Hi there. My name is Ben Steinberg and thank you for joining us. It's a pleasure really to take part in the ACC's Quality Summit. Again, thank you for accommodating our new virtual format. Today I'm going to talk about the why and how of selecting a lead and location. As you can see, I've modified the title slightly to reflect what I think is an interest in novel pacing leads in the setting of patients who are candidates for defibrillators or cardiac resynchronization therapy devices. And so instead of talking about the ICD lead itself, we are going to be talking mostly about the pacing leads that may be added or part of systems in patients undergoing ICD device implant. These are my disclosures. As you can see, I've worked with a number of different companies and derived support from a number of different organizations. Of note, I have worked with a variety of manufacturers who develop and produce some of the hardware we'll be talking about today. I think it's important first to review the native intrinsic conduction system of the heart in order to understand what we're trying to achieve with different pacing technologies. In this slide on the left, unfortunately, is the right side of the heart, and on the right is the left side of the heart. So looking first at the left side is through the right ventricle, showing the AV node, the proximal or the penetrating His bundle, excuse me, in the branching His bundle in the P and B, and then the more distal right bundle branch and its divisions. On the right side of the slide is looking through the left ventricle. Shown behind is the right bundle branch, and then in the foreground is shown the left bundle branch with its anterior and posterior divisions. So as part of this talk, we will be talking about discussing different pacing approaches in an effort really to recreate or copy the intrinsic conduction system among patients whose conduction systems be diseased. And so this is really the gold standard, is the heart's intrinsic conduction system. By way of background, many of you are familiar with classic cardiac resynchronization therapy, CRT-D or CRT-P systems. These have previously been demonstrated to improve outcomes among patients with heart failure and wide QRS or native conduction disease. More recently, it was demonstrated that patients with any, really any LV dysfunction with an ejection fraction less than or equal to 50%, among whom will need significant pacing, usually defined as greater than 40%, that CRT was favored. The mechanism of CRT is generally thought and believed to be related to synchronized wavefront electrical activity. And the way we've classically approached that is shown on the right, and it includes a common right atrial lead, a regular right ventricular lead for pacing, and then a lead that goes posteriorly around the back of the heart to the coronary sinus and its tributaries in order to facilitate electrical stimulation of the left ventricle, and thereby try to achieve near simultaneous left and right ventricular electrical activation. This has been available now for many years, is widely adopted and implemented, and there are a number of different techniques, approaches, and hardware available to accommodate the procedure. Of note, however, it does have its limitations, primarily those related to coronary sinus anatomy, availability of coronary sinus branches for lead deployment, leads themselves, the technology, as well as the underlying myocardium and the availability of a capture of the left ventricular myocardium. Lastly, on occasion, deployment of a lead is significantly limited by capture of the phrenic nerve on the outside of the heart. And so while CRT has been the mainstay of electrical resynchronization therapy for patients, it's not without limitations. However, the evidence base for CRT is relatively wide and deep. However, CRT in general represents a relatively roundabout and limited means of correcting electrical synchrony. That is, it does not replicate the heart's intrinsic system, whereas physiologic pacing, which we'll describe in a minute, represents a potentially more elegant and possibly more effective alternative by mimicking or harnessing the heart's intrinsic electrical system. Shown here is a nice schematic highlighting the alternatives. On the right is the classic biventricular or cardiac resynchronization therapy pacing I've described just now with a RV septal lead on the left side of the diagram and a coronary sinus lead around posteriorly to the lateral left ventricle. Obviously, this requires two leads for biventricular pacing, but is widely available in different centers. On the left is a diagram of His bundle pacing or capture of the heart's intrinsic His Purkinje system. You'll note a single lead, which is placed much more proximally near the AV annulus or tricuspid valve annulus, and is able to capture the His system and generate a neuro QRS, which we'll review again shortly. The His bundle pacing paradigm, again, yields a QRS or an electrical activation much more similar to the heart's native conduction typically, may result in shorter procedure time, however, may be limited in its implant success, particularly in less experienced hands, and often will require higher outputs to capture the His system and may have downstream effects on battery life. We'll review this option in detail, but this provides a nice basic schematic of the differences between physiologic pacing, here represented by His bundle pacing, and classic biventricular pacing on the right. For the remainder of the presentation, we will focus on two alternative resynchronization approaches, namely physiologic pacing approaches diagrammed here. I will focus primarily on options one and three on the left diagram, number one being His bundle pacing, as I've just described, which is more proximal pacing in the His-Purkinje system, or the intrinsic conduction system of the heart, again, shown with option number one on the left, and a lead that is rather high on the septum, or actually on the AV annulus. Additionally, we will discuss even newer approaches, including LV septal pacing, or left bundle branch pacing, shown here as option number three on the left. These leads are lower down in the septum and deeper in the septum to capture the left bundle, which we will describe in detail shortly. This talk will not focus on even more experimental approaches, options two and four. On the right is a nice, simpler diagram of the zoomed in of the heart's His-Purkinje system, and demonstrating the implications for level of block in patients with intrinsic conduction disease. His bundle pacing may help recruit or correct bundle branch blocks, shown in subdiagram B, that are due to very proximal block with the little red squiggly in option B. In contrast, more distal block in option C may or may not be corrected through His bundle pacing, and so a level of pacing sometimes can be dictated by potential level of block and resulting QRS morphology with different pacing approaches. Shown here, I've tried to highlight the different potential QRS morphologies with these different pacing approaches, and some results may vary and may be dictated by different pacing locations, lead design, outputs, lead position. But on the left is the patient's baseline EKG. I've simplified it to include patients with normal narrow QRS, those with right bundle branch block morphology conduction defects, and those with left bundle branch block morphology defects. In general, His bundle pacing approximate or proximal in the His-Purkinje system will result in a QRS that should relatively mimic the patient's intrinsic or native conduction. For example, those with a narrow QRS ideally will result in a near exact replica of their normal QRS with His bundle pacing. Those with intrinsic or distal right bundle or left bundle branch block may have the same defects. However, depending on the level of block, as I showed on the previous slide and shown in the dotted lines here, conduction defects, right bundle or left bundle, may be corrected with His bundle pacing depending on the output of the lead, the position of the lead, and the level of block. In contrast, on the lower right are the potential morphologies with left bundle branch pacing. Once again, depending on the level of pacing in the output, a normal narrow QRS may result in a narrow QRS. However, it is often likely to result in a right bundle branch morphology. Most relevant in this slide are the patients with left bundle branch block and the potential for recruitment or correction of that left bundle branch block with a left bundle branch pacing distal to the block or at higher outputs, which may result in, in fact, a narrow QRS or a modest right bundle branch morphology. Obviously, this is not guaranteed, and thus all of the potential morphologies are possible. So what are the clinical outcomes and long-term data related to these pacing approaches? Here is the extensive experience of the Geisinger Health System and Dr. Vijay. This was published a few years ago, looking at a few hundred patients and long-term outcomes out to five years. As you'll note, this patient has a baseline EKG with atrial fibrillation and a narrow QRS. A His bundle pacing lead is implanted as well as an atrial lead, and at one year, the patient is actually in sinus rhythm with a relatively narrow QRS that is near identical, if not identical, to the intrinsic baseline QRS due to proximate capture of the His-Purkinje system. Importantly, this QRS appears stable at five years in this patient, and this lead continues to capture the His-Purkinje system in the His-Purkinje system and yields still a narrow QRS. This is a very experienced center. One of the significant considerations with His bundle pacing has been stability of the lead and thresholds over time, as the His-Purkinje system is relatively insulated. Historically, it has required increased output to capture the His-Purkinje system with subsequent or concordant impact on battery life, as well as lead stability in maintaining that capture. And once again, the same cohort of 192 patients, the investigators compared those who underwent His-Purkinje, His bundle pacing on the left, 94 patients, compared with those who went traditional RV pacing. This was a non-randomized retrospective analysis. You'll note His bundle pacing was achieved in 80 patients, so a lower success rate. Device parameters were significantly different with more than double a threshold required for the His bundle pacing group. The pulse width is noted similarly here. Lead revisions were slightly higher, as were generator changes in the His bundle pacing group. However, QRS duration and left ventricular ejection fraction, as well as rates of pacing-induced cardiomyopathy, all appeared to favor the His bundle pacing group, as did death or heart failure, particularly among patients with greater than 40% ventricular pacing. These are more detailed lead parameters that implant in five years in this same cohort. You'll note, once again, His bundle pacing thresholds were relatively higher compared to RV pacing thresholds, and appeared to rise modestly over five years. Also noted here are the lower R waves on the His bundle pacing lead, as reflecting the more approximate location of the lead, and closer to the atrial side of the annulus yields lower ventricular signals on that lead, particularly those that are very approximate and on the very approximate His bundle. The investigators also looked at subsequent ejection fraction at baseline and follow-up, and found favorable effects among patients with His bundle pacing versus RV pacing. These effects, as one might expect, were more pronounced among those who were paced greater than 40% of the time. Patients with His bundle pacing were much more likely to maintain their ejection fraction compared to those who had traditional RV pacing. Lastly, the investigators also looked at clinical outcomes in these two cohorts. On the left, based on intention to treat or deliver His bundle leads. On the right, the actual on-treatment analysis for the combined endpoint of death or heart failure hospitalization. As you can see, the use of His bundle pacing appeared to be favorable compared to RV pacing, and was particularly more favorable among patients with greater than 40% particular pacing, as you would expect from the pathophysiology of pacing-induced cardiomyopathy, most likely to manifest among patients with high ventricular pacing burden. It is a note these are non-randomized comparison among patients less than 200 in this expert cohort. What about comparisons between his funnel pacing and classic cardiac resynchronization therapy with coronary sinus leads? This is analysis now approximately five years old of 29 patients who underwent placement of both CS and his leads and were used as their own controls by crossover through different programming of the device. In general, the investigators found his bundle pacing among these patients who are candidates for classic CRT. His bundle pacing appeared relatively favorable, if not better, for clinical outcomes of ejection fraction, New York Heart Association class quality of life and six-minute walk. Once again, this was a non-randomized crossover study of 29 patients. Notably, thresholds were expectedly higher for his bundle leads. Shown here is the HisSync study, a pilot randomized trial comparing his pacing and CRT. However, crossover was allowed based on anatomy and availability of lead implant. And so despite randomization, there was significant crossover in this study of 41 patients. Nevertheless, there was a significant reduction in QRS duration associated with his pacing as well as a favorable change in ejection fraction with his pacing compared with classic biventricular CRT. We're going to shift gears now and discuss left bundle branch pacing shown here on the left or fluoroscopic views of an atrial lead and a left bundle branch lead in the RO and LAO projections. You'll note the left bundle branch lead is relatively distal in comparison to his leads and is relatively deep in the septum in the LAO view. On the right at the top is a diagram of different pacing or helix deployment locations. Relatively shallow on the left in the right bundle and peribundal myocardium. In the middle, deeper towards the left bundle and in the right, deepest capturing directly the left bundle. Below is shown the relative, the accordant pacing morphologies with these different lead locations. In the far right, capturing directly the left bundle with a relatively narrower QRS duration. Of particular interest with regard to left bundle branch pacing is the potential to correct left bundle branch block specifically among patients with a non-ischemic cardiomyopathy that could be and can be related to intrinsic dyssynchrony from a left bundle branch block. Shown here is a another diagram of left ventricular pacing. In the middle is the lead relatively high in the septum and deep capturing the mid left bundle branch distal to the site of block as noted. Below that is the fluoroscopic views roughly an LAO on the left as well as a CT scan demonstrating the lead through the septum nearly into the left ventricular cavity. On the left is the patient's intrinsic left bundle branch block morphology EKG with a wide QRS typical of patients with such a non-ischemic cardiomyopathy. With this lead position ostensibly distal to the site of left bundle branch block on the right we see pacing from the lead morphology which is narrow and correct select bundle branch block and a QRS of 104 milliseconds. This certainly is appealing as an alternative to classic cardiac resynchronization therapy comma as it may be more consistently corrective of left bundle and narrowing of QRS and technically may be widely achievable or available across operators in the future. It is important to highlight that with physiologic pacing particularly left bundle branch pacing the resulting QRS is not only a related to lead position and lead output and location of block but additionally is importantly reflective of programming as programming is a vital component of classic CRT. It is also important to recognize programming will dramatically influence QRS morphology for left bundle branch pacing. Shown here is a diagram on the bottom left of pacing location and block location and how that influences pacing morphology. At the top are different AV program delays and the resulting QRS morphologies. The shorter the AV delay demonstrates a relatively narrow QRS however there clearly is a happy medium of an intermediate AV delay with the narrowest QRS reflecting the competition between right bundle conduction and LV left bundle branch pacing stimulation. Ideally we aim to simulate the heart's intrinsic His-Purkinje system with near simultaneous activation. On the bottom right is a fluoroscopic view of this pacing system. You'll note this particular patient has a right atrial lead has a classic RV defibrillator lead in the RV apex and has this left bundle branch lead. It should be noted that among patients who are candidates for defibrillator therapy his bundle and left bundle branch leads do not typically include a coil for defibrillation in those patients still need an RV coil lead. For many operators this also represents a pacing backup in a possibly more stable RV apical location should a physiologic His bundle or left bundle pacing lead become dislodged or fail to capture abruptly. Shown here is a nice summary of the studies of left bundle branch pacing derived from this nice review in JCE. You'll note there have been a number of observational studies very few randomized studies and roughly a total of 1300 patients undergoing left bundle branch pacing. The success rate is approximately 90 percent and probably represents that comparable to classic CRT and potentially slightly higher than the success rates reported for His bundle pacing in broad cohorts. However you'll note again modest sample size, paced QRSs that vary and thresholds that vary. Again there remains a relative paucity of randomized clinical data for left bundle branch pacing. What about comparisons between left bundle branch pacing and classic CRT? These authors compared in an observational fashion patients who underwent left bundle branch pacing versus classic CRT for left ventricular ejection fraction absolute values, the left ventricular ejection fraction change, and left ventricular anastolic volume. As shown here they found favorable results with left bundle branch pacing at 6 and 12 months. However once again this is non-randomized data and thresholds and battery longevity are not part of these specific results and remain to be seen. Nevertheless left bundle branch pacing clearly represents a promising alternative to classic CRT. So how do we compare and contrast these two physiologic relatively novel pacing approaches? Well His bundle pacing the procedure requires targeting of a relatively narrow target zone in the proximal His Purkinje system and for that reason may be technically more challenging. However it is the most physiologic pacing as it captures the most proximate His Purkinje system and harnesses the heart's native intrinsic conduction. This may be favorable for patients with native narrow QRSs however it may be proximate to site of block for patients with intrinsic conductive disease and therefore may not be desirable in other patients. There may be incomplete capture of the His Purkinje system. There may be sensing challenges for these more proximate leads that are closer to the atrium and may not harness much ventricular myocardium for sensing. There can be threshold challenges in terms of battery longevity and selective versus non-selective His capture and again it may not correct distal conduction disease. In contrast left bundle branch pacing usually targets a broader zone of the left bundle branch for implementation and deployment and therefore may represent an easier or less complex implant technique. However the implant is deeper on the septum and therefore may increase the risk of specific complications specifically iatrogenic VSD or distal lead dislodgement into the left ventricular cavity. However there are likely to be fewer sensing issues. Nevertheless there is even less long-term data for left bundle branch pacing compared with His pacing which combined have less long-term data than does classic CRT. So why isn't His or left bundle branch pacing standard of care for patients undergoing ICD and or CRT implant? Well there has been slow adoption and skill uptake among electrophysiologists broadly. This is likely represents the novel approach, variabilities, and success rates and to be frank implant tools still remain relatively rudimentary that is there are relatively few sheets and leads specifically designed for physiologic pacing. Importantly despite small cohorts with up to five-year follow-up broad long-term data for these leads is relatively low particularly in comparison to classic pacing and CRT systems. There remains a lack of device generator programming support. A number of these leads and implementations require novel sensing and pacing algorithms that devices historically have not been programmed and understandably have been slow to adopt as it represents you could represent a relatively major paradigm shift in device firmware and hardware to accommodate these novel issues of pacing timing sensing and capture detection. And in and lastly and probably most importantly the evidence base for His and left bundle branch pacing still remains relatively bare by comparison to classic CRT. Classic CRT has been around now for a few decades and is based in many or several randomized prospective clinical trials that have enrolled thousands of patients in total and has a good long-term track record of improving clinical outcomes across different cohorts. Certainly there are limitations of classic CRT but it is grounded in a firm evidence base currently. So what drives the decision of what to implant among a specific patient whether we're just talking about His bundle leads left brand bundle branch pacing or classic CRT? Well to be honest there are not a lot of data and it's not entirely clear which patients across institutions are being selected for what. It is likely driven by patient anatomy availability for example of coronary sinus tributaries for classic CRT or availability of His signals. There are likely underlying disease and electrophysiology aspects for example patients with sarcoid well described to have progressive conduction disease and thus may not be suitable for very proximate His bundle pacing for example. Additionally hardware availability may limit novel pacing approaches in certain areas and for certain vendors and operators that are limited to specific vendors and thus the technology may just not be available for some implanters. However I believe the most likely driver of the decision are operator specific considerations particularly operators that may or may not be familiar with physiologic pacing considerations. Availability to them of the technology and experience in implanting these leads likely varies dramatically from operator to operator. It is worth noting that physiologic pacing is currently part of the device implantation guidelines starting roughly in 2018. So physiologic pacing does lend a is included as a two-way recommendation with level evidence B among patients with AV block and mild to moderate LV dysfunction particularly who are expected to require pacing greater than 40 percent of the time as well as across patients with AV block irrespective of ventricular function well the corresponding recommendation to be level evidence B. In summary classic CRT or cardiac resynchronization therapy with a coronary sinus lead has been the standard for electrical resynchronization across patient cohorts and it remains the standard consistently. However physiologic pacing with his bundle or left bundle branch pacing represents a newer alternative however it remains a relatively novel procedure with novel hardware and requires additional implanter expertise and maintains a relatively lower evidence base in comparison to classic CRT. Nevertheless it is a promising alternative. Patient and operator factors likely influence implant decision across populations and cohorts and more data and device development are needed to make such physiologic pacing technologies more broadly and widely available. Thank you again for joining us for ACC's Quality of Summit in our new virtual format. We hope to see you again soon.

ICD leads

pacing leads

cardiac resynchronization therapy

His bundle pacing

left bundle branch pacing

long-term data

physiological pacing technologies