WAMIF : Young Women Presenting Acute Myocardial Infarction in France
Condition: Acute Myocardial Infarction; Women Over 18 and Under 50 Years of Age
MeSH terms: Myocardial Infarction; Infarction
Study type: Interventional

Summary: 
      MI in elderly women seems to share the same pathophysiology than in men, especially plaque
      rupture associated with conventional risk factors. Therefore the questions is not solved on
      the pathophysiology and specific risk factors in young women whose prognosis is more severe.
      A complete descriptive analysis appears mandatory to understand the peculiarities, including
      not only morphological but also biological explorations as well.

      To date no systematic descriptive analysis has been performed including clinical
      characteristics, cardiac and extra-cardiac morphological exploration and hormonal and
      immunological assays, particularly in young premenopausal women presenting MI.

      This study will provide for the first time a complete analysis, including hormonal assays,
      never made in an "acute" population.

      The main objective of this clinical study is to systematically pool clinical, morphological
      and biological data of young women (< 50 years) presenting an Acute MI and to assess their
      short-term (in-hospital) and mid-term (12 months) prognosis. The definition of MI is the one
      adopted in the Third definition published in 2012. As such an event occurs in a young
      patient, diagnostic and treatment may vary among centres. The incidence of such cases in each
      centre being low and practice inhomogeneous, no conclusion could be advanced concerning the
      study of associated, indeed predisposing factors.

      The work aims to comprehensively and systematically collect all the clinical and laboratory
      data and the results of the all morphological explorations carried out during the care of
      these young women admitted for acute MI in high-volume centres.

      No additional invasive act, without any direct benefit for the care of patients will be
      realized for research purposes.

      All these examinations, in particular invasive morphological, are more and more integrated in
      the practice of modern interventional cardiology especially for complex or infrequent
      situations, like this setting. They afford accurate diagnosis of coronary disease on one hand
      and on the second hand they determine the causal or at least participating factor.

      A comprehensive and systematic analysis of this particular entity that is MI in young woman,
      would improve our knowledge of this disease and then enable to offer patients a more
      appropriate treatment and monitoring. It is necessary to progress in the understanding of the
      mechanisms of the early onset of coronary artery disease in its most acute and most serious
      presentation and to clearly define the specificities of coronary disease in young women.
      Moreover, a more precise identification of risk factors of MI in a woman under 50 will allow
      a better screening and even introduction of preventive strategies.
    

Detailed description: 
      Cardiovascular disease is the leading cause of death among women in France. In-hospital
      mortality after acute coronary syndrome (ACS) remains significantly higher than in men, with
      a relative risk of up to 150%, especially among young women1,2. Early mortality rate of
      myocardial infarction (MI) continues to decline but that of women remains higher.

      Background The risk of ACS increases with age, especially after menopause and in the presence
      of classic cardiovascular risk factors such as hypertension or diabetes. Nevertheless
      premenopausal women presenting MI are not exceptional even in the absence of risk factors.
      The worse prognosis in women, particularly in individuals under 50 years could result from
      the combination of harsher clinical presentation, less typical symptoms, and delayed
      diagnosis. Moreover, it is not uncommon that an ACS occurs in young women without the usual
      risk factors. Hormonal changes in particular related to contraceptive treatments have been
      incriminated, likewise chronic inflammation related to systemic diseases. To date the impact
      of hormonal, inflammatory or thrombophilia changes has not been elucidated.

      Nowadays use of endovascular imaging during diagnostic coronary angiography is become common
      practice in particular in the absence of obvious culprit thrombotic or obstructive lesion.
      These invasive imaging techniques such as intravascular ultrasound (IVUS) or OCT (Optical
      Coherence Tomography), bring highly relevant complementary information in this setting,
      particularly to clarify the mechanism of MI such as rupture or erosion of atherosclerotic
      plaque, spontaneous dissection or intramural hematoma. The incidence of these particular form
      of acute coronary artery lesions are higher in women, especially among the youngest one.

      In young, an angioCT or angioMRI (aortic and/or cerebral) are often performed looking for
      other atherosclerotic risk locations or morphological abnormalities in favour of a particular
      disease such as a fibrodysplasia. PET scan (18FDGlusose scintigraphy), when available,
      provides a valuable complement: it is a functional imaging research for other arterial
      locations for hypermetabolic inflammatory arteritis.

      Usual laboratory tests will be made at admission and discharge as done in routine practice.
      These tests include blood count, electrolytes, blood urea, creatinine, prothrombin time,
      activated partial thromboplastin time, glucose, HbA1C, lipide profil, hemoglobin
      electrophoresis, CRP, fibrinogen.

      Moreover some tests are recommended in case of ACS in a young patient not made
      systematically. It is the objective of our work to make a comprehensive and systematic
      analyse. Some assays require special techniques, to avoid any variability and therefore bias
      in interpretation of results, those will be, after preparation of the samples in the original
      department, centralized: such as homocysteine, markers of thrombophilia and hormone assays.
      Individually, these markers have been associated with the presence and progression of
      atheroma. However, these assays are rarely made and have not been comprehensively and
      systematically studied in the population of young woman presenting MI.

      Moreover it has long been accepted that women were less exposed than men to the risk of
      cardiovascular disease due to the protective role of oestrogen. However this assumption has
      been questioned by recent work on the hormonal treatment of menopause. The administration of
      oestrogen does not prevent ischemic arterial disease in postmenopausal women and may even be
      deleterious in older women. Then it then appears crucial to analyse hormone levels in the
      acute phase of MI in order to progress in the understanding of the hormonal role in ACS, so
      far this has never been made in this context.

      Study design This is a prospective multicentric observational clinical study. All women under
      50 years admitted in one of the 32 participating centres, for acute MI, with and without ST
      segment elevation, will be included.

      Experimental plan

        -  For any women admitted for acute MI with or without ST segment elevation in an
           investigation centre, participation in the study will be proposed.

        -  Coronary angiography will be performed in emergency at admission according to current
           guidelines in case of STEMI. In case of NSTEMI, patients will benefit from coronary
           angiography according to defined risk stratification.

        -  An IVUS imaging will be done in centers that practice this technique, the data will be
           collected as part of the study. This imaging will be performed if possible during the
           initial coronary angiography in order to objectify intraluminal thrombus, plaque
           rupture, hematoma or spontaneous dissection. This diagnostic strategy is carried out in
           common practice in the participating centers in atypical situations, particularly in the
           absence of obstructive lesion or visible thrombus at angiography. OCT may be carried out
           in a second step after mechanical and/or pharmacological thrombectomy in order to
           improve sensitivity.

        -  Participation in the study will be proposed and agreement will be signed before
           discharge.

        -  In the centers performing cardiac MRI, the MRI data will be collected as part of the
           study. Cardiac MRI will be done at the earliest after coronary angiography during the
           same hospitalization.

        -  The usual blood tests will be performed at the patient's admission and then repeated at
           least 24 hours after coronary angiography, including repeated sampling assays for
           troponin, in order to measure the peak, following the routine of the department

        -  The specific assays, corresponding to the tests carried out as part of the WAMIF study
           will be sampled before discharge.

        -  During one of these blood samples a 5 ml sample of blood will be made for later analysis
           in the context of a serum bank.

        -  Some assays, including hormonal and thrombophilia will be centralized in order to
           standardize the results and their interpretation

        -  A second angiography associated with a challenge test by Methergin® can be planned, at
           the discretion of the referring cardiologist, within 5 days after the index event. This
           test will be especially recommended if no etiology has been found by OCT or MRI in order
           to diagnose a spastic angina. The test will be performed during coronary angiography
           with intravenous injection of 0.4 mg of Methergin® (méthylergotamine) followed by a
           control angiography 3 minutes followed by a test after intracoronary injection of
           nitrates.

        -  All the data will be collected locally with the help of clinical studies technicians
           from the WAMIF study

        -  All the biological data will be pooled and analyzed by IVS

        -  The data management will be performed by the clinical research assistant from the SFC

        -  A telephone interview will be conducted at 12 months to collect the major cardiovascular
           events (death from any cause, cardiovascular death, recurrent MI, stent thrombosis,
           stroke and major bleeding). These events will be specified through hospital reports.

      Total study duration: 18 months + follow up at to 12 months: 30 months Inclusion period: 18
      months Duration of participation for one patient: 12 months Number of participating centers:
      32 Average number of inclusions per month per center: 0.5 to 1
    

Intervention name(s): Specific blood sample of women under 50 years with acute MI
Intervention type(s): Other
Intervention description(s): The specific assays, corresponding to the tests carried out as part of the WAMIF study will be sampled before discharge. Some assays, including hormonal and thrombophilia will be centralized in order to standardize the results and their interpretation. All the biological data will be pooled and analyzed by IVS. a sample of blood will be made for later analysis in the context of a serum bank.
Other intervention name(s): specific assays
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: Myocardial infarction; Women; Young; Primary PCI; Hormone