Pollak Uri, Zemmour Hai, Shaked Elior, Magenheim Judith, Fridlich Ori, Korach Amit, Serraf Alain E, Mishaly David, Glaser Benjamin, Shemer Ruth, Dor Yuval
Section of Pediatric Critical Care, Hadassah University Medical Center, Jerusalem, Israel.
Pediatric and Congenital Cardiac Surgery, Edmond J. Safra International Congenital Heart Center, The Edmond and Lily Safra Children's Hospital, The Chaim Sheba Medical Center, Tel Hashomer, Israel.
J Cardiovasc Transl Res. 2023 Feb;16(1):199-208. doi: 10.1007/s12265-022-10295-0. Epub 2022 Aug 17.
The use of cardiopulmonary bypass (CPB) is thought to cause delayed cardiac damage. DNA methylation-based liquid biopsies are novel biomarkers for monitoring acute cardiac cell death. We assessed cell-free DNA molecules as markers for cardiac damage after open-heart surgery. Novel cardiomyocyte-specific DNA methylation markers were applied to measure cardiac cfDNA in the plasma of 42 infants who underwent open-heart surgery. Cardiac cfDNA was elevated following surgery, reflecting direct surgery-related tissue damage, and declined thereafter in most patients. The concentration of cardiac cfDNA post-surgery correlated with the duration of CPB and aortic cross clamping. Strikingly, cardiac cfDNA at 6 h predicted duration of mechanical ventilation and maximal vasoactive-inotropic score better than did maximal troponin levels. Cardiac cfDNA reveals heart damage associated with CPB, and can be used to monitor cardiac cell death, to predict clinical outcome of surgery and to assess performance of cardioprotective interventions.
体外循环（CPB）的使用被认为会导致迟发性心脏损伤。基于DNA甲基化的液体活检是监测急性心脏细胞死亡的新型生物标志物。我们评估了无细胞DNA分子作为心脏直视手术后心脏损伤的标志物。将新型心肌细胞特异性DNA甲基化标志物应用于测量42例接受心脏直视手术婴儿血浆中的心脏游离DNA（cfDNA）。术后心脏cfDNA升高，反映了与手术直接相关的组织损伤，此后大多数患者的cfDNA下降。术后心脏cfDNA浓度与CPB持续时间和主动脉交叉阻断时间相关。令人惊讶的是，术后6小时的心脏cfDNA比最大肌钙蛋白水平能更好地预测机械通气时间和最大血管活性药物评分。心脏cfDNA揭示了与CPB相关的心脏损伤，可用于监测心脏细胞死亡、预测手术临床结局以及评估心脏保护干预措施的效果。
