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Moreover, Ca 2+ leak and elevated diastolic Ca 2+ levels increase Ca 2+ extrusion via NCX, promoting an inward depolarizing current which is electrogenic and promotes triggered activity and arrhythmia formation ( Sustained Sympathetic Activation Leads to -ARs Desensitization/Down-Regulation in HF HF is characterized by sympathetic activation and elevated blood catecholamine levels ( -AR desensitization in HF is caused by phosphorylation of -ARs themselves by PKA and G-protein coupled receptor kinases (GRKs) ( In the Presence of Abnormal Ca 2+ Handling, Further Enhancing Adrenergic Signaling Could Be Detrimental Rather Than Beneficial in HF RyR2 dysfunction and Ca 2+ leak in HF are caused by sustained adrenergic signaling ( 2+ leak (Figure 1)