βarr1 appears to be cardiotoxic, since (a) it is this cardiac βarr isoform that is responsible for β1AR desensitization (G protein uncoupling) and downregulation, processes significantly contributing to the decline of cardiac β-adrenergic and inotropic reserves that underlies the pathophysiology of HF [27]; and (b) the G protein-independent signaling from cardiac β1AR it mediates is largely cardiotoxic (inhibition of EGFR transactivation and CaMKII induction leading to cardiac apoptosis, SERCA2a activity lowering leading to reduced contractility, etc.) [27] (Figure 1). This evidence concerns the gene CAMK2G and hydrops fetalis.