Perspective:

The activation of the sympathetic nervous system and renin–angiotensin–aldosterone system in heart failure (HF), and the eventual aldosterone breakthrough that results with angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker (ACE-I/ARB) therapy and high-dose loop diuretics may lead to acute decompensation characterized by mineralocorticoid receptor (MR) activation, and worsening cardiovascular and renal function. Despite optimal treatment with ACE-Is/ARBs and beta-blockers, early post-discharge re-hospitalization and mortality rates remain unacceptably high in acute HF syndrome (AHFS) patients. MR antagonists (MRAs) may potentially augment diuresis, reduce dyspnea, and minimize neurohumoral-mediated renal dysfunction. Current limitations in AHFS therapy may possibly be due to incomplete suppression of the neurohumoral axis and/or delayed implementation of neurohumoral antagonists. MRAs may provide an additional means of neurohumoral inhibition in AHFS, and therefore, reduce the risk of progressive HF, worsening renal function, sudden cardiac death, and death due to progressive HF. Further studies are needed to evaluate the efficacy and safety of MRAs to overcome diuretic resistance and elucidate their effect on clinical outcomes in patients with AHFS.