https://doi.org/10.1007/s00392-025-02625-4
1LMU Klinikum der Universität München Medizinische Klinik und Poliklinik I München, Deutschland; 2Kardiologie Ammer-Lech Drs. D. Braun/ M. Orban Dießen, Deutschland; 3LMU München Lehrstuhl für Virologie Oberschleissheim, Deutschland
Introduction: Atrial Fibrillation (AF) is the most common arrhythmia. Major pathophysiological hallmarks of AF are structural and electrical remodeling processes establishing a proarrhythmic atrial substrate. Susceptibility for remodeling-inducing triggers (e.g. ischemia), however, is largely variable suggesting a genetic impact.
Objective: To evaluate the genetic influence on proarrhythmic remodeling.
Methods: Ischemic heart failure (IHF) was induced by balloon occlusion of the LAD for 90 minutes in two pig breeds, Pietrain and German Landrace. Pigs were evaluated in vivo 30 days later by right/left heart catheterization, ECG and electrophysiology studies. AF was induced by burst pacing. Fibrosis was histologically quantified by Masson Trichrome staining.
Results: In both breeds, LAD occlusion resulted in IHF indicated by significantly reduced left ventricular (LV) ejection fraction (EF, Fig.1A) and significantly elevated LV end-diastolic pressure (LVEDP, Fig.1B). IHF increased the vulnerability for AF similarly in both breeds observed by an increased inducibility of AF (Fig.1C-D) and an enhanced AF burden (Fig.1E). Significant left atrial fibrosis was elevated in Pietrain pigs (Fig.1J) whereas in Landrace pigs with IHF a shortening of the atrial effective refractory period (AERP, Fig.1F-I) was observed.
Conclusion: In Pietrain pigs with IHF atrial fibrosis is enhanced indicating a proarrhythmic structural substrate while in Landrace pigs AERP shortening can be observed indicating an electrical substrate, both leading to similarly enhanced vulnerability for AF. These findings suggest that the genetic background determines the atrial remodeling response to a proarrhythmic trigger such as ischemia.