Efficient termination of cardiac arrhythmias using optogenetic resonant feedback pacing

Abstract

Malignant cardiac tachyarrhythmias are associated with complex spatiotemporal excitation of the heart. The termination of these life-threatening arrhythmias require high-energy electrical shocks that have significant side effects, including tissue damage, excruciating pain, and worsening prognosis. This significant medical need has motivated the search for alternative approaches that mitigate the side effects, based on a comprehensive understanding of the nonlinear dynamics of the heart. Cardiac optogenetics enables the manipulation of cellular function using light, enhancing our understanding of nonlinear cardiac function and control. Here, we investigate the efficacy of optically resonant feedback pacing (ORFP) to terminate ventricular tachyarrhythmias using numerical simulations and experiments in transgenic Langendorff-perfused mouse hearts. We show that ORFP outperforms the termination efficacy of optical single-pulse (OSP) approach. At a termination rate of 50%, ORFP requires two orders of magnitude less light intensity per pulse than OSP. We demonstrate that even at light intensities below the excitation threshold, ORFP enables the termination of arrhythmias by spatiotemporal modulation of excitability inducing spiral wave drift.