Karakulak Ugur Nadir, Aladag Elifcan, Hekimsoy Vedat, Sahiner Mehmet Levent, Kaya Ergun Baris, Ozer Necla, Aksu Salih, Demiroglu Haluk, Goker Hakan, Buyukasik Yahya, Ozcebe Osman, Sayinalp Nilgun, Haznedaroglu Ibrahim Celalettin
Department of Cardiology, Hacettepe University Faculty of Medicine, Sihhiye, 06100, Ankara, Turkey.
Department of Hematology, Hacettepe University Faculty of Medicine, Ankara, Turkey.
Cardiovasc Toxicol. 2021 Mar;21(3):216-223. doi: 10.1007/s12012-020-09613-2. Epub 2020 Oct 17.
Tyrosine kinase inhibitors (TKIs) are established treatment for haematological malignancies. However, cardiac adverse effects, including the reduction in left ventricular ejection fraction and symptomatic heart failure remain clinical problems. The purpose of this study was to evaluate the left ventricular systolic functions in patients with chronic myeloid leukaemia receiving TKIs. A cross-sectional and observational study was conducted of 37 patients with chronic myeloid leukaemia receiving dasatinib or nilotinib after imatinib failure. Left ventricular systolic functions were evaluated using four-dimensional speckle tracking echocardiography derived global longitudinal (GLS), circumferential (GCS), radial (GRS), and area (GAS) strain indices. Mean ejection fraction, stroke volume, cardiac output and left ventricular mass index were similar between control and patient groups and within normal limits. GLS (- 16.7% vs - 20.8%, p < 0.001), GCS (- 13.0% vs - 15.6%, p = 0.002), and GAS (- 26.2% vs - 31.0, p < 0.001) values were significantly higher in the patient population than those of the controls. Dasatinib and nilotinib groups did not show differences regarding strain indices. In multivariate regression analysis, only the usage of dasatinib or nilotinib was found to be an independent risk factor for diminished GAS (β = 4.406, p = 0.016), GLS (β = 3.797, p = 0.001), and GCS (β = 2.404, p = 0.040). Although imatinib, nilotinib, and dasatinib seem to be clinically safe in terms of cardiac function, monitoring of systolic functions using strain imaging, and long-term observation of patients may provide early detection of the possible cardiac toxicity.
酪氨酸激酶抑制剂(TKIs)是血液系统恶性肿瘤的既定治疗方法。然而,包括左心室射血分数降低和症状性心力衰竭在内的心脏不良反应仍然是临床问题。本研究的目的是评估接受TKIs治疗的慢性髓性白血病患者的左心室收缩功能。对37例伊马替尼治疗失败后接受达沙替尼或尼洛替尼治疗的慢性髓性白血病患者进行了一项横断面观察性研究。使用基于四维斑点追踪超声心动图得出的整体纵向(GLS)、圆周(GCS)、径向(GRS)和面积(GAS)应变指数评估左心室收缩功能。对照组和患者组之间的平均射血分数、每搏输出量、心输出量和左心室质量指数相似,且在正常范围内。患者群体的GLS(-16.7%对-20.8%,p<0.001)、GCS(-13.0%对-15.6%,p=0.002)和GAS(-26.2%对-31.0,p<0.001)值显著高于对照组。达沙替尼组和尼洛替尼组在应变指数方面未显示出差异。在多变量回归分析中,仅发现使用达沙替尼或尼洛替尼是GAS降低(β=4.406,p=0.016)、GLS降低(β=3.797,p=0.001)和GCS降低(β=2.404,p=0.040)的独立危险因素。尽管伊马替尼、尼洛替尼和达沙替尼在心脏功能方面似乎临床安全,但使用应变成像监测收缩功能以及对患者进行长期观察可能有助于早期发现潜在的心脏毒性。