<prompt> The only reliable means of diagnosing acute cardiac rejection before substantial myocardial damage has occurred isEchocardiographyECGEndomyocardial biopsyUltrasound  <response>: Of the major complications, allograft rejection is the primary problem requiring surveillance; scheduled endomyocardial biopsy is the only reliable means of diagnosing acute cardiac rejection before substantial myocardial damage has occurred and at a stage that is reversible in the majority of instances. Rejection is characterized by interstitial lymphocytic inflammation that, in its more advanced stages, damages adjacent myocytes; the histology resembles myocarditis. When myocardial injury is not extensive, the rejection episode is usually either self-limited or successfully reversed by increased immunosuppressive therapy. Advanced rejection may be irreversible and fatal if it is not promptly treated. 