We find that RyR2 activity determines the potency of open-state blockers FLEC and R-propafenone [RPROP] for suppressing arrhythmogenic Ca2+ waves in cardiomyocytes, a mechanism likely relevant to antiarrhythmic drug efficacy in CPVT. The gene discussed is RYR2; the disease is catecholaminergic polymorphic ventricular tachycardia.