Lozano-Edo Silvia, Sánchez-Lázaro Ignacio, Portolés Manuel, Roselló-Lletí Esther, Tarazón Estefania, Arnau-Vives Miguel Angel, Ezzitouny Meryem, Lopez-Vilella Raquel, Almenar-Bonet Luis, Martínez-Dolz Luis
Heart Failure and Transplantation Unit, Cardiology Department, University and Polytechnic La Fe Hospital, Valencia, Spain.
Myocardial Dysfunction and Cardiac Transplantation Unit, Health Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain.
Transplantation. 2022 Apr 1;106(4):887-893. doi: 10.1097/TP.0000000000003798.
Noninvasive detection of primary graft dysfunction (PGD) remains a major challenge. SERCA2a plays an important role in cardiac homeostasis and its dysregulation has been associated with ventricular dysfunction and rejection. This study aimed to determine the potential utility of plasma levels of SERCA2a as a biomarker of PGD.
One hundred thirty-five plasma samples were collected from adult recipients 2-6 hours before heart transplantation (HT). Plasma concentrations of SERCA2a were determined using a specific sandwich ELISA. Variables related to the recipient, the donor, and the periprocedural were collected to determine a multivariate predictive model of PGD.
Levels of SERCA2a were decreased in patients who developed PGD (median 0.430 ng/mL [interquartile range, 0.260-0.945] versus 0.830 ng/mL [interquartile range, 0.582-1.052]; P = 0.001). Receiver operating characteristic curve analysis revealed that SERCA2a discriminated between patients with and without PGD (AUC = 0.682; P = 0.001), and a cutoff point ≥ 0.60 ng/mL was a protective independent predictor of PGD (odds ratio 0.215 [P = 0.004]). Three independent predictors of PGD in this study were reduced levels of pre-HT SERCA2a, increased bilirubin levels, and short-term mechanical circulatory support bridge to transplantation. The analysis of the receiver operating characteristic curve of the model obtained a significant AUC 0.788, P = 0.0001.
Our findings suggest that assessment of SERCA2a plasma levels may improve risk prediction for the occurrence of PGD and could be considered as a novel noninvasive biomarker in patients undergoing HT.
原发性移植物功能障碍（PGD）的无创检测仍然是一项重大挑战。肌浆网Ca2+-ATP酶2a（SERCA2a）在心脏内环境稳定中起重要作用，其失调与心室功能障碍和排斥反应有关。本研究旨在确定血浆中SERCA2a水平作为PGD生物标志物的潜在效用。
在心脏移植（HT）前2 - 6小时从成年受者收集135份血浆样本。使用特异性夹心酶联免疫吸附测定法（ELISA）测定血浆中SERCA2a的浓度。收集与受者、供者和围手术期相关的变量，以确定PGD的多变量预测模型。
发生PGD的患者中SERCA2a水平降低（中位数0.430 ng/mL[四分位间距，0.260 - 0.945]对比0.830 ng/mL[四分位间距，0.582 - 1.052]；P = 0.001）。受试者工作特征曲线分析显示SERCA2a可区分有PGD和无PGD的患者（曲线下面积[AUC]=0.682；P = 0.001），且截断点≥0.60 ng/mL是PGD的保护性独立预测因子（比值比0.215[P = 0.004]）。本研究中PGD的三个独立预测因子是HT前SERCA2a水平降低、胆红素水平升高以及短期机械循环支持过渡到移植。该模型的受试者工作特征曲线分析得到显著的AUC 0.788，P = 0.0001。
我们的研究结果表明，评估血浆中SERCA2a水平可能改善PGD发生的风险预测，并可被视为HT患者一种新的无创生物标志物。
