评估超声心动图和生物标志物在接受蒽环类药物、紫杉烷类药物和曲妥珠单抗治疗的患者中心脏毒性的扩展预测。
Assessment of echocardiography and biomarkers for the extended prediction of cardiotoxicity in patients treated with anthracyclines, taxanes, and trastuzumab.
机构信息
Cardiac Ultrasound Laboratory and Division of Cardiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
出版信息
Circ Cardiovasc Imaging. 2012 Sep 1;5(5):596-603. doi: 10.1161/CIRCIMAGING.112.973321. Epub 2012 Jun 28.
BACKGROUND
Because cancer patients survive longer, the impact of cardiotoxicity associated with the use of cancer treatments escalates. The present study investigates whether early alterations of myocardial strain and blood biomarkers predict incident cardiotoxicity in patients with breast cancer during treatment with anthracyclines, taxanes, and trastuzumab.
METHODS AND RESULTS
Eighty-one women with newly diagnosed human epidermal growth factor receptor 2-positive breast cancer, treated with anthracyclines followed by taxanes and trastuzumab were enrolled to be evaluated every 3 months during their cancer therapy (total of 15 months) using echocardiograms and blood samples. Left ventricular ejection fraction, peak systolic longitudinal, radial, and circumferential myocardial strain were calculated. Ultrasensitive troponin I, N-terminal pro-B-type natriuretic peptide, and the interleukin family member (ST2) were also measured. Left ventricular ejection fraction decreased (64 ± 5% to 59 ± 6%; P<0.0001) over 15 months. Twenty-six patients (32%, [22%-43%]) developed cardiotoxicity as defined by the Cardiac Review and Evaluation Committee Reviewing Trastuzumab; of these patients, 5 (6%, [2%-14%]) had symptoms of heart failure. Peak systolic longitudinal myocardial strain and ultrasensitive troponin I measured at the completion of anthracyclines treatment predicted the subsequent development of cardiotoxicity; no significant associations were observed for left ventricular ejection fraction, N-terminal pro-B-type natriuretic peptide, and ST2. Longitudinal strain was <19% in all patients who later developed heart failure.
CONCLUSIONS
In patients with breast cancer treated with anthracyclines, taxanes, and trastuzumab, systolic longitudinal myocardial strain and ultrasensitive troponin I measured at the completion of anthracyclines therapy are useful in the prediction of subsequent cardiotoxicity and may help guide treatment to avoid cardiac side-effects.
背景
由于癌症患者的生存期延长，与癌症治疗相关的心脏毒性的影响也在加剧。本研究旨在探讨在接受蒽环类药物、紫杉烷类药物和曲妥珠单抗治疗的乳腺癌患者中，心肌应变和血液生物标志物的早期改变是否可预测治疗期间发生的心脏毒性。
方法和结果
本研究共纳入 81 例新诊断的人表皮生长因子受体 2 阳性乳腺癌患者，这些患者接受蒽环类药物序贯紫杉烷类药物和曲妥珠单抗治疗，在整个癌症治疗过程中（共 15 个月）每 3 个月接受 1 次超声心动图和血液样本检查。计算左心室射血分数、收缩期峰值纵向、径向和周向心肌应变。还检测了超敏肌钙蛋白 I、氨基末端脑利钠肽前体和白细胞介素家族成员（ST2）。在 15 个月内，左心室射血分数降低（64±5%至 59±6%；P<0.0001）。26 例（32%[22%至 43%]）患者根据心脏审查和评估委员会审查曲妥珠单抗的标准被定义为发生心脏毒性；其中 5 例（6%[2%至 14%]）患者出现心力衰竭症状。蒽环类药物治疗结束时测量的收缩期峰值纵向心肌应变和超敏肌钙蛋白 I 可预测随后发生的心脏毒性；而左心室射血分数、氨基末端脑利钠肽前体和 ST2 与心脏毒性无显著相关性。所有随后发生心力衰竭的患者的纵向应变均<19%。
结论
在接受蒽环类药物、紫杉烷类药物和曲妥珠单抗治疗的乳腺癌患者中，蒽环类药物治疗结束时测量的收缩期峰值纵向心肌应变和超敏肌钙蛋白 I 可用于预测随后发生的心脏毒性，并可能有助于指导治疗以避免心脏副作用。
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