As proposed by Higuchi et al. [68], the opposite effects of TNFR1 and TNFR2 on cardiac remodeling and HF progression could rely on their opposite regulation of Akt, a pro-survival kinase, potently inhibited by the TNFR1-induced second messenger ceramide [75], as illustrated in Figure 3. Here, TNFRSF1A is linked to hydrops fetalis.