Proliferation signal inhibitors in heart transplantation: a 5-year experience

Calcineurin inhibitors (CNI) are associated with multiple complications, especially renal dysfunction and tumor development. Proliferation signal inhibitors (PSI) show renal protection and an antineoplastic effects, and may retard allograft vasculopathy. The objective of the current study was to present our initial experience center with PSI therapy.

We analyzed all heart transplants (HT) performed in our center who received a PSI at any time. We assessed the clinical profiles, indications for and strategies of PSI introduction, complications, causes of discontinuation, and renal functional evolutions.

Among 604 HT performed in our center, 82 patients (13.5%) received a PSI: sirolimus (n=2) or everolimus (n=80). Their mean age was 53±12 years and 90% were men. PSI introduction occurred at 75±53 months posttransplantation. The strategy was CNI minimization in 17% of cases, and total conversion from CNI in 83%. The PSI indication was renal dysfunction (40%), tumors (38%), allograft vasculopathy (17%), and other reasons (5%). After PSI introduction, 15.8% of patients suffered a rejection episode and 20%, a significant infection. The PSI discontinuation rate was 8.5%: due to infection (2.4%), edema (1.2%), inadequate cicatrization (1.2%), and other reasons (3.7%). Creatinine was 1.68±0.64 mg/dL the year before and 1.72±0.79 mg/dL at and 1.82±1.61 mg/dL 1 year after PSI conversion.

PSIs showed few complications with a low withdrawal rate, and maintained renal function. The main indications for their use were renal dysfunction, tumors, or development of allograft vasculopathy.