The lecture for today is Cardiac Conduction System Pacing Theory and Practice. These are my disclosures. Prior to embarking on conduction system pacing, it's important to understand the anatomy of the conduction system. As you can see, the left bundle branch area and the his bundle pacing locations is in a small region in the membranous interventricular septum. The his bundle starts at the proximal atrial component of the interventricular septum and continues as a branching portion on the ventricular aspect of the interventricular septum. As you can see in this mounted autopsy macroscopic view of the conduction system, the his bundle is a small region in the AV annulus, as you can visualize this long strand of conduction tissue. It can be anywhere from 2 to 4 millimeters in width up to 2 centimeters in length, and it can be variable depending on where it lies along the membranous septum or into the portions of the muscular interventricular septum just below the membranous septum. Compared to the his bundle region, the left bundle branch continues from the branching portion of the his bundle onto the left ventricular septum. It provides a cascade of Purkinje system and possibly a better target for conduction system pacing, with the exception being this wide area of target lies on the left ventricular side, but we are to access it from the right ventricular aspect of the ventricular interventricular septum. And let's talk about his bundle pacing in AV nodal block. Here is a patient with a narrow QRS complex and complete heart block. Intracardiac electrogram recorded during his bundle pacing from the pacing lead itself shows this evidence for atrial to his block and an escape rhythm with a his potential prior to the QRS, suggesting the conduction system after the his bundle is relatively normal. And pacing at this location, the his bundle, can result in perfectly normal looking QRS. How about patients who have so-called HV block? Here's a patient with 2 to 1 AV block with underlying right bundle branch block. Intracardiac electrogram shows evidence for HV block, as you can see, atrial signal followed by his signal and non-conducted beat, followed by a conducted beat with a longer HV interval. But pacing in the his location from the electrode can result in recruitment of the distal right and left bundle branch in this patient and restore conduction, suggesting that this is indeed an intrahysion block, and the block is not well below the his, but rather at the his bundle itself. This was one of the recommendation statements from an expert group of implanters well versed in his bundle pacing, who developed this criteria for his bundle pacing. And it would be good to review this particular article, where we have described the criteria for his bundle pacing as a component called selective his bundle pacing or non-selective his bundle pacing in those with narrow QRS and those with underlying conduction disease. We'll go over some of the examples of his bundle pacing in patients with normal Purkinje conduction. In those patients whom we have what we call a selective his bundle pacing, capture of the his bundle alone without capturing any surrounding myocardial tissue, atrial or ventricular, do have certain characteristics, and we can go over in examples. Here in this example, the native QRS is about 90 millisecond in duration, and the HV interval is 40 milliseconds, as demonstrated by the HV interval here. And during pacing, there is selective capture of the his bundle with the paced QRS duration of one similar 90 millisecond, with the stimulus to ventricular onset of 40 millisecond, with a discrete local electrogram in the pacing electron. In these patients, you only have one capture threshold, capture of the his bundle alone. That's very typical of selective his bundle pacing. On the other hand, in non-selective his bundle pacing, there is capture of both right ventricle and his bundle. So you may be able to identify separate capture threshold for the myocardium, as well as the his bundle. As a result, the paced QRS duration is usually wider than the native QRS, but with rapid normalization of precardial and limb lead axis, and rapid DBDT in the QRS complexes. Because there is capture of the local ventricular myocardium, there would not be any discrete electrograms on the pacing artifact. And in addition, the QRS usually starts immediately after the pacing stimulus, although some patients may have a pseudo delta wave, where it looks like a very slow onset delta wave. So here is an example of a non-selective his bundle pacing in a patient with narrow QRS. And you can see the paced QRS is about 120 milliseconds, compared to the native QRS at 80 milliseconds, with the HV interval of 40 milliseconds. As your output is decreased, the QRS prolongs. Now you've reached the his bundle capture threshold. Now you have only RV myocardial capture, as demonstrated by a prolongation of the retrograde conduction time, suggesting that the his bucking system is not directly engaged. Here's another form of non-selective his bundle pacing. As you do threshold testing, you go from this non-selective, relatively narrow QRS complex to this completely normal QRS, where you have transition from non-selective his bundle pacing to selective his bundle pacing, where you've reached right ventricular capture threshold. And then the his capture threshold is much lower than the ventricular capture threshold. Also notice that when the his bucking conduction system is engaged, the retrograde activation time for the atrium is remaining constant. Now let's move on to his bundle pacing in patients with conduction disease, like patients who have bundle branch blocks or HV block. So in this situation, the criteria are somewhat similar, except that the pace QRS is often much narrower than the native QRS, unlike inpatient normal his bucking conduction system, where it's already as narrow as it can be. In addition, inpatient selective his bundle pacing, you may find two different capture threshold, one for his bundle pacing with bundle branch block correction, another without bundle branch block correction. And these needs to be identified. In looking at this example, you can see a patient with a wide QRS and a right bundle branch block for 180 milliseconds. And at 1.2 volts, there is transition with perfect capture of his bundle and correction of the underlying right bundle branch block with QRS duration 100 milliseconds. As you come down on the output, you lose that correction of the right bundle branch fibers, and you only have left bundle branch fiber capture and the residual right bundle branch block. But the actual his threshold can be much lower than this without correction for the bundle branch block. Here is another example of a patient with a wide left bundle branch block, QRS duration 190 milliseconds. And during his bundle pacing at 2 volts, there is selective capture of the his bundle, including the left bundle branch fibers, resulting in complete normalization of the QRS with a duration of 95 milliseconds. Look at the discrete electrical component in the his bundle lead, suggesting there is no myocardial capture. And at a lower output, you have still his capture with discrete local electrogram and isoelectric interval, but the left bundle branch block is not corrected. It's identical to the native left bundle branch block, suggesting that this is his capture without the left bundle branch block correction. How about non-selective his bundle pacing? In this situation, as described before, your QRS onset will be immediately after the pacing artifact, and the local ventricular electrogram will be pulled into the pacing artifact. And the pace QRS can be equal or narrower than the baseline wide QRS. However, you may have up to three different capture thresholds, where there is bundle branch block correction, no bundle branch block correction, without RB pacing at different levels. Let's look at an example of a patient with the right bundle branch block. QRS duration of 160. At 1.2 volts, you have capture of the local ventricular myocardium and complete normalization of the right bundle branch block with a QRS duration of 110 milliseconds. There is a delta wave onset immediately after the pacing artifact. And at a lower output, you lose the right bundle branch capture. So there is residual right bundle branch block partially corrected with RB fusion. And as you come down on the output, you lose the left bundle branch capture, and you only have RB pacing. So different fibers in the Hispokinetic conduction system can be captured at different outputs. And now, a patient with the left bundle branch block, QRS duration 195 milliseconds. And when pacing at a higher output, you have some narrowing of the QRS with significant shortening of the QLV or stimulus-to-LV activation times here. Nonetheless, QRS is still wide, but it's better visualized here at a lower output when there is selective capture of the Hispundle with significant shortening of the QRS duration from 195 to 125 milliseconds with some residual IVCD. And at a lower output, you have only selective capture of the Hispundle without left bundle branch block correction. So all these things have to be factored in when interpreting Hispundle pacing in patients with underlying conduction disease. How about patients with HV block? Here's a patient with intrahysion HV block. You can see 2 to 1 AV block during atrial pacing, but with narrow complex. But you can see A followed by His with no ventricular activation. Hispundle pacing can selectively capture at this point because you're at or slightly beyond the side of block and achieve perfectly narrow QRS with selective Hisp pacing and capture of the distal conduction system. Another patient with complete HV block with the right bundle branch block escape rhythm and pacing with a higher output, you can see non-selective capture of the entire conduction system. And as you do threshold testing, you can see selective capture of the left bundle branch fibers in a patient with complete HV block. So the ECG characteristics of Hispundle pacing are rather straightforward and simple in most situations. And almost more than 90% to 95% of patients will have easy identifiable transitions during threshold testing, helping you define Hispundle capture. As you can see, there's different types of capture. You can go from non-selective to selective to loss of capture or non-selective to myocardial capture to loss of capture. And in the 5% to 10% of patients where it's not very clear, program pacing can identify differential capture of myocardium as well as Hisp block in your conduction system. Nonetheless, there are certain morphological features of Hispundle pacing, especially when trying to differentiate myocardial capture from non-selective Hispundle pacing. It is anticipated that in Hispundle capture, there shouldn't be any plateaus in lead 1 or AVL or V5, V6, and no notching in V1 or inferior leads. And the stem-to-peak R-wave times in V6 should be less than 100 milliseconds, suggesting that you have Hispundle capture with rapid activation. These numbers can be variable in patients with underlying Purkinje disease and without correction of the conduction system. While Hispundle pacing has the most physiologic activation of the ventricles, there have been some challenges over the years. And some of these are high pacing threshold at implant due to the fibrous nature of the AV analysts and the inability to reach the Hispundle itself in some patients with deeper location of the Hispundle. More importantly, there is a certain percentage of patients that have unpredictable threshold rise during follow-up, and ultimately leading to lead revision in up to 5% of patients. Sometimes there is challenges with ventricular sensing and atrial over-sensing due to the proximity of the atrial tissue. This led to the development of left bundle branch pacing because of the perceived superior features of left bundle branch pacing. It has a wider landing zone if you happen to get into the left ventricular conduction system. There's almost always good amount of left ventricular septal myocardium providing safety net for capture thresholds. While physiology may be less pronounced than Hispundle pacing, it's perceived that the procedure time is fairly easy and shorter, and it can be used in any types of conduction disease in patient with AV nodal block as well as infernoidal AV block. And thresholds and sensing seem to be more than optimal compared to histone pacing. So let's look at left pulmonary branch pacing. And because it's in the distal part of the conduction system, you happen to have low and stable threshold. And we'll describe how this type of pacing can achieve consistent pacing beyond the site of conduction disease as compared to histone pacing. So in terms of definitions, there are few terminologies have crept into the literature. While left pulmonary branch pacing should be, there should be evidence for direct capture of the left pulmonary branches, which is invariably associated with left ventricular septal myocardial capture. And when you're very clear that there is only left ventricular septal myocardial capture and no evidence for direct conduction system capture, it's called LV septal pacing. The term left pulmonary branch area pacing often is used to denote either left ventricular septal pacing or left pulmonary branch pacing without a clear distinction between the two to describe as a group. This came into existence because of challenges associated with convincingly confirming left pulmonary branch capture in most patients. The criteria for left pulmonary branch pacing has been established over the years and recently updated in the Heart Rhythm Society 2023 guidelines for cardiac physiologic pacing. And the criteria as described here we'll go over most of them in detail is you need to have the lead placed in the left ventricular septal location, that is in the deep septum. Needs to be confirmed by either using fulcrum sign, contrast injection, echocardiogram CT, or differential assessment of the LV ring threshold and impedance. And in addition, most of these patients should have a right pulmonary branch conduction delay pattern in lead one, except in rare situations. In addition to these two, there should be evidence for left pulmonary branch capture, which is where this numerous multitude of criteria exists because of lack of consistent single criteria that can be achieved in every single patient. We'll go over some of these criteria. So rule number one, the location of the left bundle branch pacing should be at least 1 to 2 centimeters distal to the his bundle. Ideally, you don't want it to be too far down the conduction system. You want to try to stay in the proximal conduction system. And during pacing from those site, need to have a right ventricular conduction delay pattern or right bundle branch block pattern, suggesting that you're capturing the LV septal myocardium than the RV myocardium, and usually unipolar pacing. And then if you're in the left bundle branch location, you should be able to demonstrate left bundle branch potential. Well, presence of a potential does not constitute left bundle branch capture. Evidence for left bundle branch injury current, as demonstrated here, is a strong sign for left bundle branch capture because you're directly embedded in the left bundle branch. And then during left bundle branch pacing, you can show that early activation of the Hispokin system by demonstrating a short retrograde stimulus to His interval, as demonstrated in this picture. In addition, as discussed earlier, we can confirm the location of the lead in the deep interventricular septum by injecting a few cc of contrast along the septal myocardium, showing the length of the lead in the interventricular septum, as demonstrated in this left anterior oblique view. So let's talk about various types of capture, what we call as non-selective left bundle branch pacing. And when you have non-selective left bundle branch pacing, means you capture the left bundle and the LV septal myocardium at the same time. There is no latency on the based QRS morphology. And the local electrogram usually does not show any discrete electrogram because it's capturing both the left bundle and the local myocardium. When there is transition to left bundle branch capture only, which is called a selective left bundle branch pacing, there is a stimulus to QRS latency, as you can demonstrate on the surface electrograms. And you can also see there is a local discrete electrogram because that myocardial tissue is not captured. In patients with left bundle branch pacing, this is only achieved at a very near threshold, as the amount of ventricular septal myocardium is fairly abundant near the left bundle branch location. As a result, you have a short stimulus to LV activation time as measured in V6. And that remains constant between non-selective and selective captures. Some of the other finer points of left bundle branch pacing is you advance the lead in the ventricular septum. Here, there is some semblance of a left bundle branch potential on the local electrogram. But pacing at 3 volts, the stimulus to peak LV activation time is 105 millisecond. Press increase the output. You can see that peak activation time is shortened. And you have a more robust right bundle branch delay pattern in V1, suggesting that the lead needs to be advanced a little further. And when the lead is advanced further, you can see a stronger left bundle branch potential with left bundle branch injury current. And as you pace and do threshold testing, there is transition from non-selective to selective with the discrete local electrogram, as well as similar constant in a short peak LV activation time in lead V6. And you can also see the short stimulus to retrograde is activation time, suggesting direct engagement of the ispokinje system. These findings become somewhat complex in patients with left bundle branch block. While we would like to have similar features of a left bundle branch area pacing, so anatomical location, pace morphology of the right bundle branch block delay pattern, as well as if you're able to demonstrate left bundle branch potential, which is usually absent in a patient with left bundle branch block, as there is block above the level where the lead is generally placed. But left bundle branch potential can be demonstrated if you perform his bundle pacing as you restore conduction along the left bundle branch, or sometimes during PVCs generated from the lead placement at the left bundle branch itself. So let's look at some of the examples in this patient with the left bundle branch block, QRS duration 180 milliseconds. There is no left bundle potential preceding the ventricle electrogram in the local electrogram. But some patients may have retrograde left bundle branch potential as RV gets activated and engages the conduction system late. During his bundle pacing, here there is correction of the left bundle branch block. QRS gets narrowed. And you can see the demonstration of left bundle branch potential itself in the electrograms. And during threshold testing, you can demonstrate transition from non-selective left bundle branch pacing to selective left bundle branch pacing as demonstrated here in morphology in lead B1 and B2. And you can see the separation of the local electrogram and simultaneously showing constant and short LV activation time as demonstrated by a coronary sinus electron in this example. Here's another example of a patient with left bundle branch block. No pre-potential before the local electrogram. However, when you perform his bundle pacing with correction of the underlying bundle branch block, the left bundle branch potentials are restored as conduction through the left bundle is present now. The patient still has a certain amount of conduction delayed due to intraventricular conduction deficit. How else can we confirm left bundle branch capture? So in this patient with the narrow QRS, there is a multipolar catheter placed along the LV septum recording left bundle branch potentials and the Purkinje potentials. And during pacing at a lower output in the first lead location, you don't see any pre-potential, even though you may have a right bundle branch delay pattern. But at a high output, you can see this left bundle branch potential restored on the surface. And as the lead is advanced deeper, both at high and low output, there is evidence for Purkinje potential preceding the QRS and the ventricular activation normalized, as you see in the normal narrow complex. How about in patient with left bundle branch block? As you can see, the same septal catheter does not record any left bundle branch potential. And as you pace from the lead at the first location, low output, there is no left bundle branch potential activation. But at higher output, with shortening of the peak LV activation time in lead V6, there's a restoration of Purkinje potentials in the septal electrode. The lead is advanced deeper, and now you have, at high and low output, the Purkinje potentials consistently restored, suggesting that you have left bundle branch capture. Again, confirming during his bundle pacing and restore conduction in the left bundle branch pacing electrode, as well as in the distant Purkinje system. Confirming that you're able to restore conduction both by his bundle pacing and left bundle branch pacing. When none of these findings that we described to confirm direct confirmation of left bundle branch capture, we call it left ventricular septal pacing. But we've developed some criteria to use for identification as an indirect criteria. This may not always be highly specific and sensitive, but it provides an idea to help you decide whether you have left bundle branch capture. These are physiology based. And when you have intrinsic QRS, you have a left bundle branch potential. The potential to peak LV activation time in lead V6 should be similar during pacing. On the other hand, when you have only septal myocardial capture, that conduction time will be longer. So as you can see, if you measure the peak LV activation time from QRS onset, both during non-selective and selective left bundle branch pacing, they remain short and similar to native. While when there is only LV septal pacing, these activation times get prolonged. You can measure from the left bundle potential to R wave peak times in V6. And you see, again, LV septal pacing is similar. Left bundle branch pacing, it is similar. While LV septal pacing, it gets prolonged, again, demonstrated in these two case examples. However, is there a specific criteria that you can use? These criteria were determined in predominantly patients with narrow QRS undergoing conduction system pacing for bradycardia indications. In these patients, narrow QRS and right bundle branch block, you can see the distribution curves of R wave peak times during LV septal pacing and non-selective left bundle branch pacing. There is a significant overlap. However, if you want to use an absolute criteria for high specificity, it's suggested that LV R wave peak times are less than 74 milliseconds, provided your lead is in a proximal location and you have a predominant R wave in lead V6. In patients with bundle branch blocks, or IVCD, it's anticipated that these intervals will be somewhat longer. Again, understanding the limitation of this criteria due to significant overlap. We have come up with a different method, especially for patients with left bundle branch block. You perform his bundle pacing. You assess the peak LV activation time during his bundle pacing with correction of the bundle branch block, as shown with 103 milliseconds. And during left bundle branch pacing, you can see from non-selective selective transition, less peak LV activation time is significantly shorter. And during LV septal pacing, it is longer. And when we perform distribution curves, we can assess this delta R wave peak times from his bundle pacing to left bundle pacing. We would anticipate a timing of more than 10 milliseconds to provide high specificity. Again, provided the lead is placed in a proximal left bundle branch location, not in a distal, posterior, or apical location. Moving on to how does it translate into clinical practice in patients with AV block. Here's a series of 333 patients with conduction disease, AV block. Predominantly, these patients had block at the AV nodal, as demonstrated by AH block, very easy to demonstrate. And his bundle pacing performed well in these patients. With patients with intranodal block, where we normally demonstrate HV block, we confirmed this block to be intrahysian, contrary to historic identification of intrahysian block, as only those with HV block and a narrow QRS, or those with split his potentials, as demonstrated here. We confirmed this to be intrahysian by pacing the his bundle and correcting the distal conduction system. And that was in the majority of patients. Or if you place the lead in the left bundle location, and your left bundle potential to cure its duration is significantly shorter than 35 milliseconds. This would suggest that the cell connection is intact, and the block is at the intrahacian level. And the true infrahacian block, block well below the His bundle itself, was observed in only 4% of patients, as demonstrated here. So left bundle branch potential, but during atrial pacing, you have a 2 to 1 left bundle potential to ventricular block. Or in those patients with escape rhythm, you demonstrate a very diseased conduction system, here demonstrating left bundle potential to cure a duration of 95 milliseconds. And these phenomena was present only in about 4% of patients. And in about 7% of patients, we were unable to determine, but still were able to achieve relatively narrow cures. So overall, Hispokinetic conduction system pacing was feasible in 97% of the patients. As this translated into improved clinical outcome, this is a two-center comparison of His bundle pacing with some RV pacing, a non-randomized, but institutionally randomized observational series of patients. About 765 patients with a two-year follow-up minimum. When we looked at the primary outcome of death, heart failure hospitalization, or a need to upgrade to biventricular pacing, it was significantly reduced in those who underwent His bundle pacing. And these outcome differences were primarily in those patients with ventricular pacing burden greater than 20%. All of these differences were primarily attributable to a reduction in heart failure hospitalization. And this reduction in heart failure hospitalization is only seen in patients who needed high ventricular pacing burden. In another study of 200 patients with a five-year follow-up, we were able to identify that the incidence of pacing-induced cardiomyopathy was very low at 2% with His bundle pacing, compared to 22% in patients who underwent traditional RV pacing, as confirmed in many other historic publications. How about left bundle branch area pacing in this bradycardia population? This is another two-center study. Unlike the prior one, this was not an intention-to-treat analysis. This was on-treatment analysis of about 700-plus patients. This group of patients, again, were able to demonstrate a significant reduction in the risk for death, heart failure hospitalization, or need of upgrade to by RV pacing. When we looked at individual outcomes, there was some evidence for even reduction in mortality, in addition to secondary endpoint of heart failure hospitalization. And all of these differences occurred primarily in patients with high pacing burden requirements. Here's another real-world evidence study. Now, looking at about 23,000 patients, about 6,000 patients undergoing conduction system pacing. This is from Medicare Clinical Evidence Development Study. When we looked at this 23,000 patients, the incidence of heart failure hospitalization was significantly reduced in patients undergoing conduction system pacing, compared to right ventricular pacing. More importantly, there was a suggestion with a strong difference in the mortality outcomes between the RV pacing and conduction system pacing. This is only within six months follow-up itself. As you can see, the divergence of the curve showing the power of conduction system pacing in patients requiring ventricular pacing. As a result of many of these studies, the current guidelines have been updated from the Heart Rhythm Society guidelines released in 2023. So in patients with indication for pacemaker therapy and an anticipated substantial ventricular pacing, which is considered as 20% to 40%, if the LV function is preserved, then cardiac physiologic pacing with either bi-V pacing, hispinal pacing, or left frontal branch area pacing is considered a 2B indication. While in those patients with reduced LV ejection fraction, then these approaches become class 2A indication. Again, in most patients with LV ejection fraction 36% to 50% and anticipated high ventricular pacing, cardiac physiologic pacing is a reasonable approach, 2A indication for reducing the risk of pacing reduced cardiomyopathy. In patients with preserved LV function, it is reasonable to consider treating them with cardiac physiologic pacing to reduce the risk of pacing reduced cardiomyopathy. And when you pursue hispinal pacing, it's also considered reasonable to provide a backup lead for providing sensing as well as potential mitigation of the risk for high capture threshold. In patients with less than substantial ventricular pacing, currently, hispinal or left frontal branch pacing is considered a class 2B indication. There's no role for bi-ventricular pacing when there is no indication for ventricular pacing. How about patients with heart failure? Conduction system pacing has a special role to play in patients with heart failure. Why is that? This is a very elegant study done from the Imperial College looking at patients with left frontal branch block and heart failure. And they compared hispinal pacing with bi-V pacing in the same set of patients and using innovative body surface ECG mapping. And they were able to demonstrate that hispinal pacing compared to bi-V pacing resulted in significantly further reduction in QRS duration, improvement in LV activation time, detection in the left ventricular desynchrony index, in addition to improvement in hemodynamics. This is on top of what could be achieved with bi-ventricular pacing. So you can achieve greater electromechanical resynchronization with hispinal pacing in patients with left frontal branch block. Similar study, but performed with LV septal endocardial pacing, again, an alternate form of body surface ECG imaging, and intracardiac LV pressure measurement demonstrated that the LV septal pacing, as a surrogate for left frontal branch area pacing, was providing similarly better LV activation times and comparable improvement in hemodynamic benefits with hispinal pacing or bi-ventricular pacing. For the last decade, you've had several small to medium to large observational studies and multiple small randomized studies that have shown the benefits of conduction system pacing for cardiac resynchronization therapy with more than 5,000 patient data available currently. Here's one of the early randomized study of hispinal pacing versus bi-ventricular pacing in left frontal branch block. The importance of this study is that 96% of these patients, 24 out of 25 patients, they were able to correct the underlying left frontal branch block as defined by Strauss criteria. But hispinal pacing was not achievable in about 28% due to high CAPGETs are shown. Nonetheless, on the analysis of intention to treat, the outcomes were similar to bi-ventricular pacing. But on protocol analysis, the LVE of improvement was greater with hispinal pacing compared to bi-ventricular pacing. This set the stage for left frontal branch pacing because you can place the lead distal to the hispinal, distal to the site of conduction block, and result in near normalization of the QRS, albeit with a little bit of a right ventricular conduction delay. But the success can be achieved in a much higher percentage of patient, as demonstrated in this observational study, were successful in more than 90% of patients with left frontal branch block pattern with significant QRS narrowing. And associated improvement in LVE injection fraction and functional class. This set the stage for confirming and performing randomized pilot trials. It's a 40-patient study comparing left frontal pacing versus bi-ventricular pacing with a high success rate of 90% compared to 80% with bi-V pacing. And the study results showed that the change in LVE injection fraction in this highly selected non-ischemic dilated cardiomyopathy patient were 21% improvement in LVE function compared to 15% improvement with bi-V pacing, suggesting you can achieve greater electromechanical improvement with conduction system pacing. We looked at it in a two-center study comparing conduction system pacing versus bi-V pacing for clinical outcomes. This demonstrates the study flow showing that high success rates for conduction system pacing is a first approach. And we had a series of about 477 patients looking at the primary endpoint of death. The heart failure hospitalization was significantly reduced with conduction system pacing compared to bi-ventricular pacing. And these effects are more pronounced in patients with underlying left frontal branch block, suggesting that there's a particular group that benefits from bi-V pacing, but you can achieve greater benefit with conduction system pacing. Comparatively, there is greater reduction in QRS duration, greater improvement in LVE injection fraction. Now, moving on to real-world evidence, we looked at this, again, observational study retrospective in a larger patient group from 15 centers around the world showed that the incidence of death of heart failure hospitalization can be further reduced with left frontal branch area pacing compared to bi-ventricular pacing. In patients with LVE injection fraction, less than 35% indication of cardiac recyclization therapy. And this is, again, more pronounced in patients with left frontal branch block. And overall, the LVE injection fraction improved significantly more in patients undergoing left frontal branch area pacing. And the echocardiographic response and hyper-response rates were higher in patients with left frontal branch area pacing compared to bi-ventricular pacing. One additional benefit that we noticed in this group, this is a propensity score match population of 1,400 patients in the same study, showed that the new incidence for sustained VTVF among these patients was significantly reduced with left frontal branch area pacing compared to bi-V pacing. Suggest better electrical resynchronization, better improvement in hemodynamics may result in reduced ventricular arrhythmia risk. More importantly, it can also reduce the risk for nuanced atrial fibrillation in this population. Now, there's been several meta-analyses of conduction system pacing versus bi-ventricular pacing in CRT, demonstrating the heart failure hospitalization benefits, as well as mortality benefits that may be achievable in this population. We looked at the mildly reduced LVE injection fraction in a group of 1,000 patients, comparing bi-ventricular pacing versus conduction system pacing. Again, this study demonstrated reduction in the primary outcome of death, the heart failure hospitalization, and primarily due to a significant reduction in the heart failure hospitalization in the conduction system pacing group compared to bi-ventricular pacing. The recent guidelines, again, have updated indications for physiologic pacing, inclusive of hispinal pacing and left spinal branch area pacing, in addition to bi-ventricular pacing. So now, the society guidelines have moved hispinal pacing or left spinal branch area pacing as a class 2A indication in patients in whom effective CRT cannot be achieved with conventional bi-ventricular pacing. And if you look at patients with high pacing burden or pacing reduced cardiomyopathy, while IV pacing remains a class 1 indication, but conduction system pacing is a class 2A indication in these patients. And additionally, it's a class 2B indication in non-left spinal branch block patients. These are the various recommendations, and I suggest you strongly review these criteria as published in the updated guidelines in terms of when you can use conduction system pacing compared to bi-ventricular pacing in patients requiring cardiac resynchronization therapy, both in patients with left spinal branch block as well as non-left spinal branch block. It's a special group of patients with atrial fibrillation who undergo AV junction ablation. In this patient, especially if the LV ejection fraction is less than 50%, then it's preferential to do CRT with IV pacing as a class 2A indication, while his spinal pacing or left spinal branch pacing has been used as a class 2B indication. If the ejection fraction is normal, then his spinal pacing and left spinal branch area pacing may be preferred in those patients. The ongoing clinical trials, there are several of them, large trials looking for hard endpoints of death or heart failure hospitalization. And these trials hopefully will give us an answer in the coming years to help us place the conduction system pacing in the right hierarchy of when to use and how to use them. So in summary, his Purkinje conduction system pacing is feasible and safe in most patients requiring cardiac pacing as well as cardiac resynchronization therapy. And conduction system pacing is elegant in its simplicity and its ability to repair existing conduction problems. And the ongoing clinical trials will establish the role of conduction system pacing in our daily practice. Thank you very much. Thank you.

cardiac conduction system

His-Purkinje system

His bundle pacing

left bundle branch pacing

atrioventricular nodal block

clinical outcomes

heart failure

pacing-induced cardiomyopathy