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Can non‐invasive methodology predict rejection and either dictate or obviate the need for an endomyocardial biopsy in pediatric heart transplant recipients?

In this issue of Pediatric Transplantation, Bennhagen et al. (1) continue the search for a non-invasive methodology that will obviate the need for an endomyocardial biopsy to diagnose cardiac allograft rejection. Shortly after the first human heart transplant was performed, early detectionof acute cellular rejectionwas recognized as crucial to preserving graft function (2). Biopsydirected immunosuppressive therapy quickly became standard of care in the adult and pediatric transplant recipient (3). Endomyocardial biopsy techniques evolved to allow the procedure to be performed safely and reproducibly in both adult and pediatric patients (4–6). The risks of endomyocardial biopsy in children are low; however, perforation, arrhythmia, vessel damage, tricuspid regurgitation, anesthetic-associated complications, and death are among the complications that have been reported (7–10). In addition to procedural risks, the negative impact of endomyocardial biopsy on quality of life following heart transplant in children is an important concern. Pediatric heart transplant centers differ widely in the use of endomyocardial biopsy to direct post-transplant immunosuppression in small infants and children, as the higher procedural risk may outweigh the benefit of frequent surveillance biopsies. Despite this, virtually all centers incorporate endomyocardial biopsy in the management of the older pediatric recipient, because of the low sensitivity and specificity of non-invasive methods in the detection of rejection in this age group (11). As a result, there is a strong impetus to identifyingmethods that would either eliminate or decrease the need for biopsy in children. The search for a non-invasive method to detect rejection began simultaneously with the institution of endomyocardial biopsy as the gold standard in the diagnosis of acute cellular rejection. The methods studied provide a history of the development of non-invasive tools to assess cardiac function over the past 25 years. These methods range from intramyocardial leads placed at the time of transplantation (12) to the use of myocardial scintillography to detect changes in cardiac perfusion during rejection (13). As each new tool was incorporated into the care of the patient with heart disease, studies of its potential applicability in the diagnosis of cardiac allograft rejection inevitably followed. In pediatric recipients, the use of the intramyocardial electrogram has shown promise; however, widespread use of this technique has been hindered by technical considerations and the need for daily home monitoring (14). The current article by Bennhagen et al. (1) continues the search for an electrocardiographic correlate of cellular rejection by measuring changes in signal-averaged electrocardiographic parameters associated with rejection in a small group of pediatric transplant recipients. The study found a significant increase in filtered QRS duration and late potentials during biopsy-proven rejection episodes. Unfortunately, the sensitivity and specificity of these findings were not sufficient to preclude the need for biopsy. The authors suggest further studies to determine if the negative predictive value of this methodology supports its use as a screen for acute cellular rejection. The conclusions are a familiar refrain heard throughout the history of the search for non-invasive markers of cardiac allograft rejection. There has been a great deal of investigation into the role of echocardiographic changes in the Pediatr Transplantation 2005: 9: 697–699 2005 The Author Journal Compilation 2005 Blackwell Munksgaard