Carnitine and Cardiac Dysfunction in Childhood Cancer Survivors Treated with Anthracyclines
Carnitine and Cardiac Dysfunction in Childhood Cancer Survivors Treated with Anthracyclines
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DOI：
10.1158/1055-9965.epi-13-1384
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发表时间：
2014-06-01
影响因子：
3.8
通讯作者：
Bhatia, Smita
中科院分区：
文献类型：
--
作者：
Armenian, Saro H.;Gelehrter, Sarah K.;Bhatia, Smita
与一般人群相比，儿童癌症幸存者发生充血性心力衰竭（CHF）的风险较高，且CHF风险随蒽环类药物剂量呈剂量依赖性增加。这种情况发生的机制尚未完全阐明。代谢组学是对小分子代谢物的综合分析，具有深入了解疾病状态的发病机制和发现治疗靶点的诊断标志物的潜力。我们对150例既往接受过蒽环类药物治疗的无症状儿童癌症幸存者进行了超声心动图检测和血浆代谢组学分析（8种途径; 354种代谢物）。从癌症诊断到参与研究的中位时间为12.4年（2.6-37.9年）; 64%的患者接受了血液恶性肿瘤治疗;蒽环类药物的中位剂量为350 mg/m2（25-642 mg/m2）。35例（23%）参与者有心脏功能障碍，定义为超声心动图显示的左心室收缩末期室壁应力>2SD。三种代谢途径（碳水化合物，氨基酸和脂质代谢）中的15种化合物的血浆水平在心功能不全和收缩功能正常的个体之间存在显著差异。校正多重比较后，心功能不全患者血浆肉毒碱水平显著低于收缩功能正常者[相对比值（RR）为0.89; P < 0.01]。这些研究结果可能有助于制定一级预防（蒽环类药物给药前/给药期间治疗肉毒碱缺乏症）和二级预防策略（筛选和治疗长期存活者），在CHF的风险最高的患者。(C)2014年AACR。
Childhood cancer survivors are at high risk of developing congestive heart failure (CHF) compared with the general population, and there is a dose-dependent increase in CHF risk by anthracycline dose. The mechanism by which this occurs has not been fully elucidated. Metabolomics, the comprehensive profile of small-molecule metabolites, has the potential to provide insight into the pathogenesis of disease states and discover diagnostic markers for therapeutic targets. We performed echocardiographic testing and blood plasma metabolomic analyses (8 pathways; 354 metabolites) in 150 asymptomatic childhood cancer survivors previously treated with anthracyclines. Median time from cancer diagnosis to study participation was 12.4 years (2.6-37.9 years); 64% were treated for a hematologic malignancy; median anthracycline dose was 350 mg/m(2) (25-642 mg/m(2)). Thirty-five (23%) participants had cardiac dysfunction-defined as left ventricular end-systolic wall stress >2SD by echocardiogram. Plasma levels of 15 compounds in three metabolic pathways (carbohydrate, amino acid, and lipid metabolism) were significantly different between individuals with cardiac dysfunction and those with normal systolic function. After adjusting for multiple comparisons, individuals with cardiac dysfunction had significantly lower plasma carnitine levels [relative ratio (RR), 0.89; P < 0.01] in relation to those with normal systolic function. These findings may facilitate the development of primary prevention (treatment of carnitine deficiency before/during anthracycline administration) and secondary prevention strategies (screening and treatment in long-term survivors) in patients at highest risk for CHF. (C) 2014 AACR.