Utility of Tissue Doppler and Strain Rate Imaging in the Early Detection of Trastuzumab and Anthracycline Mediated Cardiomyopathy
Utility of Tissue Doppler and Strain Rate Imaging in the Early Detection of Trastuzumab and Anthracycline Mediated Cardiomyopathy
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DOI：
10.1016/j.echo.2009.01.016
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发表时间：
2009-04-01
影响因子：
6.5
通讯作者：
Singal, Pawan K.
中科院分区：
文献类型：
--
作者：
Jassal, Davinder S.;Han, Song-Yee;Singal, Pawan K.
背景：曲妥珠单抗在乳腺癌的辅助治疗中提供了相当大的疗效。然而，当与阿霉素联合使用时，其心脏毒性的发生率增加而限制了其使用。虽然Myocet(脂质体包裹的阿霉素)对心脏的毒性较小，但其与曲妥珠单抗的心脏安全性还不是很清楚。这项研究的目的是确定左心功能不全的敏感指标，特别是多普勒组织成像(DTI)是否有助于早期发现曲妥珠单抗和蒽环类药物介导的心脏毒性。方法：在急性小鼠模型中，野生型C57BI/6小鼠(n=60)接受以下药物方案之一：(1)对照组，(2)阿霉素，(3)Myocet，(4)曲妥珠单抗，(5)阿霉素+曲妥珠单抗，或(6)Myocet+曲妥珠单抗。连续5天测量DTI测量的心内膜收缩峰值速度、应变率和左心室射血分数。第5天处死小鼠，取心脏、肺和肝脏进行组织病理学和免疫印迹分析。结果：与阿霉素加曲妥珠单抗治疗组相比，Myocet+曲妥珠单抗治疗组小鼠心脏毒性最小。在阿霉素联合曲妥珠单抗治疗的第4天，观察到进行性的左室扩张和左室收缩功能障碍，并与其余组保留的左室射血分数进行比较。在阿霉素单独用药组和阿霉素加曲妥珠单抗治疗组，DTI参数在24小时内降低，并预测早期死亡率。在实验第5天，阿霉素+曲妥珠单抗组的存活率仅为20%，而接受曲妥珠单抗、Myocet或Myocet+曲妥珠单抗的小鼠的存活率为100%。结论：DTI可以在常规超声心动图指标改变之前发现早期左心功能不全，并预测接受阿霉素+曲妥珠单抗的小鼠的早期死亡率。(J Am Soc超声心动图2009；22：418-424。)
Background: Trastuzumab provides considerable therapeutic benefits in the adjuvant setting of breast cancer. However, its use is limited by an elevated incidence of cardiotoxicity when used in combination with doxorubicin. Although Myocet (liposomal encapsulated doxorubicin) is less cardiotoxic, its cardiac safety profile with trastuzumab is not well known. The aim of this study was to determine if sensitive indices of left ventricular (LV) dysfunction, specifically Doppler tissue imaging (DTI), would be useful for addressing the early detection of trastuzumab and anthracycline-mediated cardiotoxicity.Methods: In an acute murine model, wild-type C57BI/6 mice (n = 60) received one of the following drug regimens: (1) control, (2) doxorubicin, (3) Myocet, (4) trastuzumab, (5) doxorubicin plus trastuzumab, or (6) Myocet plus trastuzumab. DTI-derived peak endocardial systolic velocity, strain rate, and LV ejection fraction were measured serially for 5 days. On day 5, the hearts, lungs, and livers were removed for histopathologic and Western blot analyses.Results: Mice treated with Myocet plus trastuzumab demonstrated minimal cardiotoxicity compared with those treated with doxorubicin plus trastuzumab. Progressive LV dilatation and LV systolic dysfunction were observed by day 4 of treatment with doxorubicin plus trastuzumab, compared with preserved LV ejection fraction in the remaining groups. DTI parameters decreased within 24 hours in the doxorubicin alone and doxorubicin plus trastuzumab groups and predicted early mortality. The survival rate was only 20% at day 5 of the experiment in the doxorubicin plus trastuzumab group, whereas 100% of mice receiving trastuzumab, Myocet, or Myocet plus trastuzumab survived the 5 days.Conclusion: DTI can detect early LV dysfunction prior to alterations in conventional echocardiographic indices and predicts early mortality in mice receiving doxorubicin plus trastuzumab. (J Am Soc Echocardiogr 2009;22:418-424.)