Optoelectronic control of cardiac rhythm: Toward shock‐free ambulatory cardioversion of atrial fibrillation

Abstract

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia, progressive in nature, and known to have a negative impact on mortality, morbidity, and quality of life. Patients requiring acute termination of AF to restore sinus rhythm are subjected to electrical cardioversion, which requires sedation and therefore hospitalization due to pain resulting from the electrical shocks. However, considering the progressive nature of AF and its detrimental effects, there is a clear need for acute out‐of‐hospital (i.e., ambulatory) cardioversion of AF. In the search for shock‐free cardioversion methods to realize such ambulatory therapy, a method referred to as optogenetics has been put forward. Optogenetics enables optical control over the electrical activity of cardiomyocytes by targeted expression of light‐activated ion channels or pumps and may therefore serve as a means for cardioversion. First proof‐of‐principle for such light‐induced cardioversion came from in vitro studies, proving optogenetic AF termination to be very effective. Later, these results were confirmed in various rodent models of AF using different transgenes, illumination methods, and protocols, whereas computational studies in the human heart provided additional translational insight. Based on these results and fueled by recent advances in molecular biology, gene therapy, and optoelectronic engineering, a basis is now being formed to explore clinical translations of optoelectronic control of cardiac rhythm. In this review, we discuss the current literature regarding optogenetic cardioversion of AF to restore normal rhythm in a shock‐free manner. Moreover, key translational steps will be discussed, both from a biological and technological point of view, to outline a path toward realizing acute shock‐free ambulatory termination of AF.

Optical mapping and optogenetics in cardiac electrophysiology research and therapy: a state-of-the-art review

“…Device sensitivity for arrhythmia detection should be improved using artificial intelligence (AI) approaches, although developing and validating algorithms will require a large training data set. 146 The long-term effects of optogenetic pacing on cardiac electrophysiology and structural remodelling must be investigated. Additionally, future studies should confirm whether optical pacemakers require less energy since they only target a subgroup of cells, which may improve longevity over standard clinical pacemakers.…”