Recent research provided important insights into the development of atrial fibrillation (AF)-maintaining substrate and suggested targeting of the underlying molecular mechanisms, ‘upstream’ of the electrical aspects of AF, as a novel strategy for AF treatment (‘upstream’ therapy). Upstream therapies for AF include drugs targeting the renin-angiotensin II-aldosterone system (angiotensin converting enzyme inhibitors and AT1 receptor antagonists and aldosterone antagonists), statins, steroids and ω-3 fatty acids (fish oil). Aldosterone causes volume retention, cardiac hypertrophy and fibrosis, and systemic inflammation and coagulation that promote AF development and its complications and blockade of aldosterone receptors with spironolactone or eplerenone suppresses inducible AF. Although the clinical impact of spironolactone treatment requires validation in randomized clinical trials in AF patients, further understanding of the molecular mechanisms by which aldosterone causes atrial remodelling is likely to lead to development of novel therapeutic approaches to AF.
This article is a commentary on Zhao et al., pp. 1584–1594 of this issue. To view this paper visit http://dx.doi.org/10.1111/j.1476-5381.2009.00551.x