Non-Ischemic Heart Preservation versus Static Cold Storage in Human Heart Transplantation

Abstract

Pre-clinical studies have shown that ex vivo non-ischemic heart preservation (NIHP) method can be safely used for 24 hours. This state-of-the-art method has never been applied on humans. ໿໿The primary objective of the study was to evaluate the efficacy and safety of the NIHP method on early and late human heart allograft function compared with static cold storage (SCS). We performed a prospective, open-label, non-randomised phase II study. All adult recipients listed for heart transplantation were included, unless they met any exclusion criteria. The primary endpoint was a composite of survival free of severe primary graft dysfunction, free of ECMO use within 7 days, and free of acute cellular rejection ≥2R within 180 days. Secondary endpoints were I/R-tissue injury, immediate graft function, and adverse event. Of the 37 eligible patients, nine were assigned to the NIHP method and 28 to SCS. The median age was 51 years (interquartile range (IQR), 37-58) for the donors and 56 years (IQR, 46 - 63) for the recipients. The median preservation time was significant longer for the NIHP group, 251 min (IQR, 219-269) compared with the SCS group, 199 min (IQR, 164 - 227), P=0.008. Over the first three months, all of the patients assigned to the NIHP group achieved event-free survival, compared with 21 (75%) of those assigned to the SCS group (Kaplan-Meier estimate of event free survival 75% (95% CI 55-87%); P=0.124). CK-MB assessed 6±2 h after ending perfusion was 77 (IQR, 54-101) ng/mL for the NIHP group compared with 137 (IQR, 73-196) ng/mL for the SCS group, P=0.030. Four (16%) death within six months after transplantation and three (12%) cardiac-related adverse events were reported in the SCS group compared with no deaths or cardiac-related adverse events in the NIHP group. This first-in-human study shows the NIHP method's feasibility and safety for use in the clinic of heart transplantation.