title: Worse stroke outcome in atrial fibrillation is explained by more severe hypoperfusion, infarct growth, and hemorrhagic transformation.
abstract: BACKGROUND
  Atrial fibrillation is associated with greater baseline neurological impairment and worse outcomes following ischemic stroke. Previous studies suggest that greater volumes of more severe baseline hypoperfusion in patients with history of atrial fibrillation may explain this association. We further investigated this association by comparing patients with and without atrial fibrillation on initial examination following stroke using pooled multimodal magnetic resonance imaging and clinical data from the Echoplanar Imaging Thrombolytic Evaluation Trial and the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution studies.
  
  
  METHODS
  Echoplanar Imaging Thrombolytic Evaluation Trial was a trial of 101 ischemic stroke patients randomized to intravenous tissue plasminogen activator or placebo, and Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution was a prospective cohort of 74 ischemic stroke patients treated with intravenous tissue plasminogen activator at three to six hours following symptom onset. Patients underwent multimodal magnetic resonance imaging before treatment, at three to five days and three-months after stroke in Echoplanar Imaging Thrombolytic Evaluation Trial; before treatment, three to six hours after treatment and one-month after stroke in Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution. Patients were assessed with the National Institutes of Health Stroke Scale and the modified Rankin scale before treatment and at three-months after stroke. Patients were categorized into definite atrial fibrillation (present on initial examination), probable atrial fibrillation (history but no atrial fibrillation on initial examination), and no atrial fibrillation. Perfusion data were reprocessed with automated magnetic resonance imaging analysis software (RAPID, Stanford University, Stanford, CA, USA). Hypoperfusion volumes were defined using time to maximum delays in two-second increments from >4 to >8 s. Hemorrhagic transformation was classified according to the European Cooperative Acute Stroke Studies criteria.
  
  
  RESULTS
  Of the 175 patients, 28 had definite atrial fibrillation, 30 probable atrial fibrillation, 111 no atrial fibrillation, and six were excluded due to insufficient imaging data. At baseline, patients with definite atrial fibrillation had more severe hypoperfusion (median time to maximum >8 s, volume 48 vs. 29 ml, P = 0.02) compared with patients with no atrial fibrillation. At outcome, patients with definite atrial fibrillation had greater infarct growth (median volume 47 vs. 8 ml, P = 0.001), larger infarcts (median volume 75 vs. 23 ml, P = 0.001), more frequent parenchymal hematoma grade hemorrhagic transformation (30% vs. 10%, P = 0.03), worse functional outcomes (median modified Rankin scale score 4 vs. 3, P = 0.03), and higher mortality (36% vs. 16%, P = 0·.3) compared with patients with no atrial fibrillation. Definite atrial fibrillation was independently associated with increased parenchymal hematoma (odds ratio = 6.05, 95% confidence interval 1.60-22.83) but not poor functional outcome (modified Rankin scale 3-6, odds ratio = 0.99, 95% confidence interval 0.35-2.80) or mortality (odds ratio = 2.54, 95% confidence interval 0.86-7.49) three-months following stroke, after adjusting for other baseline imbalances.
  
  
  CONCLUSIONS
  Atrial fibrillation is associated with greater volumes of more severe baseline hypoperfusion, leading to higher infarct growth, more frequent severe hemorrhagic transformation and worse stroke outcomes.
authors.affiliation: Department of Medicine and Neurology, The Royal Melbourne Hospital, University of Melbourne, Parkville, Vic, Australia.
authors.forename: Hans T H
authors.initials: HT
authors.lastname: Tu
authors.affiliation: Department of Medicine and Neurology, The Royal Melbourne Hospital, University of Melbourne, Parkville, Vic, Australia.
authors.forename: Bruce C V
authors.initials: BC
authors.lastname: Campbell
authors.affiliation: Department of Radiology, The Royal Melbourne Hospital, University of Melbourne, Parkville, Vic, Australia.
authors.forename: Soren
authors.initials: S
authors.lastname: Christensen
authors.affiliation: Department of Radiology, The Royal Melbourne Hospital, University of Melbourne, Parkville, Vic, Australia.
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Desmond
authors.affiliation: Department of Neurology, Singapore General Hospital Campus, National Neuroscience Institute, Singapore.
authors.forename: Deidre A
authors.initials: DA
authors.lastname: De Silva
authors.affiliation: Department of Neurology and Hunter Medical Research Institute, John Hunter Hospital, University of Newcastle, Newcastle, NSW, Australia.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Parsons
authors.affiliation: Florey Neurosciences Institutes, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Leonid
authors.initials: L
authors.lastname: Churilov
authors.affiliation: Department of Neurology and Neurological Sciences and the Stanford Stroke Center, Stanford University, Stanford, CA, USA.
authors.forename: Maarten G
authors.initials: MG
authors.lastname: Lansberg
authors.affiliation: Department of Neurology and Neurological Sciences and the Stanford Stroke Center, Stanford University, Stanford, CA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Mlynash
authors.affiliation: Department of Neurology and Neurological Sciences and the Stanford Stroke Center, Stanford University, Stanford, CA, USA.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Olivot
authors.affiliation: Department of Neurology and Neurological Sciences and the Stanford Stroke Center, Stanford University, Stanford, CA, USA.
authors.forename: Matus
authors.initials: M
authors.lastname: Straka
authors.affiliation: Department of Neurology and Neurological Sciences and the Stanford Stroke Center, Stanford University, Stanford, CA, USA.
authors.forename: Roland
authors.initials: R
authors.lastname: Bammer
authors.affiliation: Department of Neurology and Neurological Sciences and the Stanford Stroke Center, Stanford University, Stanford, CA, USA.
authors.forename: Gregory W
authors.initials: GW
authors.lastname: Albers
authors.affiliation: Florey Neurosciences Institutes, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Donnan
authors.affiliation: Department of Medicine and Neurology, The Royal Melbourne Hospital, University of Melbourne, Parkville, Vic, Australia.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Davis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D061605:Administration, Intravenous; D001281:Atrial Fibrillation / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D004311:Double-Blind Method; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D064847:Multimodal Imaging; D011446:Prospective Studies; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D020521:Stroke / Q000150:complications / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D015912:Thrombolytic Therapy / Q000379:methods; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator
keywords: atrial fibrillation; brain ischemia; cerebrovascular disease; magnetic resonance imaging; stroke outcome