfortable with the satellite. Obviously the patients have to be admitted and I get a lot of pushback about that. So that's the main thing that limits the federal. I use heart failure again. I'm very comfortable with the festival light in this group. I know a lot of amiodarone is use. Uh, but the Fed light has actually been studying this higher success rates published than amiodarone. Everything's of an Iota is the most effective drug. It's not the federal it actually has higher published success rates. Uh, yeah, and the other one, the one that's been has some clinical experience of study and then second line would be disappear. Mind I will use for patients that have Sinus node dysfunction that has a big politic effect. Doesn't slow down the Sinus node. The other drug that's good for patients. Bradycardia fed light. It does not have an effect on the Sinus node in almost any patient, um, try to jump through here exists, So just a couple of pearls. You don't have time to go over the drugs in detail, but Fleck and I'd always use a navy nodal blocker. With it. It will organize a fit atrial flutter or ankle anchor atrial flutter. It will slow down the flutter rate and make it more apt to conduct one run down the V nodes. So unless you have a good reason not Thio, you should be using this drug with the Navy nodal blocker. Obviously we went over its Contra indicated the structural heart disease talked about its effects on flutter main side effect. I see his peripheral vision disturbance. It's a funny thing where patients have a but blurring of vision of the periphery. It will cause qs widening, widening states of toxicity. And you might see that under higher heart rates with the cure s goes wide path Known again, all these one C drugs you need a little blocker along with them, their contra indicated in structural disease. Pathogens kind of the go to drug for acute termination of you can use the pill in the pocket. Generally try to do that in patients on the first go round, but pre load with the Navy nodal blocker. About 30 minutes later, studies were done in 600 mg. We typically would go about 300 mg and an hour later another 1 50 mg if the patient is still in the arena. Yeah, so during their own watch out for that congestive heart failure. If somebody is in persistent agent tribulation and heart failure Internet round, they make that worse. And so there's a important study that came out showing increased mortality in that group. So just watch for that Z using congestive heart failure is contraindicated. Um, take it with food. It increases absorption. Maybe a reason why you're seeing less efficacy with this drug. And you can also get around its main side effect, which is G. I upset. So do all the big question is you started inpatient or outpatient, and basically the guidelines would suggest that you have no risk Factors for pro arrhythmia are very few of those, basically none of them you can start as an outpatient. Those things would be things like normal renal function, normal electrolytes, no bradycardia heart block, no structural heart disease, not a low body weight. You know, it's probably okay to start. This is an outpatient. We like to see a baseline Q t C interval of less than 4 60. To do that primary effect on E k g will be QT prolongation. You go toe once daily dozing if you're g frs below 60 if you're less than 40 I wouldn't use it. Differ. GF are less than 40. So it's a renal insufficiency is a big contraindications contra indication to this one. In general, renal insufficiency is one thing in my clinical practice that pushes me to, uh, Emmy odor. Um, that's the one thing one time here in checkmate when it comes to an deodorant, is if your patients at renal insufficiency that's paramount again. I mentioned that as anti coal energy side effects, it does not slow the Sinus node. The Fed light is has the highest published access rates. Good choice for patients. Bradycardia. Good choice. It's kind of very clean side effect profile other than you have to watch it for pro arrhythmia does not cause the beta blocker like side effects and very effective drug renal insufficiency again is something to be watched out for. Watched out for you have tow does suggest it. And shouldn't they say you can? But I really would not use it in somebody with the crowd in clearance. Less than 40 amiodarone. Obviously, there's this one gets a lot of use because not having any significant rate of pro arrhythmia renal diseases I mentioned exam you around. Very legitimate choice and a lot of patients, can't you, so I can't use the federal line. Can't use other drugs and patients structural heart seats. So that's really where I get put into check, mate and have to put in the order on Watch out for mental status changes and drop the older individuals. And in the bottom line with this drugs is very high drug discontinuation rates and published trials. I mean, you would be shocked at the number of patients that stopped this drug for side effects. Yeah, it's just way too many side effects to be a long term choice. I'll use that short term, some goal in mind. That's usually how it gets used in my practice. Very rarely do it. Put somebody on a long term and leaving there God
