John M. Mandrola, MD: Hi, everyone. This is John Mandrola from theheart.org on Medscape. I am here in London at the European Society of Cardiology meeting with Dr Vivek Reddy, who is an electrophysiologist at Mount Sinai Hospital and the senior lead investigator for the LEADLESS II trial.[1,2] Vivek, congratulations on the trial. Can you tell us a little bit about the basics of it?
Vivek Y. Reddy, MD: Thanks for having me, John. The LEADLESS II trial was designed to look at the safety and effectiveness of a leadless pacemaker.
By way of background, as you know, we have been putting in pacemakers for half a century. Overall, it is a mature technology—highly reliable devices. Having said that, pacemakers do have some limitations. There is a pulse generator, which is implanted surgically in the pocket. Then there is the lead, which is a wire that connects the pacemaker to the heart itself, which travels in the vasculature. Over the lifetime of the pacemaker, the lead, as it bends and flexes over time, can fracture and get infected. Removing pacemaker leads can be a difficult thing, especially when they are implanted chronically.
Within this context, the leadless pacemaker was developed. The idea is to encapsulate everything in a pacemaker—the battery, the electronics, as well as the pacing element—into a small-enough form such that the device can be implanted directly within the heart. This device is a little over 4 cm long, 6 mm in diameter, and the idea is to put it at the end of a catheter, advance it through the vascular system (using a femoral venous puncture), up the inferior vena cava, through the right atrium, across the tricuspid valve into the right ventricle itself, and screw it into the ventricular myocardium just as a stand-out pacemaker lead. Ultimately, everything is within the heart. The LEADLESS II trial was designed in a large, multicenter fashion to try to examine this particular device.
Dr Mandrola: There was a LEADLESS I trial and this was a much bigger trial.
Dr Reddy: That's right. The LEADLESS I trial[3] was the first-in-man experience of any leadless pacemaker. It was a small trial—three centers, 33 patients—and it basically established the feasibility of this concept. The LEADLESS II trial is a US Food and Drug Administration trial involving 56 centers in three countries (United States, Canada, and Australia), with exactly 100 operators, of which 99 had never performed a leadless pacemaker implant.
Dr Mandrola: That is pretty important, because one of the comments I got on social media was that the complication rates were a little higher than for a normal pacemaker, but clearly there is a learning curve.
Dr Reddy: Absolutely. All procedures have a learning curve, and because there was no run-in phase, no roll-in patients, this trial captured all of the learning curve. I think that is one of the strengths of the trial. Now, this was a nonrandomized trial. We don't have an active comparator group; we compared to historical experience with traditional pacemakers. Having said that, complications do occur; they are important and we need to talk about them.
Dr Mandrola: Give us a brief rundown of the success rate, and how often these got implanted and what actual the complication rate was.
Dr Reddy: The device was successfully implanted in 96% of the patients. The effectiveness criteria was basically the ability to implant as well as the ability for the device to sense and pace appropriately out to 6 months. That was achieved in 90% of the patients, which exceeded the performance goal. The safety event rate was 93%, which also exceeded the performance goal.
Looking at the 6.5% safety event rate, there were different types of complications. The one we worry about the most is pericardial effusion and tamponade. That occurred in 1.3% of the patients. That includes effusions that either were not hemodynamically significant and not intervened on, as well as effusions that were significant and required either surgical or percutaneous intervention. How does that compare with traditional pacemaker implantation? Contemporary data show a pericardial effusion and tamponade rate of approximately 0.5% with traditional pacemakers. But in addition, remember: You have approximately a 2% rate of pneumothorax and other potential complications. The 1.3% [in LEADLESS II] is not perfect; we want it to improve and we expect it to improve, but it is not out of line with what you would expect.
Dr Mandrola: I agree. I think 1.3% is pretty low considering that it is probably a pretty stiff sheath and a pretty stiff catheter to get that thing placed.
Dr Reddy: That is right, and over the course of the experience, we have learned that instead of putting it right at the apex, if you put it on the septum a little bit you can decrease the complications. We are going to have other registries that follow the patients appropriately to examine this. I think we will see that the complication rates will decrease with time.
Dr Mandrola: It doesn't seem that a patient who gets a leadless pacemaker gets much downside. It seems like a pretty VVIR pacemaker.
Dr Reddy: That is right. This wasn't a direct comparison, but when you think about a leadless versus a standard pacemaker, you are really going to see the advantages as you follow these patients out. In the trial, the complications that were seen occurred within the first 2 weeks. After that we didn't see anything. The mean follow-up was only 6 months, but basically it was a flat line and there were no complications after that first 2-week period.
It has a lot of advantages, but it is not perfect. Remember: This pacemaker has most of the components of traditional pacemakers, but not all of them. It can't be remotely followed at this point. Some of the diagnostic criteria are not the same as for traditional pacemakers, but it does pretty much what most pacemakers do.
Dr Mandrola: I meant in terms of sensing and pacing and also battery longevity.
Dr Reddy: We are able to follow 300 patients out to 6 months, and based on that we can estimate battery longevity. These estimates in general are pretty good. Based on the device use criteria, we estimate the battery life to be a little over 15 years. Think about that: 15 years of battery longevity, and the average age of the population was 76 years. It is pretty impressive.
Dr Mandrola: What do you see for the future of leadless? Do you see more single-lead devices being placed because it is easier?
Dr Reddy: The mean procedure time was just over half an hour. It is a pretty quick procedure, and that learning curve is pretty rapid. There are certain patients who are obvious candidates: patients who are at risk for infection, diabetics, renal failure patients, or patients with upper extremity vascular complications. What the trial showed was that in the majority of patients, this leadless device does act as an alternative to standard pacemakers. I think a lot of this is going to be driven by patients. Patients are going to want a device that doesn't involve an incision or the mobility and other limitations associated with that. The leadless device sort of disappears within your body.
Dr Mandrola: We have a few minutes left. You are on the front lines of all of this new technology. The review article in Journal of the American College of Cardiology[4] on leadless technology led with the SELECT-LV cardiac resynchronization therapy (CRT) technology. Give us an overview of where this is going in terms of the device in the left ventricle as a CRT or possibly a dual-chamber atrial device.
Dr Reddy: That is an important point. The LEADLESS II trial device is a ventricular pacemaker, so it really is designed to be placed in the right ventricle, and that is relevant to somewhere between 15% and 25% of the patients who receive pacemakers. In order to be able to perform dual-chamber pacing, you need to have a device in the atrium, as you pointed out. That means you need a small-enough device that fits in the atrium and communicates with the ventricular device. Manufacturers are working on these technologies, I think we are going to see this in the next couple of years. That allows the possibility for dual-chamber pacing, the possibility for CRT. So it paces the left ventricle also, as well as the interaction between, for example, subcutaneous defibrillators and that kind of added capability. This technology is moving forward. The SELECT-LV studyl[5] uses an ultrasound-based pacing device that paces the left ventricle for CRT therapy for heart failure patients. This is all moving forward. I think the common theme is to avoid leads as much as possible to avoid the complications associated with them.
Dr Mandrola: How close do you think we are to a leadless pacemaker connecting to a subcutaneous defibrillator?
Dr Reddy: That is an active project for many of these companies. We are a couple of years away—probably 2-3 years away—from this actually being used in patients.
Dr Mandrola: Pretty exciting. Thanks for being with us.
Dr Reddy: Thank you very much, John.
Dr Mandrola: This is John Mandrola from theheart.org on Medscape, at the European Society of Cardiology meeting.
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Cite this: John M. Mandrola, Vivek Y. Reddy. LEADLESS II: Dr Vivek Reddy Interviewed - Medscape - Sep 04, 2015.
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