Abstract 4351296: Early Detection of Chemotherapy-Related Cardiotoxicity Using Global Longitudinal Strain

Abstract

Background: Global Longitudinal Strain (GLS), derived from speckle-tracking echocardiography, has emerged as a highly sensitive and quantitative marker for detecting early systolic dysfunction. Its application in small animal preclinical models remains underutilized. Early identification of cardiac dysfunction in such models is essential for testing cardioprotective therapies. This study aimed to evaluate the utility of GLS for early detection of myocardial injury in a murine model of doxorubicin-induced cardiomyopathy and to assess the cardioprotective effects of Chromonar, a coronary-specific vasodilator. Methods: Male mice were treated with intraperitoneal doxorubicin (5 mg/kg/week) for six weeks to induce progressive cardiac dysfunction. A preventive treatment group received Chromonar concomitantly with doxorubicin from the onset of chemotherapy. Transthoracic echocardiography was performed at baseline, and at 3, 6, and 9 weeks post-treatment initiation. Cardiac function was evaluated using conventional measures, including left ventricular ejection fraction (LVEF), along with GLS obtained through speckle-tracking analysis to assess myocardial deformation. Results: Mice in the doxorubicin-only group exhibited a significant and progressive decline in GLS beginning at week 3, which continued through weeks 6 and 9, indicating early and worsening systolic dysfunction. Notably, these changes in GLS preceded measurable reductions in LVEF. In contrast, the Chromonar-treated group maintained GLS values near baseline throughout the study, suggesting that Chromonar effectively attenuated doxorubicin-induced myocardial impairment. Conventional echocardiographic parameters remained largely preserved in the early phases, underscoring the superior sensitivity of GLS in detecting subclinical dysfunction. Conclusions: GLS serves as a robust, noninvasive marker for the early detection of chemotherapy-induced cardiac injury in murine models. Its ability to detect functional impairment before conventional measures such as LVEF decline enhances its value for preclinical screening. Furthermore, Chromonar demonstrated a significant cardioprotective effect in this model, supporting its potential as an adjunct therapeutic strategy to mitigate anthracycline-related cardiotoxicity. These findings provide important translational insights relevant to cardio-oncology and support the broader adoption of GLS in preclinical cardiotoxicity studies.