Functional and biochemical biomarkers of cardiac graft quality measured during normothermic ex-situ heart perfusion in a porcine model of donation after circulatory death.

Donation after circulatory death (DCD) provides excellent patient outcomes in heart transplantation and substantially increases graft availability. The lack of validated biomarkers for graft function constrains reliable graft assessment and highlights the need for more effective assessment strategies. Using a porcine model of DCD, hearts underwent 0 (= sham), 10, 20, or 30 minutes of warm, in-situ ischemia followed by normothermic ex-situ heart perfusion for 3 hours in an unloaded mode and then 1 hour with left ventricular loading. During unloaded perfusion, left ventricular function and the release of cell death markers were measured at regular intervals. These potential biomarker measurements were correlated with recovery outcomes determined at the end of loaded reperfusion. During unloaded ex-situ heart perfusion, perfusate levels of heart-type fatty acid binding protein (H-FABP), and several catheter-based measurements of left ventricular (LV) function, particularly LV work (developed pressure-heart rate product) correlated with functional recovery outcomes (p< 0.05 for all). We report several new biomarkers of cardiac graft quality, such as left ventricular function and H-FABP that are enabled by normothermic ex-situ heart perfusion. These biomarkers are particularly promising as they are amenable to clinical application and may improve our precision in cardiac DCD graft evaluation.