So, good morning, everyone. Thank you to be here. I'm Dr. Mondeser from Montreal Heart Institute in Canada. It's my pleasure to co-chair this session with my colleague, Dr. Zanon, from Italy, on the CRT and the LBB. So, if you have not already done, please download the app for the question, and then you can submit your question on the system, on the app, and we can answer that at the end of the session. So, now, it's my pleasure to introduce our first speaker, who is going to be pro-the CSP, to replace the CRT implant, Dr. Neeraj from the Cleveland Clinic. Thank you very much. Good morning, ladies and gentlemen. So, I am going to speak about conduction system pacing as a replacement for CRT. So, this is a debate, but I think the question's already been answered, that this is the way to go. So, I would like to begin by sharing some points about my opponent. It's very important to understand your opponent in a debate. So, Judith Mackle, she's a Cleveland resident, and she grew up in Parma, Ohio, which is an idyllic suburb of Cleveland. And then she moved to University Hospitals, Case Western Reserve University. This is important, and I'll bring up that point later. This is a distance of about 12 and a half miles. It's a very intrepid journey. But via automobile, it takes 20 minutes. I suggest on a tricycle, it may take longer. But there, she's risen to this eminent position of Medical Director of the Cardiac Device Clinic, Program Director of the EP Fellowship, Spitzmaster Clinician of University Hospitals, and Moll Professor of Case Western Reserve University. So, now you understand that I have quite a daunting task here. But there is one essential weakness here, and that is she's remained loyal to this vehicle. This is her conveyance, even now. APACE, RV-PACE, and LV-PACE, atrial biventricular pacing. And this is surprising, because it's a parallel technology that's evolved, and overtaken, I would suggest. I mean, we have the bicycle here. So, A and CSP. This is a better technology. This is our conveyance of today. And more so because, from 100 years ago, from Carl Wiggers, at Dr. Mackel's institution, Lakeside Hospital of Case Western Reserve University, Carl Wiggers showed that LV epicardial pacing is slow, it excites the ventricle in reverse to natural conduction, and it is hemodynamically compromising. So, this is a very poor solution. And we've known this for 100 years. And this started from case itself. And Eugene Braunwald, in his eulogy to Carl Wiggers, said that he's the unchallenged king of cardiovascular physiology. And yet, 100 years later, at university hospitals, they're still using LV epicardial pacing. 80 years later, Yoram Rudy's group showed ECGI. And this is the first depiction of normal activation of the ventricle. This is the activation in left bundle branch block, a large line of block here. But then the solution of LV pacing widens the QRS and slows LV conduction. So, this is a problem. This is a problem. A solution is to pace from different points. And actually, one of your PhD students invented the quadrupolar lead as a rescue to help you out a little bit, Dr. Mackel, here. And simultaneously pace this with multipoint pacing. But pacing all these sites together consumes energy. And in large randomized trials, it was ineffective. So, this is not helpful. Can you optimize the various wave fronts, AV interval, VV interval? This is complicated. This is very complicated and time consuming. Can you automate it? But yes, the automatic algorithms also fail to show any benefit. So, there is a significant restriction here. A significant limitation. But I will emphasize that there is a considerable body of data, which I'm sure Dr. Mackel will go over, to support CRT. Multiple trials showing that this vehicle is effective. It does get you so far. But if you look at the hazard ratios, they're really rather modest. So, can we do better? I think we can do better, particularly with physiological pacing. Because the lesion is at the his bundle or the left bundle branch block here. And we can pace at that site. It is distal to that site. And obviously recover normal activation of the left ventricle. This is much more physiological. And it leads to significant improvements in outcomes, which I'll go over. So, physiological pacing. I've shown you ECGI maps before and showing the line of block in left bundle branch block. With his bundle pacing here, smooth rapid activation across the line of block. We see that the QRS from left bundle branch block completely normalizes. This is a normal QRS with conduction system pacing here. If we look at measurements taken during CSP here, activation of the left ventricle, biventricular pacing here, and then his bundle pacing and left bundle area pacing. Completely normal activation here. Much faster activation. We see total ventricular activation time significantly improved compared to biventricular pacing. We see that acute hemodynamic improvement is significantly improved with his bundle pacing, left bundle area pacing, compared to biv pacing. Really supporting the observations of Wiggers from 100 years ago. In long-term follow-up, we see that time to death or heart failure hospitalization is significantly reduced with left bundle area pacing. If we look at a very interesting observation, we see similar benefits of conduction system pacing in patients with left bundle branch block and non-left bundle branch block in terms of QRS duration, in terms of New York Heart Association class, LVEF, end diastolic diameter for both left bundle branch block and non-left bundle branch block. In red here, left bundle area pacing and baseline here. So very, very important effects. There are multiple randomized controlled trials. Not enrolling as many patients for CRT, but CRT has been around for a long time, of course. Multiple randomized controlled trials supporting CSP versus BIV, superior outcomes. And these are consistent results. These are consistent results. So this is a very strong signal. If we look at meta-analyses of these, they're all leaning towards CSP. Again, not so many patients, but for LVEF, significant improvement here. ESV, trend towards significant improvement. Hospitalizations, trends here again, certainly non-inferior. And mortality, trends to improvement. So the early signals from CSP are highly encouraging for improved patient outcomes. If we look at specific aspects here, if we look at arrhythmic risk, with biventricular pacing, you have a much higher incidence of ventricular tachycardia and ventricular fibrillation compared to CSP. Also for atrial fibrillation, nuance at atrial fibrillation significantly suppressed with conduction system pacing during follow-up periods here. So CSP is also antiarrhythmic. What about safety? This is very important. If we look at safety, complications of left front branch area pacing compared to biventricular pacing in candidates for CRT, we see far fewer complications with conduction system pacing here compared to biventricular pacing. Periprocedural complications in meta-analyses, again, significant reduction here in complications associated with this. Notably, pacing thresholds are much lower with CSP versus biventricular pacing. Pacing thresholds acutely and at six months. This is important because it reduces the need for generator changes, which, of course, are associated with infection, lead fracture, extraction risks. So they're costly not only for the generator, but in terms of patient morbidity and also health care resources. So this effect on pacing thresholds has significant long-term implications. And, of course, CSP rescues failed by V. We know the incidence, even in randomized trials, of failed delivery of the left ventricular electrode occurs in a significant proportion of patients, maybe 5% to 10%. And CSP has been used as a rescue. Initially, this was from 12 years ago, this paper, and CSP was used very effectively here. Since then, there have been multiple studies to show this. And, in fact, the guidelines from two years ago indicated that the success rates to rescue after failed LV placement or non-responders to CRT ranged approximately at 90%. So this is a very important bailout procedure. And that receives a class two way indication in the guidelines, CSP versus biventricular pacing. And, of course, the technology is moving. This technology is moving. And in the future, we look forward to leadless left bundle area pacing. This was a milestone that was announced by one of the companies, the first leadless left bundle branch area pacing procedure delivered from the right ventricle. This is not actually the device that was used, but the device that was used is a development of this. And last week, FDA approved LV leadless pacing. So leadless LV pacing, this electrode is the size of a grain of rice, and it can be delivered to the left bundle branch, which is, of course, just underneath the left ventricular endocardium. So a very exciting way, the YCRT system, for achieving leadless conduction system pacing. CSP can reshape guidelines. We see here patients with mildly reduced left ventricular ejection fraction. Primary outcome of death or heart failure hospitalization in patients with left bundle branch block. So this is not our usual population of LBBB and HFREF. These patients have EFs above 35%, but still left bundle branch block. And we know that's a marker of morbidity in this patient group. So CSP had a far better efficacy compared to standard biventricular pacing. So this is likely to reshape guidelines. A very exciting development comes here. Non-ischemic cardiomyopathy with left bundle branch block. There's a controversy raging just now over whether non-ischemic cardiomyopathy with HFREF should receive prophylactic ICD therapy. So the guidelines still support this, but we know that the incidence of sudden cardiac death is very low. So should we be practicing this? Well, one risk stratifier is MRI findings of LGE, so late catilinium enhancement. So the hypothesis here was that if patients did not have scar on MRI and non-ischemic cardiomyopathy and left bundle branch block, they had no arrhythmic risk. So why implant an ICD? But you could still resynchronize them with a pacemaker or a left bundle branch area RV lead coupled to a pacemaker. And here we see time-to-death heart failure hospitalizations or sustained VT or VF negligible, absolutely negligible in patients stratified by MRI. So they came out with a hypothesis that a DDD pacemaker without an ICD platform may be concerted in this group of patients who have low scar burden. So this has significant economical implications and also patient morbidity implications. In a group of patients with left bundle branch block, non-ischemic cardiomyopathy, and no scar burden. So this is a window into the future. So I would summarize by saying that atrial biventricular pacing is very stately, but it belongs to a different century. And really, we're in a powered area of atrial pacing with CSP leads, two leads. Thank you very much. Thank you. Thank you very much. And now we have to listen to the opposite in this debate, which now has become real. And some years ago was completely in favor of CRT. Now things seem to be more equal. So please, I invite Mekhal Judith to say if CRT is better. Please. Thank you. Okay, thanks. Good morning, and thank you, chairs. And thanks to the Heart Rhythm Society for inviting me to face my formidable former colleague, Dr. Neeraj Varma. I have been given the task of, I guess, defending CRT. I hope he wasn't meaning that I am from the last century, but that might be part of what he was implying. I would like to make three points over the next few minutes, which I think will make my case that conduction system pacing should not replace CRT. And I'd like to just look at the level of evidence for biventricular pacing and then review whether or not you can actually achieve conduction system pacing in every heart failure patient, and finally talk about some of the lead considerations that we have to factor into our equation. So for those of you who haven't been in this space, cardiac pacing for heart failure was really designed to treat patients with heart failure who have slow conduction, and that's about 25% to 30% of patients who present with heart failure. And we determine that by looking at the electrocardiogram and seeing a widened QRS. And this delay in timing to the left posterior and posterolateral wall results in a desynchronous contraction. And so when we talk about physiologic pacing, we're talking about how to restore synchrony to a left ventricle and improve cardiac output. And biventricular pacing, really first proposed by a case report, I think in 1994, showed remarkable improvement in severe heart failure. We contrast this to conduction system pacing, where the lead is drilled into the septum to try to jump onto the Purkinje system and use that superhighway to get the activation around the ventricle in a quick and organized way. And his pacing has been around also for over 20 years, but we have evolved to discussing more about left bundle branch area pacing, and we'll talk a minute about that. So after the recognition that we could overcome conduction delay, excuse me, by pacing from the LV epicardium, there were numerous randomized control clinical trials that were undertaken in the late 90s and through the early 2000s, and all published results really within the first decade of the 2000s. And these trials looked at patients with mild, moderate, and severe heart failure with depressed ejection fractions, intraventricular conduction delay, on guideline-directed medical therapy, which we will acknowledge is not the same as what guideline-directed medical therapy for heart failure is now. But in that era, it meant beta blocker, ACE or ARB, and a mineralocorticoid antagonist. And these trials really enrolled a lot of patients. So this is over 7,000 patients in a randomized controlled clinical trial. And the data was actually very consistent among the studies. This was a meta-analysis, looking at five of the large trials, but really showing a reduction in all-cause mortality and the combined endpoint of heart failure, hospitalization, and mortality of 30 to 40%. So this is really high-quality data. And that's why in 2023, when the guidelines for physiologic pacing were published, they assigned biventricular pacing a class one indication or 2A, and the level of evidence or the quality of evidence is the highest there is. Now, let's look at the randomized controlled trials of conduction system pacing. I didn't include the earlier HYST trials, but what we learned from that is that even though we could restore narrow QRS and have good outcomes, achieving HYST bundle pacing was somewhat challenging because your target is much smaller, and over time, the thresholds rose. And that became, I think, the biggest issue with HYST bundle pacing. But we do have two randomized controlled trials of conduction system pacing using left bundle branch area pacing. They have short follow-up, six months, and they looked at really reverse remodeling as the endpoint of these trials. And this is 140 patients. So even though Dr. Varma showed us data from registries that contain over thousands of patients, the randomized controlled trial data is not strong. And therefore, the guidelines, when they assign conduction system pacing, predominantly a 2B indication, the level of evidence is really limited data or much weaker. And so I think we need to keep that in mind. Now, I should have pointed out on the previous slide that in those two randomized controlled trials, they were actually able to achieve left bundle branch area pacing in 86 to 90% of patients. But it raises the question of whether you can achieve conduction system pacing in patients who have cardiomyopathy, septal scar, conduction system disease that's more distal. This study, which was the MILO study, the multicenter European left bundle branch area pacing outcome study, was a prospective multicenter registry looking at real world data. And they looked at conduction system pacing in patients who had both Brady indications and a heart failure indication. And you can see, let me see if I can do that, that for patients who had heart failure as their indication, they were successful in 82.2% of patients. And in fact, having heart failure as an indication for your conduction system lead was one of the independent predictors for failure of LBBAP pacemaker placement, lead placement. Now, we're talking about conduction system pacing and we're talking about screwing the lead into the septum and hooking on to the conduction system. And getting the conduction system, we're gonna focus lower on the septum. When we talk about the left bundle branch area, we're talking about really getting into one of the posterior fascicles. And we have a large target area on the septum, right? But if we don't capture the conduction system, we end up somewhere in the middle. And that falls into this category of LV septal pacing, which, if you're not capturing the conduction system, you really have deep septal pacing. So that's really RV pacing. And I love that we're both pulling up Carl Wigger's data. But what he showed in that paper was that it didn't matter where you stimulated the ventricle anywhere in the right ventricle, you lost LV efficiency. You had a drop in your LVDPDT. And we have seen this in other conduction system trials that if you are not able to capture the conduction system, you essentially have RV pacing. And in the heart failure population, RV pacing compared to Bi-V pacing is not a good thing. And this was, of course, data from Block HF, which looked at patients with reduced ejection fraction who were going to require a high burden of pacing. And you know what's interesting about this study? I don't know how many of you in the room participated. It was a long study. There were actually two groups, the groups in the 35 to 50 and the group less than 35 because you could get an ICD or you could just get biventricular pacing. And the response to Bi-V pacing was the same regardless of which group you were in, which tells us that you can achieve resynchronization kind of independent of the ejection fraction, which I think is important. Here's some very tantalizing data that was published in 2023. This was, again, a prospective observational study, multi-center study. And they looked at patients who were undergoing CRT and they looked at patients prospectively. They decided between the patient and the implanter whether the patient would accept a conduction system lead or go traditionally. And in this group of 172 patients who were going to have conduction system pacing, they were successful in 141 patients. The ones who were not successful fell into the LV septal pacing group. And even though it didn't achieve significance, this curve looking at the combined outcome of heart failure, hospitalization, and mortality looks much worse than biventricular pacing or conduction system pacing. It was driven by heart failure hospitalizations. And what's very fascinating is that the improvement in LVEF with LV septal pacing was actually minimal. So I think that a caution to conduction system pacing when you can't achieve conduction system capture. And again, their success rate, 82%, compared to a BIVI success rate of 94%. Now, let's talk a little bit about the lead. Dr. Varma kind of brushed over this a little bit, telling you that the complication rate is much lower. Well, the complication rate is lower, but there are much different complications. We don't usually see chest pain, septal hematoma, coronary artery fistula. That probably concerns me less because that's all treated conservatively. But what worries me a little bit is this risk of entanglement of the lead in the septum and not being able to withdraw it. This idea that you're going to dislodge or perforate. And you know, you can build up a lot of torque on these leads and think you're done, and it can then, after you peel, move one way or the other. So I think we don't know. The idea that we could have a partial perforation into the left ventricle with the screw still have good capture thresholds, but not know that we've now got this nidus for thrombus sitting in the LV, it worries me a little bit. Additionally, if the patient needs an ICD at this time, they're gonna have two leads across the tricuspid valve, one for the defibrillator and one for the conduction system lead. And as we said, we don't really know how easy these leads are gonna be to take out. And we actually don't have long-term data on how these leads will perform in this location. And I'm not gonna dwell on that, but if you look at the lead in the septum, it's got this funny little hinge point that doesn't seem normal. And I know Dr. Varma has been around as long as I have, and we lived through the AccuFix Telectronics J lead. So there's always this concern that the lead data is not yet there. So I hope that I have convinced you this morning that the level of evidence for conduction system pacing is comprised of predominantly registry data, unlike what we have for Bi-V in cardiac resynchronization therapy, that the success rates actually for heart failure patients, Dr. Varma rounded up to 90, I rounded down to 80, but it's in the mid-80s for most of the studies. There is a component of LV septal pacing that may not achieve resynchronization therapy, and in fact, then, you are leaving the patient with RV pacing. And then, as we said, lead considerations that at this time are not yet known. Thank you. Thank you, Dr. Mackel. As Dr. Mackel said, we were colleagues for many years. So you're as persuasive as you used to be, you're very persuasive. But I would like to point out, I would agree with the fact that CSB has limited data, but all the data from limited trial data are very consistent for efficacy and for safety. But there are limitations, and mainly technical limitations. Those registries span developments in technologies. So delivery tools have improved significantly, and the success rate now, I think, is significantly higher than it was at the outset, as we moved from HISS pacing to left bundle branch area pacing and the delivery tools that we have to do that. So the 82% success rate in patients with heart failure, predominantly because of dilated left ventricles and heart failure, was really because these were stylet-driven CSB leads. But now we have an extensive range of delivery sheets for that. Yes, many of those leads were not designed, and we do not know what their long-term performance is because of the hinge points, but these are being addressed by the manufacturers. And also, as we move towards leadless pacing, we will avoid many of those complications, and also the tricuspid valve regurgitation complication. So I think this is a technology, as I emphasized, that is moving, that is moving very fast. As opposed to CRT, which is static, we've tried multipoint pacing, we've tried two quadrupolar leads delivered to the LV, we've tried optimization algorithms. Nothing has moved the field forwards there, but in CSP, the field is moving forwards very quickly. But the outstanding question remains, substrate. Not only conduction system substrate, because a significant proportion of patients who have a left bundle branch block on their surface ECG do not actually have disease of the hispokinesia system on the left side of the heart. So where is that lesion? Maybe it's due to intramyocardial conduction. And a lead delivered to pace the left bundle when the left bundle is intact is not going to achieve anything. So we need to understand substrate, we need to understand intramyocyte conduction in heart failure. So this is very important. And I think in this group of challenging patients, it needs to be well defined, we will come to a combination. We'll use a conduction system pacing lead, and we shall use a left ventricular lead, a conventional left ventricular lead. So I think that is where the field is going. I of course agree with everything that Dr. Varma said, but I would like to just mention a couple of things that we didn't touch on that I do think are important. So, this is the guideline document for patients who have an indication for pacing and who have preserved heart function. Because I think that there is a tendency in the field to place the dual-chamber pacemaker and put a conduction system lead in. And in the guidelines, it did receive a 2B indication that you could consider conduction system pacing in this population. But we now know from Biopace that the likelihood of developing heart failure if you have normal EF with RV pacing is actually quite low. And that, at least in this Biopace trial, if you started with a high burden of pacing and a normal EF, there was no benefit between the traditional RV pacing lead and biventricular pacing. So, I think you can claim success if you mitigate heart failure with RV pacing. But if your EF is normal, mitigating heart failure in a situation where it's unlikely to happen is probably not a success. And at this time, perhaps exposing your patient to a long-term risk. So, after Milos was published, these two leaders in the field of pacing published an editorial where they point out the problem with observational studies and registry data. When you don't have controlled trial data, you open the results to investigator bias. And I think we're all, all of these electrophysiologists in this trial who want the very best for their patients, they're very good electrophysiologists. And so, their ability to select patients may influence the data. Now, I think that I can happily say that all of these people on the Guideline Committee agree with me. And I want to also point out that look who's on the Guideline Committee. Dr. Varma. So, he agrees with me too. Thank you. Long-term data? No. No, it's a comparative CSP. Well, long-term is we do have some long-term on his less long-term for left bundle, of course. But I think success and efficacy are equivalent for lumen-less versus those with a lumen. It's data-driven. In terms of stability, have you seen any differences in between the lumen-less and the driven-stated leads? I'm sorry? In terms of stability. In terms of stability? Yeah. Do you have any difference? I believe that the data that are available show equivalent stability as well. Yeah. Sorry. No, this is an interesting question. Do we have obligation to teach fellow both strategies? I think it's my personal view, of course. More technique we know, more chance we give to our patient. Yeah, I would agree, I do think. Yes. I can, yeah. No, go ahead. I completely agree. I think we need to teach both techniques. There is a tendency, because CSB is very appealing, just because it's physiological, it's a neat solution. But as the points were made, that we don't have long-term data on this. But there is a tendency to simply switch to CSB, and in some programs, fellows are losing the training of LV lead delivery. So, CRT is becoming a more difficult procedure now. But I think that's a mistake. I think we need to teach both techniques, because I think in the future, we should be using both techniques, depending on the individual patient. Yeah, and especially, I think that my personal approach is start with his, go, if not a good parameter, go to LV. And in case of fibrous tissue, or you cannot resynchronize, go to CRT. So, you have to be really familiar with both, with all the three technique in such a way to give the best option to the patient. You know, I would just like to comment an extension of that question to, if you are implanting and have not started conduction system pacing. You know, if you look at the Milos Registry, it's a little bit daunting, because they published that the learning curve was really like 100 patients. But in fact, as Dr. Varma was alluding to, with the current delivery sheaths, the ability to reach the septum, to map the septum, is all much better. And as a tool, and a learning tool for an experienced implanter, I think it is something that everybody is probably at some point gonna want to learn. I totally agree. We need both of the techniques in our hands, and we still need to teach that. In the same range of question, a fellow is just asking if there is any data comparing the stability between CSP leads and Bi-V lead. In his experience, there is more displacement with the CSP lead. So I think the LV lead is, I've hardly ever seen an LV lead displace out of the tributary. It can change position within the CS tributary itself, and thresholds might change. With CSP, I think the issue is electrical stability, because sometimes the paste QRS in the lab, that might be perfect, but several months later has evolved, perhaps because of fibrosis around the lead tip. So this is something that we need to track. So I think the electrical stability of a CSP lead needs to be tracked better. I'll just get your comments on that. Yeah, definitely. We are now collecting data on his bundle pacing, and we have a collaboration also with Pugal Data. And it's very interesting, because also there is no data on 10 years data, no standard pacemaker, I mean. And it's quite interesting. Of course, there is some, approximately 10% of losing of pacing, but we don't know how much is in standard pacemaker after 10 years, because especially if you consider the patient population are very old, the average is approximately 80. So it's difficult to have such a long. This is for his, of course, the LB, if you think the first publication was seven years ago, but now data are increasing and increasing, yeah. But I have to say that for conventional CRT, if we look at our super responders, who come back for two, three generator changes, the LB lead stays stable, and they do very, very well. So we do have long-term data on conventional LB leads, and it is very impressive. And their response is maintained. So their improvement is maintained over many years, which I think is important. There is some questions about left ventricular septal pacing and LBBAP. Should we still consider the left ventricular septal pacing as LBBAP? LBBAP? So there are not many data on this. I mean, there are not many data in the CSP space altogether, and there are very few data on LV septal pacing or deep septal pacing versus successful CSP. The older data show that if you reach the LV endocardium, not necessarily the conduction system, you actually are achieving rapid LV activation. But as Dr. Michael said, if you're only achieving mid-septal pacing, that might not be successful. Although there are some data that suggests that those patients simply catch up. They need more time to catch up with successful CSP. So I think these data are mixed. I don't think we can make conclusions from it. But I will say that in the last study that I cited, the Madurai LVBP study, where they went to a pacemaker in patients with non ischemic cardiomyopathy, left frontal branch block, and no scar, they were very careful, very, very careful with adjudicating successful CSP. And if they felt they had not achieved successful CSP at strict criteria, then they considered that deep septal pacing. And under those conditions, they also delivered a left ventricular lead. So this is not CRT. There are some other questions, many. So this question is, for a patient that need a CRT-D device, are you going with CS lead as default or as LBAP lead as a default option? For both of you. I am starting with a CRT-D and a CS lead, and using conduction system pacing as a bailout. Again, because of my concern about two leads across the tricuspid valve, but also the great data in this space that we have right now. So I think that's what I'm doing. So in patients with a class 1A indication for CRT, left bundle branch block and a QRS of more than 150, I go with a conventional CRT first and only use CSP as a bailout. Yeah, I think if we have to be educational, I think that we have to follow, in this moment, guidelines. And if there's an action fraction, 30 and LB. So maybe you can consider different option if it's right bundle or something like this. But in case of the typical class 1 indication, I agree that even if many observation, but still observation are not clear evidence guided by randomized trial. But that is coming with the left versus left trial. Yeah. So that will answer that question definitively. What do you think on the left versus left? Do you agree that maybe the end point is superiority? Do you think that could win or maybe was more easy to do non-inferiority? I mean, non-inferiority, if you can compare, you could have, in case of simple pacing, you can have just one lead less. So it gains. It gains, it gains. No, I agree. I think non-inferiority would be a gain. It would be a step. But they're powered for superiority. Given the observational data that are there, which are consistent, and I appreciate the fact that they're limited, but they are multi-center. I mean, there are 20, 30 sites in that, and the signal is consistent for superiority. So I think a superiority end point is justified. Yeah. There is some question about the risk of perforation, acute and late, and the risk of extraction and perforation of the septum at the time of the extraction of the lead in 20 years. What do you think about that risk? Well, I think acutely, I have seen it all. I think that acutely, and even within the first 24 hours, which is kind of a late-ish perforation, it is fairly simple to remove the lead with no sequelae and place a new lead, or at least make sure that the tip is clean. But I think the long-term extraction data, we have long-term extraction data on the HISS position, which seems feasible and without issue. I expect that it will likely be the same for the CSP, but we don't have that data yet. It's been published, a serial of more than 300. Also, we gave some patient, and the complication rate is very, very low. There is also some question about the septal score. If the conduction capture is not good enough, good enough, is the electro-mapping, anatomical mapping is used in your practice, is useful? So I think septal scar has been consistently shown to be an impediment to successful CSP. Delivering a left bundle branch area pacing lead is usually ineffective in patients with large septal scar. On the other hand, in some patients with a smaller septal scar, achieved it successfully. So there's no harm in trying, but overall, the data suggests that you're going to be unsuccessful, and I think you have to go with conventional CRT under those conditions. Yeah, maybe in ideal world, you should have each patient MRI, so see for scar and so on. But yeah, of course, every institution has its organization, limitation, different facility and so on. But in ideal world, to have an MRI in each patient would be ideal. So there's a question on the, your indication of the LOD CRT. When are you using the LOD CRT? So I think that's a great question. I think that's really the open space just now. We were discussing it before the meeting. Here, we are guided by conduction patterns. And if it's not possible to successfully achieve CSP with the appropriate ECG with conduction system pacing, we go to LOD CRT. But the ECG now doesn't tell us very much. And I think this happens in patients with advanced heart failure, large ventricles, more conduction pathways, less intercellular conduction. So this is a complicated substrate. And both CSP and LV pacing achieve slow conduction, but maybe in combination, they will achieve the degree of resynchronization. But it's hard to tell this from the ECG because ECG under those conditions is virtually non-interpretable. So there is a question about whether we should use non-invasive imaging techniques to try and guide this like ECGI that I showed and some of my slides, which was invented at your hospital, Dr. Michael. So you may have a comment on it. Well, again, I think we need more data in the LOD CRT space because I think in the published trial, it was five patients that had the CRT lead and the conduction system lead. It is kind of the epitome of multi-site pacing, widely spaced to try to overcome this conduction slowing. And the reality is we don't have a lot of places to go. I mean that the conduction system space seems big, but where you get that LV lead in the real world, you may have one spot, one vein. So I think targeting areas like that, even if you used ECGI for practical application, I think is limited or difficult. Any comments from the chairs? Yeah, I perfectly agree. If we have, no doubt, if we have a narrow QRS, as you show, this mean complete recruitment of the conduction system is no doubt. The problem is when we have this large QRS in which we don't understand what we are doing, are we resynchronized or what? So what we need, and this is an unmet need, is to find some simple method during the procedure to understand if we have to move forward and say, I put a CS, do we need a conduction system also or vice versa? That's what an unmet need. And we hope that the company and technician will develop some easy tool, I mean, because it has to be intra-operatory tool, yeah. Do you have any QRS with just numbers where with the CRT you want to put a LBB after that just to try to narrow your QRS or in the other way, not the CRT first and the LBB? When do you add the lot? Yeah, so this is interesting because when you LV epicardly pace, I showed the Wiggers diagram. It's a very wide QRS. But in patients in real life, sometimes that QRS is narrow, LV pace QRS. So whatever the conduction pathways is, it is depolarizing the ventricle quickly. At other times, the QRS can be very wide and this is simply LV pacing, not LV fusion pacing. And personally, I use a metric of 200 milliseconds. If the LV pace QRS is more than 200 milliseconds, then I think this is not going to be successful resynchronization conventionally. Because I've gone to atrial biventricular pacing under those conditions and shown that we can't narrow the QRS because the LV pace wave front is so slow, even with LV pre-pacing, so pre-excited pacing. There is data in the RV upgrade literature that once that QRS duration is over 200 milliseconds, you're really selecting out patients who have significant myocardial conduction disease and resynchronization is not successful or more difficult. So 200 seems to be a cut point. Yeah. Yeah, of course, one easy patient is a chronic permanent, a fib in which you have a free port that you can utilize. So the last one. Yeah, which one do you want? Well, this could be interesting. When to stop turning LV AP lead to prevent septal perforation. This is a practical. Oh, drop in impedance. Yeah, as soon as you get a drop in impedance that's 100 or more, you should stop screwing. Yeah. I think. Which other one? Choose one. Then we'll finish. In the LBB area pacing, is it equivalent to pace the left anterior fascicle and the left, or the left posterior fascicle? Well, it should be equivalent, but I think that when you're targeting the anterior fascicle you're now increasing, I think, your risk of hitting a septal perforator. I think the complication rate is a little higher in the anterior septum, but I think the ability to jump onto the conduction system is the same. I think in practice, we often hit the left posterior fascicle and the results, as far as we can see, are equivalent. They're fine. Yeah, absolutely. So, we're almost nine o'clock now, so we will thank you to be there this morning for the early session, and that was a fantastic debate. Thank you to the debaters and to my co-chair, and we wish you a good day. Thank you.

conduction system pacing

cardiac resynchronization therapy

heart failure

CSP vs CRT

pacing technologies

leadless pacing

randomized controlled trials

patient outcomes

training