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Tacrolimus Monotherapy Is Sufficient For Partial Heart Transplantation
Herra Javed, MBBS, Mohammed Ahmed Zaghw, M.D, Amna Qasim, M.D, Meagan Rogers, NP, Tori Beach, DNP, Simon Chung, B.S, Rodolfo Henrich-Lobo, M.D, Brian Reemtsen, M.D, Taufiek Konrad Rajab, M.D.
Arkansas Children Hospital, Little rock, AR, USA.
Objective(s): We evaluated the growth and immune rejection of pulmonary valve partial heart transplants under tacrolimus monotherapy in a porcine model.
Methods: Twenty GFP transgenic piglets were assigned to four groups: triple-therapy (n=5), tacrolimus monotherapy (n=5) , positive control (unoperated, n=5), and homovital-homografts (negative control, n=5). Donor pulmonary roots were harvested and transplanted into recipients via cardiopulmonary bypass and maintained on tacrolimus trough levels of 5-15 ng/mL. Weekly echocardiography was performed until recipients had doubled in weight (mean follow‑up 32±11 days). At study end-point, the hearts were explanted; histology, immunohistochemistry and immunofluorescence analysis was performed.
Results: There was no statistically significant gradient difference in tacrolimus monotherapy (Slope=0.037mmHg/day, p=0.577) compared to both, triple-therapy (Difference=0.020, p=0.997) and positive control (Difference=0.022, p=0.995). Homovital-homografts developed peak transvalvular gradients of 49.101±7.656 mmHg (p<0.001 vs. positive controls), consistent with severe stenosis by postoperative day 60. The Tacrolimus monotherapy group showed steady valvular growth (Slope=0.008cm/day, p<0.001), matching triple-therapy (Difference<0.001,p=0.996) and positive controls (Difference=0.002, p=0.839). Immunohistopathology for tacrolimus monotherapy revealed focal clusters of CD3⁺ T cell at the hinge regions without any structural disarray. In comparison, homovital-homograft displayed marked CD3⁺ infiltration throughout the leaflet with endothelial cell hyperplasia.
Conclusions: Tacrolimus monotherapy is sufficient for partial heart transplantation. This evidence transforms clinical practice by minimizing side effects of immunosuppression in children with partial heart transplants.
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