Regadenoson Stress-MRI to Identify Coronary Artery Disease in Atrial Fibrillation Patients
Condition: Atrial Fibrillation; Coronary Artery Disease
MeSH terms: Atrial Fibrillation; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease
Study type: Interventional
Phase: Phase 2

Summary: 
      Atrial fibrillation (AF) is growing into an epidemic affecting 1 in 4 adults. There is a need
      for research to elucidate the prevalence of ischemic cardiomyopathy in patients diagnosed
      with AF. The objective of this study is to demonstrate the utility of MRI in assessment of
      coronary artery disease. The specific objective is to demonstrate sensitivity/specificity
      comparable to that reported in meta-analyses of non-AF patients and adenosine (90% /80%) in
      an AF population using the time-efficient vasodilator regadenoson that requires only a single
      intravenous (IV).
    

Detailed description: 
      Scientific Background/Rationale:

      Atrial fibrillation (AF) is a large and growing healthcare problem worldwide. Over 7 million
      people in the U.S. and Europe currently suffer from atrial fibrillation, and this number is
      expected to double before 2050. The lifetime risk of AF is high: ~24% at age 40, and this
      risk remains fairly constant at older ages, with 22% lifetime risk at age 80 [1]. AF
      significantly increases the risk of stroke and mortality, and can greatly limit quality of
      life. Little research has been done on AF and ischemic cardiomyopathy, though it is a
      relatively common co-morbidity. CT found increased prevalence (41% vs 27%) of coronary artery
      disease (CAD) in patients with AF compared to patients with similar pre-test risk but no AF
      [2]. AF patients with a positive SPECT scan for CAD have a worse prognosis for cardiac events
      than patients with positive SPECT but without AF [3]. It was recently reported that in a
      study of 253 AF patients, that AF patients with positive SPECT studies had a very high number
      of false positives - only 15% of patients had significant CAD by angiography (compared to 67%
      in the control group) [4, 5]. Just over half of the patients were in sinus rhythm at SPECT,
      but since similar numbers of positives were seen in each half, the authors did not feel that
      imaging during AF was the cause of the poor specificity.

      Use of MRI for assessment of CAD is a growing area that entails no radiation exposure to the
      patient. Advances in MRI have made it possible to accurately detect CAD, either as well or
      better than SPECT in unselected populations [6, 7]. However, adoption of MRI myocardial
      perfusion scans has been limited in part due to the challenges associated with the use of
      adenosine. Adenosine requires starting a second IV, and to use either a special expensive
      MRI-compatible infusion pump to deliver the drug, or long lengths of tubing to run to a pump
      outside the scanner room. Neither solution is ideal, and regadenoson would not require any
      such pumps or the starting of a second IV. Here the investigators propose to determine the
      sensitivity/specificity for dynamic contrast-enhanced myocardial perfusion MRI with the
      vasodilator regadenoson in a subpopulation of patients - those with atrial fibrillation.

      The investigators have a great deal of experience with stress and rest myocardial perfusion
      MRI. In a preliminary study imaging three patients with AF that then went to X-ray
      angiography (cath), two of the three subjects had significant stenoses by cath, and one did
      not. This agreed with the regadenoson stress perfusion MRI findings. These MRI acquisitions
      were performed on a Siemens Verio MRI scanner. The Verio operates at twice the magnetic field
      strength (3 Tesla, or 3T) of most MRI scanners, which operate at 1.5T. The higher magnetic
      field offers images with significantly less noise (almost twice the signal-to-noise ratio).

      Objective: To demonstrate sensitivity/specificity comparable to that reported in
      meta-analyses of non-AF patients and adenosine (90%/80% [6, 7]), in an atrial fibrillation
      population while using the time-efficient vasodilator regadenoson that requires only a single
      IV.

      Study Design: This will be a prospective, open-label, comparative trial using MRI.
      Non-invasive MRI measurements of resting flow and flow at regadenoson stress will be obtained
      in each subject during a one hour MRI exam using our advanced MRI acquisition techniques.
      Sensitivity/specificity of regadenoson stress MRI will be determined using x-ray angiography
      as the standard. X-ray angiography will be done as standard-of-care, and is not an
      intervention of this clinical trial.

      Study Procedure: Each subject will undergo a single MRI scanning session. Caffeine will be
      stopped 12 hours prior to the procedure. One IV will be started and subjects positioned in
      the scanner. Resting perfusion with Multihance Gd-BOPTA contrast agent will be performed
      first. The perfusion acquisition acquires 3-6 short axis slices each heartbeat and lasts for
      one minute. Then a standard regadenoson injection of 400ug/5cc will be given and MR imaging
      performed with a Gd-BOPTA contrast agent bolus 60-100 seconds later [9] [10].
    

Intervention name(s): Regadenoson MRI; Gadobenate dimeglumine
Intervention type(s): Drug; Drug
Intervention description(s): AF patients will be provided with a regadenoson stress MRI to see if coronary artery disease can be detected with more sensitivity /specificity.; Resting perfusion with Multihance Gd-BOPTA contrast agent will be performed first, then a regadenoson injection will be given and MR imaging performed with a Gd-BOPTA contrast agent bolus 60-100 seconds later.
Other intervention name(s): Lexiscan; Gd-BOPTA; Multihance
Intervention MeSH terms: Regadenoson
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: MRI; Atrial Fibrillation