Objectives: We hypothesised that high-sensitivity troponin I (hs-TnI) might predict long-term rhythm outcome after cardioversion for persistent atrial fibrillation (AF), and that maintenance of sinus rhythm and/or treatment with the angiotensin II type 1 receptor blocker candesartan would reduce hs-TnI levels. Methods: In a double-blind, placebo-controlled study, 171 patients referred for electrical cardioversion for AF were randomised to receive candesartan or placebo for 3-6 weeks before cardioversion and for 6 months after electrical cardioversion. Blood samples for analysis of hs-TnI (Abbott Diagnostics) were available in 129 patients at baseline and in 60 successfully cardioverted patients at study end. Results: Hs-TnI was detectable in all subjects, with a median value of 5.3 ng/l (25th percentile 3.7, 75th percentile 7.2). hs-TnI at baseline was not predictive of rhythm outcome 6 months after electrical cardioversion for persistent AF. Treatment with candesartan did not influence the levels of hs-TnI. hs-TnI was unchanged from baseline to study end in patients who maintained sinus rhythm [4.9 (3.7, 7.0) and 5.0 (4.0, 6.4) ng/l, respectively; p = 0.699). Conclusions: hs-TnI did not predict AF recurrence after cardioversion. hs-TnI levels were unchanged in patients maintaining sinus rhythm for 6 months after electrical cardioversion. hs-TnI levels were not influenced by treatment with candesartan.

Keywords:
Atrial fibrillation, Cardioversion, High-sensitivity troponin I, Angiotensin II type I receptor blocker
1.
Hussein AA, Bartz TM, Gottdiener JS, Sotoodehnia N, Heckbert SR, Lloyd-Jones D, Kizer JR, Christenson R, Wazni O, deFilippi C: Serial measures of cardiac troponin T levels by a highly sensitive assay and incident atrial fibrillation in a prospective cohort of ambulatory older adults. Heart Rhythm 2015;12:879-885.
2.
Rienstra M, Yin X, Larson MG, Fontes JD, Magnani JW, McManus DD, McCabe EL, Coglianese EE, Amponsah M, Ho JE, Januzzi JL Jr, Wollert KC, Fradley MG, Vasan RS, Ellinor PT, Wang TJ, Benjamin EJ: Relation between soluble ST2, growth differentiation factor-15, and high-sensitivity troponin I and incident atrial fibrillation. Am Heart J 2014;167:109-115.
3.
Filion KB, Agarwal SK, Ballantyne CM, Eberg M, Hoogeveen RC, Huxley RR, Loehr LR, Nambi V, Soliman EZ, Alonso A: High-sensitivity cardiac troponin T and the risk of incident atrial fibrillation: the Atherosclerosis Risk in Communities (ARIC) study. Am Heart J 2015;169:31-38.
4.
Hijazi Z, Oldgren J, Andersson U, Connolly SJ, Ezekowitz MD, Hohnloser SH, Reilly PA, Vinereanu D, Siegbahn A, Yusuf S, Wallentin L: Cardiac biomarkers are associated with an increased risk of stroke and death in patients with atrial fibrillation: a Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) substudy. Circulation 2012;125:1605-1616.
5.
Hijazi Z, Siegbahn A, Andersson U, Granger CB, Alexander JH, Atar D, Gersh BJ, Mohan P, Harjola VP, Horowitz J, Husted S, Hylek EM, Lopes RD, McMurray JJ, Wallentin L: High-sensitivity troponin I for risk assessment in patients with atrial fibrillation: insights from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial. Circulation 2014;129:625-634.
6.
van den Bos EJ, Constantinescu AA, van Domburg RT, Akin S, Jordaens LJ, Kofflard MJ: Minor elevations in troponin I are associated with mortality and adverse cardiac events in patients with atrial fibrillation. Eur Heart J 2011;32:611-617.
7.
Latini R, Masson S, Pirelli S, Barlera S, Pulitano G, Carbonieri E, Gulizia M, Vago T, Favero C, Zdunek D, Struck J, Staszewsky L, Maggioni AP, Franzosi MG, Disertori M: Circulating cardiovascular biomarkers in recurrent atrial fibrillation: data from the GISSI-atrial fibrillation trial. J Intern Med 2011;269:160-171.
8.
Abu-El-Haija B, Giudici MC: Predictors of long-term maintenance of normal sinus rhythm after successful electrical cardioversion. Clin Cardiol 2014;37:381-385.
9.
Tveit A, Seljeflot I, Grundvold I, Abdelnoor M, Smith P, Arnesen H: Effect of candesartan and various inflammation markers on maintenance of sinus rhythm after electrical cardioversion for atrial fibrillation. Am J Cardiol 2007;99:1544-1548.
10.
Celebi OO, Celebi S, Canbay A, Ergun G, Aydogdu S, Diker E: The effect of sinus rhythm restoration on high-sensitivity C-reactive protein levels and their association with long-term atrial fibrillation recurrence after electrical cardioversion. Cardiology 2011;118:168-174.
11.
Masson S, Aleksova A, Favero C, Staszewsky L, Bernardinangeli M, Belvito C, Cioffi G, Sinagra G, Mazzone C, Bertocchi F, Vago T, Peri G, Cuccovillo I, Masuda N, Barlera S, Mantovani A, Maggioni AP, Franzosi MG, Disertori M, Latini R: Predicting atrial fibrillation recurrence with circulating inflammatory markers in patients in sinus rhythm at high risk for atrial fibrillation: data from the GISSI-atrial fibrillation trial. Heart 2010;96:1909-1914.
12.
Tveit A, Seljeflot I, Grundvold I, Abdelnoor M, Smith P, Arnesen H: Levels of PAI-1 and outcome after electrical cardioversion for atrial fibrillation. Thromb Res 2008;121:447-453.
13.
Mollmann H, Weber M, Elsasser A, Nef H, Dill T, Rixe J, Schmitt J, Sperzel J, Hamm CW: NT-proBNP predicts rhythm stability after cardioversion of lone atrial fibrillation. Circ J 2008;72:921-925.
14.
Tveit A, Seljeflot I, Grundvold I, Abdelnoor M, Arnesen H, Smith P: Candesartan, NT-proBNP and recurrence of atrial fibrillation after electrical cardioversion. Int J Cardiol 2009;131:234-239.
15.
Therkelsen SK, Groenning BA, Kjaer A, Svendsen JH, Jensen GB: ANP and BNP in atrial fibrillation before and after cardioversion - and their relationship to cardiac volume and function. Int J Cardiol 2008;127:396-399.
16.
Ulimoen SR, Enger S, Norseth J, Pripp AH, Abdelnoor M, Arnesen H, Gjesdal K, Tveit A: Improved rate control reduces cardiac troponin T levels in permanent atrial fibrillation. Clin Cardiol 2014;37:422-427.
17.
Goette A, Bukowska A, Lendeckel U, Erxleben M, Hammwohner M, Strugala D, Pfeiffenberger J, Rohl FW, Huth C, Ebert MP, Klein HU, Rocken C: Angiotensin II receptor blockade reduces tachycardia-induced atrial adhesion molecule expression. Circulation 2008;117:732-742.
18.
Kumagai K, Nakashima H, Urata H, Gondo N, Arakawa K, Saku K: Effects of angiotensin II type 1 receptor antagonist on electrical and structural remodeling in atrial fibrillation. J Am Coll Cardiol 2003;41:2197-2204.
19.
Fogari R, Mugellini A, Zoppi A, Preti P, Destro M, Lazzari P, Derosa G: Effect of telmisartan and ramipril on atrial fibrillation recurrence and severity in hypertensive patients with metabolic syndrome and recurrent symptomatic paroxysmal and persistent atrial fibrillation. J Cardiovasc Pharmacol Ther 2012;17:34-43.
20.
Tveit A, Grundvold I, Olufsen M, Seljeflot I, Abdelnoor M, Arnesen H, Smith P: Candesartan in the prevention of relapsing atrial fibrillation. Int J Cardiol 2007;120:85-91.
21.
Apple FS, Ler R, Murakami MM: Determination of 19 cardiac troponin I and T assay 99th percentile values from a common presumably healthy population. Clin Chem 2012;58:1574-1581.
22.
Omland T, Pfeffer MA, Solomon SD, de Lemos JA, Rosjo H, Saltyte Benth J, Maggioni A, Domanski MJ, Rouleau JL, Sabatine MS, Braunwald E: Prognostic value of cardiac troponin I measured with a highly sensitive assay in patients with stable coronary artery disease. J Am Coll Cardiol 2013;61:1240-1249.
23.
Hijazi Z, Siegbahn A, Andersson U, Lindahl B, Granger CB, Alexander JH, Atar D, Gersh BJ, Hanna M, Harjola VP, Horowitz J, Husted S, Hylek EM, Lopes RD, McMurray JJ, Wallentin L: Comparison of cardiac troponins I and T measured with high-sensitivity methods for evaluation of prognosis in atrial fibrillation: an ARISTOTLE substudy. Clin Chem 2015;61:368-378.
24.
Bugnicourt JM, Rogez V, Guillaumont MP, Rogez JC, Canaple S, Godefroy O: Troponin levels help predict new-onset atrial fibrillation in ischaemic stroke patients: a retrospective study. Eur Neurol 2010;63:24-28.
25.
Lim HS, Schultz C, Dang J, Alasady M, Lau DH, Brooks AG, Wong CX, Roberts-Thomson KC, Young GD, Worthley MI, Sanders P, Willoughby SR: Time course of inflammation, myocardial injury, and prothrombotic response after radiofrequency catheter ablation for atrial fibrillation. Circ Arrhythm Electrophysiol 2014;7:83-89.
26.
Aksu T, Golcuk SE, Guler TE, Yalin K, Erden I: Prediction of mid-term outcome after cryo-balloon ablation of atrial fibrillation using post-procedure high-sensitivity troponin level. Cardiovasc J Afr 2015;26:1-6.
27.
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.
28.
Savelieva I, Kakouros N, Kourliouros A, Camm AJ: Upstream therapies for management of atrial fibrillation: review of clinical evidence and implications for European Society of Cardiology guidelines. I. Primary prevention. Europace 2011;13:308-328.
29.
White HD: Pathobiology of troponin elevations: do elevations occur with myocardial ischemia as well as necrosis? J Am Coll Cardiol 2011;57:2406-2408.
30.
McDonough JL, Arrell DK, Van Eyk JE: Troponin I degradation and covalent complex formation accompanies myocardial ischemia/reperfusion injury. Circ Res 1999;84:9-20.
31.
Bergmann O, Bhardwaj RD, Bernard S, Zdunek S, Barnabe-Heider F, Walsh S, Zupicich J, Alkass K, Buchholz BA, Druid H, Jovinge S, Frisen J: Evidence for cardiomyocyte renewal in humans. Science 2009;324:98-102.
32.
Bergmann O, Jovinge S: Cardiac regeneration in vivo: mending the heart from within? Stem Cell Res 2014;13:523-531.
33.
Hickman PE, Potter JM, Aroney C, Koerbin G, Southcott E, Wu AH, Roberts MS: Cardiac troponin may be released by ischemia alone, without necrosis. Clin Chim Acta 2010;411:318-323.
34.
Feng J, Schaus BJ, Fallavollita JA, Lee TC, Canty JM Jr: Preload induces troponin I degradation independently of myocardial ischemia. Circulation 2001;103:2035-2037.
35.
Hijazi Z, Oldgren J, Andersson U, Connolly SJ, Ezekowitz MD, Hohnloser SH, Reilly PA, Siegbahn A, Yusuf S, Wallentin L: Importance of persistent elevation of cardiac biomarkers in atrial fibrillation: a RE-LY substudy. Heart 2014;100:1193-1200.
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2015
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