Boosting NAD+ content using the NAD+ precursor NR but not NAM increased peak INa in heterologous expression systems and RNCMs through both acetylation-independent and acetylation-dependent mechanisms. In addition, NR supplementation decreased INa,L in RNCMs and shortened QTc in mice. These findings reinforce the potential role of the NAD+ supplementation in cardiac electrophysiology and warrant investigation of NR supplementation as an antiarrhythmic strategy in inherited and acquired disorders associated with abnormal Na+ currents.