Precision Monitoring of Immunosuppressive Agent Concentrations in Cardiac Tissue of Pediatric Heart Transplant Recipients

Background Management of immunosuppressive therapy after heart transplantation is typically guided by blood trough levels. Although tissue concentrations of immunosuppressive agents reportedly correlate with acute rejection in liver and kidney allografts, data in pediatric heart transplant recipients remain limited. Methods We enrolled 41 pediatric heart transplant recipients who underwent follow-up endomyocardial biopsy (EMB) between July 2021 and December 2023. For nine of those patients, serial data were collected up to 24 weeks post-transplantation. Myocardial tissue concentrations of tacrolimus (TAC), everolimus (EVR), mycophenolic acid (MPA), and mycophenolic acid glucuronide (MPAG) were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS), while blood concentrations were quantified by LC-MS/MS or immunoassays. Results Significant correlations were observed between myocardial and blood concentrations at EMB for TAC (r = 0.73, p < 0.0001), MPA (r = 0.79, p < 0.0001), and MPAG (r = 0.50, p < 0.0001). However, for EVR there was no significant correlation. Longitudinal analysis demonstrated that the tissue-to-blood TAC and EVR ratios decreased with age. No significant rejection events were observed during the study period, precluding the analysis of rejection risk. Conclusion Myocardial TAC, MPA, and MPAG concentrations are associated with blood levels, whereas those of EVR showed no significant correlation. Further, the tissue perfusion efficiencies of TAC and EVR decreased with age. This study highlights the value of LC-MS/MS for immunosuppressant monitoring after pediatric heart transplantation.