Has the 2004 revision of the International Society of Heart and Lung Transplantation grading system improved the reproducibility of the diagnosis and grading of cardiac transplant rejection?

Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA.
Cardiovascular pathology: the official journal of the Society for Cardiovascular Pathology (Impact Factor: 2). 08/2008; 18(4):198-204. DOI: 10.1016/j.carpath.2008.05.003
Source: PubMed


We compared the interobserver reproducibility of the 1990 and 2004 International Society for Heart and Lung Transplantation (ISHLT) grading system for cardiac rejection. The 2004 ISHLT grading system for cardiac allograft rejection did not improve reproducibility partly due to pathologists' disagreement in diagnosing Grades 1B/1R and 3A/2R rejection. To achieve better reproducibility, better criteria for defining 1B/1R vs. 3A/2R rejection and markers of myocyte injury are needed.

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    • "Although early reports indicated inter-operator variability in the interpretation of EMB results [22], the use of the standardized grading system has improved the reliability and validity of the measurement. Current variability in interpretation of biopsy results occurs mainly in the diagnosis of Grade 2 rejection by local pathologists which may be misinterpreted in the presence of endocardial infiltrates called Quilty lesions [23,24]. To control for potential variability, we will monitor and record clinical and hemodynamic indicators of myocardial performance, which are obtained at the time of each biopsy or at regular clinical assessments, to support the biopsy interpretation, particularly regarding Grade 2 rejection. "
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    ABSTRACT: Acute allograft rejection is a major cause of early mortality in the first year after heart transplantation in adults. Although endomyocardial biopsy (EMB) is not a perfect "gold standard" for a correct diagnosis of acute allograft rejection, it is considered the best available test and thus, is the current standard practice. Unfortunately, EMB is an invasive and costly procedure that is not without risk. Recent evidence suggests that acute allograft rejection causes delays in ventricular repolarization and thereby increases the cellular action potential duration resulting in a longer QT interval on the electrocardiogram (ECG). No prospective study to date has investigated whether such increases in the QT interval could provide early detection of acute allograft rejection. Therefore, in the Novel Evaluation With Home Electrocardiogram And Remote Transmission (NEW HEART) study, we plan to investigate the potential benefit of daily home QT interval monitoring to predict acute allograft rejection. The NEW HEART study is a prospective, double-blind, multi-center descriptive research study. A sample of 325 adult heart transplant recipients will be recruited within six weeks of transplant from three sites in the United States. Subjects will receive the HeartViewâ„¢ ECG recorder and its companion Internet Transmitter, which will transmit the subject's ECG to a Core Laboratory. Subjects will be instructed to record and transmit an ECG recording daily for 6 months. An increase in the QTC interval from the previous day of at least 25 ms that persists for 3 consecutive days will be considered abnormal. The number and grade of acute allograft rejection episodes, as well as all-cause mortality, will be collected for one year following transplant surgery. This study will provide "real world" prospective data to determine the sensitivity and specificity of QTC as an early non invasive marker of cellular rejection in transplant recipients during the first post-transplant year. A non-invasive indicator of early allograft rejection in heart transplant recipients has the potential to limit the number and severity of rejection episodes by reducing the time and cost of rejection surveillance and by shortening the time to recognition of rejection. NCT01365806.
    Full-text · Article · Mar 2012 · BMC Cardiovascular Disorders
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    ABSTRACT: We sought to use cardiac magnetic resonance (CMR) to establish sensitive and reliable indexes for noninvasive detection of acute cardiac allograft rejection. Appropriate surveillance for acute allograft rejection is vitally important for graft survival. The current gold standard for diagnosing and staging rejection after organ transplantation is endomyocardial biopsy, which is not only invasive but also prone to sampling errors. The motivation of this study is to establish a CMR-based alternative that is noninvasive and sensitive for early detection of allograft rejection before irreversible damage occurs. We employed a noninvasive 2-pronged approach to detect acute cardiac allograft rejection using a rodent working heart and lung transplantation model. We used CMR to detect immune-cell infiltration at sites of rejection by monitoring the accumulation of dextran-coated ultra-small superparamagnetic-iron-oxide-labeled immune cells (in particular macrophages) in vivo. Simultaneously, we used CMR tagging and strain analysis to detect regional myocardial function loss resulting from acute rejection. Immune cells infiltration, mainly macrophages and monocytes, could be identified with CMR by in vivo labeling with ultra-small superparamagnetic-iron-oxide. Our data show that immune-cell infiltration in cardiac allograft rejection was highly heterogeneous. Thus, it is not surprising to find inconsistencies between rejection and endomyocardial biopsy results because of the limited number and small samples available. Tagged CMR and strain analysis showed that, as with immune-cell infiltration, ventricular functional loss was also heterogeneous. Although changes in global systolic function were generally not observed until the later stages of rejection, our data revealed that a functional index derived from local strain analysis correlated well with rejection grades, which may be a more sensitive parameter for detecting early rejection. CMR is noninvasive and provides a 3-dimensional, whole-heart perspective of the rejection status, potentially allowing more reliable detection of acute allograft rejection.
    Full-text · Article · Jul 2009 · JACC. Cardiovascular imaging
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