Background:We investigated the role of a high-sensitive cardiac troponin T (hsTnT) increase below the upper limit of normal (ULN) in patients with breast cancer (BC). hsTnT assays accurately quantify very low plasma troponin concentrations and enable the early detection of cardiomyocyte injury before a drop in the left ventricular ejection fraction (LVEF). The increase in hsTnT below the ULN in response to chemotherapy has not previously been studied.Method:This was an open-label pilot study. Female patients with newly diagnosed BC scheduled to receive systemic cancer treatment were recruited. Blood sampling and echocardiography were performed at baseline, at 3 and 6 months of cancer treatment. hsTnT concentrations were measured using the Elecsys TnT hs assay (Roche Diagnostics). The limit of blank and 99th percentile cutoff values for the hsTnT assay were 3 and 14 ng/L. We calculated the rise in hsTnT (ΔhsTnT) by the difference (%) between its baseline level and during follow-up (FU) in each patient.Results:Among eligible subjects, we excluded 4 patients before the start of treatment and 17 patients during the follow-up with values for the hsTnT >14 ng/L. Finally, 60 women with a median age of 48.6 ± 1.3 years were included in the study. The median baseline hsTnT concentration was 5.5 ± 1.4 ng/L. During 6 months of cancer treatment, hsTnT increased in all patients by up to 10–305% from baseline, with an average of 94.2%. LV EF was normal at baseline and decreased significantly compared to the value before cancer treatment (61.9 ± 3.3% vs. 56.3 ± 7.0%;p< 0.045). We correlated the hsTnT rise with a drop in LV EF ≥ 10% from its baseline level. Logistic regression analysis showed that Δ hsTnT has a good predictive value for LV dysfunction, 0.78 (p= 0.05), 95% CI (0.67–0.90). The increase in hsTnT > 81% was determined as the optimal threshold value for detecting early biochemical cardiotoxicity.Conclusion:It was investigated that hsTnT rise within the cutoff < 14 ng/L can be used as a marker of early biochemical cardiotoxicity and is valuable for predicting LV drop in 6 months of FU. We conclude that BC patients with increased hsTnT plasma concentration > 81% from the baseline value should be considered as high-risk patients for cardiotoxicity and need more precise cardiac monitoring and early preventive medical intervention strategies.
背景：本研究探讨了高敏心肌肌钙蛋白T（hsTnT）在乳腺癌患者中低于正常值上限（ULN）的升高所起的作用。hsTnT检测能够精确量化极低浓度的血浆肌钙蛋白，从而在左心室射血分数（LVEF）下降之前实现心肌细胞损伤的早期识别。此前尚未对化疗引起的hsTnT低于ULN的升高进行过研究。 方法：本研究为一项开放性初步研究。招募了计划接受系统性癌症治疗的新诊断乳腺癌女性患者。在基线、癌症治疗3个月和6个月时分别进行血液采样和超声心动图检查。采用Elecsys TnT hs检测法（罗氏诊断）测定hsTnT浓度。该hsTnT检测的空白限和99百分位临界值分别为3 ng/L和14 ng/L。我们通过计算每位患者基线水平与随访期间hsTnT水平的差值百分比，得出hsTnT的升高值（ΔhsTnT）。 结果：在符合条件的受试者中，我们排除了治疗开始前hsTnT >14 ng/L的4名患者以及随访期间hsTnT >14 ng/L的17名患者。最终，60名中位年龄为48.6 ± 1.3岁的女性被纳入研究。基线hsTnT浓度中位数为5.5 ± 1.4 ng/L。在6个月的癌症治疗期间，所有患者的hsTnT均较基线升高10–305%，平均升高94.2%。基线时LVEF正常，但与癌症治疗前相比显著下降（61.9 ± 3.3% vs. 56.3 ± 7.0%；p < 0.045）。我们将hsTnT升高与LVEF较基线下降≥ 10%相关联。Logistic回归分析显示，ΔhsTnT对左心室功能障碍具有良好的预测价值，AUC为0.78（p = 0.05），95% CI（0.67–0.90）。hsTnT升高 > 81%被确定为检测早期生化心脏毒性的最佳阈值。 结论：研究发现，hsTnT在临界值< 14 ng/L范围内的升高可作为早期生化心脏毒性的标志物，并对预测6个月随访期内左心室功能下降具有价值。我们得出结论，血浆hsTnT浓度较基线升高 > 81%的乳腺癌患者应被视为心脏毒性高风险患者，需要更精确的心脏监测和早期预防性医疗干预策略。
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