Home ECG Monitoring to Detect Allograft Rejection Following Heart Transplantation

描述（由申请人提供）：本研究的长期目标是应用新技术检测供体器官（同种异体移植物）3排斥反应，以改善心脏移植后的患者结局。本研究的具体目标是确定使用简单的家用设备每天监测移植受体的心电图（ECG）并传输到ECG核心实验室是否可以提供急性排斥反应的早期生物标志物。 尽管常规免疫抑制剂治疗，急性排斥反应是常见的，特别是在移植手术后的前6 - 7个月内。为了检测排斥反应，经常进行心脏组织的肌内膜活检。肌内膜活检是在医院心导管实验室进行的一项昂贵且有创的手术，具有相关风险。最近的证据表明，急性同种异体移植排斥反应10导致心室复极延迟，导致ECG上QT间期延长。该研究的具体目的是：1）确定心脏移植后前6个月期间QT间期的增加是否是急性排斥反应的敏感和特异性生物标志物;和2）确定QT间期相对于轻度/中度/重度排斥反应的活检诊断阶段增加的时间。次要目标是：3）确定QT间期的增加是否预测1年死亡率;以及4）探索可能预测排斥反应或死亡的其他ECG测量。16计划进行一项前瞻性、双盲、描述性和相关性研究设计。分析ECG数据的研究者将对活检结果设盲;医疗保健提供者将对QT测量设盲。将从3个移植中心招募325名成年心脏移植受者的样本：哥伦比亚大学-纽约约克长老会医学中心19名;加州大学，洛杉矶和雪松-20西奈医学中心，洛杉矶。每名受试者将使用HeartOne TM 21设备每天记录30秒ECG;该设备将自动将ECG传输至加州大学旧金山分校弗朗西斯科的ECG核心实验室。对于主要目的#1，将进行对数回归分析，其中23个自变量为存在/不存在ECG标准（QTC e25毫秒X 3天），24个因变量为存在/不存在急性同种异体移植物排斥反应。将报告比值比和置信区间，以及新诊断工具的既定评价标准（灵敏度、特异性、阳性/阴性预测值、预测准确性）。对于主要目的#2，将使用描述性统计量27报告ECG标准制定与活检证据28拒绝之间的平均时间段。找到一种可以在家中测量的同种异体移植排斥反应的简单ECG生物标志物的潜在好处是，它可能会更早地检测到排斥反应，允许更及时的治疗，并降低急性同种异体移植排斥反应的死亡率。

DESCRIPTION (provided by applicant): The long-term goal of this research is to apply novel technology for detection of donor organ (allograft) 3 rejection to improve patient outcomes following heart transplantation. The specific goal of this study is to 4 determine whether daily monitoring of the transplant recipient's electrocardiogram (ECG) using a simple home 5 device with transmission to an ECG Core Laboratory would provide an early biomarker for acute rejection. 6 Despite routine immunosuppressant drug therapy, acute rejection is common, especially within the first 6 7 months following transplant surgery. To detect rejection, frequent endomyocardial biopsies of heart tissue are 8 performed. An endomyocardial biopsy is a costly and invasive procedure performed in a hospital cardiac 9 catheterization laboratory that has associated risks. Recent evidence suggests that acute allograft rejection 10 causes delays in ventricular repolarization resulting in a longer QT interval on the ECG. The specific aims of 11 the study are to: 1) determine whether an increase in the QT interval during the first 6 months following heart 12 transplant is a sensitive and specific biomarker for acute rejection; and 2) determine the timing of QT interval 13 increases relative to biopsy-diagnosed stages of mild/moderate/severe rejection. Secondary aims are to: 3) 14 determine whether an increase in the QT interval predicts 1-year mortality; and 4) explore additional ECG 15 measurements that might predict rejection or death. 16 A prospective, double-blind, descriptive and correlational research design is planned. Investigators who 17 analyze ECG data will be blinded from biopsy results; healthcare providers will be blinded from QT 18 measurements. A sample of 325 adult heart transplant recipients will be recruited from 3 transplant centers: 19 Columbia University-New York Presbyterian Medical Center; University of California, Los Angeles and Cedars- 20 Sinai Medical Center, Los Angeles. Each subject will record a 30-second ECG daily using the HeartOneTM 21 device; the device will automatically transmit the ECG to an ECG Core Laboratory at the University of 22 California, San Francisco. For Primary Aim #1, a log regression analysis will be performed with the 23 independent variable being presence /absence of the ECG criteria ( QTC e25 milliseconds X 3 days) and the 24 dependent variable being presence /absence of acute allograft rejection. Odds ratios and confidence intervals 25 will be reported, as well as established evaluative criteria for new diagnostic instruments (sensitivity, specificity, 26 positive /negative predictive value, predictive accuracy). For Primary Aim #2, descriptive statistics will be used 27 to report the average time period between the development of the ECG criterion and biopsy evidence of 28 rejection. The potential benefit of finding a simple ECG biomarker of allograph rejection that could be 29 measured at home is that it might yield earlier detection of rejection, allow more timely therapy and reduce 30 mortality from acute allograft rejection.