Sirolimus as primary immunosuppressant reduces left ventricular mass and improves diastolic function of the cardiac allograft.
BACKGROUND
Left ventricular hypertrophy (LVH) and diastolic dysfunction occur after cardiac transplantation. We investigated sirolimus (SRL) as primary immunosuppression for the attenuation of LVH and diastolic dysfunction of the cardiac allograft.


METHODS
Seventy cardiac transplant recipients were converted to SRL, 5.79+/-3.90 years after transplant, with complete calcineurin-inhibitor (CNI) withdrawal. Three consecutive echocardiographic studies, 1 year apart, were analyzed for changes in left ventricular (LV) mass and diastolic function during CNI and SRL treatment.


RESULTS
Changes in systolic (P=0.69) and diastolic blood pressures (BP) (P=0.32) did not differ between SRL and CNI treatment. LV mass and LV mass index increased (185.03+/-41.59-197.21+/-47.39 g, P=0.033 and 94.20+/-18.64-98.93+/-20.08 g/m; P=0.030) during CNI and decreased (197.21+/-47.39-187.59+/-48.88 g, P=0.025 and 98.93+/-20.08-94.06+/-20.31 g/m P=0.050) during SRL. The difference in Delta LV mass and Delta LV mass index was significant (P=0.011 and P=0.017, respectively) and was not associated with changes in BP. Left atrium volume index increased during CNI (46.73+/-16.3 5-54.20+/-18.47 cm/m, P=0.006) and decreased during SRL (54.20+/-18.47-49.75+/-18.40 cm/m, P=0.0036). The difference in left atrium (Delta LA) volume index was significant (P=0.002) and was not associated with changes in BP.


CONCLUSIONS
Withdrawal of CNI and replacement with SRL in cardiac transplant recipients results in a decrease in LV mass and improvement in diastolic function. SRL may be useful to attenuate LVH and improve cardiac allograft diastolic function.
Raichlin
Eugenia
E
Division of Cardiovascular Diseases and the William J. von Liebig Transplant Center, Mayo Clinic, Rochester, MN 55905, USA.
Chandrasekaran
Krishnaswamy
K
Kremers
Walter K
WK
Frantz
Robert P
RP
Clavell
Alfredo L
AL
Pereira
Naveen L
NL
Rodeheffer
Richard J
RJ
Daly
Richard C
RC
McGregor
Christopher G A
CG
Edwards
Brooks S
BS
Kushwaha
Sudhir S
SS
D000328:Adult; D000368:Aged; D065095:Calcineurin Inhibitors; D009202:Cardiomyopathies / Q000145:classification / Q000601:surgery; D003971:Diastole / Q000502:physiology*; D004452:Echocardiography; D005260:Female; D005500:Follow-Up Studies; D006331:Heart Diseases / Q000145:classification / Q000601:surgery; D016027:Heart Transplantation / Q000276:immunology / Q000502:physiology*; D006439:Hemodynamics; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020123:Sirolimus / Q000627:therapeutic use*; D013599:Systole / Q000187:drug effects; D014184:Transplantation, Homologous; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000517:prevention & control*; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology*
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D020123:Sirolimus