Blood concentration of tacrolimus and age predict tacrolimus-induced left ventricular dysfunction after bone marrow...

Tacrolimus (TAC) is used for the prophylaxis and treatment of acute graft-versus-host disease after bone marrow transplantation (BMT). However, few have reported on TAC-induced left ventricular hypertrophy. This study aimed to assess the relationship between blood concentration of TAC and development of TAC-induced left ventricular (TI-LV) dysfunction in adult BMT patients with hematologic malignant diseases, and to evaluate whether TAC concentration can predict TI-LV dysfunction occurrence in these patients.

We enrolled 16 consecutive patients (mean age 44.6 ± 13.0 years) who received TAC after BMT. Echocardiography was performed before and after BMT, and blood concentrations of TAC were evaluated in terms of AUC₁₅ (area sum of TAC > 15 ng/ml during follow-up). We assessed the relationship between AUC₁₅ and development of TI-LV dysfunction after TAC.

During the follow-up period (mean duration 47.6 ± 13.7 days), interventricular septum thickness (IVST, P = 0.001) and posterior wall thickness (PWT, P < 0.001) increased, and E' decreased (P = 0.006). AUC₁₅ was associated with post-IVST (R = 0.627, P = 0.009), post-PWT (R = 0.669, P = 0.005), and post-E' (R = - 0.767, P = 0.001). In multivariate analysis, AUC₁₅ and age independently predicted the increase in IVST and PWT and decrease in E' after BMT. The combination of AUC₁₅ and older age predicted post-PWT with a sensitivity of 77.8% and specificity of 71.4%.

TAC concentrations should be maintained at < 15 ng/ml and age should be considered in patients undergoing BMT to avoid TI-LV dysfunction.