Transvenous pacemakers (TVPs) using pectoral pulse generators and transvenous leads are a well-established treatment for bradyarrhythmias and have served us well for 6 decades [1]. However, implantation of these pacemaker devices are not devoid of substantial complications. The complications are primarily related to the need for pacemaker pockets and the requirement for leads for right ventricular pacing. Around half of them are attributable to lead-and generator [2-4].

TVPs have been found to be associated with a 7.76% to 12.4% risk of serious complications at 90 days and have a 1% to 2% risk of complications per year on the longer term, mainly related to lead failure and infection. 3 Serious complications are experienced about 1 in 6 patients with a TVPs by 3 years. These complications are exceedingly costly to treat [4,5].

The need to mitigate the shortcomings of these traditional systems has led various researchers to focus on leadless pacing systems.

The concept of leadless pacing began some 50 years ago and along that journey much technological progress has been made [6,7]. The technological advancements, including circuit miniaturizations, improved battery technology and electrodes, and sophisticated fixation mechanisms which have taken place over the past 10–15 years, have facilitated development of leadless pacing systems. Companies over the past decade have focused resources on bringing these concepts and innovations to many patients, with increasing recognition of the downsides of traditional lead-based pacing systems.

First in- human clinical trials on leadless pacemakers viz Nanostim (Abbott) and Micra (Medtronic) began in late 2013. As a result of the Micra Transcatheter Pacing Study (TPS), a multicenter, multicountry trial involving 726 patients, the US Food and Drug Administration (FDA) (April 6, 2016) and the US Centers for Medicare & Medicaid Services (CMS) (March 9, 2017) approved Micra, a VVI(R) device, for use [8]. Continuing this journey further, Micra AV, a novel VDD device, has also been approved by the FDA (January 21, 2020) and CMS (February 5, 2020). To date >85,000 Micra/Micra AV leadless pacemakers have been implanted, with over half implanted in the United States (US). The LEADLESS II clinical trial involving Nanostim leadless pacemakers was also completed, although it has not yet been approved [9].

Recently the first systematic review and meta-analysis examining the safety and efficacy of leadless pacemakers implanted in the right ventricle was published [10]. This meta-analysis included total 36 observational studies of Nanostim and Micra leadless pacemakers, with largely (69.4%) reporting outcomes for the Micra. The pooled incidence of complications for Micra, at 90 days (n=1608) was 0.46% (95% CI, 0.08%–1.05%) and at 1 year (n=3194) was 1.77% (95% CI, 0.76%–3.07%).

With 1-year follow-up in 5 studies, Micra was associated with 51% lower odds of complications compared with transvenous pacemakers (3.30% versus 7.43%; odds ratio [OR], 0.49; 95% CI, 0.34–0.70). Of 1,376 patients implanted with Micra, at 1 year, 98.96% (95% CI, 97.26%–99.94%) had good pacing capture thresholds. For Nanostim, the incidence of complications ranged from 6.06% to 23.54% at 90 days and 5.33% to 6.67% at 1 year, with 90% to 100% having good pacing capture thresholds at 1 year (pooled result not estimated because of the low number of studies). Overall, this meta-analysis have shown that the Micra leadless pacemakers are associated with a low incidence of complications (0.46% at 90 days and 1.77% at 1 year) and at 1 year after implantation electrical performance was also good, with >90% of devices having an acceptable capture threshold.

In total Micra as compared with a transvenous pacemaker, is associated with 51% lower odds of complications.

In the January–February 2021 issue of Indian Pacing and Electrophysiology Journal, we described our experience in North India of Implantation of the Micra transcatheter pacing system [11]. In this prospective single center nonrandomized study, the device was successfully implanted in all 28 (100%) subjects. The mean intraoperative sensing value was 9.04 ± 1.5 mV and the impedance was 766.89 ± 213.9 ohm. At the time discharge from hospital, those values were 13.2 ± 15.83 mV and 855 ± 111.7, respectively. In all subjects, the achieved mean pacing threshold value was 0.78 V, i.e.≤ 1 V at 0.24 ms. No adverse event or complications were reported for any of the subjects. Mean discharge time from hospitalization was 1.5 days. We concluded that the Micra leadless cardiac pacemaker was capable of providing effective and safe pacemaker function in the short term and long-term follow-up (3 years) in a varied group of patients who had indications for long-term pacing therapy. However, for long term outcomes, our study further suggests multicentric randomized controlled clinical trials of Micra TPS with long term follow up.

Among the pacemaker implanters and sites, only a small fraction of patients receiving new pacemakers currently are implanted with a leadless pacemaker despite rapid dissemination of the Micra device. Although there are many potential reasons for this (including increased cost of the Micra compared with traditional pacemakers, challenges regarding replacement of leadless pacemakers when the batteries become depleted, and lack of training among many operators with leadless implant techniques), the inability to perform atrial synchronized ventricular pacing for atrioventricular (AV) block with available leadless pacemakers is a large barrier to widespread adoption of them. To overcome this, an algorithm has been developed to allow temporary atrial-sensed ventricular (VDD) pacing in existing Micra pacemakers, based on accelerometer detection of passive ventricular filling and atrial contraction. This VDD algorithm were first used in the MARVEL (Micra Atrial Tracking Using a Ventricular Accelerometer) study [12]. Thereafter in the MARVEL 2 study further refined VDD algorithm temporarily programmed into Micra pacemakers [13]. As compared to the first-generation algorithm used in the MARVEL study, the MARVEL 2 study VDD algorithm incorporates improvements in accelerometer signal filtering, automatic threshold adjustments, and mode switching out of VDD mode during intact AV conduction and high sensed patient activity. For AV block patients, these refinements to the VDD algorithm resulted in further increased average AV synchrony (based on Holter monitoring evaluating AV relationships on a beat-by beat basis) from approximately 80% in MARVEL to 89% in MARVEL 2. This compares to approximately 27% AV synchrony in patients with AV block whose devices were programmed to VVI in MARVEL 2.

So, in AV block patients, a VDD algorithm that could be feasibly incorporated into future leadless pacemakers has demonstrated the potential to bring reasonable rates of AV synchrony.

Currently the leadless pacemakers are primarily implanted in patients for whom AV synchrony is not relevant or is believed to be of limited importance, including patients with chronic atrial fibrillation, frail older patients, or patients with an anticipated rare need for pacing. Further refinements to the accelerometer based VDD algorithm that improve AV synchrony beyond what was demonstrated in MARVEL 2 would be welcome, but this currently available VDD algorithm is also acceptable for clinical use and expanding the use of leadless pacing to some patients with AV block also who till recent past used to receive transvenous devices only. Now recently many centers in the world as well as in India have started to implant this VDD Micra Leadless pacemakers (incorporated with VDD algorithm) in AV block patients also.

This VDD algorithm is the next big advancement for leadless pacemakers. These leadless pacemakers will be embraced by operators and patients alike when the remaining technical hurdles are surmounted to allow clinical use. It is clearly the beginning and not the end of the evolution of leadless pacing.

The journey of leadless pacing has just begun, and future will be bright.