The promise of protein-based and gene-based clinical markers in heart transplantation: from bench to bedside.

Advances in immunosuppression, guided by invasive endomyocardial biopsy for the assessment of graft rejection, have ushered heart transplantation into the clinical arena by the demonstration of acceptable 1-year outcomes. Further decreases in the risk of malignancy and cardiac allograft vasculopathy that improve long-term outcomes, are, however, still desired. Attention has become directed towards the use of markers that can be detected noninvasively to provide insight into underlying molecular and cellular events associated with the immune response and graft function. Various candidate, protein-based markers have been identified: those of alloimmune activation; those of microvascular injury, such as cardiac-specific troponins; those of inflammation, including C-reactive protein; and surrogate markers of cardiac function, including natriuretic peptides such as brain natriuretic peptide. In the realm of genomics, it is becoming increasingly clear that a single molecular marker is unlikely to prove to be useful, but rather that multiple genes from a number of pathways are needed to capture biological complexity and overcome variability in the general population. Thus, the field of protein-based and gene-based biomarkers is advancing rapidly to define its place in clinical therapeutics and to guide immunosuppression according to molecular mechanisms of disease. We discuss here the main findings for the more-successful protein markers identified so far, and the genomic molecular approaches being used to improve heart transplant outcomes.