Journal of the American College of Cardiology, 03/2019, Vol.73(9), pp.989-999
Key Words atrial fibrillation; cognitive dysfunction; microbleeds; silent cerebral infarcts; white matter lesions Abstract Background Patients with atrial fibrillation (AF) have an increased risk of cognitive decline, potentially resulting from clinically unrecognized vascular brain lesions. Objectives This study sought to assess the relationships between cognitive function and vascular brain lesions in patients with AF. Methods Patients with known AF were enrolled in a multicenter study in Switzerland. Brain magnetic resonance imaging (MRI) and cognitive testing using the Montreal Cognitive Assessment (MoCA) were performed in all participants. Large noncortical or cortical infarcts (LNCCIs), small noncortical infarcts (SNCIs), microbleeds, and white matter lesions were quantified by a central core laboratory. Clinically silent infarcts were defined as infarcts on brain MRI in patients without a clinical history of stroke or transient ischemic attack. Results The study included 1,737 patients with a mean age of 73 [plus or minus] 8 years (28% women, 90% taking oral anticoagulant agents). On MRI, LNCCIs were found in 387 patients (22%), SNCIs in 368 (21%), microbleeds in 372 (22%), and white matter lesions in 1715 (99%). Clinically silent infarcts among the 1,390 patients without a history of stroke or transient ischemic attack were found in 201 patients with LNCCIs (15%) and 245 patients with SNCIs (18%). The MoCA score was 24.7 [plus or minus] 3.3 in patients with and 25.8 [plus or minus] 2.9 in those without LNCCIs on brain MRI (p 〈 0.001). The difference in MoCA score remained similar when only clinically silent LNCCIs were considered (24.9 [plus or minus] 3.1 vs. 25.8 [plus or minus] 2.9; p 〈 0.001). In a multivariable regression model including all vascular brain lesion parameters, LNCCI volume was the strongest predictor of a reduced MoCA ([beta] = -0.26; 95% confidence interval: -0.40 to -0.13; p 〈 0.001). Conclusions Patients with AF have a high burden of LNCCIs and other brain lesions on systematic brain MRI screening, and most of these lesions are clinically silent. LNCCIs were associated with worse cognitive function, even among patients with clinically silent infarcts. Our findings raise the question of MRI screening in patients with AF. Abbreviations and Acronyms AF, atrial fibrillation; FLAIR, fluid-attenuated inversion recovery; LNCCI, large noncortical or cortical infarct; MoCA, Montreal Cognitive Assessment; MRI, magnetic resonance imaging; SNCI, small noncortical infarct; TIA, transient ischemic attack Author Affiliation: (a) Cardiology Division, Department of Medicine, University Hospital Basel, Basel, Switzerland (b) Cardiovascular Research Institute Basel, Basel, Switzerland (c) Population Health Research Institute, McMaster University, Hamilton, Canada (d) Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland (e) Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland (f) Department of Cardiology, Triemli Hospital Zurich, Zurich, Switzerland (g) Departement of Medicine, Cantonal Hospital of Baden and Molecular Cardiology, University Hospital of Zurich, Zurich, Switzerland (h) Department of Cardiology, Kantonsspital St. Gallen, St. Gallen, Switzerland (i) Department of Cardiology, Ospedale Regionale di Lugano, Lugano, Switzerland (j) Division of Cardiology, Fondazione Cardiocentro Ticino, Lugano, Switzerland (k) Department of Internal Medicine, HFR-Hopital Cantonal Fribourg, Fribourg, Switzerland (l) Department of Cardiology, Luzerner Kantonsspital, Lucerne, Switzerland (m) Division of Cardiology, Department of Medical Specialties, University Hospital Geneva, Geneva, Switzerland (n) Department of Cardiology, Burgerspital Solothurn, Solothurn, Switzerland (o) Department of Cardiology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland (p) Department of Cardiology, Ospedale San Giovanni, Bellinzona, Switzerland (q) Department of Neurology and Stroke Center, University Hospital Basel, University of Basel, Basel, Switzerland (r) Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland (s) Memory Clinic, Universitare Altersmedizin, Felix Platter Spital Basel, University of Basel, Basel, Switzerland (t) Department of Neuroradiology, University Hospital Zurich, Zurich, Switzerland (u) Medical Image Analysis Center (MIAC AG) and Department of Biomedical Engineering, University of Basel, Basel, Switzerland (v) Epidemiology, Biostatistics, and Prevention Institute, University of Zurich, Zurich, Switzerland * Address for correspondence: Dr. David Conen, Population Health Research Institute, 237 Barton Street East, Hamilton, Ontario, Canada. Article History: Received 13 September 2018; Revised 14 November 2018; Accepted 3 December 2018 (footnote) The Swiss-AF cohort study is supported by grants of the Swiss National Science Foundation (grants 33CS30_1148474 and 33CS30_177520), the Foundation for Cardiovascular Research Basel, and the University of Basel. The Department of Radiology, University Hospital Basel, Basel holds a general research agreement with Siemens and receives support from Guerbet, Bracco, and Bayer all unrelated to this work. Dr. Conen has a McMaster University Department of Medicine Mid-Career Research Award; his work is supported by the Hamilton Health Sciences RFA Strategic Initiative Program; and has received consulting fees from Servier, Canada. Dr. Rodondi has received a grant from the Swiss Heart Foundation. Dr. Muller has received consulting fees from Biosense Webster, Switzerland. Dr. Beer has received grants from the Swiss National Science Foundation, the Swiss Heart Foundation, and Bayer; and has received consultancy honoraria from Bayer and Daiichi-Sankyo. Dr. Auricchio has received speaker fees from Boston Scientific and Microport; and is a consultant to Boston Scientific, Microport, Daiichi-Sankyo, and Biosense Webster. Dr. Kobza has received grants from Biotronik, Biosense Webster, Boston Scientific, Medtronic, and Abbott. Dr. Shah has received speaker fees from Biosense Webster, Daiichi-Sankyo, Boehringer Ingelheim, Bristol-Myers Squibb, and Bayer; and has received consultancy honoraria from Biosense Webster. Dr. Sticherling has received speaker honoraria from Biosense Webster and Medtronic; and has received research grants from Biosense Webster, Daiichi-Sankyo, and Medtronic. Dr. Bonati has received grants from the Swiss National Science Foundation, the University of Basel, the Swiss Heart Foundation, The Stroke Association, and AstraZeneca; and has received consulting and advisory board fees from Amgen, Bayer, Bristol-Myers Squibb, and Claret Medical. Dr. Monsch has received honoraria or grant support from AC Immune, AbbVie, Roche, Takeda, and Vifor Pharma. Dr. Stippich has received grants from the Swiss National Science Foundation, Siemens, Bracco, Guerbert, Schering, Bayer, Amgen, Merck Sharp and Dohme, Novartis, Pfizer, and The Medicines Company. Dr. Wuerfel is CEO of the Medical Image Analysis Center, Basel; has served on advisory boards for Actelion, Biogen, Genzyme-Sanofi, Novartis, Roche, and the Guthy Jackson Charitable Foundation; has received research grants from Novartis; has received speaker honoraria from Bayer, Biogen, Genzyme, Novartis, and Teva; and has received support by the European Union (Horizon2020), the German Research Association, the German Ministry of Education and Research (BMBF/KKNMS), and the German Ministry of Economy (BMWi). Dr. Schwenkglenks has received grants unrelated to the submitted work from Amgen, Merck Sharp and Dohme, Novartis, Pfizer, and The Medicines Company; has received fees unrelated to the submitted work from Amgen; and has received a grant from the Swiss National Science Foundation. Dr. Kuhne has received consultant fees from Bayer, Boehringer Ingelheim, Pfizer-BMS, Daiichi-Sankyo, Medtronic, Biotronik, Boston Scientific, Biosense Webster, AstraZeneca, and Novartis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. (footnote) Listen to this manuscript's audio summary by Editor-in-Chief Dr. Valentin Fuster on JACC.org (http://JACC.org/). (footnote)* Drs. Kuhne and Osswald are joint senior authors and contributed equally to this work. (footnote)[Dagger] A list of all Swiss-AF investigators is provided in the . Byline: David Conen, MD, MPH [email@example.com] (a,b,c,*), Nicolas Rodondi, MD, MAS (d,e), Andreas Muller, MD (f), Juerg H. Beer, MD (g), Peter Ammann, MD (h), Giorgio Moschovitis, MD (i), Angelo Auricchio, MD, PhD (j), Daniel Hayoz, MD (k), Richard Kobza, MD (l), Dipen Shah, MD (m), Jan Novak, MD (n), Jurg Schlapfer, MD (o), Marcello Di Valentino, MD (p), Stefanie Aeschbacher, PhD (a,b), Steffen Blum, MD (a,b), Pascal Meyre, MD (a,b), Christian Sticherling, MD (a,b), Leo H. Bonati, MD (q), Georg Ehret, MD (m), Elisavet Moutzouri, MD (d,e), Urs Fischer, MD, MS (r), Andreas U. Monsch, PhD (s), Christoph Stippich, MD (t), Jens Wuerfel, MD (u), Tim Sinnecker, MD (q,u), Michael Coslovsky, PhD (b), Matthias Schwenkglenks, PhD, MPH (v), Michael Kuhne, MD (a,b,*), Stefan Osswald, MD (a,b,*), Sebastian Berger, Raffaele Bernasconi, Lorin Frohlich, Tobias Goldi, Rebecca Gugganig, Thomas Kofler, Philipp Krisai, Michel Mongiat, Christiane Pudenz, Javier Ruperti Repilado, Aleksandra Schweizer, Anne Springer, Samuel Stempfel, Thomas Szucs, Jan van der Stouwe, Gian Voellmin, Leon Zwimpfer, Drahomir Aujesky, Juerg Fuhrer, Laurent Roten, Simon Jung, Heinrich Mattle, Luise Adam, Carole Elodie Aubert, Martin Feller, Claudio Schneider, Axel Loewe, Tanja Fluckiger, Cindy Groen, Nathalie Schwab, Christopher Beynon, Roger Dillier, Franz Eberli, Simone Fontana, Christine Franzini, Isabel Juchli, Claudia Liedtke, Jacqueline Nadler, Thayze Obst, Xiaoye Schneider, Katrin Studerus, Dominik Weishaupt, Silke Kuest, Karin Scheuch, D...
Atrial Fibrillation -- Care And Treatment ; Atrial Fibrillation -- Analysis ; Brain Damage -- Care And Treatment ; Brain Damage -- Analysis;
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