Abstract 2579: Donor Myocardial Hypoxia Inducible Factor-1α Expression is an Independent Predictor of Cardiac Allograft Dysfunction
Primary graft dysfunction (PGD) is a severe complication in cardiac transplantation, associated with a high mortality rate. Higher risk donor hearts that may have been deemed unsuitable previously because of poor hemodynamics or prolonged ischemia time are being increasingly accepted due to donor organ shortage. Thus, markers that could identify donor hearts at risk for PGD, preferably at graft harvest, are highly desirable. The transcription factor hypoxia inducible factor-1 (HIF-1) is involved in oxygen homeostasis and tissue stress and is quickly activated by hypoxia as well as by cytokines. Increased HIF-1α expression in donor hearts may therefore indicate tissue damage. Whether tissue HIF-1α mRNA levels could predict PGD in cardiac transplantation is unclear. In a prospective 7-year study, 857 left ventricular biopsies were obtained from 200 donor hearts before and after aortic cross-clamping and at 10, 30 and 60 minutes following reperfusion. Tissue HIF-1α mRNA expression was examined by real time reverse transcription PCR and correlated to clinical parameters. PGD occurred in 44 patients. HIF-1α myocardial expression was significantly higher after aortic cross-clamping in donors (p=0.001) and at 10 min after reperfusion (p<0.0001) in PGD patients compared to those without PGD. In receiver operating characteristic curve analysis and at a cut-off level of 200 arbitrary units, HIF-1α expression after aortic cross clamping in donors identified PGD patients with a sensitivity of 78% and a specificity of 83% (p=0.003, AUC=0.877, CI=1.003–1.023); and HIF-1α levels 10 min after reperfusion identified patients with PGD with a sensitivity of 85% and a specificity of 83% (p=0.0001, AUC=0.881, CI=1.001–1.010). When all data were entered into a stepwise multiple logistic regression analysis, the predictive ability of HIF-1α was even superior to clinical parameters. HIF-1α is a sensitive, specific and quick-response predictor of PGD in cardiac transplantation.