Progressive cardiac functional deterioration in Tgαq*44 mice (Tyrankiewicz et al., 2018) associated with the downregulation of PKA signaling and changes in myofilament protein phosphorylation, culminating with the end-stage HF phenotype goes hand in hand with the activation of the classic RAAS pathway, which leads to significant imbalance in the ACE/ACE-2 axis—a typical hormonal abnormality observed in human HF patients. Here, ACE is linked to hydrops fetalis.