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

Area of Science:

• Cardiovascular Research
• Animal Models
• Heart Failure Pathophysiology

Background:

• Nonrevascularizable coronary artery disease frequently causes hibernating myocardium, a precursor to heart failure (HF).
• Current therapeutic options for this condition are limited.
• A significant gap exists in animal models that accurately replicate the clinical features of hibernating myocardium.

Purpose of the Study:

• To develop and characterize a large animal model of hibernating myocardium.
• To assess the model's resemblance to human hibernating myocardium and associated heart failure.
• To establish a preclinical platform for testing novel interventions.

Main Methods:

• Yucatan minipigs underwent surgical implantation of a casein ameroid around the left anterior descending coronary artery (LAD) to induce progressive stenosis.
• Serial multimodality imaging, including coronary angiography, cardiac magnetic resonance (CMR), and 18F-Fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT), was performed.
• 43 pigs were followed for 120 ± 37 days, with monthly imaging assessments.

Main Results:

• 56% of pigs (24/43) died during follow-up; survivors exhibited severe LAD stenosis.
• In 19 long-term survivors, 90% (17/19) developed left ventricular systolic dysfunction (median LVEF 35%).
• Viable myocardium was confirmed by CMR in all 17 affected pigs, with 14 showing increased glucose uptake on FDG-PET/CT, indicating a metabolic switch.

Conclusions:

• The developed pig model accurately recapitulates key features of human hibernating myocardium and heart failure.
• This model demonstrates systolic dysfunction, viable myocardium, and a metabolic shift to glucose utilization.
• This human-like preclinical model is suitable for evaluating novel therapeutic strategies for nonrevascularizable coronary artery disease and ischemic heart failure before clinical trials.