Cardiac glial cells release neurotrophic S100B upon catheter-based treatment of atrial fibrillation

Abstract

Atrial fibrillation (AF), the most common sustained heart rhythm disorder worldwide, is linked to dysfunction of the intrinsic cardiac autonomic nervous system (ICNS). The role of ICNS damage occurring during catheter-based treatment of AF, which is the therapy of choice for many patients, remains controversial. We show here that the neuronal injury marker S100B is expressed in cardiac glia throughout the ICNS and is released specifically upon catheter ablation of AF. Patients with higher S100B release were more likely to be AF free during follow-up. Subsequent in vitro studies revealed that murine intracardiac neurons react to S100B with diminished action potential firing and increased neurite growth. This suggests that release of S100B from cardiac glia upon catheter-based treatment of AF is a hallmark of acute neural damage that contributes to nerve sprouting and can be used to assess ICNS damage.

Impact of the ablation technique on release of the neuronal injury marker S100B during pulmonary vein isolation

“… 6 It is important to note that sympathetic and parasympathetic structures cannot be considered separately: even though the intracardiac nervous system and its ganglionated plexi are classically considered as ‘parasympathetic’, they also contain sympathetic cell bodies and fibres. 10 As both types of cardiac nerves and neurons within ganglionated plexi are surrounded by S100B-expressing glial cells, 2 differentiating between the type of denervation would not be possible using S100B and was not the goal of this study.…”

“…The protocol has been described in detail in the previous study, in which 113 patients with AF were enrolled 2016 and 2017 in our institution. 2 This sub-study aimed to compare S100B release between the different energy forms used for PVI and excluded patients with persistent AF. Assignment to the ablation technique was performed in a mixed non-randomized order and ablation was carried out by the same operators.…”

“…Samples were processed immediately and frozen at −80°C as described previously. 2 S100B concentrations were assessed using a commercially available enzyme-linked immunosorbent assay (Merck Millipore, Darmstadt, Germany). Cardiac troponin I was determined using a highly sensitive immunoassay (HsTnI, Architect i2000SR, Abbott Diagnostics, USA).…”

“… 1 Recently, we were able to demonstrate that S100B is released by cardiac glial cells during neural injury induced by pulmonary vein isolation (PVI). 2 While targeted autonomic denervation in addition to PVI is feasible and has shown increased success rates for the treatment of paroxysmal atrial fibrillation (AF), 3 it is also well known that PVI induces concomitant cardiac denervation. 4 This disruption of autonomic nerve fibres and ganglia has been demonstrated by indirect functional parameters such as autonomic responses (e.g.…”

Human adult cardiac autonomic innervation: Controversies in anatomical knowledge and relevance for cardiac neuromodulation

“…In patients who underwent sympathetic ganglion blockade, the effect of right and left blockade was equivalent and the impact on each atrium was comparable regardless of the site of block (Leftheriotis et al, 2016). In addition, catheter-ablation of AF likely also affects the cardiac ganglia, which may improve the procedural success rate, at least at short term (Scherschel et al, 2019).…”