Translational large animal model of hibernating myocardium: characterization by serial multimodal imaging

Abstract

Nonrevascularizable coronary artery disease is a frequent cause of hibernating myocardium leading to heart failure (HF). Currently, there is a paucity of therapeutic options for patients with this condition. There is a lack of animal models resembling clinical features of hibernating myocardium. Here we present a large animal model of hibernating myocardium characterized by serial multimodality imaging. Yucatan minipigs underwent a surgical casein ameroid implant around the proximal left anterior descending coronary artery (LAD), resulting in a progressive obstruction of the vessel. Pigs underwent serial multimodality imaging including invasive coronary angiography, cardiac magnetic resonance (CMR), and hybrid 18F-Fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT). A total of 43 pigs were operated on and were followed for 120 ± 37 days with monthly multimodality imaging. 24 pigs (56%) died during the follow-up. Severe LAD luminal stenosis was documented in all survivors. In the group of 19 long-term survivors, 17 (90%) developed left ventricular systolic dysfunction [median LVEF of 35% (IQR 32.5-40.5%)]. In 17/17, at-risk territory was viable on CMR and 14 showed an increased glucose uptake in the at-risk myocardium on 18FDG-PET/CT. The present pig model resembles most of the human hibernated myocardium characteristics and associated heart failure (systolic dysfunction, viable myocardium, and metabolic switch to glucose). This human-like model might be used to test novel interventions for nonrevascularizable coronary artery disease and ischemia heart failure as a previous stage to clinical trials.