Carnitine and Cardiac Dysfunction in Childhood Cancer Survivors Treated with Anthracyclines

被引:19
作者
Armenian, Saro H. [1 ]
Gelehrter, Sarah K. [6 ]
Vase, Tabitha [1 ]
Venkatramani, Rajkumar [3 ,5 ]
Landier, Wendy [1 ]
Wilson, Karla D. [1 ]
Herrera, Claudia [1 ]
Reichman, Leah [3 ]
Menteer, John-David [4 ,5 ]
Mascarenhas, Leo [3 ,5 ]
Freyer, David R. [3 ,5 ]
Venkataraman, Kalyanasundaram [2 ]
Bhatia, Smita [1 ]
机构
[1] City Hope Natl Med Ctr, Dept Populat Sci, Div Outcomes Res, Duarte, CA 91010 USA
[2] City Hope Natl Med Ctr, Dept Cardiol, Duarte, CA 91010 USA
[3] Childrens Hosp Los Angeles, Div Hematol Oncol & Blood & Marrow Transplantat, Los Angeles, CA 90027 USA
[4] Childrens Hosp Los Angeles, Div Cardiol, Los Angeles, CA 90027 USA
[5] Univ So Calif, Keck Sch Med, Dept Pediat, Los Angeles, CA 90033 USA
[6] Univ Michigan, CS Mott Childrens Hosp, Dept Pediat & Communicable Dis, Div Pediat Cardiol, Ann Arbor, MI 48109 USA
关键词
DOXORUBICIN THERAPY; PATHOPHYSIOLOGY; TOXICITY;
D O I
10.1158/1055-9965.EPI-13-1384
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:1109 / 1114
页数:6
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