So the next speaker is Gaurav Upadhyay, who's from University of Chicago Medicine. Gaurav, in conjunction with his partner, Rod Tong, and several others in Chicago, have done really elegant work recently characterizing the subpopulations of patients who actually narrow their QRS in response to his bundle pacing. Gaurav. Thank you very much. Respected chairs, ladies and gentlemen, good afternoon. It's really a pleasure to be here to share the podium with respected colleagues and speakers and hopefully we'll build on some of the points that have already been raised. I've been charged with providing some long-term data behind his bundle pacing, specifically with respect to lead longevity and impact on cardiac function. Here are some disclosures. And the agenda today, and indeed our whole session, has to do with the 360-degree perspective of his bundle pacing. And that really requires a discussion both of potential risks, so both potential concerns with using his bundle pacing, particularly with respect to lead longevity, as well as weighing those risks against benefits regarding the impact on physiology and the improvements which we can expect. So what data do we have? The first clinical experience which was reported with permanent his bundle pacing, the credit goes to Dr. Deshmukh, approximately two decades ago, who studied 18 patients with chronic atrial fibrillation and pursued AV node ablation and his bundle pacing. He was really hamstrung by the tools that were available at the time, used a sweet-tip lead, which was a fixed non-retractable helix, and utilized modified J-curved dilates in order to deliver the lead to the his bundle region. Although there were improvements along multiple echocardiographic parameters, his conclusions are notable in that he noted future studies with better lead designs are warranted to improve the pacing threshold and success rates. Now we're a little bit better two decades later, but many of us who perform his bundle pacing would say that we're still in the field's nascency with respect to the potential of his bundle pacing. And for some reason here, it looks like it's gone away. I have data overloaded here, guys, at the beginning of the talk. With respect to the current workhorse, we're utilizing the 3830 lead, which is a lead that is also a passively fixed lead and is delivered through a sheath to the his bundle region. Utilizing this new lead, we've seen improvements with respect to implant success, particularly in a narrow QRS population. Utilizing modern tool sets, his bundle pacing is achievable in over 80% of patients. But what is the longevity information of this lead, the 3830 lead? And with respect to that, let's go back to the original guidelines, actually the original approval data from the FDA. So that was submitted August 3rd, 2005 here in the United States. And as part of the approval process, Medtronic goes through a series of maneuvers in order to determine whether or not a lead is able to be actually implanted in humans. Here requiring 2 times 10 to the 5th cycles of a bend radius, 4 times 10 to the 8th cycles looking for lead fatigability. And the lead passed all of those normal testing protocols. Interestingly, if we go back to the initial approval document, elevated pacing thresholds were noted at this lead in the atrial and ventricular locations in a clinical study of 266 patients. This is in 2005. Now when we ask the question, what is the longevity of the lead in clinical practice, we can turn to the pediatric literature for some perspective. Because this lead was adopted for pediatric use far before it began being utilized for his bundle pacing. In the pediatric literature, we have some data that suggests that actually at 10 years of follow-up, lead thresholds in the atrial or traditional ventricular locations was quite reasonable. This is a series of over 100 patients by Bunsell and colleagues reported in 2015. Interestingly in a more recent investigation at a different center with slightly shorter follow-up, when compared to conventional lead, there appears to be a greater dispersion of captured thresholds. So what do I mean by that? In general, the 3830 performs similarly to conventional 5076 or other pacing leads. But there are some outliers. And that draws often the averages or the average threshold of this lead higher. And certainly that experience has been reported at multiple centers at the location for his bundle pacing. So the chronic threshold reported for his bundle pacing for even a narrow QRS population is slightly higher. And in Dr. Vijayaraman's large retrospective case series, he also noted that there was a significant difference when compared to a cohort of patients receiving a traditional RV pacing lead. So here 1.56 volts versus 0.76 volts. In addition to the importance of threshold, we're also interested, of course, in freedom from complications. So here again, going to the pediatric literature, another large group reported that compared to the 1488 leads in the atrial position, there was no significant difference in atrial lead complications, and also no significant difference in ventricular position complications. Both of these curves overlapping one another. And this is in line with data that's been published by Medtronic, which suggests that a freedom from complications is present up to eight years in 97% of leads at eight years of follow-up. Why is this relevant? Because as we use this lead more, we will inevitably run into situations in which we find complications in which we should also consider extraction. So the extraction literature is very limited. So again, going to the pediatric population here with respect to extraction, the select secure lead, when compared to conventional leads in a set of 57 patients, was associated with actually less complex extraction, probably having to do with the smaller lumen size of the lead, so that it was actually easier to remove from a traditional ventricular location. In trying to review literature for extraction at the His bundle location, we have only anecdotal data. So only very small sort of individual case reports. So overall, I would argue that there's a favorable safety profile of this lead, but there are increased thresholds when pacing at the His bundle location. And of course, then that is then associated with increased battery drain and increased generator changes over the lifetime of the patient. So is the benefit worth it? So what is the impact on physiology? So a discussion of physiology begins with understanding how form affects function. And I would just remind the audience here that the heart itself is a helical structure. So at each layer of the heart, the heart simply does not squeeze, it twists. And in order for that twisting function to happen, there is a richly innervated His Purkinje network, which involves the synchronous depolarization of the heart. And this is why His bundle pacing, when compared to RV pacing, may be associated with benefit, particularly in patients who require at least a moderate degree of ventricular pacing. So in this study, a retrospective case series published by the Geisinger Group and Dr. Vijay Raman, there was a 31% reduction in the composite endpoint of death, heart failure, hospitalization, or upgrade to biventricular pacing. And it is because of this, as Dr. Adjijola pointed out, that now physiologic pacing with either His bundle pacing or traditional biventricular pacing is recommended in the guidelines for patients with a low or moderately reduced ejection fraction, and also in patients with AV node block. Permanent AV block, either preexisting or planned for AV node ablation in the treatment of atrial fibrillation, is associated with a particularly favorable use case. And in some literature suggests that near normalization of cardiac function is achievable for patients who have a tachycardia-induced cardiomyopathy. So I'll share the same baby picture as Dr. Adjijola. Everyone has one of these. I say that they're like baby pictures because they're adorable. But the question is, what's the data? What is the data with respect to QRS correction in patients who are receiving His bundle pacing? So His bundle pacing for QRS correction begins with a seminal paper that was published by Dr. Nerula in 1977, in which 22 patients at the time of EP study was corrected with His bundle pacing, followed shortly after by a study with Dr. El-Sharif and colleagues, seven patients, 1978. And then there was a relative lull until 2005, in which, in a fortunate circumstance, a patient presented with complete AV block and left bundle branch block and underwent an EP study at a Spanish center. And they found that they could narrow this patient during the time of the EP study on the evening before the pacemaker was planned. The next day, the original plan was to actually pursue a traditional biventricular pacing device, but the coronary sinus could not be cannulated. And so in this patient, because they knew the data from the day before that the QRS could be narrowed, they pursued a tendril. And this patient did well. In the same group, Dr. Barbara Pichardo's group published the first case series in 2011. And since then, there have been now been a handful of case reports as well as case series evaluating the role of His bundle branch, His bundle pacing for QRS correction in humans. Dr. Barbara Pichardo's group published their results in 2013, followed by Dr. Luskarton's paper in 2015. Dr. Wong's group actually presented very important results having to do with adjusting the pacing chamber from the tip to ring to tip to RV coil to improve longevity of pacing at this location. Dr. Adjijola presented his results for LD lead in lieu of a traditional CS lead. And then Dr. Sharma presented their multicenter cohort. Dr. Arnold's group published their acute results. And then more recently with right bundle branch block, as well as Dr. Wong's elegant case series, which we'll return to, and finally today. So in one page, this is the data that we have for His bundle pacing for QRS correction in humans. And I would just point out to you that the success rate has been variable. And this is not a function of chance. This is a function of pathophysiology. And it has to do probably because of where left bundle branch occurs. So building upon the discussions already started by Dr. Saxena and Dr. Adjijola, the question is, is left bundle branch occurring proximally? Is it occurring distally? Is it focal? Or is it diffuse? And the theories that have been proposed thus far, many of which have been discussed, include longitudinal dissociation of the His bundle, as mentioned already by Dr. El-Sharif and colleagues, left bundle conduction delay due to sourcing mismatch, or simply focal left bundle branch block. So we sought to investigate this with biceptal mapping of the conduction system in 88 patients with either a narrow or wide QRS pattern in order to prognosticate correction for patients referred to device therapy or for patients with ventricular tachycardia. Here's our experimental setup with a lead, a duodecapolar lead, that's placed along the LV septum using a retrograde aortic approach and a standard diagnostic recording catheter on the right side. To give you a sense of perspective in terms of where these leads are located or where these diagnostic catheters are recording their potentials, one catheter is placed on the right side of the septum in the standard location and another catheter is placed retrograde aortic along the left side of the septum. And the key observations here are what is happening to the His Purkinje potentials on the left side, because we're talking about correcting left bundle branch block. So importantly, we found that QRS correction occurs because of a recruitment of latent Purkinje fibers. So here in this example, a wide QRS becomes narrow when the Purkinjes can be recruited. And perhaps the most important observation is that intact Purkinje activation or intraventricular conduction delay cannot be corrected. So in this example, this patient with intact Purkinje activation cannot be corrected from the right or the left. Why is that? The data from the VT mapping is actually quite illustrative of this. In a patient with intact Purkinje activation, there's smooth continuous activation of the His Purkinje system. Pacing from the His won't make this any faster. The delay is occurring beyond the septum. Versus patients with proximal left bundle branch block, the block is occurring at the septum. A substantial portion of delay is occurring at the septum. And therefore, reengaging the His Purkinje network at this location can improve ventricular performance. And this summary diagram has been shown. We found that proximal bundle branch block is associated with the most common cause of left bundle branch block. Finally, I'll leave you with, well, what's the long-term data? Dr. Wong is here. This is a terrific study of 75 patients at a single center in which we have three-year follow-up with bundle branch block correction and terrific improvement in LVEF with stable corrected thresholds. So briefly here, the EF went from 30% to 57% for patients at a year and remained stable. And thresholds, importantly, were also stable for these patients. So LVEF improvement across CRT studies ranged between 3% and 8%. In cohort studies of the His Bundle Pacing, they've been substantially harder. Clearly, we have to phenotype patients correctly in order to achieve this success. But I'd argue that the future is conduction system pacing, that data with the 3830 lead is consistent with traditional leads but is likely associated with higher thresholds. The complication and safety profile appears favorable. The case for His Bundle Pacing with the NeuroQRS is quite clear, as guideline indicated. And why QRS underlying conduction matters. Patients left intrahiscient block have the best chance for success. And importantly, nonspecific IVCD is less likely to benefit. So new delivery tools and pacing systems are on the horizon. Thank you very much. Thank you.

University of Chicago Medicine

His bundle pacing

3830 lead

physiology impact

QRS correction