BACKGROUND: Association between clinical effect and serum concentration of amiodarone (AMI) and its active metabolite desethylamidarone (DEA) in patients after surgical ablation (SA) of atrial fibrillation (AF) has not yet been studied. AIMS: We wanted to find a correlation between AMI and DEA serum concentration and maintaining sinus rhythm (SR) after SA of AF. METHODS: Sixty eight patients with AF who had undergone surgical ablation between 2014 and 2017 were included in a single-centre, prospective, observational study. Maintaining of SR was evaluated by standard 12-lead ECG and 24-hour Holter ECG monitoring at months 1, 3, 6 and 12 following surgery. Therapeutic monitoring of AMI and DEA concentrations was done to optimize therapy and adverse effects were followed up. RESULTS: We have noticed a high success rate in maintaining of SR (overall 83%). The median of serum concentration of AMI was 0.81 mg/L (range 0.16-2.35 mg/L) and DEA 0.70 mg/l (range 0.19-2.63 mg/L). No significant differences were found in the serum concentratration of AMI, DEA or DEA/AMI concentratration ratios between patients with SR and persistent supraventricular tachyarrhythmia except on the second outpatient visit. We observed significant correlation between serum concentration of DEA and thyroid-stimulating hormone elevation. CONCLUSION: We confirmed the efficacy of AMI and DEA at the measured serum concentrations. However, analysis of these concentrations alone cannot replace assessment of the clinical response for treatment. Establishment of individual AMI (and DEA) concentrations at which the optimal therapeutic response is achieved seems to be advantageous. Therapeutic monitoring of AMI and DEA is helpful in personalised pharmacotherapy after SA of AF.

Department of Cardiac Surgery University Hospital Ostrava 17 Listopadu 1790 708 52 Ostrava Czech Republic

Department of Clinic Subjects Faculty of Medicine University of Ostrava Syllabova 19 703 00 Ostrava Czech Republic

Department of Clinical Pharmacology Department of Laboratory Medicine University Hospital Ostrava 17 Listopadu 1790 708 52 Ostrava Czech Republic

Department of Clinical Pharmacology Faculty of Medicine University of Ostrava Syllabova 19 703 00 Ostrava Czech Republic

Zobrazit více v PubMed

Ad N., Holmes S.D., Shuman D.J., Pritchard G., Miller C.E. Amiodarone after surgical ablation for atrial fibrillation: Is it really necessary? A prospective randomized controlled trial. J. Thorac. Cardiovasc. Surg. 2016;151:798–803. doi: 10.1016/j.jtcvs.2015.07.034. Epub 2015 Jul 17. PubMed DOI

Altman R.K., Proietti R., Barrett C.D., Paoletti Perini A., Santangeli P., Danik S.B., Di Biase L., Natale A. Management of refractory atrial fibrillation post surgical ablation. Ann. Cardiothorac. Surg. 2014;3:91–97. doi: 10.3978/j.issn.2225-319X.2013.12.08. PubMed DOI PMC

Anastasiou-Nana M., Koutras D.A., Levis G., Souvatzoglou A., Boukis M.A., Moulopoulos S.D. The correlation of serum amiodarone levels with abnormalities in the metabolism of tyroxine. J. Endocrinol. Invest. 1984;7:405–407. PubMed

Barta J., Brat R. Assessment of the effect of left atrial cryoablation enhanced by ganglionated plexi ablation in the treatment of atrial fibrillation in patients undergoing open heart surgery. J. Cardiothorac. Surg. 2017;12:69. doi: 10.1186/s13019-017-0625-1. PubMed DOI PMC

Bogazzi F., Bartalena L., Brogioni S., Burelli A., Raggi F., Ultimieri F., Cosci C., Vitale M., Fenzi G., Martino E. Desethylamiodarone antagonizes the effect of thyroid hormone at the molecular level. Eur. J. Endocrinol. 2001;145:59–64. PubMed

Calkins, H., Hindricks, G., Cappato, R., Kim, Z.H., Saad, E.B., Aguinaga, L., Akar, J.G., Badhwar, V., Brugada, J., Camm, J., Chen, P.S., Chen, S.A., Chung, M.K., Nielsen, J.C., Curtis, A.B., Davies, D.W., Day, J.D., d’Avila, A., de Groot, N.M.S.N., Di Biase, L., Duytschaever, M., Edgerton, J.R., Ellenbogen, K.A., Ellinor, P.T., Ernst, S., Fenelon, G., Gerstenfeld, E.P., Haines, D.E., Haissaguerre, M., Helm, R.H., Hylek, E., Jackman, W.M., Jalife, J., Kalman, J.M., Kautzner, J., Kottkamp, H., Kuck, K.H., Kumagai, K., Lee, R., Lewalter, T., Lindsay, B.D., Macle, L., Mansour, M., Marchlinski, F.E., Michaud, G.F., Nakagawa, H., Natale, A., Nattel, S., Okumura, K., Packer, D., Pokushalov, E., Reynolds, M.R., Sanders, P., Scanavacca, M., Schilling, R., Tondo, C., Tsao, H.M., Verma, A., Wilber, D.J., Yamane, T., 2017. 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: Executive summary. J. Arrhythm. 33, 369-409. https://doi: 10.1016/j.joa.2017.08.001. Epub 2017 Sep 15. PubMed

Calkins H., Hindricks G., Cappato R., Kim Z.H., Saad E.B., Aguinaga L., Akar J.G., Badhwar V., Brugada J., Camm J., Chen P.S., Chen S.A., Chung M.K., Nielsen J.C., Curtis A.B., Davies D.W., Day J.D., d’Avila A., de Groot N.M.S.N., Di Biase L., Duytschaever M., Edgerton J.R., Ellenbogen K.A., Ellinor P.T., Ernst S., Fenelon G., Gerstenfeld E.P., Haines D.E., Haissaguerre M., Helm R.H., Hylek E., Jackman W.M., Jalife J., Kalman J.M., Kautzner J., Kottkamp H., Kuck K.H., Kumagai K., Lee R., Lewalter T., Lindsay B.D., Macle L., Mansour M., Marchlinski F.E., Michaud G.F., Nakagawa H., Natale A., Nattel S., Okumura K., Packer D., Pokushalov E., Reynolds M.R., Sanders P., Scanavacca M., Schilling R., Tondo C., Tsao H.M., Verma A., Wilber D.J., Yamane T. HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation. Europace. 2018. 2017;20:1–160. doi: 10.1093/europace/eux274. PubMed DOI PMC

Connolly S.J., Gupta R.N., Hoffert D., Roberts R.S. Concentration response relationships of amiodarone and desethylamiodarone. Am. Heart. J. 1988;115:1208–1213. PubMed

Cox, J.L., Churyla, A., Malaisrie, S.Ch., Kruse, J., Pham, D.T., Kislitsina, O.N., McCarthy, P.M., 2018. When Is a Maze Procedure a Maze Procedure? Can. J. Cardiol. 11, 1482-1491. https://doi: 10.1016/j.cjca.2018.05.008. Epub 2018 Jun 20. PubMed

Gillis, A.M., 2016. Guidelines for Potassium Channel Blocker Use. Card. Electrophysiol. Clin. 8, 495-501. https://doi: 10.1016/j.ccep.2016.02.010. Epub 2016 Mar 14. PubMed

Greenberg M.L., Lerman B.B., Shipe J.R., Kaiser D.L., DiMarco J.P. Relation between amiodarone and desethylamiodarone plasma concentrations and electrophysiologic effects, efficacy and toxicity. J. Am. Coll. Cardiol. 1987;9:1148–1155. PubMed

Haffajee C.I., Love J.C., Canada A.T., Lesko L.J., Asdourian G., Alpert J.S. Clinical pharmacokinetics and efficacy of amiodarone for refractory tachyarrhythmias. Circulation. 1983;67:1347–1355. PubMed

Hrudikova Vyskocilova, E., Grundmann, M., Duricova, J., Kacirova, I., 2017. Therapeutic monitoring of amiodarone: pharmacokinetics and evaluation of the relationship between effect and dose/concentration. Biomed. Pap. Med. Fac. Univ. Palacky. Olomouc Czech Repub. 161, 134-143. https://doi:10.5507/bp.2017.016. Epub 2017 Mar 31. PubMed

Kaski J.C., Girotti L.A., Messuti H., Rutitzky B., Rosenbaum M.B. Long-term management of sustained, recurrent, symptomatic ventricular tachycardia with amiodarone. Circulation. 1981;64:273–279. PubMed

Kirchhof, P., Benussi, S., Kotecha, D., Ahlsson, A., Atar, D., Casadei, B., Castellá, M., Diener, H.C., Heidbuchel, H., Hendriks, J., Hindricks, G., Manolis, A.S., Oldgren, J., Alexandru Popescu, B., Schotten, U., Van Putte, B., Vardas, P., 2016. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur. Heart. J. 37, 2893-2962. https://doi:10.1093/eurheartj/ehw210. Epub 2016 Aug 27 PubMed

Kolek M., Brat R. Cardiac rhythm and atrial transport function after surgical ablation of atrial fibrillation using cryoenergy: predictors and effectiveness of the procedure. Biomed. Pap. Med. Fac. Univ. Palacky Olomouc Czech Repub. 2010;154:55–68. PubMed

Kumar K., Zimetbaum P.J. Antiarrhythmic drugs 2013: state of the art. Curr. Cardiol. Rep. 2013;15:410. https://doi:10.1007/s11886-013-0410-2 PubMed

Lafuente-Lafuente, C., Alvarez, J.C., Leenhardt, A., Mouly, S., Extramiana, F., Caulin, C., Funck-Brentano, C., Bergmann, J.F., 2009. Amiodarone concentrations in plasma and fat tissue during chronic treatment and related toxicity. Br. J. Clin. Pharmacol. 67, 511-519. https://doi:10.1111/j.1365-2125.2009.03381.x. Epub 2009 Feb 2. PubMed PMC

Mostow N.D., Rakita L., Vrobel T.R., Noon D.L., Blumer J. Amiodarone: correlation of serum concentration with suppression of complex ventricular ectopic aktivity. Am. J. Cardiol. 1984;54:569–574. PubMed

Mostow N.D., Vrobel T.R., Noon D., Rakita L. Rapid suppression of refractory ventricular arrhythmias with high-dose oral amiodarone. Circulation. 1986;73:1231–1238. PubMed

Nielsen K.D., Møller S. Amiodarone for rapid cardioversion of chronic atrial tachyarrhythmia? Pharmacol. Toxicol. 2000;86:283–286. PubMed

Rotmensch H.H., Swanson B.N., Greenspon A.J., Shoshani D., Greenspan A.M. Amiodarone: individualizing dosage with serum concentrations. Pacing. Clin. Electrophysiol. 1983;6:1327–1335. PubMed

Rotmensch H.H., Belhassen B., Swanson B.N., Shoshani D., Spielman S.R., Greenspon A.J., Greenspan A.M., Vlasses P.H., Horowitz L.N. Steady-state serum amiodarone concentrations: relationships with antiarrhythmic efficacy and toxicity. Ann. Intern. Med. 1984;101:462–469. PubMed

Saksena S., Rothbart S.T., Cappello G. Chronic effects of amiodarone in patients with refraktory ventricular tachycardia. Int. J. Cardiol. 1983;3:339–352. PubMed

Stäubli M., Bircher J., Galeazzi R.L., Remund H., Studer H. Serum concentrations of amiodarone during long term therapy. Relation to dose, efficacy and toxicity. Eur. J. Clin. Pharmacol. 1983;24:485–494. PubMed

Tieleman R.G., Gosselink A.T., Crijns H.J., van Gelder I.C., van den Berg M.P., de Kam P.J., van Gilst W.H., Lie K.I. Efficacy, safety, and determinants of conversion of atrial fibrillation and flutter with oral amiodarone. Am. J. Cardiol. 1997;79:53–57. PubMed

Yamato, M., Wada, K., Fujimoto, M., Hosomi, K., Hayashi, T., Oita, A., Takada, M., 2017. Association between N-desethylamiodarone/amiodarone ratio and amiodarone-induced thyroid dysfunction. Eur. J. Clin. Pharmacol. 73, 289-296. https://doi:10.1007/s00228-017-2195-5. Epub 2017 Jan 12. PubMed