Abstract
Clinical evidence suggests a link between fibrosis in the left atrium (LA) and atrial fibrillation (AF), the most common sustained arrhythmia. Image-derived fibrosis is increasingly used for patient stratification and therapy guidance. However, locations of re-entrant drivers (RDs) sustaining AF are unknown and therapy success rates remain suboptimal. This study used image-derived LA models to explore the dynamics of RD stabilization in fibrotic regions and generate maps of RD locations. LA models with patient-specific geometry and fibrosis distribution were derived from late gadolinium enhanced magnetic resonance imaging of 6 AF patients. In each model, RDs were initiated at multiple locations, and their trajectories were tracked and overlaid on the LA fibrosis distributions to identify the most likely regions where the RDs stabilized. The simulations showed that the RD dynamics were strongly influenced by the amount and spatial distribution of fibrosis. In patients with fibrosis burden greater than 25%, RDs anchored to specific locations near large fibrotic patches. In patients with fibrosis burden below 25%, RDs either moved near small fibrotic patches or anchored to anatomical features. The patient-specific maps of RD locations showed that areas that harboured the RDs were much smaller than the entire fibrotic areas, indicating potential targets for ablation therapy. Ablating the predicted locations and connecting them to the existing pulmonary vein ablation lesions was the most effective in-silico ablation strategy.
Highlights
The prevalence of atrial fibrillation (AF) is increasing to epidemic proportions: worldwide over 33 million individuals have AF [1]
We reported the overall distribution of the re-entrant drivers (RDs) across different regions of the atrial wall in the patient-specific left atrium (LA) models and found that RDs are most likely to be present at fibrotic regions in patients with fibrosis burden (FB) from Utah category 3 and 4
The main observations of this study were as follows: (i) in AF patients from Utah 4 and 3 with high FB (>25%) RDs were more likely to be found at fibrotic regions compared to pulmonary veins (PV) (Fig 4A), (ii) RDs anchored to specific regions within the atrial walls–target areas (TA) identified from RD tip probability maps (Fig 8), (iii) a higher percentage of TAs were located within the fibrotic tissue region in patients in Utah 3 and 4 categories compared to patients in Utah 2 category (Fig 9A), and (iv) performing virtual catheter ablation (CA) of the TAs and connecting them with linear lesions to the nearest PVs or mitral valve (MV)
Summary
The prevalence of atrial fibrillation (AF) is increasing to epidemic proportions: worldwide over 33 million individuals have AF [1]. Even advanced CA procedures have suboptimal long-term outcomes in patients with chronic forms of AF: over half of the patients return for additional treatment within three years [5]. This can be explained by the highly empirical nature of CA therapy, which targets “usual suspect” areas without knowledge of the underlying arrhythmogenic mechanisms. CA therapy based on electrical isolation of the pulmonary veins (PV) has low success rates in chronic AF patients, where extensive ablation of remodelled non-PV areas is commonly applied [6]
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