Key result
Switching to sirolimus for 12 months in cardiac transplant recipients significantly reduced left ventricular mass from 196.15 g to 182.21 g (P=0.05), whereas it did not change in controls.
Why the study?
Does sirolimus reduce left ventricular mass in cardiac transplant recipients compared to calcineurin inhibitors?
Cohort (n=141)
Does sirolimus reduce left ventricular mass in cardiac transplant recipients compared to calcineurin inhibitors?
p-value: p=0.05
Switching from calcineurin inhibitors to sirolimus in heart transplant recipients reduces left ventricular mass and left atrial volume index, suggesting a direct beneficial effect on adverse ventricular remodeling.
Sirolimus switch was associated with reduced LV mass in transplants; hypothesis-generating and requires randomized confirmation before practice change.
AIMS: The cellular mechanisms underlying cardiac hypertrophy may 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 cardiac hypertrophy after cardiac transplantation. METHODS AND RESULTS: Fifty-eight cardiac transplant recipients were withdrawn from treatment with calcineurin inhibitors (CNIs) and treated with sirolimus. Eighty-three control subjects were maintained on CNIs. After 12 months, left ventricular (LV) mass decreased from 196.15 +/- 48.28 to 182.21 +/- 43.56 g (P = 0.05) and LV mass index from 99.25 +/- 20.08 to 93.82 +/- 20.22 g/m(2) (P = 0.031) in sirolimus-treated subjects but did not change in controls. The left atrial volume index of sirolimus-treated subjects decreased from 52.44 +/- 17.22 to 48.40 +/- 15.14 cc/m(2) (P = 0.008) and increased from 52.07 +/- 19.45 to 57.03 +/- 19.93 cc/m(2) (P = 0.0012) in controls. The difference between the groups was independent of blood pressure. The number of cells in myocardial biopsies positive for p27Kip1, a protein induced by mTOR inhibition, increased in sirolimus-treated subjects (P = 0.0005) and did not change in controls (P = 0.54) suggesting sirolimus acted directly on myocardium. CONCLUSION: Sirolimus may inhibit adverse ventricular remodelling resulting in cardiac hypertrophy and have potential in the treatment of conditions in which severe hypertrophy compromises cardiac function.
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Kushwaha et al. (2008) conducted a cohort in Cardiac hypertrophy after cardiac transplantation (n=141). Sirolimus vs. Calcineurin inhibitors (CNIs) was evaluated on Left ventricular (LV) mass (p=0.05). Switching to sirolimus for 12 months in cardiac transplant recipients significantly reduced left ventricular mass from 196.15 g to 182.21 g (P=0.05), whereas it did not change in controls.
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