New methodological approaches to atrial fibrillation drug discovery

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.

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.

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 effective in-vitro drug screening than conventional methodologies.