to our session. It's, we were all debating. I was actually debating, it's the end of the day. Usually these are attended by five or six people that we may just do a discussion. But there's actually quite a lot of people. So we're going to stick to the agenda. Thank you. Thank you all for coming. As you can see, we have a very distinguished panel with a lot of expertise in conduction system pacing. So we're excited to have them and hopefully share their own thoughts about the field and their experiences as well. We will do Q&A towards the end. Hopefully we don't run out of time, but we're going to try to stick to the deadline around 3 o'clock. Only reason being that some of you have to catch flights and so on. So there's going to be an audience response where there'll be a QR code as you can see. And please ask your questions as we go along. That's going to collect and at the end hopefully we can get through some of them. And we're going to change the schedule around a little bit. Dr. Valentina Kutifa has to take a plane ride. So she's going to start out first. So without any further ado. And Dr. Kutifa is from, most of you almost here know, from University of Rochester. Great. And thank you so much, Gopi. And I'm just really excited to see so many of you here today. This is an incredibly important topic and we have made quite some progresses, but we have a lot more to do. So in my talk today I'm going to focus on heart failure and right bundle branch block, whether we should use his bundle pacing, left bundle branch pacing, or biventricular pacing. These are my disclosures. And I'm just going to start by saying that about 20 years ago I started my PhD that was focusing on cardiac resynchronization therapy. So I spent a good two decades of my life dedicated to clinical trials and seeing the amazing effects cardiac resynchronization therapy has in heart failure patients. With advanced heart failure, improving symptoms, extending survival, and also keeping the patients out of the hospital. And I was participating in the MADIT-CRT study focusing on mild heart failure patients. And as you can see, these studies enrolled about 9,000 patients. But none of these studies focused on right bundle branch block alone or non-left bundle branch block. They just enrolled all of the patients with the right QRS. So that's a very important point to make. And what we find actually in our MADIT-CRT study is that QRS morphology really matters. When you look here, the red box is right bundle branch block, you know, very interesting. In left bundle branch block, there is a huge benefit and reduction in heart failure or death. But in right bundle branch block patients, there is no difference between CRTD and ICD. There does not seem to be a benefit. So this started a long-term investigation of our groups and a few studies I will share today. We also know that this was confirmed in other studies, not just MADIT-CRT, CARE-HF, RAFT, and registries as well. Patients with right bundle branch block do not respond to CRT the same way as patients with left bundle branch block. When we looked at the MADIT-CRT long-term follow-up data, we actually found that all of the patients with non-left bundle branch block actually have an increased risk of mortality with a 57% increase of dying. We are potentially posing the patients to harm when we implant CRT devices. So is there a subgroup of patients who could maybe benefit? Is there maybe a subgroup of patients with non-left bundle branch block or right bundle branch block? Well, our study did not suggest QRS duration to be a good candidate. But there was a variable that many of you know, a long PR interval in patients with non-left bundle branch block identified responders. And these patients had a remarkable almost 80% reduction in the risk of heart failure or death when implanted with a CRT device. So this subgroup seems to be a good candidate. Other studies suggested that maybe QRS duration might matter. And this is a meta-analysis from John Cleland suggesting that patients with wider QRS might have more benefit. And a more recent publication from a consortium that I participated in from Dan Friedman from Duke suggested that the QRS duration threshold might be actually very different for patients with left bundle branch block or right bundle branch block. And here the suggestion is that only patients with right bundle branch block and a QRS duration of 230 milliseconds would benefit, which is not a sufficient response for the need of the patients we have today. So we have to find different ways of treating these patients and pacing these patients. And that might not be cardiac resynchronization therapy. Just quickly showing here the guidelines that were in effect until yesterday. And then I will show you new guidelines at the end of the presentation of what we can do today for patients with right bundle branch block. So I'm not going to go into details here. And just make a very important point here of why I think patients with right bundle branch block do not benefit from cardiac resynchronization therapy. We know that cardiac resynchronization therapy is an electrical treatment for a specific disorder, which is actually left bundle branch block, or in cases when the late activated left ventricular areas are in the postural or the lateral wall. But patients with right bundle branch block do not have those regions as late activated. They typically have the delays in the right ventricular region or the postural base or left ventricular wall. So to think that cardiac resynchronization therapy could be effective in this patient population, I believe was futile from the very beginning. We also know that patients with right bundle branch block actually have a very large scar tissue or scar zones. And this certainly complicates the issue. As we know, scar burden is a predictor of non-response in CRT. I'm going to skip this few slides here just in sake of time, and then I will just show you this very intriguing analysis we recently did looking at echocardiographic response in patients with non-left bundle branch block, including RBBB. And what we found is that if we are able to gain good response with cardiac resynchronization therapy, and if the patients have an echo volume reduction of more than 25%, they actually have a benefit, even if they have non-left bundle branch block. And when you look at the separation of this curve, this is very similar to the left bundle branch block curve. So if we would be able to find a way to provide more effective pacing and resynchronization in this patient population, we believe they could benefit. So what are these other ways of pacing in patients with right bundle branch block? I'm not sure Parikh is here in the audience, but Parikh did this intriguing study looking at his bundle pacing published back in 2018, five years ago now. They implanted 39 patients with right bundle branch block, and they've been able to gain successful his bundle pacing in 95% of the patients. And they saw a remarkable response with an increase in left ventricular ejection fraction from 31 to 39%, an improvement in heart failure symptoms as well. So there's some evidence that benefiting these patients is possible with his bundle pacing. Here on the left side, you see this incredible change and quick activation of the left ventricle with non-selective his bundle pacing, an improvement in constructility showing on the right on the strain images. We also have some data from his sync, although we only had two patients with right bundle branch block. But this is important because this was a randomized study, you know, more of the standard that should be utilized in this population and showed QRS shortening LVDI response. And I wanted to show the HOPE-HF trial, and I'm hoping Zach will comment on this more. But HOPE-HF included patients with narrow QRS, also patients with right bundle branch block and a long PR interval, which we think is a great clinical scenario for potential response. And they did a very thorough crossover, randomized analysis of utilizing his pacing. Their control group was no pacing, so that's just something to keep in mind. And they found some hopeful results, but I think more hope is needed. They showed improvement in quality of life. They did not show significant increase in peak oxygen uptake, but I think definitely more studies are needed in this field. And one of these studies is actually ongoing right now called HCRT, randomizing patients with right bundle branch block to his bundle pacing or physiologic pacing strategy versus CRT pacing. So note that the control group here is cardiac resynchronization therapy, which is currently gold standard in this population. This study is currently ongoing and we have 10% of the patients enrolled. Left bundle branch pacing could be a promising alternative to his bundle pacing. And I don't know if I can just take one, you know, maybe quick 30 second poll here. If I could ask the audience, you know, how many of you use his bundle pacing? Hands up if you use his bundle pacing. Oh, not too many. Okay, how many of you use left bundle branch pacing? There you go. That's why we are talking about this topic today. So left bundle branch pacing is easier. I think there's a shorter learning curve. The thresholds are more stable. The lead position can be achieved much quicker. So there are many advantages and it's a relatively newer technique, but it's being widely implemented here in the United States and all over the world. There's a publication from Pugal actually showing specific data on patients with right bundle branch block. And they showed that the success rate in this population was 88%. So somewhat lower compared to his bundle pacing actually. That's something important to note. But these patients still had a significant shortening of the QRS duration, an increase in left ventricular ejection fraction and improvement in heart failure symptoms. We also know that we can achieve a complete elimination of the right bundle branch block when we use non-selective left bundle branch pacing and Arnoldo capture. This is a beautiful, elegant image from that group. So this is definitely an area to further watch. I think in conclusion, I will just show you here my optimistic view of his bundle pacing and left bundle branch IRA pacing in comparison of CRT. I think there's a lot of excitement and hope and some data on his bundle pacing and left bundle branch pacing. Somewhat limited experience, but promising studies showing striking improvement in this patient population. And with left bundle branch IRA pacing and newer techniques, it's more achievable at all of the centers all around the world. There's some concerns of course long-term performance of the leads and long-term studies are definitely needed. And we need randomized clinical trials looking at these new methods of pacing to better understand the benefit as well as some potential concerns over time. I'm not gonna spend time talking about CRT right now because I really wanted to show you the new guidelines that just came out yesterday focusing on cardiac physiologic pacing. And I wanted to show here the new recommendations for patients with non-left bundle branch block. And I'm excited to share with you that now in patients with non-left bundle branch block, an ejection fraction less than equal 35%, QRS duration about 150, and your class two symptoms, there's a class two indication for both CRT and his bundle pacing and left bundle branch IRA pacing. So the first time now, although data are only available from smaller studies, retrospective studies, we have guideline-based recommendation to use this new technique widely in our patients to improve their outcomes, to provide better forms of pacing in patients with non-left bundle branch block and especially right bundle branch block. There's another to be indication here shown as well. I'm not gonna go through all of that. And so again, for all of the indications for non-left bundle branch block, CRT is a currently available method to use as well as his bundle pacing and left bundle branch IRA pacing. So just in conclusion, as I showed you today, we have many data available from prior studies that patients with non-left bundle branch block do not benefit from cardiac resynchronization therapy, especially RBBB. They might have a harm. We still have a large number of implantations in this cohort. And better identifying response and providing better pacing techniques using his bundle pacing or left bundle branch IRA pacing is feasible, available. It's currently in the guidelines. And we have more clinical trials on the way. Thank you. Maybe one question from the audience because Valentina is gonna be leaving us here soon or maybe from the panel, if they have a question. Maybe I'll start with one here. We talk a lot about not all left bundle branch blocks are equal. What do we think about right bundle branch block? Are all right bundle branch blocks the same? Are they different? Excellent question. I think we need further studies. You know, we know that patients, especially with a non-left bundle branch block, especially with a wide right bundle branch block might have some other underlying issues. They might have concealed IVCD. So this is certainly a group that I think we need to focus on a little more and maybe provide even better, even more tailored pacing options in that population. You know, maybe more distal placement, maybe septal pacing. So definitely that's a special cohort. I think they also have just, you know, QRS duration also indicates greater sky burden. And I think that's a very complex situation to deal with any kind of pacing modality. Thank you. For time's sake, we're gonna move on to the next speaker here, Dr. Zachary Winnett from the Imperial College in London. And he will be talking to us about his bundle pacing techniques. Hopefully, here we go, working. So somehow this is not the expected presentation. OK, let's make do. So we're looking at his bundle pacing in clinical trials. So the aim of pacing therapy for heart failure is obviously to restore normal physiological activation. Actually, yeah, maybe we'll do that, yeah. Sorry about that. I think there's a wrong talk that's loaded here, so we're going to go to Dr. Mihail Kailu from Baylor College of Medicine, who will start his talk. Sorry for the confusion. So you'll be talking to us about Lufthansa branch placing, who, when, how, and why. Sounds like most of you are not doing this one, basically, anyway, so maybe. Thank you for the introduction, and thank you for the invitation to speak. Here are my disclosures. So I added to the talk why. So we'll start with reminding everyone what we are doing now and why we are looking for other methods of placing. So I listed here on the left side of the slide the frequent clinical scenarios that require frequent ventricular pacing and the clinical scenarios where frequent ventricular pacing, mostly by ventricular pacing, is desired. And based on the ejection fraction, we use different pacing strategy, whether it's pacemakers or biventricular pacemakers with and without a defibrillator. So for an ejection fraction of less than 35%, as Valentina presented before, we have data in over 8,500 patients that showed that biventricular pacing leads to improved survivability, decreased hospitalization, improved exercise capacity and quality of life for patients. However, there are limitations to that. Depending on the measure used, there are anywhere between 20% and 40% of patients that do not respond to biventricular pacing. Now, looking at the patients with ejection fraction being 35% and 50%, based on block HF, at least in the United States, for the most part, we use biventricular pacing. And that showed benefits in a composite index of all-cause death, heart failure, hospitalization, and an index of low ventricular remodeling, the low ventricular volume index. This was driven mostly by heart failure, hospitalization, and remodeling. However, many of you may be aware that there was a study that was only presented and never published biopace that didn't show any difference. Therefore, biventricular pacing is not widely used outside of US. And then when you go to the normal ejection fraction population, or we typically use pacemaker, and that is a population that has high-degree AV block that will require frequent RV pacing, we know from David and most that a significant percentage of patients will develop pacing-induced cardiomyopathy. So that leads us to the question, can we do better than that? And what would be a candidate for it? So really, what we are trying to achieve for patients with normal EF that require frequent RV pacing, we like to prevent low ventricular electrical and subsequent mechanical desynchrony and prevent development of cardiomyopathy. While for patients that already have low ventricular electrical and mechanical desynchrony and heart failure, we like to reverse or at least stall it. So I call that the PR campaign for conduction system pacing. Now, if we examine the anatomy and the physiology of conduction system in the heart, here on the left, you have a bovine heart, and the left ventricle is open and you can see a stain with India ink, the left bundle, and the ramification of the other Hispokinji system. And that matches up with some structures in the heart, for example, with the anterolateral papillary muscle. And here is an example on how the heart is activated. These are explanted hearts with up to 170 electrodes at different depths. And what you can see, the initial breakout, it's on three sites in close proximity. In the septum, and within 20 milliseconds, these areas have little confluence of, and then there is propagation both toward the epicardium and toward other areas of the heart with the latest activation, the basal portion of the heart. That leads to a coordinated contraction of the heart with shortening on the basal apical axis, torque from the apex, and then at the very end, the base will contract. And that results in an effective cardiac output. So, how, therefore, engaging the conduction system may prove as a good alternative to what we are doing now. So, let's examine how this is done. The first case was reported by Dr. Wei-Jian Huang in 2017, and he's shown in a patient with heart failure that if you capture the left bundle, this is a patient where he attempted, had an indication for CRT, he attempted the LV lead, coronary sinus lead, and that failed. And then they went on to develop the technique for left bundle area pacing. And he has shown that this patient with capture of the left bundle area pacing, the ejection fraction improved at one year, the left ventricular and diastolic diameter improved, BNP, Neuro Heart Association, and there was a stable threshold. So, there are now a number of techniques, but probably the most practical, the most So, there are now a number of techniques, but probably the most practical, the most used technique is using a lead in a sheet to direct the lead toward the basal septum. And if you have intact conduction, you can map the His bundle and then go more apical about 10 to 15 millimeters. And then if you look in RAO, you would aim for 2 o'clock or 10 to 40 degrees, and ideally you would monitor the QRS morphology as you rotate very quickly the lead, and this really refers to the 3830 lead. And as you advance the lead into the septum, you are going to see at some point a QRS that has a right bundle branch morphology, and then you can stop at that point and do maneuvers to verify that you captured the left bundle branch and adjust the depth of the lead more slowly. I'm not going to go in a lot of detail, but this is one of the most talked about in terms of verifying the capture of conduction system, but there is a very good publication from Buri and colleagues, a consensus statement that describes the criteria that you can use to verify capture of the lead bundle branch area. Now, in terms of techniques, the industry, all major device makers have developed tools to help us with different anatomies, and you can see here from all of them different sheet shapes, and most of them are fixed curve, but there are a few models of deflectible catheters, and really the most frequently used appears to be the C315 with a 3830 lead by Medtronic. There are also a number of leads that are being used by different operators, and I listed here some of the characteristics, but by and large, you have stylet-driven leads and the luminous lead from Medtronic. So now we go to ask the question why and when to do this. Here I listed the clinical trials that have been published for different clinical scenarios. For, as you can see, most of them are in the up to 35 or maybe 40 percent range, and I listed both the HIS or lead bundle trials, and those clinical trials are fairly small, anywhere between 29 patients and 167 patients, and they've shown that a number of surrogate parameters are improved. However, they didn't give us, they weren't, the follow-up was not long enough, and they were not powerful enough to tell us about hard outcomes. Now, if you add a number of clinical retrospective studies, we can say that this technique is fairly successful, and it has a pretty good safety profile. So I'm just going to go over a few retrospective studies. So the MELO studies in Europe from Mariusz Jastrzewski and his colleagues has shown in 25, 33 participants that this technique can be successful for bradycardia indication in over 90 percent and for a heart failure indication a little lower in the 80 percent range. And they reported really the highest rate of complication, but if you can, if you look here, a lot of complications are acute and can be corrected if you recognize up to 3.7 percent acute perforation into the LV cavity. And we'll skip this one for, to save some time. And then Pugal Vijayaraman published a study last year from Geisinger and Raj that showed in a retrospective study some of the outcomes, heart failure, hospitalization, and death, and there was benefit of conduction system pacing over biventricular pacing. And that was mostly driven by heart failure hospitalization, and that was the case also for the subset of patients only with left bundle branch block. And just this morning, Pugal again put a collaborative effort together with 15 centers throughout Europe, U.S., and China, much larger cohort of patients, 1,778 patients. And again, there is, seems to be, at least in a retrospective study, benefit in terms of composite of heart failure hospitalization and all-cause death in conduction system pacing versus biventricular pacing. And that's driven mostly by heart failure hospitalization. And again, there are benefits in a number of other parameters. Now, I would say that it's fair to say the studies done so far have shown feasibility, safety, and improvement surrogate endpoints, and some benefit in some hard endpoints in retrospective studies. But we know that all retrospective studies have some built-in bias. And the most exciting development is that there are a number of clinical trial, large and powered, to detect hard endpoints. And I listed here the larger one based on injection fraction. So, you have Michael Vinter here with HisAl2. This is without name. PhysioSync heart failure. This is mostly from Brazil. HisSync2, which, as far as I know, is not funded yet by Rotang and Valentina. And then we also have a number of clinical trials in the 35, 50 to 50 percent with the largest PROTECT-HF by Zachary Winnett here on the panel. And then finally, we have our own study here, Left vs. Left, which is led by Kellen Lembogan and I. That will include 2,136 patients corrected here, 54 sites in the U.S. and 10 in Canada. And the primary efficacy endpoint is death or heart failure hospitalization. And we designed this study to be a pragmatic study. And here are all the guidelines for CRT for any ejection fraction. So, we will enroll any patient that currently qualifies for CRT, including AFib with avenoid ablation and so on. The study has started on January 1st, and we anticipate to start enrollment in mid-September. The study will take about five and a half years long, so we believe that should be sufficiently powered. So, final thoughts. We have evolving tools, improving tools. There are no RCTs for outcomes in lab underbranch spacing. Retrospective data, however, showed feasibility and safety in most clinical scenarios and also improved outcomes. And we have a number of ongoing randomized clinical trials in all major clinical scenarios. Thank you. or prior speaker, Dr. Zachary Winnett from Imperial College, will be talking to us about all things hispundal pacing. Sorry about that, everyone. That was a slightly unexpected surprise. Hopefully, this should be working now. So why should we consider hispundal pacing? Well, to put it simply, hispundal pacing is the most physiological method for delivering ventricular pacing. So we can stimulate the proximal conduction system and preserve normal physiological ventricular activation. And it's, importantly, biventricular activation. So if we look at activation maps, we can see that this patient here has normal intrinsic activation. And when we have selective hispundal capture, we've got normal physiological activation. So rapid activation from apex to base in the ventricle, and so rapid activation. Non-selective hispundal pacing, the LV activation remains entirely physiological. The RV, if we have non-selective capture, we do have some local myocardial capture. But overall, the RV still activates mainly in a physiological way. Depends a little bit on the delay, on the HV delay. And if we use it for CRT, we can see this patient has a broad left bundle branch block. And we can often correct the left bundle branch block and restore physiological left ventricular activation and near normal right ventricular activation. And this is very different to what we see with biventricular pacing. Biventricular pacing, we bring in earlier LV activation, but it's still non-physiological. So if we're thinking about indications, well, actually, the indications, we can argue, is anybody where having normal physiological ventricular activation is useful. We know RV myocardial pacing can be harmful in patients. If we deliver it to vulnerable patients with left ventricular impairments, it increases mortality and death. If we deliver it to patients who have pre-existing normal ventricular function, we also increase the risk of heart failure hospitalization. So if we're thinking about Brady indications, maybe we want a more physiological way of pacing. If we're thinking about CRT indications and left bundle branch block patients, we can see that with HISS CRT, we can deliver a greater reduction in QRS duration, improved overall left ventricular activation times, less dyssynchronous activation, and greater improvements in acute hemodynamics. So who should get HISS bundle pacing? Well, if we think about Bradycardia indications, we've seen the data of left bundle branch block patients. Well, actually, this is a group of patients with a Brady indication from the Geisinger Institute. And what they very nicely demonstrate is the patients who got RV myocardial pacing had worse outcomes than those who had more synchronous activation with HISS bundle pacing. So another thing we're going to think about when we're selecting patients is where their level of block is. Of course, we don't want to pace proximal to the block. So this is a nice trace published by Professor Vijay Raman. And you can see he's mapping the HISS here. And here's a non-conducted beat. And you can see in the more proximal HISS location, there's a HISS before, and then nothing conducts. So at that position, he's proximal to the block. So it's not a good idea to pace there. But if you go more distal on the HISS bundle, then you're beyond the level of block. So important to make sure you're beyond the level of block. He published this nice series along with Gopi, which essentially reassures us that the majority of patients with AV block have disease proximally. And only small numbers of patients have infrahissian block. So HISS pacing is not necessarily a bad approach in this situation. If we think about left bundle branch block and CRT indications, again, the level of block is important. And this was a nice study by the Chicago group. And this population of patients with left bundle branch block, at least 50%, well, 50%, they found that the block was in the left bundle. So you can get distal to this with left bundle pacing. And they showed improved outcomes. So obviously, we've heard lots about left bundle area pacing in the previous talk. How does HISS compare with left bundle? Well, what we see is if you look at total ventricular activation time in CRT patients, we can deliver greater reductions with HISS bundle pacing compared to left bundle area pacing. But in our study here, we didn't detect a hemodynamic difference between HISS and left bundle area pacing across all patients. But there may be specific groups of patients where that more biventricular physiological activation is important, such as patients with RV impairments or possibly pulmonary hypertension. I'm not going to dwell on this because we've already heard about the right bundle. I will briefly touch on the, so there are other patient populations where we might think that HISS bundle pacing is superior to left bundle area pacing. Now, if we're thinking about the long PR interval, Valentina nicely showed that having a long PR interval is associated with worse outcomes because it adversely impacts filling. And we can nicely shorten AV delay without inducing ventricular dyssynchrony using HISS bundle pacing. And we looked at this in the HOPE-HF trial, which was a randomized crossover trial. We had multi-center in the UK, and we showed there were 93% success rates in terms of the HISS bundle implantation in these patients. And you've seen these results. So our primary outcome was peak VO2. But I think many of our patients have, with heart failure, the thing that they ask you is, is our treatment going to help my symptoms? So just because we haven't demonstrated an improvement in peak VO2, I don't think we should underestimate the importance of improving symptoms in our patients with heart failure. And we saw a clear improvement in quality of life and a clear symptomatic benefit. So yes, it'd be nice to have further studies, but maybe even we should design them to look at heart failure symptoms. But another important aspect of this study was the potential for harm with pacing. And reassuringly, there was no signal of harm with ventricular pacing in these patients who've got impaired ventricular function. And that's very different to what we've seen in other studies. We know RV pacing's harmful, but we even know that biventricular pacing is harmful if you deliver it to patients who've got a narrow QRS duration and left ventricular impairment. Because you're actually inducing a degree of ventricular dyssynchrony compared to that. So in the ECHO-CRT study, mortality was increased with biventricular pacing. And importantly, what we found was there was no signal of harm in the, if we deliver biventricular pacing, sorry, his bundle pacing to this group of patients. Atrial fibrillation is another potential group of patients where you might, if it's combined with AV node ablation, there's promising data with biventricular pacing that improves outcomes. And there's this nice study led by Professor Huang in China, which is called the Alternative AF Trial. So all the patients, so patients with heart failure, symptomatic heart failure, and persistent atrial fibrillation all had AV node ablation and both a his bundle lead and a biventricular pacing lead. And they were crossed over between the treatment arms, both nine-month periods of treatment. And what they found was nice improvements in ejection fraction, which was the primary endpoints with by-V pacing. But a modest but significant additional improvements during the his pacing period. So that extra ventricular synchrony, the more physiological activation may be important. So what technique should we use? Well, as we've heard, there have been challenges with his bundle pacing with higher capture thresholds, lower R-wave amplitudes, and rising thresholds, which was one of the big reasons for the drive to try and pace the conduction system more distally. And if we look at the early large registries of his bundle pacing, they certainly found that the overall capture thresholds are a bit higher in this position, and R-wave amplitudes and a slight risk of atrial over-sensing does exist. And the need for re-intervention was about 6% to 8% in these studies, which is higher than for RV pacing and is not ideal. So I think technique is important. So one of the things to think about is the proximity of the leads to the his bundle. So look at this example here, which is where a lead is deployed, and we can see a nice his potential here, but a capture threshold of 1.9 volts. With an extra turn, we see now an injury current on the his bundle, and the threshold drops. So that proximity to the his bundle is likely to be important, and Professor Vijay Raman nicely showed that actually his presence of a his injury was associated with lower capture thresholds. So technique is important, because if we are parahysian rather than actually in very close proximity to the his or have penetrated the bundle, we're likely to have higher outputs. And if we get localized fibrosis, then thresholds may rise as well. Probably the distal his position is better. Here's an example, a published example, where we see in the proximal his position, the capture threshold is a little bit higher. And then they use a dual lead technique, went more distal, and the capture threshold was much, much lower. Obviously that's also to do with the proximity of the leads to the his bundle. There are some advantages with a more distal position. This study found that the sensing thresholds of the R wave was better in a more distal position, and the myocardial capture thresholds were lower. So maybe distal position is better. The relationship of the lead slack has been shown to be important. So this U-shaped slack was found to be much more beneficial, and actually you're more likely to have a rise in thresholds if you have too little or too much slack. So technique is there. And actually, if we look at studies that used experienced operators with good technique, this is the data from the his alternative study. We can see that you can get nice, low thresholds and stable thresholds with his pacing. Now some of these, so this was experienced operators. Now there are challenges still with his pacing in certain patients, and hopefully with development of more advanced tools, maybe leads that are more suited for pacing in a his bundle area, we can make sure that these findings are replicated in everybody's hands. So in conclusion, for me, his bundle pacing is one option as part of a conduction system pacing approach. So I wouldn't accept a high threshold acutely at implants. We've got other options. But if you get good thresholds, you're happy with the way the lead is engaged, then you've got a very good chance of having a good long-term outcome. There are potential advantages for his bundle pacing. It is the only way that we can, or the most physiological way of delivering physiological biventricular activation. We've got a clear landing zone. So we can, the his bundle tells us we're in the right place, whereas left bundle area pacing is not quite the same. It's very easy for us to confirm conduction system capture with his bundle pacing. And there are certain circumstances where maybe that more proximal conduction system capture may be advantageous, particularly patients with right ventricular impairments or pulmonary hypertension. So sorry about the switch up in the talks, but I think it was worth the wait, hopefully. Thank you. Our next speaker is Dr. Bengt Haurig from University of South Florida, and he will be talking to us about hot blot CRT. Pleasure to be here. Thank you for having me. I want to briefly review the historical timeline of CRT and conduction system pacing. So normalization of bundle bench block by distal hiss pacing was initially described by Al-Sharif and coworkers in the late 70s, acutely in the lab using a catheter, but also in animals. But for many, many years, it was impossible to achieve permanent conduction system pacing. For that reason, the mid-90s, biventricular pacing was introduced, initially four-chamber pacing initially described by Kazo and coworkers. In 2000, Deshmukh and coworkers first achieved permanent his bundle pacing in a population of patients undergoing AV junction ablation. It took another 10 years, and then Lustgarten showed correction of left bundle bench block by his bundle pacing. And then in a randomized controlled trial in 14 showed benefit. Then it took until 2017 until direct left bundle pacing became available. And then in 2019, Hott and Lott CRT, the combination of conduction system pacing and left ventricular pacing was introduced. So this is a cartoon showing you the different options, how we can pace a conduction system and combine it with epicardial left ventricular pacing from the coronary venous system. Any combination is possible as long as you can somehow connect it to the device. So how does this look clinically? Like the workflow, for example, in our lab is you have a patient with left bundle bench block with IVCD or with AV block, and we usually start with conduction system pacing. And then there are different scenarios. You can get a nice QIS narrowing to a QIS of less than 130 milliseconds, and then you settle for conduction system pacing. That could be a dual chamber pacemaker or a CRTD with a conduction system lead in the LV port. Second scenario is you have less, you have only partial correction of the conduction abnormality. The QIS is still more than 130, you're unpleased. Then you can consider to combine conduction system pacing with epicardial LV pacing, Hott or Lott CRT. And the other scenario is that the QIS remains wide or is maybe even unchanged. And here you can go back to conventional CRT, or you can still combine the two, thinking that in a patient, for example, with AV block, there may be benefit to combine conduction system pacing with conventional CRT, because you get fused CRT, which you can't achieve in AV block. So I want to briefly, before going into the pacing, I want to briefly review the manifestation of IVCD, because that's relevant to my topic. On the top, you see the left side. On the bottom, the right side. These are ladder diagrams. This is a freestanding IVCD. So the conduction delay here is purely on my cardial cell-to-cell level. The conduction system theoretically is healthy. IVCD can also manifest itself in conjunction with a left bundle branch block. And then you have essentially more delayed myocardial impulse propagation from the right to the left side. Or it could even manifest itself in pacing. None of these things are electrocardiographically explored yet. We don't know how to keep all of this apart. This is purely a theoretical consideration. This is an ECG of a patient with a left bundle branch block. He has notching there in the mid-QIS, but he also has these ugly inverted QIS complexes laterally here that don't belong into a left bundle branch block. So this is a combination or the coexistence of a left bundle with an IVCD. So how does this look? On the left side, you see a myocardial scar, very circumscribed, not a big deal. But if you get a left bundle branch block, you force the impulse to propagate through the myocardium, through the scar, and you activate the lateral wall of the left ventricle late or the area behind the scar. The same is true for pacing in the third cartoon. And then on the right-hand side, our attempt to correct this. So conventional CRT looks like something like this in the setting of IVCD. And in AV block, it looks very similar. So in the MATED CRT trial, ICD therapy was compared to CRTd. And left bundle patients responded very nicely to CRT, and their probability of heart failure hospitalization or death dramatically diminished. So when you break this down into left bundle and IVCD patients, in left bundle patients, the event rates dramatically diminished. But in IVCD patients, actually, they went up. So we heard this before from Valentina. So HOD and LOT CRT essentially attempt to combine conduction system pacing, either from the HYST side or from the left bundle side, with epicardial LV pacing from the cardiac venous system. So this is our first study, HYST-optimized cardiac resynchronization therapy to maximize electrical resynchronization. And these were patients with a predominantly ischemic cardiomyopathy, sick patients. They had a variety of conduction abnormalities. 63% had left bundle ventricle block. The other ones had either IVCD or right ventricular pacing. By the way, these were non-responders and only 15%. The other ones were de novo implants. The baseline EF was low, 24%. And the QoS duration was 183 milliseconds, so rather wide. They were sick. 37% were class IV. This is an example of a HOD CRT case. On the left side, a wide QoS complex, ugly, IVCD-like looking, 210 milliseconds. Selective HYST bundle pacing in the middle. The QoS goes down to 146 milliseconds. It goes down dramatically, but it doesn't go down to normal or to an acceptable range. So then the combination of sequential HYST to LV pacing with a delay of 50 milliseconds yielded a QoS complex of 110 milliseconds. That's a whopping reduction of 100 milliseconds. Here's the x-ray, corresponding lead position, his lead, and left ventricular coronavenous lead. Next case. Here a left bundle branch block, biventricular pacing, improvement. His bundle pacing, looking better, right? And here the combination of his sequential his-to-LV pacing, very narrow QRS complex. Corresponding x-ray, you can even see that the heart size at follow-up is dramatically diminished. In another case, baseline QRS wide, his bundle pacing reduction. The QLV, the LV lead was not placed in a bad place. QLV is 180 milliseconds. However, the combination of the two methods yields the most narrow QRS, but also if you look at the area under the curve of the QRS complex, probably the minimized, most minimal QRS iso area. Here the corresponding x-ray again, his lead. So in this study, 27 patients, we looked at QRS duration at baseline. You can see that that diminished with biventricular pacing moderately, with his bundle pacing more, but with a combination of both dramatically. This is the corresponding echocardiographic data. Ejection fraction went up. Left ventricular volumes were diminished. Left ventricular diameter dramatically diminished, and the NYHA function class also down. All of this looks great, observational study. So this is another study that was performed by the group of Harambhuri. And it's interesting in that it included 19 patients who actually, in whom his bundle pacing failed to correct bundle branch block. So then they resorted to combine his bundle pacing with left ventricular epicardial pacing. 31% ejection fraction at baseline. QRS duration was not that wide. It was 142 milliseconds. But these results are impressive. You see here the QRS duration, the left ventricular activation time, and the right ventricular activation time. And you can see that compared to his bundle pacing without left bundle capture, and all modality of biventricular pacing, hot CRT yields the shortest QRS duration, the shortest left ventricular activation time, but also the shortest right ventricular activation time. Please also notice they tried different CRT approaches. They looked at QRV-guided optimization, echo-guided optimization, and even multipoint pacing. So a small study that was done with echocardiographic imaging and essentially showed an interesting, impressive result. And you can see up there on the echocardiographic images in the middle, hot CRT yielded the least dispersion of left ventricular activation. So this is another study we did. Left bundle branch-optimized cardiac resynchronization therapy. Another collaborative effort here, a cartoon showing how these leads were connected. In general, the LV lead went to the LV port, and some patients who also put it into the atrial port when they had atrial fibrillation. You can see how the wave fronts there on the cartoon collide. The baseline EF in these patients was 28%. Baseline QR is 180 milliseconds in a broad variety of problems. Half of the patients had a left bundle branch block, the other ones either right bundle IVCD or IVRV pacing. You can see an endocardial activation map on the left side with left bundle branch block. Huge dispersion of left ventricular activation. And then on the right side, after a lot of CRT, you see much less dispersion of left ventricular activation. So these are the QRS durations in this study. They look very similar to the HOT-CRT trial. Maximally diminished by LOT-CRT. The combination of left bundle pacing with epicardial coronary venous pacing. So here the echo parameters, ejection fraction went up, left ventricular volumes diminished, left ventricular diameter diminished, and the NYHA functional class diminished. So currently there's a study ongoing. Enrollment is completed. The conduction system pacing optimized therapy tri-C-SPOT. And C-SPOT has already enrolled 60 patients. They qualified for CRT. They preferentially were supposed to have an IVCD, but there was some patients with baseline left bundle branch block. Acute invasive hemodynamic comparison between BIV or LV pacing, left bundle pacing, and LOT-CRT. And there's a six-month follow-up patient with each patient serving as its own control. The primary endpoint of the study was the standard deviation of the activation time, which was accessed by an ECG belt, but also an invasive measurement of left ventricular and DPDT max with a MILAR catheter. The secondary endpoint are echocardiographic parameters and clinical response. So the study has not been analyzed yet. It's in progress, and we'll hear about it soon. Then there's the HOT-CRT trial that was yesterday presented in the late-breaking clinical trial session. There were patients with an EF of less than 35% QIS duration of more than 120, and also patients with an EF between 35 and 50% who had a right ventricular pace burden of more than 40%, expected pace burden of more than 40%. And HOT and LOT-CRT versus biventricular pacing. It's important to understand that this was more of an approach. So these patients first underwent conduction system pacing, and if that failed, then they underwent HOT-CRT. So in the end, in the trial, only a relative minority of the patients really made it through to HOT or LOT-CRT. Most of them responded well to conduction system pacing. So essentially, it's a conduction system pacing study. Primary endpoint, left ventricular ejection fraction, freedom from major complications. Secondary endpoints, heart failure hospitalization, ICD therapies, NYHA functional class QIS duration, left ventricular dimensions, and quality of life. Here you can see the 102 patients that were enrolled, 50 into the bivy arm, 50 in the HOT-CRT arm. There was some crossover. More crossover from the biventricular to the HOT-CRT arm, nine patients, and less so from the HOT to the bivy arm, only two patients. Success rate was slightly bigger in the HOT-CRT arm, actually. So the failure crossover rate was 4% and 18% in the bivy arm. Complication rates, higher in the biventricular arm, surprisingly, and the fluoroscopy times, procedure times, very comparable. Fluoroscopy times slightly longer in the bivy arm. And pacing thresholds, very comparable. QIS reduction, also comparable. The clinical outcomes were very comparable in both arms. I don't have the slides available to me. I think the ejection fraction improvement was a little bit better in the HOT-CRT arm, but overall, very comparable. It's a small study. So in summary, in patients with left bundle branch block, IVCD, or complete AV block, his bundle pacing or left bundle pacing alone may only partially narrow the QIS complex. HOT or LOT-CRT can result in improved electrical resynchronization when compared to conventional biventricular pacing, his bundle pacing, or left bundle pacing alone. HOT and LOT-CRT may address conduction delays at the level of the hispokinesis system as well as late activated myocardium. Fusion optimization usually requires sequential pacing, advancing his or left bundle pacing in front of AV pacing. In patients with AV block, HOT-CRT allows reliable fusion optimization between hispokine activation and left ventricular pacing, independent of conduction. So you get kind of an equivalent of adaptive CRT there. So the observational studies resulted in improved electrical resynchronization. Improved electrical resynchronization with HOT or LOT-CRT may translate into better clinical and echocardiographic outcomes. And finally, does this appear attractive in patients with AV block where we don't get fused adaptive CRT? And that includes patients after AV junction ablation. In CRT non-responders with pre-existing AV lead, and the AV lead could even be in a suboptimal position. In patients with AFib, because they have an available atrial port. And in patients who have coexisting left bundle and IVCD intervened on at different levels. Thank you. And our last speaker for this session is Dr. Jack Rickert from Johns Hopkins. He will actually be closing this with a very controversial topic about LV septal pacing. Well, I was at Johns Hopkins. I'm at the Cleveland Clinic now. Both places are great. Let's see. All right, so left ventricular septal pacing, is it ready for prime time? So the way I took this topic was, are we ready to do conduction system pacing for everybody, really? I mean, we've heard some great talks throughout this entire meeting, but the question we all wanna know is, in 2023, do we give it to everybody? So let's look at that. These are my disclosures. So when we talk about this, we're gonna break it down into two categories, right? So patients who have a preserved LVF with bradycardia versus the traditional CRT candidates, right? Low EF, traditional left bundle, right bundle, IVCD candidates. So I think when we think about whether this is ready for prime time for everybody, we gotta kind of subdivide who we mean that should be getting this. All right, one of the things that hasn't been touched on, and I think this is very important, and when you look at this great paper that just came out of ERA, is LBB area pacing compared to deep septal pacing. So we're not gonna talk about the HISS, we're just gonna talk about LBB area pacing, and when I think of that, that refers to either left bundle branch block pacing, where you're actually engaging the proximal left bundle itself, left ventricular septal pacing, which is where you're deep in the septum, you're close to the LV endocardium, but you're not quite in the conduction system, per se. And then left vesicular pacing, when you're a little more apical, and you're engaging the fascicle rather than more proximal. Now, what is deep septal pacing? Deep septal pacing is when you're in the septum, you're deeper than you would normally put an RV lead in, you're deep, but you're really not on the left side of the septum, and that produces no R prime in V1, and also, you don't have other evidence of conduction system pacing, and that's how we and this group defines deep septal pacing. And the big question is, is this good enough or not? And is it good enough in patients who have a preserved EF? Is it good enough if you don't have a preserved EF? Because when this goes nationwide, worldwide, guarantee you, some of these leads are not gonna be on the left side of the septum, they're gonna end up on the right side of the septum. So when we think about taking conduction system pacing to every man, woman, and child doing this, this is an important consideration. So I'm not gonna belabor this, because we already have talked about it, but RV apical pacing is not good. When you look at some of the early work by Princeton and colleagues, looking at RV apical pacing versus just pacing in the right atrium, pacing the right atrium using the hysperikingy system naturally, you get very nice uniformity in terms of circumferential strain between the RV apex and the LV base. That is very different when you look at RV apical pacing, where you get a very positive initial strain pattern in the RV apex, followed by this massive negative strain in the LV base. And that's kind of the same when it comes to work. You pace the right atrium, you get this nice, the hysperikingy system activates normally, you get a very nice uniform work pattern between the RV apex and LV base, and that's the exact opposite with RV apical pacing. So the hemodynamic effects of RV apical pacing are poor, and I think everyone in this room kind of recognizes that. What do we know about conduction system pacing in terms of how the LV does? Well, this is a great doc study by Mills and colleagues from Circa Rhythmi a couple of years back, looking at internal stretch fraction, as well as global peak shortening delays, comparing RV apical pacing versus septal pacing. And as you can tell, the RV apical pacing is much more asynchronous. The work pattern and the hemodynamics are far inferior to LV septal pacing. In fact, when you look at global peak shortening delays, LV septal pacing and normal conduction are essentially the same. So we have pretty good evidence that conduction system pacing really does a fantastic job of at least kind of mimicking normal conduction. What we don't tell us about is what is the effect of deep septal pacing? Because in this paper, RV septal pacing was not deep septal, it wasn't all the way through. And again, this is a big consideration when this gets unleashed to everyone doing this, how many of these leads are really gonna achieve LV conduction system pacing versus how many are gonna be stuck on the right side of the septum. Not gonna belabor this, we've seen this three times, RV apical pacing is bad. Most trial, when you get to 40% RV pacing, five time fold greater incidence of heart failure, hospitalizations compared to not pacing. So pretty compelling. Data from Cleveland Clinic, RV apical pacing and systolic dysfunction. For 4.3 or follow up, 12.3% of patients developed a pacemaker-mediated cardiomyopathy. So what's the problem in these AV block patients? So it's anywhere between nine and 12% have a big problem, either dropping EF or they're hospitalized. And I would argue a far greater number suffer symptoms from it as well that may not even be captured in these trials. So clearly, RV apical pacing has its issues. So what do we know about left ear area pacing? You know, before we decide to take this on and give everyone a conduction system lead, what are the complications? We've seen this. 8.25% complication rate per the MELAS registry, but I think this is not truly fair. Because if you look, 3.67% of these complications were intraprocedural perforation to the LV cavity. And everyone in this room has done this. How does that happen? You pull it back and basically nothing happens. And is that really a complication? No, not really in my mind. And some of these other rare complications are just that, they're rare. So I think the MELAS registry really shows us that conduction system pacing is quite safe, the complications are rare. Do you have these weird outliers of chest pain? Yes, it happens, but it's uncommon. The other thing for the MELAS registry is that the success rate in heart failure is 82%. It's actually a bit lower than it would be in a traditional CRT population. And these were very, very meticulous, experienced operators doing this. All right, so then the next thing. We're gonna take this around the world, we're gonna keep doing this, we're gonna give it to everybody. What do we know about having to take these things out? So I know there's all these satellite-driven leads coming out, all the manufacturers are having them. But in 2023, still the dominant one is the 3830. And you see, I think the market share for 3830s is dramatically higher than all the others currently. So eventually some of these leads are gonna fail in 10 years, and now we're gonna be dealing with how to take them out. This is data Wilcoff and colleagues put this out recently, trying to see what the best way to extract a 3830 would be. And I would look at test number five, the retained conductor method, where you just kind of retain the conductor at the end without cutting it. MLA is a mid-lead adhesion, which is what you're gonna be facing in eight to 10 years. The most torque you're gonna get on this lead is with a snare. And I tell you, I extract, a lot of us in this audience extract, the snare techniques have a long way to go. And especially with this lead, which is small, trying to find and capture it may not be so easy. What do we know about the clinical experience of extracting 3830s? Well, the answer is not a lot. We know that the lead functions well. In the pediatric population, this was a study looking at duration, looking at freedom from lead complications, and the lead has very good characteristics, but only nine of these leads had to be extracted. They were only 1.4 years old, and they were all removed with manual extraction. But how these leads will function in 10 years, your guess is as good as mine. So, should all patients with a preserved EF and need for ventricular pacing get conjunction system pacing? AV, no disease. So what are the pros? Adverse effects of RV apical pacing are well-documented. Physiologic effects of conjunction system pacing are well-studied. Instance of pacing-induced cardiomyopathy, 9% to 12%. The burden of disease to patients is probably worse, and the complications attributable to conjunction system pacing are quite low. The con, there's actually not a study showing clinical data that conjunction system pacing actually reduces pacemaker-mediated cardiomyopathy. My team and others are working on it. But I think suffice it to say, it's very likely to be positive that it does. Extraction of old luminous leads maybe pose a significant challenge. And a lot of the data from conduction system pacing is coming out of very highly experienced centers. All that's starting to change, I think, as more and more people around the world are doing this. So I would argue that the risk-benefit profile certainly favors conduction system pacing. If you've got a preserved EF and a heart block, we do it in every patient in the Cleveland Clinic meet that. What about sinus node dysfunction? So now you've got a patient who is not going to require significant RV pacing, at least not when you put this lead in. So there's different cultures between Europe and the United States, and it's commonly putting RV leads in. So the question is, if you're going to have an RV lead, why not conduction system pacing? Otherwise, why would you just not place an atrial lead? The con on this one is no compelling clinical data and outcomes in this. RV pacing less than 20% is not really associated with a tremendously high burden of pacemaker-mediated cardiomyopathy. It's there, but it's not super high. And then, do you want every RV lead in your entire practice to be a 38-30 that's 8 to 10 years old at some point? And that's a consideration. So I would say the risk-benefit profile is unclear depending on extraction data, in my mind. If you do it, I don't have a problem with it. If you don't, I don't really have a problem with that either. What do we know about conduction system pacing in the low EF population? Well, we've seen pretty good data. It's all non-randomized. This is 61 non-consecutive patients, six centers, all left bundle, all non-ischemic. Great response in terms of ejection fraction. And not just the response rate, it's a rate of super response to conduction system pacing, which is so exciting. So these left bundles, conduction system pacing, you've got an unbelievable amount of patients that either normalize their ejection fraction or come close to it. And we're not really seeing that to that level with traditional CRT. Same thing in this study, 37 patients with left bundle branch block, EF less than 35%, similar outcomes, great results in terms of ejection fraction improvement, reducing LV endothelic diameter, and improving symptoms. Again, non-randomized data. We've already seen this study. This is, to my knowledge, the largest study, or one of the largest studies on this done, as I can tell. Non-randomized cohort pool study, 477 patients. Again, 54% non-ischemic, 6% mixed, so really it's 60% non-ischemic in a way. A whole different hodgepodge, not just left bundle branch block anymore. And a benefit of conduction system pacing over biventricular pacing. Again, non-randomized. And the possibilities of selection bias clearly are there. Very thought provoking though, and as we've heard already that we're going to get the answer to this in a couple of years. But again, non-randomized. Let me show you a picture. So I run a clinic at the Cleveland Clinic called the CRT-HF Clinic, where we see every conduction system patient and every heart failure patient who got a CRT device or a conduction system device at six months post-op with myself and a heart failure doctor in the room at the same time. 72-year-old male, non-ischemic, EF 33% left bundle. NYJ class 3, had an ICD, prevents for a upgrade. Very experienced operator in terms of conduction system pacing. They decide to go right to LBB area pacing rather than going to CRT. Procedure note, R prime and V1 noted, LVAT was 80. This was the substrate. Strauss left bundle branch block, 160 milliseconds. Next day, not as compelling. No R prime and V1, kind of a wide QRS. It's 138 milliseconds, still narrower than the intrinsic left bundle branch block that the patient had. So I would consider it as deep septal pacing. Chest x-ray, see the bundle lead. It's not that abnormal. Here's the echo. Big apical rock, no improvement at all. And we've seen a number of patients that have come across our halls where if the patient has, in this low EF population, if you end up with deep septal pacing, we're not seeing good benefit. That's very different than the patients we're seeing who've got a nice R prime and V1 where we are. And again, when the thought is, is this ready for prime time, if you're going to do this, you've got to get deep septal pacing. Is it as pertinent in the preserved EF population to get conduction versus deep septal? I don't think we know the answer to that. But I would urge the operators that are going to do this in the left bundle branch block, CRT population, if you're going to do it, you've got to get it. You've got to get deep septal. You can't just leave them with deep septal pacing because we keep seeing this, and this is not the only case of this that I've seen. So conduction system pacing versus CRT in the low EF population. Favors conduction system pacing, non-randomized data, really amazing results, higher super response rate, probably better, quote unquote, response rate as well. And it may be technically easier than traditional CRT for a lot of operators. What favors traditional CRT? Well, we've got 20 years of data with 20 randomized controlled trials showing its benefit. There's been no well-powered randomized trials of conduction system pacing versus traditional CRT. That is changing. The data for conduction system pacing in atypical left bundle IV, CD, RV paced upgrades and right bundle is sparse. We've heard about right bundle. But again, take it from a grain of salt, the data is sparse. These substrates oftentimes are sicker. They have this more ischemic disease. They've got more LV dilatation. They're going to have more distal delay in the hysperkinesia system. Majority of patients in the CSP studies were non-ischemic, by the way. So how this does in the ischemics, we've got data, but we got much more data in non-ischemics. Extraction of traditional CS leads, we know a lot about. And the implantation success with conduction system pacing was only 82% in the MULUS registry. So what do I think, to summarize? CSP may be reasonable up front in patients with typical left bundle, particularly in non-ischemic population. But I would argue you've got to get conduction system pacing. In atypical left bundle, right bundle IVCD, I personally still opt for traditional CRT over conduction system pacing. That may change as we get more experience. Pace upgrades, less than 13% of the MULUS registry. Really too sparse to comment on what to do here. But I definitely, if you're going to do traditional CRT, conduction system pacing, absolutely, before you ever consider sending a patient for another epicardial LV lead surgically, would absolutely try this instead of doing that. So is it ready for prime time? AV node disease, preserved LVF, I would argue, absolutely. I would say every single man, woman, and child should get a conduction system pacemaker if you've got preserved EF and AV node disease. Sinus node dysfunction, I want more extraction data. It's not wrong, it's not right. Low LVF population, you saw the great guidelines that just came out yesterday, a lot of 2A, 2B recommendations. For us, if you've got a Strauss left bundle, go for it. However, I would argue you have to get conduction system pacing. The non-LVF bundles, I still go with traditional CRT. Thank you. We have a few minutes here for a few questions. Since we ended with a little controversy here, we're probably going to start with a controversial question that I am asking, actually. So interesting that we have guidelines now, we have data now, at least a lot of data showing at least observational stuff with LVF pacing. So should we be routinely attempting left panel bench area pacing in patients who would otherwise get biventricular pacing based on existing data? I know we know how you feel, Jack, because you summarized it well. But Bengt, for the rest of the panel, is this something that we should be routinely attempting in a patient who clearly has an indication for biventricular pacing at the current time? Well, the data for biventricular pacing is so solid, and our conduction system data is in the beginnings right now. So I think you can only do that if you're confident, if you're getting a good result. So if you're not able to resynchronize the left panel, I would move on and either took a combination of both or the conventional CRT. But we can do that during the case. For IVCD, I'm not that sure. I think that in some IVCD scenarios, we may be able to do better than CRT. I showed you a mated CRT. The outcomes in IVCDs was very poor. So I have big hopes to get better results, maybe either with conduction system pacing alone or the combination. But it has a lot to do with your confidence level. I share a lot of the concerns you raised. And Mikhail and Jack. I think, you know, the low resistance ways to attempt conduction system pacing and maybe do LV lead too and then you can turn off the LV lead. You have the hardware in place. You can always reprogram the LV lead to pacing later if you lose capture. But that's what I've done in the beginning. And as the confidence increases, then you could forfeit the LV lead. Yeah, for me, I agree with Ben. The bar is higher for CRT indications compared to BRADI indications. BRADI indications is easy. We've just got to make sure that we deliver effective BRADI cardio pacing when required and that our safety outcomes aren't worse. CRT, we're up against mortality benefit. And so for me, it's very easy as a bailout. I completely agree with that. But I generally do this as part of clinical studies. So we consent patients. And it's difficult to justify first line. Even though I believe it's better, we've got to be careful. So we do it generally as part of clinical studies. But we certainly use it for bailout quite frequently because we can be more selective. If we've got a suboptimal LV position, then that's straightforward. We've got a good option that's different. There's another thing. When you put an LV lead in, in the epicardial venous system, and you see a very slew at onset and a late peak, you know already that you're screwed. You know that you're not going to get anywhere with biventricular pacing. So there are scenarios where we're doing the implant actually can see this is not going to work. And we can vice versa for the other side, also identify already who will fail. So I think it's nice to consider both things. And I think it's important for the audience to realize when you're doing CRT pacing, there's no reason not to actually try to do conduction system pacing, even with an LV lead. It's a good way to experience how to do this because you're going to put an RV lead anyway. And so I think that's probably one place for all of you who don't do it routinely to start learning how to do conduction system pacing, maybe. Along the same lines, another controversy here, Zach, for you, and maybe the others can chime in as well. If all the data that's coming out says hispundal pacing is just as, or left ponderbranchiary pacing is just as good as hispundal pacing, at least so far, none of them have shown that one's inferior to the other, why even bother doing hispundal pacing anymore? Yeah, no, it's a good point. And I think to a certain degree, it depends on how comfortable you are with hispundal pacing and your outcomes. Because the great thing about left bundle area pacing is, as I showed, that we got good, reliable thresholds. And with hispundal pacing, that can be an issue if you're not, where the lead isn't positioned. So I think it's difficult at the moment to argue that you should just do hispundal pacing over left bundle pacing in all patients. But I think there are certain populations, so patients where you're a bit worried about the right ventricle, and where you think RV activation is gonna be very helpful, and we've certainly seen that. So patients with pulmonary hypertension, where we've had much bigger responses, hemodynamically, when we've done hispundal pacing versus left bundle area pacing. But ultimately, you've gotta be happy that your patient's gonna be safe, and that you're not gonna have a higher reintervention rate. So I think there's a degree of variability, and some people who still do exclusively hispundal pacing and get good results. So I think we, as the question says, we haven't got the data yet to prove it one way or the other. So I think it's what you're comfortable with, and what you can comfortably deliver. This will be an interesting question because of what you said, Jack. Ken's group just had an abstract showing that whether it's a QR pattern, a QS pattern, an RSR pattern, it didn't make any difference, and they're very small, very small. I saw it yesterday. Yeah, I took a picture of it. The QS pattern in V1, and I think it's, I've asked a lot of people about this. Do you need to have an R-prime in V1 to have conduction system pacing? Do you have a situation where you have just a QS, no R-prime at all, and somehow still have conduction system pacing? I've probably gotten six answers from six different operators who've done a ton of these. I've heard a septal, some sort of fascicular fiber migrating into the septum, and you're capturing that, and somehow that doesn't give you a, it's a small abstract, small numbers. So I think one of the, yeah, go ahead. The lats were all really short. They're all, the average 70 millisecond lats. So they had to be LV septal to have a lat of 70, right? So you can, I was listening to your talk thinking, the implication I got from your talk was if we don't see an R-prime, we're probably not on the LV side of the septum, but the poster that I saw, just like you guys, suggests otherwise. It's the first data I've seen that showed that, to be honest with you, and I took a picture of that poster, and it's like 10 patients, though. Yeah, I think one of the criticisms, and there's actually on social media, I can pick up now, is with his bundle pacing, at least there's a consensus on what we should be looking at. There's clear definitions of what's selective, what's non-selective, and with left ponder branch area pacing right now, there's really no consensus. I think one of the criteria, some of the people are criticizing was everybody has their own LVAT definitions. Now, we see these kinds of abstracts saying whether it's a IQS pattern should be maybe okay. What does it mean? And then yesterday, Garo was showing in a left ponder branch block, the LVAT times exceed about 80 milliseconds or so by definition. So, and there are people who show examples with LVATs of 80 saying it's left ponder branch area pacing. So, I think there's a lot of, you know, everybody has their own definitions, and I think it's creating a lot of chaos, and I think it's imperative that people who do this actually come up with a consensus based on what we think at least physiologically makes sense to come up with some criteria. Otherwise, like you're suggesting, what is deep septal pacing? Now, if abstract says it's a QS, it doesn't matter, and then LVAT times are different by everybody's measurements. How do we now tell at the time of procedure that we're actually getting left ponder branch? So, the ERA document, which is beautiful, which has been studied, I think, by almost all of us here, it just came out, actually had a definition for deep septal pacing, and that was no R prime and V1 and no other criteria for conduction system pacing. So, that was how they defined it. Maybe one last question. So, when you're doing lot-hot CRT, how do you decide? Do you decide pre-procedure based on ECG, or what parameters do you use intraoperatively to say, you know what, I'm gonna attempt putting an LV lead here, or maybe I'll go the other way and add a conduction system pacing lead? So, two different scenarios. One scenario is upgrade, right? We already have an LV lead. We have a failing CRT device, non-responder. Obviously, that's easy. We know before the procedure that we're considering this. As a de novo implant, it's something only I consider if I don't achieve my goals with the regular strategy of conduction system pacing or biventricular pacing. So, I do want to know beforehand, because obviously that might make a difference in terms of which, if you're doing it as an ICD, which ICD lead do you use? We've got a paper in preparation where we looked at this. Everybody's talked about Strauss, which is a pretty good way of doing it, and we've compared a whole host of other measurements, including pre-procedure MRI, but the key thing seems to be electrical measurements, and not electrical measurements in terms of QRS duration, but patterns. So, Strauss is pretty good, not perfect. If you're looking at patterns in terms of activation maps, we've looked at non-invasive mapping using the CGI system. That's very predictive, but obviously expensive. Ultra-high frequency CG seems to work. If you look at pattern, not overall time. So, it seems to be electrical pattern is the key thing, rather than sort of any echo measurement, or MRI can be a bit helpful, but not perfect. So, that's the ideal scenarios. You can pre-plan your procedure. I think we're at time here, so thank you all for joining, and thanks to our panel again.

Conduction system pacing

Heart conditions

His bundle pacing

Left bundle branch pacing

Biventricular pacing

Heart function

Heart failure

Ejection fraction

Quality of life

Right bundle branch block

Left bundle branch area pacing

Bradycardia

Lead extraction