Transplantation is an effective treatment modality for infants1 and children2 with end-stage cardiac diseases. Rejection remains a major complication (Figure 1), even in newborn infants.3 Acute rejection can best be operationally defined by clinical findings, histopathology, and/or abnormalities of ventricular function of new origin that require, and respond to, intensified immunosuppression. Mechanistically, the ability to detect acute rejection is critically dependent on the detection of significant new myocytic injury, damage, and/or death. Surveillance for rejection is critically important in determining both long and short-term outcomes following cardiac transplantation. The ideal strategy for surveillance should have a high negative predictive value, correctly identifying the absence of myocytic injury, with high specificity, such that it does not falsely predict such injury.4