Home ECG Monitoring to Detect Allograft Rejection Following Heart Transplantation

描述(由申请人提供)：这项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)3排斥反应，以改善心脏移植后的患者预后。这项研究的具体目标是确定使用简单的家用设备传输到心电核心实验室的移植受者的日常心电监测是否可以提供急性排斥反应的早期生物标志物。6尽管常规的免疫抑制药物治疗，急性排斥反应是常见的，特别是在移植手术后的头6个7个月内。为了检测排斥反应，对心脏组织进行了频繁的心内膜心肌活组织检查。心内膜心肌活检是在医院心导管实验室进行的一种昂贵且有侵入性的程序，具有相关的风险。最近的证据表明，急性同种异体移植排斥反应10会导致心室复极延迟，从而导致心电图上QT间期延长。11这项研究的具体目的是：1)确定心脏12移植后前6个月QT间期延长是否是急性排斥反应的敏感和特异的生物标志物；2)确定QT间期13相对于活检诊断的轻度/中度/重度排斥反应阶段增加的时间。次要目标是：3)14确定QT间期的增加是否预测一年的死亡率；4)探索额外的心电图15测量，可能预测排斥或死亡。16计划进行前瞻性、双盲、描述性和相关性研究设计。分析心电数据的调查人员将被活检结果蒙蔽；医疗保健提供者将被QT 18测量蒙蔽。325名成人心脏移植受者的样本将从3个移植中心招募：19个哥伦比亚大学-纽约长老会医学中心；加州大学洛杉矶分校和洛杉矶锡达斯-20西奈医学中心。每位受试者每天将使用HeartOneTM 21设备记录30秒的心电；该设备将自动将心电传输到加州大学旧金山分校的心电核心实验室。对于主要目标#1，将进行对数回归分析，其中23个自变量是有无心电图标准(QTC e25毫秒×3天)，24个因变量是有无急性同种异体移植排斥反应。将报告优势比和可信区间25，以及新诊断工具的既定评估标准(灵敏度、特异度、26个阳性/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27来报告心电标准的制定和28例排斥的活检证据之间的平均时间段。寻找一种简单的同种异体移植排斥反应的心电图生物标志物的潜在好处是，它可能会更早地发现排斥反应，允许更及时的治疗，并减少30例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.