Together with our superb partners in science of the Technical University Delft (Tianyi, Catilin, Rene and Kouchi) we have published a new paper on optical termination of cardiac arrhythmias: Engineering and Cardiology meets once more!
Congratulations to Emile for steering this project through tough and unpredictable times (i.e. all sorts of covid-19 related issues).
Our paper is freely available via open-access publishing, see below.
Emile C A Nyns, Tianyi Jin, Magda S Fontes, Titus van den Heuvel, Vincent Portero, Catilin Ramsey, Cindy I Bart, Katja Zeppenfeld, Martin J Schalij, Thomas J van Brakel, Arti A Ramkisoensing, Guo Qi Zhang, René H Poelma, Balazs Ördög, Antoine A F de Vries, Daniël A Pijnappels
Abstract
Aims: Ventricular tachyarrhythmias (VTs) are common in the pathologically remodelled heart. These arrhythmias can be lethal, necessitating acute treatment like electrical cardioversion to restore normal rhythm. Recently, it has been proposed that cardioversion may also be realized via optically controlled generation of bioelectricity by the arrhythmic heart itself through optogenetics and therefore without the need of traumatizing high-voltage shocks. However, crucial mechanistic and translational aspects of this strategy have remained largely unaddressed. Therefore, we investigated optogenetic termination of VTs 1) in the pathologically remodelled heart using a 2) implantable multi-LED device for 3) in vivo closed-chest, local illumination.
Methods and Results: In order to mimic a clinically relevant sequence of events, transverse aortic constriction (TAC) was applied to adult male Wistar rats before optogenetic modification. This modification took place three weeks later by intravenous delivery of adeno-associated virus vectors encoding red-activatable channelrhodopsin (ReaChR) or Citrine for control experiments. At 8 to 10 weeks after TAC, VTs were induced ex vivo and in vivo, followed by programmed local illumination of the ventricular apex by a custom-made implanted multi-LED device. This resulted in effective and repetitive VT termination in the remodelled adult rat heart after optogenetic modification, leading to sustained restoration of sinus rhythm in the intact animal. Mechanistically, studies on the single cell and tissue level revealed collectively that, despite the cardiac remodelling, there were no significant differences in bioelectricity generation and subsequent transmembrane voltage responses between diseased and control animals, thereby providing insight into the observed robustness of optogenetic VT termination.
Conclusion: Our results show that implant-based optical cardioversion of VTs is feasible in the pathologically remodelled heart in vivo after local optogenetic targeting because of preserved optical control over bioelectricity generation. These findings add novel mechanistic and translational insight into optical ventricular cardioversion.
