MICRA VR, MICRA AV, AND AVEIR VR MODELS
PEER-REVIEWED LITERATURE
El-Chami et al. (2024a) reported results on a 5-year follow-up of the Micra VR postapproval registry study. The major complication rate for individuals with an attempted Micra VR implant procedure (n=1809) was 4.47% at 60 months and there were no Micra VR removals due to infection reported during follow-up. The 5-year all-cause mortality rate was 39.5%, although this rate is not unexpectedly high given the age and comorbidities of the individuals in the study.
In 2021, Piccini et al. published initial data from the ongoing Longitudinal Coverage with Evidence Development Study on Micra VR Leadless Pacemakers (Micra CED). Individuals who received implants between March 2017 and December 2018 were identified and included from a fee-for-service population with at least 12 continuous months of Medicare enrollment prior to device implantation. A total of 5746 individuals with single-chamber leadless Micra VR pacemakers and 9662 individuals with transvenous pacemakers were analyzed. Individuals with a Micra pacemaker were more likely to have end-stage kidney disease (P<0.001) and a higher mean Charlson Comorbidity Index score (5.1 vs. 4.6; P<0.001). The unadjusted acute 30-day complication rate was higher in the Micra subgroup (8.4% vs. 7.3%; P=0.02), but no significant difference was found following adjustment for individual characteristics (P=0.49). Pericardial effusion and/or perforation within 30 days of implantation was significantly higher in the Micra population in the adjusted model (0.8% vs. 0.4%; P=0.004). Individuals with Micra pacemakers had a 23% lower risk of complications at 6 months compared to individuals receiving a transvenous pacemaker (hazard ratio [HR], 0.77; P=0.02) and a 37% reduction in rates of device revision after adjustment for individual baseline characteristics. The 30-day all-cause mortality rate was not significantly different between groups in both unadjusted (P=0.14) and adjusted analyses (P=0.61).
El-Chami et al. (2022) subsequently compared reinterventions, chronic complications, and all-cause mortality at 2 years in individuals implanted with the Micra VR leadless pacemaker or a transvenous pacemaker in the Micra VR Coverage with Evidence Development study. Individuals receiving leadless (n=6219) or transvenous pacemakers (n=10,212) were identified from Medicare claims data and compared contemporaneously. Individuals receiving leadless pacemakers had higher rates of end-stage renal disease (12.0% vs. 2.3%) and a higher Charlson comorbidity index (5.1 vs. 4.6). Individuals with leadless pacemakers received 37% fewer reinterventions (adjusted HR, 0.62; P=0.003), defined as system revision lead revision or replacement, system replacement, system removal, or system switch or upgrade to an alternative device. Individuals receiving implanted leadless pacemakers also experienced fewer chronic complications (2.4% vs. 4.8%; adjusted HR, 0.69; P<0.0001). However, individuals receiving leadless pacemakers experienced significantly more other complications, driven by higher rates of pericarditis (adjusted HR, 1.6% vs. 0.8%; P<0.0001). Adjusted all-cause mortality at 2 years was not significantly different between groups (adjusted HR, 0.97; P=0.37) despite the higher comorbidity index in individuals receiving a Micra VR device. Study interpretation is limited by reliance on claims data. It is unclear whether all individuals receiving leadless devices were considered medically eligible for transvenous devices.
In 2023, Boveda et al. reported 2-year outcomes from the Micra VR CED study in a subgroup of individuals at higher risk of pacemaker complications. Participants were considered high-risk if they had a diagnosis of chronic kidney disease stages 4 to 5, end-stage renal disease, malignancy, diabetes, tricuspid valve disease (TVD), or chronic obstructive pulmonary disease (COPD) 12 months prior to implant. They compared outcomes between high-risk individuals with leadless-VVI pacemakers (n=9858) and transvenous-VVI pacemakers (n=12,157). The leadless-VVI group had fewer complications compared to the transvenous-VVI group in those with malignancy (HR, 0.68), diabetes (HR, 0.69), TVD (HR, 0.60), and COPD (HR, 0.73), had fewer reinterventions in those with diabetes (HR, 0.58), TVD (HR, 0.46), and COPD (HR, 0.51), and lower rates of combined outcome of device complications and select reinterventions in those with malignancy (HR, 0.52), diabetes (HR, 0.52), TVD (HR, 0.44), and COPD (HR, 0.55). The authors conclude that in this real-world study, individuals with leadless pacemakers had lower 2-year complications and reinterventions rates than individuals with transvenous pacemakers in several high-risk subgroups.
Three-year outcomes from the Micra VR Coverage with Evidence Development study were published by Crossley et al. in 2023. Individuals receiving leadless pacemakers had a 32% lower rate of chronic complications (HR, 0.68; P<0.001) and a 41% lower rate of any reinterventions compared with individuals receiving a transvenous pacemaker (HR, 0.59; P=0.0002). Use of a leadless system was also associated with a 49% lower rate (=.01) of upgrades to a dual-chamber system and a 35% lower rate (p=.002) of upgrades to cardiac resynchronization therapy. Heart failure hospitalizations at 3 years were slightly, but significantly lower in adjusted time-to-event models (HR, 0.90; p=.005) in individuals receiving a leadless system. All-cause mortality rates at 3 years between leadless and transvenous systems were not significantly different after accounting for differences in baseline characteristics (HR, 0.97; p=.32). No significant differences in the composite endpoint of time to heart failure hospitalization or death were observed for the original full cohort (p=.28) or in a subgroup of individuals without a history of heart failure (p=.98).
Crossley et al (2024) reported outcomes from the Micra AV Coverage with Evidence Development (CED) study comparing individuals implanted with Micra AV (n=7,471) to a comparator cohort (n=107,800) of individuals implanted with a dual-chamber transvenous pacemaker regardless of pacing indication. At 30 days, the adjusted overall complications were 8.6% for Micra AV group and 11.0% for dual chamber transvenous group (p<.0001) and the adjusted all-cause mortality was 6.0% for the Micra AV group and 3.5% for the dual chamber transvenous group (p<.0001). At 6 months, the Micra AV group had significantly lower rates of complications (adjusted HR, 0.50; P<0.0001), lower reinterventions (adjusted HR, 0.46; P<0.0001), and higher all-cause mortality (adjusted HR, 1.69; P<0.0001) compared with the dual chamber transvenous group. The authors noted limitations to the study. First, Medicare claims data were used, which is a secondary database without traditional clinical adjudication. Second, the comparator cohort included all individuals regardless of pacing indications, because it could not be reliably determined from the data.
El-Chami et al. (2024b) reported 2-year outcomes from the Micra AV CED study comparing individuals receiving the Micra AV implant (n=7552) to a comparator cohort (n=110,558) of individuals receiving a dual-chamber transvenous pacemaker regardless of pacing indication. They found that the individuals with Micra AV compared to the comparator cohort experienced statistically significantly fewer chronic complications (5.3% vs. 9.6%; adjusted HR, 0.544; P<0.0001) and device-related re-interventions (3.5% vs. 5.6%; adjusted HR, 0.624; P<0.0001). However, all-cause mortality remained higher in the Micra AV group compared with the comparator cohort (34.0% vs. 23.8%; adjusted HR, 1.528; P<0.0001). The authors noted limitations including reliance on administrative claims data without clinical adjudication, lack of data on pacing indication and AV synchrony, potential residual confounding due to unmeasured frailty, and limited generalizability to non-Medicare populations.
Reddy et al. (2022) reported on the pivotal IDE trial of the Aveir leadless pacemaker, which was a multicenter, prospective single cohort study enrolling 200 individuals with a guidelines-based indication for single-chamber pacing. Implantation of the Aveir leadless pacing system was successful in 196 of 200 (98%) trial subjects (mean age, 75.6 years; 37.5% female). The primary indication for pacing was chronic atrial fibrillation with second- or third-degree AV block (52.5%). The trial had two primary endpoints related to safety and efficacy. The trial would meet its safety endpoint if the lower bound of the 97.5% confidence interval (CI) for the complication-free rate exceeded 86% at 6 weeks. A complication was defined as a device- or procedure-related serious adverse event, including those that prevented initial implantation. The trial would meet its efficacy endpoint if the lower bound of the 97.5% CI for the composite success rate exceeded 85% at 6 weeks. The confirmatory effectiveness endpoint was considered met if the pacing threshold voltage was less than or equal to 2.0 V at 0.4 ms and the sensed R-wave amplitude was either greater than or equal to 5.0 mV at the 6-week visit or greater than or equal to the value at implant.
At 6 weeks, the trial met both of its confirmatory safety and efficacy endpoints, including freedom from device- or procedure-related complications in 96% of individuals, compared with a performance goal of 86%, and a composite success rate of 95.9% of individuals, compared with a performance goal of 85%. The 6-month complication-free rate was 94.9%. The most frequent complications included three cardiac tamponade events and three premature deployment events. The rate of cardiac perforation/tamponade/pericardial effusion was 1.5%. No dislodgement events were reported in the Aveir cohort.
Confirmatory secondary endpoints included assessment of an appropriate and proportional rate-response during a Chronotropic Assessment Exercise Protocol (CAEP) exercise protocol and an estimated 2-year survival rate. The CAEP assessment was initiated in 23 subjects, of which 17 were considered analyzable. The rate-response slope was 0.93, which fell within the prespecified range of 65% to 135%. The estimated 2-year survival rate based on the Nanostim (Aveir VR's predecessor) Phase 1 cohort (N=917) was 85.3%, which exceeded the performance goal of 80%.
Reddy et al. (2023) reported 1-year outcomes from the Aveir VR pivotal trial. Confirmatory safety and efficacy endpoints at 1 year were both met, including freedom from device- or procedure-related complications in 93.2% of individuals, compared with a performance goal of 83%, and a composite success rate of 95.1%, compared with a performance goal of 80%. Most complications (11/15) were reported within the first 3 days postimplantation, including four cardiac tamponade events, three premature deployments with or without device migration, two access site bleeding events, one pulmonary embolism, and one case of deep vein thrombosis. Four long-term complications were reported between 3.8 and 9.5 months postimplantation, including two cases of heart failure and two cases of pacemaker-induced cardiomyopathy. Based on the device-use conditions in this analysis cohort, the investigators estimate that mean device battery longevity is 17.6 ± 6.6 years.
Tam et al. (2024) conducted a nonrandomized retrospective analysis of pacing threshold performance on the Aveir VR (n=123) compared to the Micra VR (n=139). The primary endpoint was pacing threshold at various time points before, during, and through 3 months after the procedure. High pacing threshold was defined as greater than or equal to 1.5 V at 0.4 ms for the Aveir VR and greater than or equal to 1.5 V at 0.24 ms for the Micra VR. At the end of the procedure, more individuals in the Aveir VR group had a high pacing threshold (11.5%) compared to that in the Micra VR group (2.2%) (P=0.004). At 3 months, there was no difference in the probability of a high pacing threshold between the Aveir VR group (2.3%) and the Micra VR group (3.1%) (P=1.000). The authors note the Aveir VR demonstrated satisfactory performance; however, the study was limited by its small sample size and lack of randomization.
While there are limitations to these studies of right-ventricular leadless pacemakers, there is a robust evidence base that continues to demonstrate safety and effectiveness time and time again. All-cause mortality, reintervention rate, and hospitalization rate were investigated in numerous trials, such that expectations regarding performance and limitations are well characterized.
PROFESSIONAL SOCIETY GUIDELINES
In 2025, eight organizations, including the American College of Cardiology, American Heart Association, and Heart Rhythm Society, among others, published an appropriate use criteria for various implantable cardiac devices. In the section on leadless pacing, the highest rating of “Appropriate" was designated for individuals with long-standing persistent or permanent AF and normal LVEF, where the device longevity is greater than survival, and pacing is anticipated to be less than 40%. Leadless pacing was also “Appropriate" for individuals who had multiple cardiovascular implantable electronic device infections and normal LVEF, where pacing is anticipated to be less than 40%. The authors note that a major limitation of leadless devices is the difficulty of replacement and concerns regarding sufficient space for multiple devices. Further, the authors state, “Randomized clinical trials will be critical to help define optimal implant strategies and help inform individual selection." At the time the criteria was written, only right ventricular pacing options were approved by the US Food and Drug Administration.
The American Heart Association provided a scientific statement in 2024 regarding cardiovascular implantable electronic device infections. The authors note that leadless pacemakers may be considered in those at high risk of infection or as a bridge to permanent devices.
In 2022, four organizations, including the European Heart Rhythm Association and Heart Rhythm Society among others, published a position paper on practical considerations for implantable electronic devices. The authors provide a “may be used or recommended" position for “extraction of leadless pacemaker is feasible if needed," while also providing the same recommendation for “additional leadless pacemaker may be implanted in the right ventricle." Additionally, the authors do not advise individuals under the age of 20 years old aside from medical circumstances that would preclude a traditional pacemaker, and that a traditional pacemaker should be preferred in individuals less than 60 years old.
The European Society of Cardiology published a cardiac pacing and resynchronization therapy evidence based guideline in 2021. Within the “Alternative pacing strategies and sites" section of the guideline, leadless pacing is discussed. The following recommendations are provided:
- Leadless pacemakers should be considered as an alternative to transvenous pacemakers when no upper extremity venous access exists or when risk of device pocket infection is particularly high, such as previous infection and individuals on hemodialysis (IIa).
- Leadless pacemakers may be considered as an alternative to standard single-lead ventricular pacing, taking into consideration life expectancy and using shared decision-making (IIb).
The guidelines go on to note the lack of randomized controlled trials comparing leadless pacemakers to traditional pacemakers, the limited long-term data on retrievability and end of life strategy, and careful consideration for those with a life expectancy greater than 20 years.
Professional Society Guideline Summary
There is consistency throughout the professional society guidelines that is worth highlighting. At least three themes can be found:
- Traditional transvenous pacing remains the gold standard pacing option, such that leadless pacing should be considered only when transvenous pacing is not feasible or poses a high risk of infection.
- Younger individuals and individuals with an expected survival greater than device longevity require extra careful consideration, such that decision-making is made at the individual-level.
- Related to the above, long-term management (e.g., replacement, abandonment, end-of-life service) is a concern due to the lack of experience.
While leadless pacing improves on the lead and infection complications that are common among individuals with transvenous pacemakers, there is insufficient evidence to support parity between the devices. The guidelines consistently recommend leadless pacing as an alternative to transvenous pacing, never suggesting either option can be used for “standard" individuals with a pacing indication.
Additionally, given the long-term management concerns, younger individuals and those with an expected survival greater than device longevity require individual-level decision-making. Because there is a paucity of evidence supporting a particular end-of-life strategy for leadless devices, guidelines consistently recognize the potential complications this may pose for these populations. While there is no expectation that randomized controlled trials would be the evidence necessary to establish safety and effectiveness in this scenario, a robust evidence base of case series, observational cohorts, and registries that consistently display safety and effectiveness would provide increased confidence in the appropriate handling of device end-of-life management. In turn, it would be expected to see recommendations from professional organizations for leadless pacing for younger individuals and those with expected survival greater than device longevity in the future.
AVEIR DR MODEL
In 2023, Knops et al. reported results from the pivotal, single-arm trial of the Aveir DR system. The dual-chamber system was successfully implanted in 295 of the 300 enrolled individuals. The primary safety endpoint (freedom from complications) and two primary performance endpoints (right atrial pacemaker performance and atrioventricular synchrony) were assessed at 90 days. Thirty-five complications in 29 individuals were reported within 90 days, thus exceeding the predetermined safety goal of 78% of individuals free from complications. The right atrial pacemaker performance endpoint was also met as 90.2% of individuals had an atrial capture threshold less than or equal to 3 V with an atrial sensing amplitude of greater than or equal to 1 mV. This atrial pacemaker performance goal failed in 27 individuals (~9%). The atrioventricular synchrony performance endpoint, as defined by paced or sensed ventricular beat within 300 ms of a paced or sensed atrial beat occurring in greater than 70% of cardiac cycles of a 5-minute seated recording, occurred in 97.3% of individuals. Greater than 95% of individuals met the 70% threshold in a variety of postures and gaits.
Subsequently, in 2025, Knops et al. reported the 1-year outcomes of the trial. Again, the freedom from complications and right atrial performance endpoints were studied. Both endpoints were achieved, as 88.6% of individuals remained free of complications, and pacemakers of 92.8% of individuals had adequate atrial capture and sensing.
Additionally, Reddy et al. (2025) published the expected battery longevity of the pacemakers from individuals in the pivotal trial. The authors only used data from the 6- to 12-month timeframe to estimate battery longevity. They found the median longevity of atrial devices to be 5.3 years, while that of the ventricular devices was 9.9 years. As expected, different variables (e.g., pacing percentage, event rate, impendence) had an effect on the projected battery life. The authors provide various analyses to support the suggestion that, if certain device and individual characteristics were different, then battery longevity would increase.
Across these three analyses of the pivotal trial, there are notable limitations. First, the pivotal trial is severely limited by its lack of a comparator. Despite an estimated 30,000 dual-lead transvenous pacemakers being implanted in the United States alone each year (Shah Syed et al., 2023), this gold standard treatment was not included in the trial as a comparator. Because transvenous pacemakers have a longstanding history of providing safe and effective pacing, and the severity of the consequences of an ineffective device are detrimental, this lack of comparison is a major limitation for ensuring those with a pacing indication receive the device most suitable for their needs. Second, the trial has only been analyzed out to 12 months. As such, there are no data supporting the long-term safety and effectiveness of this device, which is crucial given the 1) novelty of the technology/procedure, 2) length of implantation, and 3) the unclear end-of-life management of each pacemaker. Third, the short battery longevity of the atrial pacemaker is of concern. Despite the authors' suggestion of alternative parameters to increase battery duration, the programming of the devices should be individualized to accommodate individual needs. Therefore, the median battery longevity should be considered (5.3 years). While no direct comparison is made, 5.3 years is significantly shorter than the expected lifespan of a transvenous lead seen in a conventional pacemaker. This, of course, would require individuals to have surgeries for leadless pacemaker replacements far more frequently than for traditional pacemakers.
Long-term data studying all-cause mortality, reintervention rate, and hospitalization rate have not been developed. Beyond the pivotal trial, there is no high-quality peer-reviewed evidence that aids in the understanding of the safety and effectiveness of Aveir DR.
RIGHT-ATRIAL LEADLESS PACEMAKER (I.E., AVEIR AR)
There are no high-quality peer-reviewed studies that investigate the Aveir AR, right atrial leadless pacemaker, as an isolated intervention. The literature is limited to case series and reports, the pacemaker being used as part of a dual-chamber system, and animal studies. As such, the safety and effectiveness of the Aveir AR device cannot be established.
