Safety and long-term outcomes of leadless vs. conventional lead-based pacemakers

Symptomatic bradycardia is a common clinical condition that may result in fatigue, syncope, or worsening heart failure, for which permanent pacemaker implantation remains the cornerstone of treatment. Leadless pacemakers (LPs) have emerged as alternatives to conventional transvenous pacemakers (TVPs), with the goal of reducing lead- and pocket-related complications. This systematic review evaluated the safety, efficacy, and intermediate- to long-term outcomes of LPs compared with TVPs in adults with symptomatic bradycardia, based on a PubMed literature search from 2020 to 2025 that identified observational and cohort studies reporting clinical outcomes. Study quality was assessed using the Newcastle-Ottawa Scale, and pooled hazard ratios with 95% confidence intervals were estimated using a random-effects model to account for potential heterogeneity between studies. Quantitative meta-analysis of two high-quality observational studies demonstrated a numerical trend toward lower rates of device-related complications with leadless pacemakers; however, the pooled estimate did not reach statistical significance. This pooled analysis should be interpreted as exploratory and hypothesis-generating, given the limited number of eligible studies. Across individual studies, LPs—especially the Micra™ AV system—were associated with lower rates of complications such as lead dislodgement, infection, and device-related pain, as well as fewer re-interventions, compared with TVPs. Although higher all-cause mortality was observed in some LP cohorts, this appeared to be largely attributable to greater baseline comorbidity burden rather than device-related causes, and device upgrades or removals were uncommon. Overall, current evidence suggests that LPs may offer a favorable safety profile compared with TVPs in selected clinical scenarios, with the Micra™ AV system showing promise in reducing lead-related risks; however, randomized controlled trials and longer-term follow-up are needed to establish durability, effectiveness, and generalizability across broader patient populations. Such a Bayesian adaptive, randomized, controlled trial comparing AV-synchronous leadless pacing vs dual-chamber transvenous pacing, with pre-specified response-adaptive randomization and sample-size re-estimation is proposed.