Clinical Trial: Detection and Significance of Heart Injury in ST Elevation Myocardial Infarction.

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Observational

Official Title: Cardiac Magnetic Resonance Imaging: New Pathological Insights and Their Functional and Clinical Significance in ST Elevation Acute Myocardial Infarction.

Brief Summary: 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.

Detailed Summary:

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
Sponsor: NHS National Waiting Times Centre Board

Current Primary Outcome: Myocardial salvage [ Time Frame: Baseline and 6 months after date of index hospitalisation for STEMI ]

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.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Myocardial salvage index [ Time Frame: Baseline and 6 months ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    Left ventricular end-diastolic volume (millilitres)
  • Left ventricular end-systolic volume [ Time Frame: Baseline and follow-up MRI at 6 months ]
    Left ventricular end-systolic volume (millilitres)
  • Index of microvascular resistance [ Time Frame: Day 0 at initial hospital admission ]
    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 ]
    Patient-reported quality of life and health status will be assessed at baseline a

    Original Secondary Outcome:

    • Myocardial salvage index [ Time Frame: Baseline and 6 months ]
      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 ]
      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 ]
      Myocardial haemorrhage 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 ]
      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 ]
      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 ]
      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 ]
      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 ]
      The myocardial T1 relaxation time (ms) will be estimated using a Modified Look-Locker Inversion recovery method (Siemens Healthcare).
    • Myocardial T2 time [ Time Frame: Baseline and follow-up MRI at 6 months ]
      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 ]
      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 ]
      Left ventricular end-diastolic volume (millilitres)
    • Left ventricular end-systolic volume [ Time Frame: Baseline and follow-up MRI at 6 months ]
      Left ventricular end-systolic volume (millilitres)
    • Index of microvascular resistance [ Time Frame: 1 day at initial hospital admission ]
      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.


    Information By: NHS National Waiting Times Centre Board

    Dates:
    Date Received: February 25, 2014
    Date Started: May 2011
    Date Completion: May 2020
    Last Updated: July 19, 2016
    Last Verified: July 2016