Research ArticleAtrial Fibrillation

An automated hybrid bioelectronic system for autogenous restoration of sinus rhythm in atrial fibrillation

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Science Translational Medicine  27 Feb 2019:
Vol. 11, Issue 481, eaau6447
DOI: 10.1126/scitranslmed.aau6447

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Atrial fibrillation treatment lightens up

Atrial fibrillation is an irregular, rapid heartbeat that interrupts normal blood flow and increases risk of stroke and clots. Normal heart rhythm can be restored by electroshock (electrical cardioversion), but implantable cardioverter defibrillators can cause pain and damage myocardial tissue. Rather than supply exogenous current, Nyns et al. combined atrial gene painting to deliver viral vectors encoding light-activatable ion channels with an implantable light source and rhythm detector, developing an autogenous arrhythmia termination system. This optogenetic approach restored normal heart rhythm in rat hearts ex vivo and in vivo under closed-chest conditions. Further testing in larger animal models is necessary, but results suggest that this could be a pain-free alternative to electroshock.

Abstract

Because of suboptimal therapeutic strategies, restoration of sinus rhythm in symptomatic atrial fibrillation (AF) often requires in-hospital delivery of high-voltage shocks, thereby precluding ambulatory AF termination. Continuous, rapid restoration of sinus rhythm is desired given the recurring and progressive nature of AF. Here, we present an automated hybrid bioelectronic system for shock-free termination of AF that enables the heart to act as an electric current generator for autogenous restoration of sinus rhythm. We show that local, right atrial delivery of adenoassociated virus vectors encoding a light-gated depolarizing ion channel results in efficient and spatially confined transgene expression. Activation of an implanted intrathoracic light-emitting diode device allows for termination of AF by illuminating part of the atria. Combining this newly obtained antiarrhythmic effector function of the heart with the arrhythmia detector function of a machine-based cardiac rhythm monitor in the closed chest of adult rats allowed automated and rapid arrhythmia detection and termination in a safe, effective, repetitive, yet shock-free manner. These findings hold translational potential for the development of shock-free antiarrhythmic device therapy for ambulatory treatment of AF.

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