Comprehensive Cardiac Structure-Function Analysis in Heart Transplantation

摘要/摘要 心脏移植(TX)手术是一种公认的挽救生命的手术，但与心脏移植后的 介入性风险，如急性心脏排斥反应(ACR)，这是导致心脏移植患者死亡的主要原因之一 移植后第一年。第一年以后，心脏移植物血管病变(CAV)是最大的风险。 五年死亡率的因素。因此，监测患者的移植后事件至关重要。标准 然而，监控策略依赖于频繁的(仅在第一年就有12-16个监控节点)入侵和 昂贵的手术包括心内膜心肌活组织检查(EMB)和导管血管造影术。由于教统局和 由于采样误差(ACR)或疾病的弥漫性，导管血管造影术的敏感性有限 (CAV)是早期检测ACR和CAV的一种可靠的非侵入性替代方法，因此希望减少 需要侵入性程序，提高敏感度，降低成本。 我们最近开发和应用了心脏MRI技术来无创性地评估 心肌水肿(T2标测)、弥漫性纤维化(增强前后T1标测)、心肌运动速度 (组织时相图)和微血管定量灌注。我们已经证明，这些技术可以 确定心脏中与心脏状况相关的明显的区域性结构和功能改变 异体移植。基于这些发现，使用马尔可夫模型和决策树进行了详细的成本效益分析 分析表明，心脏磁共振具有巨大的潜力，可以将监测成本降低40%-50% 仅在德克萨斯州之后的第一年。 这个提议建立在这些有希望的发现的基础上，我们的目标是开发一个新的15分钟结构-功能 心脏MRI方案用于改进检测与ACR(水肿、纤维化、 功能障碍)和CAV(血流灌注功能障碍)。磁共振与超声心动图及血管内成像的结合 超声(IVUS)将为同种异体移植物提供独特的多模式评估。中的应用程序 纵向临床研究结合最先进的成本效益分析将允许重新定义最 有效的后TX混合监测策略。其目的是帮助临床医生确定最佳的混合体 监测战略，即多模式成像(结构-功能MRI、ECHO、IVUS)的最佳组合 和侵入性程序(EMB、导管血管造影术)，提供最佳结果(调整后的生命质量) 为个体心脏移植患者提供最低的成本。

SUMMARY / ABSTRACT 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 the 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.