Cardiovascular MRI Evaluation of Myocardial Injury and Temporal Trends in a Miniature Swine Model of Cancer Therapy-Related Cardiovascular Toxicity (RF_FR_430)

Friday, January 31, 2025

3:10 PM – 3:20 PM East Coast USA Time

Location: Blue Room PreFunction

Presenting Author(s)

rs

rui shi, PhD

student
west china hospital,Sichuan university, China (People's Republic)

Primary Author(s)

ZY

Zhigang Yang, MD, PhD

Proffessor
West China Hospital, China (People's Republic)

Co-Author(s)

LS

Liting Shen, MD

N/A
West China Hospital, China (People's Republic)

Background: Doxorubicin (DOX), are widely used in the treatment of breast cancer and hematologic malignancies, effectively reducing the risk of death in cancer patients. However, their cardiotoxicity limits their broader clinical application[1, 2] Left Ventricular Ejection Fraction (LVEF) is a commonly used indicator for monitoring this type of cardiotoxicity, and a decline in LVEF often reflects the later stages of myocardial injury, at which point treatment options are typically limited [3-5].Studies based on a miniature pig model suggest that prolonged T2 time (with normal T1 and ECV) may indicate intracellular edema in cardiomyocytes, providing a reversible early imaging marker for anthracycline-induced cardiotoxicity[6, 7].However, whether T2 prolongation can serve as a marker for clinical intervention and improve patient outcomes remains inconclusive. This study aims to establish a chronic myocardial injury model in miniature pigs and conduct continuous cardiac MR monitoring during and after doxorubicin administration to assess the long-term impacts on cardiac structure and function. It explores the potential links between cardiac MRI parameter changes during doxorubicin administration and myocardial pathological changes.

Methods:

Sixteen female Bama miniature pigs were treated with doxorubicin every two weeks over four cycles. Cardiac MRI was performed before each doxorubicin administration and one, three, and six months after the last dose. Cardiac pathology samples were collected in the fourth, eighth week, and three months after doxorubicin administration (three pigs each time). Data from serial cardiac MRI images were analyzed to track the trends over time in cardiac function and histological features. Detailed pathological analyses of cardiac samples were conducted to evaluate the histopathological changes caused by doxorubicin-induced myocardial injury.

Results:

During the doxorubicin administration period, overall longitudinal strain of the left ventricle showed a decreasing trend at some time points (ns(Time, df = 3)1: β=-1.869, P=0.251; ns(Time, df = 3)2: β=-3.187, P=0.021; ns(Time, df = 3)3: β=-1.052, P=0.150); T2 relaxation time showed an increasing trend (ns(Time, df = 3)1: β= 1.685, P=0.024; ns(Time, df = 3)2: β=2.065, P=0.144; ns(Time, df = 3)3: β= 2.490, P=0.015). During the follow-up period, there were slight fluctuations in overall longitudinal strain of the left ventricle without a clear upward or downward trend (P >0.05); overall circumferential and radial strains of the left ventricle showed a decreasing trend (P< 0.001 and P=0.001, respectively). T2 relaxation time showed a decreasing trend during the follow-up period (P=0.003). The trend in T2 relaxation time changes was closely associated with the observed changes in the severity of mitochondrial damage in cardiomyocytes under electron microscopy, while HE staining and Masson's trichrome staining showed no significant pathological changes at any time point.

Conclusion:

Early changes in T2 relaxation time reflect acute myocardial injury induced by doxorubicin, whereas changes in LVEF and myocardial strain reveal a long-term process of gradual cardiac function impairment over time. This difference suggests that evaluating doxorubicin-induced cardiotoxicity should consider multiple cardiac function indicators across different time points to comprehensively understand the changes and degree of cardiac function impairment.