Kouloubinis Alexandros, Sofroniadou Sofia, Panoulas Vasileios F, Makaritsis Konstantinos, Revela Ioanna, Karavolias George, Voudris Vasileios, Adamopoulos Stamatios
Onassis Cardiac Surgery Center, Department of Cardiology, 356 Siggrou Avenue,17674 Athens, Greece.
Center for Nephrology «G.Papadakis», General Hospital of Pireaus, Pireaus, Greece.
Int J Cardiol Heart Vasc. 2015 Jan 9;6:85-90. doi: 10.1016/j.ijcha.2015.01.002. eCollection 2015 Mar 1.
Anthracycline-induced cardiotoxicity typically presents as congestive heart failure (CHF). As immuno-inflammatory activation and apoptosis are important mechanisms in the process of heart failure, the use of biomarkers that could detect cardiovascular toxicity before the clinical presentation is of great importance. We studied whether sTNF-a, sTNF-RI, sTNF-RII, Fas/FasLigand system and NT-proBNP associate with early cardiac dysfunction in patients receiving cardiotoxic drugs.
Two groups of breast cancer patients-group A with metastatic disease under chemotherapy with epirubicin and group B with no residual disease under a less cardiotoxic regimen-as well as healthy women were included in this prosprective study. NT-proBNP, sTNF-a, sTNF-RI, sTNF-RII, sFas, sFas-Ligand and left ventricular ejection fraction (LVEF) were determined in all patients before and after the completion of chemotherapy.
In Group A, an increase in sFas levels ( < 0.001), a decrease in the sFasL levels ( = 0.010), an NT-proBNP increase ( < 0.001) and a significant reduction of LVEF ( < 0.001) was recorded post-chemotherapy. The decrease in LVEF correlated significantly with the increase in sFas, the decrease in sFasL and the rise in NT-proBNP levels. In Group B, TNF-RI levels were higher ( = 0.024) and mean sFas-L levels lower ( = 0.021) post chemotherapy with no LVEF drop. Two of group A (7.6%) patients developed symptomatic CHF 12 and 14 months respectively after the end of chemotherapy.
SFas, sFas-L and NT-proBNP correlate with reductions in LVEF and could be used as sensitive biochemical indices for the detection of asymptomatic left ventricular dysfunction in cancer patients under cardiotoxic chemotherapy.
蒽环类药物引起的心脏毒性通常表现为充血性心力衰竭(CHF)。由于免疫炎症激活和细胞凋亡是心力衰竭过程中的重要机制,因此使用能够在临床表现出现之前检测心血管毒性的生物标志物具有重要意义。我们研究了sTNF-a、sTNF-RI、sTNF-RII、Fas/Fas配体系统和NT-proBNP是否与接受心脏毒性药物治疗的患者早期心脏功能障碍相关。
两组乳腺癌患者——A组为接受表柔比星化疗的转移性疾病患者,B组为接受心脏毒性较小方案治疗且无残留疾病的患者——以及健康女性纳入了这项前瞻性研究。在所有患者化疗开始前和结束后测定NT-proBNP、sTNF-a、sTNF-RI、sTNF-RII、sFas、sFas配体和左心室射血分数(LVEF)。
在A组中,化疗后记录到sFas水平升高(<0.001)、sFasL水平降低(=0.010)、NT-proBNP升高(<0.001)以及LVEF显著降低(<0.001)。LVEF的降低与sFas的升高、sFasL的降低以及NT-proBNP水平的升高显著相关。在B组中,化疗后TNF-RI水平较高(=0.024),平均sFasL水平较低(=0.021),LVEF无下降。A组中有两名(7.6%)患者在化疗结束后分别于12个月和14个月出现了有症状的CHF。
sFas、sFas-L和NT-proBNP与LVEF降低相关,可作为检测接受心脏毒性化疗的癌症患者无症状左心室功能障碍的敏感生化指标。