Abstract 4371518: Vitrified Partial Heart Transplants Grow at the Same Rate as Fresh Partial Heart Transplants and Retain Viable Donor Cells In-Vivo

Abstract

Introduction: Partial Heart Transplants (PHT) retain shortcomings intrinsic to transplantation, including the requirement to transplant grafts urgently after donation to maintain cellular viability.We evaluated the graft viability growth potential, hemodynamic function and immune rejection of pulmonary valve partial heart transplants vitrified for a month in a porcine model. Methods: PHT grafts from GFP+ donor piglets were vitrified for one month. Vitrified PHT grafts (n=3) and fresh PHT grafts (n=3) were orthotopically transplanted into wildtype recipient piglets. Post-operatively, recipient piglets (n=6) and unoperated positive control (n=3) underwent serial echocardiography to analyze valve size and valve function until recipients had doubled in weight. At study end-point, the hearts were explanted, immunohistochemistry and immunofluorescence analyses were performed. Linear mixed-effects models were used to model growth trajectories of Pulmonary Valve Gradient and Annulus over time. Marginal predictions and their corresponding 95% confidence intervals were derived to support model-based inference. Results: There is no statistically significant difference in the post-operative growth of gradient for vitrified cohort (Slope = 0.262 [0.113, 0.411] mmHg/day, p < 0.001) compared to fresh PHT cohort (Difference in slopes = 0.225 [-0.070, 0.521] mmHg/day, p = 0.166) and positive controls (Difference in slopes = 0.236 [-0.066, 0.538] mmHg/day, p = 0.152)). The vitrified PHT cohort showed steady valvular growth (Slope = 0.003 [-0.000, 0.006] cm/day, p = 0.095), matching fresh PHT (Difference in slopes = -0.005 [-0.010, 0.000] cm/day, p = 0.065) and positive controls (Difference in slopes = -0.002 [-0.009, 0.004] cm/day, p = 0.661). The vitrified PHTs had excellent hemodynamic function with no more than mild stenosis or regurgitation despite recipients doubling in weight. GFP mRNA was normalized to b-actin and compared to negative control pancreatic cancer cells (PA16C cell line) (p < 0.001). Conclusion: Vitrified PHTs grow at the same rate as fresh PHTs and retain viable donor cells in vivo. These findings have the potential to transform clinical practice by eliminating wait times for critically ill children.