Suppression of Arrhythmia by Enhancing Mitochondrial Ca 2+ Uptake in Catecholaminergic Ventricular Tachycardia Models.

•Fast transfer of Ca2+ from the sarcoplasmic reticulum into mitochondria in cardiomyocytes can be enhanced by the MiCUps efsevin, targeting the VDAC2, and kaempferol, targeting the MCU.•Enhancing sarcoplasmic reticulum-to-mitochondria Ca2+ transfer with MiCUps suppresses arrhythmogenic Ca2+ events and spontaneous action potentials in cardiomyocytes from a mouse model of CPVT.•In vivo treatment of CPVT mice with MiCUps reduces episodes of ventricular tachycardia after adrenergic stimulation.•In induced pluripotent stem cell-derived cardiomyocytes from a CPVT patient, both MiCUps reduce arrhythmogenic Ca2+ events.•Our data establish fast mitochondrial Ca2+ uptake as a promising candidate structure for pharmacological treatment of human cardiac arrhythmia.