Association of Cyclosporine Time in Therapeutic Range With Acute Cellular Rejection in Heart Transplantation: A 13-Year Single-Center Study

Background: Cyclosporine (CsA), a calcineurin inhibitor, is widely used to prevent acute cellular rejection (ACR) after heart transplantation (HT). However, the association between the time in therapeutic range of CsA (CsA-TTR) and ACR risk remains unclear. This study aimed to evaluate the association between CsA-TTR and first-year ACR among Thai heart transplant recipients (HTRs). Methods: This single-center retrospective cohort study included adult HTRs who survived until discharge between January 2009 and December 2021. CsA trough levels were collected from the first outpatient visit to 1 year post-HT or until the first ACR. CsA-TTR was calculated using the Rosendaal method and analyzed using the median and tertile categories. Associations with the ACR were assessed using Cox regression analyses. Results: Fifty HTRs (mean age, 43.5 years) were included. The median CsA-TTR was 29.4%. Patients with higher CsA-TTR had a significantly lower risk of ACR than those with lower CsA-TTR (HR, 0.33; 95% CI, 0.16–0.68; P = 0.003). The lowest CsA-TTR tertile showed a markedly higher rejection risk than the highest tertile (HR, 3.24; 95% CI, 1.38–7.60; P = 0.007). Conclusions: A higher CsA-TTR was associated with a significantly lower risk of first-year ACR. Prospective studies are warranted to validate CsA-TTR as a predictor of rejection. Clinical trial registration: Thai Clinical Trials Registry (TCTR) ID: TCTR20240319005.