Aldosterone and the Mineralocorticoid Receptor in Atrial Fibrillation

Atrial fibrillation represents the most prevalent cardiac arrhythmia and is associated with substantial morbidity, including an increased risk for stroke and heart failure. The pathophysiology of atrial fibrillation involves electrical and structural remodeling of the atria, often referred to as atrial myopathy, that together increase the risk for arrhythmias. However, a specific approach to target the proarrhythmic substrate of atrial fibrillation is still lacking. Aldosterone and the mineralocorticoid receptor are well-known drivers of cardiac remodeling, and recent clinical and experimental studies indicate that they play a critical role in the pathogenesis of atrial fibrillation. Elevated aldosterone levels, for example, in primary aldosteronism, are associated with a higher risk for atrial fibrillation. Mineralocorticoid receptor antagonists reduce the onset of atrial fibrillation across various patient populations, including patients with hypertension, heart failure, chronic kidney disease, or undergoing cardiac surgery. In patients with preexisting atrial fibrillation, mineralocorticoid receptor antagonists may decrease atrial fibrillation recurrence when added to antiarrhythmic therapies. Experimental studies provide a direct link between aldosterone and atrial remodeling and arrhythmia. Mineralocorticoid receptor activation modulates several key cellular processes involved in atrial inflammation, fibrosis, and arrhythmogenesis, including fibroblast activation, cardiomyocyte dysfunction, and ion channel activity. Here, we review what is currently known about the role of aldosterone and the mineralocorticoid receptor in atrial fibrillation, summarize the mechanistic basis as supported by experimental studies, and discuss the potential of mineralocorticoid receptor antagonists in the prevention and treatment of atrial fibrillation.