Regadenoson Stress-MRI to Identify Coronary Artery Disease in Atrial Fibrillation Patients

NCT ID: NCT01710254

Last Updated: 2017-12-13

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-01-31

Study Completion Date

2016-10-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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 \[9\] \[10\].

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Atrial Fibrillation Coronary Artery Disease

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

MRI Atrial Fibrillation

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Regadenoson MRI

Participants with AF receiving regadenoson stress MRI, using Gadobenate dimeglumine

Group Type EXPERIMENTAL

Regadenoson MRI

Intervention Type DRUG

AF patients will be provided with a regadenoson stress MRI to see if coronary artery disease can be detected with more sensitivity /specificity.

Gadobenate dimeglumine

Intervention Type DRUG

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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Regadenoson MRI

AF patients will be provided with a regadenoson stress MRI to see if coronary artery disease can be detected with more sensitivity /specificity.

Intervention Type DRUG

Gadobenate dimeglumine

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.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Lexiscan Gd-BOPTA Multihance

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

Patients with confirmed persistent or paroxysmal AF and suspected coronary artery disease who will undergo catheterization X-ray angiography

Exclusion Criteria

1. Critically ill patients, patients on ventilators patients with hypotension, asthmatics, and other patients whose medical care or safety may be compromised from undergoing an MRI examination will be excluded.
2. Patients with claustrophobia will also be excluded since MRI is conducted in a closed environment.
3. Patients with contraindications to MRI (pacemaker, metal implants).
4. Pregnant subjects (or women who may become pregnant), minors, and prisoners will be excluded from this study.
5. Subjects are over 60 or have any suspicion of abnormal kidney function (a blood test to determine Glomerular filtration rate (GFR) will be performed prior to imaging. Subjects with GFR\<30 will be excluded from the study. This is standard practice for clinical scans in Radiology due to the extremely small but not negligible relationship between gadolinium contrast agent and nephrogenic systemic fibrosis in patients with severely impaired renal function.
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

University of Utah

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Brent Wilson

Associate Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Brent Wilson, MD

Role: PRINCIPAL_INVESTIGATOR

University of Utah

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

University of Utah

Salt Lake City, Utah, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

Lloyd-Jones DM, Wang TJ, Leip EP, Larson MG, Levy D, Vasan RS, D'Agostino RB, Massaro JM, Beiser A, Wolf PA, Benjamin EJ. Lifetime risk for development of atrial fibrillation: the Framingham Heart Study. Circulation. 2004 Aug 31;110(9):1042-6. doi: 10.1161/01.CIR.0000140263.20897.42. Epub 2004 Aug 16.

Reference Type BACKGROUND
PMID: 15313941 (View on PubMed)

Nucifora G, Schuijf JD, Tops LF, van Werkhoven JM, Kajander S, Jukema JW, Schreur JH, Heijenbrok MW, Trines SA, Gaemperli O, Turta O, Kaufmann PA, Knuuti J, Schalij MJ, Bax JJ. Prevalence of coronary artery disease assessed by multislice computed tomography coronary angiography in patients with paroxysmal or persistent atrial fibrillation. Circ Cardiovasc Imaging. 2009 Mar;2(2):100-6. doi: 10.1161/CIRCIMAGING.108.795328. Epub 2009 Jan 26.

Reference Type BACKGROUND
PMID: 19808575 (View on PubMed)

Abidov A, Hachamovitch R, Rozanski A, Hayes SW, Santos MM, Sciammarella MG, Cohen I, Gerlach J, Friedman JD, Germano G, Berman DS. Prognostic implications of atrial fibrillation in patients undergoing myocardial perfusion single-photon emission computed tomography. J Am Coll Cardiol. 2004 Sep 1;44(5):1062-70. doi: 10.1016/j.jacc.2004.05.076.

Reference Type BACKGROUND
PMID: 15337220 (View on PubMed)

Smit MD, Tio RA, Slart RH, Zijlstra F, Van Gelder IC. Myocardial perfusion imaging does not adequately assess the risk of coronary artery disease in patients with atrial fibrillation. Europace. 2010 May;12(5):643-8. doi: 10.1093/europace/eup404. Epub 2009 Dec 17.

Reference Type BACKGROUND
PMID: 20022875 (View on PubMed)

Nandalur KR, Dwamena BA, Choudhri AF, Nandalur MR, Carlos RC. Diagnostic performance of stress cardiac magnetic resonance imaging in the detection of coronary artery disease: a meta-analysis. J Am Coll Cardiol. 2007 Oct 2;50(14):1343-53. doi: 10.1016/j.jacc.2007.06.030. Epub 2007 Sep 17.

Reference Type BACKGROUND
PMID: 17903634 (View on PubMed)

Hamon M, Fau G, Nee G, Ehtisham J, Morello R, Hamon M. Meta-analysis of the diagnostic performance of stress perfusion cardiovascular magnetic resonance for detection of coronary artery disease. J Cardiovasc Magn Reson. 2010 May 19;12(1):29. doi: 10.1186/1532-429X-12-29.

Reference Type BACKGROUND
PMID: 20482819 (View on PubMed)

Ablitt NA, Gao J, Keegan J, Stegger L, Firmin DN, Yang GZ. Predictive cardiac motion modeling and correction with partial least squares regression. IEEE Trans Med Imaging. 2004 Oct;23(10):1315-24. doi: 10.1109/TMI.2004.834622.

Reference Type BACKGROUND
PMID: 15493698 (View on PubMed)

S. E. Litwin, J. Fluckiger, L. Chen, T. H. Kim, N. Pack, B. Matthews, C. McGann, R. Jiji, et al. Does fixed-dose regadenoson induce comparable myocarial perfusion reserve in patients of widely varying body size? A quantitative MRI study. American Heart Association, chicago, 2010.

Reference Type BACKGROUND

O. J. Booker, P. Bandettini, P. Kellman, J. Wilson, S. Leung, S. Vasu, S. Shanbhag, J. Henry, et al. Time resolved measure of coronary sinus flow following regadenoson administration. Journal of cardiovascular magnetic resonance, 13(1): O74, 2011.

Reference Type BACKGROUND

Harper R, Reeves B. Reporting of precision of estimates for diagnostic accuracy: a review. BMJ. 1999 May 15;318(7194):1322-3. doi: 10.1136/bmj.318.7194.1322. No abstract available.

Reference Type BACKGROUND
PMID: 10323817 (View on PubMed)

Bieging ET, Haider I, Adluru G, Chang L, Suksaranjit P, Likhite D, Shaaban A, Jensen L, Wilson BD, McGann CJ, DiBella E. Rapid rest/stress regadenoson ungated perfusion CMR for detection of coronary artery disease in patients with atrial fibrillation. Int J Cardiovasc Imaging. 2017 Nov;33(11):1781-1788. doi: 10.1007/s10554-017-1168-1. Epub 2017 May 20.

Reference Type DERIVED
PMID: 28528431 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

REGA-12F08

Identifier Type: -

Identifier Source: org_study_id