Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Editorial Comment Cardiology 2011;118:238 DOI: 10.1159/000329505 Aldosterone Pathway in Atrial Fibrillation Adam S. Budzikowski  Division of Cardiovascular Medicine, EP Section, SUNY Downstate, Brooklyn, N.Y., USA tients in sinus rhythm. It is very possible that other factors than the change in atrial mechanics associated with sinus rhythm are responsible for the declining levels of aldoste- rone, as the available evidence seems to suggest that aldo- sterone is not synthesized in atrial tissue [5]. Even though no plasma renin activity was measured in these patients, this population represents typically healthier patients with AF much better than any studied population so far [6]. Al- though no causative relationship can be established from these data between AF and high aldosterone levels, it clear- ly generates a hypothesis that is worth further exploring experimentally. Blockade of aldosterone in high aldoste- rone states (primary hyperaldosteronism or systolic heart failure) has been associated with a decrease in the frequen- cy of AF [2, 3]. Blockade of aldosterone receptors has been associated with decreased myocardial fibrosis as well as de- creased calcium overload and hence arrhythmogenesis [5, 7, 8]. Utility of aldosterone antagonism in patients with AF and no significant structural heart disease remains a very attractive therapeutic option, yet it still awaits experimen- tal proof. The epidemiologic impact of atrial fibrillation (AF) cre- ates constant interest in better understanding the neuro- hormonal mechanism in the development and mainte- nance of this arrhythmia and the development of upstream therapies. Activation of the renin angiotensin system has a well-documented role in the development of AF, and block- ade of angiotensin II synthesis or angiotensin II receptors has been shown to decrease the frequency of AF in various disease states [1]. The final step in this process is the pro- duction of aldosterone. High aldosterone states have been associated with increased prevalence of AF [2–4]. Animal experimental evidence also suggests increased density of mineralocorticoid receptors in atrial cells undergoing rap- id depolarization but no significant difference in aldoste- rone levels in patients with AF [5] . This would suggest that only density of aldosterone receptors is responsible for del- eterious effects of aldosterone in patients with AF. In this issue of Cardiology, Soeby-Land et al. [6] provide evidence that AF is actually associated with increased plasma con- centration of aldosterone. Interestingly, aldosterone levels decline as sinus rhythm is restored and remain low in pa- Received: May 13, 2011 Accepted: May 16, 2011 Published online: July 5, 2011 Adam S. Budzikowski, MD, PhD Division of Cardiovascular Medicine, EP section SUNY Downstate 450 Clarkson Ave., Box 1199, Brooklyn, NY 11203 (USA) E-Mail abudzikowski  @  downstate.edu © 2011 S. Karger AG, Basel 0008–6312/11/1184–0238$38.00/0 Accessible online at: www.karger.com/crd References 1 Iravanian S, Dudley SC Jr: The renin-angioten- sin-aldosterone system (RAAS) and cardiac ar- rhythmias. Heart Rhythm 2008;5(suppl 6):S12– S17. 2 Milliez P, Girerd X, Plouin PF, Blacher J, Safar ME, Mourad JJ: Evidence for an increased rate of cardiovascular events in patients with pri- mary aldosteronism. J Am Coll Cardiol 2005; 45:1243–1248. 3 Milliez P, Deangelis N, Rucker-Martin C, et al: Spironolactone reduces fibrosis of dilated atria during heart failure in rats with myocardial in- farction. Eur Heart J 2005;26:2193–2199. 4 Yang SS, Han W, Zhou HY, et al: Effects of spi- ronolactone on electrical and structural remod- eling of atrium in congestive heart failure dogs. Chin Med J (Engl) 2008;121:38–42. 5 Tsai CT, Chiang FT, Tseng CD, et al: Increased expression of mineralocorticoid receptor in hu- man atrial fibrillation and a cellular model of atrial fibrillation. J Am Coll Cardiol 2010;55: 758–770. 6 Soeby-Land C, Dixen U, Therkelsen SK, Kjaer A: Increased plasma aldosterone during atrial fibrillation declines following cardioversion. Cardiology 2011;118:239–244. 7 Sun Y, Ramires FJ, Weber KT: Fibrosis of atria and great vessels in response to angiotensin II or aldosterone infusion. Cardiovasc Res 1997; 35:138–147. 8 Zhao J, Li J, Li Y, Shan H, Gong Y, Yang B: Ef- fects of spironolactone on atrial structural re- modeling in a canine model of atrial fibrillation produced by prolonged atrial pacing. Br J Phar- macol 2010;159:1584–1594.