Comprehensive Evaluation of Ischemic Heart Disease Using MRI

• Sponsor: Northwestern University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01234870
• Collaborator: Astellas Pharma US, Inc. (Industry), Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma (Industry)
• Enrollment: 40
• Location: 1
• Arm: 1
• Duration (Months): 19
• Patients Per Site Per Month: 2.1

Study Details

Study Description

Brief Summary

The purpose of the study is to assess the diagnostic performance of fully automated motion corrected (MC) first pass myocardial perfusion MRI, compared to the original non-corrected first pass myocardial perfusion images in a cohort of patients with suspected ischemic heart disease, using coronary angiography as the reference standard. It is expected that this improved comprehensive protocol for cardiac MRI be accurate at detecting significant coronary artery disease and may obviate the need for other more expensive and invasive diagnostic tests currently used.

Condition or Disease	Intervention/Treatment	Phase
Heart Disease, Ischemic; Atherosclerosis, Coronary	Drug: Gadolinium; Drug: Adenosine	Phase 2/Phase 3

Detailed Description

Coronary heart disease is the leading cause of death and disability in the US, accounting for about one-third of all deaths in subjects over age 35.

With the development of newer Magnetic Resonance Imaging (MRI) techniques, such as faster pulse sequences and parallel imaging, cardiac MRI has become a routine tool for the evaluation and detection of myocardial ischemic disease. First pass myocardial perfusion (FPMP) using MRI is increasingly being used to assess ischemic heart disease. MRI offers the advantages of spatial resolution sufficient to differentiate between subendocardial and subepicardial perfusion; shorter examination time and also lack of ionizing radiation. Left ventricle cine gradient echo imaging can be used to assess regional ventricular function. Left ventricular myocardial viability can also be easily assessed at the same time in order to determine the amount of viable left ventricular myocardium and the percentage of irreversibly scarred myocardium by delayed enhanced images. Viability imaging is usually added to the perfusion protocol to increase specificity by allowing detection of fixed perfusion defects, which represent scar. The ultimate cardiac MRI protocol would be to combine both of these imaging strategies with a reliable and accurate coronary Magnetic Resonance Angiography(MRA) technique, such that obstructive coronary artery disease could be evaluated comprehensively at the same time. If all of these techniques can be combined together in a single study, it may be feasible to finally achieve a "one stop shop" for cardiac Magnetic Resonance Imaging.

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Comprehensive Evaluation of Ischemic Heart Disease Using MRI
• Study Start Date: Jun 1, 2010
• Actual Primary Completion Date: Jan 1, 2012
• Actual Study Completion Date: Jan 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ischemic heart disease patients Patients with suspected ischemic heart disease prospectively recruited for first pass myocardial perfusion MRI. All subject to receive Gadolinium infusion of 0.075 mmol/kg at rate of 4 ml/sec. Adenosine administered at a rate of 0.14 mg/kg/min for a duration of 4 minutes to induce stress.	Drug: Gadolinium; Other Names: Magnevist, Bayer HealthCare Pharmaceuticals ; Drug: Adenosine

Outcome Measures

Primary Outcome Measures

1. Magnetic Resonance Image Quality Rating [Cross sectional study; magnetic resonance images were obtained on all patients using two different acquisition methods.]

   The purpose of the study is to assess the incremental value of diagnostic performance using a fully-automated, motion-corrected (MC) first pass myocardial perfusion image acquisition protocol compared to images obtained under a non-corrected, breath-hold, shallow-breathing first pass myocardial perfusion image acquisition protocol in patients with suspected ischemic heart disease. The MR images resulting from two different image acquisition techniques, including Non-Corrected Breath-Hold Shallow-Breathing and Motion-Corrected, were assessed independently by two radiologists (average of 7 years of experience in reading cardiac MRI) using the American Heart Association modified 16 segment model and were evaluated using a four point Likert scale (1 = poor, 2 = fair, 3 = good, and 4 = excellent) for image quality

Secondary Outcome Measures

1. Number of Participants With Adverse Events to Demonstrate Feasibility of a Comprehensive Cardiac Magnetic Resonance Imaging Protocol [14 days]

   Adverse events relating to administration of adenosine during a coronary heart disease comprehensive cardiac MRI study.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Under an Institutional Committee on Human Research board approved protocol 80 patients with a suspected myocardial ischemic disease recruited from the cardiac cath laboratory will be recruited in this prospective study. Volunteers will be recruited for the purpose of protocol development and will not be included in analysis. All subjects will be screened for glomerular filtration rate (GFR) within 24 hours before the exam. All patients must have a GFR > 30 mL/min/1.73m2 to be part of the study.

All subjects will be selected following the Nephrogenic Systemic Fibrosis (NSF) guidelines. All dialysis patients or end-stage renal disease patients with a creatinine clearance of < 30 mL/min will not be selected for the study to avoid NSF. Patients with GFR < 60 ml/min but >30 ml/min will receive a reduced dose of Gadolinium contrast (0.1 ml/kg).

Exclusion Criteria:

1. Age <18 years;

2. Known contraindication to MR imaging (such as pacemaker placement, magnetic implants, etc);

3. Claustrophobia;

4. Inability to perform an adequate breath-hold for imaging,

5. Inability to provide informed consent;

6. all subjects will be will be screened for GFR within 24 hours before the exam and subjects presenting with GFR < 30 ml/min will be excluded;

7. Pregnant and lactating women;

8. Patients with hypersensitivity to gadolinium contrast agents, metoprolol, adenosine, or nitroglycerin;

9. Contra indication for Adenosine

10. 2nd- or 3rd-degree atrioventricular block (except in patients with a functioning artificial pacemaker)

11. Sinus node disease (except in patients with a functioning artificial

pacemaker)

1. Unstable angina

2. Acute myocardial infarction

3. Known or suspected bronchoconstrictive or bronchospastic lung

disease (e.g., asthma)

1. Hypersensitivity to adenosine

2. Caffeine within 12-24 hours

3. Theophylline and Dipyridamole products within 24 hours.

4. Contra indication for Metoprolol

5. sinus bradycardia

6. heart block greater than first degree

7. Cardiac Failure

8. Bronchospastic Disease

9. Contra indication for Nitroglycerin

10. Early myocardial infarction, severe anemia, increased intracranial pressure, and those with a known hypersensitivity to nitroglycerin.

b .Administration of Nitrostat (nitroglycerin tablets, USP) is contraindicated in patients who are using Viagra® since Viagra has been shown to potentiate the hypotensive effects of organic nitrates.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northwestern University	Chicago	Illinois	United States	60611

Sponsors and Collaborators

• Northwestern University
• Astellas Pharma US, Inc.
• Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma

Investigators

• Principal Investigator: James C Carr, MD, Northwestern University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: James Carr, Director of Cardiovascular Imaging, Department of Radiology,Associate Professor of Radiology and Medicine, Northwestern University Feinberg School of Medicine, Northwestern University
• ClinicalTrials.gov Identifier: NCT01234870
• Other Study ID Numbers: CR1_STU00006013; ASCA-9J02
• First Posted: Nov 4, 2010
• Last Update Posted: Sep 26, 2014
• Last Verified: Sep 1, 2014

• Keywords provided by James Carr, Director of Cardiovascular Imaging, Department of Radiology,Associate Professor of Radiology and Medicine, Northwestern University Feinberg School of Medicine, Northwestern University: Myocardial Perfusion Imaging; Magnetic Resonance Imaging
• Additional relevant MeSH terms: Heart Diseases; Atherosclerosis; Myocardial Ischemia; Coronary Artery Disease; Ischemia; Adenosine

Study Results

Participant Flow

Arm/Group Title	Ischemic Heart Disease Patients
Arm/Group Description	Patients with suspected ischemic heart disease prospectively recruited for first pass myocardial perfusion MRI. All subject to receive Gadolinium infusion of 0.075 mmol/kg at rate of 4 ml/sec. Adenosine administered at a rate of 0.14 mg/kg/min for a duration of 4 minutes to induce stress.
Period Title: Overall Study
STARTED	40
COMPLETED	40
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Adenosine
Arm/Group Description	Adenosine (Adenoscan) will be infused intravenously at a dose of 0.14mg/kg/min for a total of 4 mins. adenosine: Adenosine will be infused intravenously at a dose of 0.14mg/kg/min for a total of 4 mins
Overall Participants	40
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.9 (8.21)
Sex: Female, Male (Count of Participants)
Female	13 32.5%
Male	27 67.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	6 15%
White	30 75%
More than one race	0 0%
Unknown or Not Reported	4 10%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 5%
Not Hispanic or Latino	32 80%
Unknown or Not Reported	6 15%
Region of Enrollment (participants) [Number]
United States	40 100%
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	29.57 (5.83)

Outcome Measures

1. Primary Outcome

Title	Magnetic Resonance Image Quality Rating
Description	The purpose of the study is to assess the incremental value of diagnostic performance using a fully-automated, motion-corrected (MC) first pass myocardial perfusion image acquisition protocol compared to images obtained under a non-corrected, breath-hold, shallow-breathing first pass myocardial perfusion image acquisition protocol in patients with suspected ischemic heart disease. The MR images resulting from two different image acquisition techniques, including Non-Corrected Breath-Hold Shallow-Breathing and Motion-Corrected, were assessed independently by two radiologists (average of 7 years of experience in reading cardiac MRI) using the American Heart Association modified 16 segment model and were evaluated using a four point Likert scale (1 = poor, 2 = fair, 3 = good, and 4 = excellent) for image quality
Time Frame	Cross sectional study; magnetic resonance images were obtained on all patients using two different acquisition methods.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ischemic Heart Disease Patients
Arm/Group Description	Patients with suspected ischemic heart disease prospectively recruited for first pass myocardial perfusion MRI. All subject to receive Gadolinium infusion of 0.075 mmol/kg at rate of 4 ml/sec. Adenosine administered at a rate of 0.14 mg/kg/min for a duration of 4 minutes to induce stress.
Measure Participants	40
Motion Corrected Images	3.57 (0.66)
Non-Corrected Breath-Hold, Shallow-Breathing Image	2.55 (0.81)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ischemic Heart Disease Patients
	Comments	The MR images resulting from two different image acquisition techniques, including Non-Corrected Breath-Hold Shallow-Breathing and Motion-Corrected, were assessed independently by two radiologists (average of 7 years of experience in reading cardiac MRI) using the American Heart Association modified 16 segment model and were evaluated using a four point Likert scale (1 = poor, 2 = fair, 3 = good, and 4 = excellent) for image quality
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Secondary Outcome

Title	Number of Participants With Adverse Events to Demonstrate Feasibility of a Comprehensive Cardiac Magnetic Resonance Imaging Protocol
Description	Adverse events relating to administration of adenosine during a coronary heart disease comprehensive cardiac MRI study.
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Adenosine
Arm/Group Description	Adenosine (Adenoscan) will be infused intravenously at a dose of 0.14mg/kg/min for a total of 4 mins. adenosine: Adenosine will be infused intravenously at a dose of 0.14mg/kg/min for a total of 4 mins
Measure Participants	40
Number [occurances of adverse events]	0

Adverse Events

Time Frame	Patients were monitored for adverse events for 14 days following administration of adenosine.
Adverse Event Reporting Description	Patients were monitored for adverse events on the day of the MR scan. Following administration of adenosine for stress testing, patients were monitored until fifteen minutes after patient vitals returned to baseline. Following the day of participation, patients were monitored for any serious adverse experiences for 14 days.
Arm/Group Title	Adenosine
Arm/Group Description	Adenosine (Adenoscan) will be infused intravenously at a dose of 0.14mg/kg/min for a total of 4 mins. adenosine: Adenosine will be infused intravenously at a dose of 0.14mg/kg/min for a total of 4 mins
All Cause Mortality
	Adenosine
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Adenosine
	Affected / at Risk (%)	# Events
Total	0/40 (0%)
Other (Not Including Serious) Adverse Events
	Adenosine
	Affected / at Risk (%)	# Events
Total	0/40 (0%)

Limitations/Caveats

The small number of subjects results in reduced statistical power; The cohort was selected from patients at a single medical center, potentially reducing generalizability; Variability in patient behavior during MR scans may affect analyses

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.