Clinical trial NCT01655043: Absolute Quantification of Coronary Flow Reserve by Stress Perfusion MRI
Official title: Absolute Quantification of Coronary Flow Reserve by Stress Perfusion MRI
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Myocardial Ischemia
Keywords: Magnetic Resonance Imaging
regadenoson
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: Astellas Pharma Global Development, Inc.
First posted: 2012-08-01
Enrollment: 20
Sex: ALL
Minimum age (years): 19
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: Coronary artery disease (CAD, coronary heart disease) is the leading cause of death in the U.S., causing 1 in 5 deaths in 2005. The current method for diagnosing coronary artery disease that is considered most accurate is coronary angiography however it involves risk and radiation. Alternatively nuclear imaging test and MRI stress test only permits the semi qualitative analysis of the myocardial perfusion images.

In this proposal the investigators will develop a means to calculate Coronary Flow Reserve (CFR) using the MRI. the investigators approach has the potential to reduce mortality from myocardial infarction by effecting a change in the patient management paradigm. Absolute quantification of myocardial perfusion will detect coronary stenosis and CAD in patients with more accuracy than the semi-quantitative or qualitative analysis of perfusion images. Measurement of Coronary Flow Reserve is important for the following reasons: decrease of coronary flow reserve has been identified as a first effect of CAD; it provides an objective measure of treatment efficacy.

The purpose of this study is to compare images from nuclear stress test and/or coronary angiography with Magnetic Resonance Imaging (MRI) that will evaluate subjects with coronary artery disease calculating myocardial blood flow using a novel MRI technique combined to an extracellular Gadolinium-based contrast agent and stressor agent

Detailed description: The main hypothesis the investigators will test is that changes in myocardial blood volume, under physiologic stress, correlate with myocardial flow reserve as measured in low spatial resolution nuclear SPECT scans. Secondary hypothesis is that stress perfusion as quantified with bolus height corrected gadofosveset trisodium images, better correlate with SPECT perfusion than uncorrected, relative perfusion values.

The investigators propose implementing the scan protocol using a 1.5T or 3.0T MRI scanner. The investigators will scan a series of 20 patients recruited from the nuclear stress lab at Northwestern Memorial Hospital. These subjects will be approached and enrolled into a HIPPA Compliant, IRB approved research study to assess the effectiveness of myocardial perfusion and blood volume images to measure myocardial blood volume. Subjects will be scanned with a modified version of the clinical stress-perfusion protocol. Correlation analysis will be used to test the hypothesis that quantitative blood volume is an indicator of myocardial flow reserve.

Eligibility criteria: Inclusion Criteria:

Under an Institutional Committee on Human Research board approved protocol, 20 patients with a suspected myocardial ischemic disease with positive stress nuclear medicine test laboratory will be recruited in this prospective study. All subjects will be screened for GFR within 24 hours before the exam. All patients must have a GFR \> 30 mL/min/1.73m2 to be included in 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 \< 30mL/min will not be selected for the study to avoid NSF.

Exclusion Criteria:

1. Age 18 to 89 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 \< 60 ml/min will be excluded;
7. Pregnant and lactating women;
8. Patients with hypersensitivity to gadolinium contrast agents, metoprolol, adenosine, or nitroglycerin;

10) Contra indication for Regadenoson

1. 2nd- or 3rd-degree AV block (except in patients with a functioning artificial pacemaker)
2. Sinus node disease (except in patients with a functioning artificial pacemaker)
3. Unstable angina
4. Acute myocardial infarction
5. Known or suspected bronchoconstrictive or bronchospastic lung disease (e.g., asthma)
6. Hypersensitivity to adenosine
7. Caffeine within 12-24 hours
8. Theophylline and Dipyridamole products within 24 hours

Primary outcomes:
measure: Quantification of Myocardial Blood Volume
timeFrame: outcome measured following single MRI scan
Secondary outcomes:
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
Study officials:
affiliation: Northwestern University
name: James C Carr, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rosamond W, Flegal K, Friday G, Furie K, Go A, Greenlund K, Haase N, Ho M, Howard V, Kissela B, Kittner S, Lloyd-Jones D, McDermott M, Meigs J, Moy C, Nichol G, O'Donnell CJ, Roger V, Rumsfeld J, Sorlie P, Steinberger J, Thom T, Wasserthiel-Smoller S, Hong Y; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2007 Feb 6;115(5):e69-171. doi: 10.1161/CIRCULATIONAHA.106.179918. Epub 2006 Dec 28. No abstract available.
citation: Elkington AG, Gatehouse PD, Ablitt NA, Yang GZ, Firmin DN, Pennell DJ. Interstudy reproducibility of quantitative perfusion cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2005;7(5):815-22. doi: 10.1080/10976640500287877.
citation: Wu KC, Zerhouni EA, Judd RM, Lugo-Olivieri CH, Barouch LA, Schulman SP, Blumenthal RS, Lima JA. Prognostic significance of microvascular obstruction by magnetic resonance imaging in patients with acute myocardial infarction. Circulation. 1998 Mar 3;97(8):765-72. doi: 10.1161/01.cir.97.8.765.