Yucatan Miniswine Model of Atrial Fibrillation: Clinical Relevance

Introduction Persistent atrial fibrillation (AFib) is the most common chronic arrhythmia in adults in the United States and is associated with significant morbidity, including thromboembolic events, stroke, and heart failure. Despite available therapies such as catheter ablation and antiarrhythmic drugs, AFib remains incurable for many patients. Our study aims to develop a large-animal model of AFib in Yucatan miniswine to support investigation of new therapeutic approaches for this disease. Methods Yucatan miniswine were selected for their physiological similarity to humans and suitable size for long-term studies. Each animal was initially fitted with an external FitBark 2.0 collar to track activity as a surrogate for quality of life. Animals then underwent implantation of an atrial pacing lead in the right atrial appendage, a pacing generator, and an insertable cardiac monitor (ICM Reveal LINQ™) implanted subcutaneously along the left scapula. One week after the pacemaker implantation, animals underwent rapid atrial pacing to induce persistent AFib. All procedures were performed in accordance with relevant institutional and regulatory guidelines. Results Atrial fibrillation was successfully induced in 4 of 6 animals within 80.3 ± 22.3 days of initiating pacing with three animals going into persistent AFib and one animal going into paroxysmal AFib. The definition of persistent AFib was that animals remained in AFib for more than 14 days after pacing was discontinued. Paroxysmal AFib was defined as AFib lasting less than 14 days. Activity levels decreased following persistent AFib onset, indicating a decline in overall health and quality of life. Histopathological analyses showed significant increases in fibrosis and loss of atrial cardiomyocytes after persistent AFib was induced in swine. Several anatomical and technical challenges, particularly related to vascular access and cardiac dimensions, were overcome through customized surgical strategies, including jugular venous cut-downs, lateral cervical ICM implantation, long vascular sheaths, custom styluses, and perioperative antibiotic coverage. These innovations were critical to establishing a robust and reproducible persistent AFib model.