Agents such as beta-blockers, angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin receptor blockers in ACE-I intolerant individuals, angiotensin receptor neprilysin inhibitors (ARNI), mineralocorticoid antagonists (MRA), and more recently the sodium-glucose cotransporter-2 (SGLT2) inhibitors are currently considered essential foundational therapies in the management of heart failure with reduced ejection fraction [37]. This evidence concerns the gene ACE and heart failure.