New methodological approaches to atrial fibrillation drug discovery

Introduction Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice and rhythm control using pharmacological agents is required in selected patients. Nonetheless, current medication is only modestly efficacious and associated with significant cardiovascular and systemic side effects. More efficacious and safe drugs are required to restore and maintain sinus rhythm in patients with AF. Areas covered In this review, several potential drug targets are discussed including trans-membrane ion channels, intracellular calcium signaling, gap junction signaling, atrial inflammation and fibrosis, and the autonomic nervous system. New tools and methodologies for AF drug development are also reviewed including gene therapy, genome-guided therapy, stem cell technologies, tissue engineering, and optogenetics. Expert opinion In recent decades, there has been an increased understanding of the underlying pathogenesis of AF. As a result, there is a gradual paradigm shift from focusing only on trans-membrane ion channel inhibition to developing therapeutic agents that target other underlying arrhythmogenic mechanisms. Gene therapy and genome-guided therapy are emerging as novel treatments for AF with some success in proof-of-concept studies. Recent advances in stem cell technology, tissue engineering, and optogenetics may allow more effectivein-vitrodrug screening than conventional methodologies.

Automated summary

Atrial fibrillation (AF) is a common arrhythmia requiring rhythm control, but current medications have limited efficacy and significant side effects. This review explores potential drug targets and new methodologies, such as gene therapy and stem cell technologies, in the development of more effective treatments for AF. Recent advances in understanding the underlying mechanisms of AF are leading to a shift towards developing therapeutic agents targeting these mechanisms, with promising results in novel treatment approaches.