Background and Aims: During atrial fibrillation (AF), the renin-angiotensin-aldosterone system (RAAS) may be activated.In this study, our aim was to evaluate at a long-term follow-up visit the levels of plasma aldosterone and natriuretic peptides as markers of neurohormonal remodeling in patients with earlier, documented AF in relation to present heart rhythm, clinical data, and the left ventricular ejection fraction (LVEF). We hypothesized that increased levels of aldosterone and natriuretic peptides were significantly associated with present AF as markers of RAAS activation during the arrhythmia. Methods: We studied 158 patients with earlier ECG-documented AF followed by restored sinus rhythm (SR) attending a follow-up visit 2.6 years (mean) after primary inclusion. Results: At follow-up, 93 patients had SR. Heart rhythm at follow-up visit (SR/AF), plasma aldosterone, plasma N-terminal pro Brain Natriuretic Peptide (Nt- proBNP), plasma N-terminal pro Atrial Natriuretic Peptide (Nt-proANP), LVEF, medication, and clinical characteristics were recorded. Standard linear multiple regression analysis including age, sex, weight, hypertension, congestive heart failure, ischemic heart disease, present AF at follow-up, total duration of AF disease, ongoing medication, and the LVEF as explanatory variables showed that only ongoing treatment with diuretics was significantly associated (likelihood ratio test, p = 0.0057) with a raised log-transformed plasma aldosterone, although present AF at follow-up was related to a high aldosterone level (p = 0.09). For the natriuretic peptides, present AF at follow-up (p < 0.0001), age (p < 0.0001), female gender (p = 0.0047), ischemic heart disease (p = 0.0154), and ongoing treatment with sotalol (p = 0.0003) were all independently associated with high log-transformed plasma Nt-proANP. Likewise, present AF at follow-up (p = 0.0008) as well as age (p < 0.0001) were associated with high log-transformed plasma Nt-proBNP. Conclusions: In patients with earlier AF, AF at long-term follow-up visit was independently associated with raised levels of Nt-proANP and Nt-proBNP and to some extent with plasma aldosterone indicating neurohormonal activation during arrhythmia.

1.
Benjamin EJ, Wolf PA, D’Agostino RB, Silbershatz H, Kannel WB, Levy D: Impact of atrial fibrillation on the risk of death: the Framingham Heart Study. Circulation 1998;98:946–952.
2.
Friberg J, Buch P, Scharling H, Gadsboll N, Jensen GB: Rising rates of hospital admissions for atrial fibrillation. Epidemiology 2003;14:666–672.
3.
Kannel WB, Wolf PA, Benjamin EJ, Levy D: Prevalence, incidence, prognosis, and predisposing conditions for atrial fibrillation: population-based estimates. Am J Cardiol 1998;82:2N–9N.
4.
Nishino M, Hoshida S, Tanouchi J, Ito T, Kato J, Iwai K, Tanahashi H, Hori M, Yamada Y, Kamada T: Time to recover from atrial hormonal, mechanical, and electrical dysfunction after successful electrical cardioversion of persistent atrial fibrillation. Am J Cardiol 2000;85:1451–1454.
5.
Redfield MM, Kay GN, Jenkins LS, Mianulli M, Jensen DN, Ellenbogen KA: Tachycardia-related cardiomyopathy: a common cause of ventricular dysfunction in patients with atrial fibrillation referred for atrioventricular ablation. Mayo Clin Proc 2000;75:790–795.
6.
Tepper D: Frontiers in congestive heart failure: tachycardia-related cardiomyopathy: a common cause of ventricular dysfunction in patients with atrial fibrillation referred for atrioventricular ablation. Congest Heart Fail 2000;6:284.
7.
Dao Q, Krishnaswamy P, Kazanegra R, Harrison A, Amirnovin R, Lenert L, Clopton P, Alberto J, Hlavin P, Maisel AS: Utility of B-type natriuretic peptide in the diagnosis of congestive heart failure in an urgent-care setting. J Am Coll Cardiol 2001;37:379–385.
8.
Maisel AS, Koon J, Krishnaswamy P, Kazenegra R, Clopton P, Gardetto N, Morrisey R, Garcia A, Chiu A, De Maria A: Utility of B-natriuretic peptide as a rapid, point-of-care test for screening patients undergoing echocardiography to determine left ventricular dysfunction. Am Heart J 2001;141:367–374.
9.
Goette A, Hoffmanns P, Enayati W, Meltendorf U, Geller JC, Klein HU: Effect of successful electrical cardioversion on serum aldosterone in patients with persistent atrial fibrillation. Am J Cardiol 2001;88:906–909, A8.
10.
Jourdain P, Bellorini M, Funck F, Fulla Y, Guillard N, Loiret J, Thebault B, Sadeg N, Desnos M: Short-term effects of sinus rhythm restoration in patients with lone atrial fibrillation: a hormonal study. Eur J Heart Fail 2002;4:263–267.
11.
Tuinenburg AE, van Veldhuisen DJ, Boomsma F, Van Den Berg MP, De Kam PJ, Crijns HJ: Comparison of plasma neurohormones in congestive heart failure patients with atrial fibrillation versus patients with sinus rhythm. Am J Cardiol 1998;81:1207–1210.
12.
Dixen U, Joens C, Parner J, Rasmussen V, Pehrson SM, Jensen GB: Prolonged signal-averaged P wave duration after elective cardioversion increases the risk of recurrent atrial fibrillation. Scand Cardiovasc J 2004;38:147–151.
13.
Brilla CG, Matsubara LS, Weber KT: Antifibrotic effects of spironolactone in preventing myocardial fibrosis in systemic arterial hypertension. Am J Cardiol 1993;71:12A–16A.
14.
Ueng KC, Tsai TP, Yu WC, Tsai CF, Lin MC, Chan KC, Chen CY, Wu DJ, Lin CS, Chen SA: 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.
15.
Madrid AH, Bueno MG, Rebollo JM, Marin I, Pena G, Bernal E, Rodriguez A, Cano L, Cano JM, Cabeza P, Moro C: Use of irbesartan to maintain sinus rhythm in patients with long-lasting persistent atrial fibrillation: a prospective and randomized study. Circulation 2002;106:331–336.
16.
Pedersen OD, Bagger H, Kober L, Torp-Pedersen C: Trandolapril reduces the incidence of atrial fibrillation after acute myocardial infarction in patients with left ventricular dysfunction. Circulation 1999;100:376–380.
17.
Wachtell K, Lehto M, Gerdts E, Olsen MH, Hornestam B, Dahlof B, Ibsen H, Julius S, Kjeldsen SE, Lindholm LH, Nieminen MS, Devereux RB: Angiotensin II receptor blockade reduces new-onset atrial fibrillation and subsequent stroke compared to atenolol: the Losartan Intervention For End Point Reduction in Hypertension (LIFE) study. J Am Coll Cardiol 2005;45:712–719.
18.
Wachtell K, Hornestam B, Lehto M, Slotwiner DJ, Gerdts E, Olsen MH, Aurup P, Dahlof B, Ibsen H, Julius S, Kjeldsen SE, Lindholm LH, Nieminen MS, Rokkedal J, Devereux RB: Cardiovascular morbidity and mortality in hypertensive patients with a history of atrial fibrillation: The Losartan Intervention For End Point Reduction in Hypertension (LIFE) study. J Am Coll Cardiol 2005;45:705–711.
19.
Heidbuchel H: A paradigm shift in treatment for atrial fibrillation: from electrical to structural therapy? Eur Heart J 2003;24:2077–2078.
20.
Rowland NE, Morian KR: Roles of aldosterone and angiotensin in maturation of sodium appetite in furosemide-treated rats. Am J Physiol 1999;276:R1453–R1460.
21.
Burnier M, Brunner HR: Neurohormonal consequences of diuretics in different cardiovascular syndromes. Eur Heart J 1992;13:28–33.
22.
Wyse DG, Waldo AL, DiMarco JP, Domanski MJ, Rosenberg Y, Schron EB, Kellen JC, Greene HL, Mickel MC, Dalquist JE, Corley SD: A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med 2002;347:1825–1833.
23.
Wozakowska-Kaplon B, Opolski G: Concomitant recovery of atrial mechanical and endocrine function after cardioversion in patients with persistent atrial fibrillation. J Am Coll Cardiol 2003;41:1716–1720.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.