Abstract 4359566: Multimodal Imaging Characterization of Chronic Cardiac Pathologies in Aged Cynomolgus Monkeys: Translational Insights into Heart Failure and Amyloidosis

Abstract

Background: Non-human primates (NHPs), particularly aged cynomolgus monkeys, share key physiologic, metabolic and genetic similarities with humans, offering valuable translational models for chronic cardiac diseases. Objective: This study aimed to establish and characterize chronic heart failure phenotypes, and investigate the presence of myocardial amyloidosis in aged NHPs using advanced multimodal imaging and biomarker profiling. Methods: Over 1,000 aged male cynomolgus monkeys underwent comprehensive cardiac evaluation. Ventricular structure and function were assessed by 2D-echocardiography (2D echo) and cardiac magnetic resonance imaging (MRI). Left ventricular myocardial proton density fat fraction (LV-PDFF) and epicardial adipose tissue (EAT) volume were determined. Myocardial amyloidosis was detected via 18F-florbetapir PET-CT. Circulating biomarkers of cardiac injury and inflammation (NT-proBNP, troponin I, hs-CRP, IL-1, IL-6, TNF-α) were measured. Healthy young NHPs served as controls. Results: Left-sided HF was present in 30% of aged NHPs with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) was equally represented. HFrEF models showed markedly reduced ejection fraction (EF<60%; 53 ± 4.6% vs. 73 ± 4.3% controls). HFpEF, was defined by normal/preserved EF (≥60%) and diastolic dysfunction markers (E/A<1, e'>7, and E/e'>11 for mild HFpEF; E/A>1, e'/a'<1, e'<7, and E/e'>11 for moderate HFpEF). Reduced MRI LV global longitudinal strain (GLS) and elevated extracellular volume fraction (ECV) were recorded for both HF subtypes indicating myocardial fibrosis. LV-PDFF was increased in HFpEF and HFrEF groups compared to controls. PET-CT identified myocardial amyloidosis in a subset of aged animals, independent of HF classification. Biomarkers of cardiac stress and systemic inflammation were significantly elevated in HF-affected NHPs. Conclusion: This study establishes aged cynomolgus monkeys as a translational model that recapitulates key features of human cardiac dysfunction, including heterogeneous HF phenotypes, and myocardial amyloidosis. The integration of multimodal imaging and biomarker profiling provides a robust platform for preclinical evaluation of novel therapeutics targeting HF subtypes and related cardiac pathologies.