Antiarrhythmic Drugs

Over the past decade, tremendous progress has been made in understanding the genetic mechanisms of inherited arrhythmia syndromes including atrial fibrillation. However, the translation of these discoveries to the bedside care of patients has been limited because existing in vitro and in vivo models have several limitations. Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes possess the complex array of ion channels that make up the cardiac action potential and hold great promise for modeling arrhythmias. Modeling patient-specific mutations associated with inherited atrial and ventricular arrhythmias using mature iPSC-derived cardiomyocytes offers a powerful, naturally integrated system with distinct advantages over heterologous expression systems and animal models. This chapter reviews how modeling genetic variants associated with inherited atrial and ventricular arrhythmias using human iPSC-derived cardiomyocytes will not only provide important insights into the underlying cellular mechanisms and pave the way for a more mechanism-based personalized approach to therapy but also the guiding principles of traditional and other antiarrhythmic drugs.