Independent and Incremental Value of Deformation Indices for Prediction of Trastuzumab-Induced Cardiotoxicity
Independent and Incremental Value of Deformation Indices for Prediction of Trastuzumab-Induced Cardiotoxicity
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DOI：
10.1016/j.echo.2013.02.008
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发表时间：
2013-05-01
影响因子：
6.5
通讯作者：
Marwick, Thomas H.
中科院分区：
文献类型：
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作者：
Negishi, Kazuaki;Negishi, Tomoko;Marwick, Thomas H.
背景：在以曲妥珠单抗为基础的化疗期间，由于潜在的心脏毒性，评估左心室收缩功能是必要的。变形指数已被提出作为临床危险因素和射血分数（EF）的辅助，但最佳参数和最佳截止值是不确定的。本研究的目的是确定早期检测的最佳手段，随后减少EF的乳腺癌患者治疗trastuzumab.Methods：81连续妇女（平均年龄50 +/- 11岁）接受曲妥珠单抗进行了前瞻性研究，其中37人同时接受蒽环类药物。在基线、6个月和12个月时测量常规超声心动图指数（二尖瓣环收缩[s ']和舒张[e']速度）和心肌变形指数（总体纵向收缩期峰值应变[GLS]、总体纵向收缩期峰值应变率[GLSR-S]和总体纵向舒张早期应变率[GLSR-E]）。结果：在24例（30%）后来发生心脏毒性的患者中，心肌变形指数在6个月时下降（GLS，P <0.001; GLSR-S，P = 0.009; GLSR-E，P = 0.002 vs基线），但e'不变。心脏毒性的最强预测因子是Delta GLS（曲线下面积，0.84）;降低11%（95%置信区间，8.3%-14.6%）是最佳临界值，灵敏度为65%，特异性为94%。在序贯模型中，GLSR-S（chi（2）= 14.7，P = 0.03）改善了临床模型（chi（2）= 10.2），GLSR-E（chi（2）= 18.0，P = 0.005）或GLS（chi（2）= 21.3，P = 0.0008）改善更明显。通过添加GLS的辨别力改善被证实为18.6%的综合辨别力改善（95%置信区间，8.6%-28.6%; P = .0003）。净29%未发生事件的患者被重新分类为低风险类别，净48%发生事件的患者被重新分类为高风险类别，导致总持续净重新分类改善（>0）为0.77（95%可信区间，0.33-1.22; P = 0.036）结论：GLS是EF后期降低的独立早期预测因子，在有曲妥珠单抗诱导心脏毒性风险的患者中，GLS增加到通常的预测因子。
Background: Assessment of left ventricular systolic function is necessary during trastuzumab-based chemotherapy because of potential cardiotoxicity. Deformation indices have been proposed as an adjunct to clinical risk factors and ejection fraction (EF), but the optimal parameter and optimal cutoffs are undefined. The aim of this study was to determine the best means of early detection of subsequent reduction of EF in patients with breast cancer treated with trastuzumab.Methods: Eighty-one consecutive women (mean age, 50 +/- 11 years) receiving trastuzumab were prospectively studied, 37 of whom received concurrent anthracyclines. Conventional echocardiographic indices (mitral annular systolic [s'] and diastolic [e'] velocities) and myocardial deformation indices (global longitudinal peak systolic strain [GLS], global longitudinal peak systolic strain rate [GLSR-S], and global longitudinal early diastolic strain rate [GLSR-E]) were measured at baseline and at 6 and 12 months. Cardiotoxicity was defined as a > 10% decline as a percentage of baseline EF in 12 months.Results: In the 24 patients (30%) who later developed cardiotoxicity, myocardial deformation indices decreased at 6 months (GLS, P < .001; GLSR-S, P = .009; GLSR-E, P = .002 vs baseline), but e' was unchanged. The strongest predictor of cardiotoxicity was Delta GLS (area under the curve, 0.84); an 11% reduction (95% confidence interval, 8.3%-14.6%) was the optimal cutoff, with sensitivity of 65% and specificity of 94%. In sequential models, the clinical model (chi(2) = 10.2) was improved by GLSR-S (chi(2) = 14.7, P = .03) and even more so by GLSR-E (chi(2) = 18.0, P = .005) or GLS (chi(2) = 21.3, P = .0008). Discrimination improvement by adding GLS was confirmed by an integrated discrimination improvement of 18.6% (95% confidence interval, 8.6%-28.6%; P = .0003). A net 29% of the patients without events were reclassified into lower risk categories, and a net 48% of the patients with events were reclassified into higher risk categories, resulting in a total continuous net reclassification improvement (>0) of 0.77 (95% confidence interval, 0.33-1.22; P = .036).Conclusions: GLS is an independent early predictor of later reductions in EF, incremental to usual predictors in patients at risk for trastuzumab-induced cardiotoxicity.