{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T09:19:13Z","timestamp":1791537553087,"version":"4.3.4"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T00:00:00Z","timestamp":1655078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,10,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>The value of additional ablation beyond pulmonary vein isolation for atrial fibrillation (AF) ablation is unclear, especially for persistent AF. The optimal target for substrate modification to improve outcomes is uncertain. We investigate the utility of low-voltage area (LVA) substrate modification in patients undergoing catheter ablation for AF.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>This meta-analysis was reported according to the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. Medline, Scopus and Cochrane Central Register of Controlled Trials were systematically searched to identify relevant studies. Risk of bias was assessed using the Cochrane risk of bias tool. Only randomized studies were included. AF patients who underwent catheter ablation with voltage-guided substrate modification targeting LVA (LVA group) vs. conventional ablation approaches not targeting LVA (non-LVA group) were compared. Four studies comprising 539 patients were included (36% female). Freedom from arrhythmia (FFA) in patients with persistent AF was greater in the LVA group [risk ratio (RR) 1.30; 95% confidence interval (CI) 1.03\u20131.64]. There was no difference in FFA in patients with paroxysmal AF between groups (RR 1.30; 95% CI 0.89\u20131.91). There was no difference in total procedural time (mean difference \u221217.54\u2005min; 95% CI \u221264.37 to 29.28\u2005min) or total ablation time (mean difference \u221236.17\u2005min; 95% CI \u221293.69 to 21.35\u2005min) in all included patients regardless of AF type between groups. There was no difference in periprocedural complications between groups in all included patients regardless of AF type (RR 0.93; 95% CI 0.22\u20133.82).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>This meta-analysis demonstrates improved FFA in persistent AF patients who underwent voltage-guided substrate modification targeting LVA.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/europace\/euac089","type":"journal-article","created":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T16:01:25Z","timestamp":1655136085000},"page":"1585-1598","source":"Crossref","is-referenced-by-count":52,"title":["Low-voltage area substrate modification for atrial fibrillation ablation: a systematic review and meta-analysis of clinical trials"],"prefix":"10.1093","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9411-1478","authenticated-orcid":false,"given":"Joey","family":"Junarta","sequence":"first","affiliation":[{"name":"Department of Medicine, Thomas Jefferson University Hospitals , Philadelphia, PA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad U","family":"Siddiqui","sequence":"additional","affiliation":[{"name":"Department of Medicine, Thomas Jefferson University Hospitals , Philadelphia, PA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua M","family":"Riley","sequence":"additional","affiliation":[{"name":"Department of Medicine, Thomas Jefferson University Hospitals , Philadelphia, PA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean J","family":"Dikdan","sequence":"additional","affiliation":[{"name":"Jefferson Heart Institute, Thomas Jefferson University Hospitals , 925 Chestnut Street, Mezzanine Level, Philadelphia, PA 19107 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akash","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Medicine, Thomas Jefferson University Hospitals , Philadelphia, PA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7645-6405","authenticated-orcid":false,"given":"Daniel R","family":"Frisch","sequence":"additional","affiliation":[{"name":"Jefferson Heart Institute, Thomas Jefferson University Hospitals , 925 Chestnut Street, Mezzanine Level, Philadelphia, PA 19107 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,6,13]]},"reference":[{"key":"2022101319381890500_euac089-B1","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":"2022101319381890500_euac089-B2","article-title":"2017 HRS\/EHRA\/ECAS\/APHRS\/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary","author":"Calkins"},{"key":"2022101319381890500_euac089-B3","doi-asserted-by":"crossref","first-page":"1921","DOI":"10.1016\/j.jacc.2012.04.060","article-title":"Catheter ablation of long-standing persistent atrial fibrillation: 5-year outcomes of the Hamburg Sequential Ablation Strategy","volume":"60","author":"Tilz","year":"2012","journal-title":"J Am Coll Cardiol"},{"key":"2022101319381890500_euac089-B4","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1016\/j.hrthm.2010.01.017","article-title":"Outcomes of long-standing persistent atrial fibrillation ablation: a systematic review","volume":"7","author":"Brooks","year":"2010","journal-title":"Heart Rhythm"},{"key":"2022101319381890500_euac089-B5","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.1016\/j.hrthm.2020.06.020","article-title":"Cryoballoon ablation of pulmonary veins for persistent atrial fibrillation: results from the multicenter STOP Persistent AF trial","volume":"17","author":"Su","year":"2020","journal-title":"Heart Rhythm"},{"key":"2022101319381890500_euac089-B6","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.jacep.2018.11.020","article-title":"Pulmonary vein reconnection no longer occurs in the majority of patients after a single pulmonary vein isolation procedure","volume":"5","author":"De Pooter","year":"2019","journal-title":"JACC Clin Electrophysiol"},{"key":"2022101319381890500_euac089-B7","doi-asserted-by":"crossref","first-page":"758408","DOI":"10.3389\/fcvm.2021.758408","article-title":"Cryoballoon ablation strategy in persistent atrial fibrillation","volume":"8","author":"Straube","year":"2021","journal-title":"Front Cardiovasc Med"},{"key":"2022101319381890500_euac089-B8","doi-asserted-by":"crossref","first-page":"2044","DOI":"10.1016\/j.jacc.2003.12.054","article-title":"A new approach for catheter ablation of atrial fibrillation: mapping of the electrophysiologic substrate","volume":"43","author":"Nademanee","year":"2004","journal-title":"J Am Coll Cardiol"},{"key":"2022101319381890500_euac089-B9","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.hrthm.2004.03.072","article-title":"Electrophysiologic and clinical consequences of linear catheter ablation to transect the anterior left atrium in patients with atrial fibrillation","volume":"1","author":"Sanders","year":"2004","journal-title":"Heart Rhythm"},{"key":"2022101319381890500_euac089-B10","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1056\/NEJMoa1408288","article-title":"Approaches to catheter ablation for persistent atrial fibrillation","volume":"372","author":"Verma","year":"2015","journal-title":"N Engl J Med"},{"key":"2022101319381890500_euac089-B11","doi-asserted-by":"crossref","first-page":"2743","DOI":"10.1016\/j.jacc.2015.09.088","article-title":"Pulmonary vein isolation versus defragmentation: the CHASE-AF clinical trial","volume":"66","author":"Vogler","year":"2015","journal-title":"J Am Coll Cardiol"},{"key":"2022101319381890500_euac089-B12","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.hrthm.2015.10.006","article-title":"Biatrial linear ablation in sustained nonpermanent AF: results of the substrate modification with ablation and antiarrhythmic drugs in nonpermanent atrial fibrillation (SMAN-PAF) trial","volume":"13","author":"Wynn","year":"2016","journal-title":"Heart Rhythm"},{"key":"2022101319381890500_euac089-B13","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1161\/CIRCEP.111.966226","article-title":"Randomized ablation strategies for the treatment of persistent atrial fibrillation: RASTA study","volume":"5","author":"Dixit","year":"2012","journal-title":"Circ Arrhythm Electrophysiol"},{"key":"2022101319381890500_euac089-B14","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1161\/CIRCEP.109.899021","article-title":"Characterization, mapping, and catheter ablation of recurrent atrial tachycardias after stepwise ablation of long-lasting persistent atrial fibrillation","volume":"3","author":"Rostock","year":"2010","journal-title":"Circ Arrhythm Electrophysiol"},{"key":"2022101319381890500_euac089-B15","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1161\/CIRCEP.112.971259","article-title":"Prevalence and types of pitfall in the assessment of mitral isthmus linear conduction block","volume":"5","author":"Shah","year":"2012","journal-title":"Circ Arrhythm Electrophysiol"},{"key":"2022101319381890500_euac089-B16","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.jacc.2004.10.035","article-title":"Pre-existent left atrial scarring in patients undergoing pulmonary vein antrum isolation: an independent predictor of procedural failure","volume":"45","author":"Verma","year":"2005","journal-title":"J Am Coll Cardiol"},{"key":"2022101319381890500_euac089-B17","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1001\/jama.2014.3","article-title":"Association of atrial tissue fibrosis identified by delayed enhancement MRI and atrial fibrillation catheter ablation: the DECAAF study","volume":"311","author":"Marrouche","year":"2014","journal-title":"JAMA"},{"key":"2022101319381890500_euac089-B18","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1111\/pace.13015","article-title":"Left atrial substrate modification targeting low-voltage areas for catheter ablation of atrial fibrillation: a systematic review and meta-analysis","volume":"40","author":"Blandino","year":"2017","journal-title":"Pacing Clin Electrophysiol"},{"key":"2022101319381890500_euac089-B19","doi-asserted-by":"crossref","first-page":"264","DOI":"10.7326\/0003-4819-151-4-200908180-00135","article-title":"Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement","volume":"151","author":"Moher","year":"2009","journal-title":"Ann Intern Med"},{"key":"2022101319381890500_euac089-B20","doi-asserted-by":"crossref","first-page":"d5928","DOI":"10.1136\/bmj.d5928","article-title":"The Cochrane Collaboration\u2019s tool for assessing risk of bias in randomised trials","volume":"343","author":"Higgins","year":"2011","journal-title":"BMJ"},{"key":"2022101319381890500_euac089-B21","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.jclinepi.2017.12.004","article-title":"Recommendations for assessing the risk of bias in systematic reviews of health-care interventions","volume":"97","author":"Viswanathan","year":"2018","journal-title":"J Clin Epidemiol"},{"key":"2022101319381890500_euac089-B22","volume-title":"Advanced Topics in Systematic Reviews: Fixed-Effects and Random-Effects Models","author":"Murad","year":"2014"},{"key":"2022101319381890500_euac089-B23","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1093\/ije\/dys041","article-title":"Predicting the extent of heterogeneity in meta-analysis, using empirical data from the Cochrane Database of Systematic Reviews","volume":"41","author":"Turner","year":"2012","journal-title":"Int J Epidemiol"},{"key":"2022101319381890500_euac089-B24","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1136\/ebmed-2017-110668","article-title":"Rating the certainty in evidence in the absence of a single estimate of effect","volume":"22","author":"Murad","year":"2017","journal-title":"Evid Based Med"},{"key":"2022101319381890500_euac089-B25","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.ijcard.2014.05.022","article-title":"A novel individualized substrate modification approach for the treatment of long-standing persistent atrial fibrillation: preliminary results","volume":"175","author":"Wang","year":"2014","journal-title":"Int J Cardiol"},{"key":"2022101319381890500_euac089-B26","doi-asserted-by":"crossref","first-page":"e005405","DOI":"10.1161\/CIRCEP.117.005405","article-title":"STABLE-SR (Electrophysiological Substrate Ablation in the Left Atrium During Sinus Rhythm) for the treatment of nonparoxysmal atrial fibrillation: a prospective, multicenter randomized clinical trial","volume":"10","author":"Yang","year":"2017","journal-title":"Circ Arrhythm Electrophysiol"},{"key":"2022101319381890500_euac089-B27","doi-asserted-by":"crossref","first-page":"1766","DOI":"10.1093\/europace\/eux310","article-title":"Individually tailored vs. standardized substrate modification during radiofrequency catheter ablation for atrial fibrillation: a randomized study","volume":"20","author":"Kircher","year":"2018","journal-title":"Europace"},{"key":"2022101319381890500_euac089-B28","doi-asserted-by":"crossref","first-page":"e015927","DOI":"10.1161\/JAHA.120.015927","article-title":"Additional low-voltage-area ablation in patients with paroxysmal atrial fibrillation: results of the randomized controlled VOLCANO trial","volume":"9","author":"Masuda","year":"2020","journal-title":"J Am Heart Assoc"},{"key":"2022101319381890500_euac089-B29","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1016\/j.jacc.2013.03.081","article-title":"Inverse relationship between fractionated electrograms and atrial fibrosis in persistent atrial fibrillation: combined magnetic resonance imaging and high-density mapping","volume":"62","author":"Jadidi","year":"2013","journal-title":"J Am Coll Cardiol"},{"key":"2022101319381890500_euac089-B30","doi-asserted-by":"crossref","first-page":"1758","DOI":"10.1161\/CIRCULATIONAHA.108.811877","article-title":"Detection and quantification of left atrial structural remodeling with delayed-enhancement magnetic resonance imaging in patients with atrial fibrillation","volume":"119","author":"Oakes","year":"2009","journal-title":"Circulation"},{"key":"2022101319381890500_euac089-B31","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1111\/jce.14957","article-title":"Efficacy of LGE-MRI-guided fibrosis ablation versus conventional catheter ablation of atrial fibrillation: the DECAAF II trial: study design","volume":"32","author":"Marrouche","year":"2021","journal-title":"J Cardiovasc Electrophysiol"},{"key":"2022101319381890500_euac089-B32","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1002\/clc.23677","article-title":"The efficacy and safety of left atrial low-voltage area guided ablation for recurrence prevention compared to pulmonary vein isolation alone in patients with persistent atrial fibrillation trial: design and rationale","volume":"44","author":"Sunaga","year":"2021","journal-title":"Clin Cardiol"},{"key":"2022101319381890500_euac089-B33","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1111\/jce.13002","article-title":"Correlation of left atrial voltage distribution between sinus rhythm and atrial fibrillation: identifying structural remodeling by 3-D electroanatomic mapping irrespective of the rhythm","volume":"27","author":"Yagishita A","year":"2016","journal-title":"J Cardiovasc Electrophysiol"},{"key":"2022101319381890500_euac089-B34","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1093\/europace\/eux274","article-title":"2017 HRS\/EHRA\/ECAS\/APHRS\/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation","volume":"20","author":"Calkins","year":"2018","journal-title":"Europace"},{"key":"2022101319381890500_euac089-B35","doi-asserted-by":"crossref","first-page":"e006576","DOI":"10.1161\/CIRCEP.118.006576","article-title":"Use of ablation index-guided ablation results in high rates of durable pulmonary vein isolation and freedom from arrhythmia in persistent atrial fibrillation patients: the PRAISE study results","volume":"11","author":"Hussein","year":"2018","journal-title":"Circ Arrhythm Electrophysiol"},{"key":"2022101319381890500_euac089-B36","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.jacep.2017.06.023","article-title":"Evaluation of a strategy aiming to enclose the pulmonary veins with contiguous and optimized radiofrequency lesions in paroxysmal atrial fibrillation: a pilot study","volume":"4","author":"Taghji","year":"2018","journal-title":"JACC Clin Electrophysiol"},{"key":"2022101319381890500_euac089-B37","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/j.hrthm.2017.01.003","article-title":"Revisiting pulmonary vein isolation alone for persistent atrial fibrillation: a systematic review and meta-analysis","volume":"14","author":"Voskoboinik","year":"2017","journal-title":"Heart Rhythm"},{"key":"2022101319381890500_euac089-B38","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1093\/europace\/euaa055","article-title":"Benefit of ultra-high-density mapping-guided radiofrequency reablation in pulmonary vein isolation non-responders after initial cryoballoon procedure","volume":"22","author":"Straube","year":"2020","journal-title":"Europace"},{"key":"2022101319381890500_euac089-B39","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.hrthm.2015.10.023","article-title":"Prevalence and distribution of focal triggers in persistent and long-standing persistent atrial fibrillation","volume":"13","author":"Santangeli","year":"2016","journal-title":"Heart Rhythm"},{"key":"2022101319381890500_euac089-B40","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1046\/j.1540-8167.2005.40665.x","article-title":"Catheter ablation of atrial fibrillation originating from the non-pulmonary vein foci","volume":"16","author":"Chen","year":"2005","journal-title":"J Cardiovasc Electrophysiol"},{"key":"2022101319381890500_euac089-B41","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s10840-017-0234-x","article-title":"Prevalence of right atrial non-pulmonary vein triggers in atrial fibrillation patients treated with thyroid hormone replacement therapy","volume":"49","author":"Kim","year":"2017","journal-title":"J Interv Card Electrophysiol"},{"key":"2022101319381890500_euac089-B42","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1016\/j.jacc.2017.01.014","article-title":"Complexity and distribution of drivers in relation to duration of persistent atrial fibrillation","volume":"69","author":"Lim","year":"2017","journal-title":"J Am Coll Cardiol"},{"key":"2022101319381890500_euac089-B43","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":"Di Biase","year":"2016","journal-title":"J Am Coll Cardiol"},{"key":"2022101319381890500_euac089-B44","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1016\/j.ahj.2015.09.019","article-title":"Percutaneous alternative to the Maze procedure for the treatment of persistent or long-standing persistent atrial fibrillation (aMAZE trial): rationale and design","volume":"170","author":"Lee","year":"2015","journal-title":"Am Heart J"},{"key":"2022101319381890500_euac089-B45","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1001\/jama.2020.16195","article-title":"Effect of catheter ablation with vein of Marshall ethanol infusion vs catheter ablation alone on persistent atrial fibrillation: the VENUS randomized clinical trial","volume":"324","author":"Valderrabano","year":"2020","journal-title":"JAMA"},{"key":"2022101319381890500_euac089-B46","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1016\/j.jacc.2020.07.007","article-title":"Pulsed field ablation in patients with persistent atrial fibrillation","volume":"76","author":"Reddy","year":"2020","journal-title":"J Am Coll Cardiol"}],"container-title":["EP Europace"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/europace\/article-pdf\/24\/10\/1585\/46500587\/euac089.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/europace\/article-pdf\/24\/10\/1585\/46500587\/euac089.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T19:39:41Z","timestamp":1665689981000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/europace\/article\/24\/10\/1585\/6607479"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,13]]},"references-count":46,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,6,13]]},"published-print":{"date-parts":[[2022,10,13]]}},"URL":"https:\/\/doi.org\/10.1093\/europace\/euac089","relation":{},"ISSN":["1099-5129","1532-2092"],"issn-type":[{"value":"1099-5129","type":"print"},{"value":"1532-2092","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,10,6]]},"published":{"date-parts":[[2022,6,13]]}}}