Comprehensive Cardiac Structure-Function Analysis in Heart Transplantation

描述（由申请人提供）：心脏移植（Tx）手术是一种公认的挽救生命的手术，但与介入后风险相关，如急性心脏排斥反应（ACR），这是移植后第一年死亡的主要原因之一。1年后，同种异体心脏移植血管病变（CAV）是5年死亡率的最大危险因素。因此，监测患者移植后的事件是至关重要的。然而，标准的监测策略依赖于频繁的（仅第一年就有12-16个监测节点）侵入性和昂贵的手术，包括心内膜活组织检查（EMB）和导管血管造影。由于采样误差（ACR）或疾病弥漫性（CAV）， EMB和导管血管造影的灵敏度有限，因此需要一种可靠的非侵入性替代方法来早期检测ACR和CAV，以减少对侵入性手术的需求，提高灵敏度并降低成本。我们最近开发并应用了心脏MRI技术，用于无创评估心肌水肿（t2制图）、弥漫性纤维化（对比前和对比后的t1制图）、心肌速度（组织相制图）和微血管定量灌注。我们已经证明，这些技术可以识别心脏中与同种异体移植物状态相关的不同区域结构和功能改变。基于这些发现，使用马尔可夫模型和决策树分析的详细成本效益分析表明，仅在Tx后的第一年，心脏MR就具有将监测成本降低40-50%的巨大潜力。基于这些有希望的发现，我们的目标是开发一种新的15分钟结构-功能心脏MRI方案，以改进与ACR（水肿、纤维化、功能障碍）和CAV（灌注、功能障碍）相关的区域异常的检测。MRI与超声心动图和血管内超声（IVUS）的结合将为同种异体移植物提供独特的多模态评估。在纵向临床研究中的应用

DESCRIPTION (provided by applicant): Heart transplant (Tx) surgery is a well-established life-saving procedure, but is associated with post- interventional risks such as acute cardiac rejection (ACR) which is one of the leading causes of death in the first year after transplant. Beyond the first year, cardiac allograft vasculopathy (CAV) is the single greatest risk factor for 5-year mortality. Monitoring the patient for post-transplant events is thus paramount. The standard monitoring strategy, however, relies on frequent (12-16 monitoring nodes during year 1 alone) invasive and costly procedures including endomyocardial biopsies (EMB) and catheter angiography. Since EMB and catheter angiography have limited sensitivity due to sampling errors (ACR) or the diffuse nature of the disease (CAV), a reliable non-invasive alternative for the early detection of ACR and CAV would be desirable to reduce the need for invasive procedures, improve sensitivity, and reduce cost. We have recently developed and applied cardiac MRI techniques for the non-invasive assessment of myocardial edema (T2-mapping), diffuse fibrosis (pre- and post-contrast T1-mapping), myocardial velocities (tissue phase mapping), and microvascular quantitative perfusion. We have shown that these techniques can identify distinct regional structural and functional alterations in the heart that correlate with te status of the allograft. Based on these findings, a detailed cost-effective analysis using Markov modeling and decision tree analysis has demonstrated that cardiac MR has tremendous potential to reduce monitoring costs by 40-50% during the first year after Tx alone. This proposal builds on these promising findings and our aim is to develop an new 15-minute structure-function cardiac MRI protocol for the improved detection regional abnormalities associated with ACR (edema, fibrosis, dysfunction) and CAV (perfusion, dysfunction). Integration of MRI with echocardiography and intravascular Ultrasound (IVUS) will provide unique multi-modality assessment of the allograft. The application in a longitudinal clinical study coupled with state-of-the-art cost-effectiveness analysis will allow redefining the most effective post-Tx mixed monitoring strategy. The aim is to to help clinicians identify the optimal mixed monitoring strategy, i.e. the optimal combination of multi-modality imaging (structure-function MRI, echo, IVUS) and invasive procedures (EMB, catheter angiography) which provide best outcome (quality adjusted life days) and lowest cost for the individual cardiac transplant patient.