While many of the drugs recommended for HF management are administered twice daily (including sacubitril/valsartan, some beta-blockers, ACE-inhibitors, and angiotensin-receptor-blockers) [95], the potential influence of time-of-the-day on efficacy and adverse effects could be explored for other agents administered once-daily (e.g., mineralocorticoid-receptor-antagonists, bisoprolol, and nebivolol). The gene discussed is ACE; the disease is hydrops fetalis.