Rejection Surveillance and Immunosuppressive Therapy

Rejection surveillance was performed by routine endomyocardial biopsy (EMB) of median (interquartile range [IQR]) 16 (14–18) times (during the first year after transplantation and at 4 y post-HTx). After that period, EMBs were only taken when rejection was suspected. All patients included presented for routine EMB. Grading of the histological findings was done according to International Society for Heart and Lung Transplantation (ISHLT) standards.

Several regimens of induction therapy (intravenous anti-T-cell antibodies immediately after transplantation) have been used over time (Table S1, SDC, http://links.lww.com/TP/B827). From 2000, the maintenance immunosuppression therapy changed from cyclosporine-based to a tacrolimus-based scheme combined with prednisone and MMF. The standard dose of MMF used at our institution is from 2 × 750 mg/d (if combined with tacrolimus) up to 2 × 1500 mg/d (if combined with cyclosporin), modified based on trough level (optimum 1–3 mg/L). Either MMF or prednisone was stopped at 1-year posttransplant depending on the amount of rejections and on the side effects of these drugs (eg, infections, diabetes mellitus, obesity). Acute cellular rejection episodes were treated with pulsed high-dose methylprednisolone; in the case of steroid-resistant rejection, rabbit antithymocyte globulin was used. Antibody-mediated rejection was treated only in case of signs of graft failure in combination with histological and immunopathologic findings.