{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T05:06:27Z","timestamp":1779253587602,"version":"3.51.4"},"reference-count":42,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Atrial fibrillation (AF) is the most common cardiac arrhythmia, present in up to 14\u201320% of patients undergoing cardiac surgery, with the number of patients expected to double within the next decade. Despite a Class I recommendation for concomitant surgical ablation and a Class I-B recommendation for left atrial appendage (LAA) occlusion in patients with AF undergoing cardiac surgery (Class IIa for endoscopic or hybrid AF ablation), both procedures remain substantially underutilized in clinical practice. The design of the Mapping atrial fibrillation after Epicardial Surgical Ablation plus AtriClip to Guide Endocardial ablation (MESAGE) prospective study is presented. Materials and Methods: A narrative literature review was conducted using PubMed through March 2025. Randomized controlled trials, multicenter registries, meta-analyses and current clinical guidelines were prioritized. The MESAGE study protocol is presented in accordance with the SPIRIT recommendations. Results: Randomized evidence demonstrates that hybrid ablation achieves 32\u201348% greater arrhythmia freedom than catheter ablation (CA) alone in persistent and long-standing persistent AF, with comparable safety and significantly fewer interventions at two-year follow-up. Epicardial LAA occlusion with the AtriClip device achieves complete occlusion in all patients with an 87.5% relative reduction in ischemic stroke risk in anticoagulation-free follow-up. Continuous implantable loop recorder (ILR)-based monitoring reveals AF recurrence in substantially more patients than conventional monitoring, with AF burden emerging as a more meaningful endpoint than arrhythmia freedom. The MESAGE study enrolls 40 patients undergoing cardiac surgery who have pre-existing AF, pre-randomized 1:1 to pulmonary vein isolation (PVI) alone versus PVI-BOX, with mandatory pre-operative ILR implantation, intra-operative AtriClip LAA exclusion, and systematic Day-60 endocardial mapping and supplementary ablation using the Affera dual-energy system. Conclusions: Hybrid epicardial\u2013endocardial ablation combined with LAA exclusion and continuous ILR monitoring represents a comprehensive, mechanistically rational and evidence-informed approach to AF management in patients undergoing cardiac surgery, although current evidence remains heterogeneous, and the benefits depend on the AF phenotype and monitoring strategy. The MESAGE pilot study will generate hypothesis-generating prospective comparative data on epicardial PVI versus PVI-BOX in the concomitant surgical setting, assessed through systematic post-surgical endocardial mapping and continuous rhythm monitoring.<\/jats:p>","DOI":"10.3390\/medicina62050890","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T07:36:23Z","timestamp":1778052983000},"page":"890","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Beyond the Maze: Hybrid Ablation and Left Atrial Appendage Occlusion in Cardiac Surgery: Evidence Synthesis and the MESAGE Study Protocol"],"prefix":"10.3390","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1785-3198","authenticated-orcid":false,"given":"Sotirios C.","family":"Kotoulas","sequence":"first","affiliation":[{"name":"Department of Cardiothoracic Surgery, 401 General Military Hospital of Athens, Panagiotis Kanellopoulos Avenue, 11525 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vasileios","family":"Kolovos","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Electrophysiology, 401 General Military Hospital of Athens, 11525 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8667-5142","authenticated-orcid":false,"given":"Nikolaos","family":"Tsiamis","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Sismanoglio General Hospital, 15126 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Athanasios","family":"Kotoulas","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, 401 General Military Hospital of Athens, Panagiotis Kanellopoulos Avenue, 11525 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charalampos","family":"Georgiou","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, 401 General Military Hospital of Athens, Panagiotis Kanellopoulos Avenue, 11525 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Panteleimon","family":"Tsipas","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, 401 General Military Hospital of Athens, Panagiotis Kanellopoulos Avenue, 11525 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ioannis","family":"Panagiotou","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, 401 General Military Hospital of Athens, Panagiotis Kanellopoulos Avenue, 11525 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dimitrios","family":"Antoniadis","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Electrophysiology, 401 General Military Hospital of Athens, 11525 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0940-9975","authenticated-orcid":false,"given":"Christophoros","family":"Kotoulas","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, 401 General Military Hospital of Athens, Panagiotis Kanellopoulos Avenue, 11525 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3314","DOI":"10.1093\/eurheartj\/ehae176","article-title":"2024 ESC Guidelines for the management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS)","volume":"45","author":"Rienstra","year":"2024","journal-title":"Eur. Heart J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1016\/j.hlc.2024.07.007","article-title":"Atrial Fibrillation Surgery in Australia: Are We Doing Enough?","volume":"33","author":"Kirk","year":"2024","journal-title":"Heart Lung Circ."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1080\/14779072.2026.2621670","article-title":"Ensuring long-term arrhythmia freedom: What are the options for long-standing persistent atrial fibrillation?","volume":"24","author":"Kotoulas","year":"2026","journal-title":"Expert Rev. Cardiovasc. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1161\/CIRCULATIONAHA.119.042622","article-title":"Cryoballoon or Radiofrequency Ablation for Atrial Fibrillation Assessed by Continuous Monitoring: A Randomized Clinical Trial","volume":"140","author":"Andrade","year":"2019","journal-title":"Circulation"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/j.jacep.2022.12.011","article-title":"Hybrid Ablation Versus Repeated Catheter Ablation in Persistent Atrial Fibrillation: A Randomized Controlled Trial","volume":"9","author":"Weberndorfer","year":"2023","journal-title":"JACC Clin. Electrophysiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"102052","DOI":"10.1016\/j.eclinm.2023.102052","article-title":"Efficacy and safety of hybrid epicardial and endocardial ablation versus endocardial ablation in patients with persistent and longstanding persistent atrial fibrillation: A randomised, controlled trial","volume":"61","author":"Doll","year":"2023","journal-title":"eClinicalMedicine"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.ahj.2020.02.016","article-title":"Convergence of Epicardial and Endocardial RF Ablation for the Treatment of Symptomatic Persistent AF (CONVERGE Trial): Rationale and design","volume":"224","author":"DeLurgio","year":"2020","journal-title":"Am. Heart J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2245","DOI":"10.1016\/j.jtcvs.2019.06.062","article-title":"Prevalence of atrial fibrillation before cardiac surgery and factors associated with concomitant ablation","volume":"159","author":"McCarthy","year":"2020","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.athoracsur.2020.05.125","article-title":"Variability and Utilization of Concomitant Atrial Fibrillation Ablation During Mitral Valve Surgery","volume":"111","author":"Mehaffey","year":"2021","journal-title":"Ann. Thorac. Surg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.athoracsur.2017.05.016","article-title":"Surgical Ablation of Atrial Fibrillation in the United States: Trends and Propensity Matched Outcomes","volume":"104","author":"Badhwar","year":"2017","journal-title":"Ann. Thorac. Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.xjon.2023.10.013","article-title":"Trends in surgical ablation at the time of cardiac surgery among patients with atrial fibrillation","volume":"16","author":"Jenkins","year":"2023","journal-title":"JTCVS Open"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1056\/NEJM199809033391003","article-title":"Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins","volume":"339","author":"Haissaguerre","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/S0008-6363(02)00258-4","article-title":"Electrical, contractile and structural remodeling during atrial fibrillation","volume":"54","author":"Allessie","year":"2002","journal-title":"Cardiovasc. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2731","DOI":"10.1093\/eurheartj\/eht194","article-title":"Human atrial fibrillation substrate: Towards a specific fibrotic atrial cardiomyopathy","volume":"34","author":"Kottkamp","year":"2013","journal-title":"Eur. Heart J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1111\/jce.13482","article-title":"Impact of left atrial volume, sphericity, and fibrosis on the outcome of catheter ablation for atrial fibrillation","volume":"29","author":"Cabanelas","year":"2018","journal-title":"J. Cardiovasc. Electrophysiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"54","DOI":"10.21037\/acs-2023-afm-0129","article-title":"Hybrid atrial fibrillation ablation","volume":"13","author":"Aerts","year":"2024","journal-title":"Ann. Cardiothorac. Surg."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Gerculy, R., Benedek, I., Kovacs, I., Rat, N., Rodean, I.P., Matyas, B.B., Blindu, E., Pacurar, D., Grigoroaea, C.G., and Benedek, T. (2025). Coronary Artery Inflammation and Epicardial Adipose Tissue Volume in Relation with Atrial Fibrillation Development. Diagnostics, 15.","DOI":"10.3390\/diagnostics15162003"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/S0022-5223(19)36684-X","article-title":"The surgical treatment of atrial fibrillation. III. Development of a definitive surgical procedure","volume":"101","author":"Cox","year":"1991","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"104","DOI":"10.14797\/mdcj-11-2-104","article-title":"Surgical Ablation of Atrial Fibrillation","volume":"11","author":"Ramlawi","year":"2015","journal-title":"Methodist Debakey Cardiovasc. J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1016\/j.jtcvs.2017.09.147","article-title":"Long-term outcome following concomitant mitral valve surgery and Cox maze procedure for atrial fibrillation","volume":"155","author":"Ad","year":"2018","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1177\/15569845221126524","article-title":"Efficacy of a Novel Bipolar Radiofrequency Clamp: An Acute Porcine Model","volume":"17","author":"Yates","year":"2022","journal-title":"Innovations"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3006","DOI":"10.1111\/jocs.16777","article-title":"Mid-term outcomes of concomitant Cox-Maze IV: Results from a multicenter prospective registry","volume":"37","author":"Gerdisch","year":"2022","journal-title":"J. Card. Surg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1055\/s-0041-1730969","article-title":"The German CArdioSurgEry Atrial Fibrillation Registry: In-Hospital Outcomes","volume":"71","author":"Wehbe","year":"2023","journal-title":"Thorac. Cardiovasc. Surg."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1053\/j.jvca.2019.09.021","article-title":"Concomitant Cardiac Surgery and Radiofrequency Ablation of Atrial Fibrillation: A Retrospective Single Center Study","volume":"34","author":"Raissouni","year":"2020","journal-title":"J. Cardiothorac. Vasc. Anesth."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.hroo.2022.11.007","article-title":"Hybrid epicardial-endocardial ablation for long-standing persistent atrial fibrillation: A subanalysis of the CONVERGE Trial","volume":"4","author":"DeLurgio","year":"2023","journal-title":"Heart Rhythm O2"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"ezaf146","DOI":"10.1093\/ejcts\/ezaf146","article-title":"Durable effectiveness and safety of hybrid ablation versus catheter ablation: 2-year results from the randomized CEASE-AF trialdagger","volume":"67","author":"Doll","year":"2025","journal-title":"Eur. J. Cardiothorac. Surg."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1562","DOI":"10.1016\/j.hrthm.2024.05.022","article-title":"Long-term clinical outcomes and cost-effectiveness of catheter vs thoracoscopic surgical ablation in long-standing persistent atrial fibrillation using continuous cardiac monitoring: CASA-AF randomized controlled trial","volume":"21","author":"Boyalla","year":"2024","journal-title":"Heart Rhythm"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1007\/s10840-024-01839-2","article-title":"Hybrid ablation for persistent\/long-standing persistent atrial fibrillation: A meta-analysis and trial sequential analysis of randomized controlled trials","volume":"68","author":"Rivera","year":"2025","journal-title":"J. Interv. Card. Electrophysiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.hroo.2022.05.006","article-title":"Hybrid Convergent ablation for atrial fibrillation: A systematic review and meta-analysis","volume":"3","author":"Shrestha","year":"2022","journal-title":"Heart Rhythm O2"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"euaf196","DOI":"10.1093\/europace\/euaf196","article-title":"Epicardial and hybrid surgical ablation of atrial fibrillation: 1-year follow-up outcomes of the EORP EHAFA registry","volume":"27","author":"Vroomen","year":"2025","journal-title":"Europace"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.hrthm.2020.10.004","article-title":"Combined epicardial and endocardial ablation for atrial fibrillation: Best practices and guide to hybrid convergent procedures","volume":"18","author":"Makati","year":"2021","journal-title":"Heart Rhythm"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1001\/jama.2022.23722","article-title":"Effect of Catheter Ablation Using Pulmonary Vein Isolation With vs Without Posterior Left Atrial Wall Isolation on Atrial Arrhythmia Recurrence in Patients With Persistent Atrial Fibrillation: The CAPLA Randomized Clinical Trial","volume":"329","author":"Kistler","year":"2023","journal-title":"JAMA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1016\/j.jacep.2024.01.017","article-title":"Impact of Left Atrial Posterior Wall Ablation During Pulsed-Field Ablation for Persistent Atrial Fibrillation","volume":"10","author":"Turagam","year":"2024","journal-title":"JACC Clin. Electrophysiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1161\/CIRCULATIONAHA.125.074485","article-title":"Pulsed Field Ablation of Persistent Atrial Fibrillation with Continuous Electrocardiographic Monitoring Follow-Up: ADVANTAGE AF Phase 2","volume":"152","author":"Reddy","year":"2025","journal-title":"Circulation"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1056\/NEJMoa2101897","article-title":"Left Atrial Appendage Occlusion during Cardiac Surgery to Prevent Stroke","volume":"384","author":"Whitlock","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e105","DOI":"10.1093\/europace\/eux211","article-title":"Epicardial left atrial appendage AtriClip occlusion reduces the incidence of stroke in patients with atrial fibrillation undergoing cardiac surgery","volume":"20","author":"Caliskan","year":"2018","journal-title":"Europace"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1016\/j.hlc.2024.02.010","article-title":"Thoracoscopic Left Atrial Appendage Occlusion with the AtriClip PRO2: An Experience of 144 Patients","volume":"33","author":"Wang","year":"2024","journal-title":"Heart Lung Circ."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1093\/icvts\/ivs053","article-title":"Ablation for atrial fibrillation during mitral valve surgery: 1-year results through continuous subcutaneous monitoring","volume":"15","author":"Zheleznev","year":"2012","journal-title":"Interact. Cardiovasc. Thorac. Surg."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e13","DOI":"10.1016\/j.hrthm.2024.12.021","article-title":"A novel focal lattice-tip catheter toggling between pulsed field energy and radiofrequency for atrial arrhythmia ablation: Results from a real-world, multicenter registry","volume":"22","author":"Vetta","year":"2025","journal-title":"Heart Rhythm"},{"key":"ref_40","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_41","doi-asserted-by":"crossref","first-page":"euae088","DOI":"10.1093\/europace\/euae088","article-title":"Dual energy for pulmonary vein isolation using dual-energy focal ablation technology integrated with a three-dimensional mapping system: SmartfIRE 3-month results","volume":"26","author":"Duytschaever","year":"2024","journal-title":"Europace"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1177\/0962280215588241","article-title":"Estimating the sample size for a pilot randomised trial to minimise the overall trial sample size for the external pilot and main trial for a continuous outcome variable","volume":"25","author":"Whitehead","year":"2016","journal-title":"Stat. Methods Med. Res."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/5\/890\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T04:14:51Z","timestamp":1779250491000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/5\/890"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,5]]},"references-count":42,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["medicina62050890"],"URL":"https:\/\/doi.org\/10.3390\/medicina62050890","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,5]]}}}