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

• Published in: Basic research in cardiology Vol. 115; no. 3; p. 33
• Main Authors: Martínez-Milla, Juan, Galán-Arriola, Carlos, Carnero, Manuel, Cobiella, Javier, Pérez-Camargo, Daniel, Bautista-Hernández, Victor, Rigol, Montserrat, Solanes, Nuria, Villena-Gutierrez, Rocío, Lobo, Manuel, Mateo, Jesús, Vilchez-Tschischke, Jean Paul, Salinas, Beatriz, Cussó, Lorena, López, Gonzalo Javier, Fuster, Valentín, Desco, Manuel, Sanchez-González, Javier, Ibanez, Borja
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.05.2020; Springer Nature B.V
• Subjects: Angiography; Animal models; Blood vessels; Cardiology; Cardiovascular disease; Casein; Clinical trials; Computed tomography; Coronary artery; Coronary artery disease; Coronary vessels; Glucose; Heart failure; Hibernation; Hogs; Ischemia; Magnetic resonance; Medical imaging; Medicine; Medicine & Public Health; Myocardium; Original Contribution; Positron emission; Positron emission tomography; Stenosis; Surgical implants; Swine; Tomography; Ventricle; Heart failure; FDG-PET/CT; Dilated cardiomyopathy; Metabolic switch; Cardiac magnetic resonance; Hibernating myocardium; Large animal models; 18FDG-PET/CT
• ISSN: 0300-8428; 1435-1803
• DOI: 10.1007/s00395-020-0788-0

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 18 F-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 18 FDG-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.