Advancing Assessment Methods for Human Cardiac Grafts During Normothermic Machine Perfusion

BACKGROUND: Heart failure, a leading global health challenge, affects over 23 million people worldwide, with heart transplantation being the gold standard for end-stage disease. However, the scarcity of viable donor hearts presents a significant barrier, with only one-third of available grafts being used because of stringent selection criteria. Machine perfusion technologies, particularly normothermic machine perfusion (NMP), offer promise for improving graft preservation and assessment, yet their full potential for predicting transplantability remains underexplored. METHODS: This study investigates 3 assessment methods to enhance human heart evaluation during NMP, focusing on mitochondrial function, left ventricular performance, and inflammatory markers. First, resonance Raman spectroscopy is used to assess mitochondrial redox state as a proxy for metabolic competency, offering a noninvasive and dynamic evaluation of mitochondrial function during ex vivo preservation. Second, left ventricular function is quantified using intraventricular balloons, providing critical insights into graft viability and performance. Third, inflammatory markers and endothelial activation are assessed from the perfusate to aid the prediction of posttransplant outcomes. RESULTS: These methods were successfully tested on human donor hearts that were declined for transplantation, preserved via static cold storage, and subsequently assessed with NMP in Langendorff mode. CONCLUSIONS: The results demonstrate that these parameters can be easily integrated into existing clinical perfusion workflows and hold potential for improving heart transplantation outcomes by enhancing graft selection and optimizing donor heart use. Future studies will further validate these biomarkers across different preservation techniques and evaluate their clinical applicability.