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Clinical trial

The GRAFT Study: Evaluation of Graft Function, Rejection and Cardiac Allograft Vasculopathy in First Heart Transplant Recipients.

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Last updated:28th Feb 2014

Objective:

  • To assess the relationship between coronary allograft vasculopathy (CAV) and graft function, and to evaluate non-invasive methods for CAV diagnosis.
  • To assess left ventricular (LV) and right ventricular (RV) function in the acute phase and serially during the first year after transplantation.
  • To evaluate the impact of acute and repetitive rejection on the longitudinal myocardial function Hypothesis

    1. Timing of development and degree of CAV can be measured non-invasively combining myocardial longitudinal deformation (by advanced echocardiography) and coronary flow velocity reserve (CFVR) (by echocardiography and PET). This combination of methods can detect CAV before it is angiographically visual and gives supplementary information of the impact on myocardial graft function.
    2. Longitudinal deformation, 3D echocardiography, cardiac magnetic resonance imaging (CMRI) and PET can be used for RV and LV myocardial function assessment and represent more valid markers of the function than standard echocardiography in heart transplant (HTX) patients.
    3. Myocardial longitudinal deformation is a better marker of acute rejections than conventional ejection fraction (EF).

Importance of the GRAFT study Diagnosing CAV in the early phases by non-invasive methods can improve the treatment and reduce the use of CAG. The study will provide better tools for balancing the immunosuppressive treatment, which could lower the incidence of treatment related cancer and impaired renal function.

By serial examinations we will obtain new important knowledge of the physiology of the graft and the influence of rejections and CAV development during the first year. We seek prognostic markers for these complications. Hopefully the treatment of acute graft failure and prevention of complications is thereby improved. If rejections can be diagnosed by non-invasive methods, many biopsies can be spared, complications avoided and life quality improved.

Background The most frequent heart related death causes after HTX are CAV, acute graft failure and rejection.

CAV is characterized by diffuse concentric intima thickening involving both epicardial vessels and the coronary microvascular system. In our clinical approach HTX-patients are followed with annual CAG and standard echocardiography with estimation of LV systolic function by EF. Standard echocardiography has not proven benefit in the diagnosis of CAV. CAG often misses CAV in early phases.

In various cardiac diseases it is well known that ischemia and fibrosis often affect the endocardial longitudinal oriented layers. Longitudinal deformation by advanced echocardiography has shown to be better markers for systolic function in HTX patients compared to standard EF. Longitudinal LV systolic function is dependent of endocardial perfusion. CFVR represents the capacity of the coronary circulation to dilate due to metabolic demands and has been shown to correlate with longitudinal deformation in myocardial infarction. CFVR measurements in HTX patients with advanced echocardiography and PET scan have shown a significant correlation to CAV.

RV failure is an early, potentially fatal, complication to HTX. The function and change over time of RV have not been fully studied using modern echocardiographic techniques or assessment by CMRI.

Acute rejection is an inflammatory response often diagnosed by routine biopsies (gold standard). These are expensive, time consuming and inconvenient for the patient. The role of conventional echocardiography has not yet found a significant role in the diagnostics of acute rejections and furthermore how repeated rejections influence on graft function is not well described.

Study 1 A cross sectional study consisting of 50 stabile HTX patients. These will be selected with 25 patients with no or light CAV and 25 patients with moderate or severe CAV.

Severity of CAV will be evaluated by:

  • CAG
  • CFVR measurement by advanced echocardiography and PET.

Graft function will be evaluated by:

  • Advanced echocardiography at rest end during bicycle exercise.
  • CMRI including assessment of LV and RV EF, strain and mass.
  • During rest and bicycle exercise echocardiography simultaneously right heart catheterization are performed for hemodynamic measurement

Study 2 A prospective cohort study with 20-25 newly transplanted patients over a period of 12 months.

LV and RV function will be measured by:

  • Advanced echocardiography
  • CFVR measurement (echocardiography and PET)
  • CMRI for LV and RV EF, strain and mass
  • Right heart catheterization

Study 3 Prospective examination of correlation between graft function, CAV and rejection. Information of former episodes of acute rejection is collected retrospective. Study objectives are all living HTX patients (approx. 200) in the period of 2011-2013.

Advanced echocardiography (including longitudinal deformation), biopsies (rejection evaluation) and CAG (CAV evaluation).

Category Value
Study start date 2014-02-28

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