Baron Kaitlin B, Brown Jennifer R, Heiss Brian L, Marshall Joanne, Tait Nancy, Tkaczuk Katherine H R, Gottlieb Stephen S
University of Maryland School of Medicine, Divisions of Cardiology and Hematology/Oncology, Department of Medicine, Baltimore, MD.
University of Maryland School of Medicine, Divisions of Cardiology and Hematology/Oncology, Department of Medicine, Baltimore, MD.
J Card Fail. 2014 Aug;20(8):555-9. doi: 10.1016/j.cardfail.2014.05.012. Epub 2014 Jun 4.
Although it is known that trastuzumab causes cardiotoxicity, its extent and reversibility are still in question. Earlier studies have not evaluated consecutive patients with reproducible nuclear ventriculography.
We sought to evaluate the baseline characteristics which predispose patients to increased risk of trastuzumab cardiotoxicity and to determine the natural history of the cardiotoxicity.
Left ventricular ejection fraction (LVEF) was measured in 76 women aged 36-73 years who had been treated with trastuzumab at the University of Maryland Greenebaum Cancer Center. LVEF was determined at baseline and then 3, 6, 9, and 12 months after treatment initiation. Cardiotoxicity was defined as ≥ 16% decrease in LVEF or ≥ 10% decrease in LVEF to <50%. There were no differences in comorbidities, earlier treatment, or demographics between patients with and without trastuzumab-induced cardiomyopathy except that African Americans were more likely to develop decreased LVEF (P < .05). Twenty-one patients (28%) met criteria for cardiotoxicity. Four of those patients were continued on trastuzumab and 17 patients had therapy withheld at some point. Only 1 patient developed symptomatic heart failure requiring inpatient hospitalization. LVEF improved in most patients regardless of whether or not trastuzumab was continued.
Decreased LVEF while undergoing trastuzumab therapy occurs frequently and is usually reversible. African Americans had a higher risk of developing decreased LVEF. These findings raise clinically important questions as to whether it is necessary to discontinue trastuzumab for asymptomatic decrease in LVEF and whether African Americans are more predisposed to a decrease in LVEF while receiving trastuzumab. Further studies carefully assessing LVEF should address these hypotheses.
尽管已知曲妥珠单抗会导致心脏毒性，但其程度和可逆性仍存在疑问。早期研究尚未对连续患者进行可重复的核素心室造影评估。
我们试图评估使患者易发生曲妥珠单抗心脏毒性风险增加的基线特征，并确定心脏毒性的自然病程。
在马里兰大学格林ebaum癌症中心，对76名年龄在36 - 73岁接受曲妥珠单抗治疗的女性进行左心室射血分数（LVEF）测量。在基线时以及治疗开始后的3、6、9和12个月测定LVEF。心脏毒性定义为LVEF降低≥16%或LVEF降低≥10%至<50%。有或无曲妥珠单抗诱导的心肌病患者在合并症、早期治疗或人口统计学方面无差异，只是非裔美国人更易发生LVEF降低（P <.05）。21名患者（28%）符合心脏毒性标准。其中4名患者继续使用曲妥珠单抗，17名患者在某个时间点停止治疗。只有1名患者出现症状性心力衰竭需要住院治疗。无论是否继续使用曲妥珠单抗，大多数患者的LVEF都有所改善。
接受曲妥珠单抗治疗时LVEF降低很常见，且通常是可逆的。非裔美国人发生LVEF降低的风险更高。这些发现引发了关于是否有必要因无症状的LVEF降低而停用曲妥珠单抗以及非裔美国人在接受曲妥珠单抗治疗时是否更易发生LVEF降低的重要临床问题。进一步仔细评估LVEF的研究应解决这些假设。
