Key result
Persistent rapid ventricular pacing and subsequent atrial fibrillation led to a significant increase in left atrial fibrosis volumes compared to non-paced controls (median %MF 2.96% vs 0.95%, P=0.009).
Why the study?
AF is associated with extracellular matrix remodelling and often coexists with myocardial fibrosis, but causality between these conditions is not well established.
Does rapid ventricular pacing to induce atrial fibrillation increase left atrial fibrosis in a canine model?
Does rapid ventricular pacing to induce atrial fibrillation increase left atrial fibrosis in a canine model?
Absolute Event Rate: 2.96% vs 0.95%
p-value: p=0.009
In a canine model, rapid ventricular pacing and subsequent atrial fibrillation led to a significant increase in left atrial fibrosis as quantified by 3D LGE-CMR.
Preclinical canine data link AF to LA fibrosis; leaves open human causality and clinical relevance.
BACKGROUND: Atrial fibrillation (AF) is associated with extracellular matrix (ECM) remodelling and often coexists with myocardial fibrosis (MF); however, the causality of these conditions is not well established. OBJECTIVE: We aim to corroborate AF to MF causality by quantifying left atrial (LA) fibrosis in cardiac magnetic resonance (CMR) images after persistent rapid ventricular pacing and subsequent AF using a canine model and histopathological validation. METHODS: Twelve canines (9 experimental, 3 control) underwent baseline 3D LGE-CMR imaging at 3T followed by insertion of a pacing device and 5 weeks of rapid ventricular pacing to induce AF (experimental) or no pacing (control). Following the 5 weeks, pacing devices were removed to permit CMR imaging followed by excision of the hearts and histopathological imaging. LA myocardial segmentation was performed manually at baseline and post-pacing to permit volumetric %MF quantification using the image intensity ratio (IIR) technique, wherein fibrosis was defined as pixels > mean LA myocardium intensity + 2SD. RESULTS: Volumetric %MF increased by an average of 2.11 ± 0.88% post-pacing in 7 of 9 experimental dogs. While there was a significant difference between paired %MF measurements from baseline to post-pacing in experimental dogs (P = 0.019), there was no significant change in control dogs (P = 0.019 and P = 0.5, Wilcoxon signed rank tests). The median %MF for paced animals was significantly greater than that of non-paced dogs at the 5-week post-insertion time point (P = 0.009, Mann Whitney U test). Histopathological imaging yielded an average %MF of 19.42 ± 4.80% (mean ± SD) for paced dogs compared to 1.85% in one control dog. CONCLUSION: Persistent rapid ventricular pacing and subsequent AF leads to an increase in LA fibrosis volumes measured by the IIR technique; however, quantification is limited by inherent image acquisition parameters and observer variability.
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Farrag et al. (2022) studied Atrial fibrillation and myocardial fibrosis (n=12). Rapid ventricular pacing vs. No rapid ventricular pacing (surgical insertion of pacing device only) was evaluated on Median volumetric percentage of myocardial fibrosis (%MF) at 5 weeks (p=0.009). Persistent rapid ventricular pacing and subsequent atrial fibrillation led to a significant increase in left atrial fibrosis volumes compared to non-paced controls (median %MF 2.96% vs 0.95%, P=0.009).
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