GNAS and heart failure: That β-AR signaling is detrimental to cardiac function is supported by clinical studies in humans showing that blockade of β-AR receptors improves survival in heart failure patients [19], and by studies on transgenic mice, showing that chronic activation of the cAMP-PKA pathway by cardiac-specific overexpression of β-AR, Gsα, and the α-catalytic subunit of PKA result in cardiomyopathy [2,20].