Copyright © 2004 by the European Society of Cardiology.
Letter to the Editor
Atrial remodelling in persistent atrial fibrillation: the potential role of aldosterone: Reply
Division of Cardiology, Institute of Medicine, Chung-Shan Medical University, Taichung. 110, Sec. 1, Chien-Kuo N. Road, Taichung, Taiwan
School of Medicine, Taipei Veterans General Hospital-Taipei, National Yang-Ming University, Taiwan
* Tel.: +886-4-2253-2603; Fax: +886-4-2252-3626
E-mail address: ueng.kc{at}msa.hinet.net
The letter by Dr. Korantzopoulos and co-workers made several good points that are of general interest to the issue of aldosterone in atrial fibrillation (AF). Without a doubt, our findings provide mechanistic support for clinical observations pointing to efficacy against AF-induced structural remodelling of angiotensin converting enzyme (ACE) inhibitors after cardioversion of persistent AF.1 Increased understanding of pathophysiology of AF has shown that activation of the renin–angiotensin–aldosterone (RAA) system has been implicated in the progression of atrial structural remodelling in this setting. Goette et al.2 has shown that atrial expression of ACE is increased in interstitial tissue of fibrillating human atria. In addition to direct effects of angiotensin II on myocardial tissue, angiotensin II causes the release of aldosterone from the adrenal gland and extra-adrenal tissues. Recently, it has been shown that aldosterone is also produced in the failing human heart. Aldosterone has been shown to stimulate cardiac collagen synthesis and fibroblast proliferation via activation of local mineralocorticoid receptors, or indirectly, interfering with angiotensin II type 1 receptors and enhancing local ACE expression.3
Surprisingly, to date, clinical data directly linking aldosterone with AF are scarce. Systemic aldosterone levels are increased in patients with persistent AF. Thus, it seems likely that elevated systemic levels of alodosterone, perhaps as well as increased local synthesis of aldosterone acting in a paracrine/autocrine fashion, during AF may contribute to atrial remodelling.
The deleterious effect of an activated RAA system has been clearly demonstrated in patients with heart failure. A recent clinical trial4 has shown a marked benefit in patients with chronic heart failure from co-administration of the aldosterone receptor antagonist and ACE-inhibitor compared with using ACE-inhibitor alone, and the beneficial outcome in this study was shown to be associated with the suppression of the marker of cardiac collagen turnover leading to decreased cardiac fibrosis.
Li et al.5 demonstrated the development of angiotensin II-dependent atrial structural remodelling in an AF animal model. In this study, atrial fibrosis still occurred despite administration of enalapril. Incomplete protection may have been because enalapril attenuated, but did not eliminate, the tissue angiotensin II and aldosterone increase associated with heart failure, which may be, at least in part, explained by so called "aldosterone escape". Although renin–angiotensin system blockade reduces plasma aldosterone levels, this effect is only transitory, a phenomenon referred to as "aldosterone escape", potentially attenuating the cardiac protective effects of this class of drugs. This raises the possibility that local activation of aldosterone, even under conditions of renin–angiotensin system blockade may participate in the enhancement of extracellular matrix deposition. In this sense, we fully agree with Dr. Korantzopoulos that aldosterone may play a role in the progression of atrial remodelling. However, further evidence is required to prove that a local aldosterone system is functional in the atrial myocardium and to determine whether interfering with the RAA system using aldosterone antagonist can further reverse established arrhythmogenicity in AF-induced structural remodelling.
References
- Ueng KC, Tsai TP, Yu WC et al. Use of enalapril to facilitate sinus rhythm maintenance after external cardioversion of long-standing persistent atrial fibrillation: results of a prospective and controlled study. Eur. Heart J. 2003;24:2090–2098.
[Abstract/Free Full Text] - Goette A, Staack T, Rocken C et al. Increased expression of extracellular signal-regulated kinase and angiotensin-converting enzyme in human atria during atrial fibrillation. J. Am. Coll. Cardiol. 2000;35:1669–1677.
[Abstract/Free Full Text] - Harada E, Yoshimura M, Yasue H et al. Aldosterone induces angiotensin-converting enzyme gene expression in cultured neonatal rat cardiocytes. Circulation. 2001;104:137–139.
[Abstract/Free Full Text] - Pitt B, Zannad F, Remme WJ et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure: Randomized Aldactone Evaluation Study Investigators. N. Engl. J. Med. 1999;341:709–717.
[Abstract/Free Full Text] - Li D, Shinagawa K, Pang L et al. Effects of angiotensin-converting enzyme inhibition on the development of the atrial fibrillation substrate in dogs with ventricular tachypacing-induced congestive heart failure. Circulation. 2001;104:2608–2614.
[Abstract/Free Full Text]
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