C22 - Assessment of Cardiotoxicity After Combretastatin A4-phosphate Administration in Dogs Using Two-dimensional Speckle Tracking Echocardiography

Abstract: Background - Combretastatin A4-phosphate (CA4P) is a vascular disrupting agent recently described for treatment of solid tumors in dogs. Conventional echocardiography did not show signs of cardiotoxicity. However, the gold standard for assessing myocardial damage in humans receiving cardiotoxic chemotherapeutics is two-dimensional speckle tracking echocardiography (2D-STE).



Hypothesis/objectives - The aim of this study was to evaluate the cardiotoxic effect of CA4P in dogs, based on 2D-STE measurements.



Animals - Echocardiographic images of healthy dogs and cancer patients that received CA4P were retrospectively reviewed. Seven healthy beagles and five cancer patients were included.



Methods - Peak global longitudinal strain (GLS), peak global circumferential strain (GCS) and peak global radial strain (GRS) were measured before and 24 hours after administration of CA4P. Strain measurements were compared with cardiac troponin I (cTnI) measurements. On seven echocardiographic examinations, each strain parameter was measured by 3 observers on 3 consecutive days to obtain intra-observer and inter-observer variability.



Results - Median GCS and GLS values decreased by 17.6% (P = 0.002) and 24.0% (P = 0.0005), respectively. Median GRS values were not significantly different (P = 0.16). The decrease in GLS was correlated with a rise in cTnI (Spearman rho = -0.63, P = 0.03). The intra-observer coefficient of variation was 0.04, 0.13 and 0.09 for GCS, GRS and GLS, respectively, while the corresponding inter-observer coefficients were 0.12, 0.20 and 0.11.


Conclusions and clinical importance - Administration of CA4P has a cardiotoxic effect, which can be detected by 2D-STE strain measurements and correlates with cTnI concentrations.