THE IMPACT OF SIROLIMUS AS A PRIMARY IMMUNOSUPPRESSANT ON MYOCARDIAL FIBROSIS AND DIASTOLIC FUNCTION FOLLOWING HEART TRANSPLANTATION

Purpose Myocardial fibrosis is an important contributor for development of diastolic dysfunction (DD) following heart transplantation (HT). Small studies have reported superiority of sirolimus (SRL) over calcineurin inhibitor (CNI) in mitigating DD assessed by echocardiography. However, data on invasive hemodynamic assessment is lacking, and the impact of SRL on myocardial fibrosis progression remains unclear. We aimed to investigate the impact of SRL on DD and fibrosis progression among HT recipients. Methods A cohort of 100 HT recipients who were either treated with CNI alone (n =51) or converted from CNI to SRL (n=49) as primary immunosuppression was analyzed. Diastolic function parameters were assessed using serial echocardiograms and right heart catheterizations (RHC). Myocardial fibrosis was quantified on serial myocardial biopsies by automated digital analysis, blinded to the type of therapy. Results After 3 years, left ventricular end diastolic diameter (LVEDD) increased in the SRL group (45.7 ± 5.1 to 48.3 ± 5.5 mm, paired p Conclusion Early conversion to SRL is associated with improvement in DD and LV filling pressures which can be partially explained by attenuation of myocardial fibrosis progression as compared to CNI therapy.