Sirolimus in heart transplantation: a single center initial experience

Sirolimus (SRL) is a potent non-nephrotoxic immunosuppressant. In our unit, SRL was administered to 17 heart transplant (HT) recipients at 1770+/-1234 days' posttransplant surgery, for the following reasons: (1) calcineurin inhibitor (CI) withdrawal due to renal insufficiency (RI; n=6); (2) neurotoxicity (n=1) and pancytopenia (n=1); (3) vascular graft disease (VGD) treatment (n=5); (4) immunosuppression optimization due to lung cancer (n=2); (5) CI use was delayed due to postsurgery RI (n=2). The mean follow-up was 190+/-165 days. Mean SRL doses (mg)/concentrations (ng/mL) at 7 (n=17), 30 (n=14), and 180 (n=8) days were: 1.2+/-0.6/5.9+/-6; 1.6+/-0.8/4.8+/-3.1; and 1.7+/-1.0/5.2+/-3.7. Among group 1, CI patients were discontinued without favorable functional impact. Neurotoxicity and pancytopenia improved, but there were no major clinical events in the VGD group. One "bridge" to CI was successfully performed (postsurgery RI). Total leukocyte count fell while hemoglobin, platelet, and cholesterol profiles were not affected. Ten of 15 patients (67%) were discontinued from CI without rejection and with a dose reduction of mycophenolate mofetil. There were 8 episodes (47%) of SRL-related toxicity, leading to 4 discontinuations (23%); 8 patients (47%) have died during follow-up. This retrospective analysis of outcomes in the context of severe complicated patients suggests that more premature introduction SRL is preferable, particularly in a large patient cohort.