Dr. Nicholas Olson discusses the history of cardiac implantable electronic devices, procedure related complications, and patient outcomes while highlighting the benefits of leadless pacing to improve outcomes for designated patients.
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we're gonna move on to Dr Dr Olsen next. Correct? Yeah. And he's gonna talk about trans catheter pacing technology. Very exciting development here and that. Now we have pacemakers just sit entirely down inside of the heart muscle. The weak link of pacemakers historically has been the wires that connect the pulse generator to the heart on also got some exciting big technology to talk to us about, Right. Thanks for the introduction, Doug. Good topic discussion on a fib. Management. Um, I'm very excited to present this section on trans catheter pacing technology. It's a the topic that's very near and dear to my heart. I've been involved with the research and development of this technology over the last six years, and hopefully I can convince you that it's ah, step in the right direction. Some disclosures I always like to start off with this slide this year demonstrates where we've been with pacing technology since its inception in the 19 fifties. If you look over to the left, we see way back in the 19 fifties, the first pacemaker technology clearly constructed in the role Botkins Garage in Minnesota. The first device was very simple, actually, an external device where the lead emanated from this thing. Pacing pulse generator, which was very large and heavy more externally in the lead, went into the body through the vascular chair down into the heart. Uh, soon after its development. It was miniaturized and implant to completely under the skin, 1960. And then, as you can see over the years, ah, lot of advancements took place. Obviously, improvements in battery technology pacing algorithms were able to pace multiple chambers. Both the atrium, the ventricle, ultimately the left ventricle. We work on wireless technology, Emery conditionality, baby, and clearly the algorithms have improved over the years as well. But if you take a look at the overall design, not the overall design has not really changed over that entire time period. We still have a device that's implanted under the skin and long wires that extending the vasculature through the heart valve down into the heart, and that results in way more complications than we often like to admit. Clearly, we have to make a pocket under the skin. These patients are often anti coagulated, and we get complications from them pocket hematomas, bleeding infections. Here we see preparation of the pacemaker lead through the heart. Ah, large hematoma. The pulse generator pocket an older patients that air six. Sometimes the device can actually erode out of the skin infections. Designing a lead that extends into the heart that lasts for decades and decades without breaking is a technically very challenging engineering feat. And oftentimes we result results in problems. We have to replace those leads, which could be very tricky to Dio. And lastly, with all that foreign device material in the body, there's the risk of infection both in the pocket for the devices and on the leads from Battery MIA. And unfortunately, as most foreign devices in the body, if there's an infection and can't be fixed with antibiotics and everything has to be removed, ast faras statistics go. Um, that could always vary on what you call a complication. However, undoubtedly, the statistics are not as good as we would like them to be. These Siris of studies here demonstrate pocket related complications and leader lead related complications over the course of a device implant can be upward, and one in 10 patients now an infection is not necessarily same. Thing is a hematoma that resolves in just with some expected management. However, undoubtedly there's some serious complications in here that it would be nice if we could be avoided. Speaking specifically about infections. Uh, device related infections are one of the most serious complications related to a pacemaker or device implantation, which are associated with significant morbidity and mortality. Looking at some statistics here, about 1 to 4% of patients with an implanted device will experience some type of infection over the course of their over the course of their life. The average time in the hospital for device related infections about 9 to 18 days. The average out of cost ah cost to a patient is about $2000 about a three times increased mortality rate. With those patients that develop an infection, that's not necessarily causal. Patients who do get infections obviously have higher risk factors and co. Morbidity co co morbidity is associated with it. But nonetheless, infection can lead to increased mortality. In addition to morbidity. Now, from the hospital administrative perspective, device related infections are very, very costly and oftentimes result in a significant margin of loss financially for the hospital institution as well. Average cost of a hospital to treat an infection device related infections 48 $83,000 and a loss of 5 to 30 $36,000 and that that glosses over the whole patient experience as well. You know, we're usedto, you know, in in the field of electrophysiology, we do an ablation and way on a fib. Ablation takes us two hours, technically a lot more challenging. But from a patient perspective. After the procedure is completed, they don't even have it. They don't often times don't have knowledge of anything that even happen other than the fact that hopefully they stay in normal rhythm but a device related, uh, patient experience. They will always have a visual reminder that they have a medical condition. Whether that causes discomfort or not, they still have a reminder every time they look in the mirror that they have some type of medical condition. So with that in mind, the leaderless pacing concept was born with the the following goals. One. Improve a patient experience, no physical deformity, bump physical reminder. Eliminate pocket related complications such as infections, Hema hematoma or erosions, and eliminate lead related complications. A zwelling such as fractures, insulation breaches venous thrombosis from the lead or damage to the valves. Well, the concept of leaderless space making is not actually new. Here is an interesting publication from 1970 in the journal Electro cardiology bringing up the possibility of a leaderless pacing device this using nuclear decay as the energy origin it was planted, implanted completely within the heart. Ultimately, the conclusion of the article was that this was not possible by current engineering technology and feasibility. But the concept, however, remained fast forward till the last 5 to 10 years. And we have the development of leaderless pacing technology. The three devices that are currently being usual are being worked on Are the micro by Medtronic? Uh, this is now Abbott Nano Stem and Boston Scientific's and Power. I'm gonna talk a little bit mostly about the micro device, as this was the first to be investigated and completed its i d try. Alana's FDA approved. The other two devices are remain in the development. This is how the devices implanted from the far left. A large catheter about the size of your thumb is advanced up to the level of the heart through that catheter or sheath a delivery catheter in the middle here is advanced up into the heart. The handle controls the flexion of the device and also the tip of the device which houses the pacing capsule. You can see within this little cup here there is a pacing capsule. Overall size is one millimeter. There are various fixation mechanisms that have been tried using this technology. The one that, uh, the Medtronic device uses is ah tien mechanism that is, once it's ejected out of its delivery catheter grabs onto the tissue and holds it in place. We have Ah, once it's injected, we still have connection to the delivery catheter so it could be tested and retrieved if we don't like the numbers that we see or the positioning or stability. Three. Nano stem device by Abbott has more of a screw mechanism that they're working on. Boston Scientific's device has a a time mechanism. A swell. Here is the device being deployed in action. As you can see here, there is the delivery sheath, very large sheath and the delivery catheter through that sheath one more time. Once we have the device in the right ventricle, Thebe device is released from the sheath tested, and then it could be released on bond. Once we're adequately satisfied with the electrical variables with it once it's released, we want to make sure that it is holding in place these time mechanisms. You can pull slightly on it, and you can see those times pull back knowing that that has good a tissue opposition, and I won't dislodge now. This is the device with the goals of reducing complications as previously mentioned. Obviously, we need to test to make sure that those goals are achieved. Now, Um, all the data that I'm about Thio describe is for the micro device by Medtronic, as the other two devices are still in their early stages of, of, of, of design, of their idea trials. Um, however, soon that data will be available, hopefully within the next couple of years as well. So with the micro device, we do have two big data sets. So far, the original is the Micra I D trial, which was 726 patients, 56 centers. This took place in 2013 to 2015. This was a single arm study, so there was not a random I study outcomes were compared to a historical control cohort, which consisted of previously published trans venous pacemaker studies. Now single chamber pacemaker studies were quite rare, so in that historical control cohort used for comparison, dual chamber devices were used with the complications related to the atrial lead removed. Now it's not obviously a perfect comparison. A zone a randomized trial. But it does give us some idea of how we're performing compared to trans Venice devices. Now, after completion of this I. D trial, a subsequent registry study was initiated. Has finished enrollment, but completing follow up is expected so much longer study and estimated to monitor up until 2027. That study consistent of 1823 patients looking at the exact same outcome, safety and efficacy is through the trial did no. Just to emphasize this, these devices are the first stage of pacing technology. They are on Lee single chamber devices so they can on Lee pace the ventricle. It can't pace the atrium. It can't tain. You can't maintain synchrony between the atrium and the ventricle. Therefore, the indications for pacing are somewhat limited. Pacing and the ventricle. When you're in Sinus rhythm can result in a distinct pretty between the atrium and the ventricle, as every pace ventricular impulse goes up to the atrium, causing the atrium to contract after the ventricle. If there is complete heart block pacing the ventricle, the atrium and the ventricle will be completely dissing Crignis. And if that occurs, some patients can develop a syndrome called pacemaker syndrome, where they can feel that atrial, uh, the atrium contracting against a closed valve symptoms, including palpitations, fatigue, low energy, poor heart performance. So predominantly, this device is indicated for people who haven't chronic or persistent atrial arrhythmia. Most commonly atrial fibrillation or atrial flutter on bradycardia associated with that. Now, whether that's bradycardia that I estrogenic from a Navy note ablation or intrinsic both, that was a mix of patients in the i D trial. But again, most of these patients 64% had atrial fib relation or atrial flutter atrial tachycardia. Now there were some other patients in the trial that did have heart block or Sinus node dysfunction. However, the indication for using a Micra or the leaderless pacing technology, was that they wouldn't require pacing frequently. For example, a patient that had a Sinus pause or, um, intermittent heart block that wasn't expected to need frequent pacing or if they had some cool morbidity is often times, for example, human dialysis patient with very limited vasculature options than the device was implanted despite sacrificing the fact that they might get pacemaker syndrome as a result of that, what do we look at from a method standpoint? Safety and efficacy, pretty standard safety analysis, death, permanent loss of therapy, hospitalization, prolonged hospitalization or need for system revision? Efficacy was simply looking at stable pacing, thresholds and electrical values. Make sure that the device was able to do what it was intended to do over the follow up period, which was six and 12 months for the trial and much longer for the registry child taking a look at the procedure itself. Now this was a completely new implant procedure. Standard pacemakers are put in under the show under the clavicles. This was a new technology, and despite being a completely new procedure, there was an extremely high success rate greater than 99% implant success with over 300 planters and draw your attention to this. This is a very very short procedure. The median implant time was about 28 to 32 minutes. Ah, standard pacemakers, uh, very rarely take this short duration of time. Now, the majority of these implants were achieved in three deployments. Remember the devices tethered to the delivery catheter? And if we don't like the electrical values, we can retract it and read and read Deliver the device. And that require was required occasionally, but not more than three deployments in a large majority of cases. And with all the devices, pacing, thresholds and electrical values were very stable throughout the follow up period. Now, I believe this is a very impressive sly looking at the projected longevity of the device being a much smaller advice, I would expect, uh, the pacing or the device toe last a lot shorter duration. However, with the battery being placed so close to the pacing tissue on the pulse with or how much energy needs to be delivered per heartbeat, the actual duration of the device, the longevity device, actually exceeded. Um, nearly all of the standard trans venous pace making systems an average battery longevity 12 years again, this is a projected longevity. We haven't had the devices implanted for sufficient time to see if this projection holds true. But I'll be interested to see how this plays out over the next 5 to 10 years. Looking at the complication rates, uh, overall in looking at this slide here in in orange or yellowish, that is the historical control cohort looking at, um uh, this is of trans venous devices, looking at the same safety endpoints that we previously discussed in the light blue. Here is the micro I D trial. And as you can see, there is a 63% reduction in complications related with using the legal system compared to the standard trans venous system. And if we move on to the registry study here in gray, we see that the complication rates are reduced even further after we gain some insight during the I d. Try Alon techniques to improve our outcomes and reduce complication rates. Now, this was largely driven by the need for system revision. So pacemaker if the lead dislodges during implant or there's an infection or there's a break in one of the leads fractures again, that's gonna be a complication. That scene further down the line But there was overall a 75% reduction in the need to revisit the system, and that was largely gym in the fact that during the trial there was no dislodge mints of the device and no infections. Now, looking at the specific complications related to the implant procedure, one that got a lot of press and the most complicated are the most common complication during the initial trial was ah, pair card of the fusion or cardiac preparation. Um, and I think a largely stems from the fact that we're using a new tool in the right ventricle, which tends to be a very a thin walled, sensitive structure. Um, fortunately, most of those did not require intervention, and those that did require intervention did not require surgery to did require surgery in the overall 726 patient cohort. Despite being a very large introducer, very rare complications in the groin pacemaker syndrome, as I mentioned earlier, was very rare, even in those patients that were implanted even with some significant number of patients and planted that were in Sinus rhythm, heart block without atrial arrhythmias. Now, further comment about the most notable a complication during the I D trial was cardiac preparation and infusion around 1.6%. Looking at the post approval study with the techniques that were learned use of contrast, attempting to shoot the device into the inter ventricular septum as opposed to the apex. That complication rate drops significantly down to 0.4%. And if you look at other trials of standard trans Venus pacemaker systems accomplish the preparation right actually is quite a bit lower, especially in the post approval studies compared to those other historical studies. Now, one comment or one uh, issue that comes up with leaderless pace making systems, however, is what do you do when the battery dies In a standard trans venous system, we're able to just open up the skin, pull out the pulse generator and put in a new one and a Zilong as the Leeds Working okay way could extend the longevity of the system. However, with these leaderless systems, what happens is over the course of a year, the heart tissue grows completely over the device, which is a curse and a blessing, the blessing being that the device is not exposed to the bloodstream. So if bacteria occurs. It doesn't see the device. However, once it's encapsulated like that, it becomes very, very challenging to get out. So fortunately, the devices only one millimeter in size and multiple devices can be implanted. And with a projected battery longevity of of up to 10 years are up to 12 years on average, we could get a significant number of years of pacing by putting multiple devices. And so when the battery runs dead, we can actually turn it off and place a new device. This is a study looking at cadavers, even the smallest heart. You could fit a minimum of three devices in it without any interaction, and most likely able thio place other devices as well. And this is without any advancement in pacing battery technology over the next decade, or with some tools that are looking to be developed to help capture this and perhaps pull the device out even after encapsulation. So all these things are being worked on. Now, before that encapsulation occurs, you can pull the device out. We can use this long deflect herbal sheath has demonstrated in the fluoroscope pick image. Here, we can advance the sheet through this outer catheter on. We can use the snare to grab the device and actually retrieve it. This could only be done usually because in the first year, before encapsulation occurs far left here we can see the video. This was a patient that was referred because hey had a micro implant and it was causing some PVCs that were symptomatic. So I was ableto snare the device and pull it out. This was approximately nine months after implantation. In this case, we could have put the device back in in, um, or a pickle position. However, the referring doctor preferred to put a regular transmission system. So that was the first generation of leaderless pacemaker. Now, you look over here on the left. You can see that, um, indications for pacing in blue. This is where the original first generation pacemaker fell. That is, patients with chronic arrhythmias in the atrium, atrial arrhythmias with heart block on bradycardia, relatively small number of patients or percentage of the pie. Ah, much larger percentage is patients that come in normal rhythm. But with heart block on Lee, I think as we develop more and more of these self expanding Travers, I think this is probably going to be larger, larger piece of the pie. So the second generation of leaderless pacemaker, actually, which has been, uh, recently approved in the last year, looks thio maintain a V synchrony through a through the same device and this is a V D d pace making system. So how does this work? It's actually the exact same device as the original leaderless pacemaker. Now, these leaderless pacemakers do have a small motion sensor in them. In the original device there used to, uh, you use for the rate response sensor. So this little motion sensor in the device can actually determine when a patient is moving around. And the more movement Yeah, the device interprets that is the patients trying to exercise and will augment the heart rate accordingly, with from a base rate of whatever we choose 60 70 beats per minute all the way up 220 130 beats per minute. Now that same little motion sensor engineers have been able to figure out that we can actually sense the atrium contracting. So when the atrium contracts up here, it ejects blood across the trick husband valve and it shakes or moves the leaderless pacemaker and the ventricle and all the other cardiac motion in human and physical motion of the patient can be filtered out and isolated and use that atrial contraction to time when to pace the ventricle. Now we can't pace the atrium, right, because there's no device up here, but it can. If the patient has normal Sinus rhythm and heart block, it can sense tho contraction and then subsequently pace the ventricle. And this is the second generation of leaders pace making technology. Now, a complete I. D trial was not completed because it was, in fact, the same device. But we did the way the way Thio test this theory or this thing type of engineering was a download study. So what we did was we took 75 patients that were implanted with leaderless pacemakers already in Europe, United States in Southeast Asia. And what they did is they downloaded the new software into the existing device. Now, this was only for up to five hours because we didn't want Thio lose. Ah, lot of battery longevity. Um and we wanted to see exactly how the device was able to maintain a V synchrony So the primary safety objective, obviously, was to make sure that the device didn't stop pacing or paste too quickly because of the algorithm. And the secondary objective was to demonstrate how much synchrony was. Um, uh, The secondary objective was to demonstrate a higher, not only demonstrate that was able to maintain a V synchrony, but also to demonstrate that the heart actually increased cardiac output through evaluating the echocardiogram thick parameters called the time velocity, integral between the two two months. So here are the results of that download study. As you can see in the V I 50 mode versus V. D D mode, there was a significant increase, as one would expect with a V synchrony. The algorithm didn't work perfectly. Theory Judge uh, patient. The A V synchrony increased about 95% which is the median. So most patients had a very high A V synchrony. The mean a V synchrony increased to about 89% and that was dropped a little bit about some out. A few outliers, which, for technical reasons, we're not able to measure or track the atrial contraction for a variety of reasons, most commonly that the atrium probably was just not producing a significant atrial contraction or away from for the device to detect. Uh, additionally, the improve stroke volume or the time velocity integral looking at the theoretic valve, thes patients in general uh, increase the amount of heart output with each heartbeat when they were in the V D D V. This is actually a type of here but V D D mode versus V v I mode. There was a couple outliers here, but that was because they forgot during the study. They didn't accurately changed the pacing rate to be the same in the V I and V d d mode. So, in general, all patients that was accurately done on did have an increase in stroke volume, which was expected. Also, the Sinus rate did decrease significantly when you went from Vevey mode to VVD mo overall, no pauses, no instances of over sensing. There were six adverse events collected, none related to the device, Um, and no adverse events reported due to a lack of synchrony. Yeah, Now one issue with V. D. D systems is obviously you can't pasty atrium. So there's some concerned that if we put one of these devices in and the patient develops a need for atrial pacing. In the future. We have to upgrade the device or put a hole trans venous system. And because we don't have an atrial pacing needless device now looking at that actually statistically, that's a very rare occurrence. This was a study looking at 320 patients that had trans Venus VVD pacemakers placed and on Lee Won only two are only three of them required upgrade, which was about 1% to a D D d system over a follow up about six years. So very rarely was that an indication for upgrade. Lastly, where are we going in the future? A. Zai mentioned. This is the first two generations of the device are only able to pace the ventricle. One is a sink, a synchronously. The other is able to sense the atrium but not pasty atrium. Now the companies are obviously working on developing Ah, device And I think the next generation device that's gonna come out I think we're going to start testing in the first quarter of next year is an atrial device. So we're able to put a device in the atrium Theoretically, with that in place, you will be able to pace the atrium. And with the V D. E D device two devices, you would be able to pace both chambers and maintain synchrony. Um, one of the company. But it's nano stem is working on their their their their system will actually communicate not mechanically but electrically. And hopefully we'll maintain even higher degree of a V synchrony with the two device system. And lastly, how do we pace the left ventricle? A huge, uh, component of what we do for pacing now is is maintaining synchrony and the ventricle, especially with low ejection fractions of you by ventricular pacemakers or by ventricular defibrillators. This is a bit of a challenge. Placing an Endo cardio device in the left ventricle has a lot more risk in terms of thrombosis and stroke. Technically, it's a lot harder to get there. One concept that was being evaluated that which installed a little bit because of blood clots and strokes, was a device that you implant in the left ventricular endo cardio. This is the device here, and then a subcutaneous device delivers a high intensity ultrasound impulse, which change, which will stimulate that device to then start but create a pacing impulse in the ventricle. So then when the battery dies, you just simply change this device and the end of cardio aspect of it, which is very, very, very small and completely and author realizes will remain in place. Um, but other concepts are being developed as well. Once that could go on the outside like a standard by ventricular pacing sistemas well.
