Aldosterone Antagonism in Heart Failure with Preserved Ejection Fraction

Heart failure with preserved ejection fraction (HFpEF) accounts for roughly half of all heart failure presentations and is characterised by normal or near‐normal left ventricular systolic function alongside impaired diastolic relaxation, elevated filling pressures and systemic congestion. Aldosterone, a mineralocorticoid hormone, promotes sodium and water retention, myocardial fibrosis and vascular remodelling. Antagonism of the mineralocorticoid receptor using agents such as spironolactone, eplerenone and non‐steroidal antagonists aims to counter these effects. In HFpEF, the therapeutic rationale centres on ameliorating diastolic dysfunction, reducing interstitial fibrosis, improving endothelial function and attenuating the neurohormonal overactivation that underpins symptom burden and hospitalisation risk. Clinically, trials have yielded mixed results: reductions in surrogate measures of diastolic filling pressures and left atrial size have been reported, yet consistent mortality or hard outcome benefits remain elusive. Safety considerations, particularly the risk of hyperkalaemia and renal impairment, demand careful patient selection and monitoring. Ongoing research explores the heterogeneity of HFpEF phenotypes, optimal dosing strategies, combinations with other renin–angiotensin–aldosterone system inhibitors and the role of novel non‐steroidal agents to extend the therapeutic window and enhance tolerability.

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Aldosterone Antagonism in Heart Failure with Preserved Ejection Fraction publication trend

The graph below shows the total number of articles in aldosterone antagonism in heart failure with preserved ejection fraction across all publications each year (not limited to Nature Index journals).

Technical terms

Heart failure with preserved ejection fraction (HFpEF): A syndrome of heart failure symptoms and signs in the presence of normal or near‐normal left ventricular ejection fraction (typically ≥50%) and evidence of diastolic dysfunction.

Mineralocorticoid receptor antagonist (MRA): A class of drugs that block aldosterone binding at the mineralocorticoid receptor, reducing sodium retention, fibrosis and adverse remodelling.

E/e′ ratio: An echocardiographic index comparing early mitral inflow velocity (E) to mitral annular tissue velocity (e′) as a surrogate of left ventricular filling pressure.

Diastolic dysfunction: Impaired relaxation and increased stiffness of the left ventricle, leading to elevated filling pressures during diastole.

Hyperkalaemia: An elevated serum potassium concentration that may complicate treatment with mineralocorticoid receptor antagonists and requires monitoring to avoid cardiac arrhythmias.

References

1. Mineralocorticoid receptor antagonists in heart failure: an individual patient level meta-analysis. The Lancet (2024).
2. Effect on cardiac function among patients with type 2 diabetes following high-dose mineralocorticoid receptor antagonist using echocardiography; data from the MIRAD randomized clinical trial. BMC Cardiovascular Disorders (2023).
3. Plasma Biomarker Profiling in Heart Failure Patients with Preserved Ejection Fraction before and after Spironolactone Treatment: Results from the Aldo-DHF Trial. Cells (2021).