{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T12:48:22Z","timestamp":1790772502894,"version":"4.1.0"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2019,8,30]]},"abstract":"<jats:sec>\n            <jats:title>Rationale:<\/jats:title>\n            <jats:p>Costly proprietary panoramic multielectrode (64\u2013256) acquisition systems are being increasingly used together with conventional electroanatomical mapping systems for persistent atrial fibrillation (PersAF) ablation. However, such approaches target alleged drivers (rotational\/focal) regardless of their activation frequency dynamics.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Objectives:<\/jats:title>\n            <jats:p>To test the hypothesis that stable regions of higher than surrounding instantaneous frequency modulation (iFM) drive PersAF and determine whether rotational activity is specific for such regions.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results:<\/jats:title>\n            <jats:p>First, novel single-signal algorithms based on instantaneous amplitude modulation (iAM) and iFM to detect rotational-footprints without panoramic multielectrode acquisition systems were tested in 125 optical movies from 5 ex vivo Langendorff-perfused PersAF sheep hearts (sensitivity\/specificity, 92.6\/97.5%; accuracy, 2.5-mm) and in computer simulations. Then, 16 pigs underwent high-rate atrial pacing to develop PersAF. After a median (interquartile range [IQR]) of 4.4 (IQR, 2.5\u20139.9) months of high-rate atrial pacing followed by 4.1 (IQR, 2.7\u20135.4) months of self-sustained PersAF, pigs underwent in vivo high-density electroanatomical atrial mapping (4920 [IQR, 4435\u20135855] 8-second unipolar signals per map). The first 4 out of 16 pigs were used to adapt ex vivo optical proccessing of iFM\/iAM to in vivo electrical signals. In the remaining 12 out of 16 pigs, regions of higher than surrounding average iFM were considered leading-drivers. Two leading-driver + rotational-footprint maps were generated 2.6 (IQR, 2.4\u20132.9) hours apart to test leading-driver spatiotemporal stability and guide ablation. Leading-driver regions (2.5 [IQR, 2.0\u20134.0] regions\/map) exactly colocalized (95.7%) in the 2 maps, and their ablation terminated PersAF in 92.3% of procedures (radiofrequency until termination, 16.9 [IQR, 9.2\u201335.8] minutes; until nonsustainability, 20.4 [IQR, 12.8\u201344.0] minutes). Rotational-footprints were found at every leading-driver region, albeit most (76.8% [IQR, 70.5%\u201383.6%]) were located outside. Finally, the translational ability of this approach was tested in 3 PersAF redo patients.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Both rotational-footprints and spatiotemporally stable leading-driver regions can be located using iFM\/iAM algorithms without panoramic multielectrode acquisition systems. In pigs, ablation of leading-driver regions usually terminates PersAF and prevents its sustainability. Rotational activations are sensitive but not specific to such regions. Single-signal iFM\/iAM algorithms could be integrated into conventional electroanatomical mapping systems to improve driver detection accuracy and reduce the cost of patient-tailored\/mechanistic approaches.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.119.314930","type":"journal-article","created":{"date-parts":[[2019,8,1]],"date-time":"2019-08-01T09:00:26Z","timestamp":1564650026000},"page":"609-627","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":40,"title":["Instantaneous Amplitude and Frequency Modulations Detect the Footprint of Rotational Activity and Reveal Stable Driver Regions as Targets for Persistent Atrial Fibrillation Ablation"],"prefix":"10.1161","volume":"125","author":[{"given":"Jorge G.","family":"Quintanilla","sequence":"first","affiliation":[{"name":"From the Myocardial Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain (J.G.Q., J.M.A.-A., J.J., D.F.-R.)"},{"name":"Arrhythmia Unit, Cardiology Department, Cardiovascular Institute, Instituto de Investigaci\u00f3n Sanitaria del Hospital Cl\u00ednico San Carlos (IdISSC), Madrid, Spain (J.G.Q., N.P.-C., J.P.-V., D.F.-R.)"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain (J.G.Q., N.P.-C., J.J., J.P.-V., D.F.-R.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Manuel","family":"Alfonso-Almaz\u00e1n","sequence":"additional","affiliation":[{"name":"From the Myocardial Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain (J.G.Q., J.M.A.-A., J.J., D.F.-R.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicasio","family":"P\u00e9rez-Castellano","sequence":"additional","affiliation":[{"name":"Arrhythmia Unit, Cardiology Department, Cardiovascular Institute, Instituto de Investigaci\u00f3n Sanitaria del Hospital Cl\u00ednico San Carlos (IdISSC), Madrid, Spain (J.G.Q., N.P.-C., J.P.-V., D.F.-R.)"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain (J.G.Q., N.P.-C., J.J., J.P.-V., D.F.-R.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandeep V.","family":"Pandit","sequence":"additional","affiliation":[{"name":"Center for Arrhythmia Research, Department of Internal Medicine, University of Michigan, Ann Arbor (S.V.P., J.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Jalife","sequence":"additional","affiliation":[{"name":"From the Myocardial Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain (J.G.Q., J.M.A.-A., J.J., D.F.-R.)"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain (J.G.Q., N.P.-C., J.J., J.P.-V., D.F.-R.)"},{"name":"Center for Arrhythmia Research, Department of Internal 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