Abstract 2961: Sirolimus affects Cardiomyocytes to Reduce Left Ventricular Mass in Heart Transplant Recipients
Background: Cardiac hypertrophy compromises cardiac function and decreases survival. in coronary disease, hypertension and following cardiac transplantation. The cellular mechanisms underlying cardiac hypertrophy may in part result from changes in cardiac myocyte growth and differentiation. We tested whether sirolimus, an immunosuppressive agent that inhibits mTOR, a protein that regulates cell division and differentiation, might modify adverse cardiac remodeling after cardiac transplantation.
Methods: Fifty-eight cardiac transplant recipients were withdrawn from treatment with calcineurin inhibitors and treated instead with sirolimus, an immunosuppressive agent that inhibits mTOR. Immunosuppressive therapy was not otherwise changed. Eighty-three other subjects were maintained on calcineurin inhibitors as controls.
Results: The systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreased in sirolimus treated subjects. After treatment of up to 12 months, left ventricular (LV) mass and LV mass index decreased in sirolimus treated subjects while LV mass and LV mass index did not change in controls. The left atrial (LA) volume index of decreased in sirolimus treated subjects and increased in controls. The difference between the groups was independent of blood pressure and did not reflect differences in rejection episodes or degree of immunosuppression. The number of cells in myocardial biopsies positive for p27Kip1, a protein induced by mTOR inhibition, increased in sirolimus treated subjects and did not change in controls suggesting sirolimus acted directly on myocardium.
Conclusion: Sirolimus may inhibit adverse ventricular remodeling and have potential in the treatment of conditions in which severe remodeling compromises cardiac function. Hemodynamic, echocardiographic and P27 expression assessment