Direct procurement and ex-situ assessment of donor hearts after controlled circulatory death: A French national pilot study.

BACKGROUND

Heart transplantation following donation after controlled circulatory death (DCD) is not authorized in France, hence a feasibility study was mandatory.

AIMS: To conduct a preclinical study to validate the feasibility of DCD heart procurement. We further sought to investigate the metabolic signature of DCD hearts during normothermic ex-situ perfusion (NESP).

METHODS

The study design was approved by the Agence de la biomedecine (PFS20-004, La Plaine Saint-Denis, France). Five patients were considered for DCD heart procurement. Femoral vessels were canulated to ensure abdominal normothermic regional perfusion (A-NRP). Direct procurement followed by 4hours of NESP was performed. Donors' demographics and duration of functional warm ischaemic time (fWIT) were collected. Lactate levels were assessed every 30minutes during NESP. Plasma and left ventricular biopsies were collected every 30 and 60minutes, respectively, for untargeted metabolomic analyses using liquid chromatography coupled to high-resolution mass spectrometry.

RESULTS

Mean±standard deviation donor age was 40±11 years and fWIT for the hearts was 26±10min. DCD lungs and kidneys were transplanted except in one case each (impaired ex vivo lung perfusion and premature arrest of A-NRP, respectively). DCD livers were all transplanted when allocated. All hearts were successfully perfused for 4hours. Lactate decreased during NESP for all hearts with a mean±standard deviation initial lactate at 5.42±0.98mmol/L and a final concentration at 3.02±0.86mmol/L (P=0.003). In plasma samples, there were notable changes for 166 metabolites. Most of them either initially increased and stabilized (64/166; 38.6%, e.g. carnitines) or continuously increased (67/166; 40.4%, e.g. purines, medium-chain fatty acids and amino acids). In biopsy samples, there were notable changes for 103 metabolites. Most of them initially decreased and stabilized, such as carnitines and nucleotides.

CONCLUSION

DCD heart procurement is feasible in France. Lactate trends were consistent with suitability of these hearts for transplantation. The metabolomic signature was characterized by nucleotide catabolism along with consumption of carnitines.