In this study, we report that Wenxin Keli (also known as Wenxin granule), a clinically available Chinese patent medicine used for preventing and treating heart failure–related arrhythmias, modulates energy metabolism and improves Cx43 function by activating AMPK/SIRT1/PGC-1α signaling pathway. Here, PPARGC1A is linked to cardiac arrhythmia.