{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T05:18:39Z","timestamp":1787807919629,"version":"build-2784847793"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cryoballoon ablation (CBA) for atrial fibrillation (AF) is associated with reduced procedural radiation exposure as operator experience accumulates, yet the mechanistic underpinning of this improvement remains incompletely characterized. We hypothesized that ablation temperature parameters, reflecting balloon-tissue contact quality, serve as a quantifiable mediator linking operator experience to radiation dose.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We retrospectively analyzed 804 consecutive patients undergoing first-time CBA for symptomatic AF at a single tertiary center. Cumulative sum (CUSUM) analysis identified learning curve inflection points. Patients were stratified into early (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009385) and plateau (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009419) phases. Multivariable linear regression, restricted cubic spline (RCS) analysis, and formal causal mediation analysis (bootstrap 1,000 iterations) were performed to evaluate worst pulmonary vein (PV) minimum temperature as a mediator between learning curve phase and log-transformed radiation dose.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      CUSUM analysis identified learning curve inflection points at case 385 (procedural time), 301 (radiation dose), and 329 (fluoroscopy time). Compared with the early phase, median radiation dose in the plateau phase decreased by 15.4% (506 vs. 428 mGy,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&amp;lt;\u20090.001), procedural time by 27.0% (89 vs. 65\u2005min,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&amp;lt;\u20090.001), and fluoroscopy time by 26.3% (19 vs. 14\u2005min,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&amp;lt;\u20090.001). In multivariable analysis (adjusted R\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090.509), worst PV minimum temperature was an independent predictor of radiation dose (exp[\u03b2]\u2009=\u20091.012 per\u2005\u00b0C, 95% CI 1.008\u20131.017,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&amp;lt;\u20090.001), as was plateau phase (exp[\u03b2]\u2009=\u20090.895, 95% CI 0.847\u20130.946,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&amp;lt;\u20090.001). BMI exhibited a significant nonlinear association with radiation dose (\n                      <jats:italic>p<\/jats:italic>\n                      for nonlinearity\u2009&amp;lt;\u20090.001), with an inflection threshold near 25\u2005kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      . Mediation analysis demonstrated that worst PV minimum temperature mediated 14.5% (95% CI 5.5%\u201335.4%) of the total learning curve effect on radiation dose (average causal mediation effect [ACME]\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&amp;lt;\u20090.001; performed on 734 patients with complete mediator data).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Greater operator experience was associated with lower radiation exposure and more favorable cryoablation temperature profiles. Worst PV nadir temperature statistically mediated a modest proportion of the association between learning curve phase and radiation dose, although most of the association remained unexplained by this temperature metric. These findings support a potential role of balloon\u2013tissue contact quality in experience-related procedural improvement but should be interpreted as hypothesis-generating rather than evidence of a causal mechanism or improved clinical outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcvm.2026.1931483","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T04:27:23Z","timestamp":1787804843000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanistic insights into the learning curve of cryoballoon ablation: ablation temperature mediates the effect of operator experience on radiation exposure"],"prefix":"10.3389","volume":"13","author":[{"given":"Tian-Yu","family":"Li","sequence":"first","affiliation":[{"name":"Department of Cardiology, The Affiliated Wuxi People\u2019s Hospital of Nanjing Medical University, Wuxi People\u2019s Hospital, Wuxi Medical Center, Nanjing Medical University","place":["Wuxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Ming","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Affiliated Wuxi People\u2019s Hospital of Nanjing Medical University, Wuxi People\u2019s Hospital, Wuxi Medical Center, Nanjing Medical University","place":["Wuxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","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)","volume":"42","author":"Hindricks","year":"2021","journal-title":"Eur Heart J"},{"key":"B2","doi-asserted-by":"publisher","first-page":"100157","DOI":"10.1016\/j.lanepe.2021.100157","article-title":"Atrial fibrillation epidemiology, disparity and healthcare contacts: a population-wide study of 5.6 million individuals","volume":"7","author":"Chung","year":"2021","journal-title":"Lancet Reg Health Eur"},{"key":"B3","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1111\/jce.15759","article-title":"Atrial fibrillation: epidemiology, pathophysiology, and clinical complications (literature review)","volume":"34","author":"Bizhanov","year":"2023","journal-title":"J Cardiovasc Electrophysiol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1056\/NEJMoa2029980","article-title":"Cryoablation or drug therapy for initial treatment of atrial fibrillation","volume":"384","author":"Andrade","year":"2021","journal-title":"N Engl J Med"},{"key":"B5","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1056\/NEJMoa2029554","article-title":"Cryoballoon ablation as initial therapy for atrial fibrillation","volume":"384","author":"Wazni","year":"2021","journal-title":"N Engl J Med"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1093\/europace\/euab029","article-title":"Cryoballoon ablation vs. Antiarrhythmic drugs: first-line therapy for patients with paroxysmal atrial fibrillation","volume":"23","author":"Kuniss","year":"2021","journal-title":"Europace"},{"key":"B7","doi-asserted-by":"publisher","first-page":"2235","DOI":"10.1056\/NEJMoa1602014","article-title":"Cryoballoon or radiofrequency ablation for paroxysmal atrial fibrillation","volume":"374","author":"Kuck","year":"2016","journal-title":"N Engl J Med"},{"key":"B8","doi-asserted-by":"publisher","first-page":"e0265482","DOI":"10.1371\/journal.pone.0265482","article-title":"Efficacy and safety of cryoballoon pulmonary vein isolation for paroxysmal and persistent atrial fibrillation: a comparison with radiofrequency ablation","volume":"17","author":"Choi","year":"2022","journal-title":"PLoS One"},{"key":"B9","doi-asserted-by":"publisher","first-page":"518","DOI":"10.2459\/JCM.0000000000000493","article-title":"Learning curve using the second-generation cryoballoon ablation","volume":"18","author":"Velagi\u0107","year":"2017","journal-title":"J Cardiovasc Med (Hagerstown)"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1208250","DOI":"10.3389\/fcvm.2023.1208250","article-title":"Implementation of the multielectrode radiofrequency-balloon in real-world clinical practice-operator learning curve and procedural outcome at a high-volume center","volume":"10","author":"Zylla","year":"2023","journal-title":"Front Cardiovasc Med"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1002\/joa3.12780","article-title":"X-ray exposure in cryoballoon versus radiofrequency ablation for atrial fibrillation over 7 years: a single center study","volume":"38","author":"Heinroth","year":"2022","journal-title":"J Arrhythm"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1385","DOI":"10.1111\/jce.14468","article-title":"Femoral vascular complications after catheter ablation in the current era: the utility of computed tomography imaging","volume":"31","author":"Ishikawa","year":"2020","journal-title":"J Cardiovasc Electrophysiol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1093\/europace\/euaa415","article-title":"Relationship between procedural volume and complication rates for catheter ablation of atrial fibrillation: a systematic review and meta-analysis","volume":"23","author":"Tonchev","year":"2021","journal-title":"Europace"},{"key":"B14","doi-asserted-by":"publisher","first-page":"101516","DOI":"10.1016\/j.ijcha.2024.101516","article-title":"Impact of overweight and obesity on radiation dose and outcome in patients undergoing pulmonary vein isolation by cryoballoon and pulsed field ablation","volume":"55","author":"Jungen","year":"2024","journal-title":"Int J Cardiol Heart Vasc"},{"key":"B15","doi-asserted-by":"publisher","first-page":"664538","DOI":"10.3389\/fcvm.2021.664538","article-title":"Cryoballoon ablation of atrial fibrillation without demonstration of pulmonary vein occlusion-the simplify Cryo study","volume":"8","author":"K\u00fchne","year":"2021","journal-title":"Front Cardiovasc Med"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1367","DOI":"10.1007\/s10840-022-01429-0","article-title":"Cryoballoon temperature parameters during cryoballoon ablation predict pulmonary vein reconnection and atrial fibrillation recurrence","volume":"66","author":"Chahine","year":"2023","journal-title":"J Interv Card Electrophysiol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1007\/s00392-023-02361-7","article-title":"Temperature to time catch-up: a novel procedural endpoint to predict durable pulmonary vein isolation after cryoballoon ablation of paroxysmal atrial fibrillation","volume":"114","author":"Willy","year":"2025","journal-title":"Clin Res Cardiol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1058485","DOI":"10.3389\/fcvm.2023.1058485","article-title":"Thawing plateau time indicating the duration of phase transition from ice to water is the strongest predictor for long-term durable pulmonary vein isolation after cryoballoon ablation for atrial fibrillation-data from the index and repeat procedures","volume":"10","author":"Shi","year":"2023","journal-title":"Front Cardiovasc Med"},{"key":"B19","doi-asserted-by":"publisher","first-page":"101040","DOI":"10.1016\/j.ijcha.2022.101040","article-title":"Durability of pulmonary vein isolation following cryoballoon ablation: lessons from a large series of repeat ablation procedures","volume":"40","author":"Mugnai","year":"2022","journal-title":"Int J Cardiol Heart Vasc"},{"key":"B20","doi-asserted-by":"publisher","first-page":"55","DOI":"10.3390\/jcdd10020055","article-title":"Best practice guide for cryoballoon ablation in atrial fibrillation: the compilation experience of more than 1000 procedures","volume":"10","author":"Tsiachris","year":"2023","journal-title":"J Cardiovasc Dev Dis"},{"key":"B21","doi-asserted-by":"publisher","first-page":"868","DOI":"10.1093\/europace\/euaa406","article-title":"Optimizing cryoballoon pulmonary vein isolation: lessons from >1000 procedures- the Frankfurt approach","volume":"23","author":"Bordignon","year":"2021","journal-title":"Europace"},{"key":"B22","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1002\/clc.23391","article-title":"Procedural outcomes and learning curve of cardiac arrhythmias catheter ablation using remote magnetic navigation: experience from a large-scale single-center study","volume":"43","author":"Li","year":"2020","journal-title":"Clin Cardiol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1111\/jce.16526","article-title":"Impact of the individual operator experience and learning curve of a novel size adjustable cryoballoon","volume":"36","author":"Hayashi","year":"2025","journal-title":"J Cardiovasc Electrophysiol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v059.i05","article-title":"Mediation: r package for causal mediation analysis","volume":"59","author":"Tingley","year":"2014","journal-title":"J Stat Softw"},{"key":"B25","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1111\/jce.16135","article-title":"Acute procedural efficacy and safety of a novel expandable diameter cryoballoon in atrial fibrillation ablation: early results from a multicenter ablation registry","volume":"35","author":"Isonaga","year":"2024","journal-title":"J Cardiovasc Electrophysiol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.ijcard.2019.11.089","article-title":"Predictors of durable pulmonary vein isolation after second-generation cryoballoon ablation with a single short freeze strategy\u2014different criteria for the best freeze of the 4 individual PVs","volume":"301","author":"Miyazaki","year":"2020","journal-title":"Int J Cardiol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"101244","DOI":"10.1016\/j.ijcha.2023.101244","article-title":"Cryoballoon pulmonary vein isolation for atrial fibrillation in obese patients: a non-inferiority analysis","volume":"47","author":"Boehmer","year":"2023","journal-title":"Int J Cardiol Heart Vasc"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1400","DOI":"10.1002\/joa3.13179","article-title":"Achieving reduced radiation exposure with maintained fluoroscopy effectiveness using ultralow-dose settings in cryoballoon ablation","volume":"40","author":"Kaneshiro","year":"2024","journal-title":"J Arrhythm"},{"key":"B29","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1007\/s10840-023-01582-0","article-title":"Regional variations in patient selection and procedural characteristics for cryoballoon ablation of atrial fibrillation in the cryo global registry","volume":"67","author":"Scazzuso","year":"2024","journal-title":"J Interv Card Electrophysiol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1177\/1740774520947644","article-title":"Exploring mechanisms of action in clinical trials of complex surgical interventions using mediation analysis","volume":"17","author":"Sharples","year":"2020","journal-title":"Clin Trials"},{"key":"B31","doi-asserted-by":"publisher","first-page":"euad231","DOI":"10.1093\/europace\/euad231","article-title":"Systematic workflow and electrogram guidance to reduce x-ray exposure time during cryoballoon ablation of atrial fibrillation: the SWEET-Cryo strategy","volume":"25","author":"Rodr\u00edguez Mu\u00f1oz","year":"2023","journal-title":"Europace"},{"key":"B32","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1007\/s10840-020-00737-7","article-title":"Reducing radiation exposure in second-generation cryoballoon ablation without compromising clinical outcome","volume":"60","author":"Holl","year":"2021","journal-title":"J Interv Card Electrophysiol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1093\/europace\/eux066","article-title":"Significant reduction of radiation exposure in cryoballoon-based pulmonary vein isolation","volume":"20","author":"Reissmann","year":"2018","journal-title":"Europace"},{"key":"B34","doi-asserted-by":"publisher","first-page":"2101","DOI":"10.1007\/s10840-024-01837-4","article-title":"History of stroke as a predictor of high left atrial fibrosis in patients with persistent atrial fibrillation-insight from the DECAAF II randomized trial","volume":"67","author":"El Hajjar","year":"2024","journal-title":"J Interv Card Electrophysiol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1111\/pace.70154","article-title":"Impact of pulmonary vein anatomy on outcomes in patients undergoing cryoballoon ablation for atrial fibrillation","volume":"49","author":"Keresteci","year":"2026","journal-title":"Pacing Clin Electrophysiol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1002\/joa3.12801","article-title":"Clinical utility of the \u201cballoon lever technique\u201d in the right inferior pulmonary vein cryoballoon ablation","volume":"39","author":"Wakabayashi","year":"2022","journal-title":"J Arrhythm"},{"key":"B37","doi-asserted-by":"publisher","first-page":"794834","DOI":"10.3389\/fcvm.2021.794834","article-title":"Comparison of using second-generation cryoballoon and radiofrequency catheter for atrial fibrillation ablation in patients with the common ostium of Inferior pulmonary veins","volume":"8","author":"Li","year":"2022","journal-title":"Front Cardiovasc Med"},{"key":"B38","doi-asserted-by":"publisher","first-page":"2091","DOI":"10.1007\/s10840-023-01538-4","article-title":"The absence of real-time pulmonary vein isolation during cryoballoon ablation is associated with atrial fibrillation recurrence and pulmonary vein reconnection: insights from the middelheim-PVI registry 2","volume":"66","author":"De Greef","year":"2023","journal-title":"J Interv Card Electrophysiol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1420","DOI":"10.1093\/europace\/euac100","article-title":"Polarx cryoballoon metrics predicting successful pulmonary vein isolation: targets for ablation of atrial fibrillation","volume":"24","author":"Honarbakhsh","year":"2022","journal-title":"Europace"},{"key":"B40","doi-asserted-by":"publisher","first-page":"746820","DOI":"10.3389\/fcvm.2021.746820","article-title":"Predicting phrenic nerve palsy in patients undergoing atrial fibrillation ablation with the cryoballoon-does sex matter?","volume":"8","author":"Pott","year":"2021","journal-title":"Front Cardiovasc Med"},{"key":"B41","doi-asserted-by":"publisher","first-page":"6226","DOI":"10.1038\/s41598-021-85618-3","article-title":"Long-term course of phrenic nerve injury after cryoballoon ablation of atrial fibrillation","volume":"11","author":"Tokuda","year":"2021","journal-title":"Sci Rep"},{"key":"B42","doi-asserted-by":"publisher","first-page":"e010516","DOI":"10.1161\/CIRCEP.121.010516","article-title":"Phrenic nerve injury during cryoballoon-based pulmonary vein isolation: results of the worldwide YETI registry","volume":"15","author":"Heeger","year":"2022","journal-title":"Circ Arrhythm Electrophysiol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1007\/s10840-023-01645-2","article-title":"Feasibility and efficacy of a novel size adjustable cryoballoon for ablation of atrial fibrillation","volume":"67","author":"Frommeyer","year":"2024","journal-title":"J Interv Card Electrophysiol"},{"key":"B44","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1111\/jce.16220","article-title":"One-year outcomes of pulmonary vein isolation with a novel cryoballoon: primary results of the FROZEN AF trial","volume":"35","author":"Ellenbogen","year":"2024","journal-title":"J Cardiovasc Electrophysiol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1111\/jce.15288","article-title":"The established and the challenger: a direct comparison of current cryoballoon technologies for pulmonary vein isolation","volume":"33","author":"Moser","year":"2022","journal-title":"J Cardiovasc Electrophysiol"},{"key":"B46","doi-asserted-by":"publisher","first-page":"1237","DOI":"10.1093\/europace\/euab018","article-title":"Acute safety, efficacy, and advantages of a novel cryoballoon ablation system for pulmonary vein isolation in patients with paroxysmal atrial fibrillation: initial clinical experience","volume":"23","author":"Anic","year":"2021","journal-title":"Europace"},{"key":"B47","doi-asserted-by":"publisher","first-page":"1917","DOI":"10.1093\/europace\/euac148","article-title":"Novel cryoballoon ablation system for pulmonary vein isolation: multicenter assessment of efficacy and safety-ANTARCTICA study","volume":"24","author":"Heeger","year":"2022","journal-title":"Europace"},{"key":"B48","doi-asserted-by":"publisher","first-page":"euad329","DOI":"10.1093\/europace\/euad329","article-title":"Efficacy and safety of pulmonary vein isolation with pulsed field ablation vs. Novel cryoballoon ablation system for atrial fibrillation","volume":"25","author":"Badertscher","year":"2023","journal-title":"Europace"},{"key":"B49","doi-asserted-by":"publisher","first-page":"1305","DOI":"10.1056\/NEJMoa2019422","article-title":"Early rhythm-control therapy in patients with atrial fibrillation","volume":"383","author":"Kirchhof","year":"2020","journal-title":"N Engl J Med"},{"key":"B50","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1016\/j.jacc.2021.06.038","article-title":"Cryoballoon ablation as initial treatment for atrial fibrillation: JACC state-of-the-art review","volume":"78","author":"Andrade","year":"2021","journal-title":"J Am Coll Cardiol"}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2026.1931483\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T04:27:24Z","timestamp":1787804844000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2026.1931483\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,27]]},"references-count":50,"alternative-id":["10.3389\/fcvm.2026.1931483"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2026.1931483","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,27]]},"article-number":"1931483"}}