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However, the ways in which pulmonary vein isolation (PVI) affects the dynamics of rotor\/multiple wavelets in PeAF patients remain elusive. Real-time phase-mapping (ExTRa mapping, EXT) in the whole left atrium (LA) was performed during PeAF before and after PVI (<jats:italic>n<\/jats:italic>\u2009=\u2009111). The percentage of time in which rotor\/multiple wavelets (phase singularities) was observed during each 5-s phase-mapping recording (non-passive activation ratio, %NP) was measured as an index of its burden. The mapping areas showing %NP\u2009\u2265\u200950% were defined as rotor\/multiple-wavelet substrates (RSs). Before PVI, RSs were globally distributed in the LA. After PVI, %NP decreased (&lt;\u200950%) in many RSs (PVI-modifiable RSs) but remained high (\u2265\u200950%) in some RSs, especially localized in the anterior\/septum\/inferior regions (PVI-unmodifiable RSs, 2.3\u2009\u00b1\u20091.0 areas\/patient). Before PVI, vagal response (VR) to high-frequency stimulation was observed in 23% of RSs, especially localized in the inferior region. VR disappearance after PVI was more frequently observed in PVI-modifiable RSs (79%) than in PVI-unmodifiable RSs (55%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05), suggesting that PVI affects autonomic nerve activities and rotor\/multiple wavelet dynamics. PVI-unmodifiable RSs were adjunctively ablated in 104 patients. The 1-year AT\/AF-free survival rate was 70% in those with PVI alone (<jats:italic>n<\/jats:italic>\u2009=\u2009115), and 86% in patients with the adjunctive ablation (log-rank test\u2009=\u20097.65, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01). PVI suppresses not only ectopic firing but also rotor\/multiple wavelets partly via modification of autonomic nerve activities. The adjunctive ablation of PVI-unmodifiable RSs improved the outcome in PeAF patients and might be a novel ablation strategy beyond PVI.<\/jats:p>","DOI":"10.1007\/s00380-022-02209-6","type":"journal-article","created":{"date-parts":[[2022,11,27]],"date-time":"2022-11-27T20:13:19Z","timestamp":1669579999000},"page":"699-710","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Effect of pulmonary vein isolation on rotor\/multiple wavelet dynamics in persistent atrial fibrillation, association with vagal response and implications for adjunctive ablation"],"prefix":"10.1007","volume":"38","author":[{"given":"Asuka","family":"Nishimura","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2345-9557","authenticated-orcid":false,"given":"Masahide","family":"Harada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Ashihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Nomura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Motoike","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Koshikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takehiro","family":"Ito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiichi","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukio","family":"Ozaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideo","family":"Izawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,11,27]]},"reference":[{"key":"2209_CR1","doi-asserted-by":"publisher","first-page":"1812","DOI":"10.1056\/NEJMoa1408288","volume":"372","author":"A Verma","year":"2015","unstructured":"Verma A, Jiang CY, Betts TR, Chen J, Deisenhofer I, Mantovan R, Macle L, Morillo CA, Haverkamp W, Weerasooriya R, Albenque JP, Nardi S, Menardi E, Novak P, Sanders P, Investigators STARAFII (2015) Approaches to catheter ablation for persistent atrial fibrillation. 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