The emerging technology of optogenetics uses optical and genetic means to monitor and modulate the electrophysiological properties of excitable tissues. While transforming the field of neuroscience, the technology has recently gained popularity also in the cardiac arena. Here, we describe the basic principles of optogenetics, the available and evolving optogenetic tools, and the unique potential of this technology for basic and translational cardiac electrophysiology. Specifically, we discuss the ability to control (augment or suppress) the cardiac tissue's excitable properties using optogenetic actuators (microbial opsins), which are light-gated ion channels and pumps that can cause light-triggered membrane depolarization or hyperpolarization. We then focus on the potential clinical implications of this technology for the treatment of cardiac arrhythmias by describing recent efforts for developing optogenetic-based cardiac pacing, resynchronization, and defibrillation experimental strategies. Finally, the significant obstacles and challenges that need to be overcome before any future clinical translation can be expected are discussed.

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Problem The COVID-19 pandemic has challenged health care systems in an unprecedented way by imposing new demands on health care resources and scientific knowledge. There has also been an exceedingly fast accumulation of new information on this novel virus. As the traditional peer-review process takes time, there is currently a significant gap between the ability to generate new data and the ability to critically evaluate them. This problem of an excess of mixed-quality data, or infodemic, is echoing throughout the scientific community. Approach The authors aimed to help their colleagues at the Rambam Medical Center, Haifa, Israel, manage the COVID-19 infodemic with a methodologic solution: establishing an in-house mechanism for continuous literature review and knowledge distribution (March–April 2020). Their methodology included the following building blocks: a dedicated literature review team, artificial intelligence–based research algorithms, brief written updates in a graphical format, large-scale webinars and online meetings, and a feedback loop. Outcomes During the first month (April 2020), the project produced 21 graphical updates. After consideration of feedback from colleagues and final editing, 13 graphical updates were uploaded to the center’s website; of these, 31% addressed the clinical presentation of the disease and 38% referred to specific treatments. This methodology as well as the graphical updates it generated were adopted by the Israeli Ministry of Health and distributed in a hospital preparation kit. Next Steps The authors believe they have established a novel methodology that can assist in the battle against COVID-19 by making high-quality scientific data more accessible to clinicians. In the future, they expect this methodology to create a favorable uniform standard for evidence-guided health care during infodemics. Further evolution of the methodology may include evaluation of its long-term sustainability and impact on the day-to-day clinical practice and self-confidence of clinicians who treat COVID-19 patients.

Background Optogenetics, using light‐sensitive proteins, emerged as a unique experimental paradigm to modulate cardiac excitability. We aimed to develop high‐resolution optogenetic approaches to modulate electrical activity in 2‐ and 3‐dimensional cardiac tissue models derived from human induced pluripotent stem cell (hiPSC)‐derived cardiomyocytes. Methods and Results To establish light‐controllable cardiac tissue models, opsin‐carrying HEK293 cells, expressing the light‐sensitive cationic‐channel CoChR, were mixed with hiPSC‐cardiomyocytes to generate 2‐dimensional hiPSC‐derived cardiac cell‐sheets or 3‐dimensional engineered heart tissues. Complex illumination patterns were designed with a high‐resolution digital micro‐mirror device. Optical mapping and force measurements were used to evaluate the tissues' electromechanical properties. The ability to optogenetically pace and shape the tissue's conduction properties was demonstrated by using single or multiple illumination stimulation sites, complex illumination patterns, or diffuse illumination. This allowed to establish in vitro models for optogenetic‐based cardiac resynchronization therapy, where the electrical activation could be synchronized (hiPSC‐derived cardiac cell‐sheets and engineered heart tissue models) and contractile properties improved (engineered heart tissues). Next, reentrant activity (rotors) was induced in the hiPSC‐derived cardiac cell‐sheets and engineered heart tissue models through optogenetics programmed‐ or cross‐field stimulations. Diffuse illumination protocols were then used to terminate arrhythmias, demonstrating the potential to study optogenetics cardioversion mechanisms and to identify optimal illumination parameters for arrhythmia termination. Conclusions By combining optogenetics and hiPSC technologies, light‐controllable human cardiac tissue models could be established, in which tissue excitability can be modulated in a functional, reversible, and localized manner. This approach may bring a unique value for physiological/pathophysiological studies, for disease modeling, and for developing optogenetic‐based cardiac pacing, resynchronization, and defibrillation approaches.