Discussion
In this nationwide comparative evaluation of 6,219 leadless VVI versus 10,212 transvenous VVI de novo pacemaker implants, leadless VVI pacemakers were associated with a 32% reduction in the rate of chronic complications and a 41% reduction in the rate of reintervention at 3 years. These results build off of the published 2-year results of the Micra CED Study, which showed a 31% reduction in complications and a 38% reduction in reinterventions at 2 years in this cohort.3 Lower rates of complications among leadless pacing patients have now been observed in both clinical trials and real-world clinical practice.4,5 This present analysis suggests the reductions in the risk of complications and reinterventions associated with leadless pacing, previously seen at 6 months and 2 years of follow-up, persist and continue to accrue in the medium-to-long-term. This analysis provides valuable new information on the expected rate of accrual of additional complications and need for system revision over time. At the 3-year endpoint, most complications that patients continue to experience are related to device (device breakdown, mechanical failure, etc.) or pocket in the transvenous VVI arm. Because the differential benefit of leadless pacing is largest with respect to these device-related complications, it would be reasonable to assume that the benefits observed at 2 and now 3 years would persist over longer time horizons.
The present analysis also provides new insight into the robustness of the 2-year results, particularly related to device reinterventions. This present analysis found a 29% lower rate of reinterventions requiring a new device (device removal and replacement, and upgrades to dual-chamber and CRT devices) among leadless VVI patients, demonstrating that the lower rate of reintervention is not solely driven by the need for lead revisions and lead-related reinterventions, which are less invasive and costly than reinterventions requiring a whole new system.
As discussed in El-Chami et. al.,3 rates of device reintervention can be influenced by both adverse events, like pacing-induced cardiomyopathy, as well as patient selection. The advantage that leadless pacemakers have in terms of absence of leads can also be a limitation in that leadless pacemaker systems can be less adaptable to modular upgrades, such as an addition of a CRT lead. The current study shows no significant difference in all-cause mortality after adjustment for differences in baseline patient characteristics and a 10% lower rate of heart failure hospitalizations at 3 years. These results are comforting and suggest the reduction in reinterventions observed among leadless-VVI patients are not coming at the expense of worse pacing outcomes (such as untreated pacing-induced cardiomyopathy). In fact, these results appear to bolster previous findings suggesting lower rates of pacing-induced cardiomyopathy among patients implanted with a leadless pacemaker, potentially due to greater frequency of mid-septal placement associated with leadless implants.12 It would be valuable to explore this hypothesis further in a randomized clinical trial.
The Micra CED Study also continues to demonstrate the benefits of leadless pacing with regards to device infection. While the total rate of device infection requiring full device removal in the transvenous VVI comparator arm is low (0.7%), it is significantly higher than in the leadless VVI arm. CMS reporting rules prevent us from displaying cell values less than 10 in order to prevent patient identification. If we assume that the value is actually 10, the infection rate requiring device removal in the leadless group is only 0.16%. Prior literature has demonstrated the serious risk of patient mortality and other adverse clinical and economic outcomes posed by device infection.13
To our knowledge, this is the first analysis to report on heart failure hospitalizations among leadless pacing patients and is possible because the large sample size and long-term follow-up of the Micra CED study allows for the capture of an adequate number of events of interest. The ability to capture and report on this endpoint highlights some of the significant advantages of using real-world data to supplement traditional clinical studies for post-market device evaluation.