Design and rationale of the MR-INFORM study: stress perfusion cardiovascular magnetic resonance imaging to guide the management of patients with stable coronary artery disease

Abstract

Background: In patients with stable coronary artery disease (CAD), decisions regarding revascularisation are primarily driven by the severity and extent of coronary luminal stenoses as determined by invasive coronary angiography. More recently, revascularisation decisions based on invasive fractional flow reserve (FFR) have shown improved event free survival. Cardiovascular magnetic resonance (CMR) perfusion imaging has been shown to be non-inferior to nuclear perfusion imaging in a multi-centre setting and superior in a single centre trial. In addition, it is similar to invasively determined FFR and therefore has the potential to become the non-invasive test of choice to determine need for revascularisation.

Trial design: The MR-INFORM study is a prospective, multi-centre, randomised controlled non-inferiority, outcome trial. The objective is to compare the efficacy of two investigative strategies for the management of patients with suspected CAD. Patients presenting with stable angina are randomised into two groups: 1) The FFR-INFORMED group has subsequent management decisions guided by coronary angiography and fractional flow reserve measurements. 2) The MR-INFORMED group has decisions guided by stress perfusion CMR. The primary end-point will be the occurrence of major adverse cardiac events (death, myocardial infarction and repeat revascularisation) at one year. Clinical trials.gov identifier NCT01236807.

Conclusion: MR INFORM will assess whether an initial strategy of CMR perfusion is non-inferior to invasive angiography supplemented by FFR measurements to guide the management of patients with stable coronary artery disease. Non-inferiority of CMR perfusion imaging to the current invasive reference standard (FFR) would establish CMR perfusion imaging as an attractive non-invasive alternative to current diagnostic pathways.

Figure 1

Study Flow diagram outlining the study design. *CXA = Coronary Angiography.

Figure 2

MR-INFORM cardiac magnetic resonance protocol. After individual patient planning using survey scans, intravenous adenosine is given according to the protocol. First pass stress perfusion imaging is done during stress visualizing the first passage of a 0.75 mmol/kg contrast agent bolus through the myocardium. Short axis (SA) cine images are acquired. Rest perfusion images are acquired during an injection of a second bolus of 0.75 mmol/kg contrast agent. 10 minutes after an additional injection of 0.05 mmol/kg of contrast agent to increase the total dose of contrast agent to 0.2 mmol/kg is given. A modified Look-Locker inversion time scout is performed prior to late gadolinium enhancement imaging in short axis and long axis views. During the wait time after the last contrast agent injection long axis images in the 4 chamber, 3 chamber and the 2 chamber views are obtained.