Anthracycline Therapy Is Associated With Cardiomyocyte Atrophy and Preclinical Manifestations of Heart Disease.
Anthracycline Therapy Is Associated With Cardiomyocyte Atrophy and Preclinical Manifestations of Heart Disease.
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DOI：
10.1016/j.jcmg.2018.05.012
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发表时间：
2018-08
期刊：
影响因子：
--
通讯作者：
Coelho-Filho OR
中科院分区：
文献类型：
--
作者：
Ferreira de Souza T;Quinaglia A C Silva T;Osorio Costa F;Shah R;Neilan TG;Velloso L;Nadruz W;Brenelli F;Sposito AC;Matos-Souza JR;Cendes F;Coelho OR;Jerosch-Herold M;Coelho-Filho OR
本研究的目的是证明心脏磁共振可以揭示蒽环类药物诱导的早期组织重构及其与心功能不全和左心室（LV）萎缩的关系。心功能不全的血清生物标志物，尽管在化疗后升高，但对心肌组织改变的机制缺乏特异性。共有27例乳腺癌女性患者（平均年龄51.8 ± 8.9岁，平均体重指数26.9 ± 3.6 kg/m2）在蒽环类药物治疗前和治疗后接受了3次心脏磁共振检查。心脏磁共振变量包括左心室射血分数、心肌水肿的标准化T2加权信号强度、细胞外容积（ECV）、左心室心肌细胞质量、细胞内水寿命（τic;心肌细胞大小的标志物）和晚期钆增强。基线时，患者的心血管事件风险相对较低（10年）（中位数5%），LV射血分数正常（平均69.4 ± 3.6%），LV质量指数正常（51.4 ± 8.0 g/m2），平均ECV为0.32 ± 0.038，平均τic为169 ± 69 ms，无晚期钆增强。蒽环类药物治疗后351 - 700天（240 mg/m2），平均LV射血分数下降12%至58 ± 6%（p < 0.001），平均LV质量指数从19 g/m2降至36 ± 6 g/m2（p < 0.001），平均ECV增加0.037至0.36 ± 0.04（p = 0.004），而平均τic减少62 ms至119 ± 54 ms（p = 0.004）。心肌水肿在146 ~ 231天达到高峰（p < 0.001）。LV质量指数与τic相关（τic每增加100 ms，β = 4.1 ± 1.5 g/m2，p = 0.007），但与ECV无关。心肌肌钙蛋白T（基线时平均4.6 ± 1.4 pg/ml）在蒽环类药物治疗后显著升高（p < 0.001）。总左心室心肌细胞质量，估计为：（1 - ECV）×左心室质量，蒽环类药物治疗后下降更快，峰值心肌肌钙蛋白T >10 pg/ml。没有证据表明10年心血管事件风险与蒽环类药物治疗效果之间存在任何显著的相互作用。蒽环类药物治疗后左室质量的减少可能是由于心肌细胞萎缩，这表明除了间质纤维化和水肿以外的机制可以提高ECV。蒽环类药物治疗后，心肌肌钙蛋白T峰值评估显示，左室心肌细胞质量损失随心肌细胞损伤程度增加而增加。（乳腺癌患者中多柔比星相关心脏重塑伴CMR; NCT 03000036）（J Am科尔Cardiol Img 2018;11：1045-55）© 2018由美国心脏病学会基金会提供。
The goal of this study was to demonstrate that cardiac magnetic resonance could reveal anthracycline-induced early tissue remodeling and its relation to cardiac dysfunction and left ventricular (LV) atrophy. Serum biomarkers of cardiac dysfunction, although elevated after chemotherapy, lack specificity for the mechanism of myocardial tissue alterations. A total of 27 women with breast cancer (mean age 51.8 ± 8.9 years, mean body mass index 26.9 ± 3.6 kg/m2), underwent cardiac magnetic resonance before and up to 3 times after anthracycline therapy. Cardiac magnetic resonance variables were LV ejection fraction, normalized T2-weighted signal intensity for myocardial edema, extracellular volume (ECV), LV cardiomyocyte mass, intracellular water lifetime (τic; a marker of cardiomyocyte size), and late gadolinium enhancement. At baseline, patients had a relatively low (10-year) Framingham cardiovascular event risk (median 5%), normal LV ejection fractions (mean 69.4 ± 3.6%), and normal LV mass index (51.4 ± 8.0 g/m2), a mean ECV of 0.32 ± 0.038, mean τic of 169 ± 69 ms, and no late gadolinium enhancement. At 351 to 700 days after anthracycline therapy (240 mg/m2), mean LV ejection fraction had declined by 12% to 58 ± 6% (p < 0.001) and mean LV mass index by 19 g/m2 to 36 ± 6 g/m2 (p < 0.001), and mean ECV had increased by 0.037 to 0.36 ± 0.04 (p = 0.004), while mean τic had decreased by 62 ms to 119 ± 54 ms (p = 0.004). Myocardial edema peaked at about 146 to 231 days (p < 0.001). LV mass index was associated with τic (β = 4.1 ± 1.5 g/m2 per 100-ms increase in τic, p = 0.007) but not with ECV. Cardiac troponin T (mean 4.6 ± 1.4 pg/ml at baseline) increased significantly after anthracycline treatment (p < 0.001). Total LV cardiomyocyte mass, estimated as: (1 - ECV) × LV mass, declined more rapidly after anthracycline therapy, with peak cardiac troponin T >10 pg/ml. There was no evidence for any significant interaction between 10-year cardiovascular event risk and the effect of anthracycline therapy. A decrease in LV mass after anthracycline therapy may result from cardiomyocyte atrophy, demonstrating that mechanisms other than interstitial fibrosis and edema can raise ECV. The loss of LV cardiomyocyte mass increased with the degree of cardiomyocyte injury, assessed by peak cardiac troponin T after anthracycline treatment. (Doxorubicin-Associated Cardiac Remodeling Followed by CMR in Breast Cancer Patients; NCT03000036) (J Am Coll Cardiol Img 2018;11:1045–55) © 2018 by the American College of Cardiology Foundation.
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DOI：
10.1186/1532-429x-13-13
发表时间：
2011-02-18
期刊：
Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance
影响因子：
--
作者：
Eitel I;Friedrich MG
通讯作者：
Friedrich MG
健康志愿者和小鼠的T1测量值的心肌外体积分数：与衰老和心脏维度的关系。
影响因子：
14
作者：
Neilan, Tomas G.;Coelho-Filho, Otavio R.;Shah, Ravi V.;Abbasi, Siddique A.;Heydari, Bobak;Watanabe, Eri;Chen, Yucheng;Mandry, Damien;Pierre-Mongeon, Francois;Blankstein, Ron;Kwong, Raymond Y.;Jerosch-Herold, Michael
通讯作者：
Jerosch-Herold, Michael
影响因子：
--
作者：
Carbone I;Childs H;Aljizeeri A;Merchant N;Friedrich MG
通讯作者：
Friedrich MG
影响因子：
4
作者：
Kitayama, Hiromitsu;Kondo, Tomohiro;Tsuji, Yasushi
通讯作者：
Tsuji, Yasushi
DOI：
10.1152/ajpregu.00082.2014
发表时间：
2014-09-15
影响因子：
2.8
作者：
Sturgeon, Kathleen;Schadler, Keri;Libonati, Joseph R.
通讯作者：
Libonati, Joseph R.