The literature on conduction system pacing continues to grow with an emphasis on comparison with traditional CRT for patients with traditional indications. In the episode of The Lead, recorded live from the Asia Pacific Heart Rhythm Society meeting in Sydney, Australia, we will be discussing conduction system pacing compared to biventricular pacing for cardiac resynchronization therapy in patients with heart failure and mildly reduced left ventricular ejection fraction. This is from the International Collaborative Left Bundle Branch Area Pacing Study, the I-Class Group, being presented here and published simultaneously in Heart Rhythm by Dr. Vijaya Raman from Geisinger Heart Institute for the I-Class Group. I'm Jason Jacobson, director of the Complex Arrhythmia Ablation Program at Westchester Medical Center, and joining me for this discussion are Dominic Lins from Maastricht University Medical Center and Jared Bunch from the University of Utah School of Medicine and editor of Heart Rhythm Case Reports. Thank you both for taking the time during APHRS to discuss this paper. Dom, would you summarize the paper for us? Or would Jared? I'll go ahead and do it. Great. Thank you. So this is an interesting study. It's a retrospective comparative study, and it looked at approximately 1,000 patients. There were 178 patients in an arm that received CRTP versus approximately 800 that had physiologic pacing, predominantly left bundle area pacing. And these patients, as you mentioned, were an area that there's a little less certainty that had an ejection fraction of 36 to 50 percent, sort of that. But they are patients that expected frequent pacing. And that was maintained. They had a variety of indications. The group that ended up with physiologic pacing tended to have more pacing-related indications, where those with CRTP had slightly more heart failure pacing indications. But both groups had in the high 90s, 96 versus 97 percent pacing during follow-up. And they looked at heart outcomes. They looked at mortality and heart failure hospitalization. And this is a group that's exceptionally invested and interested in physiologic pacing. And I think we can see this a little bit in their preference of choice of what they used. But in the group that had physiologic pacing, the average QRS was approximately 120. The mean QRS, 120 milliseconds versus 140 milliseconds. And then we could see both a reduction over time in heart failure hospitalization and mortality with physiologic pacing, almost a relative reduction of 50 percent with the two arms. And so more observational evidence to help us understand the role of physiologic pacing. Great, Jared. Thanks for that summary. Dom, could you talk about the limitations and how this might be put into practice? Yes. I think, first of all, we have to congratulate, of course, all the investigators and also putting together those 16 centers, all in all, then actually ending up with 1,000 patients. I think that's a great, great effort, but particularly important in this evolving field with conduction system pacing, where the evidence is still not complete. And we, of course, still need additional data. Given this big, big data set, I think it's very important to realize that this was not a randomized comparative study, but it was actually more or less a registry of consecutive patients who were treated either with biventricular pacing or with conduction system pacing. In conduction system pacing, it was his spinal pacing and left spinal branch area pacing. So actually a combination of different approaches. One thing which was directly obvious is that the proportion of biventricular pacing in this population was quite small compared to conduction system pacing. It was actually more or less 200 versus 800 patients, which actually means that already from this perspective, there's an unbias concerning the number of patients in the different groups. But on the other hand, it also actually shows how active those centers are in performing conduction system pacing. So certainly not centers who just do this once in a while, but actually centers who are very, very routined in doing conduction system pacing, which also will explain the comparable risk of complications, but also actually the quite good outcome with conduction system pacing compared to biventricular pacing. What I think what we learned is conduction system pacing works. You get shorter QRS complexes and also an improvement in ejection fraction. But if we actually look at the outcomes of, for example, the difference is mainly also driven by a difference in heart failure hospitalization, which actually means that there might be differences in some way, maybe due to the pacing or maybe due to the patient selection who actually got the either or the other treatment. Those are of course limitations which we cannot just investigate in this setting, but which needs to be studied in more detail in future, really randomized and prospective studies. Yeah. And I think that point you made is really critical. It's really the best of physiologic pacing. These are the leaders. These are the innovators versus routine CRTP. And that may not, the findings may not be applicable if you go to somebody who does it equally or doesn't have as much interest and involvement and dedication to getting the perfect parameters with left ventral area pacing, which they specify, they have very specific parameters, and they would continue to do that. And so it has to be borne out in a prospective randomized trial, and of course that's ongoing with left versus left, led by Mihail Kalu and Ken Ellenbogen. And that trial fortunately got past the feasibility and will launch into full enrollment and should give a nice randomized perspective take on this. But I think it also shows that this population which is currently treated by either b-ventricular pacing or by conduction system pacing, because if you actually look at the mortality rate, a lot of patients still die nowadays once we actually think about implanting actually some re-synchronization therapy, which actually means that there's still a lot of room for improvement, which probably also goes beyond just implanting a pacemaker, but also actually treating heart failure right and really focusing on this population. I think this was for me actually, again, really convincing that this is a high risk population which we should really follow up in detail and also take care for the comorbidities. One of my questions about the study that I noticed is that in the b-ventricular pacing group, there's actually a higher proportion of ischemic cardiomyopathy patients and wider left bundle branch block QRS complex, and I think greater left bundle versus those who just needed a high percentage of pacing. How do you think this really affects our ability to interpret the results of this paper? Yeah, well, you need a pure randomization. Those people will fall out in an equal amount in a pure randomization, but it does reflect, you know, when I look at that, and we know there's data on left bundle area pacing that it can recruit the left bundle and it can narrow things, but if I see this broad left bundle, my thoughts go to what I'm more familiar with and that's CRTP and what I select that person. We also know, you know, what can be recovered when there's ischemic and dead tissue is limited as well, but I really think that the mortality highlights that. When you put in a, whether it's a his bundle, a left bundle, or a CRTP, these patients in an international trial, 30% were dead at six months, and why did they, is it aging? Is it comorbidities? Is it arrhythmia? We don't have that data, but it gets to your points. These were, some of these people were quite sick, and if they tend to select them into one group, they're going to bias that group pretty quickly into an observational design, which they admit in their limitations, but you're absolutely right about that. Yes, I think what we actually mainly learned is that in a big, big proportion of patients, conduction system pacing might be an alternative to biventricular pacing. I think this is what becomes here already clear, also in this non-randomized setting, because, well, the differences were not big, and of course the fact is that a lot of patients can treat it with conduction system pacing, which I think is really, really convincing. Also points like how long does this procedure take? So conduction system pacing, if I'm right, was a little bit shorter, needed less fluoro, and a couple of other things, and the complication with the lead were also not different in both groups, with actually the left ventricular lead versus the conduction system pacing lead, which I think also is actually convincing more and more everybody that conduction system pacing can be an alternative for the future. I think it's also interesting in following these patients up with their left bundle branch pacing, the different definitions of what constitutes left bundle capture, but that's an implant. How do we follow these patients? They didn't really outline how to ensure over time that there was left bundle pacing, so I think that's another area that'll be very interesting to see moving forward. How do we follow these patients? How do we confirm that they have left bundle pacing over time, or does that even matter? I think it matters because our outcomes aren't great. It's not like the heart failure medication trials where very few events. We still have a lot of events, and my practice is we put the left bundle in, it looks great at implant, it looks great the next day, and then we follow the pacemaker diagnostics, and I don't know if it's moved back. I know it's pacing a lot, and perhaps if I'm more interested in surveillance of the electrophysiology parameters that could help those patients, it's something that I can take to my practice because there's still a lot of events that we can take advantage of and try to improve lives. I think the group also looked at the occurrence of arrhythmias, for example, and this was atrial fibrillation, but on the other hand also ventricular arrhythmias, and I think this also should be, of course, part of every interrogation of every device at every time point when this is done, and conduction system pacing might have some advantages versus biventricular pacing in this regard, which also might actually open their opportunities for the future, but again this is just based now on this observational data, and of course also for this we need randomized trials. I just think about, for example, also pace and ablate approaches for atrial fibrillation where also a reduction in AF burden despite the fact that we actually have this ablation still might benefit the patient versus actually being in atrial fibrillation continuously. Any final thoughts before we wrap up this session of the league? I echo both of your thoughts. Congratulations to this team. The lead author, this was carried on his back, and he believed in it, and our complete societies and all of us interested owe a debt of gratitude for him and many of these authors. They've pushed this through and given us a new way of approaching this, and then I think again, I think it really, if you're enrolling in this prospective trial, please do. We need these long-term data, and we need long-term randomized prospective data. The background data is there. I think there's still equipoise, even despite this, in randomization, and in that trial really tell us how it's going to perform. Yeah, also from me again, congratulations, of course, to the complete team putting this data together. It's super important not just to show that something works, but also to show that what you do actually is safe and also effective, and I think this at least adds significantly to the field here. At the moment, 1,000 patients from 16 centers, which actually is very, very useful, and I really enjoyed reading this manuscript, and I'm looking forward to see this published in HeartRhythm. Great. Well, thank you, and on behalf of the HRS Digital Education Committee, I'd like to thank the iClass group for really championing this technique and moving forward with such a large cohort of patients. I'd like to thank HeartRhythm for publishing this paper simultaneously, and once again, thanks to Drs. Lins and Dr. Bunch for an interesting discussion. Goodbye from Sydney and APHRS.

conduction system pacing

biventricular pacing

heart failure

cardiac resynchronization

I-Class Group