Conventional pacemakers are antibradycardia pacing systems consisting of a pulse generator connected to transvenous leads. Although these devices are highly effective, they are associated with complications related to the pocket housing the generator and the leads themselves (infection, hematoma, lead dysfunction, venous thrombosis, tricuspid valve injury, etc.).
Totally intracardiac leadless pacemakers, implanted via transcatheter, were developed to overcome these limitations and represent an excellent option for specific patient profiles, such as those who have experienced an infection with a prior pacing device, are at high risk of infection, have developed fractures in conventional pacemaker leads, or present with subclavian vein thrombosis, complicated venous access, tricuspid valve disease, or bioprosthesis at that level.
To date, only a single-chamber leadless pacemaker for right ventricular pacing was available, which neither allows atrial pacing nor achieves optimal atrioventricular (AV) synchrony, making it suboptimal for patients with sinus node dysfunction or those requiring nearly 100% AV synchrony. In this context, the leadless dual-chamber pacing system emerged.
The AVEIR DR™ i2i™ (Abbott™, Chicago, Illinois, USA) study is a prospective, multicenter, single-group trial evaluating the safety and efficacy of the leadless dual-chamber pacemaker. The study included 300 patients with conventional indications for dual-chamber pacing and an age of ≥18 years. Patients with mechanical tricuspid prostheses, inferior vena cava (IVC) filters, or preexisting leads were excluded. The primary safety endpoint was freedom from device- or procedure-related complications at 90 days. The primary efficacy endpoint was a combination of adequate atrial capture threshold (≤3 V/0.4 ms) and sensing amplitude (P wave ≥1 mV) at 90 days. The secondary efficacy endpoint was AV synchrony of at least 70% at 3 months. As there was no control group, outcomes were compared against prespecified safety and efficacy targets.
A total of 300 patients were included, with a mean age of 69 years, and 62% were male. The primary indications for implantation were sinus node dysfunction (63%) and atrioventricular block (AVB) (33%). The implantation procedure was successful (both leadless pacemakers implanted with proper function and communication) in 98.3% of cases.
The primary safety endpoint (absence of device- or procedure-related complications at 90 days) was achieved in 90.3% of patients, surpassing the prespecified target of 78% (p < .001). A total of 35 device- or procedure-related complications occurred in 29 patients, spanning a wide severity range (from cardiac tamponade to urinary retention). Among the 35 complications, notable events included 9 episodes of atrial fibrillation, 2 pericardial effusions related to atrial pacemaker implantation (one requiring pericardiocentesis), 6 intraprocedural pacemaker dislocations (5 atrial and 1 ventricular), and 5 postprocedural atrial pacemaker dislocations (all displaced pacemakers were retrieved percutaneously). There were no device- or procedure-related deaths.
The primary efficacy endpoint (adequate atrial capture threshold and atrial sensitivity amplitude at 90 days) was achieved in 90.2% of patients, surpassing the prespecified target of 82.5% (p < .001). The median atrial pacing threshold was 0.82 ± 0.70 V at 0.4 ms, and the median P-wave amplitude was 3.58 ± 1.88 mV. This criterion was not met in 22 patients with inadequate P-wave sensing and 6 patients with an inadequate pacing threshold.
AV synchrony of at least 70% was achieved in 97.3% of patients, exceeding the prespecified target of 83% (p < .001).
The authors conclude that the leadless dual-chamber pacemaker met the primary safety endpoint and provided atrial pacing and adequate AV synchrony during a 3-month follow-up period post-implantation.
COMMENTARY:
For over half a century, cardiac pacing for bradycardia has been achieved with systems comprising a subcutaneous pulse generator connected to one or more transvenous leads. While effective, these systems are associated with serious complications related to the pocket and leads, particularly infections and lead dysfunction, which can affect up to 1 in 6 patients with transvenous systems after 3 years of follow-up.
Leadless pacemakers overcome the limitations of conventional pacemakers and are an excellent option for patients at high risk of infection, those with prior lead dysfunction, or those with challenging venous access, among others. However, until now, no leadless pacemakers capable of achieving nearly 100% AV synchrony have been available.
The AVEIR DR™ i2i™ study offers the first human experience with a fully intracardiac, percutaneously implanted dual-chamber leadless pacemaker system. This system retains the benefits of existing leadless pacemakers by eliminating pocket- and lead-related complications, while overcoming their limitations by offering atrial pacing and AV synchrony, making it an appealing alternative for select patients.
Nevertheless, this study has several limitations, most notably the lack of a control group, so outcomes were compared to prespecified targets. To date, no randomized clinical trial has directly compared leadless pacemakers with conventional pacemakers (comparisons have been made with historical cohorts). Despite these limitations, published studies and accumulated clinical experience support their use given demonstrated functionality, electrical performance, and safety.
Other limitations include the small sample size and short follow-up, which limit conclusions regarding long-term complications, battery longevity, and management at battery depletion. Several questions will need to be addressed in the future: Is extraction or abandonment preferred upon battery depletion? Is it possible to implant a new leadless pacemaker in parallel? Is the implantation of multiple devices in the atrium feasible and safe?
In conclusion, this study presents a promising leadless dual-chamber pacing system that offers the advantages of avoiding pocket- and lead-related complications and expands its indications by providing atrial pacing and nearly 100% AV synchrony. Nonetheless, further data are needed before integrating it into routine clinical practice. A randomized trial with a control group is also essential to compare this new pacemaker system with conventional dual-chamber pacemakers and to provide longer-term follow-up to assess the stability of electrical parameters, battery longevity, and optimal management at battery depletion. Finally, optimizing implantation technique and device technology will be crucial to improve safety, particularly regarding the number of dislocations.
REFERENCE:
Knops RE, Reddy VY, Ip JE, Doshi R, Exner DV, Defaye P, et al. Aveir DR i2i Study Investigators. A Dual-Chamber Leadless Pacemaker. N Engl J Med. 2023 Jun 22;388(25):2360-2370. doi: 10.1056/NEJMoa2300080.
