title: Uncovering Atrial Fibrillation Beyond Short-Term Monitoring in Cryptogenic Stroke Patients: Three-Year Results From the Cryptogenic Stroke and Underlying Atrial Fibrillation Trial.
abstract: BACKGROUND
  Atrial fibrillation (AF) can be a cause of previously diagnosed cryptogenic stroke. However, AF can be paroxysmal and asymptomatic, thereby making detection with routine ECG methods difficult. Oral anticoagulation is highly effective in reducing recurrent stroke in patients with AF, but its initiation is dependent on the detection of AF. Cryptogenic Stroke and Underlying Atrial Fibrillation (CRYSTAL AF) is the first randomized study to report the detection of AF in cryptogenic stroke patients using continuous long-term monitoring via insertable cardiac monitors (ICM).
  
  
  RESULTS
  Patients with prior cryptogenic stroke were randomized to control (n=220) or ICM (n=221) and followed for ≤36 months. Cumulative AF detection rates in the ICM arm increased progressively during this period (3.7%, 8.9%, 12.4%, and 30.0% at 1, 6, 12, and 36 months, respectively), but remained low in the control arm (3.0% at 36 months). This resulted in oral anticoagulation prescription in 94.7% of ICM patients with AF detected at 6 months, 96.6% at 12 months, and 90.5% at 36 months. Among ICM patients with AF detected, the median time to AF detection was 8.4 months, 81.0% of first AF episodes were asymptomatic, and 94.9% had at least 1 day with >6 minutes of AF.
  
  
  CONCLUSIONS
  Three-year monitoring by ICM in cryptogenic stroke patients demonstrated a significantly higher AF detection rate compared with routine care. Given the frequency of asymptomatic first episodes and the long median time to detection, these findings highlight the limitations of using traditional AF detection methods. The majority of patients with AF were prescribed oral anticoagulation therapy.
  
  
  BACKGROUND
  Clinicaltrials.gov; Unique identifier: NCT00924638.
authors.affiliation: From the Department of Cardiology, Hospital Klinikum Coburg, Teaching Hospital of the University of Würzburg, Coburg, Germany (J.B.); Department of Medicine, Population Health Research Institute, McMaster University, Hamilton, ON, Canada (C.A.M.); Department of Cardiac Intensive Care, Institute of Cardiology, Catholic University of the Sacred Heart, Rome, Italy (T.S.); Department of Neurology, Institute of Neurology, Università Campus Bio-Medico, Rome, Italy (V.D.L.); Department of Neurology & Stroke Center, University Hospital Essen, Essen, Germany (H.-C.D.); Davee Department of Neurology (R.A.B.) and Bluhm Cardiovascular Institute (R.S.P.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Kansas Medical Center, Kansas City, KS (M.R.); Departments of Diagnostics and Monitoring Research (P.D.Z.) and Statistics (S.L.), Medtronic, Mounds View, MN; and Bluhm Cardiovascular Institute, Northwestern University Feinberg School of Medicine, Chicago, IL (R.S.P.). johannes.brachmann@klinikum-coburg.de.
authors.forename: Johannes
authors.initials: J
authors.lastname: Brachmann
authors.affiliation: From the Department of Cardiology, Hospital Klinikum Coburg, Teaching Hospital of the University of Würzburg, Coburg, Germany (J.B.); Department of Medicine, Population Health Research Institute, McMaster University, Hamilton, ON, Canada (C.A.M.); Department of Cardiac Intensive Care, Institute of Cardiology, Catholic University of the Sacred Heart, Rome, Italy (T.S.); Department of Neurology, Institute of Neurology, Università Campus Bio-Medico, Rome, Italy (V.D.L.); Department of Neurology & Stroke Center, University Hospital Essen, Essen, Germany (H.-C.D.); Davee Department of Neurology (R.A.B.) and Bluhm Cardiovascular Institute (R.S.P.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Kansas Medical Center, Kansas City, KS (M.R.); Departments of Diagnostics and Monitoring Research (P.D.Z.) and Statistics (S.L.), Medtronic, Mounds View, MN; and Bluhm Cardiovascular Institute, Northwestern University Feinberg School of Medicine, Chicago, IL (R.S.P.).
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Morillo
authors.affiliation: From the Department of Cardiology, Hospital Klinikum Coburg, Teaching Hospital of the University of Würzburg, Coburg, Germany (J.B.); Department of Medicine, Population Health Research Institute, McMaster University, Hamilton, ON, Canada (C.A.M.); Department of Cardiac Intensive Care, Institute of Cardiology, Catholic University of the Sacred Heart, Rome, Italy (T.S.); Department of Neurology, Institute of Neurology, Università Campus Bio-Medico, Rome, Italy (V.D.L.); Department of Neurology & Stroke Center, University Hospital Essen, Essen, Germany (H.-C.D.); Davee Department of Neurology (R.A.B.) and Bluhm Cardiovascular Institute (R.S.P.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Kansas Medical Center, Kansas City, KS (M.R.); Departments of Diagnostics and Monitoring Research (P.D.Z.) and Statistics (S.L.), Medtronic, Mounds View, MN; and Bluhm Cardiovascular Institute, Northwestern University Feinberg School of Medicine, Chicago, IL (R.S.P.).
authors.forename: Tommaso
authors.initials: T
authors.lastname: Sanna
authors.affiliation: From the Department of Cardiology, Hospital Klinikum Coburg, Teaching Hospital of the University of Würzburg, Coburg, Germany (J.B.); Department of Medicine, Population Health Research Institute, McMaster University, Hamilton, ON, Canada (C.A.M.); Department of Cardiac Intensive Care, Institute of Cardiology, Catholic University of the Sacred Heart, Rome, Italy (T.S.); Department of Neurology, Institute of Neurology, Università Campus Bio-Medico, Rome, Italy (V.D.L.); Department of Neurology & Stroke Center, University Hospital Essen, Essen, Germany (H.-C.D.); Davee Department of Neurology (R.A.B.) and Bluhm Cardiovascular Institute (R.S.P.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Kansas Medical Center, Kansas City, KS (M.R.); Departments of Diagnostics and Monitoring Research (P.D.Z.) and Statistics (S.L.), Medtronic, Mounds View, MN; and Bluhm Cardiovascular Institute, Northwestern University Feinberg School of Medicine, Chicago, IL (R.S.P.).
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Lazzaro
authors.affiliation: From the Department of Cardiology, Hospital Klinikum Coburg, Teaching Hospital of the University of Würzburg, Coburg, Germany (J.B.); Department of Medicine, Population Health Research Institute, McMaster University, Hamilton, ON, Canada (C.A.M.); Department of Cardiac Intensive Care, Institute of Cardiology, Catholic University of the Sacred Heart, Rome, Italy (T.S.); Department of Neurology, Institute of Neurology, Università Campus Bio-Medico, Rome, Italy (V.D.L.); Department of Neurology & Stroke Center, University Hospital Essen, Essen, Germany (H.-C.D.); Davee Department of Neurology (R.A.B.) and Bluhm Cardiovascular Institute (R.S.P.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Kansas Medical Center, Kansas City, KS (M.R.); Departments of Diagnostics and Monitoring Research (P.D.Z.) and Statistics (S.L.), Medtronic, Mounds View, MN; and Bluhm Cardiovascular Institute, Northwestern University Feinberg School of Medicine, Chicago, IL (R.S.P.).
authors.forename: Hans-Christoph
authors.initials: HC
authors.lastname: Diener
authors.affiliation: From the Department of Cardiology, Hospital Klinikum Coburg, Teaching Hospital of the University of Würzburg, Coburg, Germany (J.B.); Department of Medicine, Population Health Research Institute, McMaster University, Hamilton, ON, Canada (C.A.M.); Department of Cardiac Intensive Care, Institute of Cardiology, Catholic University of the Sacred Heart, Rome, Italy (T.S.); Department of Neurology, Institute of Neurology, Università Campus Bio-Medico, Rome, Italy (V.D.L.); Department of Neurology & Stroke Center, University Hospital Essen, Essen, Germany (H.-C.D.); Davee Department of Neurology (R.A.B.) and Bluhm Cardiovascular Institute (R.S.P.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Kansas Medical Center, Kansas City, KS (M.R.); Departments of Diagnostics and Monitoring Research (P.D.Z.) and Statistics (S.L.), Medtronic, Mounds View, MN; and Bluhm Cardiovascular Institute, Northwestern University Feinberg School of Medicine, Chicago, IL (R.S.P.).
authors.forename: Richard A
authors.initials: RA
authors.lastname: Bernstein
authors.affiliation: From the Department of Cardiology, Hospital Klinikum Coburg, Teaching Hospital of the University of Würzburg, Coburg, Germany (J.B.); Department of Medicine, Population Health Research Institute, McMaster University, Hamilton, ON, Canada (C.A.M.); Department of Cardiac Intensive Care, Institute of Cardiology, Catholic University of the Sacred Heart, Rome, Italy (T.S.); Department of Neurology, Institute of Neurology, Università Campus Bio-Medico, Rome, Italy (V.D.L.); Department of Neurology & Stroke Center, University Hospital Essen, Essen, Germany (H.-C.D.); Davee Department of Neurology (R.A.B.) and Bluhm Cardiovascular Institute (R.S.P.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Kansas Medical Center, Kansas City, KS (M.R.); Departments of Diagnostics and Monitoring Research (P.D.Z.) and Statistics (S.L.), Medtronic, Mounds View, MN; and Bluhm Cardiovascular Institute, Northwestern University Feinberg School of Medicine, Chicago, IL (R.S.P.).
authors.forename: Marylin
authors.initials: M
authors.lastname: Rymer
authors.affiliation: From the Department of Cardiology, Hospital Klinikum Coburg, Teaching Hospital of the University of Würzburg, Coburg, Germany (J.B.); Department of Medicine, Population Health Research Institute, McMaster University, Hamilton, ON, Canada (C.A.M.); Department of Cardiac Intensive Care, Institute of Cardiology, Catholic University of the Sacred Heart, Rome, Italy (T.S.); Department of Neurology, Institute of Neurology, Università Campus Bio-Medico, Rome, Italy (V.D.L.); Department of Neurology & Stroke Center, University Hospital Essen, Essen, Germany (H.-C.D.); Davee Department of Neurology (R.A.B.) and Bluhm Cardiovascular Institute (R.S.P.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Kansas Medical Center, Kansas City, KS (M.R.); Departments of Diagnostics and Monitoring Research (P.D.Z.) and Statistics (S.L.), Medtronic, Mounds View, MN; and Bluhm Cardiovascular Institute, Northwestern University Feinberg School of Medicine, Chicago, IL (R.S.P.).
authors.forename: Paul D
authors.initials: PD
authors.lastname: Ziegler
authors.affiliation: From the Department of Cardiology, Hospital Klinikum Coburg, Teaching Hospital of the University of Würzburg, Coburg, Germany (J.B.); Department of Medicine, Population Health Research Institute, McMaster University, Hamilton, ON, Canada (C.A.M.); Department of Cardiac Intensive Care, Institute of Cardiology, Catholic University of the Sacred Heart, Rome, Italy (T.S.); Department of Neurology, Institute of Neurology, Università Campus Bio-Medico, Rome, Italy (V.D.L.); Department of Neurology & Stroke Center, University Hospital Essen, Essen, Germany (H.-C.D.); Davee Department of Neurology (R.A.B.) and Bluhm Cardiovascular Institute (R.S.P.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Kansas Medical Center, Kansas City, KS (M.R.); Departments of Diagnostics and Monitoring Research (P.D.Z.) and Statistics (S.L.), Medtronic, Mounds View, MN; and Bluhm Cardiovascular Institute, Northwestern University Feinberg School of Medicine, Chicago, IL (R.S.P.).
authors.forename: Shufeng
authors.initials: S
authors.lastname: Liu
authors.affiliation: From the Department of Cardiology, Hospital Klinikum Coburg, Teaching Hospital of the University of Würzburg, Coburg, Germany (J.B.); Department of Medicine, Population Health Research Institute, McMaster University, Hamilton, ON, Canada (C.A.M.); Department of Cardiac Intensive Care, Institute of Cardiology, Catholic University of the Sacred Heart, Rome, Italy (T.S.); Department of Neurology, Institute of Neurology, Università Campus Bio-Medico, Rome, Italy (V.D.L.); Department of Neurology & Stroke Center, University Hospital Essen, Essen, Germany (H.-C.D.); Davee Department of Neurology (R.A.B.) and Bluhm Cardiovascular Institute (R.S.P.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Kansas Medical Center, Kansas City, KS (M.R.); Departments of Diagnostics and Monitoring Research (P.D.Z.) and Statistics (S.L.), Medtronic, Mounds View, MN; and Bluhm Cardiovascular Institute, Northwestern University Feinberg School of Medicine, Chicago, IL (R.S.P.).
authors.forename: Rod S
authors.initials: RS
authors.lastname: Passman
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage; D001281:Atrial Fibrillation / Q000150:complications / Q000175:diagnosis* / Q000503:physiopathology; D002170:Canada / Q000453:epidemiology; D002544:Cerebral Infarction / Q000453:epidemiology / Q000209:etiology* / Q000517:prevention & control; D015716:Electrocardiography, Ambulatory / Q000379:methods*; D005060:Europe / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006339:Heart Rate / Q000502:physiology*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D015203:Reproducibility of Results; D013997:Time Factors; D014481:United States / Q000453:epidemiology
chemical_list: D000925:Anticoagulants
keywords: anticoagulation; atrial fibrillation arrhythmia; diagnosis; electrophysiology; insertable cardiac monitor; stroke