From constraint to opportunity: 10 °C static cold storage allows prolonged ischemic time and attenuates severe primary graft dysfunction risk in adult heart transplantation.

Abstract

Allograft ischemic time remains a major constraint in heart transplantation, with ice-based static cold storage (SCS) limiting safe transport to 4 hours. We evaluated whether 10 °C SCS alters the relationship between ischemic time and early cardiac allograft function in a contemporary single-center cohort. We retrospectively analyzed adult heart transplants performed from January 2020 to June 2025. Only allografts preserved with SCS (ice or 10 °C) were included; multiorgan and complex congenital transplants were excluded. The primary exposure was preservation strategy (ice vs 10 °C) and total allograft ischemic time. The primary outcome was severe primary graft dysfunction (PGD); secondary outcomes included early biventricular function, vasoactive inotrope score, renal-replacement therapy, length of stay, and 30- and 90-day mortality. Weighted regression was used to assess the effect of ischemic time and its interaction with storage type on severe PGD. In a prespecified subgroup with ischemic time >4 hours, g-computation estimated counterfactual risks if all grafts had been stored at 10 °C. Regression-based causal mediation analysis quantified the net effect of prolonged ischemic time with 10 °C SCS on severe PGD. Among 506 recipients (median age 58.3 years; 25.5% female), 40.9% received 10 °C-preserved grafts and 59.1% received ice-preserved grafts. Compared with ice, the 10 °C cohort more often received hearts from older donors (36.0 vs 29.9 years; P < .001) with longer ischemic times (235 vs 202 minutes; P < .001), yet early outcomes were similar overall. In weighted models, each additional hour of ischemia in ice-preserved grafts increased the odds of severe PGD by 2.7-fold (P < .001). At 4 hours of ischemic time, 10 °C storage was associated with markedly lower odds of severe PGD compared with ice (odds ratio, 0.21; 95% CI, 0.09-0.45; P < .001) and the ischemic time risk curve flattened in 10 °C cohort. In the ischemic time >4-hour subgroup, 10 °C corresponded to a relative risk reduction in severe PGD of 90.9% (95% CI, 59.7-99.5). Mediation analysis estimated a net risk reduction in severe PGD of 3.5 percentage points for 10 °C versus ice (95% CI, -7.7 to -0.2; P = .042) despite accumulating high ischemic time risk. In this contemporary cohort, 10 °C SCS decoupled the traditional link between prolonged ischemic time and severe PGD. 10 °C preservation conferred a net reduction in severe PGD and improved early graft performance compared with ice in adult heart transplantation.