Mampaey Gitte, Hellemans Arnaut, de Rooster Hilde, Schipper Tom, Abma Eline, Broeckx Bart J G, Daminet Sylvie, Smets Pascale
Small Animal Department, Faculty of Veterinary Medicine, Ghent University, 9820 Merelbeke, Belgium.
Department of Veterinary and Biosciences, Faculty of Veterinary Medicine, Ghent University, 9820 Merelbeke, Belgium.
Animals (Basel). 2022 Nov 2;12(21):3005. doi: 10.3390/ani12213005.
Combretastatin A4-phosphate (CA4P) is a vascular disrupting agent that was recently described for the treatment of solid canine tumors. Conventional echocardiography and pulsed wave tissue Doppler imaging did not reveal cardiotoxicity in dogs, however, the gold standard for assessing myocardial damage in humans receiving cardiotoxic chemotherapeutics is two-dimensional speckle-tracking echocardiography. The current study evaluated the cardiotoxic effect of a single dose of CA4P in dogs using peak systolic strain measurements and the variability of these measurements. Echocardiographic examinations of seven healthy beagles and five canine cancer patients that received CA4P were retrospectively reviewed. Peak systolic regional longitudinal strain (LSt), peak systolic regional circumferential strain (CSt), and peak systolic regional radial strain (RSt) were measured before and 24 h after administration of CA4P. Peak systolic strain measurements were compared to serum cardiac troponin I (cTnI). To quantify intra- and inter-observer measurement variability, seven echocardiographic examinations were selected and each strain parameter was measured by three observers on three consecutive days. After CA4P administration, the median LSt and CSt values decreased by 21.8% ( = 0.0005) and 12.3% ( = 0.002), respectively, whereas the median RSt values were not significantly different ( = 0.70). The decrease in LSt was correlated with increased serum cTnI values (Spearman rho = -0.64, = 0.02). The intra-observer coefficients of variation (CV) were 9%, 4%, and 13% for LSt, CSt, and RSt, respectively, while the corresponding interobserver CVs were 11%, 12%, and 20%. Our results suggest that regional peak systolic strain measurements may be useful for the early detection of cardiotoxicity that is caused by vascular disrupting agents and that LSt may be promising for the follow-up of canine cancer patients.
磷酸考布他汀A4（CA4P）是一种血管破坏剂，最近被用于治疗犬实体瘤。传统超声心动图和脉冲波组织多普勒成像未显示犬有心脏毒性，然而，评估接受心脏毒性化疗药物的人类心肌损伤的金标准是二维斑点追踪超声心动图。本研究使用峰值收缩应变测量及其测量变异性评估单剂量CA4P对犬的心脏毒性作用。回顾性分析了7只健康比格犬和5只接受CA4P治疗的犬类癌症患者的超声心动图检查结果。在给予CA4P之前和之后24小时测量峰值收缩期区域纵向应变（LSt）、峰值收缩期区域圆周应变（CSt）和峰值收缩期区域径向应变（RSt）。将峰值收缩应变测量结果与血清心肌肌钙蛋白I（cTnI）进行比较。为了量化观察者内和观察者间的测量变异性，选择了7次超声心动图检查，每个应变参数由三名观察者在连续三天内进行测量。给予CA4P后，LSt和CSt的中位数分别下降了21.8%（P = 0.0005）和12.3%（P = 0.002），而RSt的中位数无显著差异（P = 0.70）。LSt的下降与血清cTnI值的升高相关（Spearman相关系数=-0.64，P = 0.02）。LSt、CSt和RSt的观察者内变异系数（CV）分别为9%、4%和13%，而相应的观察者间CV分别为11%、12%和20%。我们的结果表明，区域峰值收缩应变测量可能有助于早期检测血管破坏剂引起的心脏毒性，并且LSt可能对犬类癌症患者的随访有前景。
