AUTHOR=Liu Xing-Li , Wang Guan-Zhong , Rui Mao-Ping , Fan Dong , Zhang Jie , Zhu Zheng-Hua , Perez Rosario , Wang Tony , Yang Li-Chuan , Lyu Liang , Zheng Jie , Wang Gang TITLE=Imaging characterization of myocardial function, fibrosis, and perfusion in a nonhuman primate model with heart failure-like features JOURNAL=Frontiers in Cardiovascular Medicine VOLUME=10 YEAR=2023 URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2023.1214249 DOI=10.3389/fcvm.2023.1214249 ISSN=2297-055X ABSTRACT=Introduction

The availability of a human-like chronic heart failure (HF) animal model was critical for affiliating development of novel therapeutic drug treatments. With the close physiology relatedness to humans, the non-human primate (NHP) HF model would be valuable to better understand the pathophysiology and pharmacology of HF. The purpose of this work was to present preliminary cardiac image findings using echocardiography and cardiovascular magnetic resonance (CMR) in a HF-like cynomolgus macaque model.

Methods

The NHP diet-induced model developed cardiac phenotypes that exhibited diastolic dysfunction with reduced left ventricular ejection fraction (LVEF) or preserved LVEF. Twenty cynomolgus monkeys with cardiac dysfunction were selected by echocardiography and subsequently separated into two groups, LVEF < 65% (termed as HFrEF, n = 10) and LVEF ≥ 65% with diastolic dysfunction (termed as HFpEF, n = 10). Another group of ten healthy monkeys was used as the healthy control. All monkeys underwent a CMR study to measure global longitudinal strain (GLS), myocardial extracellular volume (ECV), and late gadolinium enhancement (LGE). In healthy controls and HFpEF group, quantitative perfusion imaging scans at rest and under dobutamine stress were performed and myocardial perfusion reserve (MPR) was subsequently obtained.

Results

No LGE was observed in any monkey. Monkeys with HF-like features were significantly older, compared to the healthy control group. There were significant differences among the three groups in ECV (20.79 ± 3.65% in healthy controls; 27.06 ± 3.37% in HFpEF group, and 31.11 ± 4.50% in HFrEFgroup, p < 0.001), as well as for stress perfusion (2.40 ± 0.34 ml/min/g in healthy controls vs. 1.28 ± 0.24 ml/min/g in HFpEF group, p < 0.01) and corresponding MPR (1.83 ± 0.3 vs. 1.35 ± 0.29, p < 0.01). After adjusting for age, ECV (p = 0.01) and MPR (p = 0.048) still showed significant differences among the three groups.

Conclusion

Our preliminary imaging findings demonstrated cardiac dysfunction, elevated ECV, and/or reduced MPR in this HF-like NHP model. This pilot study laid the foundation for further mechanistic research and the development of a drug testing platform for distinct HF pathophysiology.