Since the 1990s, there has been a significant paradigm shift in the management of HF: (1) The approach has transitioned from a short-term focus on hemodynamics to a long-term remedial strategy aimed at modifying HF pathophysiology and implementing multi-mechanism/target therapy with an enhanced understanding of HF; (2) There has been a shift away from the use of cardiotonic, diuretic, and vasodilator medications towards the utilization of neuroendocrine inhibitors and other innovative therapeutic treatments including ARNI, SGLT-2i, and sGC agonists. The gene discussed is SGCB; the disease is hydrops fetalis.