斑点追踪技术监测低剂量蒽环类药物对乳腺癌新辅助化疗患者的心脏毒性

doi:10.3877/cma.j.issn.1672-6448.2021.02.004

目的

应用二维斑点追踪成像（2D-STI）技术评价接受低剂量蒽环类药物治疗的乳腺癌新辅助化疗患者的左心室收缩功能。

方法

选取2018年12月至2020年3月在中国医科大学附属盛京医院应用低剂量蒽环类药物行新辅助化疗的乳腺癌患者49例为化疗组，选取25例与化疗组相匹配的健康志愿者作为对照组。在每次化疗前（t0~t5）、最终手术前（t6）行超声心动图检查，获得常规超声心动图参数。应用Qlab软件对图像进行追踪分析，获得整体纵向应变（GLS）、整体径向应变（GRS）、整体圆周应变（GCS）；心尖扭转角度峰值（AP-Prot）、心底扭转角度峰值（MV-Prot）、左心室整体扭转角度峰值（LV-Tw）。对化疗组化疗前（t0）与对照组各参数、化疗组不同时间点（t0~t6）各参数的差异进行分析比较。

结果

化疗组在化疗前（t0）与对照组左心室各参数比较无明显差异；常规超声心动图参数E/A、左心室射血分数、E/e'在化疗期间较晚发生减低，其中LVEF在t4出现减低，在t0~t6分别为62.4%±2.0%、62.4%±2.0%、62.3%±2.1%、62.0%±2.0%、61.6%±1.8%、61.1%±1.7%、60.2%±1.8%（F=13.533，P＜0.05），t4与t0及t3两两比较的平均值差值分别为0.857和0.548（均P＜0.05）。应变参数GLS、GCS、GRS呈下降趋势，GLS最早在t1开始降低，在t0~t6分别为-22.0%±1.4%、-21.8%±1.4%、-21.1%±1.4%、-20.0%±1.0%、-19.3%±1.1%、-18.7%±1.2%、-18.1%±1.2%（F=62.473，P＜0.05），t1与t0比较的平均值差值为0.224（P＜0.05）；扭转参数MV-Prot的绝对值在t0~t6无明显变化（P＞0.05），AP-Prot和LV-Tw的绝对值均在t1出现降低，以AP-Prot最明显（t1 vs t0：P＜0.05）。

结论

2D-STI监测新辅助化疗期间低剂量蒽环类药物导致的心脏毒性具有重要价值，GLS和AP-Prot是最敏感的指标。

关键词: 乳腺肿瘤, 斑点追踪, 左心室功能, 二维应变, 扭转

Objective

To investigate the value of two-dimensional speckle tracking imaginein detecting the myocardial dysfunction of the left ventriclein patients with breast cancer during neoadjuvant chemotherapy with anthracyclines (ANT).

Methods

A total of 49 female patients who received ANT treatment (ANT group) at Shengjing Hospital of China Medical University from December 2018 to March 2020 and 25 healthy volunteers (control group) were collected. Echocardiography was performed before every episode of chemotherapy (t0-t5) and before surgery (t6) to obtain routine echocardiographic parameters. Speckle tracking software was used to analyze the general parameters, including global longitudinal strain (GLS), global radial strain (GRS), global circumferential strain (GCS), apical peak rotation (AP-Prot), mitral valvular peak rotation (MV-Prot), and left ventricular twist (LV-Tw). Parameters were compared among different timepoints and between the two groups.

Results

There was no significant difference in left ventricular parameters between the ANT group (t0) and the control group. The general echocardiography parameters E/A, left ventricular ejection fraction (LVEF), and E/e' decreased, among which LVEF decreased significantly at t4. LVEF values were 62.4%±2.0%, 62.4%±2.0%, 62.3%±2.1%, 62.0%±2.0%, 61.6%±1.8%, 61.1%±1.7%, and 60.2%±1.8% at t0 to t6,respectively (F=13.533, P＜0.05), and the mean difference between t4 and t0 and between t4 and t3 was 0.857 and 0.548, respectively (P＜0.05 for both). The strain parameters including GLS, GCS, and GRS showed a downward trend. GLS began to decrease at t1, and it was -22.0%±1.4%, -21.8%±1.4%, -21.1%±1.4%, -20.0%±1.0%, -19.3%±1.1%, -18.7%±1.2%, and -18.1%±1.2%at t0 to t6,respectively (F=62.473, P＜0.05), and the mean difference between t1 and t0 was 0.224 (P＜0.05). The absolute value of torsion parameter MV-prot did not change significantly. The absolute values of AP-prot and LV-TW decreased at t1. AP-prot decreased most obviously （t1 vs t0: P＜0.05).

Conclusion

Speckle tracking imaging is of great value in monitoring the cardiotoxicity caused by low dose ANT during neoadjuvant chemotherapy. GLS and AP-Protarethe most sensitive indicators to evaluate the cardiac injury in breast cancer patients receiving low dose ANT.

Key words: Breast neoplasms, Speckle tracking, Left ventricular function, Two-dimensional strain, Torsion

表1 对照组与化疗组一般资料比较 [

x ˉ

±s或例(%)]

临床资料	对照组	化疗组	t值	P值
例数	25	49
年龄(岁)	49±9	51±7	0.880	0.382
BSA(m²)	1.6±0.8	1.6±0.9	0.877	0.383
BMI(kg/m²)	20.3±2.0	20.3±2.1	-0.074	0.941
病理类型
浸润性导管癌	-	40(81.6)	-	-
浸润性小叶癌	-	9(18.4)	-	-
ANT剂量(mg/m²)
单次剂量	-	75~80	-	-
累积剂量	-	450~480	-	-
收缩压(mmHg)	114±10	113±9	-0.295	0.769
舒张压(mmHg)	77±5	76±5	-0.088	0.110
心率(次/分)	73±7	72±8	-0.132	0.895
脑钠肽(μg/L)	73±24	79±22	-1.032	0.306

表1 对照组与化疗组一般资料比较 [

x ˉ

±s或例(%)]

临床资料	对照组	化疗组	t值	P值
例数	25	49
年龄(岁)	49±9	51±7	0.880	0.382
BSA(m²)	1.6±0.8	1.6±0.9	0.877	0.383
BMI(kg/m²)	20.3±2.0	20.3±2.1	-0.074	0.941
病理类型
浸润性导管癌	-	40(81.6)	-	-
浸润性小叶癌	-	9(18.4)	-	-
ANT剂量(mg/m²)
单次剂量	-	75~80	-	-
累积剂量	-	450~480	-	-
收缩压(mmHg)	114±10	113±9	-0.295	0.769
舒张压(mmHg)	77±5	76±5	-0.088	0.110
心率(次/分)	73±7	72±8	-0.132	0.895
脑钠肽(μg/L)	73±24	79±22	-1.032	0.306

表2 化疗组与对照组常规超声心动图参数比较（

x ˉ

±s）

参数	对照组(n=25)	化疗组(n=49)							F值	P值
参数	对照组(n=25)	t0	t1	t2	t3	t4	t5	t6	F值	P值
IVSTd(mm)	7.8±0.5	7.4±0.7	7.5±0.7	7.5±0.7	7.5±0.7	7.5±0.7	7.5±0.7	7.5±0.7	0.873	0.522
PWTd(mm)	7.3±0.8	7.4±0.8	7.3±0.8	7.3±0.7	7.3±0.8	7.4±0.8	7.4±0.8	7.3±0.8	0.506	0.800
LVDd(mm)	45.8±2.5	45.6±2.7	45.8±2.7	45.8±2.6	45.8±2.9	45.7±2.5	45.8±2.5	46.0±2.5	1.279	0.287
LVDs(mm)	26.8±2.0	26.9±1.9	26.8±1.8	26.9±1.8	26.9±1.8	26.9±1.5	26.8±2.1	27.1±1.6	1.081	0.389
LVEF(%)	62.3±2.1	62.4±2.0	62.4±2.0	62.3±2.1	62.0±2.0	61.6±1.8^abc	61.1±1.7^abc	60.2±1.8^abc	13.533	0.000
E(cm/s)	76.1±8.6	75.3±8.7	75.2±9.2	75.8±6.0	74.1±6.2	75.0±6.9	73.1±7.7	73.1±7.0	1.062	0.400
A(cm/s)	58.4±9.4	58.5±9.1	59.1±9.5	58.6±8.6	58.6±7.7	58.9±9.9	58.9±8.9	60.2±16.6	1.600	0.170
E/A	1.32±0.22	1.31±0.19	1.31±0.27	1.31±0.38	1.30±0.16	1.28±0.10	1.28±0.19	1.27±0.25^ac	13.956	0.000
E/e'	6.8±2.8	7.2±1.8	7.5±1.7	7.1±1.3	6.6±2.6	6.0±2.0^ab	5.2±2.0^abc	5.1±2.0^abc	13.189	0.000

表2 化疗组与对照组常规超声心动图参数比较（

x ˉ

±s）

参数	对照组(n=25)	化疗组(n=49)							F值	P值
参数	对照组(n=25)	t0	t1	t2	t3	t4	t5	t6	F值	P值
IVSTd(mm)	7.8±0.5	7.4±0.7	7.5±0.7	7.5±0.7	7.5±0.7	7.5±0.7	7.5±0.7	7.5±0.7	0.873	0.522
PWTd(mm)	7.3±0.8	7.4±0.8	7.3±0.8	7.3±0.7	7.3±0.8	7.4±0.8	7.4±0.8	7.3±0.8	0.506	0.800
LVDd(mm)	45.8±2.5	45.6±2.7	45.8±2.7	45.8±2.6	45.8±2.9	45.7±2.5	45.8±2.5	46.0±2.5	1.279	0.287
LVDs(mm)	26.8±2.0	26.9±1.9	26.8±1.8	26.9±1.8	26.9±1.8	26.9±1.5	26.8±2.1	27.1±1.6	1.081	0.389
LVEF(%)	62.3±2.1	62.4±2.0	62.4±2.0	62.3±2.1	62.0±2.0	61.6±1.8^abc	61.1±1.7^abc	60.2±1.8^abc	13.533	0.000
E(cm/s)	76.1±8.6	75.3±8.7	75.2±9.2	75.8±6.0	74.1±6.2	75.0±6.9	73.1±7.7	73.1±7.0	1.062	0.400
A(cm/s)	58.4±9.4	58.5±9.1	59.1±9.5	58.6±8.6	58.6±7.7	58.9±9.9	58.9±8.9	60.2±16.6	1.600	0.170
E/A	1.32±0.22	1.31±0.19	1.31±0.27	1.31±0.38	1.30±0.16	1.28±0.10	1.28±0.19	1.27±0.25^ac	13.956	0.000
E/e'	6.8±2.8	7.2±1.8	7.5±1.7	7.1±1.3	6.6±2.6	6.0±2.0^ab	5.2±2.0^abc	5.1±2.0^abc	13.189	0.000

表3 化疗组与对照组左心室应变参数比较（%，

x ˉ

±s）

参数	对照组(n=25)	化疗组(n=49)							F值	P值
参数	对照组(n=25)	t0	t1	t2	t3	t4	t5	t6	F值	P值
GLS	-24.1±2.0	-22.0±1.4	-21.8±1.4^abc	-21.1±1.4^abc	-20.0±1.0^abc	-19.3±1.1^abc	-18.7±1.2^abc	-18.1±1.2^abc	62.473	0.000
GRS	43.1±4.2	41.0±9.9	41.0±9.9^c	40.9±9.8^c	39.5±9.4^abc	38.6±9.2^abc	36.8±9.4^abc	36.1±9.1^abc	14.984	0.000
GCS	-35.0±2.3	-33.9±3.2	-33.7±3.0	-33.4±3.3^ac	-32.1±3.3^abc	-31.7±3.1^abc	-31.4±3.1^abc	-30.9±3.2^abc	6.061	0.000

表3 化疗组与对照组左心室应变参数比较（%，

x ˉ

±s）

参数	对照组(n=25)	化疗组(n=49)							F值	P值
参数	对照组(n=25)	t0	t1	t2	t3	t4	t5	t6	F值	P值
GLS	-24.1±2.0	-22.0±1.4	-21.8±1.4^abc	-21.1±1.4^abc	-20.0±1.0^abc	-19.3±1.1^abc	-18.7±1.2^abc	-18.1±1.2^abc	62.473	0.000
GRS	43.1±4.2	41.0±9.9	41.0±9.9^c	40.9±9.8^c	39.5±9.4^abc	38.6±9.2^abc	36.8±9.4^abc	36.1±9.1^abc	14.984	0.000
GCS	-35.0±2.3	-33.9±3.2	-33.7±3.0	-33.4±3.3^ac	-32.1±3.3^abc	-31.7±3.1^abc	-31.4±3.1^abc	-30.9±3.2^abc	6.061	0.000

表4 化疗组与对照组左心室旋转/扭转参数比较（

x ˉ

±s）

参数	对照组(n=25)	化疗组(n=49)							F值	P值
参数	对照组(n=25)	t0	t1	t2	t3	t4	t5	t6	F值	P值
AP-Prot	6.6±2.1	6.8±2.1	6.6±2.0^a	6.3±2.0^abc	5.8±1.8^abc	5.6±1.6^abc	4.6±1.3^abc	4.2±1.1^abc	26.553	0.000
MV-Prot	-4.6±1.7	-4.6±1.7	-4.7±1.4	-4.6±1.2	-4.6±1.3	-4.6±1.4	-4.5±1.6	-4.6±1.6	1.932	0.097
LV-Tw	11.1±2.0	11.5±2.0	11.3±2.0	10.9±2.0^ab	10.5±2.1^ab	10.2±1.7^ab	9.1±2.0^ab	8.9±1.8^ab	4.787	0.001

表4 化疗组与对照组左心室旋转/扭转参数比较（

x ˉ

±s）

参数	对照组(n=25)	化疗组(n=49)							F值	P值
参数	对照组(n=25)	t0	t1	t2	t3	t4	t5	t6	F值	P值
AP-Prot	6.6±2.1	6.8±2.1	6.6±2.0^a	6.3±2.0^abc	5.8±1.8^abc	5.6±1.6^abc	4.6±1.3^abc	4.2±1.1^abc	26.553	0.000
MV-Prot	-4.6±1.7	-4.6±1.7	-4.7±1.4	-4.6±1.2	-4.6±1.3	-4.6±1.4	-4.5±1.6	-4.6±1.6	1.932	0.097
LV-Tw	11.1±2.0	11.5±2.0	11.3±2.0	10.9±2.0^ab	10.5±2.1^ab	10.2±1.7^ab	9.1±2.0^ab	8.9±1.8^ab	4.787	0.001

图1 同一乳腺癌患者在新辅助化疗期间不同时间点心尖扭转角度峰值的变化。图a为化疗前；图b 为第1 次化疗后；图c为第2 次化疗后；图d为第3 次化疗后；图e为第4 次化疗后；图f 为第5 次化疗后；图g 为手术前

1	Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials[J]. Lancet Oncol, 2018, 19(1): 27-39.
2	Dalla K, Bech-Hanssen O, Oras J, et al. Speckle tracking-vs conventional echocardiography for the detection of myocardial injury-A study on patients with subarachnoid haemorrhage[J]. Acta Anaesthesiol Scand, 2019, 63(3): 365-372.
3	Seidman A, Hudis C, Pierri MK, et al. Cardiac dysfunction in the trastuzumab clinical trials experience[J]. J Clin Oncol, 2002, 20(5): 1215-1221.
4	Piper S, McDonagh T. Heart failure and chemotherapeutic agents[J]. Future Cardiol, 2015, 11(4): 453-470.
5	Lee CH, Zhang JF, Yuan KS, et al. Risk of cardiotoxicity induced by adjuvant anthracycline-based chemotherapy and radiotherapy in young and old Asian women with breast cancer[J]. Strahlenther Onkol, 2019, 195(7): 629-639.
6	Armenian S, Bhatia S. Predicting and preventing anthracycline-related cardiotoxicity[J]. Am Soc Clin Oncol Educ Book, 2018, 38: 3-12.
7	Wolf CM, Reiner B, Kühn A, et al. Subclinical Cardiac Dysfunction in Childhood Cancer Survivors on 10-Years Follow-Up Correlates With Cumulative Anthracycline Dose and Is Best Detected by Cardiopulmonary Exercise Testing, Circulating Serum Biomarker, Speckle Tracking Echocardiography, and Tissue Doppler Imaging[J]. Front Pediatr, 2020, 8: 123.
8	Dogru A, Cabuk D, Sahin T, et al. Evaluation of cardiotoxicity via speckle-tracking echocardiography in patients treated with anthracyclines[J]. Onkologie, 2013, 36(12): 712-716.
9	中国抗癌协会乳腺癌专业委员会. 中国抗癌协会乳腺癌诊治指南与规范(2019年版)[J]. 中国癌症杂志, 2019, 29(8): 609-679.
10	蔡璐, 尹立雪, 王斯佳, 等. 超声分层应变成像技术对阿霉素致大鼠急性左心室心肌早期毒性损伤的评价[J/CD]. 中华医学超声杂志(电子版), 2019, 16(5): 386-392.
11	Anqi Y, Yu Z, Mingjun X, et al. Use of echocardiography to monitor myocardial damage during anthracycline chemotherapy[J]. Echocardiography, 2019, 36(3): 495-502.
12	Arciniegas Calle MC, Sandhu NP, Xia H, et al. Two-dimensional speckle tracking echocardiography predicts early subclinical cardiotoxicity associated with anthracycline-trastuzumab chemotherapy in patients with breast cancer[J]. BMC Cancer, 2018, 18(1): 1037.
13	Torrent-Guasp F, Kocica MJ, Corno AF, et al. Towards new understanding of the heart structure and function[J]. Eur J Cardiothorac Surg, 2005, 27(2): 191-201.
14	陈以慈. 心脏供血的解剖学[J]. 新医学, 1990, (3): 115-116.
15	Mornoş C, Petrescu L. Early detection of anthracycline-mediated cardiotoxicity: the value of considering both global longitudinal left ventricular strain and twist[J]. Can J Physiol Pharmacol, 2013, 91(8):601-607.
16	梁梦婕, 金怡, 郑哲岚. 超声二维斑点追踪技术在蒽环类化疗药物心脏毒性监测中的应用价值[J/CD]. 中华医学超声杂志(电子版), 2019, 16(10): 749-755.
17	O'Halloran N, Lowery A, Curran C, et al. A review of the impact of neoadjuvant chemotherapy on breast surgery practice and outcomes[J]. Clin Breast Cancer, 2019, 19(5): 377-382.
18	Huang J, Yan ZN, Rui YF, et al. Longitudinal rotation: a new way to detect the cardiotoxicity of anthracycline-based chemotherapy in breast cancer patients[J]. Oncotarget, 2017, 8(41): 70072-70083.
19	Hjertaas JJ, Matre K. A left ventricular phantom for 3D echocardiographic twist measurements[J]. Biomed Tech (Berl), 2020, 65(2): 209-218.

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Dynamic evaluation of cardiotoxicity of low dose anthracycline in breast cancer patients during neoadjuvant chemotherapy using two-dimensional speckle tracking imaging

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Dynamic evaluation of cardiotoxicity of low dose anthracycline in breast cancer patients during neoadjuvant chemotherapy using two-dimensional speckle tracking imaging