Detection and Significance of Heart Injury in ST Elevation Myocardial Infarction. (BHF MR-MI)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Siemens Healthcare
British Heart Foundation (Project Grant PG/11/2/28474)
Information provided by (Responsible Party):
Colin Berry, University of Glasgow
ClinicalTrials.gov Identifier:
NCT02072850
First received: February 25, 2014
Last updated: August 11, 2014
Last verified: August 2014
  Purpose

Heart imaging with magnetic resonance imaging (MRI) provides detailed insights into heart function and injury. The nature and significance of heart injury after a heart attack is incompletely understood. We propose a 'natural history' study of heart attack injury using contemporary MRI methods. In a large hospital in the West of Scotland, heart attack patients will be invited to have at least two MRI scans and also continue with life-long follow-up. The results from the MRI scans will be assessed with all of the other clinical information obtained at the time of the heart attack and during follow-up. The results of our study should provide new insights into heart attack injury and these results should help improve how heart attack patients should be treated.


Condition Intervention
Acute ST-elevation Myocardial Infarction
Device: Coronary pressure wire
Other: Magnetic resonance imaging of the heart

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Cardiac Magnetic Resonance Imaging: New Pathological Insights and Their Functional and Clinical Significance in ST Elevation Acute Myocardial Infarction.

Resource links provided by NLM:


Further study details as provided by NHS National Waiting Times Centre Board:

Primary Outcome Measures:
  • Myocardial salvage [ Time Frame: Baseline and 6 months after date of index hospitalisation for STEMI ] [ Designated as safety issue: No ]
    Myocardial salvage (% left ventricular volume) was defined as the difference between the initial jeopardised area-at-risk revealed by T2-weighted MRI (1.5 Tesla, Siemens Healthcare) at baseline and final infarct size revealed by contrast-enhanced MRI at 6 months on the same MRI scanner.


Secondary Outcome Measures:
  • Myocardial salvage index [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
    The myocardial salvage index was defined as infarct size at 6 months indexed to the initial area-at-risk revealed by T2-weighted MRI.

  • Final infarct size [ Time Frame: MRI scan at 6 months after index hospitalisation ] [ Designated as safety issue: No ]
    Final infarct size imaged on the MRI scan 6 months after initial hospitalisation for STEMI. Late gadolinium enhancement is revealed by MRI scanning 10 - 15 minutes after intravenous gadolinium contrast administration. The myocardial mass of late gadolinium (grams) will be quantified by a semi-automatic detection method using a signal intensity threshold of >5 standard deviations above a remote reference region.

  • Myocardial haemorrhage [ Time Frame: Baseline MRI scan ] [ Designated as safety issue: No ]
    Myocardial haemorrhage (a prioritised secondary outcome) is revealed by T2 weighted imaging and is defined as a confluent dark zone with a mean signal intensity <2 standard deviations of the mean signal intensity of the surrounding affected brighter area in the area of injury. Haemorrhage is specifically identified by T2* mapping, and will also be imaged with T2-weighted MRI (e.g. T2 mapping).

  • Microvascular obstruction [ Time Frame: Baseline MRI scan ] [ Designated as safety issue: No ]
    MVO is classified as present (central dark zone with a subendocardial or intra-mural distribution (binary)) and non-relevant (dots or nil) and quantified as a % of total left ventricular mass, after adjustment for the initial area-at-risk revealed by T2-weighted MRI. Late MVO is imaged by MRI 10 - 15 minutes after contrast administration. Late MVO should be preceded by abnormal first pass and early MVO on 1, 3, and 5 minute scans.

  • First pass MVO [ Time Frame: Baseline MRI ] [ Designated as safety issue: No ]
    First pass MVO is revealed by MRI scanning during the 'first pass' of gadolinium contrast in the ventricular myocardium. The extent of the first pass perfusion deficit at rest (i.e. first pass 'wash-in' MVO) will be assessed.

  • Early MVO [ Time Frame: Baseline MRI ] [ Designated as safety issue: No ]
    Early MVO is acquired with MRI scanning 1 minute after gadolinium administration and forms part of the diagnostic criteria to confirm LATE MVO.

  • Area-at-risk [ Time Frame: Baseline MRI scan ] [ Designated as safety issue: No ]
    The jeopardised area-at-risk on each axial image is defined as the percentage of left ventricular area delineated by the hyperintense zone on T2-weighted MRI with parametric maps. The initial area-at-risk will be assessed retrospectively with MRI ~2 days after initial hospitalisation for STEMI. Area-at-risk will be assessed with T2 and T1 mapping. The area-at-risk will be quantified by a semi-automatic detection method using a signal intensity threshold of >2 standard deviations above a remote reference region.

  • Myocardial T1 time [ Time Frame: Baseline and follow-up MRI at 6 months ] [ Designated as safety issue: No ]
    The myocardial T1 relaxation time (ms) pre- and post-contrast will be estimated using a Modified Look-Locker Inversion recovery method (MOLLI, Siemens Healthcare). Post-contrast MOLLI scans will be obtained approximately 15 minutes after intravenous injection of gadolinium. Haematocrit will be measured from a full blood count blood test obtained at the time of the scan.

  • Myocardial T2 time [ Time Frame: Baseline and follow-up MRI at 6 months ] [ Designated as safety issue: No ]
    The myocardial T2 relaxation time (ms) will be estimated using a balanced steady state free precession method (Siemens Healthcare).

  • Left ventricular ejection fraction [ Time Frame: Baseline and follow-up MRI at 6 months ] [ Designated as safety issue: No ]
    Left ventricular ejection fraction (LVEF) is measured by subtraction of left ventricular end-systolic volume from left ventricular end-diastolic volume. LVEF is measure of systolic function and is a prognostically validated surrogate of health outcome.

  • Left ventricular end-diastolic volume [ Time Frame: Baseline and follow-up MRI at 6 months ] [ Designated as safety issue: No ]
    Left ventricular end-diastolic volume (millilitres)

  • Left ventricular end-systolic volume [ Time Frame: Baseline and follow-up MRI at 6 months ] [ Designated as safety issue: No ]
    Left ventricular end-systolic volume (millilitres)

  • Index of microvascular resistance [ Time Frame: Day 0 at initial hospital admission ] [ Designated as safety issue: No ]
    The index of microvascular resistance (IMR) is a guidewire-derived measurement of coronary microvascular function. IMR = mean distal coronary pressure x mean transit time, measured during systemic hyperaemia induced by intravenous adenosine (140 ug/kg/min). Resting physiological parameters will also be measured.

  • Quality of life [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
    Patient-reported quality of life and health status will be assessed at baseline and during follow-up at 6 months. The Euroquol EQ-5D questionnaire will be used. Health-related quality of life will be related to other clinical information, including the MRI findings, and for estimation of quality-adjusted life years which is relevant for health economic assessments.

  • Recurrent myocardial infarction [ Time Frame: 6 months ] [ Designated as safety issue: No ]

    The clinical characteristics that might predict recurrent cardiac events in survivors of STEMI are uncertain. The risk of recurrent MI is clinically relevant since this risk is potentially modifiable by additional PCI, as observed in the Preventative Angioplasty in Acute Myocardial Infarction (PRAMI) trial (N Engl J Med 2013 DOI: 10.1056/NEJMoa1305520).

    The clinical predictors of recurrent MI, as revealed by contrast MRI at 6 months and recurrent adverse cardiac events during the longer term will be assessed. Recurrent MI may be fatal or non-fatal. The characteristics to be assessed at baseline will include clinical characteristics (e.g. age, diabetes), coronary artery disease characteristics (as revealed by quantitative coronary analysis and plaque characterisation), guidewire-derived parameters of coronary artery function, and MI characteristics as revealed by contrast-enhanced MRI.


  • Adenosine response [ Time Frame: Baseline ] [ Designated as safety issue: Yes ]
    The response to intravenous adenosine as reflected by patient-reported symptoms and changes in heart rate and blood pressure will be prospectively assessed. Adverse events, such as abnormalities in heart rate and rhythm and bronchospasm, that might be associated with the adenosine infusion will also be recorded.

  • MACE [ Time Frame: Minimum 12 months ] [ Designated as safety issue: No ]
    Major Adverse Cardiac Events are defined as cardiac death, non-fatal myocardial infarction (MI) or hospitalisation for heart failure. The event definitions will follow the FDA guidelines (Hicks K et al 2010, 2012) and the Third Universal Definition of Myocardial Infarction (Thygesen et al Eur Heart J 2012). Events will be reviewed by a cardiologist who is independent of the research team and who is blinded to the MRI results. MACE will be related to the clinical and MRI findings at baseline. The survival analysis will be performed at the end of the study and again after a minimum of 3 years follow-up in all participants. The longer term follow-up will be performed by electronic case record linkage to hospital, NHS and government records.

  • MACCE [ Time Frame: Minimum 12 months ] [ Designated as safety issue: No ]
    Major Adverse Cardiovascular Events (MACCE) is the composite of cardiovascular death, non-fatal MI, hospitalisation for TIA or stroke. The event definitions will follow the FDA guidelines (Hicks K et al 2010, 2012) and the Third Universal Definition of Myocardial Infarction (Thygesen et al Eur Heart J 2012). THE MACCE events will be reviewed by a cardiologist who is independent of the research team and who is blinded to the MRI results. MACCE will be related to the clinical and MRI findings at baseline. The survival analysis will be performed at the end of the study and again after a minimum of 3 years follow-up in all participants. The longer term follow-up will be performed by electronic case record linkage to hospital, NHS and government records.

  • Serious adverse cardiovascular events. [ Time Frame: Minimum 12 months ] [ Designated as safety issue: No ]
    All serious adverse cardiovascular events including cardiovascular death, non-fatal MI, hospitalisation for unstable angina, hospitalisation for heart failure, implantable defibrillator implantation, hospitalisation for TIA or stroke, PCI, or CABG will be evaluated. Event definitions will follow the FDA guideline (Hicks K et al 2010, 2012) and the Third Universal Definition of Myocardial Infarction (Thygesen et al Eur Heart J 2012). In order to understand the prognostic significance of the clinical and MRI findings, these baseline findings will be associated with the cardiovascular events. The events will be reviewed by a cardiologist who is independent of the research team and who is blinded to the MRI results. The follow-up analysis will be performed at the end of the study and again after a min 3 years follow-up. The longer term follow-up will be performed by electronic case record linkage to hospital, NHS and government records.

  • All-cause death or heart failure [ Time Frame: Minimum 12 months from baseline ] [ Designated as safety issue: Yes ]
    All-cause death and hospitalisation for heart failure is taken to be prognostically important and mechanistically linked to impaired heart function and injury after STEM. Event definitions will follow the FDA guideline (Hicks K et al 2010, 2012). In order to understand the prognostic significance of the clinical and MRI findings, these baseline findings will be associated with the occurrence of death or heart failure. Implantation of a cardiac defibrillator for primary or secondary prevention in a post-MI patient will also be considered. The events will be reviewed by a cardiologist who is independent of the research team and who is blinded to the MRI results. The follow-up analysis will be performed at the end of the study and again after a minimum of 3 years follow-up in all participants. The longer term follow-up will be performed by electronic case record linkage to hospital, NHS and government records.


Biospecimen Retention:   Samples With DNA

Blood and urine samples have been archived.


Enrollment: 324
Study Start Date: May 2011
Estimated Study Completion Date: May 2017
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Myocardial infarction
Patients presenting with acute-ST elevation myocardial infarction referred for emergency invasive management by primary or rescue percutaneous coronary intervention.
Device: Coronary pressure wire
Guidewire-based coronary pressure- and temperature recordings (coronary thermodilution) with and without hyperaemia induced by intravenous administration of adenosine (140 ug/kg/min) in patients with acute ST-elevation myocardial infarction treated by emergency PCI.
Other Name: Pressure wire Certus (St Jude Medical)
Other: Magnetic resonance imaging of the heart
Cardiac magnetic resonance imaging (MRI) with gadolinium contrast imaging at baseline (~ day 2) and 6 months (all participants) and in 30 subjects at 4 time-points (< 12 hours, days 2, 7-10 and at 6 months).
Other Name: Cardiac MRI

Detailed Description:

Magnetic resonance imaging (MRI) provides detailed insights into soft tissue characteristics and this technique has particular value for imaging patients with acute myocardial infarction (MI). Recent advances in MRI have the potential to reveal new insights into the evolution and functional significance of myocardial injury and repair.

Here, we will study at least 300 consecutive patients with acute ST elevation MI (STEMI) and focus on oedema, scar and bleeding in the heart using MRI in patients managed by emergency percutaneous coronary intervention (PCI). Cardiac MRI scans will be performed at 1.5 Tesla (MAGNETOM, Siemens Healthcare). MRI will be used to assess initial heart function and injury. Myocardial salvage and haemorrhage are prioritised outcomes. Novel MRI methods will also be used to quantify the extent of myocardial jeopardy representing the initial area-at-risk (AAR), and the nature of this injury (strain, haemorrhage). The MRI methods will include T1, T2 and T2* relaxometry (mapping). Secondly, we will assess coronary artery disease severity by angiography and coronary artery function at the time of the heart attack treatment using a pressure-sensitive coronary guidewire (St Jude Medical). This wire can be used instead of the usual coronary wire and can provide information on heart injury, which can be linked in turn to the MRI findings. All of this information will be linked with health outcomes in the longer term.

We hypothesise that myocardial salvage, oedema, haemorrhage, and strain as revealed by MRI, have functional and prognostic significance. In all patients MRI will be performed at baseline (~day 2) and again at 6 months. In a subgroup of 30 patients, MRI will be performed on days <12 hours, and days 2, 7-10 days and 6 months post-MI. A blood and urine sample and quality of life will be obtained at baseline and at 6 months post-MI. Clinical outcomes (e.g. rehospitalisation, death) will be assessed at the end of the study (minimum 1 year) and again during longer term follow-up (minimum 3 years, maximum 20 years) by electronic linkage through central National Health Service (NHS) and government health records in order to determine the long-term prognostic significance of our initial observations with angiography, MRI and the pressure wire. The main statistical analyses will be conducted by an independent trials unit statistician.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients with a diagnosis of ST-elevation myocardial infarction (STEMI).

Criteria

Inclusion Criteria:

  • Acute STEMI

Exclusion Criteria:

  • Major systemic illness (e.g. cancer limiting survival < 6 months);
  • Metallic implant (e.g. cochlear implant);
  • Metallic foreign body
  • Pregnancy.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02072850

Locations
United Kingdom
Golden Jubilee National Hospital
Clydebank, Dunbartonshire, United Kingdom, G84 4DY
Sponsors and Collaborators
NHS National Waiting Times Centre Board
Siemens Healthcare
British Heart Foundation (Project Grant PG/11/2/28474)
Investigators
Principal Investigator: Colin Berry, MB ChB BSc PhD FRCP FACC University of Glasgow
  More Information

Additional Information:
No publications provided

Responsible Party: Colin Berry, Professor of Cardiology and Imaging, University of Glasgow
ClinicalTrials.gov Identifier: NCT02072850     History of Changes
Other Study ID Numbers: 10/S0703/28, Research grant number, Government health research
Study First Received: February 25, 2014
Last Updated: August 11, 2014
Health Authority: United Kingdom: National Health Service
United Kingdom: National Institute for Health Research
United Kingdom: Research Ethics Committee

Keywords provided by NHS National Waiting Times Centre Board:
Myocardial infarction
Primary percutaneous coronary intervention (PCI)
Thrombolysis
Rescue PCI
Electrocardiogram
Magnetic resonance imaging
Area-at-risk
Myocardial salvage
Infarct size
Pressure wire
Coronary thermodilution
Coronary microvascular function
Index of microvascular resistance
Heart failure
Prognosis

Additional relevant MeSH terms:
Infarction
Myocardial Infarction
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on October 16, 2014