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Background: To evaluate the effectiveness of the Paragonix SherpaPak cardiac transport system (PSP) compared to the standard ice-cold storage (ICS) in extended-criteria donor grafts implanted in high-risk recipients., Methods: Data of all HTx at the University Centers of Udine and Bologna, between January 2020 and December 2023, employing extended-criteria donors in high-risk HTx conditions were retrospectively analyzed. Patient outcomes and complications after HTx were assessed. Endomyocardial biopsies were performed in donor hearts immediately after retrieval (T 0 ), before implantation (T 1 ) and at reperfusion (T 2 ) to evaluate signs of myocardial damage., Results: Overall, 90 patients who had heart transplantation (HTx) with a donor graft preserved with either ICS (n = 60) or PSP (n = 30) were included in the study. The 30-day mortality was 3% in both groups (p = 0.99), and 1-year survival 90% and 88% (p = 0.89) for recipients transplanted with PSP and ICS preserved grafts. Rates of moderate-to-severe graft dysfunction and bradi-arrhythmias for PSP and ICS groups were 7% versus 20% (p = 0.08), and 3% versus 15% (p = 0.09). Histologically, severe degrees of cellular and endothelial damage were absent in all PSP grafts while severe degree of contraction bands were higher in ICS hearts at T 2 ., Conclusions: In high-risk donor-recipient matching, donor heart preservation with PSP seems to show a tendency toward better graft protection., (© 2024 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)