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A better and more targeted ablation strategy is urgently needed to optimize outcomes of AF treatment. We sought to assess the safety and efficacy of targeting atrial fibrosis during ablation of persistent AF patients in improving procedural outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The DECAAF II trial (ClinicalTrials. gov identifier number NCT02529319) is a prospective, randomized, multicenter trial of patients with persistent AF. Patients with persistent AF undergoing a first\u2010time ablation procedure were randomized in a 1:1 fashion to receive conventional pulmonary vein isolation (PVI) ablation (Group 1) or PVI\u2009+\u2009fibrosis\u2010guided ablation (Group 2). Left atrial fibrosis and ablation induced scarring were defined by late gadolinium enhancement magnetic resonance imaging at baseline and at 3\u201312 months postablation, respectively. The primary endpoint is the recurrence of atrial arrhythmia postablation, including atrial fibrillation, atrial flutter, or atrial tachycardia after the 90\u2010day postablation blanking period. Patients were followed for a period of 12\u201318 months with a smartphone ECG Device (ECG Check Device, Cardiac Designs Inc.). With an anticipated enrollment of 900 patients, this study has an 80% power to detect a 26% reduction in the hazard ratio of the primary endpoint.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results and Conclusion<\/jats:title><jats:p>The DECAAF II trial is the first prospective, randomized, multicenter trial of patients with persistent AF using imaging defined atrial fibrosis as a treatment target. The trial will help define an optimal approach to catheter ablation of persistent AF, further our understanding of influencers of ablation lesion formation, and refine selection criteria for ablation based on atrial myopathy burden.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jce.14957","type":"journal-article","created":{"date-parts":[[2021,2,18]],"date-time":"2021-02-18T14:38:50Z","timestamp":1613659130000},"page":"916-924","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":82,"title":["Efficacy of LGE\u2010MRI\u2010guided fibrosis ablation versus conventional catheter ablation of atrial fibrillation: The DECAAF II trial: Study design"],"prefix":"10.1111","volume":"32","author":[{"given":"Nassir F.","family":"Marrouche","sequence":"first","affiliation":[{"name":"Department of Cardiology Tulane University School of Medicine New Orleans Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Greene","sequence":"additional","affiliation":[{"name":"University of Utah Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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