Mineralocorticoid Receptor Antagonism in Acute Heart Failure

Abstract

Heart failure (HF) remains a tremendous burden to health care systems and patients worldwide. The cornerstone neurohormonal disruption that leads to the debilitating sequelae in HF patients revolves primarily around aldosterone and the renin-angiotensin-aldosterone system (RAAS). Aldosterone plays a detrimental role in tissue remodeling by inducing inflammation and fibrosis within the cardiovascular and renal systems, leaving mineralocorticoid receptor antagonists (MRAs) as key pharmacological tools to slow pathogenesis and improve patient outcomes. The role of MRA in improving morbidity and mortality in outpatients with chronic HF and low ejection fraction is well established and supported by large randomized controlled trials. However, evidence-based data relating to the use of MRA in acute HF (AHF) remain somewhat limited, and therefore, the use of MRA is not ubiquitously considered in the acute setting. Current studies for the use of MRA in AHF are limited by small sample size as well as safety concerns relating to the dose-dependent effects on electrolyte homeostasis and renal function. Here, we discuss the imperative need for additional trials elucidating the potential benefits of MRA in AHF as an adjunct diuretic therapy. We not only discuss the role of MRA in neurohormonal regulation of aldosterone but also highlight a potential dose-dependent role for MRA in natriuresis. Furthermore, we showcase existing and recent evidence-based data demonstrating the effectiveness of MRA in AHF and on long-term outcomes. Finally, we look at several treatment strategies and safety concerns as they relate to MRA use so as to aid in avoidance of MRA-related complications while facilitating achievement of treatment goals.

The role of oxidative stress in the crosstalk between leptin and mineralocorticoid receptor in the cardiac fibrosis associated with obesity

“…Aldosterone through binding of mineralocorticoid receptor (MR), triggers the development of cardiac fibrosis in different pathologies, and its pharmacological blockade has demonstrated reduced interstitial fibrosis in these situations 12 – 14 . Different studies have demonstrated that aldosterone is inappropriately elevated in obesity, and MR antagonism improves left ventricle function and reduces circulating procollagen levels in patients with obesity without other comorbidities 4 , 15 .…”