{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T23:41:20Z","timestamp":1787614880385,"version":"build-2736575974"},"reference-count":17,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Atrial fibrillation (AF) remains the most common cardiac arrhythmia, with pulmonary vein isolation (PVI) established as the cornerstone of interventional treatment. However, in patients with persistent AF (PersAF), the success rates of PVI alone tend to be limited. A promising additional target is the left atrial appendage (LAA). In recent years, cryoballoon (CB) technology has become a tool for achieving durable PVI. Its application for LAAI has been investigated as a potentially advantageous alternative to radiofrequency ablation, and a positive effect on long-term outcome has been reported. However, the available data is limited. This study sought to investigate the clinical impact of CB-based LAAI in addition to PVI. Methods: This is a prospective, interventional, single-centre study. Consecutive patients with symptomatic PersAF were prospectively enrolled. In total 23 patients with PersAF underwent PVI plus LAAI using the CB system. Percutaneous LAA closure was performed within 2\u20133 months in all patients by implanting an endocardial LAA-closure device. Prior to LAA closure, LAAI durability was systematically assessed by invasive remapping studies. Results: A total of 100% of PVs were successfully isolated using the CB only (n = 91\/91). Concerning LAAIs, a total of 21\/23 (91%) remained isolated at the end of the procedure. After the ablation procedure including LAAI, all patients were scheduled for TEE assessment and LAA closure. TEE was performed after a mean of 54 \u00b1 19 days. In 6\/23 (26%) patients, LAA thrombus formation was detected after LAAI. A total of 23\/23 patients (100%) received LAAC after a mean of 72 \u00b1 45 days. Durability of LAAI was assessed utilizing a spiral mapping catheter in 23\/23 patients (100%). In a total of 17\/23 (74%) patients, durable LAA isolation was detected. Durable PVI of all PVs was detected in 16\/23 (70%) patients. During a mean follow-up of 13 \u00b1 3.4 months, stable sinus rhythm was maintained in 15 (65%) patients. The LAA showed reconnection in 3\/23 (13%) patients, with arrhythmia recurrence. During follow-up, one stroke (318 days after LAAC) and one device thrombus (56 days after LAAC) occurred. Conclusions: While CB-based LAAI may offer benefits in managing persistent AF, it presents a significant risk of thrombus formation in the LAA, even with appropriate OAC. Early closure of the LAA following LAAI appears promising in mitigating these risks, but further evidence is needed to establish clear best practices.<\/jats:p>","DOI":"10.3390\/jcm15082980","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T14:24:58Z","timestamp":1776176698000},"page":"2980","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cryoballoon-Based Left Atrial Appendage Isolation and Closure in Patients with Atrial Fibrillation\u2014The LALALAND Pilot Study"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9014-8097","authenticated-orcid":false,"given":"Christian-H.","family":"Heeger","sequence":"first","affiliation":[{"name":"University Heart Center L\u00fcbeck, Department of Rhythmology, University Hospital Schleswig-Holstein, 23538 L\u00fcbeck, Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Hamburg\/Kiel\/L\u00fcbeck, 23538 L\u00fcbeck, Germany"},{"name":"Department of Rhythmology, Asklepios Klinik Hamburg Altona, 22763 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1352-9555","authenticated-orcid":false,"given":"Samuel","family":"Reincke","sequence":"additional","affiliation":[{"name":"University Heart Center L\u00fcbeck, Department of Rhythmology, University Hospital Schleswig-Holstein, 23538 L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sorin Stefan","family":"Popescu","sequence":"additional","affiliation":[{"name":"University Heart Center L\u00fcbeck, Department of Rhythmology, University Hospital Schleswig-Holstein, 23538 L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3061-2249","authenticated-orcid":false,"given":"Sascha","family":"Hatahet","sequence":"additional","affiliation":[{"name":"University Heart Center L\u00fcbeck, Department of Rhythmology, University Hospital Schleswig-Holstein, 23538 L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Behnam","family":"Subin","sequence":"additional","affiliation":[{"name":"University Heart Center L\u00fcbeck, Department of Rhythmology, University Hospital Schleswig-Holstein, 23538 L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Traub","sequence":"additional","affiliation":[{"name":"University Heart Center L\u00fcbeck, Department of Rhythmology, University Hospital Schleswig-Holstein, 23538 L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl-Heinz","family":"Kuck","sequence":"additional","affiliation":[{"name":"University Heart Center L\u00fcbeck, Department of Rhythmology, University Hospital Schleswig-Holstein, 23538 L\u00fcbeck, Germany"},{"name":"Department of Rhythmology, Asklepios Klinik Hamburg Altona, 22763 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8733-6791","authenticated-orcid":false,"given":"Charlotte","family":"Eitel","sequence":"additional","affiliation":[{"name":"University Heart Center L\u00fcbeck, Department of Rhythmology, University Hospital Schleswig-Holstein, 23538 L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland R.","family":"Tilz","sequence":"additional","affiliation":[{"name":"University Heart Center L\u00fcbeck, Department of Rhythmology, University Hospital Schleswig-Holstein, 23538 L\u00fcbeck, Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Hamburg\/Kiel\/L\u00fcbeck, 23538 L\u00fcbeck, Germany"},{"name":"FESC, FEHRA, FHRS, Klinik f\u00fcr Rhythmologie, Universit\u00e4res Herzzentrum L\u00fcbeck, Universit\u00e4tsklinikum Schleswig-Holstein (UKSH), Ratzeburger Allee 160, 23538 L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,14]]},"reference":[{"key":"ref_1","first-page":"e1","article-title":"2024 ESC Guidelines for the management of atrial fibrillation","volume":"26","author":"Gelder","year":"2025","journal-title":"G. Ital. Cardiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1111\/jce.16561","article-title":"Concise Guidelines of the European Cardiac Arrhythmias Society (ECAS) on \u201cCatheter Ablation of Atrial Fibrillation.\u201d","volume":"36","author":"Cappato","year":"2025","journal-title":"J. Cardiovasc. Electrophysiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.jacc.2023.08.017","article-title":"2023 ACC\/AHA\/ACCP\/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation A Report of the American College of Cardiology\/American Heart Association Joint Committee on Clinical Practice Guidelines","volume":"83","author":"Members","year":"2024","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1161\/CIRCULATIONAHA.118.037451","article-title":"Left Atrial Appendage Isolation in Patients Not Responding to Pulmonary Vein Isolation","volume":"139","author":"Heeger","year":"2019","journal-title":"Circulation"},{"key":"ref_5","first-page":"e003461","article-title":"Unexpectedly High Incidence of Stroke and Left Atrial Appendage Thrombus Formation After Electrical Isolation of the Left Atrial Appendage for the Treatment of Atrial Tachyarrhythmias","volume":"9","author":"Rillig","year":"2018","journal-title":"Circ. Arrhythmia Electrophysiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.12659\/AJCR.918196","article-title":"Fourth-Generation Cryoablation Based Left Atrial Appendage Isolation for the Treatment of Persistent Atrial Fibrillation: First Case Report","volume":"20","author":"Tilz","year":"2019","journal-title":"Am. J. Case Rep."},{"key":"ref_7","first-page":"124","article-title":"Left atrial appendage thrombus formation less than 24 hours after empirical cryoballoon-based left atrial appendage isolation: A serious warning","volume":"5","author":"Tilz","year":"2019","journal-title":"Hear. Case Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1016\/j.jacc.2016.07.770","article-title":"Left Atrial Appendage Isolation in Patients With Longstanding Persistent AF Undergoing Catheter Ablation BELIEF Trial","volume":"68","author":"Biase","year":"2016","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_9","first-page":"1100","article-title":"Cryoballoon or Radiofrequency Ablation for Atrial Fibrillation","volume":"375","author":"Kuck","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1093\/europace\/eux005","article-title":"Left atrial appendage isolation in addition to pulmonary vein isolation in persistent atrial fibrillation: One-year clinical outcome after cryoballoon-based ablation","volume":"19","author":"Yorgun","year":"2017","journal-title":"Europace"},{"key":"ref_11","first-page":"euab116.056","article-title":"Second and fourth generation Cryoballoon based left atrial appendage isolation for the treatment of persistent atrial fibrillation","volume":"23","author":"Heeger","year":"2021","journal-title":"EP Eur."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1111\/j.1540-8167.2010.01739.x","article-title":"Esophageal Endoscopy Results After Pulmonary Vein Isolation Using the Single Big Cryoballoon Technique","volume":"21","author":"Chun","year":"2010","journal-title":"J. Cardiovasc. Electrophysiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1016\/j.hrthm.2015.03.021","article-title":"Best practice guide for cryoballoon ablation in atrial fibrillation: The compilation experience of more than 3000 procedures","volume":"12","author":"Su","year":"2015","journal-title":"Heart Rhythm"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1093\/europace\/euu048","article-title":"Second-generation cryoballoon ablation for paroxysmal atrial fibrillation: A step forward?","volume":"16","author":"Metzner","year":"2014","journal-title":"Europace"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1161\/CIRCEP.113.000517","article-title":"Novel Electromyographic Monitoring Technique for Prevention of Right Phrenic Nerve Palsy During Cryoballoon Ablation","volume":"6","author":"Franceschi","year":"2013","journal-title":"Circ. Arrhythmia Electrophysiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1161\/CIRCEP.115.002734","article-title":"Electromyographic Monitoring for Prevention of Phrenic Nerve Palsy in Second-Generation Cryoballoon Procedures","volume":"8","author":"Franceschi","year":"2015","journal-title":"Circ. Arrhythmia Electrophysiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1111\/jce.12358","article-title":"The Incidence of Phrenic Nerve Injury During Pulmonary Vein Isolation Using the Second-Generation 28 mm Cryoballoon","volume":"25","author":"Metzner","year":"2014","journal-title":"J. Cardiovasc. Electrophysiol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/8\/2980\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T14:38:35Z","timestamp":1776177515000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/8\/2980"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,14]]},"references-count":17,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["jcm15082980"],"URL":"https:\/\/doi.org\/10.3390\/jcm15082980","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,14]]}}}