The GRAFT Study: Evaluation of Graft Function, Rejection and Cardiac Allograft Vasculopathy in First Heart Transplant Recipients.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 65
- 试验地点
- 1
- 主要终点
- Coronary flow velocity reserve
研究概览
简要总结
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
- 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.
- 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.
- Myocardial longitudinal deformation is a better marker of acute rejections than conventional ejection fraction (EF).
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).
详细描述
Objective
- To assess the relationship between myocardial perfusion, coronary anatomy and longitudinal myocardial function in heart transplanted (HTX) patients with and without coronary allograft vasculopathy (CAV).
- Evaluation of systolic and diastolic capacity during exercise in HTX patients with and without CAV.
- Evaluation of non-invasive methods for CAV diagnosis.
- To assess left ventricular (LV) and right ventricular (RV) function in the acute phase and during follow-up (5 times) the first year after transplantation and furthermore to compare advanced echocardiographic evaluation of graft function with cardiac magnetic resonance imaging (CMRI), right heart catheterization, and positron emission tomography (PET).
- Finally, to evaluate the impact of acute and repetitive rejection on myocardial graft function measured by standard 2D echocardiography and advanced echocardiography with analysis of longitudinal myocardial function.
Hypothesis
- Timing of development and degree of CAV can be measured non-invasively combining myocardial longitudinal deformation measurement by advanced echocardiography and coronary flow velocity reserve (CFVR) by echocardiography and PET. This combination of methods can detect CAV before it is angiographic visual and gives supplementary information of the impact on myocardial graft function. This setup might be more appropriate in evaluation of the myocardial graft function and CAV than standard echocardiography and coronary angiography (CAG). Optical coherence tomography (OCT) can detect CAV in early phases and gives supplementary characterization of the plaque.
- Modern non-invasive methods (longitudinal deformation, 3D echocardiography, CMRI and PET) can be used in RV and LV myocardial function assessment and represents more valid markers of the function than standard echocardiography in HTX patients.
- During exercise patients with CAV will show impaired longitudinal myocardial deformation and restrictive filling with significant increasing LV and RV filling pressures.
- Myocardial longitudinal deformation is a better marker of acute rejections than conventional ejection fraction (EF). After an episode of severe acute rejection the graft function will improve, but instances of repetitive rejections will lead to impaired longitudinal systolic function with preserved LV EF.
Background Mean survival after HTX at our center is 15.6 years. Complications remain frequent and serious. In the first postoperative year the main causes of death are graft failure, rejections and infection. At long term follow up main causes of death are CAV and malignancies.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age 18-100
- •Informed and signed consent
排除标准
- •- Coronary stenosis within the first 3 mounts after HTX (donor transmitted coronary atherosclerosis).
- •Severe asthma or COLD with FEV1 < 50%
- •2° or 3° AV block
- •Pregnancy
- •S-creatinine >200 µmol/l
- •Allergy towards the contrast agent
结局指标
主要结局
Coronary flow velocity reserve
时间窗: September 2013 to January 2016
Assessed by tissue Doppler echocardiography and H215O-PET
pulmonary capillary wedge pressure
时间窗: September 2013 to January 2016
At rest and during exercise
global longitudinal strain
时间窗: September 2013 to January 2016
At rest and during exercise
cardiac allograft vasculopathy
时间窗: September 2013 to January 2016
Assessed by coronary angiography and optical coherence tomography
次要结局
- RV-EF(September 2013 to January 2016)
- tissue Doppler(September 2013 to January 2016)
- Quality of life(September 2013 to January 2016)
- CRP, TNT, Nt-ProBNP and fibrosis markers(September 2013 to January 2016)
- Cardiac output(September 2013 to January 2016)
- intima/media radio(September 2013 to January 2016)
研究者
Tor Skibsted Clemmensen
M.D., PhD student
Aarhus University Hospital Skejby