Optogenetic Termination of Cardiac Arrhythmia: Mechanistic Enlightenment and Therapeutic Application?

Abstract

Optogenetic methods enable selective de- and hyperpolarization of cardiomyocytes expressing light-sensitive proteins within the myocardium. By using light, this technology provides very high spatial and temporal precision, which is in clear contrast to electrical stimulation. In addition, cardiomyocyte-specific expression would allow pain-free stimulation. In light of these intrinsic technical advantages, optogenetic methods provide an intriguing opportunity to understand and improve current strategies to terminate cardiac arrhythmia as well as for possible pain-free arrhythmia termination in patients in the future. In this review, we give a concise introduction to optogenetic stimulation of cardiomyocytes and the whole heart and summarize the recent progress on optogenetic defibrillation and cardioversion to terminate cardiac arrhythmia. Toward this aim, we specifically focus on the different mechanisms of optogenetic arrhythmia termination and how these might influence the prerequisites for success. Furthermore, we critically discuss the clinical perspectives and potential patient populations, which might benefit from optogenetic defibrillation devices.

Keywords: atrial fibrillation; cardioversion; defibrillation; implantable cardioverter defibrillator; optogenetics; ventricular arrhythmia; ventricular fibrillation; ventricular tachycardia.

Figure 1

Mechanisms of cardiac arrhythmia and optogenetic termination. The leading edge of the arrhythmic wave front is shown in red, the depolarized and refractory tissue in yellow, and the excitable gap in green. The illumination is displayed in blue. (A) A stable rotor of a cardiac arrhythmia is shown at different time points during one cycle around a phase singularity. (B) Example for optogenetic arrhythmia termination by conduction block. Sustained illumination starts within a depolarized area and keeps the surrounding area depolarized until the next arrhythmic wave front entering this region is blocked by refractory tissue. (C) Optogenetic arrhythmia termination by filling of the excitable gap. Brief illumination of the excitable gap generates a second excitation wave front, which travels toward the arrhythmic wave front until both are extinguished by their collision.