New Leadless Pacemaker Promising in Safety, Efficacy

A new leadless pacemaker (LP) shows promise in safely delivering effective right ventricular pacing, and providing an alternative to current transvenous pacemakers, new research suggests.

In the LEADLESS II phase 2 IDE study, researchers investigated the Aveir LP (Abbott) in 200 patients requiring ventricular demand pacing and found an implant success rate of 98%, with most patients not requiring repositioning. Moreover, the primary safety endpoint, the absence of complications, was met in 96% of patients.

“The new Aveir pacing system holds the potential to help us advance treatment for patients who need a pacemaker, but where physicians are concerned [is with] more invasive surgery, or in circumstances where we believe a patient’s therapy needs may change in the future and where retrievability will be a critical device feature,” Vivek Y. Reddy, MD, professor of medicine and director of cardiac arrhythmia services, Mount Sinai Hospital, New York City, said in a press release.

“Additionally, this device will — in the not-too-distant-future — have the potential to be upgraded to a dual-chamber device, which we are trialing in 2022 and look forward to sharing those findings,” Reddy told theheart.org | Medscape Cardiology.

The findings were presented at the annual Scientific Sessions of the Asia Pacific Heart Rhythm Society and simultaneously published as a research letter November 11 in the Journal of the American College of Cardiology: Clinical Electrophysiology.

Important Subset

“Prior studies show that up to 1 in 6 patients with traditional transvenous pacemakers will have a serious complication by 3 years,” senior author Daniel Cantillon, MD, associate section head, Cardiac Electrophysiology and Pacing, Cleveland Clinic, Cleveland, Ohio, told theheart.org | Medscape Cardiology.

The “overwhelming majority” of these are “related to the incisional access created for the pacemaker pocket, such as bleeding or infection or leads that are threaded into the heart,” he noted.

LPs reduce complications “by not requiring incisional access or wires, but rather are directly placed into the heart,” Cantillon said.

Reddy noted that globally, roughly 10% to 15% of patients require only single-chamber pacing of the ventricle and that leadless pacemakers “currently address that population,” which he called “a smaller percentage, but a very important subset.”

The first LP, the Nanostim by St Jude Medical, was introduced in 2013 but was removed from the market because of premature battery depletion, the authors write.

Another leadless device, the Micra Transcatheter Pacing System by Medtronic, was approved in the US in 2016, although with a mandated postapproval study, and is still the only leadless pacemaker approved by the FDA.

The current redesigned Aveir LP has “key design improvements,” the authors note, including the use of standard transvenous pacemaker battery chemistry, modified docking button, enabling retrievability; a modified delivery system with an ergonomic design; and a new application-specific integrated circuit (ASIC) chip designed to provide an expandable platform to later support a dual-chamber pacing system once it’s approved.

This current phase 2 single-arm trial was developed to improve the safety and performance of the original product, the researchers note.

The LEADLESS II trial was conducted across 43 centers in the US, Canada, and Europe and enrolled 200 patients (mean age at enrollment 75.6 years, 62.5% male), with a primary pacemaker indication of atrial fibrillation (AF) with atrioventricular block (52.5%). All patients had standard VVI pacing indications.

Retrievable Device

Implant success in the phase 2 trial was superior to that of the phase 1 trial (98% vs 96.3%, respectively) and there was less repositioning required in the successful implants in phase 2 vs phase 1 (83.2% vs 70.2%, respectively).

Of the 198 participants that were evaluable, 96% (95% CI, 92.2% – 98.2%) met the primary safety endpoint, defined as “freedom from serious adverse device events (SADEs, also called complications) through 6 weeks of follow-up.” In fact, the lower bound exceeded the performance goal of 86% (P < .0001).

The most frequent complications were cardiac tamponade and premature deployment (three cases each).

Within the effectiveness endpoint analysis cohort, that is, the 196 patients who had received successful implants, 95.9% (95% CI, 92.1% – 98.2%) met the effectiveness criteria, consisting of a “composite score of acceptable pacing thresholds (≤ 2.0 V at 0.4ms) and R-wave amplitudes (≥ 5.0 mV or ≥ value at implant) through 6 weeks of follow-up).” The lower bound similarly exceeded the performance goal of 85% (P < .0001).

Eight participants did not meet effectiveness criteria: four failed the capture threshold criteria and four failed the R-wave amplitude criteria.

Both the safety and the efficacy outcomes represented an improvement over phase 1 results, they write.

The secondary outcome, appropriate and proportional rate-response pacing during graded exercise, was also met, with a mean slope of the regression line between normalized workload and normalized sensor-indicated rate (17 participants) of 0.93.

Unique aspects of this LP design include a modification to the delivery catheter, resulting in an “improved implant success rate”, the researchers note, as well as contact mapping prior to LP fixation, that results in “low repositioning rates during implantation,” compared to phase 1.

Reddy commented that the Aveir system has a “much better battery life,” compared to existing LPs and is also “the world’s only leadless pacemaker specifically designed to be retrieved when the device needs to be replaced or if a patient’s therapy needs to be changed, [which] is a critical device feature.”

Reddy noted that, although the pericardial effusion rate was 1.5%, and “we need to see that that improves, existing devices also demonstrated the same effusion rate” that improved and decreased to “much less than 1%” with increased operator experience. “I imagine the same will happen here,” he said.

Second Option

Commenting on the study for theheart.org | Medscape Cardiology, Charles Love, MD, director of cardiac arrhythmia services and professor of medicine, Johns Hopkins University, Baltimore, Maryland, said that the currently approved LP, Medtronic’s Micra, has been on the market for several years and has been “really well received, and fills an important niche.”

It represents an improvement over devices that rely upon leads because “wires are generally the weak link in the system because they dislodge, poke through the heart, and can become infected,” he said.

Love, who was not involved with the current study, said that the new device, once approved, “will do the same thing and will give us a second option for devices of this type.”

According to Love, the main disadvantage of LPs is that they pace only one chamber of the heart, but an advantage of this device under investigation is that it is “forward-compatible with a second leadless device to be placed in the atrium, so we can pace both chambers of the heart and keep them working together at the same time, which will be a big improvement over the current generation of leadless devices we’re placing right now.”

Cantillon said that the device platform “paves the way for multichamber leadless cardiac pacing,” noting that currently, LPs only meet the needs of 10% of patients requiring pacing support. “In order to serve the remaining 90%, we need to have a leadless pacemaker for both the upper and lower chambers of the heart that can communicate directly.”

FDA Warning

On November 17, the FDA issued a warning on the risk of “major complications related to cardiac perforation during implantation” of leadless pacing systems, referring to the Medtronic Micra leadless device. 

Cantillon noted that the Micra device has a “different fixation mechanism” to the cardiac tissue than the Aveir device under investigation. In particular, the Aveir device uses a helix rather than tines (small anchors) and does not require the application of forward pressure to engage into the heart.

Nevertheless, Love added, “as noted in the [FDA] notification regarding the Micra pacemaker, cardiac perforation is certainly a possibility with any pacemaker” and “perforation for Micra can be associated with pericardial tamponade,” although he called this “uncommon.”

For that reason, “one must be aware that it can happen and be ready to deal with it, just as one must be ready to deal with it in any other device,” Love said.

He suggested that the risk of perforation “may be higher when we start placing these [leadless devices] into the atrium, since the atrium is much more thin than the ventricle, and there may be a higher risk of perforation there.”

He added, “I think the FDA bulletin clearly states what all physicians need to do, and that is to balance the risks and the benefits of each procedure relative to the needs of each individual patient.”

Because of high failure rates associated with standard pacemaker wires, there “is a lot of momentum about leadless devices, said Love, and he does not think “that we will see a decrease in the enthusiasm for using these devices, even with the most recent notification by the FDA.”

Indeed, the potential for leadless pacemakers continues to expand. Earlier this wee, a novel leadless pacemaker defibrillator system manufactured by Boston Scientific was implanted in two patients at the Cleveland Clinic. The device brings together the technology of a leadless pacemaker with a subcutaneous implantable cardioverter defibrillator, managing to deliver treatment for both low and elevated heart rates.

The implantation of this device kicks off the multicenter MODULAR ATP trial that will evaluate the safety, performance, and effectiveness of the modular cardiac rhythm management system.  

Cantillon, a principal investigator in the trial, said in a press release, “Combined use of both types of devices in a leadless approach could benefit a much larger patient population…It’s our hope that the combination of a tiny, leadless pacemaker implanted directly into the heart with the subcutaneous-ICD in the soft tissue will allow the majority of lethal arrhythmias to be painlessly terminated without long-term risks.” 

The LEADLESS II study was funded by Abbott. Reddy is an unpaid consultant for Abbott; Unrelated to this manuscript, he has served as a consultant for and has equity in Ablacon, Acutus Medical, Affera, Apama Medical, Aquaheart, Atacor, Autonomix, Backbeat, BioSig, Circa Scientific, Coria Medical, Dinova-Hangzhou Nuomao Medtech Co, Ltd, East End Medical, EPD, Epix Therapeutics, EpiEP, Eximo, Fire1, Javelin, Kardium, Keystone Heart, LuxCath, Medlumics, Middlepeak, Nuvera, Sirona Medical, and Valcare; has served as a consultant for Axon, Biotronik, Cardiofocus, Cardionomic, CardioNXT/AFTx, EBR, Impulse Dynamics, Medtronic, Philips, Pulse Biosciences, Stimda, and Thermedical unrelated to this work; and has equity in Manual Surgical Sciences, Newpace, Surecor, and Vizaramed.

Cantillon is a consultant for Abbott and Boston Scientific. The other authors’ disclosures are listed on the original paper. Love is a consultant to Medtronic.

JACC Clin Electrophysiol. Published online November 11, 2021. Abstract

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