Cardiac Graft Assessment in the Era of Machine Perfusion: Current and Future Biomarkers

Figure 1. Biomarkers with reported potential value when evaluated during graft management. cTnI indicates cardiac troponin I; cTnT, cardiac troponin T; gp130, glycoprotein 130; HEP, high‐energy phosphates; Hs‐cTnT, high‐sensitivity cTnT; HTx, heart transplantation; IL‐6, interleukin 6; IL‐6R, IL‐6 receptor; MP, machine perfusion; O2C, cardiac oxygen consumption; O2E, cardiac oxygen efficiency; sTNFR, soluble tumor necrosis factor receptor; TNF‐α, tumor necrosis factor‐α; and VCAM‐1, vascular cell adhesion molecule 1.

Figure 2. Schematic protocols for conditions before and during heart procurement and storage. A, Hearts obtained with donation after circulatory death (DCD) are subjected to a period of warm, global ischemia, before procurement. In the direct procurement and perfusion protocol (DPP), grafts are stored and transported using normothermic machine perfusion (MP). In the normothermic, regional perfusion (NRP) protocol, the heart is reperfused in situ. Only after functional evaluation is it procured, stored, and transported using normothermic MP or cold, static storage (CSS). B, Hearts obtained with donation after brain death (DBD) remain perfused until organ procurement. Hearts are then stored and transported using CSS or normothermic MP.

Figure 3. Schematic overview of markers for cardiac graft evaluation. Markers can be assessed at the level of the whole organ (blue), tissue biopsies (red), or circulating in donor blood or ex situ perfusate (green). Cardiac metabolism: cardiac oxygen consumption and efficiency, lactate release, and high‐energy phosphate metabolites. Tissue injury: cardiac troponin I and cardiac troponin T. Endothelial activation: P‐, E‐, and L‐selectin expression, vascular cell adhesion molecule‐1, and thrombomodulin. Vascular function: coronary flow, vascular relaxation, vascular leakage (edema), and endothelial NO synthase coupling (peroxynitrite formation). Inflammation: tumor necrosis factor (TNF)‐α, interleukin 6, interleukin 10, glycoprotein 130, and soluble TNF receptors 1/2. Hormones: procalcitonin and brain natriuretic peptide.