Clinical trial NCT02073422: FAMOUS-NSTEMI MRI Sub-Study
Official title: Fractional Flow Reserve Versus Angiographically Guided Management to Optimise Outcomes in Unstable Coronary Syndromes - a 3.0 Tesla Stress Perfusion MRI Sub-Study (FAMOUS-NSTEMI MRI)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: NonST Elevation Myocardial Infarction
Keywords: Magnetic resonance imaging
Myocardial stress perfusion magnetic resonance imaging
Fractional flow reserve
Relaxometry
Coronary artery disease
Lead sponsor: NHS National Waiting Times Centre Board
Sponsor class: OTHER
Collaborators: name: University of Glasgow
name: British Heart Foundation
name: NHS Lanarkshire
name: NHS Greater Glasgow and Clyde
First posted: 2014-02-27
Enrollment: 106
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Medically stabilised patients with recent non-ST elevation myocardial infarction.

Brief summary: BACKGROUND: Non-ST-segment elevation myocardial infarction (NSTEMI) is the commonest type of acute coronary syndrome (ACS) and has a poor long-term prognosis. Guidewire-based coronary pressure measurement of the myocardial fractional flow reserve (FFR) is validated for measuring the severity of a coronary lesion narrowing in patients with stable angina. FFR measurement in patients with a recent ACS has theoretical limitations and is not fully validated.

AIM: To prospectively assess heart muscle blood flow and injury with guide-wire based methods at the time of the clinically-indicated angiogram and compare these results with those from a stress perfusion MRI scan in medically-stabilised NSTEMI..

HYPOTHESIS: 1) FFR measured invasively will correspond closely with findings from stress perfusion MRI, 2) MRI will provide clinically-relevant information on heart muscle injury, function and salvage, 3) Guidewire-derived measurements of coronary microvascular function will be associated with the MRI findings.

DESIGN: The MRI study will be performed in patients who give informed consent in the FAMOUS-NSTEMI clinical trial (NCT registration 01764334). All of the clinical data for these participants will be available to link with the MRI results.

Detailed description: BACKGROUND: Non-ST elevation myocardial infarction (NSTEMI) is the commonest type of acute coronary syndrome (ACS) and has a poor long-term prognosis. Guidewire-based coronary pressure measurement of the myocardial fractional flow reserve (FFR) is a prognostically-validated invasive method for measuring coronary lesion severity in patients with stable coronary artery disease. FFR measurement in patients with unstable coronary disease has theoretical limitations and is not fully validated in NSTEMI.

AIM: To prospectively evaluate ischaemia and infarction with adenosine stress perfusion cardiac MRI in medically-stabilised NSTEMI patients in whom FFR has been measured.

METHODS: In the FAMOUS-NSTEMI clinical trial (NCT registration 01764334), medically-stabilised patients with recent NSTEMI will have lesion-level ischaemia measured with FFR in all coronary artery stenoses amenable to revascularisation, as clinically appropriate.

Consecutive study participants will be invited to have an adenosine (140 µg/kg/min) stress 3.0 Tesla cardiac MRI scan to assess myocardial perfusion on up to three occasions: 1) before coronary angiography, 2) within 10 days post coronary angiography and finally, 3) 6 months after hospital admission. MRI will also assess myocardial pathophysiology including ischaemia, oedema, haemorrhage and infarct scar. MRI will provide the reference dataset. Guidewire-derived parameters were obtained and assessed blind to the MRI results.

The primary outcome is the correspondence between the presence or absence of an inducible-myocardial perfusion defect and FFR ≤ or \> 0.80 in the MRI scans at baseline or post-angiography. Secondary outcomes include the correlation between measures of infarct severity as revealed by MRI (infarct size, myocardial salvage, microvascular obstruction, myocardial haemorrhage, myocardial strain) and invasive measures of coronary function (1) coronary collateral supply (fractional coronary collateral supply), (2) microcirculatory resistance (index of microvascular resistance), and (3) vasodilator capacity (resistive reserve ratio).

The project was funded by the British Heart Foundation and Chief Scientist Office. The pressure wires were provided through a restricted grant from St Jude Medical. The funders of the study have no involvement in the study design, analysis, interpretation, or presentation of the results.

VALUE: This study will provide clinically important information on the relationships between coronary artery and microcirculatory function measured invasively and ischaemia and MI pathologies, as revealed by non-invasively by MRI.

Eligibility criteria: Inclusion Criteria:

* (1) Participation in the FAMOUS NSTEMI clinical trial (NCT registration 01764334); (2) age \>18 years; (3) written informed consent.

Exclusion Criteria:

* 1) Contra-indications to MRI including metallic devices and severe kidney disease (i.e. an estimated glomerular filtration rate \<30 ml/min/1.73 m2).

Primary outcomes:
measure: Correspondence between FFR and myocardial perfusion revealed by adenosine stress perfusion MRI.
timeFrame: MRI at baseline
Secondary outcomes:
measure: Myocardial Infarction
timeFrame: Baseline MRI scan
measure: Myocardial area-at-risk
timeFrame: Baseline MRI scan
measure: Myocardial salvage
timeFrame: Baseline and follow-up MRI (average 12 months)
measure: Myocardial salvage index
timeFrame: Baseline and follow-up MRI (average 12 months)
measure: Left ventricular ejection fraction
timeFrame: Baseline and follow-up MRI (average 12 months)
measure: Culprit artery assignment
timeFrame: Baseline MRI scan
measure: Microvascular obstruction
timeFrame: Baseline MRI scan
measure: Myocardial haemorrhage
timeFrame: Baseline MRI
measure: Regional myocardial strain
timeFrame: Baseline and follow-up MRI (average 12 months)
measure: Adenosine response
timeFrame: Baseline
Other outcomes:
Locations:
city: Glasgow
country: United Kingdom
facility: BHF Glasgow Cardiovascular Research Centre
state: Strathclyde
Study officials:
affiliation: University of Glasgow
name: Colin Berry, MB ChB BSc FRCP FACC
role: PRINCIPAL_INVESTIGATOR
References:
citation: Berry C, Layland J, Sood A, Curzen NP, Balachandran KP, Das R, Junejo S, Henderson RA, Briggs AH, Ford I, Oldroyd KG. Fractional flow reserve versus angiography in guiding management to optimize outcomes in non-ST-elevation myocardial infarction (FAMOUS-NSTEMI): rationale and design of a randomized controlled clinical trial. Am Heart J. 2013 Oct;166(4):662-668.e3. doi: 10.1016/j.ahj.2013.07.011. Epub 2013 Aug 27.
citation: Layland J, Rauhalammi S, Watkins S, Ahmed N, McClure J, Lee MM, Carrick D, O'Donnell A, Sood A, Petrie MC, May VT, Eteiba H, Lindsay M, McEntegart M, Oldroyd KG, Radjenovic A, Berry C. Assessment of Fractional Flow Reserve in Patients With Recent Non-ST-Segment-Elevation Myocardial Infarction: Comparative Study With 3-T Stress Perfusion Cardiac Magnetic Resonance Imaging. Circ Cardiovasc Interv. 2015 Aug;8(8):e002207. doi: 10.1161/CIRCINTERVENTIONS.114.002207.
citation: Layland J, Rauhalammi S, Lee MM, Ahmed N, Carberry J, Teng Yue May V, Watkins S, McComb C, Mangion K, McClure JD, Carrick D, O'Donnell A, Sood A, McEntegart M, Oldroyd KG, Radjenovic A, Berry C. Diagnostic Accuracy of 3.0-T Magnetic Resonance T1 and T2 Mapping and T2-Weighted Dark-Blood Imaging for the Infarct-Related Coronary Artery in Non-ST-Segment Elevation Myocardial Infarction. J Am Heart Assoc. 2017 Mar 31;6(4):e004759. doi: 10.1161/JAHA.116.004759.