Genetic approaches aimed at reducing or abrogating ANP/NPR-A signaling receptor in mice leads to a blood pressure-independent exacerbation of cardiac hypertrophy, fibrosis, and left ventricular dysfunction in animal models of HF (Kishimoto et al., 2001; Knowles et al., 2001; Kuhn et al., 2002; Holtwick et al., 2003; Wang et al., 2014). This evidence concerns the gene NPPA and cardiac hypertrophy.