 Thank you all for having me. It's truly an honor to be back here in Houston. It's been a little while and I must say, so I'm originally from India and Houston was the first place I lived. Initially it was fairly quiet, but I learned to love the place. It was a bit of sweet to leave here. And a lot of, you know, the roots for research work has sprung from here in my training and my background in epidemiology and MPH. So it's great to be back and it's an honor to be here presenting and speaking in front of all of you guys. So I'm going to talk a little bit about right ventricular pacing and what's changed over the course of the past decade or so and give you guys an introduction to where we're headed and how this could change the field going forward. You're certainly going to see much more of this in your general cardiology practices as well as an EP. So it's better that you're at least introduced to this subject. Those are my disclosures, none of which are relevant for this particular talk. We're going to talk a little bit about the adverse outcomes of right ventricular pacing. The search for alternative sites, which has then led to his spinal pacing and review how this can help us prevent some of these adverse effects, but also can this help reverse some of these adverse effects that we see with right ventricular pacing? And just a brief slide or two on our program at Rush. So we are all aware that conventional RV apical pacing is associated with structural changes within the ventricles. This then translates into adverse clinical outcomes, which include increased incidence of pacing induced cardiomyopathy and heart failure, increased incidence of atrial fibrillation, and an associated increase in cardiac mortality or all cause mortality. This was an interesting study that was published in 2004 in Jack. I don't think we can replicate this again, and I'll tell you why in a moment. So these were 12 subjects that had a normal LV ejection fraction at the beginning of the study. They all had normal AV conduction, had sinus node dysfunction, and received dual chamber pacemakers. So what they did here was they essentially, as you can see, each one of these bars I'll probably just use my pointer here. So each one of these represents a MAGA scan. So you can be certain these patients were glowing by the end of this study. So they paced these patients in the atrium at 80 beats per minute and performed a baseline MAGA scan and started pacing them in the ventricle. And within an hour of pacing them in the ventricle, there was a decline in the EF in the overall patient group. After about a week of pacing them in the ventricle, you can see that the EF declined down even further. And once they stopped pacing in the ventricle and went back to atrial pacing, the EF started improving. So there's an acute decline in the LV ejection fraction with ventricular pacing. If you look closely, none of these patients had their EF declined to down to less than 50% on average. That's probably why we don't call them pacing induced cardiomyopathy, but there are acute hemodynamic effects of ventricular pacing. And if these patients are paced for long enough in the ventricle, then these effects become more pronounced and sometimes more irreversible. The most study was the first study back in the early 2000s that assessed VVI pacing, which is pacing in the ventricles versus DDD pacing, which is what they thought was physiological back then, which as you pace the atrium and let conduction occur as long as the AV delay is not too long. This was a sub-study of the most trial. And what they found was that the burden of heart failure hospitalization increases as the burden of ventricular pacing goes up. For every 10-point increase in the ventricular pacing burden, there was a 20% increase in heart failure incidence. And at about the 40% mark, 40% burden of ventricular pacing, the incidence of heart failure hospitalizations increased by 2.54. A similar trend was observed with the incidence of atrial fibrillation. This is the study that actually drives the guidelines today, where in the guidelines of a patient already has a low LV ejection fraction and is likely to pace 40% or more in the ventricle, then they would qualify for cardiac resynchronization therapy. That comes from this paper. What I want to highlight is some of the newer data that has emerged over the last few years. So we know 40% used to be considered the gold standard for a high enough ventricular pacing burden. So this was a paper published by the pen group where they looked at patients that were paced 20% or more in the ventricle. So patients that had a normal EF to begin with paced more than 20% in the ventricle, and they decided to try and evaluate what was the likelihood of developing pacing-induced cardiomyopathy. They defined pacing-induced cardiomyopathy by a drop in ejection fraction of 10% or more from their baseline, such that the EF dropped to less than 50%. Out of 257 patients, they identified that 19.5% of patients that are paced 20% or more in the ventricle were likely to develop a pacing-induced cardiomyopathy based on this definition. That is one in five patients. What they found in a multivariate analysis was that the multivariate predictors for development of pacing-induced cardiomyopathy were elderly males and patients that had a wider native QRS to begin with. What that implies is if a patient has LVH or has an IVCD type pattern as a result, then there is already an ongoing process that's causing stress and strain on the ventricles. You add injury to that where they're pacing in the ventricle with a high percent of ventricular pacing burden, they're more likely to develop a myopathy. Then came the study from the Cleveland Clinic group. They decided to conduct a similar analysis. Between 2000 and 2014, they had 823 patients in the study. The only difference was their definition of development of pacing-induced cardiomyopathy was a little bit more conservative. They said we're only going to take patients, of course, it's a given that all of these studies ensured that there was no other potential etiology for the cardiomyopathy and that these patients were paced a lot in the ventricle. They only included patients that had their LV ejection fraction drop to 40% or less, so fairly conservative. What they found was out of 823 patients with sinus node dysfunction or AV block that were paced in the ventricle, they found that 12.3% of these patients developed a pacing-induced cardiomyopathy. If this study used the same cutoff as the previous study from the Penn group, then the incidence of pacing-induced cardiomyopathy was closer to 15%. As you can see, about a third of these patients underwent an upgrade to a CRT device and about 90% of these patients that underwent an upgrade to a CRT system actually were considered responders with a significant improvement in their ejection fraction. Think about this carefully. If you could pace somewhere in the ventricles where you could avoid pacing-induced cardiomyopathy, then that would be the right way to go. The second thing is we are sometimes very quick to upgrade these patients to a CRT defibrillator system when 90% of these patients might actually improve their EF and they may not require that defibrillator. That's something that is important to talk to our patients about when we're making these decisions, about an upgrade of their system or a revision of their system. Now again, they looked at the old, you know, the gold standard which was 40% or more in terms of pacing burden and you can see patients that are paced more than 40% at worse. But again, based on the previous study from the Penn group, they said let's look at 20% or more burden and you can see that even with the RV pacing burden of 20% or more, the likelihood of developing a pacing-induced cardiomyopathy was still fairly significant. So based on this study, they found two multivariate predictors. One was patients that were paced 20% or more in the ventricle and the second was patients that had a lower pre-implant LVEF. So if you have a patient with an EF of 45 or 50% to begin with and they pace a lot in the RV, they're the most likely to develop a pacing-induced cardiomyopathy. So then we started looking for alternative sites. We said, okay, RV Apex is not a good place to place these leads. How about we place a lead somewhere on the RV septum or on the RV outflow track? So the RV septum and outflow track were evaluated in multiple studies and unfortunately the results were fairly conflicting. There was no significant difference between RV Apex or RV outflow track when it came to hard endpoints or mortality or heart failure hospitalization. This was a meta-analysis that looked at all of these studies that are available comparing RV apical versus RV non-apical sites for ventricular pacing and what they found was in those patients that had a low EF, RV non-apical pacing, is probably better when it comes to preserving LV ejection fraction. But for those patients that had a preserved EF to begin with, there was no significant benefit with RV non-apical pacing compared to RV apical pacing. So then as a field, we decided to take it to the next level. We said, what about bi-VCRT? Now again, you guys are all aware that CRT with bi-ventricular pacing is a gold standard for patients with left-punner branch block and a cardiomyopathy. But based on current guidelines, those patients that are placed more likely to pace more than 40% in the ventricles and have a low EF are also good candidates for bi-VCRT. But what about those patients with a low normal EF or a normal EF? So the first study that analyzed this was the Block HF trial. And for those of you who are updated with your guidelines based on this study, there is a new indication in the guidelines for use of bi-V pacing for patients with an EF between 35 to 50%. Why is that? So this study was performed by Ann Curtis and was a US-based study where they included about 670 odd patients that were randomized to RV pacing versus bi-V pacing. All of these patients were patients that had an EF that was less than 50%. So 35 to 50% was a predominant group. Patients that were likely to pace in the ventricle more than 40% of the time. And what they found was when you looked at the primary composite endpoint of all cause mortality or heart failure or increase in the LVN systolic volume, bi-ventricular pacing in yellow did better than RV pacing. So this is where the current guidelines reflect that bi-V pacing might be beneficial for this patient cohort. But at the same time, there was another trial that was happening outside of the US called the bi-opace trial. Included 1810 patients, one of the largest studies conducted to date in bi-ventricular pacing, randomized again to bi-V versus RV. And what they found was the curves were bang on top of each other, that there was no difference in the primary endpoint of mortality or heart failure hospitalization. So then they said, let's look at the patients with an EF less than 50%, just like Block HF did. And still there was no separation of these curves for, there was no statistical difference between bi-V versus RV in terms of these heart endpoints. Now the interesting thing is this study has never been published because it was a negative trial. It's the largest trial that was conducted, post presented at ESC in 2014, but never been published in a, in a journal. So that then brought us to what we refer to as conduction system pacing. And his bundle pacing was the first step along this way. So what is his bundle pacing? It's the implantation of a permanent pacing lead at the bundle of his, which is part of the AV conduction system at a site that is distilled to where the AV block is. So the hope is to preserve normal biventricular activation or to potentially even normalize biventricular activation in patients that have bundle branch block and we'll talk about how that's even possible. And then the second thing is, could this then translate into a prevention of some of these adverse clinical outcomes and maybe even reverse some of these adverse clinical outcomes in patients that develop a myopathy by pacing or other reasons. So just a quick slide or two on the anatomy of this region. So here is an anatomical specimen, the right atrium on the top, the right ventric on the bottom, the tricuspid annulus. This then becomes the AV node and that continues as the AV bundle or the his bundle, which travels on the lower portion of the membranous septum. Now, when you look at this more carefully, there are two portions of the his bundle. One is the atrial portion and one is the ventricular portion. If you look at the relationship of this to the membranous septum, there is a portion of this his bundle that is atrial. We've all heard of the Gerbodi defect. Why does that happen? Because the tricuspid valve is displaced more apically compared to the mitral valve. So there's a portion of the membranous septum that communicates between the right atrium and the left ventricle. The his bundle runs on the inferior portion of that membranous septum. So as part of it is atrial, before it becomes a ventricular structure and then branches out into the right bundle branch, which is a continuation of the his bundle, and the left bundle fascicles take off on the left side of the muscular septum. Now, therefore there are publications that demonstrate that if disease is proximal enough where the level of block is maybe in the AV node, these leads can actually be placed on the atrial side of the tricuspid valve and you won't deal with issues such as tricuspid regurgitation. The other advantage of doing something like this is that there is no way you can cause a perforation. Cardiac perforation is almost unheard of with his bundle base and if you actually record the electrical conduction system and place a lead there, it can cause phrenic nerve stimulation because the phrenic nerve runs outside the heart, not on the septum. So there are clear advantages of that, of this technique from an anatomical perspective, but we'll talk about whether or not this actually does result in a clinical benefit. So just to highlight, this is what RV apico pacing would look like. You see it's like creating artificial iotrogenic left bundle branch block because you're pacing the RV before the LV and that causes dyssynchrony. On the other hand, biventricular pacing is also not ideal, especially for patients that have a narrow QRS and baseline because you're creating two artificial wave fronts. One is RV endocardial and the second wave front is epicardial on the LV side. While intrinsic normal cardiac activation occurs or biventricular activation occurs from endocardium to epicardium, so you're reversing that wave front. And finally, with his bundle pacing, you place a lead distilled to the level of block and you can actually utilize the distilled hisperkingee axis to activate the ventricles in a synchronized fashion and maintain biventricular activation. So just a few examples. So here's a patient with a very long PR interval and rate-related Venkibok. When he exercised, he developed AV Venkibok and was symptomatic. So he came in for an implant and we placed the lead at the bundle of his. This is the PACE TCG. So for those of you who've never seen his bundle pacing, it looks just like your intrinsic QRS. In fact, when we first started doing this about a decade ago or so, we'd get a lot of calls from telemetry where it would say a pacemaker is not capturing because it looks like the pacer is, you know, there's a pacing spike and then there's a QRS that looks like your intrinsic QRS. But that is actually capturing the his bundle followed by the 30, 40, 50 milliseconds it takes to get down the hisperkingee axis and activate the ventricles. So that's the PACE QRS. And I'm going to overlay on top of this the patients' intrinsic QRS in blue. And they look exactly identical. When a patient that has an intact distal hisperkingee system, you can take advantage of the hisperkingee axis. There's another patient with interpreted high-grade AV block. And you can see that there's high-grade AV block with wide escape rhythms and he presented the dizziness to an outside hospital and this was picked up on a monitor. And this was his final PACE QRS. Now again, when patients have high-grade AV block, we have methods and ways of identifying that we are distilled to the site of where block is when we do these cases in the lab. But then yes, I showed you some beautiful examples of beautiful ECGs and we talked about theoretically how this could be beneficial, but does this really result in improved outcomes for our patients? So this is a summary of all the data there is in a paper that we just published in Nature Reviews on this topic that summarizes some of the early work. The first study was done in the year 2000. It was a very small concept study published in circulation, but the success rates were really low. And then we published our first work in 2015 and somewhere around that time, we had a more dedicated delivery system and a better mapping technique and success rates have only gotten better from about 80-85% to about 92% in more recently reported literature. So I'm going to show a couple of these studies just highlighting the differences, but I want to caution you about something. This has become a movement. We call it physiological pacing. It's become a movement and most of this work is physician-initiated. There has not been a lot of funding for a lot of these studies because there's not much to gain from a manufacturer perspective. We're working with the NIH to get, I'll show you some of this data, but we're working closely with the NIH to get funding for large-scale randomized control trial, but I'm going to caution you, none of these studies to date are randomized control multi-center studies. So this was the first study we conducted. This was a prospective evaluation of his spinal pacing versus RV apicope pacing or RV pacing. So 192 patients where at one site, we attempted his spinal pacing on all patients for any pacemaker indication sinus node dysfunction or AV block. At the other site, everyone received RV pacing. We were successful in achieving his spinal pacing in 80% of these cases. These were cases we performed in 2009 and 2010. So the early experience of his spinal pacing. We looked at patients that were paced 40% or more in the ventricles. And this is what we found in a very small cohort of patients that heart failure hospitalizations were almost negligible with his spinal pacing while they were pretty high with right ventricular pacing. There was also a trend towards the separation of curves when it came to mortality outcomes, but this study was not powered for and we were not trying to assess mortality outcomes as a pre specified endpoint. It was just a signal towards something that we couldn't explain. So then we did a long term follow up in this patient cohort, more than five year average follow up. And all of these patients came back for follow up echocardiograms. What we found was in blue is baseline EFs and in red is follow up EFs. When he took the entire cohort of patients, his spinal pacing demonstrated that the EF remained stable. The group with RV pacing, there was a decline in EF, which was statistically significant. Now we said, let's look at those patients that were paced a lot in the ventricle because we anticipate that those are the ones that are going to suffer the most. And clearly in that group, the decline in EF was even more significant with RV pacing, while with his spinal pacing, the EFs from still remain stable. In the intention to treat analysis, there was no statistical difference in all comers, but those patients that were paced more than 40%, there was an increased incidence of heart failure hospitalization or mortality with RV pacing compared to his spinal pacing. Now look at the N0, 59 versus 60 patients. In such a small cohort of patients in a prospective evaluation, we've been able to demonstrate a significant difference in heart endpoints. And this is the on treatment analysis where the difference was significant both in the patients that were paced and in all comers in the cohort as well. But then we said this was the early work when the success rates were low and we were still learning a lot about his spinal pacing. So then we got better at it and we did a much larger study with pre specified endpoints, 765 patients, 332 underwent an attempt at his spinal pacing and 433 with RV pacing. This time our success rate was higher, it was 92%, an average follow up of two years. We demonstrated with a primary outcome of death, heart failure hospitalization or need for upgrade to biventricular pacing that his spinal pacing in blue did better than RV pacing in red. And this was a late breaking clinical trial at ACC last year. In those patients that were paced more than 20% in the ventricle that difference was even more significant. So at least some of the data suggests that his spinal pacing might be better when it comes to preventing some of these adverse clinical outcomes. How about patients that develop adverse clinical outcomes or already have a cardiomyopathy? Can it help with those patients? Let's look at an example. This was a 75 year old gentleman. He is the father of one of our CCU nurses and she came to me saying he's in Florida and his physicians there tell him that he needs a pacemaker because he has sinus nor dysfunction. I said he has sinus pauses, his heart rates are 40s, he needs a pacemaker, he should get it done. So he gets a dual chamber pacemaker implanted in March of 2017 in Florida. And two weeks later he comes to see me because he's back from Florida and she's like I'd like for him to establish care with him. His device has checked and I'm like he's pacing 90% in the ventricle. I thought he had sinus nor dysfunction. Why is he pacing 90% of the time in the ventricle? Turns out his PR interval was 37380 milliseconds. So just for you, the people in the room that actually refer these patients for pacemakers, if you have a PR interval that's more than 330, 350 milliseconds and they get a dual chamber pacemaker unless you program them in an AAI mode there is no good way to award ventricle in a patient. So I said fine, we'll see what happens. We have programmed him AAI and he started Venkibarking. So I had to program the dual chamber device back on and I followed him carefully and this is what happened. In blue is his pacing burden. So you see his 99% paced, 92% paced, 100% paced at every three month follow-up. And this is what happened to his EF was 60% to begin with 55 to 60% becomes 50 to 55%, 45 to 50%, 35 to 40% over the course of a year. And this is what happens to his AFib burden goes from 6% to 12% to 19% to 31%. So now what came first? The chicken or the egg was at the AFib that's making predisposing him to a cardiomyopathy or is it the pacing that is leading to all of these issues? We couldn't tease it out. So put him on amioro on hoping that we'll suppress the AFib and then we'll know if his EF recovers or not. Unfortunately, wasn't able to tolerate amioro on and so we bring him in, we do an AFib ablation, take him off the amio and he does well. We repeat an EF still down. So we bring him in. Ideally a patient like this with an EF of 35% would probably get an upgrade to a biventricular CRT, maybe even a defibrillator like we know. So this is his RV paced ECG with a QRS duration of 210 milliseconds. So we bring him in and this is his intrinsic conduction. He has such a nice beautiful narrow QRS. Can anyone tell me why he has T-wave inversions? Any of the fellows in the room? Memory, right? So he's paced a lot of the time in the ventricle and so when you turn off pacing he has T-wave memory. So bring him in and this is what we do. We take the RV lead out from the ventricle because it's about a year and a half old so it comes out easily and we just place a new lead at the bundle of his which is where you'd anticipate here is the tricuspid valve plane. This is where you expect the his bundle and you can see in the left lateral view it's nicely pointing towards the septum. This is his his bundle paced ECG about 100 milliseconds and this was in red is his intrinsic QRS with the T-wave memory changes that we showed you again. So what happened to him? So this is where we performed an AFib ablation. His EF still remained at 35 to 40 percent. His AFib burden was zero. He was still pacing 100 percent of the time and so we revised his lead to the his bundle position. The same dual chamber pacemaker, the same can all we did was reposition the lead and his EF is now 55 to 60 percent. There's no cardiac symptoms. So is it possible to minimize health care expense and reverse some of these effects? Is it possible to minimize health care expense and preserve LVEF, a void heart failure which is one of the biggest reasons for health care expenses in cardiology today? Maybe it is. This was a study we did. This was multi-center experience looking at patients that had exactly this sort of a situation where they were paced in the ventricle, developed a pacing induced cardiomyopathy and underwent an upgrade or a revision of their system to his bundle pacing. This is their baseline QRS on average as a group, as a cohort. With RV pacing their average QRS width increases to about 180 milliseconds and with his bundle pacing it narrows it in. Their EF was normal to begin with. Their EF declined to average of 34 percent with RV pacing and after his bundle pacing the average EF improved to 48 percent. And there was a significant improvement in NYHA functional class after an upgrade to his bundle pacing. So with a dual chamber system just revising the lead might be sufficient to reverse cardiomyopathy in this cohort. So let's talk about another area that's gaining a lot of interest which is CRT. So we have a new term that we use that's called his CRT which means the re-synchronization using his bundle pacing. So there's BIV CRT and there's his CRT. Let me show you a few examples and we'll talk about how that's even possible. So this was one of my first referrals for CRT when I started as a new attending. She's 94 years old. She's a non-eschemic myopathy. Her EF went from 40-45 percent to 30-35 percent to down to 20 percent. NYHA classed three to four symptoms and left on a branch block as you can see. She can barely make it from her bed to her bedroom door without having to stop a couple of times because she gets so vented. Now this is not the ideal first consult because she walks into my clinic. She walks in with a walker. She weighs 42 kilos. I can see every one of her ribs so I'm wondering where this device would go if I were to put one. And the best part of it all was she walks in with three family members. All three are physicians. Okay so it's a good thing in the beginning of your career because you have an hour to spend on a new consult but you don't have that as you get busier. So I spent enough time with them walking them through the scenarios and explaining to them that I don't think that giving her a defibrillator would be the ideal thing to do in this situation. It's all about quality of life. So if we can do something to improve her quality of life maybe there's value to it. So we talked about achieving narrowing of this QRS with his bundle pacing with a dual chamber pacemaker and if that wasn't successful then we'll put a biventricular pacemaker to achieve re-synchronization. This was her dual chamber his bundle paste ECG. Do you see here she has left on a branch block of 176 milliseconds and with one single lead we've achieved re-synchronization of the ventricles with a paste QRS of 90 milliseconds. And for all the echocardiographers in the room this was her baseline echocardiogram pre-implant. Three months after implantation we repeated an echocardiogram and the EF after looking at multiple views was reported at 50 to 55 percent. She's NYHA class one now comes to see me in clinic she's still alive and now comes to see me in clinic with a cane because she has rheumatoid arthritis and has no cardiac symptoms whatsoever. So now let me show you a couple of cases of where his bundle pacing can really help with CRT and this is probably fairly valuable for the EPs in the room because this is how we've been doing this. So we all have patients that get you know be either referred out or get referred to us for CRT. This is a classic example an ischemic cardiomyopathy with an EF of 30 percent class three symptoms and a left bundle of 170 milliseconds. Patients 81 years old. So not diving too deep but the simple fact is we tried for three hours to place a biventricular or CS lead in and failed. And this was my first case as an EP fellow I've been doing his bundle pacing since I was a cardiology fellow. And this was my first bivy case as an EP fellow and after and this was one of the best implantors I know to date. And after seeing him struggle for three hours I gathered the courage to say before we send this patient for an epicardial surgical system would you want to try his bundle pacing. And he was like at this point I will try anything. So this this is how we do these we record the his electrogram so you see a atrial electrogram a his and a ventricular electrogram at this location. We place the lead there this was the final paste QRS. Plurotime of one minute and procedure time of four minutes after trying for three hours plus for a CS lead. And this this patient was a super responder despite having an ischemic cardiomyopathy his EF improved to 55 percent and YHA class one. We call this rescue his CRT which means if you fail a CS lead implant then we can try to do this as a bailout strategy. But here's another example of what we now refer to as primary his CRT which is there's a patient with a non ischemic cardiomyopathy you know there are some features of this QRS that look like a clip typical classic left bottom branch block but there are some that don't. And so in these cases what we do is we try to prove to ourselves that what we're doing is the best strategy for this patient. So here's an example of what we do. So we basically get into the CS like it's stuck but in either case we get into the CS we place a wire sorry we place a wire into the lateral CS branch and we measure what we call the QLV which tells us how delayed is the activation on the lateral wall of the left ventricle. You see here this is the CS venogram and this is the wire placed in the lateral left ventricle and we have a the QLV is 120 milliseconds. I'm not going to play the videos I'll just show you guys the images. So here is we're trying to map the bundle of his and you see an A, H and a V. This is a proximal location because the A is big and so we don't like this part we move on to a slightly superior location. You still see an A, H, V but the A is smaller and you paste here and the QRS looks narrower and the QLV gets shorter from 120 milliseconds to 90 milliseconds. And so we say let's map it on a little bit more and so we find this distal location where the A is very small there's a his and a V, fluoroscopically this is even more superior but when we paste here look at that QRS duration and look at what happens to the QLV which means the lateral wall is activated almost the same time as the RV septum. This proves that there is no better way to activate this ventricle than through the conduction system with an endo to epi approach. And this patient had a final base QRS of 88 milliseconds and is also a super responder with a normalization of her EF. So this is primary his bundle pacing for CRT what I showed you earlier was rescue his bundle pacing for CRT. Now how is this possible? We published on the mechanisms of how this is possible but to simplify things for you there's this concept of what we call the longitudinal dissociation within the his bundle. So the way I explain this to my patients is the AV conduction system is like being on a freeway. You're on a freeway with four lanes you suddenly hit the tow booth the tow booth is the AV node after you cross the tow booth the freeway divides in about a half a mile into lanes going west and lanes going east but you start seeing signs right away if you're going west take the right two lanes if you're going east take the left two lanes the same concept applies within the bundle of his the fascicles or the fibers that are about to become the right bundle branch and the left bundle branch are starting to separate and they had their insulated fibers that are starting to branch out already within this common area of the bundle of his and 85 to 90 percent of the time the disease is actually located within these proximal fibers so this is the model that we published so if you look at these fibers that are predestined to become the left bundle and the right bundle branch and diseases in this region if you can place a lead distilled to that area of disease you can completely narrow this left bundle branch block pattern that completely narrows with his bundle base so it's this concept of longitudinal dissociation within the his bundle and disease that is located within those proximal fibers that you can overcome with his bundle base so here is a summary of all the outcomes data there is on his crt and you can see we've done a lot of work in this with two big publications in this region this was the biggest study to date or series to date i should be specific we won the best publication of the award for this paper at hrs this past year and this is a multi-center experience of using his bundle pacing as an alternative for cardiac resynchronization what we had was we had two groups we had patients that we performed his bundle pacing as a rescue strategy like i showed you earlier and a second group where we perform his bundle pacing as a primary strategy and these were all comers with various crt indications and we had a success rate of about 90 percent in achieving crt with his bundle pacing what's interesting is that there were eight patients in the study and we now have 16 or 17 patients there were non-responders to traditional by v crt that had successful his bundle pacing for crt and six out of these eight patients are now responders the you can see significant improvements in lvef improvements in nyj functional class the overall response to his bundle pacing was 73 clinical response 70 plus echocardiographic response and a 40 percent super responder rate which are higher than traditional by v crt numbers that have been reported now another unique patient population that doesn't do very well with by v crt is those patients that have a cardiomyopathy and have right bundle branch block because biventricular crt is going to resynchronize the lve doesn't do much for the rv and so we performed a study on patients with right bundle branch block and cardiomyopathy and you can see a significant decrease in qrs duration improvement in lvef except for three patients in this patient cohort overall response rate was 76 percent echocardiographic response rate was 70 percent and super responder rate was 20 percent the interesting thing from this study was that even those patients that had a qrs duration between 120 and 150 milliseconds and a right bundle branch block also had a very high response rate which is not something we've seen in any reported study with by v crt i'm showing you all of this data because this is a signal this might become an alternative for cardiac resynchronization therapy and maybe both of by v and his might be available we might pick and choose which is best for our patient in a given scenario at the present time there is only one pilot randomized study that was just presented at heart rhythm that we were a part of it was called his sink that was only 40 patients but it did show us that his crt had better clinical echocardiographic response rates compared to by v crt with an average improvement in lvef of about 9.5 percent compared to 5.5 percent with by v crt this was core labs used for ecgs and echoes in a very good study that was randomized control but only 40 patients so more data needs to be available before this becomes you know an accepted standard of care so our experience at rush we've done about 273 attempted cases of which 265 have been successful with a 97 success rate as you can see majority of our patients are bundle branch block wide qrs just because of the referral patterns that we have only a quarter of all these patients receive the crt device though because as i showed you there are patients that you can achieve this with a dual chamber pacemaker and if they don't have any scar and their ef is borderline we don't put in defibrillators for them and we've done about 42 patients now with his bundle pacing and av node ablations if you have a patient that has a narrow qrs to begin with and you're going to do an av nodal ablation because they're elderly and they cannot undergo any affib ablation then putting in a biventricular crt for them is creating this synchrony so this in my opinion becomes the best strategy for that patient cohort now how has this impacted the guidelines like i said there are no randomized controlled trials to date and yet we have a class 2a indication in the guidelines based on all the data that i showed you this has created a movement in the ep community we have a program at rush where we have physicians that come to train and get proctored on his bundle pacing and at the present time there is a wait list of 700 physicians waiting to get trained and we've already trained over 350 400 so it's a class 2a indication for those patients with an ef between 35 and 50 on an anticipated pacing more than 40 where you could either choose his bundle pacing or buy v crt for that patient cohort it's a class 2b indication for those patients with av block at the level of the av known and these are these indications are coming based on the data we have and unfortunately we don't have large-scale randomized controlled trials because those studies will take millions of dollars and there is not much to gain from an industry perspective but to conclude are we pacing has been associated with adverse clinical outcomes including atrial fibrillation heart failure cardiomyopathy and associated mortality the search for an alternative site has led to his bundle pacing which is a more physiological form of ventricular activation his bundle pacing has demonstrated superior clinical outcomes in comparison with conventional are we pacing although i would caution you that these data are not randomized control and his crt might be an alternative to buy v crt but this does need further investigation i'll stop there thank you for your attention