Article

Natriuretic Peptides as Predictors of Atrial Fibrillation Recurrences Following Electrical Cardioversion

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Abstract

Electrical cardioversion (ECV) can be effective in restoring sinus rhythm (SR) in the majority of patients with atrial fibrillation (AF). Several factors that predispose to AF recurrences, such as age, AF duration and left atrial size have been used to guide a decision for cardioversion, but increasing evidence suggests that they may be rather poor markers of left atrial structural remodeling that determines the long-term success of a rhythm control strategy. In this context, the use of easily obtainable biomarkers, such as the levels of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), to predict AF recurrences may be preferable. Since ANP production is associated with the extent of functional atrial myocardium, and both ANP and BNP reflect atrial pressure and mechanical stretching, these peptides are good candidate biomarkers to assess predisposition to AF recurrences. In this review we focus on the pathophysiological mechanisms and the available clinical evidence regarding the prediction of AF recurrences following successful ECV from pre-procedural ANP and BNP levels.

Keywords

Atrial fibrillation, electrical cardioversion, atrial natriuretic peptide, B-type natriuretic peptide,

Disclosure:The authors have no conflicts of interest to declare.

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DOI:https://doi.org/10.15420/aer.2013.2.2.109

Correspondence Details:Demosthenes G Katritsis, Athens Euroclinic, 9 Athanasiadou Street, Athens 11521, Greece. E: dkatritsis@euroclinic.gr

Copyright Statement:

The copyright in this work belongs to Radcliffe Medical Media. Only articles clearly marked with the CC BY-NC logo are published with the Creative Commons by Attribution Licence. The CC BY-NC option was not available for Radcliffe journals before 1 January 2019. Articles marked ‘Open Access’ but not marked ‘CC BY-NC’ are made freely accessible at the time of publication but are subject to standard copyright law regarding reproduction and distribution. Permission is required for reuse of this content.

Atrial Fibrillation(AF) affects 1-2 % of the population, and its prevalence is expected to increase in the next 50 years.1,2 The treatment of these patients includes either restoration and maintenance of sinus rhythm (SR) or control of the ventricular rate.3

Electrical cardioversion (ECV) can be effective in restoring SR in the majority of patients; however, it is associated with several risks and complications, including thromboembolic events, post-cardioversion arrhythmias and the risks of anaesthesia.3 Furthermore, ECV is effective in less than half of the patients, since AF recurrences are common, with a 40 % rate of AF recurrences within the month.4 Factors that predispose to AF recurrence are age, AF duration before cardioversion, number of previous recurrences, increased left atrial (LA) size or reduced LA function, and the presence of coronary heart disease or, pulmonary or mitral valve disease.5 Nevertheless, increasing evidence suggests that the above-mentioned factors may be poor markers of LA structural remodeling, which determines the propensity to AF recurrences. In fact, the extent of atrial fibrosis appears to be highly variable between patients with the same risk factors for AF.6 The extent of fibrosis can be determined using delayed enhancement magnetic resonance imaging; however, it could be adequately assessed by the secretory function of the remaining atrial myocardium.

A method to choose patients for whom ECV would be more successful based on easily obtainable biomarkers, such as natriuretic peptides (NPs), may improve clinical outcomes and cost-efficiency. In this review, we focus on the pathophysiological mechanisms and the available clinical evidence regarding the prediction of AF recurrences following successful ECV from pre-procedural NP levels.

Natriuretic Peptide System
The NP system consists of three different NPs sharing a common 17-amino acid ring, namely - atrial NP (ANP), B-type or brain NP (BNP) and C-type NP (CNP) (see Figure 1). Their biological actions are mediated through membrane-bound NP receptors (NPRs) - NPR-A, NPR-B and NPR-C.
 

Natriuretic Peptides and their Respective Receptors
 

Atrial Natriuretic Peptide
Mammalian atrial myocytes have been found to contain specific granules, with characteristics compatible with a secretory function.7The importance of these granules was demonstrated by de Bold et al., who reported the occurrence of a natriuretic response following cross-animal injection of atrial myocardium extract.8 This natriuretic effect was later ascribed to a 28-amino acid peptide, which was simultaneously isolated and sequenced by several research groups, and was found to be strictly localised within the specific granules.9-11 In cardiac myocytes, ANP is synthesised and stored as a 126-amino acid precursor, pro-ANP, which is cleaved to biologically active ANP and the N-terminal portion of pro-ANP (NT-proANP) by a transmembrane cardiac serine protease, corin, during the secretion process.12

ANP secretion is primarily regulated by mechanical stretching of the atria, secondary to increased loading, but an increase in the rate of contraction also causes an increase in ANP. Equally potent stimuli for ANP release are hypoxia and myocardial ischaemia.13 Several other factors have been associated with ANP regulation, such as angiotensin II, vasopressin and adrenergic agonists, which seem to induce ANP secretion; nevertheless, there is some controversy as to whether this is due to a direct effect or due to affecting venous return or cardiac afterload.13 Paracrine factors derived from endothelial cells modulate ANP secretion as well. Endothelin, a potent vasoconstrictor, stimulates ANP secretion and enhances stretch-induced ANP secretion, whereas nitric oxide (NO), an important vasodilator, inhibits ANP secretion.13

ANP in plasma is characterised by a short half-life, which ranges between 2 and 4 minutes and rapid metabolic clearance.14,15 In contrast to BNP and NT-proBNP, ANP has much higher renal extraction, with a renal fractional extraction of approximately 50 %.16 In accordance with BNP, ANP is inactivated by two pathways; enzymatic degradation by neutral endopeptidase and lysosomal degradation after binding to NPR-C. ANP binds with greater affinity to NPR-C compared with BNP, which contributes significantly to its shorter plasma half-life.17

Brain Natriuretic Peptide
Even though BNP was initially isolated from porcine brain, and was therefore named 'brain natriuretic peptide',18 it was later found that in humans BNP is highly synthesised and secreted in the ventricles, in contrast to ANP, which is preferentially secreted from the atria.19 Nevertheless, both peptides can be synthesised in either chamber under pathological conditions.20 The BNP messenger RNA (mRNA) expression is more than twofold higher in atria than in ventricles, but the BNP production in the ventricles is considered more important for the contribution to BNP plasma concentrations due to the larger mass of the ventricles.21 In patients with AF, Inoue et al. have suggested that BNP is predominantly produced in the atrium.22

In contrast to ANP, which seems to be well conserved in mammals, BNP and NT-proBNP differ among mammalian species. Another significant difference is that, unlike ANP, BNP has minimal storage in granules and most of BNP regulation is done during gene expression, with most BNP synthesised in bursts of activation from physiological and pathophysiological stimuli when peptide secretion occurs.23

In response to left ventricular stretch and wall tension, natriuretic peptide precursor (NPPB) gene is translated into a 134-amino acid precursor, which undergoes rapid removal of a 26-amino acid signal peptide, resulting in the formation of proBNP1-108. Upon cleavage from prohormone convertases, furin and corin, an active BNP hormone comprising 32-amino acid residues (BNP1-32), along with a physiologically inactive N-terminal fragment (NT-proBNP1-76) are formed from proBNP.24

Even though BNP and NT-proBNP are produced in equimolar proportions,circulating NT-proBNP levels are approximately sixfold higher compared with BNP levels, due to a difference in half-life times.25 BNP has a half-life of approximately 20 minutes, whereas NT-proBNP has a longer half-life of approximately 120 minutes.26 Due to its longer half-life, NT-proBNP levels are more stable and less sensitive to acute stress. These differences in plasma half-lives can be ascribed to different clearance mechanisms. Even though evidence suggests that renal extraction of BNP is comparable to that of NT-proBNP and consistent with the renal extraction of other bio-active peptides,27 glomerular filtration plays only a minor role in the elimination of BNP, which is primarily eliminated by binding to NPR-C and through enzymatic degradation by neutral endopeptidases. In contrast, NT-proBNP is thought to be largely cleared by renal excretion.26

BNP exerts more potent natriuretic and blood pressure-lowering effects compared with ANP, whereas both NPs suppress the renin-angiotensin-aldosterone system to the same extent.28 Furthermore, there is evidence that BNP has a direct anti-fibrotic effect on cardiac fibroblasts, by opposing transforming growth factor-beta (TGF-beta) regulated genes related to fibrosis (such as collagen 1, fibronectin, connective tissue growth factor [CTGF], plasminogen activator inhibitor-1 [PAI-1] and tissue inhibitor of metalloproteinase-3 [TIMP3]), myofibroblast conversion and proliferation (alpha-smooth muscle actin 2 and non-muscle myosin heavy chain, platelet-derived growth factor [PDGFA], insulin-like growth factor 1 [IGF-1], fibroblast growth factor-18 [FGF18] and IGF binding protein-10 [IGFBP10]) and inflammation (cyclooxygenase-2 [COX2], Interleukin 6 [IL6], tumor necrosis factor [TNF] alpha-induced protein 6 and TNF superfamily, member 4).29

Natriuretic Peptide Receptors
The biological actions of NPs are mediated by the membrane-bound NPRs. The basic topology of NPR-A, which preferentially binds ANP and BNP, consists of an extracellular ligand-binding domain (a short hydrophobic membrane-spanning region) and an intracellular domain, which contains a guanylyl cyclase catalytic domain in its C-terminus.30 Association of NPR-A with its cognate ligand (ANP or BNP) causes a conformational change that relaxes tonic inhibition of guanylyl cyclase activity and increases production of cyclic guanosine monophosphate (cGMP).31 NPR-B, which preferentially binds CNP, shares a similar structure with NPR-A. As mentioned, NP clearance from the blood is mediated by NPR-C, which has an extracellular domain that is structurally homologous to that of the other NPRs. NPR-C binds with high affinity to all three NPs and facilitates their clearance from the circulation through receptor-mediated internalisation and degradation.31

Brain Natriuretic Peptide as a Predictor of Atrial Fibrillation Recurrences Post-electrical Cardioversion
Elevated levels of BNP and NT-proBNP in patients with AF compared with patients in SR have long been described.32-34 Upon restoration of SR, levels of BNP rapidly normalise.35,36 Furthermore, BNP and NT-proBNP levels have been shown to predict the risk of AF occurrence in various clinical settings. Elevated pre-operative levels of BNP or NT-proBNP have been associated with increased risk of new-onset AF following coronary artery bypass grafting surgery.37,38 The association of preoperative BNP levels with the post-operative development of AF has also been documented in patients undergoing general thoracic surgery and major non-cardiac surgery.39,40

Similar findings are reported in several studies assessing the recurrence of AF following catheter ablation. Patients with higher baseline levels of BNP and NT-proBNP have higher rates of AF recurrence.41,42 Whereas, both BNP and NT-proBNP have been recognised as independent predictors of AF recurrence in the majority of studies, there are reports that failed to identify such an association.43,44

In the context of the above mentioned data, several observational studies have assessed the value of BNP and NT-proBNP levels in predicting AF recurrences following ECV (see Table 1). Evidence from the majority of these studies supports an association between BNP or NT-proBNP levels before ECV and the risk of AF recurrence.45-54 Nevertheless, other studies have failed to observe a relationship.55-58 In fact, in the three most recent studies, a statistically significant association between baseline BNP or NT-proBNP levels and SR maintenance was not observed.59-61 A meta-analysis that included ten of the above-mentioned studies concluded that higher BNP levels before ECV were associated with an increased risk of AF recurrence following successful ECV, suggesting that the measurement of BNP levels could improve the initial selection of suitable patients for ECV.62
 

In the patients included in the above-mentioned studies, which mainly have preserved ejection fraction, high BNP/NT-proBNP levels may be the consequence of several pathogenic mechanisms. BNP levels may reflect a higher degree of systematic inflammation, which is consistently associated with AF.63 In vitro studies suggest that BNP may be selectively up-regulated at the transcriptional and translational level by pro-inflammatory cytokines, and that plasma BNP levels may increase as a response to systemic inflammation in the absence of haemodynamic changes.64,65 The frequent occurrence of AF in patients with inflammatory conditions, such as myocarditis and pericarditis, and the finding of marked inflammatory infiltrates, myocyte necrosis and fibrosis in atrial biopsies from patients with lone AF, support an association between AF and inflammation.66 Further evidence of a pro-inflammatory state in patients with AF comes from an observed increase in inflammatory markers, such as C-reactive protein (CRP) and interleukin-6 in patients with persistent and permanent AF compared with controls.67,68 Consequently, patients with a higher degree of inflammation observed by higher BNP levels may have greater and more active atrial structural remodeling, thereby hindering SR maintenance.69

Furthermore, high BNP or NT-proBNP levels may predict a greater predisposition to AF recurrences by reflecting increased LA pressure. Atrial arrhythmias frequently occur under conditions associated with atrial dilation.70 The effect of atrial pressure in atrial refractoriness was evaluated in several animal models as well as in humans. Increased atrial pressure results in increased susceptibility to AF that is associated with shortening of the atrial effective refractory period (AERP),71,72 possibly by opening of stretch-activated ion channels.73 Furthermore, atrial conduction delay in patients with paroxysmal AF or patients with diabetes and hypertension was associated with increased LA pressure and impaired left ventricular (LV) relaxation.74 An association between BNP and myocardial stretch, as well as intra-atrial pressures has been well established. In patients with preserved ejection fraction (EF) a significant correlation between NT-proBNP and LA appendage emptying velocity was observed reflecting atrial strain.56 Moreover, in patients with diastolic dysfunction, increased BNP levels have been associated with higher left ventricular end-diastolic pressure (LVEDP) and have been proposed as a diagnostic marker for diastolic dysfunction.75 Elevated LVEDP results in excessive tension in ventricular and also atrial walls, which may stimulate ventricular and atrial BNP production. Therefore, elevated BNP levels in patients with AF may reflect diastolic dysfunction, which is an independent predictor of AF, especially in the elderly.76 The presence and severity of diastolic dysfunction has been repeatedly demonstrated to predict AF development in patients with risk factors for cardiac disease, such as diabetes, and in patients after myocardial infarction.77-79

Atrial Natriuretic Peptide as a Predictor of Atrial Fibrillation Recurrences Post-electrical Cardioversion
The link between ANP or NT-proANP and AF has been equally well established. Patients with AF have higher ANP levels compared with patients in SR,80,81 which usually decrease following ECV and SR restoration.82,83 Elevated ANP levels can predict the development of paroxysmal AF in patients with congestive heart failure84 or following cardiac surgery.85

In accordance with these studies, there is accumulating evidence regarding the role of an assay detecting mid-regional proANP (MR-proANP). Given that NT-proANP has a much longer half-life than mature ANP and is more stable under laboratory conditions,86,87 NT-proANP seems as a more reliable analyte to measure. Available assays for the detection of NT-proANP used an antibody against the N-terminal region combined with a second antibody against either the mid-region or the C-terminal region.88-90 Since under certain conditions, the N-terminal region may be minimally accessible for antibody binding, an immunoassay for the mid-region of proANP was developed in 2004.91 Improvement in analytical performance by MR-proANP assays could improve their ability in identifying patients at increased risk for AF. In the Mälmo Diet and Cancer Study, higher MR-proANP levels predicted incident AF, whereas in the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico - Atrial Fibrillation (GISSI-AF) study, higher MR-proANP levels independently predicted a higher risk for AF recurrence.92,93 Finally, MR-proANP concentration has recently been shown to reliably identify the time from onset of AF to presentation.94

Several studies have examined the association of SR maintenance post-ECV with ANP and NT-proANP levels before the procedure (see Table 2). 51,60,95-100 In half of the existing studies, ANP levels were higher in patients who succeeded in maintaining SR,51,96,99,100 whereas in the other half, ANP levels were lower.60,95,97,98 According to the available evidence, an association between AF recurrences after successful ECV and ANP levels before the procedure cannot be established.

The discrepancies observed in the available studies can be explained considering the mechanism of ANP production in patients with AF. As mentioned, ANP secretion is mainly regulated by mechanical stretching of the atria. This can be reflected in the positive correlation between ANP levels and LA volume, which has been established in several studies using echocardiography and cardiac magnetic resonance.101-104 In accordance with BNP levels, higher ANP levels have been associated with LV diastolic dysfunction and increased filling pressures,105-107 hence patients with higher ANP levels during the acute phase of an episode of persistent AF may be predisposed to an increased risk of AF recurrences.

Apart from between-patient differences, increased ANP levels during an AF episode are probably an acute physiological response to increased atrial pressure.108 Following restoration of SR, plasma ANP concentration is rapidly decreased in conjunction with filling pressures.83 Thereafter, a gradual normalisation of ANP levels is observed concomitantly with atrial mechanical function improvement.109

When SR is not restored and AF becomes long-standing, several morphological changes, termed structural remodeling, ensue in theatrial myocardium. The main changes include interstitial fibrosis and cellular dedifferentiation and apoptosis,110-112 resulting in functional cell loss and reduced ANP production. This inverse association between atrial structural damage and ANP production has been observed in a histopathological study of patients with mitral valve disease,113 and is considered the basis of the inverse association between AF duration and ANP levels.114,115 Hence, in patients with long-standing AF, lower ANP levels reflect pronounced atrial remodeling and would predict a difficulty in maintaining SR following cardioversion.

In conclusion, according to the evidence provided, the use of BNP or NT-proBNP for prediction of long-term response to ECV appears to be useful. Therefore, further research should be done to investigate a cut-off value indicating that SR maintenance is feasible following ECV. Conversely, since ANP concentration can be influenced in an opposing manner by both filling pressure and the extent of structural remodeling, its use as a predictor of AF recurrences is not reasonable, which is also reflected in the relevant studies.

References

  1. Davis RC, Hobbs FD, Kenkre JE, et al. Prevalence of atrial fibrillation in the general population and in high-risk groups: the ECHOES study. Europace 2012;14:1553-9.
    Crossref | Pubmed
  2. Naccarelli GV, Varker H, Lin J, Schulman KL. Increasing prevalence of atrial fibrillation and flutter in the United States. Am J Cardiol 2009;104:1534-9.
    Crossref | Pubmed
  3. Camm AJ, Lip GY, De Caterina R, et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation--developed with the special contribution of the European Heart Rhythm Association. Europace 2012;14:1385-413.
    Crossref | Pubmed
  4. Gall NP, Murgatroyd FD. Electrical cardioversion for AF-the state of the art. Pacing Clin Electrophysiol 2007;30:554-67.
    Crossref | Pubmed
  5. Camm AJ, Kirchhof P, Lip GY, et al. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Europace 2010;12:1360-420.
    Crossref | Pubmed
  6. Kottkamp H. Human atrial fibrillation substrate: towards a specific fibrotic atrial cardiomyopathy. Eur Heart J 2013;34:2731-8.
    Crossref | Pubmed
  7. Kisch B. Electron microscopy of the atrium of the heart. I. Guinea pig. Exp Med Surg 1956;14:99-112.
    Pubmed
  8. de Bold AJ, Borenstein HB, Veress AT, Sonnenberg H. A rapid and potent natriuretic response to intravenous injection of atrial myocardial extract in rats. Life Sci 1981;28:89-94.
    Crossref | Pubmed
  9. Kangawa K, Matsuo H. Purification and complete amino acid sequence of alpha-human atrial natriuretic polypeptide (alpha-hANP). Biochem Biophys Res Commun 1984;118:131-9.
    Crossref | Pubmed
  10. de Bold AJ. Atrial natriuretic factor: a hormone produced by the heart. Science 1985;230:767-70.
    Crossref | Pubmed
  11. Currie MG, Geller DM, Cole BR, et al. Purification and sequence analysis of bioactive atrial peptides (atriopeptins). Science 1984;223:67-9.
    Crossref | Pubmed
  12. Yan W, Wu F, Morser J, Wu Q. Corin, a transmembrane cardiac serine protease, acts as a pro-atrial natriuretic peptide-converting enzyme. Proc Natl Acad Sci U S A 2000;97:8525-9.
    Crossref | Pubmed
  13. Dietz JR. Mechanisms of atrial natriuretic peptide secretion from the atrium. Cardiovasc Res 2005;68:8-17.
    Crossref | Pubmed
  14. Tan AC, Russel FG, Thien T, Benraad TJ. Atrial natriuretic peptide. An overview of clinical pharmacology and pharmacokinetics. Clin Pharmacokinet 1993;24:28-45.
    Crossref | Pubmed
  15. Yandle TG, Richards AM, Nicholls MG, et al. Metabolic clearance rate and plasma half life of alpha-human atrial natriuretic peptide in man. Life Sci 1986;38:1827-33.
    Crossref | Pubmed
  16. Vierhapper H, Gasic S, Nowotny P, Waldhausl W. Renal disposal of human atrial natriuretic peptide in man. Metabolism 1990;39:341-2.
    Crossref | Pubmed
  17. Suresh M, Farrington K. Natriuretic peptides and the dialysis patient. Semin Dial 2005;18:409-19.
    Crossref | Pubmed
  18. Sudoh T, Minamino N, Kangawa K, Matsuo H. Brain natriuretic peptide-32: N-terminal six amino acid extended form of brain natriuretic peptide identified in porcine brain. Biochem Biophys Res Commun 1988;155:726-32.
    Crossref | Pubmed
  19. Daniels LB, Maisel AS. Natriuretic peptides. J Am Coll Cardiol 2007;50:2357-68.
    Crossref | Pubmed
  20. Yasue H, Yoshimura M, Sumida H, et al. Localization and mechanism of secretion of B-type natriuretic peptide in comparison with those of A-type natriuretic peptide in normal subjects and patients with heart failure. Circulation 1994;90:195-203.
    Crossref | Pubmed
  21. Mukoyama M, Nakao K, Hosoda K, et al. Brain natriuretic peptide as a novel cardiac hormone in humans. Evidence for an exquisite dual natriuretic peptide system, atrial natriuretic peptide and brain natriuretic peptide. J Clin Invest 1991;87:1402-12.
    Crossref | Pubmed
  22. Inoue S, Murakami Y, Sano K, et al. Atrium as a source of brain natriuretic polypeptide in patients with atrial fibrillation. J Card Fail 2000;6:92-6.
    Crossref | Pubmed
  23. Mair J. Biochemistry of B-type natriuretic peptide--where are we now? Clin Chem Lab Med 2008;46:1507-14.
    Crossref | Pubmed
  24. Semenov AG, Tamm NN, Seferian KR, et al. Processing of pro-B-type natriuretic peptide: furin and corin as candidate convertases. Clin Chem 2010;56:1166-76.
    Crossref | Pubmed
  25. Hojs R, Bevc S, Ekart R. Biomarkers in hemodialysis patients. Adv Clin Chem 2012;57:29-56.
    Crossref | Pubmed
  26. Wang AY. Clinical utility of natriuretic peptides in dialysis patients. Semin Dial 2012;25:326-33.
    Crossref | Pubmed
  27. Goetze JP, Jensen G, M├©ller S, et al. BNP and N-terminal proBNP are both extracted in the normal kidney. Eur J Clin Invest 2006;36:8-15.
    Crossref | Pubmed
  28. Pidgeon GB, Richards AM, Nicholls MG, et al. Differing metabolism and bioactivity of atrial and brain natriuretic peptides in essential hypertension. Hypertension 1996;27:906- 13.
    Crossref | Pubmed
  29. Kapoun AM, Liang F, O'Young G, et al. B-type natriuretic peptide exerts broad functional opposition to transforming growth factor-beta in primary human cardiac fibroblasts: fibrosis, myofibroblast conversion, proliferation, and inflammation. Circ Res 2004;94:453-61.
    Crossref | Pubmed
  30. Potter LR, Hunter T. Guanylyl cyclase-linked natriuretic peptide receptors: structure and regulation. J Biol Chem 2001;276:6057- 60.
    Crossref | Pubmed
  31. Gardner DG, Chen S, Glenn DJ, Grigsby CL. Molecular biology of the natriuretic peptide system: implications for physiology and hypertension. Hypertension 2007;49:419-26.
    Crossref | Pubmed
  32. Ellinor PT, Low AF, Patton KK, et al. Discordant atrial natriuretic peptide and brain natriuretic peptide levels in lone atrial fibrillation. J Am Coll Cardiol 2005;45:82-6.
    Crossref | Pubmed
  33. Silvet H, Young-Xu Y, Walleigh D, Ravid S. Brain natriuretic peptide is elevated in outpatients with atrial fibrillation. Am J Cardiol 2003;92:1124-7.
    Crossref | Pubmed
  34. Shelton RJ, Clark AL, Goode K, et al. The diagnostic utility of N-terminal pro-B-type natriuretic peptide for the detection of major structural heart disease in patients with atrial fibrillation. Eur Heart J 2006;27:2353-61.
    Crossref | Pubmed
  35. Jourdain P, Bellorini M, Funck F, et al. Short-term effects of sinus rhythm restoration in patients with lone atrial fibrillation: a hormonal study. Eur J Heart Fail 2002;4:263-7.
    Crossref | Pubmed
  36. Wozakowska-Kaplon B. Effect of sinus rhythm restoration on plasma brain natriuretic peptide in patients with atrial fibrillation. Am J Cardiol 2004;93:1555-8.
    Crossref | Pubmed
  37. Ata Y, Turk T, Ay D, et al. Ability of B-type natriuretic peptide in predicting postoperative atrial fibrillation in patients undergoing coronary artery bypass grafting. Heart Surg Forum 2009;12:E211-6.
    Crossref | Pubmed
  38. Iskesen I, Eserdag M, Kurdal AT, et al. Preoperative NT-proBNP levels: a reliable parameter to estimate postoperative atrial fibrillation in coronary artery bypass patients. Thorac Cardiovasc Surg 2011;59:213-6.
    Crossref | Pubmed
  39. Amar D, Zhang H, Shi W, et al. Brain natriuretic peptide and risk of atrial fibrillation after thoracic surgery. J Thorac Cardiovasc Surg 2012;144:1249-53.
    Crossref | Pubmed
  40. Cuthbertson BH, Amiri AR, Croal BL, et al. Utility of B-type natriuretic peptide in predicting perioperative cardiac events in patients undergoing major non-cardiac surgery. Br J Anaesth 2007;99:170-6.
    Crossref | Pubmed
  41. Fan J, Cao H, Su L, et al. NT-proBNP, but not ANP and C-reactive protein, is predictive of paroxysmal atrial fibrillation in patients undergoing pulmonary vein isolation. J Interv Card Electrophysiol 2012;33:93-100.
    Crossref | Pubmed
  42. Hussein AA, Saliba WI, Martin DO, et al. Plasma B-type natriuretic peptide levels and recurrent arrhythmia after successful ablation of lone atrial fibrillation. Circulation 2011;123:2077-82.
    Crossref | Pubmed
  43. Nakazawa Y, Ashihara T, Tsutamoto T, et al. Endothelin-1 as a predictor of atrial fibrillation recurrence after pulmonary vein isolation. Heart Rhythm 2009;6:725-30.
    Crossref | Pubmed
  44. Yamada T, Murakami Y, Okada T, et al. Plasma atrial natriuretic Peptide and brain natriuretic Peptide levels after radiofrequency catheter ablation of atrial fibrillation. Am J Cardiol 2006;97:1741-4.
    Crossref | Pubmed
  45. Ari H, Binici S, Ari S, et al. The predictive value of plasma brain natriuretic peptide for the recurrence of atrial fibrillation six months after external cardioversion. Turk Kardiyol Dern Ars 2008;36:456-60.
    Pubmed
  46. Beck-da-Silva L, de Bold A, Fraser M, et al. Brain natriuretic peptide predicts successful cardioversion in patients with atrial fibrillation and maintenance of sinus rhythm. Can J Cardiol 2004;20:1245-8.
    Pubmed
  47. Falcone C, Buzzi MP, D'Angelo A, et al. Apelin plasma levels predict arrhythmia recurrence in patients with persistent atrial fibrillation. Int J Immunopathol Pharmacol 2010;23:917-25.
    Pubmed
  48. Freynhofer MK, Jarai R, H├Âchtl T, et al. Predictive value of plasma Nt-proBNP and body mass index for recurrence of atrial fibrillation after cardioversion. Int J Cardiol 2011;149:257- 9.
    Crossref | Pubmed
  49. Kallergis EM, Manios EG, Kanoupakis EM, et al. Effect of sinus rhythm restoration after electrical cardioversion on apelin and brain natriuretic Peptide prohormone levels in patients with persistent atrial fibrillation. Am J Cardiol 2010;105:90-4.
    Crossref | Pubmed
  50. Lellouche N, Berthier R, Mekontso-Dessap A, et al. Usefulness of plasma B-type natriuretic peptide in predicting recurrence of atrial fibrillation one year after external cardioversion. Am J Cardiol 2005;95:1380-2.
    Crossref | Pubmed
  51. Mabuchi N, Tsutamoto T, Maeda K, Kinoshita M. Plasma cardiac natriuretic peptides as biochemical markers of recurrence of atrial fibrillation in patients with mild congestive heart failure. Jpn Circ J 2000;64:765-71.
    Crossref | Pubmed
  52. M├Âllmann H, Weber M, Els├ñsser A, et al. NT-ProBNP predicts rhythm stability after cardioversion of lone atrial fibrillation. Circ J 2008;72:921-5.
    Crossref | Pubmed
  53. Shin DI, Jaekel K, Schley P, et al. Plasma levels of NT-pro- BNP in patients with atrial fibrillation before and after electrical cardioversion. Z Kardiol 2005;94:795-800.
    Crossref | Pubmed
  54. Wozakowska-Kaplon B, Opolski G. Exercise-induced natriuretic peptide secretion predicts cardioversion outcome in patients with persistent atrial fibrillation: discordant ANP and B-type natriuretic peptide response to exercise testing. Pacing Clin Electrophysiol 2010;33:1203-9.
    Crossref | Pubmed
  55. Buob A, Jung J, Siaplaouras S, et al. Discordant regulation of CRP and NT-proBNP plasma levels after electrical cardioversion of persistent atrial fibrillation. Pacing Clin Electrophysiol 2006;29:559-63.
    Crossref | Pubmed
  56. Lombardi F, Tundo F, Belletti S, et al. C-reactive protein but not atrial dysfunction predicts recurrences of atrial fibrillation after cardioversion in patients with preserved left ventricular function. J Cardiovasc Med (Hagerstown) 2008;9:581- 8.
    Crossref | Pubmed
  57. Tveit A, Seljeflot I, Grundvold I, et al. Candesartan, NT-proBNP and recurrence of atrial fibrillation after electrical cardioversion. Int J Cardiol 2009;131:234-9.
    Crossref | Pubmed
  58. Watanabe E, Arakawa T, Uchiyama T, et al. High-sensitivity C-reactive protein is predictive of successful cardioversion for atrial fibrillation and maintenance of sinus rhythm after conversion. Int J Cardiol 2006;108:346-53.
    Crossref | Pubmed
  59. Kawamura M, Munetsugu Y, Kawasaki S, et al. Type III procollagen-N-peptide as a predictor of persistent atrial fibrillation recurrence after cardioversion. Europace 2012;14:1719-25.
    Crossref | Pubmed
  60. Govindan M, Borgulya G, Kiotsekoglou A, et al. Prognostic value of left atrial expansion index and exercise-induced change in atrial natriuretic peptide as long-term predictors of atrial fibrillation recurrence. Europace 2012;14:1302-10.
    Crossref | Pubmed
  61. Barassi A, Pezzilli R, Morselli-Labate AM, et al. Serum amyloid a and C-reactive protein independently predict the recurrences of atrial fibrillation after cardioversion in patients with preserved left ventricular function. Can J Cardiol 2012;28:537-41.
    Crossref | Pubmed
  62. Tang Y, Yang H, Qiu J. Relationship between brain natriuretic peptide and recurrence of atrial fibrillation after successful electrical cardioversion: a meta-analysis. J Int Med Res 2011;39:1618-24.
    Crossref | Pubmed
  63. Guo Y, Lip GY, Apostolakis S. Inflammation in atrial fibrillation. J Am Coll Cardiol 2012;60:2263-70.
    Crossref | Pubmed
  64. Ma KK, Ogawa T, de Bold AJ. Selective upregulation of cardiac brain natriuretic peptide at the transcriptional and translational levels by pro-inflammatory cytokines and by conditioned medium derived from mixed lymphocyte reactions via p38 MAP kinase. J Mol Cell Cardiol 2004;36:505-13.
    Crossref | Pubmed
  65. de Bold AJ. Cardiac natriuretic peptides gene expression and secretion in inflammation. J Investig Med 2009;57:29-32.
    Crossref | Pubmed
  66. Ozaydin M. Atrial fibrillation and inflammation. World J Cardiol 2010;2:243-50.
    Crossref | Pubmed
  67. Conway DS, Buggins P, Hughes E, Lip GY. Relationship of interleukin-6 and C-reactive protein to the prothrombotic state in chronic atrial fibrillation. J Am Coll Cardiol 2004;43:2075-82.
    Crossref | Pubmed
  68. Psychari SN, Apostolou TS, Sinos L, et al. Relation of elevated C-reactive protein and interleukin-6 levels to left atrial size and duration of episodes in patients with atrial fibrillation. Am J Cardiol 2005;95:764-7.
    Crossref | Pubmed
  69. Rudolph V, Andri├® RP, Rudolph TK, et al. Myeloperoxidase acts as a profibrotic mediator of atrial fibrillation. Nat Med 2010;16:470-4.
    Crossref | Pubmed
  70. Solti F, Vecsey T, K├®kesi V, Juh├ísz-Nagy A. The effect of atrial dilatation on the genesis of atrial arrhythmias. Cardiovasc Res 1989;23:882-6.
    Crossref | Pubmed
  71. Calkins H, el-Atassi R, Kalbfleisch S, et al. Effects of an acute increase in atrial pressure on atrial refractoriness in humans. Pacing Clin Electrophysiol 1992;15:1674-80.
    Crossref | Pubmed
  72. Ravelli F, Allessie M. Effects of atrial dilatation on refractory period and vulnerability to atrial fibrillation in the isolated Langendorff-perfused rabbit heart. Circulation 1997;96:1686-95.
    Crossref | Pubmed
  73. Bode F, Sachs F, Franz MR. Tarantula peptide inhibits atrial fibrillation. Nature 2001;409:35-6.
    Crossref | Pubmed
  74. Vranka I, Penz P, Dukat A. Atrial conduction delay and its association with left atrial dimension, left atrial pressure and left ventricular diastolic dysfunction in patients at risk of atrial fibrillation. Exp Clin Cardiol 2007;12:197-201.
    Pubmed
  75. Lubien E, DeMaria A, Krishnaswamy P, et al. Utility of B-natriuretic peptide in detecting diastolic dysfunction: comparison with Doppler velocity recordings. Circulation 2002;105:595-601.
    Crossref | Pubmed
  76. Tsang TS, Gersh BJ, Appleton CP, et al. Left ventricular diastolic dysfunction as a predictor of the first diagnosed nonvalvular atrial fibrillation in 840 elderly men and women. J Am Coll Cardiol 2002;40:1636-44.
    Crossref | Pubmed
  77. From AM, Scott CG, Chen HH. The development of heart failure in patients with diabetes mellitus and pre-clinical diastolic dysfunction a population-based study. J Am Coll Cardiol 2010;55:300-5.
    Crossref | Pubmed
  78. Jons C, Joergensen RM, Hassager C, et al. Diastolic dysfunction predicts new-onset atrial fibrillation and cardiovascular events in patients with acute myocardial infarction and depressed left ventricular systolic function: a CARISMA substudy. Eur J Echocardiogr 2010;11:602-7.
    Crossref | Pubmed
  79. Tsang TS, Barnes ME, Gersh BJ, et al. Risks for atrial fibrillation and congestive heart failure in patients >/=65 years of age with abnormal left ventricular diastolic relaxation. Am J Cardiol 2004;93:54-8.
    Crossref | Pubmed
  80. Wallen T, Landahl S, Hedner T, et al. Atrial peptides, ANP(1- 98) and ANP(99-126) in health and disease in an elderly population. Eur Heart J 1993;14:1508-13.
    Crossref | Pubmed
  81. Rossi A, Enriquez-Sarano M, Burnett JC Jr, et al. Natriuretic peptide levels in atrial fibrillation: a prospective hormonal and Doppler-echocardiographic study. J Am Coll Cardiol 2000;35:1256-62.
    Crossref | Pubmed
  82. Lechleitner P, Genser N, Hauptlorenz S, et al. [Values of atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate (cGMP) in cardioversion]. Z Kardiol 1991;80:574-9.
    Pubmed
  83. Arakawa M, Miwa H, Noda T, et al. Alternations in atrial natriuretic peptide release after DC cardioversion of nonvalvular chronic atrial fibrillation. Eur Heart J 1995;16:977-85.
    Pubmed
  84. Yamada T, Fukunami M, Shimonagata T, et al. Prediction of paroxysmal atrial fibrillation in patients with congestive heart failure: a prospective study. J Am Coll Cardiol 2000;35:405-13.
    Crossref | Pubmed
  85. Yilmaz MB, Erbay AR, Balci M, et al. Atrial natriuretic peptide predicts impaired atrial remodeling and occurrence of late postoperative atrial fibrillation after surgery for symptomatic aortic stenosis. Cardiology 2006;105:207-12.
    Crossref | Pubmed
  86. Davidson NC, Coutie WJ, Struthers AD. N-terminal proatrial natriuretic peptide and brain natriuretic peptide are stable for up to 6 hours in whole blood in vitro. Circulation 1995;91:1276-7.
    Pubmed
  87. Hall C, Aaberge L, Stokke O. In vitro stability of N-terminal proatrial natriuretic factor in unfrozen samples: an important prerequisite for its use as a biochemical parameter of atrial pressure in clinical routine. Circulation 1995;91:911.
    Pubmed
  88. Missbichler A, Hawa G, Schmal N, Woloszczuk W. Sandwich ELISA for proANP 1-98 facilitates investigation of left ventricular dysfunction. Eur J Med Res 2001;6:105-11.
    Pubmed
  89. Stridsberg M, Pettersson T, Pettersson K. A two-site delfia immunoassay for measurements of the N-terminal peptide of pro-atrial natriuretic peptide (nANP). Ups J Med Sci 1997;102:99- 108.
    Crossref | Pubmed
  90. Numata Y, Dohi K, Furukawa A, et al. Immunoradiometric assay for the N-terminal fragment of proatrial natriuretic peptide in human plasma. Clin Chem 1998;44:1008-13.
    Pubmed
  91. Morgenthaler NG, Struck J, Thomas B, Bergmann A. Immunoluminometric assay for the midregion of pro-atrial natriuretic peptide in human plasma. Clin Chem 2004;50:234-6.
    Crossref | Pubmed
  92. Latini R, Masson S, Pirelli S, et al. Circulating cardiovascular biomarkers in recurrent atrial fibrillation: data from the GISSI-atrial fibrillation trial. J Intern Med 2011;269:160-71.
    Crossref | Pubmed
  93. Smith JG, Newton-Cheh C, Almgren P, et al. Assessment of conventional cardiovascular risk factors and multiple biomarkers for the prediction of incident heart failure and atrial fibrillation. J Am Coll Cardiol 2010;56:1712-9.
    Crossref | Pubmed
  94. Meune C, Vermillet A, Wahbi K, et al. Mid-regional pro atrial natriuretic peptide allows the accurate identification of patients with atrial fibrillation of short time of onset: a pilot study. Clin Biochem 2011;44:1315-9.
    Crossref | Pubmed
  95. Van Den Berg MP, Crijns HJ, Van Veldhuisen DJ, et al. Effects of lisinopril in patients with heart failure and chronic atrial fibrillation. J Card Fail 1995;1:355-63.
    Crossref | Pubmed
  96. Theodorakis GN, Markianos M, Kouroubetsis CK, et al. Clinical, adrenergic and heart endocrine measures in chronic atrial fibrillation as predictors of conversion and maintenance of sinus rhythm after direct current cardioversion. Eur Heart J 1996;17:550-6.
    Crossref | Pubmed
  97. Wozakowska-Kaplon B, Opolski G. Effects of sinus rhythm restoration in patients with persistent atrial fibrillation: a clinical, echocardiographic and hormonal study. Int J Cardiol 2004;96:171-6.
    Crossref | Pubmed
  98. Thomas MD, Kalra PR, Jones A, et al. Time course for recovery of atrial mechanical and endocrine function post DC cardioversion for persistent atrial fibrillation. Int J Cardiol 2005;102:487-91.
    Crossref | Pubmed
  99. Kim SK, Pak HN, Park JH, et al. Clinical and serological predictors for the recurrence of atrial fibrillation after electrical cardioversion. Europace 2009;11:1632-8.
    Crossref | Pubmed
  100. Bartkowiak R, Wozakowska-Kaplon B, Janiszewska G. ┬║Plasma NT-proANP in patients with persistent atrial fibrillation who underwent successful cardioversion. Kardiol Pol 2010;68:48-54.
    Pubmed
  101. Tripepi G, Mattace-Raso F, Mallamaci F, et al. Biomarkers of left atrial volume: a longitudinal study in patients with end stage renal disease. Hypertension 2009;54:818-24.
    Crossref | Pubmed
  102. Wozakowska-Kaplon B, Opolski G. Effects of exercise testing on natriuretic peptide secretion in patients with atrial fibrillation. Kardiol Pol 2009;67:254-61.
    Pubmed
  103. Wozakowska-Kaplon B, Opolski G, Herman Z, Kosior D. Natriuretic peptides in patients with atrial fibrillation. Cardiol J 2008;15:525-9.
    Pubmed
  104. Therkelsen SK, Groenning BA, Kjaer A, et al. ANP and BNP in atrial fibrillation before and after cardioversion--and their relationship to cardiac volume and function. Int J Cardiol 2008;127:396-9.
    Crossref | Pubmed
  105. Bakowski D, Wozakowska-Kaplon B, Opolski G. The influence of left ventricle diastolic function on natriuretic peptides levels in patients with atrial fibrillation. Pacing Clin Electrophysiol 2009;32:745-52.
    Crossref | Pubmed
  106. Grandi AM, Laurita E, Selva E, et al. Natriuretic peptides as markers of preclinical cardiac disease in obesity. Eur J Clin Invest 2004;34:342-8.
    Crossref | Pubmed
  107. Yu CM, Sanderson JE, Shum IO, et al. Diastolic dysfunction and natriuretic peptides in systolic heart failure. Higher ANP and BNP levels are associated with the restrictive filling pattern. Eur Heart J 1996;17:1694-702.
    Crossref | Pubmed
  108. Roy D, Paillard F, Cassidy D, et al. Atrial natriuretic factor during atrial fibrillation and supraventricular tachycardia. J Am Coll Cardiol 1987;9:509-14.
    Crossref | Pubmed
  109. 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;41:1716-20.
    Crossref | Pubmed
  110. Thijssen VL, Ausma J, Borgers M. Structural remodelling during chronic atrial fibrillation: act of programmed cell survival. Cardiovasc Res 2001;52:14-24.
    Crossref | Pubmed
  111. Goudis CA, Kallergis EM, Vardas PE. Extracellular matrix alterations in the atria: insights into the mechanisms and perpetuation of atrial fibrillation. Europace 2012;14:623-30.
    Crossref | Pubmed
  112. De Jong AM, Maass AH, Oberdorf-Maass SU, et al. Mechanisms of atrial structural changes caused by stretch occurring before and during early atrial fibrillation. Cardiovasc Res 2011;89:754-65.
    Crossref | Pubmed
  113. Nagata M, Hiroe M, Naruse M, et al. An integrated study employing histopathological, immunohistocytochemical and radioimmunoassay analyses of atrial natriuretic peptide in the right and left atria in patients with mitral valve disease. Jpn Circ J 1988;52:1453-6.
    Crossref | Pubmed
  114. van den Berg MP, Tjeerdsma G, Jan de Kam P, et al. Longstanding atrial fibrillation causes depletion of atrial natriuretic peptide in patients with advanced congestive heart failure. Eur J Heart Fail 2002;4:255-62.
    Crossref | Pubmed
  115. van den Berg MP, van Gelder IC, van Veldhuisen DJ. Depletion of atrial natriuretic peptide during longstanding atrial fibrillation. Europace 2004;6:433-7.
    Crossref | Pubmed
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