Potential mechanisms of endothelialisation in individuals implanted with a leadless pacemaker systems: An experimental in vitro study

Background: Leadless pacemaker technology is a promising upcoming field in clinical rhythmology. Today, the most commonly used system in the clinical setting is the Micra™ leadless pacemaker system (Medtronic). In autopsies of patients who witnessed non-pacemaker associated death, unexpected ingrowth/encapsulation within the wall of the right ventricle was reported. The occurrence of a complete encapsulation was not expected and the process of endothelialisation remains unclear. We hypothesized, that a local inflammatory response might be the cause of these findings. The aim of our experimental in-vitro study was to investigate the effect of the Micra™ system and its single components on inflammatory processes. Methods: For this purpose, whole Micra™ pacemakers were incubated in heparin plasma from 25 healthy volunteers for 48 h at 37 °C. Furthermore, 1 g gold, steel, titanium, tungsten and nitinol wires were incubated in heparin plasma for 48 h at 37 °C as well (n = 10). To detect eventual inflammatory processes, interleukin- (IL)1β, IL-6, and tumor necrosis factor alpha (TNF-α), the chemokine IL-8 were measured using enzyme-linked immunosorbent assay (ELISA). Additionally, the level of transforming growth factor beta 1 (TGF-β1)and vascular endothelial growth factor (VEGF)were analysed. Results: ELISA analyses showed that the whole Micra system leads to a significant increase in the inflammatory cytokine IL-6 which correlates with the data gained by the incubation of whole blood with the different wires. In particular, 0.5 g of tungsten showed a significant rise of IL-6 which could also be found for IL-1β and IL-8. Conclusions: The in vitro study of the Micra system showed that the material composition led to an onset of inflammatory processes in whole blood. Consequently, one may speculate that the composition of Micra pacemaker may have a local inflammatory, though subclinical, effects in patients implanted with a Micra™ pacemakers.