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接受长春新碱治疗的儿童癌症幸存者的心脏功能:DCCSS LATER 2 CARD 研究的超声心动图结果。

Cardiac function in childhood cancer survivors treated with vincristine: Echocardiographic results from the DCCSS LATER 2 CARD study.

机构信息

Department of Medical Imaging/Radiology, Medical UltraSound Imaging Centre, Radboud Institute for Health Sciences, Radboud university medical center, Nijmegen, the Netherlands.

Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.

出版信息

Int J Cardiol. 2022 Dec 15;369:69-76. doi: 10.1016/j.ijcard.2022.07.049. Epub 2022 Aug 1.

Abstract

BACKGROUND

Anthracyclines and radiotherapy involving the heart region are cardiotoxic, but the potential cardiotoxicity of vincristine remains unknown. We assessed cardiac function in vincristine-treated >5-year childhood cancer survivors (CCS).

METHODS AND RESULTS

We cross-sectionally compared echocardiograms of 101 vincristine-treated CCS (median age 35 years [range: 17-53], median vincristine dose 63 mg/m) from the national Dutch Childhood Cancer Survivor Study, LATER cohort, to 101 age- and sex-matched controls. CCS treated with anthracyclines, radiotherapy involving the heart region, cyclophosphamide or ifosfamide were excluded. Twelve CCS (14%) versus four controls (4%; p 0.034) had a decreased left ventricular ejection fraction (LVEF; men <52%, women <54%). Mean LVEF was 58.4% versus 59.7% (p 0.050). Global longitudinal strain (GLS) was abnormal in nineteen (24%) CCS versus eight controls (9%; p 0.011). Mean GLS was 19.0% versus 20.1% (p 0.001). No ≥grade 2 diastolic dysfunction was detected. In multivariable logistic regression analysis CCS had higher risk of abnormal GLS (OR 3.55, p 0.012), but not abnormal LVEF (OR 3.07, p 0.065), than controls. Blood pressure and smoking history contributed to variation in LVEF, whereas obesity and diastolic blood pressure contributed to variation in GLS. Cumulative vincristine dose was not associated with either abnormal LVEF or abnormal GLS in multivariable models corrected for age and sex (OR per 50 mg/m: 0.88, p 0.85 and 1.14, p 0.82, respectively).

CONCLUSIONS

Vincristine-treated long-term CCS showed an abnormal GLS more frequently than controls. Their risk for future clinical cardiac events and the role of risk factor modification should be further elucidated.

摘要

背景

蒽环类药物和涉及心脏区域的放射治疗具有心脏毒性,但长春新碱的潜在心脏毒性尚不清楚。我们评估了接受长春新碱治疗的 >5 岁儿童癌症幸存者(CCS)的心脏功能。

方法和结果

我们从全国荷兰儿童癌症幸存者研究 LATER 队列中,对 101 名接受长春新碱治疗的 CCS(中位年龄 35 岁[范围:17-53],中位长春新碱剂量 63mg/m)的超声心动图进行了横断面比较,与 101 名年龄和性别匹配的对照组进行比较。排除接受蒽环类药物、心脏区域放射治疗、环磷酰胺或异环磷酰胺治疗的 CCS。12 名 CCS(14%)与 4 名对照组(4%;p=0.034)的左心室射血分数(LVEF;男性<52%,女性<54%)降低。平均 LVEF 分别为 58.4%和 59.7%(p=0.050)。19 名(24%)CCS 的整体纵向应变(GLS)异常,而 8 名对照组(9%;p=0.011)。平均 GLS 分别为 19.0%和 20.1%(p<0.001)。未发现≥2 级舒张功能障碍。多变量逻辑回归分析显示,CCS 的 GLS 异常风险较高(OR 3.55,p=0.012),但 LVEF 异常风险无差异(OR 3.07,p=0.065)。与对照组相比,CCS 的血压和吸烟史与 LVEF 的变化有关,而肥胖和舒张期血压与 GLS 的变化有关。在多变量模型中,经年龄和性别校正后,累积长春新碱剂量与 LVEF 或 GLS 异常均无相关性(每增加 50mg/m 的 OR:0.88,p=0.85 和 1.14,p=0.82)。

结论

接受长春新碱治疗的长期 CCS 的 GLS 异常比对照组更常见。他们未来发生临床心脏事件的风险以及危险因素修正的作用应进一步阐明。

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