Atrial tattoos lines: a new method to terminate atrial fibrillation
Authors: Schmidt C , Wiedmann F , Wiedmann F , Blochberger P , Blochberger P , Paasche A , Paasche A , Yesilgoez B , Yesilgoez B , Kraft M , Kraft M , Loewe A , Loewe A , Kallenberger S , Kallenberger S , Frey N , Frey N 
Published: October 2022

Abstract

Introduction
Atrial fibrillation (AF) is the most common cardiac arrhythmia affecting more than 4% of the world's population. Furthermore, the vulnerable substrate underlying atrial cardiomyopathy remains far from being understood. Atrial cardiomyopathy is a highly complex and heterogeneous disease that occurs in the context of various clinical backgrounds, which explains the heterogenous success of established atrial ablation strategies such as pulmonary vein isolation. Here we developed a new interventional method for the treatment of AF using a tattooing procedure of silver nanowires in the atria to create circular lines of increased conductivity to prevent irregular electrical propagation.

Purpose
In a translational study, we tested a newly developed interventional method to terminate AF by injecting lines of silver nanowires to increase tissue conductivity.

Methods
The developed tattoo method was tested in vivo using an established large animal AF model of the domestic pig. Pigs (n=10) with atrial fibrillation were either treated with right atrial tattoo lines using a transmural injection procedure of silver nanowires as closed lines in the atrium or got a sham treatment with saline injections. Over 21 days, AF was induced and monitored (AF burden) by an intracardiac dual-chamber device with a biofeedback induction algorithm. Initially and before final termination, conventional electrophysiological investigation and atrial 3D mapping, echocardiography and epicardial multi electrode array (MEA) measurements were performed. Following the 21 days observation period, the heart was extracted and freshly isolated atrial cardiomyocytes were subjected to cellular electrophysiological, molecular and histochemical characterization. Electrophysiological data was used for in silico modelling of arrhythmia termination and wave propagation. The study protocol was approved by the animal ethics committee.

Results
The AF burden was significantly reduced (AF burden &lt;10%) in the group treated with the new atrial tattoo line method compared to sham treated pigs. The bi-atrial diameters, quantified by echocardiography, were significantly smaller in the treatment group. Atrial refractory period was significantly shorter in the sham treated pigs. A significant increase of connexin 43 was observed in the injection area of silver nanowires in the myocardium. Measurements with MEA demonstrated increased conduction velocity by a factor of 1.5–2.0 in the areas of silver nanowire injections. Additionally, in silico modelling showed the termination of AF via the created conduction lines.

Conclusion
The newly developed interventional method of the creation of atrial lines with increased tissue conductivity using silver nanowires could successfully terminate AF in pigs. Perspectively, this new myocardial tattooing technique may be a promising treatment strategy for patients with complex atrial cardiomyopathies to terminate atrial arrhythmias.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): Else Kröner Fresenius Foundation