Indeed, we have previously shown in paroxysmal AF patients with a similar phenotype that RyR2 and SERCA2a dysfunction can each promote proarrhythmic spontaneous SR Ca2+-release events and that the combination of both factors is significantly more proarrhythmic than each individually (Voigt et al., 2014). This evidence concerns the gene RYR2 and Paroxysmal atrial fibrillation.