Kenneth A. Ellenbogen, MD, discusses the role of conduction system pacing as well as ongoing evaluation and management of patients with implantable devices in this Grand Rounds presentation. Dr. Ellenbogen is the Kimmerling Professor of Cardiology at VCU School of Medicine.
Harvey. Should we go and get started? I know there's a lot that we want to cover with Dr Alan Bogan today. Sure happy to thanks from your So it's my honor to introduce Ken Ellen Bogan. No one can. For many, many, many years. Uh, Ken is currently the chair of the vision of cardiology at Virginia Commonwealth University and professor of medicine at the university. Ken went to Princeton undergraduate graduate, graduated magna cum laude, medical school at Hopkins, training in internal medicine, Hopkins and then training in cardiology at Duke. Um, Ken was lasted. Pembridge, discussing earlier about 2016, seems like yesterday when he was the Len Horowitz endowed lectureship at Penn. It's nice to have him back again. Ken is, uh, you know, in many editorial boards, he's He's a reviewer for many of the most prestigious journals in cardiology. Um, Pence. Ken CV is extensive, and I would probably take up most electric time if I went through it. But it was interesting to look through the broad, the breath of political investigation and the important questions that Ken has participated in answering over the many past years, and certainly the topic today. we're gonna talk about is his bundle pacing and left ventricular pacing and other new pacing modalities. He's been on the forefront. Okay, of all those developments, Uh, he's had over close to 400 peer reviewed articles in major journals. And importantly, Ken is now on the 7th edition of his book on pacing, which is which is the reference for pacing in this country, if not internationally. So I personally have used that book, and it's wonderful and a wonderful reference for me to learn from. And then over another 200 inviting invited lectures and hundreds and hundreds of app tracks. Um, interestingly, Ken has Dr Alan Bogan has taken on some of the vexing questions we live with every day to answer things like, How do we handle a tree for relation when we pick it up on our pacemakers? How are those? How are those patients? Best handles. So so he's fortunately helped us and continue to help us answer some of the questions we deal with every day. Um, Ken's areas of interest have not just been pacing, but certainly human dynamic pacing, um, new techniques and radio frequency ablation, which he does every day crying elevation of atrial fibrillation, new imaging technologies for for cardiology and how they interface with electrophysiology and certainly ongoing evaluation and management of patients with implantable devices. Anyway, I want to thank Ken again for coming. I'm very much looking forward to his lecture, and I will say that after you're looking through his CB, I looked have already look back, look forward to having back for other topics to discuss with us on cutting edge electrophysiology. Anyway, Ken, thanks so much for coming and again. I look forward to your lecture and I'll turn it over to you. Thanks, Harvey. Thanks, Samir. I'm going to talk about conduction system pacing what its role is today. And to do that Mhm. I'm going to, um, these are my disclosures. I'm going to try to accomplish four things for objectives. Talk a little bit about the basic human dynamics of cardiac pacing. What is a pacemaker syndrome, how often it occurs? What are the things we should be thinking about? Review the limitations of cardiac re synchronization therapy, understand the anatomy of the conduction system and review conduction system pacing both his bundle and left bundle pacing. Now, this whole area has been very humbling Because it's sort of like a circle in the sense that we've learned so much in the last 10 or 2010 years of our conduction system pacing. But actually the importance of pacing site the importance of where you pace the heart from Was discovered almost 100 years ago in this seminal paper by Carl J. Wickers. He was a physiologist at What was that? What we now call case Western Reserve University in Cleveland, Ohio. And he looked at the aortic flow curves an LV pressure volume curves in patients. Yeah, in animals. I'm sorry in animals and here we have native contraction And then we have L V a pickle pacing. And here we have native contraction in LV base pacing. So it was relatively early on relatively early on that they were able to show pacing site matters. LV Apex Not quite as good as native conduction, but better than LV based, so lv apex better than LV base. So pacing site matters. And really, when I began my career in cardiac electrophysiology Now, only 30 years ago, only 30 years ago or so it was at the time when we made a transition from single chamber pacing to dual chamber pacing to rate responsive pacing, and the state of the art was pretty much focused on the importance of a V synchrony. And here we have a Doppler aortic flow velocity curve, and this is obtained during ventricular pacing and you see how arterial pressure improves and also with improvement in arterial pressure. You get the effect of fortuitously timed P waves on the Arctic flow, and one can see an improvement in that, too. It was really at the beginning of my career in electrophysiology that I got involved with multi center, prospective randomized trials of different, different pacing modes, and the most important study was the most study. This was a study of several 1000 patients who all underwent implantation of dual chamber pacemakers. Then they were randomized to either be D d d r paste or pays from the ventricle alone. And this sub study we published now almost 20 years ago was the first one. It was a retrospective analysis of data, so it's not a prospective study, but it was the first one to show that there's a relationship between the amount of ventricular pacing and the development of congestive heart failure and the amount of ventricular pacing and the development of atrial fibrillation. So I want to tell you a couple of things about this slide and the observations here and that is these observations provide provide the core of our understanding of pacemakers, syndrome and pacing induced cardiomyopathy. But there are a couple take home messages. The first take home message that every single person who takes care of pacemaker patients should take home is that the amount of pacing or the dose of pacing is related to the risk of developing pacing induced cardiomyopathy. So if you only pace a little bit, your chance of developing pacing induced card Mafia is not zero. Although the inflection point is around 40%,, it still increases over time as the amount of pacing increases. And this group of patients is a group of patients who mostly had normal ventricular function. So it's a dose of pacing And the EF. If the F20% this curve would start higher and go higher now, as important as it is to understand the epidemiology of pacing induced cardiomyopathy, I can I show this slide because there are multiple potential different mechanisms that could result in pacing induced cardiomyopathy. But we believe we believe that the main the main path, a physiologic mechanism that causes pacing induced card, um, off these electromechanical dissing Crainey, an electromechanical dissing pretty results in altered my cardio profusion and oxygen demand results in increased my cardio contract, I'll stress and neuro hormonal and sympathetic activation, and that forms a dangerous loop that continues to feed on itself. And that's probably the mechanism for pacing induced cardiomyopathy. Pacing induced cardiomyopathy comes in different sizes and different packages, and We think the incident is between 10-20%, probably closer to 20% of 3-4 years. But it's one of those things that you have to be always vigilant about Because everyone can tell when you're dropped from 55 to 25 That once you put a pacemaker in and they're pacing 100% of the time, that's a no brainer. It's a no brainer when they have heart failure, hospitalization or a fib, but it can be much more subtle and in fact you can take a patient's EF 60 to 65% put a pacemaker in check their EF two or three years ago. They have no two or three years later, And they don't have any symptoms of heart failure. But the F has definitely decreased. It's gone from 65 to 55%. It's still normal But it's been a drop, or the af even drops to 50%. That is part of the syndrome of pacing induced cardiomyopathy. Now we now realize that there is a whole class of diseases called this synchrony induced cardiomyopathy, and we've done a lot of work in an animal model to show that that's probably the mechanism whereby PVC induced cardiomyopathy and again, like pacing induced cardiomyopathy. PVC induced crime aka. The more PVCs you have, the more likely you are to develop it. But there are other factors, such as a susceptibility to develop it, and that may be manifested Electra choreographically by the width of PVCs. I think left bundle branch block induced crime apathy is a dissing pretty induced crime apathy. How do you treat it? Well, we treated with CRT and conduction system pacing, pacing induced cardiomyopathy is, um, again related to a percent pacing burden. How wide. The pace beats are what the baseline ejection fraction is. And, um, we go from there. Okay. Algorithms to manage this are conduction system pacing CRT. And what about algorithms that minimize RV pacing? Well, before we had conduction system pacing before we had CRT, we had this minimal or manage ventricular pacing mode, which is Medtronic. Safer and safer squared is E l. A medical. Now leave a nova ventricular intrinsic preference is ST Jude now abbot with meek and navy search positive Boston Scientific. But all these algorithms that prolong the interval between the Atria and the ventricles all do that. They all reduce ventricular pacing, but at the expense of these non physiologic Avie intervals, a V interval is greater than 240 greater than 250 milliseconds. We avoid ventricular pacing and its affect on ventricular dis synchrony. But instead we get a V and R V L V d synchrony. And in addition to that, these non physiologic avian trolls are probably pro arrhythmic. Now what's the benefit of algorithms that we can put into pacemakers that minimize ventricular pacing? Because we want to do that. We want to do that Well, here's a meta analysis of persistent day fib, and what you can see here is that the P. D. A. Is not significant. There is no benefit of these pacing algorithms in terms of avoiding persistent day fib in our patients. What about all cause Hospitalization Again? value 0.9 maybe a trend, but not statistically significant. No benefit. You see the confidence intervals and what about all cause mortality? P Value 0.8 for no benefit. So forget about it. Forget about algorithms that minimize ventricular pacing. Those algorithms simply don't benefit patients enough. So now if patients have, um, if patients need ventricular pacing or they're going to be ventricular pace, what are our options? Our options are simple. CRT or CSP. So let's talk about CRT C R T. I show this slide published in Europe faced many years ago. You see, we even have a study listed here, but we look at if you look at CRT non responder rates, look at hard outcomes of mortality and cardiovascular morbidity, heart failure, hospitalizations. You see, the responder rate varies from 15 to over 40%. If you look at LV remodeling L V n systolic and diastolic volumes Again, 20 to 40 Look at clinical function, near card association class or clinical composite measures. There is a substantial number of non responders now. You might say to me, Ellen Bogan, you're showing slides that are 10 years old. Give me a break. Well, we just This paper is now impressed in the American Journal of Cardiology. We presented it at in June or I'm Sorry, July 2021. It is a randomized prospective trial just done over the last 2, 2.5 years, Okay, during covid And at six months, 26% of patients 25.9% of patients were non responders. So let me tell you, non responders continued to be the Achilles heel, the Achilles heel of CRT. Now we were able to make some of these non responders better by pacing from multiple sites in their LV. That's not the subject of my talk. I would like to. For those of you who are just in general cardiology show you this, I think important slide The causes of non response or what I call the three PS The three PS, Our Patient Selection. Suboptimal lead position. Non optimal device programming. Another three PS. The biggest one is patient selection. No dissing Grigny scar RV dysfunction. Other arrhythmias that result in inadequate LV pacing and comorbidities or leads that are placed in veins that are not in good areas that can't re synchronize the heart or problems with programming of the device or not having adequate CRT pacing. Now I'm going to share with you a number of slides that I think are amazingly insightful into what's going on with C. R T. This is the first slide I'm going to share with you. This shows you an amazing, um, take home message. These investigators took 33 patients. The vast majority of these patients had. The vast majority of these patients had non ischemic cardiomyopathy. Okay, that non ischemic cardiomyopathy and basically the patient's Catholics were placed in the coronary sinus and they looked at, um, they looked at. Two thirds of these patients were not a scheming. They looked at the maximal improvement in D, P, D. T. And the worst dp DT, depending upon different sites, and you can see some of these patients if you put the Catheter in the right branch might have a 40%, improvement in DPDT And you put in a different vein branch and they're DPDT could actually go down by almost 20%. And you can see there a couple of patients where it didn't matter where you put the catheter. They just never got much improvement. They just never got much improvement with CRT. And but you can just see how variable the responses are. So that's problem. Number one and again, 21 of these 33 patients had dilated non ischemic crime opera. These so you would have thought these patients would do particularly well Well, perhaps the problem is we need to pay cl v and a cardi. Um, we need to get into that his prick in the system. We need to get to where we need to go. And, um so let me Sorry going backwards. And so there are a variety of different ways to pace the LV and Bacardi. Um, let me remind you that I'm going to spend most of my time talking about the best way to paste the LD and accordion, and that's from in the inter ventricular septum because the conduction system lies into the inter ventricular septum. But before I get to that part of my story, I want to tell you about LV and a cardio pacing, because this is just a perfect segue from the very first slide I showed you of Carl wingers showing that LV pacing a pickle. Pacing is maybe the best or one of the best places to pace from. So we have this system, its investigational wireless LV and a cardio pacing. This system has been studied in the United States and Europe. This system consists of a receiver electrode placed where you like it in the left ventricle. This electrode is tiny, but it has a barb for active fixation to the LV and a cardi. Um, it has a separate battery here that powers the transmitter. The transmitter delivers ultrasound or acoustic energy. This is the receiver. It converts acoustic energy to electrical energy, and it is triggered by a pacemaker or RV pacing. So I'm going to go over with you the results of this LV and a cardio pacing well. The study Dunne was called the Select LV Study, and it showed sustained cardiovascular improvement for this particular end of cardio pacing system. Now I want you to take two things into consideration. Almost everyone who had the system failed implantation of a CRT system or were non responders to CRT system. The response rate to LV and cardio pacing is 85%. It was a global composite score of mortality, heart failure, hospitalization, improvement of one or more New York Heart Association classes and quality of life improvement. And you can see that 9% of patients weren't changed and about 6% of patients got worse. So 15% of patients did not help or got worse. But compare that these other CRT studies 85% versus 69 versus 54 versus 52 vs 50 something here. So very impressive. Now let me show you the actual individual patient data. You see the change in the F about 7% points, and you see they're basically about five patients here who either didn't have an improvement in EF or had a slight or significant decrease, but only five patients In this patient group, you can see ventricular remodeling by looking at baseline to six months. This is baseline and diastolic got smaller and systolic volumes got smaller. This is the fascinating data. This is data about electrical remodeling. When you have electrical remodeling, you're going to have an atomic remodeling. Look at the mean cure restoration at baseline. This is and then you have Bybee pacing because you have L V and a cardio pacing At one week. Curious is 128. two weeks. 130, 229. Now that's not going to change by be. Pacing is not going to change your cure restoration over time, right? You're facing the same way. But if you look at the intrinsic your S, you stop your body be pacing. You see, there is dramatic electrical remodeling that goes with the anatomical remodeling and that's illustrated in this slide. So pretty impressive changes of the intrinsic Urs from baseline to one month to six months with by the pacing. Now, I told you that it is my belief that India cardio pacing is better than CS Pacing coronary Sinus pacing is pacing the lbl Picardy. Um but the best place to pace if you're going to pace is not just anywhere in the Albion Endo cardi, um, but is somewhere in the septum and we'll talk about why I wanted to go back a little bit into history. This is from to Wara. And this is one of the figures he prepared in 1906 to illustrate the location of the A V conduction axis the Axis baby conduction. Here's the bundle of hiss. Here's the right bundle. Here's the left bundle and this is viewed in an Al head here, Feet here in an altitude. Italy. Correct. Uh, fashion. The atrial myocardial is here. The ventricle Mark Carney, um is here, and he deserves credit for clarifying the existence of a specialist conduction system in a special location in the heart. Now, I just like to show you the A V conduction system and approximate right bundle branch block. These slides are from the U. C. L. A Torah McAlpine project. McAlpine was a surgeon in Ohio. He did this in his basement in the spare time. Sort of makes you wonder what his wife thought of him. But here's trans illuminating the ventricular septum. And with that we can see the penetrating bundle of hiss you can see as a dives through the member and his septum. You see the septal leaflet of the tri custom valve here, and you can see this. The A B note is presumed to be here. So here's the A V nodal tissue. Um compact Davy Note going into the penetrating bundle of his as it crosses through the member is set septum again. Sepp Dietrich, Custody leaflet. You can see the pant muscles and then you can see it branching off here. Right here, into this right bundle branch block. Okay, so let me show you. You can see now we're looking at the left side of the septum. We see the aortic valve here, and you can see the left sided conduction system and we'll talk a little bit more. You can see multiple branches here, but this is taken again from the monograph a tour, or looking at the left bundle, you can see an anterior fantastical here, a poster fast ical here and believed to be present to the vast majority of patients. A septal fast ical anterior septal poster coursing towards the poster papillary muscle towards the anterior papillary muscle towards the base of papillary muscle, but this again is from two are. But now I'd like to share with you some images in the from the bovine art. And these images are not exactly things you see in many medical textbooks because these images of the bovine heart with you can see the mitral valve open. You can see the aortic valve, anterior papillary, muscle poster, papillary muscle and, of course, the left bundle. But what I want to draw your attention to is the staining of the conduction system here and with the staining of the conduction system. What you can appreciate is this rich nexus Web like Web light, uh, system that emphasizes the varied, rich multiple interconnections among the terminal branches and the branches of the cardiac conduction system. Now, these pictures are taken with from CT scans of micro pigs where they have been able to stain the conduction system. So you can see here, uh, the non coronated costs the right costs left corner. It cost right below the non coronary cusp. Here, you can see the axis of the A V conduction system and you can see him purple here and in red orange. Here, the different parts of the conduction system. This emphasizes, of course. So opening up the right ventricle and you can see on the RV septum you can see a right bundle as shown here and stained here and the peripheral network of Perkin gee fibers going into the moderator banned in other parts of the right ventricle shown here. So again, now this view emphasizes. And again, we're looking here in this cut on the left side of the septum. And you can see how much thicker, wider the left bundle is again. Powerful network, but much more robust, many more fibers. And from there I want to take you to this study because when we talk about conduction system pacing, you can't talk about conduction system pacing without talking about the human conduction system. To me, this is probably if you read one study, one study that's, you know, an old study. This is a study you need to read. Okay, This study is a study done by, um, Dark Dura and his colleagues in the Netherlands. And this is truly an amazing study. This is the basis of our understanding of the conduction system and told maybe 10 years ago, based on an end of seven end of seven, they took seven hearts from normal people who died from basically intracranial hemorrhage. Okay, Somehow their hearts were removed within 30 minutes of brain death, 30 minutes of death. And they recorded the electrical activity on the heart from the epic cardio surface of the heart. And they used intramural plunge electrodes to record the electrical activity in the wall of the heart. And, of course, they recorded from inside. Now, how did they do that? Well, they were super duper clever. The hearts were fixed and die asleep with potassium chloride to the profusion fluid. But they used beeswax. They used beeswax and they record a unit polar, bipolar, Electra, grams by hand, Measure them by hand. And here's the amazing thing. You have to chuckle a little bit when you hear this. How did they confirm? How did they confirm that this was in fact, correct? Well, they went and studied a bunch of dogs to confirm, in fact, that what they study in humans was correct. You see that the electrical activation of the heart begins high on the Paris up the wall below the attachment of the mitral valve. It goes down about one third or more on the left septal surface. Um, and then the poster para septal areas is activated, as you can see from yellow, uh, towards green. So it's activated from the apex to the base, and the anti cartel activation of the RV is near the anterior papillary muscle, as you can see here. So this is the activation of the human conduction system, As determined almost over 50 years ago. Now we are very sophisticated. We have computers Patients where there's 252 electrode body best. They go into a C T scan. They recreate their anatomy from the C T scan while wearing the vest so we know where all the surface electrodes are. And so we create a patient specific geometry and then using the unit polar and bipolar Electra grams, the inverse problem is solved, and from the surface from the surface, they can interpret late what the unit polar electro grams look like inside the heart. And that has allowed us to really understand what goes on the left bundle branch block what goes on and ripe on a branch block. What goes on when patients present with complete heart block, and we will discuss that in some detail again, just going back to the conduction system. What's the side of block? Where is it? Because that has everything to do with where we paste. So let me start off. This is a beautiful figure taken from the work of the Bordeaux group, where they use this vest mapping to map a number of patients who have left bundle branch block. These are just two patients shown here at left Bundle Branch block. What are the take home messages and left bundle branch block? Want # 1? There's no LB breakthrough immediately. Number two RV Breakthrough is rapid and centrifugal across the RV free wall with the base of the RV anterior papillary muscle getting activated the earliest, As I said from the seminal studies done over 50 years ago, LV activations impaired both entirely and post early, and the basil region of the LV is the latest to be activated Now, On top of that, I want to leave you with a couple of thoughts about how incredibly variable conduction is in that bundle branch block. These are 140 consecutive patients with heart failure who had a wide cure. Restoration. And the purpose of this slide is to emphasize the variability of trans septal conduction times slow transept of conduction times, which is the hallmark of left bundle branch block, particularly when you see curious notching. And you see there are three or four patients who don't even have any delay in transept of conduction time. So those patients probably have some other sort of conduction system disease, but not left bundle and not anything anything that can be fixed with pacing. But here you see, you know, the vast majority of these 140 patients have a substantial prolongation of the transept of conduction time, which should be about 25 or 30 milliseconds. You can see a number of patients 40 50 60 70 80 9100 millisecond transept, the conduction times. On top of that, let me talk to you about these are epic cardio maps, ice a criminal maps made during left bundle branch block in four patients who had again left bundle branch block and the epic cardio surfaces of both the right and left ventricle, or map. They are enter left lateral and post your views, and there is some overlap between adjacent views. You can see the L. A. D in the interview going down the front of the heart, and these thick black markings indicate a line or region of conduction block or profound conduction delay due to left bundle branch block. And here's an example. This patient had left bundle branch block your restoration of 140 milliseconds. They had a fair amount of dissing Quran E, and the delaying conduction is from the apex. Here's the apex to the lateral base, so that's where the area of conduction delay is here is Patient number two had even more dissing Crainey, a larger area of conduction delay. Here in this particular patient, you can see the conduction delay now is from the inferior to hear an trilateral conduction, as you can see here inferior. Here's the delay and fairly to an trilateral conduction delay. There's another patient cure. Restoration of 100 and 60 milliseconds, not as much to synchrony. You can see the LV is combined, Lee activated from the apex from the inferior wall from the superior wall, and you see the area of conduction delay here, but not extensive. And here again, you see extensive conduction delay due to anterior to infer poster conduction delay so you can't get back around here. So, um with body surface mapping so we can see they're different patterns of delaying conduction. And that is what makes that is my take home message. That's what makes charities so difficult. So you don't know the site of delay in any individual patient unless you map surface, do body surface mapping in each patient, not very practical, right? And then the question is, what are the chances that we can fix these patients with conduction system disease? Well, the take home message that we've learned is left bundle Branch block is most commonly a disease of the conduction into the left bundle rather than distal conduction system disease within the left bundle branch. So how can you understand that? Well, you can understand that by mapping the LV septum by mapping the left bundle here, you can see, because the left bundle lies across the inter ventricular septum. CIA Catherine with multiple electrodes lying across the aortic valve from the base to the apex. And you can see a beautiful his bundle recording over here His bundle recording here. And as you go further distal down this catheter you go from recording a his bundle recording left bundle potentials to recording Perkin Gee potentials as shown in this slide. And now what one sees is in left bundle branch block the for Kinji conduction is intact and in this patient with left bundle branch block there is blocked in tradition left bundle block and you can see this block somewhere here. So this patient has left bundle branch block and this patient has left bundle branch block. But despite the fact that both have left bundle branch block the mechanism for left on a branch block is completely different is here we approximate block above the side of the left bundle branch Take off here We have no blocks. We have intact breaking the conduction. We must have some sort of distal delay delay distal to the park in the system that results in that. And when one looked at that in a large series of patients with left bundle branch block, One can see that the vast majority of patients 2/3 of patients have left in tradition block and left bundle branch block. We're only about one third of patients had intact packaging conduction. And if you have intact packaging conduction, you probably you won't be able to correct that at least perfectly correct that with septal patient. Okay, what about the history of conduction system? Pacing began over 20 years ago when Deshmukh described permanent direct his bundle pacing in a small series of patients. It really was lost the clinical practice primarily because he used the K. You put a his bundle catheter up. He had always put a backup RV pacing lead in, And he describes some of these procedures taking hours. But that was a nonstarter. And in 2015, we, uh, we and others began to show his bundle implant success without the use of the catheter or backup lead was feasible. Now We described in 2017 the development of pacing not to his bundle but distal to the his bundle or so called under the tree custard valve or septal leaflet and the left bundle. And this is just an example of a patient where we use left bundle pacing to fuse with the patient's intrinsic your s and you can see the patients started out with curious. Such ended up with a narrow cure s So one of the questions that remains that has been poorly studied is what are the mechanisms of conduction of bundle, branch block or bundle branch blocks with conduction system basing The traditional explanation for which there is very, very, very little evidence was basically the theory of longitudinal dissociation. And that is, there are special fibers in the conduction system that are destined to go to the right bundle. Go to left poster fast. It'll go to the left anterior fast ical. And so here we are, pacing within the hiss bundle and selectively correcting the right bundle because somehow, even though we're in the hiss bundle somehow were able to capture specific pathways that are destined for the right bundle. In this particular example, we're talking about the left bundle, so somehow we're not pacing the left bundle. But we're pacing those fibers approximately to the left bundle, the conduction system that are predestined for the left bundle. We don't know whether that's true or not, but there are other mechanisms, the one of the main mechanisms being the virtual electrode effect shown here and that is the electrical area that's being stimulated is many, uh, many, many times larger than the tip of the electrode. And by stimulating a wide area, we are actually exciting or activating some of the other specialist conduction system. Um, go over briefly the nomenclature for you. This is an example of what we call non select. You're going to hear this quite a bit in the future. So it's important to understand what we talked about. This is, um, this and subsequent figures. We have all the Electra cryptographic leads. So what is non selective? His bundle pacing. It's his bundle pacing plus septal capture. And because you're capturing the septum, you have what appears to look like a delta way. That is a slurred cure s upstroke with no, uh, no latency from the stimulus to cure s or, in other words, no ice electric interval. Okay, this is a slur dealt away. This is non selective, his bundle pacing. And here we're going to illustrate selective his bundle pacing. If you look more closely at all the surface leads, one can see that there is an isil electric space in this particular case about 60 milliseconds between the pacing spike as shown here or shown here in any particular lead and the onset of the QRS indicating that you're not directly stimulating myocardial tissue but working your way through the conduction system to get there the same thing for non selective left bundle branch block pacing. There's no latency. There's a Q R pattern here. Conceives acu ar pattern indeed. One selective left bundle pacing only left bundle capture. What we get here is you typically get some latency from the stem to the cure s. It's hard to appreciate here from let's see, from the stem to cure s and you typically in D one, as shown here, get a right bundle Branch block Morphology. This is some forest OPIC images. Both Oreo and yellow show you where the electrode is and you see these are over laid over his bundle pacing and you can see for his bundle pacing where, um, right distal to the 80 nodal conduction system access and you can see right here where that is in between left bundle pacing. It's we know this is below. We know this is below the trick hospital. Somewhere in the septum. You can start actually very high up here And work your way, way down there as needed, particularly in the rear. And the rare cases, maybe up to 10%, 5 to 10%, where there's a fair amount of septal fibrosis. And this is what that looks like here. Um, here's a little movie I want to show you. You can. How do you know that's in the septum? Well, here's your sheath. You inject dye there, you can see there's a wallet die there. That is the inter ventricular septum. And therefore that's inside Intervention Intercept. This is an example of somebody I'm sorry with complete heart block, post aortic valve replacement. Here's a mid septal left bundle lead fixation. Final curious was 110 milliseconds with the RSR pattern in V one. And here you see, we're in the mid septum again. You see our dire contrast to show us We're really for sure in this LV septum and here can see where that patients lead ended up going and you can see how relatively good the curious is here. Maybe 100 and 20 million seconds with our s, our prime pattern Yeah. So we talked a little bit about the anatomy and of the histology. I want to show you here. The orange is his bundle. Pacing The landing zone is relatively now for his final pacing, typically above the separately for the track. Just about rarely right below it. But as we go more distal, we have left more and more and more left Bundle pacing sites. Here's histology the his bundle. These are the muscle fibers. These are fatback rules. This is extensive, extensive network of connective tissue connective tissue surrounding the his bundle. So you know, when we do his bundle pacing the virtual electrode must be getting through here taking effect. Look, a look at the contrast here. Here's left bundle pacing. And here you see left bundle Branch block Endo cardi. Um, there is some Meyer cardi. Um, here, obviously, but a lot less connective tissue. A lot less connective tissue then in this example than in the his bundle, as shown here. Um, this is just an example of non selective. His bundle pacing with correction by a right bundle. Branch block here is right. Bundle branch, block us morphology. 160 milliseconds non selective. His bundle pacing narrows it to 110. Um, you can capture now. The left bundle plus the RV 130 RV only. 100 and 70. So there you go. Um, here's what a septa Graham looks like. I show you what it looks like by injecting some contrast in here. Probably see at the beginning. And here's your you can see the echo and you can see the the Yeah. Lead is in the inter ventricular septum, almost to the elbow and accordion. This is the treatment of left bundle Branch block or C R T. This patient needs CRT. They're intrinsically bundle 1 65 milliseconds with that bundle patient and fusion of 80 nodal conduction, one can see the cure. Restoration is now 104 milliseconds. Do you see the MRI of the lead here and here you can see the difference between the location between a his bundle leave and the left bundle lead. Okay, where are we with our guidelines? Here's block heart failure, the seminal trial that showed by be pacing in patients with intermediate e f 35 to 50% Have fewer heart failure events. LV end diastolic volume is better by about 23 25%. Here is the seminal trial in his bundle pacing It was not a randomized trial. It was two centers in Pennsylvania. This is beautiful work done by Dr VJ Ramen, his center to in planters. Everybody got conduction system pacing leads the center 45 minutes Across town, everyone got RV. A pickle leads and you see the difference. His bundle pacing at 29% decrease in death, heart failure, hospitalization or upgrade to a by V. If you look at these curves and patients who are more than 40% di pace, the separation is greater and the curves are even more impressive. This, however, despite all that only received a class to be indication. A class to be indication for his bundle pacing with ventricular backup for a blade and paste and a to a indication, A two indication as a bailout for failed CRT in the A H. A a. C. C. H. R s guidelines, we have a two, a indication it is on the same footing. It's either CRT or CSP for patients who have moderately reduced es and are expected to be be paste most of the time. So it's a no brainer. Failed LV lead implant equals conduction system pacing. That's a no brainer. Okay, and there are various varieties of conduction system pacing I won't have time to go into either. Pacing the his bundle pacing left bundle hot CRT is his bundle pacing plus CRT lot CRT is left bundle pacing. Plus I'm sorry. Left bundle pacing plus C r t. Um, So here's the data for cardiac re synchronization therapy with non ischemic crime op. These using left bundle pacing you can see, uh, these patients are all non ischemic, and you can see 97% success And you can see cure s duration. Um, is goes from 168.6. The pure pacing 1 17 to fusion with the native right bundle 103 Very, very impressive. And at 12 months, pacing thresholds are great And you can see the improvement in LVE. F at six months at 12 months is really striking. It is a 22% improvement in injection for action. You can see the dramatic reduction improvement in EF here uh, 12 months. Almost 60% of patients have an EF improvement greater than 20%,, And you can see almost 86% have an improvement greater than 20% And 75% have a final yes, greater than 50%. You can see LV. Systolic volume is dramatically reduced as well. Okay. What? Here's another study from an international cooperative group again. Left bundle pacing. This included a variety of patients. Had ischemic crime apathy. You can see there's been a dramatic improvement in their function. Here is where we're going. A Danish trial randomized trial by V. C. R T vs his CRT, And you can see the problem with his bundle. Pacing is shown in this slide. In a Nutshell. of patients 28% of patients crossed over from CRT from his bundle C R T to buy B, and that number is a reflection of trying to pays to his bundle. Based on intention to treat. You can see there's a similar improvement and cure restoration. Similar improvement in New York Heart Association class and again you can see by V versus Hiss. In terms of LV, EF is about the same and again UM five V versus hits at six months. Similar improvements. Alien systolic volume. But it's hard to prove superiority if almost one third of your patients crossover left bundle C R T will be doable. I believe in 90 to 95% of patients. So this crossover problem will largely go away. Well left bundle area pacing we don't know the risk of Try custard rig Urge the risk of perforating the septum. It rarely can occur the risk of stroke Septal intramural hematoma. There's one case reported that septal corn a branch injuries or possibility risk of lead fracture because you're in the septum risk of and difficulty of future lead extraction. So we need long term follow up data. This is just a slide. I'm gonna try to run through this quickly, just showing you that by ventricular pacing and conduction system pacing produce similar increases in blood pressure which imply similar increases in stroke volume. This is a computer model simulation that shows you what CRT does, and CRT helps you optimize your left sided Avie delay and then you get a benefit of stroke volume due to ventricular re synchronization. But What conduction system pacing provides you is a market reduction in LV activation type. And this additional benefit over CRT is what conduction system pacing promises to deliver. So this additional benefit, by further reducing the activation time, will produce an improvement and stroke volume that is not at all trivial and will result in improvement in the patient. So no CRT currency. Artie, the curious goes here CRT with fusion, it gets even error. But with left bundle were probably somewhere relatively close to normal conduction in terms of where patients end up. So with that, I was going to show you one last slide. But I think I'm gonna try not to show you one more complicated slide. But this is a slide of intrinsic left on a branch block, and it shows you the amount of dissing Trinny and LV total activation time. Here you can see 100 and 1623. That's just LV activation time with intrinsic left bundle with RV pacing. We really don't change that much with conventional CRT. We bring that down from the one twenties two lb activation time of 84 with end of cardio activation and a cardio CRT. Bring it down further to the fifties, Um, with his bundle pacing LV. Total activation time is very similar to LV and a credible activation time and very similar to what we see with left bundle pacing. So in conclusion, um, in conclusion, chronic RV pacing is detrimental. Conduction system Patients should be strongly considered in patients with anticipated high RV pacing burden. Randomized controlled trials are needed for assessing long term outcomes of conduction system pacing. His bundle pacing is the ideal physiologic pacing technique, but there are technical challenges that implant and follow up left bundle branch block area pacing is the best physiologic pacing alternative. His bundle pacing large randomized trials are needed for further validation. So these are my conclusions. Have humility. There's great biological variation. Thank you very much. Thanks. Sorry I went over. That was fantastic. And thanks so much. What an enlightening talk. I'm gonna ask you. I'm gonna take the first question. The obvious one one's What is your current practice? Patient 70 year old with complete heart block and normal LV function needs a pacemaker number one and number two typical patient non ischemic cardiomyopathy left on the branch block needs Improved conduction. Howard, what are you doing today? So 109. I'm sorry. 99% of our pacemaker patients get conduction system pacing. So if you're normal, even, you know when you think about it, what's the one complicated there to complication Get from pacemakers. You gotta per for the free wall or you get an infection. You know, you can put a pouch in if you're worried about infection. We don't do that. Except maybe CRTs or Jen changes, but perforation it occurs. If you put your leads in the inter ventricular septum, your RV leads and we use we've only used active fixation leads for the last 30 years. You're never going to have a Perth. You may very rarely screw leading to the L V N d kardian, but you should be able to tell that because the impedance is going to drop going to change dramatically. But I would say that 99% of our patients get left bundle leads, and when they don't get a left bundle lead, they they end up with the lead in the L B septum. You know, because they get septal myocardial pace and We're always looking to paste the conduction system in the septum now. So that's everyone who needs a pacemaker, regardless, where they have sick Sinus syndrome. And we think they're never, ever going to pace their ventricle. Um, and that's how we implant 400 pacing leads. I'm on the call. That's how we implant 400 pacing leads in the in the you know, And that's how we get you know, 403 104 100 implants in a year for C. R T. Our approach here is more guideline, a mandated. We have a very low threshold for abandoning a non optimal CS lead. So unless we get into a lateral branch and don't have frantic pacing, that's our first choice for CRT. Okay, see RTD. And because he is an ICD lead, Um, I'd say 10% of patients we don't like the LV lead or we can't get in. And those patients, instead of getting a CS lead instead of going into the sending them to the surgeon for an epic cardio lead, we put a left bundle lead in them. We have a low threshold for doing that. I'm very good at doing that for CRT pacemakers. I will be honest and tell you if somebody's going to have a 45% and they have complete heart block, They're either going to get 8080% of the time. They get a left bundle lead, and that's it. Sometimes we'll put what we call lot CRT like get a left bundle lead and a CRT lead. And I think the it's important to consider that in patients who don't have classical left bundles, you know, if you go back to the original studies left bundle, you have to have that fragment recurs in patients who don't have typical left bundles, they have some other type of conduction system disease. It may be Kinji, maybe distal to the breaking G and those patients. We really try to do both. We think there's real benefit to that Fantastic Thank thanks, Ken. That's really again enlightening to see what you're doing and learn about these new technologies. Samira. The other questions that from the audience I know we're late here, but one question that came through in which, which I think is a great question from John Belinda. Can your thoughts on physiologic pacing in a large healthcare system. Are we at the point yet where left bundle pacing or his pacing could be a E p quality measure in terms of changing practice? Are we there yet with the data, or is that too aggressive? At this point in time, I think we need We need at least one randomized clinical trial. And there I think we're Within 3-5 years from making that a quality measurement. Because again, our friends in Canada or again, a tool Verma who deserves a lot of credit for doing, um is proposed a randomized trial. You know, our guidelines are not accepted all over the You saw the European guidelines. Um, and the Canadians are not routinely putting in CS Lewis and people have BFC 45% like we are like we do. So they're going to do a 12 already a pickle pacing versus left bundle pacing. Um, I think that trial is gonna gonna and there's other trials going on in other parts of the world where once those trials are completed, will will have no reason to do our vehicle pacing ever again. It will become septal pacing and septal or conduction system pacing. And then it's a matter of time to compare head to head Sarah T vs Syrupy. Now, as an electro physiologist, Harvey has a long history of putting catheters in the heart, and I think most of us would agree. If you can paste from the LV and Bacardi, Um, or from the end of cardio surface or the septum, you're always going to be better off than pacing from the epic Cardia. I mean, you know, there's got to be some reason why we, our electrical activation through the historic unity system, endured epic cardio. So why not try to replicate it as opposed to do something that's not natural? Hey, thanks, Ken. You know, it's kind of like deja vu. This is right, what we went through years and years ago, dual chamber pacing versus single chamber basing. And, uh, you know, it's the next next generation of that. And hopefully it won't take as long as it took to prove that physiologic pacing was the way to go. Yeah, it's like Yogi, Berra said. It's like deja vu all over again. Exactly. All right. I think Samir, we're good. There's one last question can if you've got just another moment, and then we'll wrap it up. Um, it has to do with leaderless pacing and leaderless pacemakers and how that could tie into into your talk. Well, that is a fascinating subject, and it is a source of continuous struggle. I think there's no question that every time we put a device in a patient, all all the good doctors who work with you and work with us always weigh the benefits versus risks. So for people who have infections and people who have dialysis, you're sort of stuck, at least seriously considering. Leave this pacing. There is some discussion about Well, you know, it seems like needless pacing may have a lower incidence of pacemakers syndrome that may or may not be true. It's hard to know for sure. I think if you're gonna put a leave this pacemaker in and you can be sure you're on the septum, you're probably serving yourself pretty well. I think you know, at best right now we have V D. D pacing right. We can't paste the atrium, And some people do pretty well with a V synchrony. They get it 80 90% of the time and some people are like 30 or 50% of the time. I would think if I were a patient, nothing would be more frustrating than having having and losing a B synchrony and not knowing what I did or why it's in and why it's out. But, um, I think you know the goal is to have a sleeveless pacemaker that you can, um, put in the intra ventricular septum And maybe 75, of the time capture the conduction system. So that's the Holy Grail. And that's what I think we're moving towards. But we ain't there yet. That's for sure. Alright, well again, Ken, I can't thank you enough for that wonderful talk and bring us up to date with conduction system pacing. And again, I look forward to more and more breakthrough and trials to answer these questions that are unanswered. And again, thanks for all your time and efforts and greatly appreciate it. Thanks, Harvey. I cared a lot. Can't wait to see you guys in Philadelphia next time. That would be fantastic. Love to have you up. We'll look forward to that. Thanks, everybody. Thank you. Thanks, Linda. Thanks, Samir. Everybody have a great day. Bye. Right
