{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:13:06Z","timestamp":1760148786620,"version":"build-2065373602"},"reference-count":50,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,6,7]],"date-time":"2023-06-07T00:00:00Z","timestamp":1686096000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","award":["0419-2022-0002"],"award-info":[{"award-number":["0419-2022-0002"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Science and Higher Education of the Russian Federation","award":["0419-2022-0002"],"award-info":[{"award-number":["0419-2022-0002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Although the autonomic nervous system has an evident impact on cardiac electrophysiology and radiofrequency ablation (RFA) is the conventional technique for treating persistent atrial fibrillation, the specific effects of RFA have been insufficiently studied to date. Here, we investigated whether RFA affects neurohumoral transmitter levels and myocardial 123I-metaiodobenzylguanidine (123I-MIBG) uptake. To perform this task, we compared two groups of patients with acquired valvular heart disease: patients who had undergone surgical AF ablation and patients with sinus rhythm. The decrease in norepinephrine (NE) level in the coronary sinus had a direct association with the heart-to-mediastinum ratio (p = 0.02) and a negative correlation with 123I-MIBG uptake defects (p = 0.01). The NE level decreased significantly after the main surgery, both in patients with AF (p = 0.0098) and sinus rhythm (p = 0.0039). Furthermore, the intraoperative difference between the norepinephrine levels in the ascending aorta and coronary sinus (\u0394NE) of \u2013400 pg\/mL was determined as a cut-off value to evaluate RFA efficacy, as denervation failed in all patients with \u0394NE &lt; \u2013400 pg\/mL. Hence, \u0394NE can be utilized to predict the efficacy of the \u201cMAZE-IV\u201d procedure and to assess the risk of AF recurrence after RFA.<\/jats:p>","DOI":"10.3390\/life13061340","type":"journal-article","created":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T01:34:32Z","timestamp":1686188072000},"page":"1340","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Neurohumoral Markers of Cardiac Autonomic Denervation after Surgical Ablation of Long-Standing Persistent Atrial Fibrillation"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8475-4667","authenticated-orcid":false,"given":"Alexey","family":"Evtushenko","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Surgery, Research Institute for Complex Issues of Cardiovascular Diseases, 6 Sosnovy Boulevard, Kemerovo 650002, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5537-0864","authenticated-orcid":false,"given":"Vladimir","family":"Evtushenko","sequence":"additional","affiliation":[{"name":"Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 111a Kievskaya Street, Tomsk 634012, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3147-3025","authenticated-orcid":false,"given":"Anna","family":"Gusakova","sequence":"additional","affiliation":[{"name":"Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 111a Kievskaya Street, Tomsk 634012, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatiana","family":"Suslova","sequence":"additional","affiliation":[{"name":"Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 111a Kievskaya Street, Tomsk 634012, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yulia","family":"Varlamova","sequence":"additional","affiliation":[{"name":"Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 111a Kievskaya Street, Tomsk 634012, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Konstantin","family":"Zavadovskiy","sequence":"additional","affiliation":[{"name":"Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 111a Kievskaya Street, Tomsk 634012, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denis","family":"Lebedev","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Research Institute for Complex Issues of Cardiovascular Diseases, 6 Sosnovy Boulevard, Kemerovo 650002, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8679-4857","authenticated-orcid":false,"given":"Anton","family":"Kutikhin","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Research Institute for Complex Issues of Cardiovascular Diseases, 6 Sosnovy Boulevard, Kemerovo 650002, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Pavlyukova","sequence":"additional","affiliation":[{"name":"Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 111a Kievskaya Street, Tomsk 634012, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8277-5584","authenticated-orcid":false,"given":"Sergey","family":"Mamchur","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Research Institute for Complex Issues of Cardiovascular Diseases, 6 Sosnovy Boulevard, Kemerovo 650002, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1161\/CIRCRESAHA.113.302549","article-title":"Role of the autonomic nervous system in modulating cardiac arrhythmias","volume":"114","author":"Shen","year":"2014","journal-title":"Circ. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"64","DOI":"10.21292\/2078-5658-2017-14-2-64-71","article-title":"Atrial fibrillation following cardiac surgery: Pathophysiology and prevention techniques (part 2)","volume":"14","author":"Lomivorotov","year":"2017","journal-title":"Messenger Anesthesiol. Resusc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"118","DOI":"10.15420\/aer.2018.18.2","article-title":"Risk factor management in atrial fibrillation","volume":"7","author":"Brandes","year":"2018","journal-title":"Arrhythmia Electrophysiol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1016\/S0022-5223(19)36685-1","article-title":"The surgical treatment of atrial fibrillation","volume":"101","author":"Cox","year":"1991","journal-title":"IV. Surg. Tech. J. Thorac. Cardiovasc. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1016\/j.jtcvs.2010.02.027","article-title":"The longstanding, persistent confusion surrounding surgery for atrial fibrillation","volume":"139","author":"Cox","year":"2010","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2893","DOI":"10.1093\/eurheartj\/ehw210","article-title":"ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS","volume":"37","author":"Kirchhof","year":"2016","journal-title":"Eur. Heart J."},{"key":"ref_7","first-page":"483","article-title":"Concomitant Cox-Maze IV techniques during mitral valve surgery","volume":"5","author":"Lawrance","year":"2015","journal-title":"Ann. Cardiothorac. Surg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1111\/jce.12407","article-title":"A prospective and randomized comparison of limited versus extensive atrial substrate modification after circumferential pulmonary vein isolation in nonparoxysmal atrial fibrillation","volume":"25","author":"Lin","year":"2014","journal-title":"J. Cardiovasc. Electrophysiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.jtcvs.2004.02.044","article-title":"A prospective, single-center clinical trial of a modified Cox maze procedure with bipolar radiofrequency ablation","volume":"128","author":"Gaynor","year":"2004","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_10","first-page":"16","article-title":"Combinesd treatment of paroxysmal atrial fibrillation in patients with mitral valve disease: Analysis of long-term outcomes","volume":"24","author":"Pivkin","year":"2017","journal-title":"J. Arrhythmology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1016\/j.jtcvs.2014.11.032","article-title":"A time-related parametric risk factor analysis for postoperative atrial fibrillation after heart surgery","volume":"149","author":"Melby","year":"2015","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1053\/j.jvca.2015.01.001","article-title":"Atrial fibrillation after cardiac surgery: Clinical update on mechanisms and prophylactic strategies","volume":"29","author":"Raiten","year":"2015","journal-title":"J. Cardiothorac. Vasc. Anesth."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.hfc.2015.08.023","article-title":"Postoperative atrial fibrillation: Incidence, mechanisms, and clinical correlates","volume":"12","author":"Yadava","year":"2016","journal-title":"Heart Fail. Clin."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.jacc.2006.10.033","article-title":"Impact of epicardial anterior fat pad retention on postcardiothoracic surgery atrial fibrillation incidence: The AFIST-III Study","volume":"49","author":"White","year":"2007","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1161\/CIRCRESAHA.117.309732","article-title":"Atrial Fibrillation: Epidemiology, Pathophysiology, and Clinical Outcomes","volume":"120","author":"Staerk","year":"2017","journal-title":"Circ. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2024","DOI":"10.1016\/j.athoracsur.2017.05.018","article-title":"Delayed electroanatomic mapping after surgical ablation for persistent atrial fibrillation","volume":"104","author":"Bulava","year":"2017","journal-title":"Ann. Thorac. Surg."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.hrthm.2006.01.009","article-title":"Feasibility study of endocardial mapping of ganglionated plexuses during catheter ablation of atrial fibrillation","volume":"3","author":"Lemery","year":"2006","journal-title":"Heart Rhythm"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1253\/circj.CJ-09-0967","article-title":"Effect of epicardial fat pad ablation on acute atrial electrical remodeling and inducibility of atrial fibrillation","volume":"74","author":"Chang","year":"2010","journal-title":"Circ. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"569564","DOI":"10.1155\/2013\/569564","article-title":"Denervation as a common mechanism underlying different pulmonary vein isolation strategies for paroxysmal atrial fibrillation: Evidenced by heart rate variability after ablation","volume":"2013","author":"Wang","year":"2013","journal-title":"Sci. World J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1161\/01.CIR.0000112641.16340.C7","article-title":"Pulmonary vein denervation enhances long-term benefit after circumferential ablation for paroxysmal atrial fibrillation","volume":"109","author":"Pappone","year":"2004","journal-title":"Circulation"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1016\/j.athoracsur.2008.06.077","article-title":"Ablation of ganglionic plexi during combined surgery for atrial fibrillation","volume":"86","author":"Doll","year":"2008","journal-title":"Ann. Thorac. Surg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1177\/021849230801600304","article-title":"Catheter ablation of left atrial ganglionated plexi for atrial fibrillation","volume":"16","author":"Pokushalov","year":"2008","journal-title":"Asian Cardiovasc. Thorac. Ann."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1097\/00004872-199917060-00001","article-title":"How to assess sympathetic activiry in humans","volume":"17","author":"Grassi","year":"1999","journal-title":"J. Hypertens."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/B978-0-444-53491-0.00031-6","article-title":"Heart rate variability","volume":"117","author":"Cygankiewicz","year":"2013","journal-title":"Handb. Clin. Neurol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/BF00229801","article-title":"Adrenergic hormones and control of cardiac myocyte growth","volume":"104","author":"Simpson","year":"1991","journal-title":"Mol. Cell Biochem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1113\/expphysiol.2010.053280","article-title":"Acute vagal modulation of electrophysiology of the atrial and pulmonary veins increases vulnerability to atrial fibrillation","volume":"96","author":"Oliveira","year":"2011","journal-title":"Exp. Physiology."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3829","DOI":"10.1021\/jm970267h","article-title":"Synthesis and evaluation of (S)-4-(3-(2\u2032-[11C]isopropylamino)-2-hydroxypropoxy) -2H-benzimidazol -2-one ((S)-[11C]CGP 12388) and (S)-4-(3-((1\u2032-[18F]-fluoroisopropyl)amino)-2-hydroxypropoxy) -2H- benzimidazol-2-one ((S)-[18F]fluoro-CGP 12388) for visualization of beta-adrenoceptors with positron emission tomography","volume":"40","author":"Elsinga","year":"1997","journal-title":"J. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1161\/01.CIR.87.4.1169","article-title":"Positron emission tomography with 11C CGP-12177 to assess \u03b2-adrenergic receptor concentration in idiopatic dilated cardiomyopathy","volume":"87","author":"Merlet","year":"1993","journal-title":"Circulation"},{"key":"ref_29","first-page":"281","article-title":"Imaging sympathetic innervation","volume":"43","author":"Matheja","year":"1999","journal-title":"J. Nucl. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s002590050505","article-title":"Metaiodobenzilguanidine scintigraphy of the heart: What have we learnt clinically?","volume":"27","author":"Hattori","year":"2000","journal-title":"Eur. J. Nucl. Med."},{"key":"ref_31","first-page":"6","article-title":"Cardiac sympathetic nervous system in early essential hypertension assessed by 123I-MIBG","volume":"40","author":"Sakata","year":"1999","journal-title":"J. Nucl. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1111\/j.1540-8167.2011.02123.x","article-title":"High washout rate of iodine-123-metaiodobenzylguanidine imaging predicts the outcome of catheter ablation of atrial fibrillation","volume":"22","author":"Arimoto","year":"2011","journal-title":"J. Cardiovasc. Electrophysiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1007\/s12350-010-9239-x","article-title":"Radionuclide imaging of cardiac autonomic innervation","volume":"17","author":"Ji","year":"2010","journal-title":"J. Nucl. Cardiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1093\/eurheartj\/ehaa612","article-title":"2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC","volume":"42","author":"Hindricks","year":"2021","journal-title":"Eur. Heart J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1016\/0735-1097(95)00374-6","article-title":"Iodine-123 metaiodobenzylguanidine images reflect intense myocardial adrenergic nervous activity in congestive heart failure independent of underlying cause","volume":"26","author":"Imamura","year":"1995","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1161\/CIRCRESAHA.114.303772","article-title":"Role of the autonomic nervous system in atrial fibrillation: Pathophysiology and therapy","volume":"114","author":"Chen","year":"2014","journal-title":"Circ. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1097\/ACO.0000000000000070","article-title":"Perioperative challenges of atrial fibrillation","volume":"27","author":"Philip","year":"2014","journal-title":"Curr. Opin. Anaesthesiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.jss.2015.04.047","article-title":"Predicting postoperative atrial fibrillation using CHA2DS2-VASc scores","volume":"198","author":"Kashani","year":"2015","journal-title":"J. Surg. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1007\/s10557-017-6736-z","article-title":"MicroRNAs in Atrial Fibrillation: From Expression Signatures to Functional Implications","volume":"31","author":"Kawasaki","year":"2017","journal-title":"Cardiovasc. Drugs"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1093\/ejcts\/ezx039","article-title":"Postoperative atrial fibrillation following cardiac surgery: A persistent complication","volume":"52","author":"Greenberg","year":"2017","journal-title":"Eur. J. Cardio-Thorac. Surg."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2615","DOI":"10.1161\/CIRCULATIONAHA.109.919829","article-title":"Intrinsic cardiac nerve activity and paroxysmal atrial tachyarrhythmia in ambulatory dogs","volume":"121","author":"Choi","year":"2010","journal-title":"Circulation"},{"key":"ref_42","first-page":"3","article-title":"Systematic review and meta-analysis of surgical ablation for atrial fibrillation during mitral valve surgery","volume":"3","author":"Phan","year":"2014","journal-title":"Ann. Cardiothorac. Surg."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1056\/NEJMoa1500528","article-title":"Surgical ablation of atrial fibrillation during mitralvalve surgery","volume":"372","author":"Gillinov","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1056\/NEJMoa1602002","article-title":"Rate control versus rhythm control for atrial fibrillation after cardiac surgery","volume":"374","author":"Gillinov","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"41","DOI":"10.4330\/wjc.v8.i1.41","article-title":"Surgical perspectives in the management of atrial fibrillation","volume":"8","author":"Kyprianou","year":"2016","journal-title":"World J. Cardiol."},{"key":"ref_46","first-page":"77","article-title":"Targeting the autonomic nervous system: Measuring autonomic function and novel devices for heart failure management","volume":"35","author":"Patel","year":"2014","journal-title":"Eur. Heart J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"S61","DOI":"10.1016\/j.hrthm.2006.12.006","article-title":"Autonomic nerve activity and atrial fibrillation","volume":"4","author":"Chen","year":"2007","journal-title":"Heart Rhythm"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1046\/j.1540-8167.2003.02462.x","article-title":"Role of autonomic tonus in the initiation and termination of paroxysmal atrial fibrillation in patients without structural heart disease","volume":"14","author":"Tomita","year":"2003","journal-title":"J. Cardiovasc. Electrophysiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1016\/j.jacc.2005.12.023","article-title":"Sodium-calcium exchange initiated by the Ca2+ transient: An arrhythmia trigger within pulmonary veins","volume":"47","author":"Patterson","year":"2006","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1111\/j.1540-8167.2007.00909.x","article-title":"Spontaneous pulmonary vein firing in man: Relationship to tachycardia-pause early afterdepolarizations and triggered arrhythmia in canine pulmonary veins in vitro","volume":"18","author":"Patterson","year":"2007","journal-title":"J. Cardiovasc. Electrophysiol."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/13\/6\/1340\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:50:17Z","timestamp":1760125817000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/13\/6\/1340"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,7]]},"references-count":50,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["life13061340"],"URL":"https:\/\/doi.org\/10.3390\/life13061340","relation":{},"ISSN":["2075-1729"],"issn-type":[{"type":"electronic","value":"2075-1729"}],"subject":[],"published":{"date-parts":[[2023,6,7]]}}}