Great Debates & Updates in EP: Physiological Pacing Techniques

Aseem Desai: Hi, my name is Aseem Desai. I am a cardiac electrophysiologist at Providence Mission Heritage Medical Group in Orange County, California. It is a pleasure to be on this podcast with Dr Dandamudi to discuss some of the latest interventions and the direction that things are going in the field of pacing. There is so much focus nowadays on ablation of atrial fibrillation (AF), that it is nice to switch gears and talk about device therapy.

I have a specific interest in the area of robotic ablation as well as in patient education and prevention of AF with lifestyle and trigger modification. I did my fellowship training at Stanford and was on faculty at the University of Chicago, and have been in private practice in Southern California for about 18 years.

Gopi Dandamudi: Thank you to EP Lab Digest for this opportunity. I am Gopi Dandamudi. I am an electrophysiologist by nature, but have morphed into several roles over time. I did my fellowship at Indiana University (IU), and since then, I have worked in large health care systems with an interest toward health care economics and taking on more administrative roles. Currently, in my role at Virginia Mason Franciscan Health in Seattle, I am the cardiovascular service line director for a large health care system. Probably about 30% of my time is clinical EP and the rest is administrative work for the system.

Desai: Gopi, thank you for joining us. We are very excited about the Great Debates and Updates in Electrophysiology conference on September 8th. The debate session will include my comoderator, Dr Raul Weiss from Ohio State, you will be speaking on His bundle pacing (HBP), and Mihail Chelu from Baylor speaking on left bundle branch area pacing (LBBAP). The debate portion of the conference will be followed by some discussions on third-party remote monitoring and what EPs need to know about tricuspid valve interventions. It is kind of a newer area that is being explored. Lastly, there will be a discussion on the role of social media for EPs in 2022.

Gopi, you have a great deal of experience in the area of conduction system pacing (CSP). I did a literature search on your name and a lot of information came up, which was quite impressive. Can you give us a little bit of an overview for those people who are not sure what CSP is? What are we referring to, where did it get started, and where we are now?

Dandamudi: The whole premise behind CSP is this concept of using your own electrical system to stimulate your heart. Traditionally, we have always performed pacing on the assumption that the electrical system is not working well and we need to bypass it based on the myocardial tissue itself. But what we learned over time is there is a form of pacing-induced cardiomyopathy, and it is not a trivial number. Depending on studies, a lot of these are observational and there are also randomized trials, but this can vary anywhere from 15% to almost 40% of patients. So again, as we are doing more and more pacing, we are learning that this is not a trivial thing to dismiss. The whole idea of CSP takes into account the question of what if we could preserve using our own conduction system, and by preserving that, would it reduce incidence of pacing-induced cardiomyopathy or even completely negate it?

Interestingly, this is not a new concept. People think that since they are hearing and seeing more about it that this is relatively new. However, this dates back to the 1970s, when people first studied the concept of whether we could recruit the conduction system directly. A good example is in patients with left bundle branch block (LBBB). Can we pace at the site of a block or within the proximal portions of the conduction system, and actually correct the underlying LBBB? There have been multiple theories about it. The oldest theory was the idea of longitudinal dissociation of fibers. I often explain this to fellows as taking a bunch of cables and rolling them all the way from the atrioventricular (AV) node into the left ventricle (LV), then taking a bunch of cables and rolling them from the AV node to the right ventricle (RV), and then combining all of them together into one area. That is your common bundle. These are predestined fibers within that common bundle that go toward the LB or right bundle.

A lot of these blocks that we see are very discrete blocks that happen very proximally in the conduction system. So my notion of CSP or conduction blocks is that if there is third-degree heart block, you essentially throw away the entire electrical system. If you have a LBBB, it could be anywhere, so you need to bypass the entire LBB system. What we have learned, and this has been an eye-opener for me, is that a lot of these are very discreet and focal lesions that happen proximally in the conduction system. If you pace at those sites or even distal to it, you can still use your own conduction system.

Desai: It is interesting how it has had this resurgence of interest. I think many of us underestimate that a lot of patients have a negative impact from RV apical pacing especially. I know that when I have done my research on CSP, there are multiple different areas that you can pace from, starting at the His bundle to the LB area, to the left side of the septum. What is your take on that? It seems like there is a movement from HBP toward LBBAP.

Dandamudi: Intuitively, the ideal site to pace is in the common bundle, because before the bundle branch is arborized, you want to capture both bundles. So ideally, if you had a choice, and that is how our intrinsic rhythm is, you want to be able to recruit conduction system tissue proximally before it arborizes into right bundle and LB—that way you activate both sides of the ventricles, both the RV and LV.

However, there are some drawbacks with just pure CSP and HBP. As we know, that whole area is encased in fibrous tissue—the central fibrous body—and the current design of leads and devices do not allow us to optimize for HBP, because it is a totally different tissue. If you think about pacing in general, they were designed to pace the myocardial tissue, not any other tissue specifically.

Now, when we are dealing with fibrous tissue, it requires a different way of thinking and maybe even different technology to try to pace that tissue. Using existing systems, what we learned over time is that these thresholds can potentially rise over time. Again, we are not pacing myocardial tissue per se, we are pacing a different form of tissue that is encased in fibrous tissue.

Over time, this has slowly evolved. We have evolved from doing very proximal pacing. Early on when we did this, we were able to show we are pacing on the right atrial side of the tissue. We did cardiac computed tomography and imaging to show that you do not even have to cross the valve—you can actually pace the tissue on the AV nodal side on the atrial side of things. That slowly evolved into a little bit more distal, past the leaflet, further distal into it, and now into the proximal portions of the septum. The obvious advantages are the tissue interface is totally different, as you go proximal into the septum, you are capturing myocardial tissue and fibers that are not encased like in the His bundle. These are your Purkinje fibers that are running within the myocardial septum, so you are essentially directly capturing without any interface that is encircling them or encapsulating the conduction system. Your thresholds can be significantly better, because it is essentially a myocardial type of tissue that you are capturing within the Purkinje fibers. That is how we morphed from very proximal pacing to slightly more distal pacing within the proximal portions of the conduction system.

Desai: At this year’s Heart Rhythm meeting, I think 3 studies were presented in the late-breaking clinical trials, 2 of which were retrospective and 1 was more of a prospective study, that looked at cardiac resynchronization therapy (CRT) vs CSP.¹ One of them was a retrospective review of the people who either could not achieve a target LV lead position or there was lead failure, or someone was a nonresponder to CRT. Is that the group of patients that you envisioned this for—people who are not candidates for CRT based on anatomy? Or, do you envision it for people who, from the start, you are anticipating a lot of RV pacing? For example, maybe they had a stroke, heart disease, or coronary disease. If their ejection fraction is in the low 50s and you are going to be implanting a dual-chamber pacemaker, should you be considering HBP or CSP for those patients to prevent the dyssynchrony that can occur from RV apical pacing?

Dandamudi: That is a great debate in our field. Ideally, if you think about it, you would think logically as electrophysiologists, physiological pacing is the absolute pure form of pacing, so it really should replace all forms of pacing. The issue that comes up, especially in the setting of biventricular (BiV) pacing, which has a lot of mortality and morbidity data, specifically in wide LBBB patients, is can we take that leap of faith and say, this makes sense, we have the observational studies, we can clearly correct it, and it improves LV function?

I think in those patient populations, people still struggle in terms of if this is the right choice as a first-line therapy. In the last 10 years at my practice, I have only done CSP as first-line therapy. In the last 6-7 years, even with LBB patients, I first attempt CSP, and if I fail, then my last resort is to do BiV pacing. Again, the rationale behind it being that this is the pure form of pacing and this is what we are trying to achieve. But even with BiV pacing, the fact is we cannot get electrical synchrony, we are taking this surrogate up that is mechanical synchrony trying to do BiV pacing. What if you can get electrical synchrony in all these patients? Most of the data right now, if you look at LBBAP, LV septal pacing (which is relatively new), and HBP, have been small to large observational studies. Certain centers have been doing this for quite some time.

In order for this to be mainstream across the globe, it has to be amenable, successful, and easily reproducible in the hands of most people, because pacing is a common form of therapy. It cannot just live in the hands of electrophysiologists or people who only do this as part of their profession. Cardiologists and surgeons also implant pacemakers. In remote parts of the world, even noncardiologists and nonsurgeons implant these devices.

We are at a crossroads of how to start thinking about newer ways of technology, including developing newer device algorithms, leads, and delivery mechanisms, to make it such that anybody, anywhere who does pacing can easily adapt their practice to doing this form of pacing. That is the next challenge, and along those lines, how do we do large randomized trials to show the benefits of it, and not just in the short term? For example, take ablation therapy in AF. We often look at only the 1- and 2-year outcomes. Pacing is a permanent therapy so we have to get it right from the beginning, because this is a lifelong journey for our patients once they get a device. So how do we make sure that, with confidence, we can say that this form of pacing is going to stand the test of time compared to RV apical pacing?

My mentor, John Miller at IU Health, used to tell me, “Before you were born, pacing existed. People have had RV apical pacing for a long time and survived for decades with RV apical pacing without heart failure. So for somebody to say that RV apical pacing is bad in everybody does not hold water.” He is absolutely right. A vast majority of people in the world who get RV apical pacing do just fine, so if you are going to replace it with another form of pacing in everybody, you had better make sure that not just the short-term outcomes, but also the long-term outcomes match up with existing therapies.

Desai: Do you see the learning curve as being an issue? Especially for people that have been in practice for a long time, I am thinking of considerations for the busy private practice. How much longer are these cases? Is there more fluoroscopy time involved? What is the number of CSP cases that you need to get under your belt to feel comfortable with the technique? What is your take on that?

Dandamudi: Interestingly, HBP requires more effort. This is as site-specific as it gets, as we all know with mapping the His bundle, and then in that specific site, you have to try to deploy the lead and affix the lead deep into the septum.

The advent of LBBAP has made it a lot different, because this is a larger area to focus on within the proximal septum. You can take a third of the proximal part of the septum, and go anteriorly, inferiorally, or somewhere in the mid septum. It is more of deploying the lead. There is more interest in LBB pacing than even HBP for that reason alone, because the ability to deploy the lead in a larger area without worrying about being site-specific is a lot more appealing than HBP.

I still believe HBP has a role in all this, especially with the development of better technologies. I have always believed that we can develop technologies where you can deploy something at a certain site. You go site-specific, map the His very quickly, and deploy a device such as the Micra (Medtronic) or something that is preloaded that can go to a certain site. Once you map it, you can deploy it and make it work. So it is hard to tell which way the wind is going to blow, but looking at all the global interest right now, it seems like LBBAP may be the future of CSP more so than HBP. Although I do not want to admit that, because I am going to be debating about HBP.

Desai: Exactly!

Dandamudi: Drs Chelu and Ken Ellenbogen received a $31 million grant from the Patient-Centered Outcomes Research Institute (PCORI) to perform a large clinical trial in Canada and the United States with over 2000 patients to look at long-term outcomes of CSP vs other forms of pacing. This is the kind of trial that we need, one that is sponsored by the government where we can get good data over longer periods of time to show not only that it is effective and safe, but also the long-term outcomes. We still lack long-term outcomes.

One of the differences between this and RV apical pacing or even BiV pacing is this is very much physiological pacing. It is also output-dependent pacing. You have to look for what output you are programmed and where you are capturing, especially if you get transitions between septal capture to CSP. If you assume that the device is functioning well, and you look at your algorithms and see your capture management looks good, you are going to be fooled many times, because this is really output-dependent pacing.

I am not as much worried about procedural times as I am about the long term. Are we properly programming these devices? Are we properly following these patients to make sure that they are getting CSP? One of the nice things about BiV pacing is once you put the lead there, if you are capturing, you are always getting BiV pacing. However, CSP is not going to be the same—it is going to be output dependent.

It is less of a variation with LBB pacing, because they tend to have very low thresholds where you are actually capturing the tissue. But again, we need to prove over longer periods of time that we are maintaining CSP with our current algorithms and methodologies of how we check these in clinic and remotely, to make sure that patients are getting long-term benefits from it.

Desai: That is a great point. I distinctly recall a patient who relocated from the Palm Desert area to Orange County, who had a His lead that was not capturing because he was set sort of below—I think the threshold must have risen at some point over time. So you need to be thinking long term. 

Dandamudi: That is one of the biggest concerns for us. You have to educate your patients. A lot of times, people migrate to different centers. For example, I do a lot of CSP. We educate the patients to let them know there is a reason why their capture management algorithm is not turned on or it is programmed a certain way. If the patient goes to another clinic that is not familiar with CSP, they may look at it and ask why somebody is being paced at 2.5V at .5 ms when their thresholds are only .5V at .5 ms. That is because the transition happens at 2.25V to septal pacing, and above that, there is CSP. So you go through all the effort of doing such a case, and then they go somewhere else and they program it and you are getting a septal pace.

Again, these are the kinds of nuances that our field needs to better understand and embrace, as well as build into our workflows to better assess these patients, whether they are getting CSP or not. I think these are all relatively simple. They are not as complicated as people think. These algorithms can be built into devices. A lot of us use remote technologies now, even third-party vendors that we use. There are ways to track these kinds of patients and see if they are getting CSP or not.

There are still a lot of data to be collected to see if patients are truly getting what we intended them to get. We take a lot of time to get CSP. If a patient gets a tricuspid valve placed percutaneously and it jails the lead or alludes their CSP, that is definitely a concern for us in the field of CSP, which is more instrumentation in the right ventricle.

Desai: Right. After all that hard work you do, it then ends up getting damaged. What are your thoughts about leadless pacing, especially LV leadless pacing? I know there is a lot of interest in that for people who are not traditional CRT candidates.

Dandamudi: Yes, it is the same concept. The idea is going into the LV endocardium and pacing, but an argument could be made on why even go into the LV if you could do it from the RV side with what we are doing with CSP? The hope is that in the future, we will have all these tools where we have different forms of energies like we do in cryo, radiofrequency, and LVF.

Similarly, we have pacing modalities that we can customize to the patient, so we can do deep septal pacing or LBBAP. If maybe we do not get a good outcome there, we can do LV endocardial pacing. So it is exciting for us from a physiological standpoint. My colleague, Pugal Vijayaraman at Geisinger, has done some innovative work combining BiV pacing with CSP and has produced some incredible results, different forms called His-Optimized CRT (HOT-CRT) where HBP and LV pacing have been combined, or left bundle branch-optimized CRT (LOT-CRT) pacing where there is LBBAP.

You can imagine if you have pure CSP, when you correct the conduction system, you can actually correct the problem. But not everybody has only pure conduction system problems. They also have myocardial delay, intramyocardial delay, myocardial fibrosis, and so on. So that is where you can see the benefit of combining BiV pacing with CSP and get the perfect fusion between different forms of pacing.

So I think there is a lot of excitement again in pacing. When I first came out of fellowship, doing pacemakers was the most boring thing for me, especially in the elderly population. You worry about preparation. Once we started doing physiological pacing, it became the most interesting aspect of what we did, even compared to ablations and all that, because we learned so much about physiology that we never knew existed until then: the different forms of fusion using the conduction system, understanding what is selective and what is not selective, different behaviors of pacing, and different ways of recruiting the conduction system.

It is a totally fascinating field where we are still learning a lot. I believe we are just skimming the surface at this point when it comes to understanding what exactly our conduction system is and how it really works. When we have problems, what exactly are the problems? Is it focal, is it more diffuse, is it at the level of the proximal portions, and is it at the distal portions? Again, it is a fascinating area to learn from.

Desai: Well, I think that is a perfect way to end our podcast episode. Gopi, thank you so much for your insight!

Dandamudi: Thank you again for the opportunity! 

Editor’s Note: The transcripts have been edited for clarity and length.

Listen to the podcast audio here.

Reference

1. Heart Rhythm 2022 reveals latest advances in conduction system pacing. Heart Rhythm Society. Published April 30, 2022. Accessed September 28, 2022. https://bit.ly/3UPa6Vd