Abstract 354: The progression of changes in cardiac structure and function in mice with epithelial ovarian cancer
Authors: Coyle-Asbil Bridget , Ogilvie Leslie M. , Pereira Madison , Matuszewska Kathy , Delfinis Luca J. , Gandhi Shivam , Brunt Keith R. , Perry Christopher G. , Petrik Jim , Simpson Jeremy A. 
Published: April 2023

Introduction: Cancer cachexia, characterized by the progressive loss of muscle mass (i.e., atrophy), has a significant impact on patient prognosis and quality of life. While skeletal muscle atrophy and weakness are well characterized in cancer patients, the progression of cancer-induced cardiac atrophy has received little attention. Preliminary work from our lab has shown that cardiac dysfunction, measured by invasive hemodynamic assessment, precedes the development of metastatic disease in a mouse model of epithelial ovarian cancer (EOC). Yet, the time course of changes in cardiac structure and function throughout the progression of ovarian cancer remain unknown. Thus, we non-invasively assessed changes in cardiac structure and function through the progression of EOC.

Methods: To investigate the impact of advanced ovarian cancer on cardiac structure and function, we used an orthotopic, syngeneic mouse model of EOC. This model was generated by injecting transformed murine ovarian surface epithelial cells (ID8; 1.0 × 106) or saline (surgical sham) directly under the ovarian bursa of syngeneic mice. Echocardiography was used to assess changes in cardiac structure and function throughout the progression of EOC at days 45, 60, 75, and 90 post-tumor induction (PTI). Morphometric assessments at each timepoint were used to determine the presence of cardiac atrophy.

Results: Echocardiography showed that EOC mice had preserved left ventricular (LV) function (i.e., ejection fraction) with no change in structural dimensions at days 45, 60 and 75 PTI. By day 90 PTI, LV wall thickness and end-systolic dimension decreased, suggesting evidence of cardiac atrophy. Consistent with echocardiographic data, morphometric assessment showed profound atrophy at 90 days PTI, but preserved cardiac mass at all other timepoints compared to shams.

Conclusion: Together, this work demonstrates that when non-invasive techniques are used to measure changes in cardiac structure, atrophy is not evident until advanced stage ovarian cancer (i.e., 90 days PTI). Despite this, preliminary work from our lab has shown that cardiac dysfunction is present in EOC mice by 45 days PTI when assessed by invasive hemodynamics. Although echocardiography is a widely used technique for measuring indices of cardiac structure and function, our work demonstrates it lacks sensitivity to detect cardiac deficits until the overt stages of disease that accompany cancer cachexia. Thus, it is important to consider that subclinical cardiac dysfunction may exist in the early stages of cancer progression, however, these changes may go undetected unless more sensitive hemodynamic assessments are employed.

Citation Format: Bridget Coyle-Asbil, Leslie M. Ogilvie, Madison Pereira, Kathy Matuszewska, Luca J. Delfinis, Shivam Gandhi, Keith R. Brunt, Christopher G. Perry, Jim Petrik, Jeremy A. Simpson. The progression of changes in cardiac structure and function in mice with epithelial ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 354.