Reduced AMPK signaling would be expected to have a negative impact on metabolism (Dyck and Lopaschuk, 2006; Beauloye et al., 2011; Zaha and Young, 2012), which in turn could be part of the mechanism by which AE3-deficiency leads to more rapid decompensation in heart failure (Al Moamen et al., 2011). This evidence concerns the gene SLC4A3 and heart failure.