{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T02:34:27Z","timestamp":1788489267168,"version":"build-2803163510"},"reference-count":56,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"19","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2020,10,6]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Atrial fibrillation (AF) driver mechanisms are obscured to clinical multielectrode mapping approaches that provide partial, surface\u2010only visualization of unstable 3\u2010dimensional atrial conduction. We hypothesized that transient modulation of refractoriness by pharmacologic challenge during multielectrode mapping improves visualization of hidden paths of reentrant AF drivers for targeted ablation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">Pharmacologic challenge with adenosine was tested in ex vivo human hearts with a history of AF and cardiac diseases by multielectrode and high\u2010resolution subsurface near\u2010infrared optical mapping, integrated with 3\u2010dimensional structural imaging and heart\u2010specific computational simulations. Adenosine challenge was also studied on acutely terminated AF drivers in 10 patients with persistent AF. Ex vivo, adenosine stabilized reentrant driver paths within arrhythmogenic fibrotic hubs and improved visualization of reentrant paths, previously seen as focal or unstable breakthrough activation pattern, for targeted AF ablation. Computational simulations suggested that shortening of atrial refractoriness by adenosine may (1) improve driver stability by annihilating spatially unstable functional blocks and tightening reentrant circuits around fibrotic substrates, thus unmasking the common reentrant path; and (2) destabilize already stable reentrant drivers along fibrotic substrates by accelerating competing fibrillatory wavelets or secondary drivers. In patients with persistent AF, adenosine challenge unmasked hidden common reentry paths (9\/15 AF drivers, 41\u00b126% to 68\u00b125% visualization), but worsened visualization of previously visible reentry paths (6\/15, 74\u00b114% to 34\u00b112%). AF driver ablation led to acute termination of AF.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Our ex vivo to in vivo human translational study suggests that transiently altering atrial refractoriness can stabilize reentrant paths and unmask arrhythmogenic hubs to guide targeted AF driver ablation treatment.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.120.017789","type":"journal-article","created":{"date-parts":[[2020,10,2]],"date-time":"2020-10-02T09:04:04Z","timestamp":1601629444000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":23,"title":["Unmasking Arrhythmogenic Hubs of Reentry Driving Persistent Atrial Fibrillation for Patient\u2010Specific Treatment"],"prefix":"10.1161","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1298-6415","authenticated-orcid":false,"given":"Brian J.","family":"Hansen","sequence":"first","affiliation":[{"name":"Department of Physiology &amp; Cell Biology and Frick Center for Heart Failure and Arrhythmia The Ohio State University Wexner Medical Center Columbus OH"},{"name":"Davis Heart &amp; Lung Research InstituteThe Ohio State University Wexner Medical Center Columbus OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3303-0401","authenticated-orcid":false,"given":"Jichao","family":"Zhao","sequence":"additional","affiliation":[{"name":"University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8962-0326","authenticated-orcid":false,"given":"Katelynn M.","family":"Helfrich","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Cell Biology and Frick Center for Heart Failure and Arrhythmia The Ohio State University Wexner Medical Center Columbus OH"},{"name":"Davis Heart &amp; Lung Research InstituteThe Ohio State University Wexner Medical Center Columbus OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Cell Biology and Frick Center for Heart Failure and Arrhythmia The Ohio State University Wexner Medical Center Columbus OH"},{"name":"Davis Heart &amp; Lung Research InstituteThe Ohio State University Wexner Medical Center Columbus OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2725-4129","authenticated-orcid":false,"given":"Alexander","family":"Iancau","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Cell Biology and Frick Center for Heart Failure and Arrhythmia The Ohio State University Wexner Medical Center Columbus OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander M.","family":"Zolotarev","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Cell Biology and Frick Center for Heart Failure and Arrhythmia The Ohio State University Wexner Medical Center Columbus OH"},{"name":"Skolkovo Institute of Science and Technology Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanislav O.","family":"Zakharkin","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Cell Biology and Frick Center for Heart Failure and Arrhythmia The Ohio State University Wexner Medical Center Columbus OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anuradha","family":"Kalyanasundaram","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Cell Biology and Frick Center for Heart Failure and Arrhythmia The Ohio State University Wexner Medical Center Columbus OH"},{"name":"Davis Heart &amp; Lung Research InstituteThe Ohio State University Wexner Medical Center Columbus OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Subr","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Cell Biology and Frick Center for Heart Failure and Arrhythmia The Ohio State University Wexner Medical Center Columbus OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nawshin","family":"Dastagir","sequence":"additional","affiliation":[{"name":"University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roshan","family":"Sharma","sequence":"additional","affiliation":[{"name":"University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esthela J.","family":"Artiga","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Cell Biology and Frick Center for Heart Failure and Arrhythmia The Ohio State University Wexner Medical Center Columbus OH"},{"name":"Davis Heart &amp; Lung Research InstituteThe Ohio State University Wexner Medical Center Columbus OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Salgia","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Cell Biology and Frick Center for Heart Failure and Arrhythmia The Ohio State University Wexner Medical Center Columbus OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9014-8978","authenticated-orcid":false,"given":"Mustafa M.","family":"Houmsse","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Cell Biology and Frick Center for Heart Failure and Arrhythmia The Ohio State University Wexner Medical Center Columbus OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Kahaly","sequence":"additional","affiliation":[{"name":"Davis Heart &amp; Lung Research InstituteThe Ohio State University Wexner Medical Center Columbus OH"},{"name":"Department of Internal Medicine The Ohio State University Wexner Medical Center Columbus OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M. L.","family":"Janssen","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Cell Biology and Frick Center for Heart Failure and Arrhythmia The Ohio State University Wexner Medical Center Columbus OH"},{"name":"Davis Heart &amp; Lung Research InstituteThe Ohio State University Wexner Medical Center Columbus OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7977-8717","authenticated-orcid":false,"given":"Peter J.","family":"Mohler","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Cell Biology and Frick Center for Heart Failure and Arrhythmia The Ohio State University Wexner Medical Center Columbus OH"},{"name":"Davis Heart &amp; Lung Research InstituteThe Ohio State University Wexner Medical Center Columbus OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nahush A.","family":"Mokadam","sequence":"additional","affiliation":[{"name":"Davis Heart &amp; Lung Research InstituteThe Ohio State University Wexner Medical Center Columbus OH"},{"name":"Division of Cardiac Surgery The Ohio State University Wexner Medical Center Columbus OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0040-3638","authenticated-orcid":false,"given":"Bryan A.","family":"Whitson","sequence":"additional","affiliation":[{"name":"Davis Heart &amp; Lung Research InstituteThe Ohio State University Wexner Medical Center Columbus OH"},{"name":"Division of Cardiac Surgery The Ohio State University Wexner Medical Center Columbus OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad R.","family":"Afzal","sequence":"additional","affiliation":[{"name":"Davis Heart &amp; Lung Research InstituteThe Ohio State University Wexner Medical Center Columbus OH"},{"name":"Department of Internal Medicine The Ohio State University Wexner Medical Center Columbus OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orlando P.","family":"Simonetti","sequence":"additional","affiliation":[{"name":"Davis Heart &amp; Lung Research InstituteThe Ohio State University Wexner Medical Center Columbus OH"},{"name":"Department of Biomedical Engineering The Ohio State University Wexner Medical Center Columbus OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D.","family":"Hummel","sequence":"additional","affiliation":[{"name":"Davis Heart &amp; Lung Research InstituteThe Ohio State University Wexner Medical Center Columbus OH"},{"name":"Department of Internal Medicine The Ohio State University Wexner Medical Center Columbus OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1035-4569","authenticated-orcid":false,"given":"Vadim V.","family":"Fedorov","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Cell Biology and Frick Center for Heart Failure and Arrhythmia The Ohio State University Wexner Medical Center Columbus OH"},{"name":"Davis Heart &amp; Lung Research InstituteThe Ohio State University Wexner Medical Center Columbus OH"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/europace\/eux274"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.11.079"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2012.05.022"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.005421"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCEP.117.005846"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacep.2018.08.024"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCEP.115.003648"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.115.017007"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/eht267"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacep.2017.07.019"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehv233"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1540-8167.1994.tb01288.x"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.115.021165"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.633735"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2020.01.017"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10840-020-00744-8"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2011.04.016"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(97)00385-9"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2008.07.012"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.117.005922"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1998.275.1.H301"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/europace\/euu230"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCEP.111.969022"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCEP.117.005258"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/europace\/euy095"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/ehjci\/jew304"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacep.2017.05.002"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1111\/jce.12773"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCEP.112.975144"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacep.2017.09.177"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCEP.117.005858"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1009758501195"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1253\/jcj.64.430"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-127-6-199709150-00001"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1111\/jce.14303"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(84)80233-8"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCEP.116.004899"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCEP.118.006870"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.3"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00407.2015"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1540-8167.2009.01712.x"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCEP.117.006119"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.104.517011"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jelectrocard.2006.04.009"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2011.05.061"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.311081"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCEP.116.004398"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.112.000778"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1109\/TMI.2012.2227776"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1098\/rsta.2006.1781"},{"key":"e_1_3_2_52_2","first-page":"487","article-title":"Benchmarking electrophysiological models of human atrial myocytes","volume":"3","author":"Wilhelms M","year":"2012","unstructured":"Wilhelms M, Hettmann H, Maleckar MM, Koivumaki JT, Dossel O, Seemann G. Benchmarking electrophysiological models of human atrial myocytes. Front Physiol. 2012;3:487.","journal-title":"Front Physiol"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCEP.111.967950"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1093\/europace\/euu251"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.111.300157"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep20835"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCEP.115.003064"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.120.017789","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T11:50:49Z","timestamp":1715601049000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.120.017789"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,6]]},"references-count":56,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2020,10,6]]}},"alternative-id":["10.1161\/JAHA.120.017789"],"URL":"https:\/\/doi.org\/10.1161\/jaha.120.017789","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,6]]},"assertion":[{"value":"2020-05-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-08-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-10-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e017789"}}