Defining Mechanisms for Cardiac Allograft Dysfunction to Improve Allograft Longevity and Survival in Heart-Transplant Patients
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 376
- 试验地点
- 2
- 主要终点
- Myocardial Perfusion Reserve
研究概览
简要总结
The investigators will evaluate for early evidence of cardiac allograft dysfunction by cardiac MRI and single cell sequencing to determine underlying molecular and macroscopic causes.
详细描述
Adult heart-transplant patients, excluding those with a GFR less than 30 mL/min/1.73m2, contraindications to MRI and allergies to either regadenoson or gadolinium contrast, will be enrolled over 60 months. Patients will be recruited from UCSD. The investigators will specifically enroll all eligible heart-transplant patients.
Brief protocol:
Cardiac MRI is performed. Cine images in standard views are obtained. T1 and T2 mapping sequences are performed on short axis images pre- and post-gadolinium contrast. For stress imaging, intravenous regadenoson is given as a 0.4 mg bolus followed by a 5 mL saline flush. After 30 seconds, short-axis images are acquired for 30 consecutive heartbeats with administration of gadolinium. Rest imaging is performed 30 minutes after stress imaging. Lastly, late gadolinium enhancement images are obtained in standard views. Images are analyzed offline by a blinded independent reader. Patients will be followed for at least 1 year after enrollment for MACE.
Peripheral blood and endomyocardial biopsies will also be collected, timing as per usual clinical care as well as for-cause, for single cell RNAseq analyses.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age greater than or equal to 18 years old.
- •At least three months status post heart transplantation.
排除标准
- •Biopsy proven acute rejection episode in the past 3 months.
- •Patients with symptoms or signs of acute myocardial ischemia or recent acute coronary syndrome in the past 3 months.
- •Uncontrolled obstructive ventilatory disease including asthma and COPD.
- •History of generalized tonic-clonic seizures.
- •Second or third degree AV nodal block.
- •Sinus node dysfunction.
- •Contraindications to MRI including cardiovascular implantable electronic devices.
- •Renal dysfunction with an estimated GFR less than 30 mL/min/1.73m
- •Prior adverse reaction to either regadenoson or gadolinium contrast. Prior adverse reaction to adenosine or dipyridamole will be assessed on a case-by-case basis.
- •Systolic blood pressure greater than 180 or less than 85 mmHg.
- •Diastolic blood pressure greater than 120 or less than 40 mmHg.
- •Resting heart rate greater than 120 or less than 45 beats per minute. - Severe claustrophobia.
研究组 & 干预措施
Nonspecific allograft dysfunction
Patients with nonspecific allograft dysfunction will undergo stress cardiac MRI with regadenoson in addition to performing late gadolinium enhancement and obtaining mean segmental T1 values of the heart. Peripheral blood and endomycardial biopsies will also be obtained for single cell RNAseq analyses.
干预措施: Regadenoson (Drug)
Normal graft function
Patients with normal graft function will undergo stress cardiac MRI with regadenoson in addition to performing late gadolinium enhancement and obtaining mean segmental T1 values of the heart. Peripheral blood and endomycardial biopsies will also be obtained for single cell RNAseq analyses.
干预措施: Regadenoson (Drug)
ACR/AMR
Patients with allograft dysfunction from prior episodes of acute cellular or antibody mediated rejection will undergo stress cardiac MRI with regadenoson in addition to performing late gadolinium enhancement and obtaining mean segmental T1 values of the heart. Peripheral blood and endomycardial biopsies will also be obtained for single cell RNAseq analyses.
干预措施: Regadenoson (Drug)
Cardiac allograft vasculopathy
Patients with allograft dysfunction from known cardiac allograft dysfunction will undergo stress cardiac MRI with regadenoson in addition to performing late gadolinium enhancement and obtaining mean segmental T1 values of the heart. Peripheral blood and endomycardial biopsies will also be obtained for single cell RNAseq analyses.
干预措施: Regadenoson (Drug)
结局指标
主要结局
Myocardial Perfusion Reserve
时间窗: 60 months
次要结局
- native T1 and T2 myocardial values(60 months)
- extracellular volumes(60 months)
- myocardial strain rate(60 months)
- Rest and stress myocardial blood flow(60 months)
- LGE %(60 months)
- LVEF(60 months)
- LV end-diastolic volume index(60 months)
- LV mass index(60 months)
研究者
Paul Kim
Assistant Professor
University of California, San Diego