Study of Continuous Cardiac Monitoring to Assess Atrial Fibrillation After Cryptogenic Stroke (CRYSTAL-AF)

• AF Detection Rate Within 12 Months [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  Percentage of subjects with AF detected within 12 months of follow-up
• Incidence of Recurrent Stroke or TIA (Transient Ischemic Attack) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  Percentage of subjects with recurrent stroke or TIA within 12 months of follow-up
• Use of Oral Anticoagulation (OAC) Drugs [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  Percentage of subjects who were using OAC drugs at the 12 months follow-up visit
• Use of Antiarrhythmic Drugs [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  Percentage of subjects who were using antiarrhythmic drugs at the 12 months follow-up visit
• Health Outcome as Evaluated by EQ-5D Questionnaire [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  EQ-5D VAS (visual analog scale) quality of life score, which is a continuous measure of quality of life ranging from 0 (worst) to 100 (perfect health).
• Clinical Disease Burden and Care Pathway [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  Incidence of cardiovascular (CV) or stroke/TIA related hospitalizations within 12 months
• Impact of Patient Assistant Use on AF Diagnosis [ Time Frame: Follow-up closure ] [ Designated as safety issue: No ]
  AF detection lag (days from AF occurrence to AF diagnosis) characterized by patient assistant (PA) use frequency

• Time to first documented episode of AF [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Incidence of stroke and Transient Ischemic Attack (TIA) [ Time Frame: Follow-up Closure ] [ Designated as safety issue: No ]
• Cardiovascular drug changes [ Time Frame: Follow-up closure ] [ Designated as safety issue: No ]
• Health outcome [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Clinical Disease Burden and Care Pathway [ Time Frame: Follow-up closure ] [ Designated as safety issue: No ]
• Patient Assistant impact on AF diagnosis [ Time Frame: Follow-up closure ] [ Designated as safety issue: No ]

• Cryptogenic Symptomatic Transient Ischemic Attack
• Cryptogenic Ischemic Stroke

• Active Comparator: Continuous Monitoring
  Continuous cardiac monitoring by the Reveal® XT Insertable Cardiac Monitor
  Intervention: Device: Reveal® XT Insertable Cardiac Monitor
• No Intervention: Control Arm
  Follow-up at the same frequency, but with no Insertable Cardiac Monitor

• Sacco RL, Adams R, Albers G, Alberts MJ, Benavente O, Furie K, Goldstein LB, Gorelick P, Halperin J, Harbaugh R, Johnston SC, Katzan I, Kelly-Hayes M, Kenton EJ, Marks M, Schwamm LH, Tomsick T; American Heart Association; American Stroke Association Council on Stroke; Council on Cardiovascular Radiology and Intervention; American Academy of Neurology. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke: co-sponsored by the Council on Cardiovascular Radiology and Intervention: the American Academy of Neurology affirms the value of this guideline. Stroke. 2006 Feb;37(2):577-617.
• Sinha AM, Diener HC, Morillo CA, Sanna T, Bernstein RA, Di Lazzaro V, Passman R, Beckers F, Brachmann J. Cryptogenic Stroke and underlying Atrial Fibrillation (CRYSTAL AF): design and rationale. Am Heart J. 2010 Jul;160(1):36-41.e1. doi: 10.1016/j.ahj.2010.03.032.
• Brachmann J, Morillo CA, Sanna T, Di Lazzaro V, Diener HC, Bernstein RA, Rymer M, Ziegler PD, Liu S, Passman RS. Uncovering Atrial Fibrillation Beyond Short-Term Monitoring in Cryptogenic Stroke Patients: Three-Year Results From the Cryptogenic Stroke and Underlying Atrial Fibrillation Trial. Circ Arrhythm Electrophysiol. 2016 Jan;9(1):e003333. doi: 10.1161/CIRCEP.115.003333.
• Bernstein RA, Di Lazzaro V, Rymer MM, Passman RS, Brachmann J, Morillo CA, Sanna T, Thijs V, Rogers T, Liu S, Ziegler PD, Diener HC. Infarct Topography and Detection of Atrial Fibrillation in Cryptogenic Stroke: Results from CRYSTAL AF. Cerebrovasc Dis. 2015;40(1-2):91-6. doi: 10.1159/000437018. Epub 2015 Jul 11.
• Sanna T, Diener HC, Passman RS, Di Lazzaro V, Bernstein RA, Morillo CA, Rymer MM, Thijs V, Rogers T, Beckers F, Lindborg K, Brachmann J; CRYSTAL AF Investigators. Cryptogenic stroke and underlying atrial fibrillation. N Engl J Med. 2014 Jun 26;370(26):2478-86. doi: 10.1056/NEJMoa1313600.

Inclusion Criteria:

1. Recent cryptogenic symptomatic transient ischemic attack (TIA) or cryptogenic ischemic stroke.

Exclusion Criteria:

1. Known etiology of TIA or stroke.
2. Untreated hyperthyroidism.
3. Myocardial infarction less than 1 month prior to stroke or TIA.
4. Coronary bypass grafting less than 1 month prior to stroke or TIA.
5. Valvular disease requiring immediate surgical intervention.
6. History of AF or atrial flutter.
7. Patent Foramen Ovale (PFO) and PFO is or was an indication to start oral anticoagulation (OAC).
8. Permanent indication for OAC at enrollment.
9. Permanent contra-indication for OAC.
10. Included in another clinical trial.
11. Life expectancy less than 1 year.
12. Pregnant.
13. Indicated for Implantable Pulse Generator (IPG), Implantable Cardioverter-Defibrillator (ICD), Cardiac Resynchronization Therapy (CRT) or an implantable hemodynamic monitoring system.
14. Not fit, unable or unwilling to follow the required procedures of the protocol.