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(Circulation. 2009;120:S198-S205.)
© 2009 American Heart Association, Inc.

Cardiac Transplantation and Surgery for Heart Failure

Donor Serum SMARCAL1 Concentrations Predict Primary Graft Dysfunction in Cardiac Transplantation

Seyedhossein Aharinejad, MD, PhD; Olena Andrukhova, PhD; Matthias Gmeiner, MD; Anita Thomas, MS; Arezu Aliabadi, MD; Andreas Zuckermann, MD; Katharina Krenn, MD; Michael Grimm, MD

From the Department of Cardiothoracic Surgery (S.A., M.G., A.A., A.Z., M.G.), the Laboratory for Cardiovascular Research (S.A., O.A., M.G., A.T.), Center for Anatomy and Cell Biology, and the Department of Internal Medicine II (K.K.), Medical University of Vienna, Austria.

Correspondence to Dr S. Aharinejad, Department of Cardiothoracic Surgery, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria. E-mail seyedhossein.aharinejad{at}meduniwien.ac.at

Background— Primary graft dysfunction (PGD) is a life-threatening complication in cardiac transplantation. A sensitive, specific, and easily measurable predictor in donors could facilitate PGD prevention.

Methods and Results— SMARCAL1 is a matrix-associated regulator of chromatin with helicase and ATPase activities, and its serum concentrations were significantly increased in a targeted protein array in donors whose grafts developed PGD. Therefore, this study analyzed SMARCAL1 serum concentrations by ELISA in 336 heart donors before and after aortic cross-clamping (ACC) and in recipients at 10, 30, and 60 minutes reperfusion. Demographic and hemodynamic parameters of donors and recipients as well as transplant procedure characteristics were documented. PGD (n=68) was defined as ventricular dilation and hypocontractility associated with systolic blood pressure <90 mm Hg, pulmonary capillary wedge pressure >20 mm Hg, and decreased mixed venous oxygen saturation necessitating mechanical circulatory support. SMARCAL1 serum protein concentration was significantly increased only before and after ACC in donors (P<0.0001) whose grafts developed PGD compared to those who did not. In receiver operating characteristic curve analysis, SMARCAL1 serum concentration at a cut-off level of 1.25 ng/mL before ACC in donors predicted PGD (P<0.0001, AUC=0.988, OR=17.050, 95% CI=5.200 to 55.901) with 96% sensitivity and 88% specificity. SMARCAL1 serum concentrations <1.25 ng/mL in donors before ACC resulted in 97% PGD-free outcome and SMARCAL1 concentrations 1.25 resulted in 83% PGD occurrence.

Conclusions— Donor serum SMARCAL1 may serve as a specific, sensitive, and noninvasive predictive marker in the assessment of cardiac graft quality.

Key Words: cardiac transplantation • primary graft dysfunction • marker • SMARCAL1