Atrial fibrosis heterogeneity is a risk for atrial fibrillation in pigs with ischaemic heart failure
Zhihao Zhang, Julia Vlcek, Valerie Pauly, Nora Hesse, Julia Bauer, Kavi Raj Chataut, Florian Maderspacher, Lina Sophie Volz, Katharina Buchberger, Ruibing Xia, Bianca Hildebrand, Stefan Kääb, Dominik Schüttler, Philipp Tomsits, Sebastian Clauss- Clinical Biochemistry
- Biochemistry
- General Medicine
Abstract
Background
Atrial fibrillation (AF) is the most common arrhythmia and is associated with considerable morbidity and mortality. Ischaemic heart failure (IHF) remains one of the most common causes of AF in clinical practice. However, ischaemia‐mediated mechanisms leading to AF are still incompletely understood, and thus, current treatment approaches are limited. To improve our understanding of the pathophysiology, we studied a porcine IHF model.
Methods
In pigs, IHF was induced by balloon occlusion of the left anterior descending artery for 90 min. After 30 days of reperfusion, invasive haemodynamic measurements and electrophysiological studies were performed. Masson trichrome and immunofluorescence staining were conducted to assess interstitial fibrosis and myofibroblast activation in different heart regions.
Results
After 30 days of reperfusion, heart failure with significantly reduced ejection fraction (left anterior obique 30°, 34.78 ± 3.29% [IHF] vs. 62.03 ± 2.36% [control], p < .001; anterior–posterior 0°, 29.16 ± 3.61% vs. 59.54 ± 1.09%, p < .01) was observed. These pigs showed a significantly higher susceptibility to AF (33.90% [IHF] vs. 12.98% [control], p < .05). Histological assessment revealed aggravated fibrosis in atrial appendages but not in atrial free walls in IHF pigs (11.13 ± 1.44% vs. 5.99 ± .86%, p < .01 [LAA], 8.28 ± .56% vs. 6.01 ± .35%, p < .01 [RAA]), which was paralleled by enhanced myofibroblast activation (12.09 ± .65% vs. 9.00 ± .94%, p < .05 [LAA], 14.37 ± .60% vs. 10.30 ± 1.41%, p < .05 [RAA]). Correlation analysis indicated that not fibrosis per se but its cross‐regional heterogeneous distribution across the left atrium was associated with AF susceptibility (r = .6344, p < .01).
Conclusion
Our results suggest that left atrial cross‐regional fibrosis difference rather than overall fibrosis level is associated with IHF‐related AF susceptibility, presumably by establishing local conduction disturbances and heterogeneity.