RYR2 and catecholaminergic polymorphic ventricular tachycardia: Alterations of RyR2 inducing intracellular Ca2+ leak, including constitutive PKA phosphorylation or CPVT mutations, trigger a vicious cycle, in which SR Ca2+ leak in atrial myocytes impairs mitochondrial function leading to an increase in ROS production, thereby promoting RyR2 oxidation and further Ca2+ leak.