Device-Detected Atrial Fibrillation in Patients With and Without Cryptogenic Ischemia: The ANTARCTICA Pooled Analysis

Shadi Yaghi¹, Luciano A Sposato², Liqi Shu¹, Daniel García-Rodríguez³, Victor Castro Urda³, Fabienne Kreimer⁴, Michael Gotzmann⁴, Stefan Greisenegger⁵, Fadi Nahab⁶, Qasem N Alshaer⁶, Junpei Koge⁷, Hajime Ikenouchi⁷, Alkisti Kitsiou⁴, Georgios Tsivgoulis⁸, Sokratis Triantafyllou⁸, Loreta Skrebelyte-Strøm^{9

10}, Ole Morten Rønning¹⁰, Anna Tancin Lambert^{11

12}, Anne Hege Aamodt¹³, Gabriella Bufano¹⁴, Giulia Renda¹⁴, Elisa Cuadrado Godia¹⁵, Slaven Pikija¹⁶, Brian H Buck¹⁷, Eva Ondraskova¹⁷, Jeffrey S Healey¹⁸, William F McIntyre¹⁸, Michael D Hill¹⁹, Jeffrey L Saver²⁰, Scott E Kasner²¹, Hooman Kamel²², Mitchell S V Elkind^{23

24}, Lee H Schwamm²⁵, David M Kent²⁶, Aristeidis H Katsanos²⁷, Sebastian Fridman²; ANTARTICA Investigators

Affiliations

¹ Department of Neurology, The Alpert Medical School of Brown University, Providence, RI (S.Y., L.S.).
² Department of Neurology, Western University, Hamilton, Ontario, Canada (L.A.S., S.F.).
³ Department of Neurology, Unidad de Arritmias Hospital Puerta de Hierro, Madrid, Spain (D.G.-R., V.C.U.).
⁴ Department of Neurology, St. Josef-Hospital Universitätsklinikum, Bochum, Germany (F.K., M.G., A.K.).
⁵ Department of Neurology, Medical University of Vienna, Austria (S.G.).
⁶ Department of Neurology, Emory University, Atalanta, GA (F.N., Q.N.A.S.).
⁷ Department of Cerebrovascular Medicine. National Cerebrovascular Center, Osaka, Japan (J.K., H.I.).
⁸ Second Department of Neurology, Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, Greece (G.T., S.T.).
⁹ Department of Cardiology (L.S.-S.), Akershus University Hospital (AHUS), Lørenskog, Norway.
¹⁰ Department of Neurology (L.S.-S., O.M.R.), Akershus University Hospital (AHUS), Lørenskog, Norway.
¹¹ University of Oslo, Norway (A.T.L.).
¹² Department of Neurology, Østfold Hospital, Sarpsborg, Norway (A.T.L.). Department of Neurology, Oslo University Hospital, Oslo, Norway and the Norwegian University of Science and Technology, Trondheim, Norway.
¹³ Department of Neurology, Oslo University Hospital, Norway (A.H.A.).
¹⁴ Department of Neuroscience, Imaging and Clinical Sciences, G. d'Annunzio University of Chieti-Pescara, Italy (G.B., G.R.).
¹⁵ Neurology Department, Hospital del Mar Medical Research Institute, Universitat Pompeu Fabra, Barcelona, Spain (E.C.G.).
¹⁶ Department of Neurology, Medical University of Graz, Austria (S.P.).
¹⁷ Division of Neurology, Department of Medicine, University of Alberta, Edmonton, Canada (B.H.B., E.O.).
¹⁸ Division of Cardiology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada (J.S.H., W.F.M.I.).
¹⁹ Department of Neurology, University of Calgary, Canada (M.D.H.).
²⁰ Department of Neurology, University of California at Los Angele (J.L.S.).
²¹ Department of Neurology, University of Pennsylvania, Philadelphia (S.E.K.).
²² Department of Neurology, Weill Cornell Medicine, New York, NY (H.K.).
²³ American Heart Association, Dallas, TX (M.S.V.E.).
²⁴ Vagelos College of Physicians and Surgeons and Mailman School of Public Health, Columbia University, New York, NY (M.S.V.E.).
²⁵ Department of Bioinformatics and Data Sciences (L.H.S), Yale School of Medicine, Yale University, New Haven, CT.
²⁶ Department of Internal Medicine, Tufts University, Boston, MA (D.M.K.).
²⁷ Department of Medicine (Neurology), McMaster University and Population Health Research Institute, Hamilton, Ontario, Canada (A.H.K.).

PMID: 40765508
DOI: 10.1161/STROKEAHA.125.051749

Meta-Analysis

Device-Detected Atrial Fibrillation in Patients With and Without Cryptogenic Ischemia: The ANTARCTICA Pooled Analysis

Shadi Yaghi et al. Stroke. 2025 Oct.

. 2025 Oct;56(10):2895-2903.

doi: 10.1161/STROKEAHA.125.051749. Epub 2025 Aug 6.

Authors

Affiliations

¹ Department of Neurology, The Alpert Medical School of Brown University, Providence, RI (S.Y., L.S.).
² Department of Neurology, Western University, Hamilton, Ontario, Canada (L.A.S., S.F.).
³ Department of Neurology, Unidad de Arritmias Hospital Puerta de Hierro, Madrid, Spain (D.G.-R., V.C.U.).
⁴ Department of Neurology, St. Josef-Hospital Universitätsklinikum, Bochum, Germany (F.K., M.G., A.K.).
⁵ Department of Neurology, Medical University of Vienna, Austria (S.G.).
⁶ Department of Neurology, Emory University, Atalanta, GA (F.N., Q.N.A.S.).
⁷ Department of Cerebrovascular Medicine. National Cerebrovascular Center, Osaka, Japan (J.K., H.I.).
⁸ Second Department of Neurology, Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, Greece (G.T., S.T.).
⁹ Department of Cardiology (L.S.-S.), Akershus University Hospital (AHUS), Lørenskog, Norway.
¹⁰ Department of Neurology (L.S.-S., O.M.R.), Akershus University Hospital (AHUS), Lørenskog, Norway.
¹¹ University of Oslo, Norway (A.T.L.).
¹² Department of Neurology, Østfold Hospital, Sarpsborg, Norway (A.T.L.). Department of Neurology, Oslo University Hospital, Oslo, Norway and the Norwegian University of Science and Technology, Trondheim, Norway.
¹³ Department of Neurology, Oslo University Hospital, Norway (A.H.A.).
¹⁴ Department of Neuroscience, Imaging and Clinical Sciences, G. d'Annunzio University of Chieti-Pescara, Italy (G.B., G.R.).
¹⁵ Neurology Department, Hospital del Mar Medical Research Institute, Universitat Pompeu Fabra, Barcelona, Spain (E.C.G.).
¹⁶ Department of Neurology, Medical University of Graz, Austria (S.P.).
¹⁷ Division of Neurology, Department of Medicine, University of Alberta, Edmonton, Canada (B.H.B., E.O.).
¹⁸ Division of Cardiology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada (J.S.H., W.F.M.I.).
¹⁹ Department of Neurology, University of Calgary, Canada (M.D.H.).
²⁰ Department of Neurology, University of California at Los Angele (J.L.S.).
²¹ Department of Neurology, University of Pennsylvania, Philadelphia (S.E.K.).
²² Department of Neurology, Weill Cornell Medicine, New York, NY (H.K.).
²³ American Heart Association, Dallas, TX (M.S.V.E.).
²⁴ Vagelos College of Physicians and Surgeons and Mailman School of Public Health, Columbia University, New York, NY (M.S.V.E.).
²⁵ Department of Bioinformatics and Data Sciences (L.H.S), Yale School of Medicine, Yale University, New Haven, CT.
²⁶ Department of Internal Medicine, Tufts University, Boston, MA (D.M.K.).
²⁷ Department of Medicine (Neurology), McMaster University and Population Health Research Institute, Hamilton, Ontario, Canada (A.H.K.).

PMID: 40765508
DOI: 10.1161/STROKEAHA.125.051749

Abstract

Background: Insertable cardiac monitoring (ICM) detects atrial fibrillation (AF) in substantial proportions of cryptogenic stroke, noncryptogenic ischemic stroke without known AF, and nonstroke patients who are at risk of underlying AF. Given differences in patient characteristics across studies, there may be differences in AF detection rates on ICM across these subgroups that have not been identified. We investigate whether AF detection rates on ICM are higher in cryptogenic stroke or transient ischemic attack (C-IS/TIA) patients compared with individuals with noncryptogenic stroke or without stroke, when accounting for differences in study populations.

Methods: This is an individual-participant data meta-analysis of prospective studies and randomized controlled trials of ICM in C-IS/TIA, noncryptogenic ischemic stroke, and nonstroke patients. Multilevel multivariable logistic regression models were used to test whether C-IS/TIA is associated with increased AF detection relative to other categories. We performed multiple imputation to derive values for variables with <20% missing data and used Rubin's rules to estimate adjusted odds ratios by combining 100 postimputation data sets. The primary outcome was detection of AF. The attributable risk was derived by application of Bayes' Theorem.

Results: Two randomized controlled trials and 12 prospective studies were included with a total of 1562 C-IS/TIA patients and 474 non-C-IS/TIA patients. In adjusted multilevel logistic regression analyses, AF detection was higher in C-IS/TIA patients (adjusted odds ratio, 1.90 [95% CI, 1.18-3.06]; P=0.009), indicating that 47% of AF detected in C-IS/TIA is pathogenic. Limiting the comparator group to ischemic stroke or history of stroke yielded similar results (adjusted odds ratio, 2.83 [95% CI, 1.47-5.44]; P=0.002). Days to AF detection were significantly shorter in C-IS/TIA patients (median 65 versus 169; P<0.001).

Conclusions: In this individual-participant data meta-analysis of patients undergoing ICM, AF detection was higher in C-IS/TIA patients, with shorter time to AF detection compared with noncryptogenic/nonstroke individuals. These findings suggest that some of the AF detected in patients with C-IS/TIA may be pathogenic.

Keywords: atrial fibrillation; humans; ischemic stroke; odds ratio; stroke.

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Conflict of interest statement

Dr Sposato reports compensation from Pfizer for other services; compensation from Boehringer Ingelheim for other services; compensation from Western University (Canada) for other services; compensation from W. L. Gore & Associates, Inc for other services; and grants from Medtronic. Dr García Rodriguez reports compensation from Daiichi Sankyo for other services; stock holdings in Medtronic, Inc; stock holdings in Daiichi-Sankyo; stock holdings in Novo Nordisk AS; stock holdings in Esperion Therapeutics, Inc; and stock holdings in Novartis. Dr Gotzmann reports compensation from Boehringer Ingelheim for consultant services. Dr Tsivgoulis reports grants from Teva Pharmaceutical Industries; grants from Novartis; grants from Roche; grants from Bayer; grants from Medtronic; grants from Amicus Therapeutics, Inc; grants from Shire; grants from Merck; grants from Boehringer Ingelheim; grants from AbbVie; grants from Allergan; and grants from Genesis Pharma. Dr Aamodt reports compensation from Teva Pharmaceutical Industries for other services; grants from Boehringer Ingelheim to other; compensation from H. Lundbeck A/S for other services; compensation from AbbVie, Inc for consultant services; and compensation from Novartis for consultant services. Dr Renda reports travel support from Daiichi Sankyo Europe GmbH; grants from Boehringer Ingelheim; grants from Bayer; and compensation from Bristol-Myers Squibb Company for other services. Dr Healey reports compensation from Novartis for consultant services; grants from Medtronic, Inc; compensation from Medtronic for consultant services; grants from BOSTON SCIENTIFIC CORPORATION; grants from Pfizer; compensation from Boston Scientific Corporation for consultant services; grants from Bristol-Myers Squibb; and compensation from Bayer for expert witness services. Dr McIntyre reports compensation from Trimedics for consultant services; compensation from iRhythm Technologies, Inc for other services; grants from Heart and Stroke Foundation of Canada; and compensation from AtriCure, Inc for consultant services. Dr Hill reports grants from Medtronic; employment by University of Calgary; grants from NoNO, Inc; grants from Boehringer Ingelheim; grants from Canadian Institutes of Health Research; and compensation from Merck for end point review committee services. Dr Saver reports compensation from Occlutech for data and safety monitoring services; compensation from Abbott Laboratories for consultant services; compensation from MIVI Neuroscience for data and safety monitoring services; compensation from BrainsGate for consultant services; compensation from Biogen for consultant services; compensation from boehringer Ingelheim (prevention only) for consultant services; compensation from Roche for consultant services; compensation from CSL Behring for consultant services; stock options in Neuronics Medical; stock options in Rapid Medical; compensation from BrainQ for consultant services; compensation from Aeromics for consultant services; compensation from Stream Medical for consultant services; compensation from Medtronic USA, Inc for consultant services; compensation from Bayer for consultant services; compensation from Johnson & Johnson Health Care Systems, Inc for consultant services; and stock options in MindRhythm. Dr Kasner reports grants from Medtronic to other; compensation from Medtronic for other services; compensation from Bristol-Myers Squibb for other services; grants from diamedica to other; employment by Perelman School of Medicine, University of Pennsylvania; compensation from UpToDate for other services; grants from Bayer to other; and compensation from W. L. Gore & Associates, Inc for end point review committee services. Dr Kamel reports compensation from Arthrosi Therapeutics for end point review committee services; compensation from Alnylam Pharmaceuticals, Inc for consultant services; grants from National Institutes of Health; compensation from AstraZeneca for end point review committee services; compensation from American Medical Association for consultant services; an ownership stake in Spectrum Plastics Group; an ownership stake in Ascential Technologies; compensation from Novo Nordisk for end point review committee services; an ownership stake in TET Medical; compensation from Eli LIlly for end point review committee services; compensation from National Institutes of Health for other services; compensation from Janssen Biotech for other services; employment by Weill Cornell Medical College; compensation from Population Health Research Institute for other services; compensation from Medtronic for other services; compensation from AbbVie for consultant services; and compensation from Boehringer Ingelheim for end point review committee services. Dr Elkind reports other intellectual property for I have written 3 chapters for UpToDate for which I receive royalty income. I stopped 11/31/22.; grants from BMS-Pfizer; employment by American Heart Association; and grants from Roche Diagnostics Corporation. Dr Schwamm reports compensation from Medtronic for consultant services. Dr Kent reports grants from Patient-Centered Outcomes Research Institute and grants from National Institutes of Health. Dr Katsanos reports employment by McMaster University; grants from Heart and Stroke Foundation of Canada; and compensation from Diamedica, Inc for consultant services. The other authors report no conflicts.

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Device-Detected Atrial Fibrillation in Patients With and Without Cryptogenic Ischemia: The ANTARCTICA Pooled Analysis

Affiliations

Device-Detected Atrial Fibrillation in Patients With and Without Cryptogenic Ischemia: The ANTARCTICA Pooled Analysis

Authors

Affiliations

Abstract

Conflict of interest statement

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LinkOut - more resources

Full Text Sources

Medical